125I Brachytherapy in Locally Advanced Nonsmall Cell Lung Cancer After Progression of Concurrent Radiochemotherapy

To investigate the safety and effectiveness of computed tomography (CT)-guided ¹²⁵I seed implantation for locally advanced nonsmall cell lung cancer (NSCLC) after progression of concurrent radiochemotherapy (CCRT).We reviewed 78 locally advanced NSCLC patients who had each one cycle of first-line CCRT but had progressive disease identified from January 2006 to February 2015 at our institution. A total of 37 patients with 44 lesions received CT-guided percutaneous ¹²⁵I seed implantation and second-line chemotherapy (group A), while 41 with 41 lesions received second-line chemotherapy (group B).Patients in group A and B received a total of 37 and 41 first cycle of CCRT treatment. The median follow-up was 19 (range 3–36) months. After the second treatment, the total response rate (RR) in tumor response accounted for 63.6% in group A, which was significantly higher than that of group B (41.5%) (P = 0.033). The median progression-free survival time (PFST) was 8.00 ± 1.09 months and 5.00 ± 0.64 months in groups A and B (P = 0.011). The 1-, 2-, and 3-year overall survival (OS) rates for group A were 56.8%, 16.2%, and 2.7%, respectively. For group B, OS rates were 36.6%, 9.8%, and 2.4%, respectively. The median OS time was 14.00 ± 1.82 months and 10.00 ± 1.37 months for groups A and B, respectively (P = 0.059). Similar toxicity reactions were found in both groups. Tumor-related clinical symptoms were significantly reduced and the patients’ quality of life was obviously improved.CT-guided ¹²⁵I seed implantation proved to be potentially beneficial in treating localized advanced NSCLC; it achieved good local control rates and relieved clinical symptoms without increasing side effects.     

Treatment outcomes of induction chemotherapy combined with intensity-modulated radiotherapy and adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma in Southeast China

Induction chemotherapy (IC) and adjuvant chemotherapy (AC) are used to enhance tumor locoregional control and support early treatment for distant metastases. However, optimum combinatorial treatment of these chemoradiotherapy regimens with radiotherapy in curing locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. Here, we evaluate the efficacy and therapeutic outcome of a combinatorial treatment strategy involving IC, intensity-modulated radiotherapy (IMRT), and AC, by retrospectively analyzing 243 NPC patients who were treated by IC followed by IMRT and AC. The rates of 3-/5-year local-regional control rate, distant failure-free rate (DFFR), progression-free survival (PFS), and overall survival (OS) were 93.3%/90.3%, 84.2%/79.4%, 79.6%/74.4%, and 84.0%/72.6%, respectively. The 3-/5-year OS rates of patients in stage III or IVA were 91.5%/75.1% and 86.5%/56.5%, respectively. Combination cisplatin with paclitaxel showed no significance in OS as compared to cisplatin plus 5-fluorouracil (P-value = .17). Total four-cycle IC and AC was significantly beneficious versus three-cycle in DFFR (P-value = .04), as well as total 6 chemotherapy cycles compared to 4 in DFFR and PFS (P-value = .03 and P-value = .01, respectively). All survival indicators were adversely affected by T-category, while N-category could only predict DFFR and PFS. Radiation dosage represented as a second prognostic factor for local control. We propose that IC combined with IMRT and AC for locoregionally advanced NPC shows effective treatment outcomes.     

Prognostic Value of Plasma Epstein–Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era

This study aimed to evaluate the prognostic value of plasma Epstein–Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level <4000 copies/mL, patients with an EBV DNA ≥4000 copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68–84]) versus (93%, 95% CI [90–96], P < 0.001), DMFS (83%, 95% CI [76–89]) versus (97%, 95% CI [94–99], P < 0.001), and OS (85%, 95% CI [78–92]) versus (98%, 95% CI [95–100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80–6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036–3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647–14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701–8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252–5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.     

The efficacy and safety of gemcitabine-based induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A meta-analysis

Objectives:To assess the efficacy and toxicity of gemcitabine-based induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC).Methods:Both observational studies (OBS) and randomized controlled trials (RCT) were included in the meta-analysis. Systematic online searches were conducted in Web of Sciences, PubMed, Embase, meeting proceedings and ClinicalTrials.gov from the inception to May 25, 2020. The primary endpoint of interest was overall survival.Results:five OBSs and 2 RCTs including 1680 patients were incorporated in the analysis. The evidence from the RCTs showed that adding gemcitabine-based induction chemotherapy to CCRT significantly improved progression free survival (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.40–0.88; P = .010; chi square P = .25; I² = 24%) and overall survival (HR: 0.47; 95% CI: 0.28–0.80; P = 0.005; chi square P = .49, I² = 0%) and was related to a higher risk of hematological toxicities. Furthermore, based on the data of OBSs, overall survival (HR: 0.52; 95% CI: 0.31–0.88; P = .02; chi square P = .37, I² = 6%) was significantly improved in patients treated with gemcitabine-based induction chemotherapy compared to those treated with taxane-based induction chemotherapy. However, the progression free survival (HR: 0.67; 95% CI: 0.45–1.01; P = .06; chi square P = .74; I² = 0%) showed no significant difference.Conclusions:For LA-NPC patients, adding gemcitabine-based induction chemotherapy to CCRT significantly improved overall survival and progression free survival with a higher risk of hematological toxicities when compared to CCRT alone. Also, gemcitabine-based regimen could be used as an alternative induction chemotherapy regimen to taxane-based regimen in the treatment of LA-NPC.     

Prognostic impact of eosinophils in peripheral blood and tumor site in patients with esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy

To date, no effective biological markers have been identified for predicting the prognosis of esophageal cancer patients. Recent studies have shown that eosinophils are independent prognostic factors in some cancers. This study aimed to identify the prognostic impact of eosinophils in esophageal squamous cell carcinoma patients treated with concurrent chemoradiotherapy (CCRT).This study enrolled 136 patients who received CCRT for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). We evaluated the survival time and clinical pathological characteristics of eosinophils. The Kaplan–Meier method was used to estimate survival data. The log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used to conduct a multivariate analysis.Kaplan–Meier analysis revealed that high eosinophil infiltration correlated with better overall survival (OS) (P = .008) and better progression-free survival (PFS) (P = .015). The increase in absolute eosinophil count after CCRT also enhanced OS (P = .005) and PFS (P = .007). The PFS and OS in patients with high blood eosinophil count before CCRT (>2%) was better than those with low blood eosinophil count(<2%) (P = .006 and P = .001, respectively). Additionally, the multivariate analysis revealed that disease stage and high eosinophil infiltration, increased peripheral blood absolute eosinophil count after CCRT, and high peripheral blood eosinophil count before CCRT were independent prognostic indicators.High eosinophil count of tumor site, increased peripheral blood absolute eosinophil count after CCRT, and high peripheral blood eosinophil count before CCRT are favorable prognostic factors for patients with ESCC treated with CCRT.     

Intensity-modulated radiotherapy with more than 60 Gy improved the survival of inoperable patients with locally advanced esophageal squamous cell carcinoma: A population-based real-world study

Intensity-modulated radiotherapy (IMRT) is widely applied during the treatment of esophageal squamous cell carcinoma (ESCC), but the optimal radiation dose still lacks a consensus. The aim of this study was to explore the optimal radiation dose for inoperable locally advanced ESCC patients treated with IMRT in a real-world clinical setting.A total of 90 inoperable ESCC patients with locally advanced stages of II-IVA treated with IMRT in our institute between February 1, 2014 and June 30, 2019 were included in this retrospective study. Sixty patients had received >60 Gy (high dose group) and 30 patients had received ≤60 Gy (low dose group). The median radiation dose was 66 Gy (range: 61–70 Gy) and 50.2 Gy (range: 40–60 Gy), respectively. Concurrent chemotherapies were platinum-based regimens.The median progression free survival (PFS) and overall survival (OS) of all patients were 7.6 and 14.1 months, respectively. Patients in the high dose group exhibited a significantly better PFS (1-year PFS 34.6% vs 22.8%; 2-year PFS 11.9% vs 0%, P = .008) and OS (1-year OS 57.5% vs 39.5%; 2-year OS 31.4% vs 15.8%, P = .007). The median PFS in the high and low dose groups were 8.1 and 6.1 months, and the median OS were 15.4 and 8.5 months, respectively. Multivariate Cox analysis showed that radiation dose (>60 Gy vs ≤60 Gy) was independently prognostic factor for OS (HR: 0.44; 95% CI: 0.22–0.89; P = .021), but not for PFS (HR: 0.56; 95% CI: 0.31–1.02; P = .058). There was no significant difference in treatment-related toxicities of grade ≥3 between the 2 groups (P = .402).This retrospective study confirmed that higher radiation dose (>60 Gy) resulted in better survival outcomes for inoperable patients with locally advanced ESCC treated with IMRT.     

Prognostic Value and Grading of MRI-Based T Category in Patients With Nasopharyngeal Carcinoma Without Lymph Node Metastasis Undergoing Intensity-Modulated Radiation Therapy

We investigated the prognostic value and gradation of the T category in N0 nasopharyngeal carcinoma (NPC) patients undergoing magnetic resonance imaging (MRI) and intensity-modulated radiotherapy (IMRT).A total of 749 patients were retrospectively reviewed, and a total of 181 N0 NPC patients were included in this retrospective study. All patients were restaged according to the 7th edition of the American Joint Committee on Cancer staging system. The following endpoints were estimated: overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS).The 5-year survival rates for T1 to T4 were: OS (97.3%, 100.0%, 86.1%, and 82.8%; P = 0.007), PFS (94.6%, 96.9%, 76.5%, and 76.7%; P = 0.002), LRFS (98.5%, 100.0%, 92.2%, and 86.7%; P < 0.001), and DMFS (97.3%, 96.9%, 85.5%, and 85.7%; P = 0.042), respectively. Pairwise comparisons showed that the OS, PFS, and LRFS rates were significantly poorer in the advanced T categories (T3 and T4) than the early ones (T1 and T2), and no significant differences between T1 and T2, and T3 and T4 were found. In Cox''s proportional hazard analysis, T category was found to be an independent prognostic factor only for PFS (P = 0.003). According to the primary tumor extent, we then graded all 181 N0 patients into 3 groups: group 1, early T category (n = 107); group 2, low-risk advanced T category (n = 35); and group 3, high-risk advanced T category (n = 39). The 5-year survival rates for the 3 groups were: OS (98.1%, 94.1%, and 76.3%; P < 0.001), PFS (95.3%, 88.2%, and 66.2%; P < 0.001), LRFS (99.0%, 97.0%, and 83.4%; P < 0.001), and DMFS (97.2%, 91.1%, and 80.4%; P = 0.002). The 5-year OS, PFS, and LRFS rates of group 3 differed significantly from those of groups 1 and 2, and a significant difference was observed in the DMFS rate only between groups 3 and 1. In Cox''s proportional hazard analysis, the 3-grade T category was an independent prognostic factor for OS (P = 0.002), PFS (P < 0.001), and LRFS (P = 0.002).The 3-grade T category, using MRI according to the site of invasion, has prognostic value for the outcome of IMRT treatment in N0 NPC, and could aid in developing individualized treatment strategies.     

Comparing Treatment Plan in All Locations of Esophageal Cancer: Volumetric Modulated Arc Therapy versus Intensity-Modulated Radiotherapy

The aim of this study was to compare treatment plans of volumetric modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) for all esophageal cancer (EC) tumor locations.This retrospective study from July 2009 to June 2014 included 20 patients with EC who received definitive concurrent chemoradiotherapy with radiation doses >50.4 Gy. Version 9.2 of Pinnacle³ with SmartArc was used for treatment planning. Dosimetric quality was evaluated based on doses to several organs at risk, including the spinal cord, heart, and lung, over the same coverage of gross tumor volume.In upper thoracic EC, the IMRT treatment plan had a lower lung mean dose (P = 0.0126) and lung V5 (P = 0.0037) compared with VMAT; both techniques had similar coverage of the planning target volumes (PTVs) (P = 0.3575). In middle thoracic EC, a lower lung mean dose (P = 0.0010) and V5 (P = 0.0145), but higher lung V20 (P = 0.0034), spinal cord Dmax (P = 0.0262), and heart mean dose (P = 0.0054), were observed for IMRT compared with VMAT; IMRT provided better PTV coverage. Patients with lower thoracic ECs had a lower lung mean dose (P = 0.0469) and V5 (P = 0.0039), but higher spinal cord Dmax (P = 0.0301) and heart mean dose (P = 0.0020), with IMRT compared with VMAT. PTV coverage was similar (P = 0.0858) for the 2 techniques.IMRT provided a lower mean dose and lung V5 in upper thoracic EC compared with VMAT, but exhibited different advantages and disadvantages in patients with middle or lower thoracic ECs. Thus, choosing different techniques for different EC locations is warranted.     

Estimating Cardiac Substructures Exposure From Diverse Radiotherapy Techniques in Treating Left-Sided Breast Cancer

The study compares the physical and biologically effective doses (BED) received by the heart and cardiac substructures using three-dimensional conformal RT (3D-CRT), intensity-modulated radiotherapy (IMRT), and simple IMRT (s-IMRT) in postoperative radiotherapy for patients with left-sided breast cancer.From October 2008 to February 2009, 14 patients with histologically confirmed left-sided breast cancer were enrolled and underwent contrast-enhanced computed tomography (CT) simulation and 18F-FDG positron emission tomography-CT to outline the left cardiac ventricle (LV) and other substructures. The linear-quadratic model was used to convert the physical doses received by critical points of inner heart to BED.The maximal dose, minimum dose, dose received by 99% of volume (D₉₉) and dose received by 95% of volume (D₉₅) in target areas were significantly better using IMRT and s-IMRT when compared with 3D-CRT (P < 0.05). IMRT and s-IMRT significantly reduced the maximal cardiac dose (5038.98 vs 5346.47 cGy, P = 0.002; 5146.66 vs 5346.47 cGy, P = 0.03). IMRT reduced the maximal dose to LV by 4% (P = 0.05) in comparison with 3D-CRT. The average doses to heart and LV in 3D-CRT plan were significantly lower than those in IMRT plan (P < 0.05). The average cardiac volumes receiving ≥25 Gy (V_25 Gy) in IMRT, s-IMRT, and 3D-CRT plans were 73.98, 76.75, and 60.34 cm³, respectively. The average LV volumes receiving ≥25 Gy (V_25 Gy) in IMRT, s-IMRT and 3D-CRT plans were 23.37, 24.68, and 17.61 cm³, respectively. In the IMRT plan, the mean BED to the critical points of inner heart located within the high physical dose area were substantially lower than in 3D-CRT or s-IMRT.Compared with 3D-CRT technique, IMRT and s-IMRT had superior target dose coverage and dose uniformity. IMRT significantly reduced the maximal RT dose to heart and LV. IMRT and s-IMRT techniques did not reduce the volume of heart and LV receiving high doses.     

The Prognosis of Nasopharyngeal Carcinoma Involving Masticatory Muscles: A Retrospective Analysis for Revising T Subclassifications

This work is a retrospective study of magnetic resonance imaging (MRI) and T-stage subclassifications of nasopharyngeal carcinoma (NPC) involving the masticatory muscles (MMs). We examined how involvement of MMs influences the clinical T-stage classifications and the survival outcomes of NPC patients.MRI data as well as the medical records from 816 NPC patients were analyzed retrospectively. All cases were restaged according to the seventh edition of American Joint Committee on Cancer staging system criteria. The overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed by the Kaplan–Meier method, and their survival outcomes between different degrees of MM involvement and different T classifications were compared by using the log-rank test. All statistical analyses were conducted on SPSS 18.0 software. P > 0.05 was considered significant.Of the 816 NPC patients analyzed, 283 (34.68%) had tumors that involved MMs. All of those 283 patients involved the medial pterygoid muscle, and 125 cases (15.32%) involved the lateral pterygoid muscle. Multivariate analysis identified MM involvement as an independent prognostic factor for patient''s OS (P = 0.007) and LRFS (P = 0.024). MM involvement significantly correlated with a lower OS and LRFS (P < 0.01). In addition, compared with concurrent involvement of the medial and lateral pterygoid muscle, the medial pterygoid muscle involvement correlated with a higher OS and LRFS (P < 0.05). Among NPC patients, T-classifications 1 to 4 usually predicted the ultimate OS, LRFS, and DMFS (P > 0.1), unless the cancer involved the lateral pterygoid muscle.NPC involving the lateral pterygoid muscle presents a worse survival outcome than that involving the medial pterygoid muscle. Any cancer involving the lateral pterygoid muscle should be classified in a higher T-stage subclassification.     

Definite intensity-modulated radiotherapy with concurrent chemotherapy more than 4 cycles improved survival for patients with locally-advanced or inoperable esophageal squamous cell carcinoma

We investigated which prognostic factor could improve survival for esophageal cancer patients who received definite concurrent chemoradiation (CCRT). Eighty patients with age ≥18, Karnofsky Performance Scale (KPS) ≥ 60, and clinical stage T1-4N0-3M0 esophageal squamous cell carcinoma were enrolled from July 2004 to December 2015. They underwent definite intensity-modulated radiotherapy (IMRT) with or without simultaneous integrated boost to the primary tumor, and reception of concurrent chemotherapy ≥ 1 cycle. The primary endpoints were overall survival (OS), locoregional progression-free survival (LRPFS) and distant metastasis-free survival (DMFS). The median follow-up duration for alive patients was 21.5 months. The rates of 2-, 3- and 5-year OS/LRPFS/DMFS were 23.8%/53.5%/49.3%, 19.1%/44.6%/49.3%, and 13.0%/44.6%/43.9%, respectively. Only the non-clinical complete response (non-cCR) after CCRT was an independent poor prognostic factor in OS (HR 3.101, 95% CI 1.535–6.265, p = 0.0016). Radiation dose >50.4 Gy and chemotherapy ≥4 cycles significantly predicted better LRPFS (p = 0.0361 and 0.0163, respectively). Poorly differentiated tumor and stage III disease have poor DMFS (p = 0.0336 and 0.0411, respectively), and chemotherapy ≥ 4 cycles was a better predictor (p = 0.0004). In subgroup analysis, patients who received radiation dose ≤50.4 Gy with concurrent chemotherapy ≥4 cycles had the best survival outcome with 1-, 2-, 3- and 5-year survival rates of 73.7%, 39.4%, 31.5% and 17.5%, respectively. In conclusion, definite radiotherapy with concurrent chemotherapy ≥4 cycles improved the survival for patients with inoperable or locally-advanced esophageal squamous cell carcinoma.     

Plasma Epstein–Barr Viral Deoxyribonucleic Acid Predicts Worse Outcomes in Pediatric Nonmetastatic Nasopharyngeal Carcinoma Patients: An Observational Study of 89 Cases in an Endemic Area

To evaluate the clinical significance of pretreatment levels of plasma Epstein–Barr virus DNA (pEBV DNA) on prognoses in pediatric nasopharyngeal carcinoma (NPC) patients.Eighty-nine patients aged 21 years old or younger with nonmetastatic NPC were evaluated to determine the effect of pEBV DNA levels on progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS). Survival probabilities in patient groups that were segregated by clinical stage or pEBV DNA load (low or high) were compared.The median pretreatment concentrations of pEBV DNA were 3440 copies/mL in 35 patients with stage III disease and 14,900 copies/mL in 50 patients with stage IV disease (P = 0.059). The median concentration of pEBV DNA was 34,500 copies/mL in 17 patients with relapse, which was higher than the concentration in 72 patients without relapse, who had a median level of 4985 copies/mL (P = 0.057). Further study showed that pretreatment pEBV DNA load was an independent prognostic indicator in pediatric NPC patients. High pEBV DNA was associated with adverse clinical outcomes, including PFS [3-year PFS rate = 80.5% versus 95.8%, hazard ratio (HR) = 5.00, 95% confidence interval (CI) = 1.00–25.00; P = 0.050], DMFS (3-year DMFS rate = 80.5% versus 95.8%, HR = 5.20, 95% CI = 1.04–26.00; P = 0.045), and OS (3-year OS rate = 82.9% versus 95.8%, HR = 5.41, 95% CI = 1.08–27.22; P = 0.040).Pretreatment pEBV DNA load was an independent prognostic indicator for PFS, DMFS, and OS in pediatric patients with NPC. Prospective studies, however, are needed to validate these results.     

Combined radiotherapy and chemotherapy versus radiotherapy alone in elderly patients with nasopharyngeal carcinoma: A SEER population-based study

Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.Clinical data on 529 NPC patients aged 65 years and older extracted from the Surveillance, Epidemiology, and End Results registry (2004–2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan–Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, P = .002), while no significant difference was observed in CSS (61.8% vs 51.7%, P = .074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.Among NPC patients aged 65 years and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.     

Pretreatment Serum Lactate Dehydrogenase and N Classification Predict Long-Term Survival and Distant Metastasis in Patients With Nasopharyngeal Carcinoma Who Have A Positive Family History of Cancer

The purpose of the present study was to evaluate prognostic factors in patients with nasopharyngeal carcinoma (NPC) from the endemic area of southern China who have a positive family history (FH) of cancer.Retrospective analysis of 600 patients with nondisseminated NPC and a positive FH was conducted. The prognostic value of different factors for overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and local relapse-free survival (LRFS) were assessed using Cox regression models.The 3-year OS, DMFS, DFS, and LRFS rates were 93.8%, 91.3%, 86.3%, and 93.8%, respectively. The FH tumor type was NPC for 226/600 (37.7%) patients and other cancers for 374/600 (62.3%) patients. The 3-year OS and DMFS rates for patients with an FH of NPC were 91.2% and 89.8%, respectively. Thirty of 600 (5.0%) patients had elevated pretreatment serum lactate dehydrogenase (LDH >245.0 IU/L). In multivariate analysis, N classification (HR 4.56, 95% CI 2.13–9.74, P < 0.0001) and elevated pretreatment serum LDH (HR 2.87, 95% CI 1.08–7.62, P = 0.034) were independent prognosticators for OS. Female patients (HR 0.42, 95% CI 0.19–0.95, P = 0.037) and patients with normal pretreatment serum LDH (HR 2.42, 95% CI 1.02–5.78, P = 0.046) had better DMFS.Elevated pretreatment serum LDH and N classification are independent prognostic factors for poorer survival in patients with NPC who have a positive FH of cancer.     

Long term complications and prognostic factors in locally advanced nasopharyngeal carcinoma treated with docetaxel,cisplatin, 5-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy: A retrospective cohort study

This study was conducted to evaluate the long term complications and their risk factors including of survival outcomes in patients with locally advanced nasopharyngeal cancer (NPC) treated with docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CCRT).Among the patients who were diagnosed as NPC, we consecutively evaluated the late complications in 104 patients who completed 3 cycles of TPF induction chemotherapy followed by CCRT and received regular follow-up by otolaryngologist and oncologist. The prognostic factors for overall survival, relapse free survival and each complication were analyzed based on clinical characteristics.Over a median follow-up of 54 months (range, 7.9–152.9 months), 5-year overall survival rate was 87% for stage II, 89% for stage III, 87% for stage IV patients. The significant prognostic factor for survival is complete response rate after CCRT in multivariate analysis. The most frequent toxicity was ear complication (29.8%) including of hearing loss requiring hearing aid (6.7%) and bone necrosis (3.8%). Decreased renal function over grade 2 was occurred in only 4 patients (3.8%) regardless of the cumulative dose of cisplatin. The long term complications did not affect the survival outcome. Patients who received radiation therapy more than 5400 cGy had better survival outcome than those who did not. However, ear complication was significantly related to radiation dose (≥ 6,600 cGy) and type of radiation therapy (conventional). Age over 65 years was a significant risk factor for both ear and renal toxicity. In conclusion, close follow-up to monitor long-term complications should be performed in patients treated with TPF induction chemotherapy followed by CCRT treatment, especially in elderly patients. Reestablishing the optimal chemotherapeutic agent during CCRT and adjustment of radiation dose after induction chemotherapy could be helpful to reduce the toxicity associated with the subsequent treatment strategy for locally advance NPC patients.     

Intensity-modulated radiation therapy (IMRT)-based concurrent chemoradiotherapy (CCRT) with Endostar in patients with pelvic locoregional recurrence of cervical cancer: Results from a hospital in the Qinghai-Tibet Plateau

The treatment of recurrent cervical cancer, especially pelvic locoregional recurrence, is very challenging for gynecologic oncologists. This study investigated the efficacy and safety of intensity-modulated radiation therapy (IMRT)-based concurrent chemoradiotherapy (CCRT) with Endostar, a novel modified recombinant human endostatin, in patients with pelvic locoregional recurrence of cervical cancer following surgical treatment.This phase 2 study was conducted between May 2018 and May 2019 at a single center in the Qinghai-Tibet Plateau and enrolled 31 patients with pelvic locoregional recurrence of cervical cancer following surgical treatment. All patients were treated with IMRT-based CCRT for 6 weeks and intravenous infusions of Endostar (15 mg/m²), which were administered on days 1 to 7 of CCRT, followed by rest for 4 weeks. After resting, chemotherapy with cisplatin (70 mg/m²) plus paclitaxel (135–175 mg/m²) was given every 3 weeks for a total of 4 treatments.Thirty-one patients were evaluable for the primary endpoint. The mean age was 50.03 years (SD 7.72). The objective response rate was 67.74% and the disease control rate was 83.87% (48.39% achieved a complete response, 19.35% a partial response, 16.13% had disease stabilization, and 16.13% had progressive disease). The most common adverse events were nausea, vomiting, alopecia, neutropenia, and leukopenia; most events were grade 1 or 2 in intensity. Grade 3 toxicities included thrombocytopenia and neutropenia in 2 patients each, and leukopenia in 4 patients. No cases of grade 4 acute toxicity were observed.IMRT-based CCRT with Endostar infusions is effective and safe. Our results support the use of this treatment for patients with pelvic locoregional recurrence of cervical cancer following surgical treatment.     

The Value of Palliative Gastrectomy for Gastric Cancer Patients With Intraoperatively Proven Peritoneal Seeding

The aim of this study was to evaluate the survival benefit of palliative gastrectomy for gastric cancer patients with peritoneal seeding proven intraoperatively and to identify positive predictive factors for improving survival.The value of palliative resection for gastric cancer patients with peritoneal metastasis is controversial.From 2006 to 2013, 267 gastric cancer patients with intraoperatively identified peritoneal dissemination were retrospectively analyzed. Patients were divided into resection group and nonresection group according to whether a palliative gastrectomy was performed. Clinicopathologic variables and survival were compared. Subgroup analyses stratified by clinicopathologic factors and multivariable analysis for overall survival were also performed.There were 114 patients in the resection group and 153 in nonresection group. The morbidities in the resection and nonresection groups were 14.91% and 5.88%, respectively (P = 0.014). There, however, was no difference in mortality between the 2 groups. The median survival time of patients in the resection group was longer than in nonresection group (14.00 versus 8.57 months, P = 0.000). The median survivals among the patients with different classifications of peritoneal metastasis were statistically significant (P = 0.000). Patients undergoing resection followed by chemotherapy had a significantly longer median survival, compared with that of patients who had chemotherapy alone, those who had resection alone, or those who had not received chemotherapy or resection (P = 0.000). Results of subgroup analyses showed that except for P3 patients and patients with multisite distant metastases, overall survival was significantly better in patients with palliative gastrectomy, compared with the nonresection group. In multivariate analysis, P3 disease (P = 0.000), absence of resection (P = 0.000), and lack of chemotherapy (P = 0.000) were identified as independently associated with poor survival.Palliative gastrectomy might be beneficial to the survival of gastric cancer patients with intraoperatively proven P1/P2 alone, rather than P3. Postoperative palliative chemotherapy could improve survival regardless of operation and should be recommended.     

Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer: A meta-analysis

Objectives:This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC).Materials and methods:Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3.Results:Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and NK cells was significantly increased after 1 to 2 weeks of treatment with CIK/DC-CIK cells in the treatment group (all P < .05). In addition, the results shown that 1-year overall survival was significantly prolonged (P < .0001) and quality of life was improved (P = .001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (P = .0003) as well as the levels of immunoglobulins were elevated (P < .00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (P < .00001). No fatal adverse reactions were noted (P = .04).Conclusions:It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC.     

Combination of White Blood Cell Count at Presentation With Molecular Response at 3 Months Better Predicts Deep Molecular Responses to Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients

The aim of this study was to evaluate the impact of white blood cell (WBC) counts at presentation on the achievement of deep molecular response.A total of 362 newly diagnosed chronic-phase chronic myeloid leukemia patients (CML-CP) receiving 400 mg/day imatinib were serially monitored for a median of 36 months (range 6–115).Patients showing an optimal response at 3, 6, and 12 months as defined by the 2013 European LeukemiaNet recommendations had significantly lower WBC counts at presentation than those showing nonoptimal responses (all P < 0.0001). Among the cutoff values with a similar Youden index, 150 × 10E9/L (abbreviated WBC > 150) was selected to identify the greatest amount of patients with the potential to achieve a sustained molecular response of 4.5 (MR4.5). Regardless of whether the Sokal risk score was included, the BCR-ABL^IS value at 3 months, WBC counts at presentation, hemoglobin levels, and sex were the common independent predictors for an MR4.5, with the former 2 presenting the highest hazard risk. Low Sokal risk scores did not independently predict the achievement of an MR4.5. Patients with concurrent WBC > 150 and BCR-ABL^IS ≤ 10% had a similar incidence of 4-year MR4.5 compared with patients with concurrent WBC ≤ 150 and BCR-ABL^IS > 10% and concurrent WBC > 150 and BCR-ABL^IS > 10% (13.5% vs 13.2% vs 8.8%, P = 0.47), and all of these values were significantly lower than the values for patients with concurrent WBC ≤ 150 and BCR-ABL^IS ≤ 10% (55.0%, all P < 0.0001). Patients with concurrent WBC ≤ 150 and BCR-ABL^IS ≤ 10% had better 4-year event-free survival rates, progression-free survival rates, and overall survival rates compared with patients with WBC > 150 or BCR-ABL^IS > 10%.The combination of WBC count at presentation and BCR-ABL^IS at 3 months provides improved predictions of deep molecular response in imatinib-treated CML-CP patients. Therefore, the WBC count at presentation might be used to differentiate patients at the beginning of imatinib treatment.     

Experience with combination of cetuximab plus intensity-modulated radiotherapy with or without chemotherapy for locoregionally advanced nasopharyngeal carcinoma

Purpose

To evaluate the safety and efficacy of cetuximab plus intensity-modulated radiotherapy (IMRT) with or without chemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods

From June 2007 to December 2010, 33 patients with stage II (12 %), III (33 %), IVA (33 %), and IVB (21 %) NPC were treated at our hospital. Cetuximab was administered at an initial dose of 400 mg/m² followed by weekly doses of 250 mg/m². All patients completed IMRT, and a total dose of 66–70.4, 66, 60, and 54 Gy were given to the gross tumor volume, positive neck nodes, high-risk clinical target volume, and low-risk clinical target volume, respectively. Most patients (90.9 %) received platinum-based neoadjuvant, concurrent, or adjuvant chemotherapy. The efficacy and safety were evaluated retrospectively.

Results

With a median follow-up of 40.0 months, the 3-year progression-free survival (PFS), distant metastasis-free survival, and overall survival were 70.5 % (95 % CI 54.0–87.0 %), 83.6 % (95 % CI 70.3–96.9 %), and 90.9 % (95 % CI 81.1–100.0 %), respectively. Majority (75.8 %) of patients received ≥7 cycles of cetuximab (median 7 cycles, range 2–14 cycles). Patients who received ≥7 cycles of cetuximab showed a better 3-year PFS than those receiving <7 cycles (79.1 vs. 31.2 %, p = 0.050). During cetuximab + IMRT, stomatitis was the most common acute treatment toxicity, 23 (69.7 %) and 5 (15.2 %) patients with grade 3 and grade 4 stomatitis, respectively. Temporal lobe necrosis was observed in 7 patients.

Conclusions

Cetuximab plus IMRT with or without chemotherapy for locoregionally advanced NPC is effective and tolerated. Further investigations are warranted.