Independent Prognostic Factor For Progression-free Survival Research Articles

Effect of the Number of Removed Lymph Nodes on Survival in Patients with FIGO Stage IB-IIA Cervical Squamous Cell Carcinoma following Open Radical Hysterectomy with Pelvic Lymphadenectomy: A Retrospective Cohort Study.

Objective To determine whether the number of removed lymph nodes (RLN) is associated with survival in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIA cervical squamous cell carcinoma (CSCC). Methods We reviewed the medical records of FIGO stage IB-IIA CSCC patients who underwent standardized radical hysterectomy with pelvic lymphadenectomy (RHPL) in our center between 2006 and 2014. The X-tile software was performed to calculate the optimal grouping of cutoff points for RLN. The impact of RLN on progression-free survival (PFS) and overall survival (OS) was analyzed using Cox regression analysis. Results Among 3,127 patients, the mean number of RLN was 22, and positive lymph node (LN) was found in 668 (21.4%) patients. X-tile plots identified “21” and “16” as the optimal cutoff value of RLN to divide the patients into two groups in terms of PFS and OS separately. In all patients, the number of RLN was not associated with PFS (P=0.182) or OS (P=0.193). Moreover, in both LN positive and negative patients, the number of RLN was not associated with either PFS (P=0.212 and P=0.540, respectively) or OS (P=0.173 and P=0.497, respectively). Cox regression analysis showed that the number of RLN was not an independent prognostic factor for PFS or OS. Conclusion If standardized RHPL was performed, the number of RLN was not an independent prognostic factor for survival of patients with FIGO stage IB-IIA CSCC.

Intracranial 131I-chTNT Brachytherapy in Patients with Deep-Seated Glioma: A Single-center Experience with 10-Year Follow-up fromChina.

The intracranial brachytherapy has been applied for decades, however, no results with long-term follow-up have been reported. This study investigated the long-term efficiency of intra-tumoral injection of 131I-chTNT in patients with deep-seated glioma. Thirty-five patients undergoing 131I-chTNT brachytherapy between December 2004 and May 2009 were enrolled. 131I-chTNT was injected at a dose of 1.5 mCi/cm3 at an interval of 1 month for consecutive 3 times. Serial ECT scan and MRI were performed during follow-up. Progression-free survival (PFS) and overall survival (OS) were analyzed. Adverse reactions were graded with WHO Toxicity Grading Scale for determining the severity of adverse events. ECT scan showed that enhanced accumulation of radioactive agents in the tumor lasted for more than 30 days. Three months after final injection, tumor complete remission (CR) was observed in 4 patients (11.4 %), partial remission (PR) in 11 cases (31.4 %), stable disease (SD) in 10 cases (28.6 %) and progressive disease (PD) in 10 cases (28.6 %). At 6-month, CR, PR, SD and PD were 2, 6, 12 and 15 respectively. After 10 years of follow-up, median progression-free survival (PFS) and overall survival (OS) were 5.4 and 11.4 months. One-year survival was 45.7 %, two and five-year survival was 8.6 %, ten-year survival was 5.7 %. Multivariate analysis showed that pathological grade and tumor diameter were independent prognostic factors for PFS and OS. Grade I-II adverse events occurred after drug injection, including nausea, fever, headache, hairloss and fatigue. 131I-chTNT intracranial brachytherapy is efficient and safe for patients with deep-seated glioma. It is a reliable option for inoperable glioma patients.

Choosing the right timing for interval debulking surgery and perioperative chemotherapy may improve the prognosis of advanced epithelial ovarian cancer: a retrospective study

BackgroundPrimary debulking surgery (PDS) is the main treatment for patients with advanced ovarian cancer, and neoadjuvant chemotherapy (NACT) is for bulky stage III-IV patients who are poor surgical candidates and/or for whom there is a low likelihood of optimal cytoreduction. NACT can increase the rate of complete cytoreduction, but this advantage has not translated to an improvement in survival. Therefore, we aimed to identify factors associated with the survival of patients who received NACT followed by interval debulking surgery (IDS).MethodsA retrospective study was conducted in FIGO stage IIIC-IV epithelial ovarian cancer patients who underwent PDS or IDS in our center between January 1st, 2013, and December 31st, 2018.ResultsA total of 273 cases were included, of whom 20 were lost to follow-up. Progression-free survival (PFS) and overall survival (OS) of the IDS and PDS groups were found to be similar, although the proportion of patients in stage IV and serum carbohydrate antigen 125 (CA125) levels before treatment in the IDS group were significantly higher than that in the PDS group. Body mass index (BMI), CA125 level before IDS, residual disease after surgery, and the interval between preoperative and postoperative chemotherapy were all found to be independent prognostic factors for PFS; FIGO stage, residual disease after surgery, and CA125 level before IDS were independent prognostic factors for OS. We found that PFS and OS were both significantly longer in patients with normal CA125 levels before IDS and when the interval between preoperative and postoperative chemotherapy was < 35.5 days (IDS-3 group) than for patients in the PDS group.ConclusionsThe results suggested the importance of timely IDS and postoperative chemotherapy and potentially allowed the identification of patients who would benefit the most from NACT. Normal CA125 levels before IDS and an interval between preoperative and postoperative chemotherapy no longer than 5 weeks were associated with improved prognosis in advanced ovarian cancer patients.

Prognostic value of pretreatment circulating basophils in patients with glioblastoma.

Accumulating evidence demonstrated that atopic diseases were inversely related to glioma susceptibility and associated with improved prognosis of patients with glioma. This study aimed to elucidate the impacts of basophils, one of the important effector cells in the pathobiology of atopic disease, on prognosis of patients with glioblastoma (GBM). A total of 268 patients were newly diagnosed with GBM and treated with operation at our institution from January 2010 to December 2017. The association between pre-operation circulating eosinophil, basophil, neutrophil, lymphocyte, monocyte count and GBM progression free survival (PFS) was investigated. Moreover, based on the results of multivariate analysis, a prognostic nomogram was established and evaluated. Kaplan-Meier method showed that basophils ≥0.015 × 109/L (p = 0.015) and lymphocytes ≥1.555 × 109/L (p = 0.005) were correlated with better PFS. Cox regression model showed that basophils ≥0.015 × 109/L were an independent prognostic factor for PFS. Prognostic nomogram was established and the concordance index (C-index) for PFS prediction was 0.629. The calibration plots for the probability of 0.5-, 1- and 3-year PFS showed optimal consistency between the prediction by nomogram and actual observation. Increased pre-operation circulating basophils portend better PFS, which might be a useful and novel marker for the prognosis of GBM patients.

The role of opioids in cancer response to immunotherapy

BackgroundThe response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities.MethodsThis observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival.ResultsOne hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37–2.09, p < 0.0001; median OS, 4 months vs. 35 months, HR 1.60, 95% CI 1.26–2.02, p < 0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥ 1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden.DiscussionOur study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well.ConclusionsA possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes.

Combined Ultrasound and CT-Guided Iodine-125 Seeds Implantation for Treatment of Residual Hepatocellular Carcinoma Located at Complex Sites After Transcatheter Arterial Chemoembolization.

PurposeThe purpose of this study was to evaluate the efficacy and safety of iodine-125 (125I) seeds implantation under ultrasound and computed tomography (CT) guidance in the treatment of residual hepatocellular carcinoma (HCC) located at complex sites after transcatheter arterial chemoembolization (TACE).MethodsThis retrospective study analyzed the consecutive medical records of 31 HCC patients with residual tumors located at complex sites (such as large blood vessels, gallbladder, diaphragm dome, etc.) after TACE from May 2014 to December 2018, all of whom received 125I seeds implantation therapy. Overall survival (OS), progression-free survival (PFS), recurrence, and complications were documented.ResultsA total of 607 seeds were implanted in 31 patients, with an average of 19.6±10.4 (range, 8–48) seeds per patient. Median OS and PFS were 33 months (95% CI: 27.1 months, 38.9 months) and 15 months (95% CI: 9.6 months, 20.4 months), respectively. Although univariate analysis showed that albumin, prothrombin time, alpha-fetoprotein level, Child-Pugh score, and lipiodol deposition in tumor were associated with OS, multivariate analysis showed that none of them was an independent prognostic factor for OS. Multivariate analysis showed that prothrombin time was an independent prognostic factor for PFS. No operation-related deaths in this study. Although pneumothorax was present in two patients and subcutaneous abscess in one patient, symptoms improved in all three patients with appropriate treatment. Common minor complications included fever, abdominal pain and leukopenia and no grade≥3 adverse events were observed.Conclusions 125I seeds implantation under the combined guidance of ultrasound and CT is safe and effective for patients with residual HCC located at complex sites after TACE. This is a promising treatment approach and deserves further discussion.

Assessment of the Circulating Tumor Cells and Microsatellite Instability in Colorectal Cancer Patients: Prognostic and Diagnostic Value.

BackgroundMicrosatellite instability (MSI) and circulating tumor cells (CTCs) play important roles in the diagnosis, prognosis and management of colorectal cancer (CRC) patients.MethodsCTCs and MSI were assessed in the blood and representative tumor tissues of 100 CRC patients by flow cytometry (FCM) and PCR amplification. The data were correlated to relevant clinicopathological features of the patients, progression-free survival (PFS) and overall survival (OS) rates.ResultsMSI-high was detected in 44 (44.0%) patients, MSI-low in 37 (37%), and microsatellite stable (MSS) in 19 (19.0%) patients (P=0.007). The baseline CTCs count (<4 cells/7mL blood) was reported in 39% of the patients, and CTCs ≥4 cells/7mL blood in 61% of the patients (P=0.028). Improved PFS and OS rates were associated significantly with MSI-high (P<0.001), decreased CTC levels during the course of treatment (P<0.001) and post-treatment CTCs (P=0.008). There was no significant association between MSI-high and PFS or OS in early-stage patients (P=0.187 and P=0.187; respectively); however, it was associated significantly with better PFS and OS in late-stage patients (P<0.001). Multivariate analysis showed that only a change in serial CTC levels is considered an independent prognostic factor for OS (P<0.012). Post-treatment CTCs level, serial CTCs level changes during the course of treatment, lymph nodes and distant metastasis were independent prognostic factors for PFS (P<0.001, P= 0.047, P=0.001 and P<0.001; respectively).ConclusionMSI and CTCs could be used as accurate, reliable and sensitive diagnostic and prognostic biomarkers for CRC patients’ survival rates and outcomes.

La PET/TC con 18F-FDG en el cáncer de laringe: comparación con técnicas de imagen convencional y valor pronóstico

ObjectiveThe aim of this study was to investigate the diagnostic accuracy of staging 18F-FDG-PET/CT in laryngeal cancer, compare these results with conventional imaging (CI) and assess the value of 18F-FDG-PET/CT features to predict survival. MethodsFifty-four patients with laryngeal squamous cell cancer and baseline 18F-FDG-PET/CT were retrospectively enrolled. The PET images were analyzed visually and semi-quantitatively by measuring several metabolic parameters. A combination of clinical follow-up/imaging follow-up and/or histopathology was taken as reference standard. Progression free survival (PFS) and disease specific survival (DSS) were computed using Kaplan-Meier curves. ResultsAll primary tumors were clearly identified by CI, and 52/54 by 18F-FDG-PET/CT with a sensitivity of 96.3%. Cervical nodal metastases were detected in 40/54 patients at 18F-FDG-PET/CT and in 34/49 patients at CI. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy on a patient-based analysis for nodal disease were 100%, 85.7%, 94.6%, 100% and 95.9% at 18F-FDG-PET/CT, and 91.4%, 85.7%, 94.1%, 80%, 89.8% at CI. Diagnostic performances of PET/CT and CI were not significantly different on a patient-based, side-by-side and level-by-level analysis. 18F-FDG-PET/CT recognized distant metastases in 7 patients allowing to an upstaging. At a median follow-up of 27 months, relapse/progression of disease occurred in 31 patients and death occurred in 32. Metabolic tumor volume (MTV T), MTV total and total lesion glycolysis (TLG) showed to be independent prognostic factors for PFS. ConclusionsBoth CI and PET/CT had good diagnostic performances for the staging of laryngeal cancer; baseline metabolic features (MTV and TLG) showed an important prognostic value in assessing the rate of PFS.

Transarterial chemoembolization (TACE) combined with apatinib versus TACE combined with sorafenib in advanced hepatocellular carcinoma patients: a multicenter retrospective study.

BackgroundThe combination of transarterial chemoembolization (TACE) with sorafenib has demonstrated superior efficacy over sorafenib and TACE monotherapy in hepatocellular carcinoma (HCC). Apatinib, a new targeted agent, has been recently reported to prolong the survival of HCC patients, either alone or in combination with TACE. However, the superior regimen between TACE-apatinib and TACE-sorafenib in HCC patients has not been determined. In this study, we compared the efficacy and safety of TACE-apatinib versus TACE-sorafenib in advanced stage HCC patients.MethodsThe data of 201 HCC patients who had received TACE-sorafenib or TACE-apatinib between January 2016 and June 2018 in three hospitals were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and adverse effects (AEs) between the two treatment groups were compared. A subgroup analysis based on the doses of targeted agents was also performed.ResultsNo significant differences in baseline clinicopathological features were found between the two groups except for dose reduction. The TACE-apatinib group had higher incidences of hypertension, oral or anal ulcer and proteinuria, while the TACE-sorafenib group had higher incidences of diarrhea and alopecia. Grade 3/4 AEs occurred more frequently in the TACE-apatinib group than in the TACE-sorafenib group (52.3% vs. 22.6%, P<0.001). The TACE-sorafenib group had better PFS than the TACE-apatinib group (median PFS: 5.0 vs. 6.0 months, P=0.002) while the two groups showed no difference in OS (median OS: 13.0 vs. 13.0 months, P=0.448). The TACE-apatinib group had a higher rate of targeted agent dose reduction than the TACE-sorafenib group (53.5% vs. 17.4%, P<0.001). When the patients were stratified into normal and reduced-dose subgroups, those who received TACE-sorafenib exhibited improved PFS but similar OS compared with the patients who received TACE-apatinib in the reduced-dose subgroup (median OS: 12.0 vs. 13.3 months, P=0.614; median PFS: 3.0 vs. 7.0 months, P<0.001). Multivariable analysis validated that treatments and dose reduction were independent prognostic factors for PFS among all patients.ConclusionsCompared with TACE-sorafenib, the strategy of TACE-apatinib yielded shorter PFS in advanced HCC patients while no difference in OS was observed. A high rate of AE-related dose reduction of apatinib could account for the observed differences.

The characteristic computed tomography findings of pulmonary B-cell non-Hodgkin's lymphoma and their role in predicting patient survival.

To assess the value of characteristic computed tomography (CT) findings in predicting the survival of patients with pulmonary B-cell non-Hodgkin's lymphoma (NHL). Eighty-four patients who were histopathologically confirmed with pulmonary B-cell NHL between 2004 and 2018 were retrospectively enrolled. All patients underwent chest CT scan at the time of initial diagnosis in our hospital. Characteristic CT findings and clinicopathological features of the patients were analyzed, and Cox regression models were used to determine the relationship of CT findings with overall survival (OS) and progression-free survival (PFS). Air bronchogram occurred more frequently in patients with early-stage disease, primary pulmonary lymphoma (PPL) and the indolent histological type of lymphoma than in patients with advanced-stage disease, secondary pulmonary lymphoma (SPL), and the aggressive histological type (all P<0.05). The halo sign was observed most in the SPL group (19/48, 40%; P=0.004), while the presence of cross-lobe sign was higher in patients with PPL (13/36, 36%; P=0.010). Pleural involvement and hilar/mediastinal lymphadenopathy were observed more in patients with SPL and the aggressive histological type (33/48 and 27/48; 31/46 and 26/46, respectively; all P<0.05). Survival analyses showed that the number of lung lesions, cross-lobe sign, and pleural involvement were independent prognostic factors for PFS, while the halo sign and pleural involvement were significantly correlated with OS (all P<0.05). More aggressive, advanced-stage cases and male patients showed worse outcomes. The halo sign and pleural involvement are independent prognostic factors for OS, while the number of lung lesions, cross-lobe sign, and pleural involvement are correlated with PFS.

Prognostic value of lymphocyte-to-monocyte ratio and histone methyltransferase G9a histone methyltransferase in patients with double expression lymphoma: A retrospective observational study.

In patients with diffuse large B-cell lymphoma, MYC combined with Bcl2 and/or Bcl6-based protein expression is called double expression lymphoma (DEL). R-DA-EPOCH program chemotherapy is typically recommended because these patients often have a poor prognosis. Although numerous factors affect survival of patients with DEL, the roles of the tumor biomarker histone methyltransferase G9a (G9a) and the lymphocyte-to-monocyte ratio (LMR) are unknown.We performed a retrospective analysis of data from 51 patients. These patients were newly diagnosed with DEL and treated with R-DA-EPOCH at Taizhou People’ s Hospital and Northern Jiangsu People's Hospital between June 2014 and December 2019. Receiver operator characteristic curve results were used to calculate the LMR cutoff value. We used an immunohistochemical analysis to examine G9a expression in DEL tissues. The Kaplan–Meier method was used to determine progression-free survival (PFS) and overall survival (OS) characteristics. Cox proportional-hazards models were constructed for univariate and multivariate analyses to examine the prognostic values of LMRs and G9a in patients with DEL.The cutoff value for LMR was 2.18. The 5-year PFS rate was 35.3%, and the 5-year OS rate was 39.2%. Patients with DEL with lower LMRs and who were G9a-positive predicted inferior PFS and OS. Univariate analysis revealed that patients with elevated LDH levels, high National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) scores, LMRs ≤2.18, and G9a-positive results had relatively poorer PFS and OS. The multivariate analysis revealed that LMRs ≤2.18 and a G9a-positive result were independent prognostic factors for PFS and OS in patients with DEL treated with R-DA-EPOCH.The study results suggested that peripheral blood LMRs were an important marker for evaluation of prognosis in patients with DEL. High expression of G9a was associated with worse outcomes, indicating that G9a may serve as a prognostic biomarker for patients with DEL who undergo R-DA-EPOCH program chemotherapy.

Proposed global prognostic score for systemic mastocytosis: a retrospective prognostic modelling study

Several risk stratification models have been proposed in recent years for systemic mastocytosis but have not been directly compared. Here we designed and validated a risk stratification model for progression-free survival (PFS) and overall survival (OS) in systemic mastocytosis on the basis of all currently available prognostic factors, and compared its predictive capacity for patient outcome with that of other risk scores. We did a retrospective prognostic modelling study based on patients diagnosed with systemic mastocytosis between March 1, 1983, and Oct 11, 2019. In a discovery cohort of 422 patients from centres of the Spanish Network on Mastocytosis (REMA), we evaluated previously identified, independent prognostic features for prognostic effect on PFS and OS by multivariable analysis, and designed a global prognostic score for mastocytosis (GPSM) aimed at predicting PFS (GPSM-PFS) and OS (GPSM-OS) by including only those variables that showed independent prognostic value (p<0·05). The GPSM scores were validated in an independent cohort of 853 patients from centres in Europe and the USA, and compared with pre-existing risk models in the total patient series (n=1275), with use of Harrells' concordance index (C-index) as a readout of the ability of each model to risk-stratify patients according to survival outcomes. Our GPSM-PFS and GPSM-OS models were based on unique combinations of independent prognostic factors for PFS (platelet count ≤100 × 109 cells per L, serum β2-microglobulin ≥2·5 μg/mL, and serum baseline tryptase ≥125 μg/L) and OS (haemoglobin ≤110 g/L, serum alkaline phosphatase ≥140 IU/L, and at least one mutation in SRSF2, ASXL1, RUNX1, or DNMT3A). The models showed clear discrimination between low-risk and high-risk patients in terms of worse PFS and OS prognoses in the discovery and validation cohorts, and further discrimination of intermediate-risk patients. The GPSM-PFS score was an accurate predictor of PFS in systemic mastocytosis (C-index 0·90 [95% CI 0·87-0·93], vs values ranging from 0·85 to 0·88 for pre-existing models), particularly in non-advanced systemic mastocytosis (C-index 0·85 [0·76-0·92], within the range for pre-existing models of 0·80 to 0·93). Additionally, the GPSM-OS score was able to accurately predict OS in the entire cohort (C-index 0·92 [0·89-0·94], vs 0·67 to 0·90 for pre-existing models), and showed some capacity to predict OS in advanced systemic mastocytosis (C-index 0·72 [0·66-0·78], vs 0·64 to 0·73 for pre-existing models). All evaluated risk classifications predicted survival outcomes in systemic mastocytosis. The REMA-PFS and GPSM-PFS models for PFS, and the International Prognostic Scoring System for advanced systemic mastocytosis and GPSM-OS model for OS emerged as the most accurate models, indicating that robust prognostication might be prospectively achieved on the basis of biomarkers that are accessible in diagnostic laboratories worldwide. Carlos III Health Institute, European Regional Development Fund, Spanish Association of Mastocytosis and Related Diseases, Rare Diseases Strategy of the Spanish National Health System, Junta of Castile and León, Charles and Ann Johnson Foundation, Stanford Cancer Institute Innovation Fund, Austrian Science Fund.

Diagnostic and prognostic value of heat shock protein 90α in malignant melanoma.

Malignant melanoma is one of the most common tumours of the skin. Heat shock protein 90α (HSP90α) has been applied in the auxiliary diagnosis of various malignancies, as a tumour marker. This study aims to evaluate diagnostic, therapeutic efficacy and prognostic value of plasma HSP90α levels in malignant melanoma. In this study, higher plasma HSP90α levels and abnormal rates were found in malignant melanoma patients than in healthy controls (92.63 vs. 51.84 ng/mL; P < 0.001 and 68.30 vs. 8.30%; P < 0.001). Plasma HSP90α levels were higher with Breslow thickness >4 mm, a high Clark level (IV + V), abnormal serum lactate dehydrogenase (LDH), distant metastases occurrence and Ki-67≥30% (P < 0.05). The area under the curves (AUCs) of HSP90α was greater than LDH in the training (0.847 vs. 0.677) and validation (0.867 vs. 0.672) cohort. Meanwhile, the sensitivity (76.70%) and negative predictive values (78.80%) of HSP90α were higher. Plasma HSP90α levels were significantly reduced in objective response (81.05 vs. 37.26 ng/mL; P = 0.012) and disease control patients (84.16 vs. 47.05 ng/mL; P = 0.002) post-treatment. Patients with normal HSP90α levels had slightly longer progression-free survival (PFS) than those with abnormal levels (8.0 vs. 3.5 months; P = 0.096). Unfortunately, the trend was not statistically significant. In multivariable analysis, immunotherapy was an independent prognostic factor for PFS. Nevertheless, patients with normal HSP90α levels who received chemotherapy(±targeted therapy) without immunotherapy had significantly longer PFS than patients with abnormal levels (6.0 vs. 2.0 months; P = 0.008). Therefore, HSP90α can be used for auxiliary diagnosis and predict the responses to therapy in malignant melanoma patients.

The role of lymphadenectomy in patients with stage III&IV uterine serous carcinoma: Results of multicentric Turkish study

ObjectiveThe aim of this study was to evaluate clinicopathological features, oncological outcome and prognostic factors for recurrence in advanced stage uterine serous carcinoma (USC) patients. MethodsPatients with 2009 International Federation of Gynecology and Obstetrics stage III&IV uterine serous carcinoma were enrolled from 4 gynecologic oncology centers and a study group was created. Response to therapy was evaluated according to the WHO criteria. Progression-free survival (PFS) and overall survival (OS) estimates were determinated by using the Kaplan-Meier method. Survival curves were compared with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. ResultsEntire cohort included 63 patients. Median age of cohort was 64 years. Thirty-five (55.6 %) patients were stage IV. Lymphadenectomy was performed in 57 (90.5 %) patients and lymph node metastasis was positive in 45 (71.4 %) patients. Maximal cytoreduction (no residue tumor) was achieved in 53 (84.1 %) patients. However, optimal cytoreduction (residue tumor ≤1 cm) was achieved in 6 (9.5 %) patients and suboptimal cytoreduction (residue tumor >1 cm) was achieved in 3 (4.8 %) patients. Median follow-up time was 19 (range;1–152) months. Complete clinical response was obtained in 58 (92.1 %) patients after standard adjuvant therapy. Disease failure was detected in 25 patients. Study group had a 2-year PFS of 51 % and 2-year OS of 80 %. On multivariate analysis, performing lymphadenectomy was an independent prognostic factor for PFS (Odds ratio: 24.794, 95 % Confidence Interval: 4.214−145.869; p < 0.001). ConclusionLymphadenectomy should be a part of the standard surgical therapy in advanced stage USC.

Evaluation of diagnostic and predictive values of the serum VEGF-A level and systemic immune-inflammation index in small cell lung cancer.

Purpose: To evaluate diagnostic and predictive values of the serum vascular endothelial growth factor-A (VEGF-A) level and systemic immune-inflammation index (SII) in small cell lung cancer (SCLC) patients.Methods: From January 2018 to April 2020, we prospectively enrolled 59 untreated SCLC patients in the study group and 50 non-neoplastic patients in the control group. Blood samples were collected at baseline, after the first two cycles of chemotherapy and at progression in the study group and at entry in the control group. Serum VEGF-A was measured by chemiluminescence, SII was calculated based on complete blood count results, and the relationship between the VEGF-A/SII and clinicopathological characteristics, chemotherapeutic efficacy and progression-free survival (PFS) of SCLC patients was analyzed.Results: Baseline serum VEGF-A was significantly higher in SCLC patients than in non-neoplastic patients (P<0.001), while baseline SII was not (P=0.114). There was no correlation between baseline VEGF-A and SII in SCLC patients (P=0.123); however, there was a significant correlation between baseline VEGF-A and disease stage and central nervous system (CNS) metastasis (P=0.021 and P=0.012, respectively), as well as between baseline SII and disease stage and liver metastasis (P=0.026 and P=0.018, respectively). Serum VEGF-A was significantly lower than the pretreatment level after 2 cycles of treatment (P=0.049) but was not different at progression (P=0.247). Baseline VEGF-A was correlated with the treatment response of first-line chemotherapy (P=0.001), while baseline SII was not (P=0.392). Kaplan-Meier survival analysis suggested that the PFS of first-line chemotherapy was significantly longer in the low-VEGF-A group at baseline than the high-VEGF-A group (11.37 vs. 6.17 months, P<0.001). There was a trend toward longer PFS of first-line chemotherapy in the low-SII group at baseline than the high-SII group, but the difference was not significant (12.10 vs. 9.10 months, P>0.050). Univariate and multivariate Cox regression analyses suggested that baseline VEGF-A (HR: 3.443, 95% CI: 1.330-8.908, P=0.011) was an independent prognostic factor for PFS in SCLC patients.Conclusions: Baseline serum VEGF-A and SII are associated with important clinicopathological characteristics of SCLC patients. VEGF-A, but not SII, has the ability of diagnosis and predicting first-line chemotherapeutic efficacy and prognosis in SCLC patients.

Value of pretreatment 18F-FDG PET/CT in prognosis and the reflection of tumor burden: a study in pediatric patients with newly diagnosed neuroblastoma.

Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT has been commonly used in pediatric patients with newly diagnosed neuroblastoma (NB) for diagnosis. We retrospectively reviewed 40 pediatric patients with newly diagnosed NB who underwent 18F-FDG PET/CT. Clinicopathological factors and metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were evaluated as predictive factors for progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analysis. Spearman rank correlation analyses were used to estimate the correlations between clinical factors and PET findings. The mean follow-up after 18F-FDG-PET/CT was 32.9 months. During the follow-up period 15 (37.5%) patients experienced progression, and 9 (22.5%) died. MTV (P=0.001) and TLG (p=0.004) remained significant predictive factors for tumor progression, along with lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and bone metastasis. Univariate analysis showed that bone metastasis, LDH (>1064 IU/L), NSE (>364.4 ug/L), MTV (>191 cm3) and TLG (>341.41 g) correlated with PFS, and LDH (>1064 IU/L), NSE (>364.4 ug/L) and MTV (>191 cm3) correlated with OS (p<0.05). In multivariate analysis, MTV and bone metastasis were independent prognostic factors for PFS (p=0.001 and 0.023, respectively), and MTV remained the only independent prognostic factor for OS (p= 0.004). We also found that there were correlations between semiquantitative PET/CT parameters and clinical features in NB. Our results suggested that 18F-FDG PET/CT was a useful tool to predictive progression and to reflect tumor burden for patients with NB.

Negative impact of antibiotic administration on the clinical activity in patients with advanced gastric cancer

Antibiotics (ATBs) induce dysbiosis of the gut microbiota by altering the diversity and composition of the microbiota, which mediates the efficacy and toxicity of cancer therapy. The influence of dysbiosis induced by ATB administration on primary resistance to chemotherapy in patients with advanced gastric cancer (GC) has been rarely studied. We evaluated the effect of ATB administration on chemotherapy efficacy in patients with advanced GC. Patients with GC were divided into two groups according to the status of ATB administration: ATB-treated and control groups. Tumor responses, progression-free survival (PFS) and overall survival (OS) were assessed. We found that the incidence of progressive disease in the ATB-treated group was significantly higher when compared with that in the control group that received no ATB treatment (72.73% vs. 29.55%, p = 0.007). In addition, ATB administration was associated with shorter PFS [median PFS: 1.47 vs. 4.97 months, hazard ratio (HR): 2.296, 95% confidence interval (CI): 1.214 − 4.342, p = 0.011] and reduced OS (median OS: 9.97 vs. 13.3 months, HR: 2.101, 95% CI: 1.030 − 4.286, p = 0.041) based on univariate analysis. Subsequent multivariate analysis also indicated that ATB administration was an independent prognostic factor for PFS (HR: 3.361, 95% CI: 1.592 − 7.097, p = 0.001) and OS (HR: 2.280, 95% CI: 1.042 − 4.991, p = 0.039). ATB administration is associated with reduced chemotherapy efficacy and poor prognosis in patients with advanced GC. Modulations in ATB-related dysbiosis and gut microbiota composition improve the clinical outcomes of chemotherapy. Supplemental data for this article is available online at https://dx.doi.org/10.1080/13102818.2021.1953400 .

Post-transplantation Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography in Patients with Lymphoblastic Lymphoma is an Independent Prognostic Factor with an Impact on Progression-Free Survival but not Overall Survival.

Purpose: In the present study, we mainly aimed to evaluate the prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) positron emission tomography (PET)/computed tomography (CT) after allogeneic stem cell transplantation (allo-SCT) in lymphoblastic lymphoma (LBL) patients using Deauville Scores (DS). Materials and Methods: A total of 63 LBL patients who benefited from 18F-FDG PET-CT after allo-SCT in our institution between April 2010 and August 2020 were enrolled in this retrospective study. These above-mentioned patients were divided into two groups based on the Deauville criteria. Diagnostic efficiency of 18F-FDG PET/CT and integrated CT in detecting lymphoma were calculated. Consistencies were evaluated by comparing 18F-FDG PET/CT and integrated CT results through kappa coefficient. Kaplan-Meier method was used in survival analysis, and the log-rank method was adopted in comparisons. Prognostic factor analysis was performed by the Cox regression model. Results: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy of post-SCT 18F-FDG PET-CT were 100%(12/12), 92.2%(47/51), 75.0%(12/16), 100%(47/47) and 93.7%(59/63). The consistency of 18F-FDG PET-CT and integrated CT was moderate(Kappa = .702，P < .001). Positive post-SCT 18F-FDG PET-CT was associated with lower progression-free survival (PFS) but not overall survival (OS) (p = .000 and p = .056, respectively). The 3-year PFS of the PET-positive group and PET-negative group was 18.8% and 70.2%, respectively. Multivariate analysis showed that post-SCT PET-CT findings was an independent prognostic factor for PFS (p = .000; HR, 3.957; 95%CI, 1.839-8.514). Other factors independently affecting PFS were sex (p = .018; HR, 2.588; 95% CI, 1.181 − 5.670) and lactate dehydrogenase (LDH) (p = .005; HR, 3.246; 95% CI, 1.419 − 7.426). However, none of the above-mentioned factors were associated with OS. Conclusions: Collectively, we found that 18F-FDG PET-CT after allo-SCT was a strong indicator for PFS, but not OS, which might provide important evidence for the selection of subsequent treatment regimen for LBL patients. Trial registration number: ChiCTR2100046709.

Prognostic significance of 8 weeks’ relative dose intensity of lenvatinib in treatment of radioiodine-refractory differentiated thyroid cancer patients

Lenvatinib is a standard therapy for radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, because of the high incidence of adverse events resulting from this treatment, it is not easy to maintain the dose intensity of lenvatinib, especially in Japanese patients. Although the prognostic impact of lenvatinib dose interruption has been reported, the target dose intensity of lenvatinib to optimize survival benefits remains unknown. We therefore propose a target dose intensity of lenvatinib during the first 8 weeks of treatment. We retrospectively analyzed 42 RR-DTC patients who were treated with lenvatinib for more than 8 weeks. We performed receiver operating characteristic curve analysis to determine the cut-off value of 8 weeks' relative dose intensity (8w-RDI) to predict treatment response, and identified that the optimal cut-off value of 8w-RDI was 60% (sensitivity: 81.8%; specificity: 80.6%). Median progression-free survival (PFS) (not reached [NR] vs. 11.0 months; hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.11-0.72; p < 0.01) and overall survival (NR vs. 27.6 months; HR 0.44; 95% CI 0.11-0.91; p = 0.03) were longer in the higher 8w-RDI (≥60%) patients than in the lower 8w-RDI (<60%) patients. Multivariate analysis revealed that 8w-RDI at ≥60% was an independent prognostic factor for PFS (HR 0.29; 95% CI 0.09-0.96; p = 0.04). Targeting for ≥60% of the relative dose intensity during the first 8 weeks of lenvatinib treatment can be sufficient to achieve significant tumor shrinkage and prolong PFS in RR-DTC patients.

Circulating Tumor Cells Correlate With Prognosis in Head and Neck Squamous Cell Carcinoma.

Background:To investigate the relationship of circulating tumor cells (CTCs) and the clinical characteristic parameters and prognosis in patients with head and neck squamous cell carcinoma (HNSCC).Methods:The retrospective clinical study included 95 patients with HNSCC who after surgery in Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine between December 2015 and December 2016. All patients were followed up for survival until the end of June 2019. The CTCs detection was performed by negative enrichment (NE) immunofluorescence-in situ hybridization (im-FISH) of chromosome 8.Results:Patients with higher CTCs counts are associated with a worse prognosis with an area under the receiver operator characteristic (ROC) curve of 0.756 [95% confidence interval (CI) 0.640-0.872, p = 0.001]. The CTCs-positive rate of HNSCC patients was 58.9% (56/95) by using the cut-point of 3. Both the chi-square test and binary logistic regression analysis showed that the N stage and clinical stage were significantly associated with CTCs-positive in patients with HNSCC (p < 0.05). Further Non-parametric test analysis indicated that more CTCs counts were detected in late N and clinical stages patients (p < 0.001). The Kaplan-Meier survival analysis indicated that CTCs-positive were correlated with shorter progression-free survival (PFS) (p < 0.001) and overall survival (OS) (p = 0.001). Further, the CTCs-positive was an independent prognostic factor for PFS and OS according to the Cox multivariate regression analysis (p < 0.05).Conclusion:More CTCs were associated with N stage, clinical stage, poor prognosis in patients with HNSCC, which might be used as a prognostic biomarker.