Prognostic value of prognostic nutritional index and systemic immune-inflammation index in patients with osteosarcoma

The aim of this study was to evaluate the relationship between prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) and clinical features and prognosis of osteosarcoma patients. We retrospectively investigated 126 patients with surgery for osteosarcoma between 2012 and 2018 at our hospital. The preoperative PNI was calculated as albumin level (g/L) + 5 × total lymphocyte count (10 ⁹/L). The SII was defined as platelet × neutrophil/lymphocyte counts. The optimal cut-off values for PNI and SII were evaluated with receiver operating curve analysis. Clinical features and PNI and SII were tested with the χ ² test. The effects of PNI and SII on overall survival (OS) was investigated by Kaplan–Meier method and Cox proportional hazards model. A low preoperative PNI was remarkably correlated with tumor size, Enneking stage, pathological fracture, local recurrence, metastasis, and neoadjuvant chemotherapy ( p < 0.05). Whereas, a high SII was significantly associated with tumor size, histological type, Enneking stage, and neoadjuvant chemotherapy ( p < 0.05). There was a significant negative relationship between the PNI and SII ( r = 0.384; p < 0.001). For univariate analyses, the results revealed that tumor size, local recurrence, metastasis, PNI, and SII were predictors of OS ( p < 0.05). In multivariate analyses, local recurrence ( p = 0.010), metastasis ( p < 0.001), PNI ( p < 0.001), and SII ( p = 0.029) as independent prognostic factors were significantly correlated with OS. This study suggested that PNI and SII could be important prognostic parameters for patients with osteosarcoma.     

Prognostic factors for early relapse in non-metastatic triple negative breast cancer — real world data

BackgroundTriple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse.Materials and methodsSingle-centre retrospective analysis of 127 women with TNBC, stage II–III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse.ResultsAfter 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3–22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2–6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1–1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively).ConclusionsIn this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up.     

Identification of 6 gene markers for survival prediction in osteosarcoma cases based on multi-omics analysis

Multiple-omics sequencing information with high-throughput has laid a solid foundation to identify genes associated with cancer prognostic process. Multiomics information study is capable of revealing the cancer occurring and developing system according to several aspects. Currently, the prognosis of osteosarcoma is still poor, so a genetic marker is needed for predicting the clinically related overall survival result. First, Office of Cancer Genomics (OCG Target) provided RNASeq, copy amount variations information, and clinically related follow-up data. Genes associated with prognostic process and genes exhibiting copy amount difference were screened in the training group, and the mentioned genes were integrated for feature selection with least absolute shrinkage and selection operator (Lasso). Eventually, effective biomarkers received the screening process. Lastly, this study built and demonstrated one gene-associated prognosis mode according to the set of the test and gene expression omnibus validation set; 512 prognosis-related genes (P < 0.01), 336 copies of amplified genes (P < 0.05), and 36 copies of deleted genes (P < 0.05) were obtained, and those genes of the mentioned genomic variants display close associations with tumor occurring and developing mechanisms. This study generated 10 genes for candidates through the integration of genomic variant genes as well as prognosis-related genes. Six typical genes (i.e. MYC, CHIC2, CCDC152, LYL1, GPR142, and MMP27) were obtained by Lasso feature selection and stepwise multivariate regression study, many of which are reported to show a relationship to tumor progressing process. The authors conducted Cox regression study for building 6-gene sign, i.e. one single prognosis-related element, in terms of cases carrying osteosarcoma. In addition, the samples were able to be risk stratified in the training group, test set, and externally validating set. The AUC of five-year survival according to the training group and validation set reached over 0.85, with superior predictive performance as opposed to the existing researches. Here, 6-gene sign was built to be new prognosis-related marking elements for assessing osteosarcoma cases’ surviving state.     

Long-term survival results after treatment for oligometastatic brain disease

AimThe aim of this study was to characterize the survival results of patients with up to four brain metastases after intense local therapy (primary surgery or stereotactic radiotherapy) if extracranial metastases were absent or limited to one site, e.g. the lungs.BackgroundOligometastatic disease has repeatedly been reported to convey a favorable prognosis.Material and methodsThis retrospective study included 198 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status and other variables was collected. Uni- and multivariate tests were performed.ResultsMedian survival was 16.5 months (single brain metastasis) and 9.8 months (2–4, comparable survival for 2, 3 and 4), respectively (p = 0.001). After 5 years, 15 and 2% of the patients were still alive. In patients alive after 2 years, added median survival was 23 months and the probability of being alive 5 years after treatment was 26%. In multivariate analysis, extracranial metastases were not significantly associated with survival, while primary tumor control was.ConclusionLong-term survival beyond 5 years is possible in a minority of patients with oligometastatic brain disease, in particular those with a single brain metastasis. The presence of extracranial metastases to one site should not be regarded a barrier towards maximum brain-directed therapy.     

Innovative approaches for treatment of osteosarcoma

Osteosarcoma (OS) is the most common primary malignant bone tumor, which usually occurs in children and adolescents. It is generally a high-grade malignancy presenting with extreme metastases to the lungs or other bones. The etiology of the disease is multifaceted and still remains obscure. A combination of surgery and chemotherapy has played a major role in the treatment of OS over the past three decades, and consequently, the overall survival rates for the disease have remained unchanged. Therefore, there is an urgent need to employ new comprehensive analyses and technologies to develop significantly more informative classification systems, with the aim of developing more effective and less toxic therapies for OS patients. This review discusses the existing knowledge of OS therapy and potential methods to develop novel therapeutic agents for the disease.     

The LabBM score is an excellent survival prediction tool in patients undergoing palliative radiotherapy

Background and aimThe prognostic assessment of patients referred for palliative radiotherapy can be conducted by site-specific scores. A quick assessment that would cover the whole spectrum could simplify the working day of clinicians who are not specialists for a particular disease site. This study evaluated a promising score, the LabBM (validated for brain metastases), in patients treated for other indications.Materials and methodsThe LabBM score was calculated in 375 patients by assigning 1 point each for C-reactive protein and lactate dehydrogenase above the upper limit of normal, and 0.5 points each for hemoglobin, platelets and albumin below the lower limit of normal. Uni- and multivariate analyses were performed.ResultsMedian overall survival gradually decreased with increasing point sum (range 25.1–1.1 months). When grouped according to the original three-tiered model, excellent discrimination was found. Patients with 0–1 points had a median survival of 15.7 months. Those with 1.5–2 points had a median survival of 5.8 months. Finally, those with 2.5–3.5 points had a median survival of 3.2 months (all p-values ≤ 0.001).ConclusionThe LabBM score, which is derived from inexpensive blood tests and easy to use, stratified patients into three very distinct prognostic groups and deserves further validation.     

Long-term results after microlymphaticovenous anastomoses for the treatment of obstructive lymphedema

Over the last 14 years, 134 patients with obstructive lymphedema have been treated with microlymphaticovenous anastomoses. Ninety patients were available for long-term follow-up study. Of these, 52 patients were treated by microlymphatic surgery only and 38 of them also had segmental or radical reduction surgery, either at the same time or secondarily. Objective assessment was undertaken by volume and circumferential measurements. Initially, lymphangiography was used, but a study demonstrated increased edema immediately following the investigation in one-third of the patients and it was abandoned, both preoperatively and postoperatively. In the microlymphaticovenous anastomoses only group (N = 52), subjective improvement occurred in 38 patients (73 percent). Objectively, volume changes showed a significant improvement in 22 patients (42 percent), with an average reduction of 44 percent of the excess volume. In the microlymphaticovenous anastomoses and reduction surgery, usually segmental, group (N = 38), subjective improvement occurred in 30 patients (78 percent) and objective improvement occurred in 23 patients (60 percent), with an average reduction of 44 percent of the excess volume. Of those followed up, 67 patients (74 percent) have been able to discontinue the use of conservative measures, with an average follow-up of 4.0 years and average reduction in excess volume of 26 percent. There was a 58 percent reduction in the incidence of cellulitis following surgery. In those patients who were improved, drainage resulted in increased softness of the limbs. Edema of the hand diminished considerably in most patients, although this was difficult to measure. These long-term results indicate that microlymphaticovenous anastomoses have a valuable place in the treatment of obstructive lymphedema and should be the treatment of choice in these patients. Reduction surgery can be used as an adjunct in some of these patients, especially in the posteromedial aspect of the upper arm. Liposuction has been used in failed cases or in patients in whom no lymphatics could be found. Improved results can be expected with earlier operations because patients referred earlier usually have less lymphatic disruption.     

Current research progress in targeted anti‐angiogenesis therapy for osteosarcoma

Osteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%‐70% 5‐year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre‐clinical and developmental research of targeted anti‐angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti‐angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti‐angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti‐angiogenesis therapy in OS.     

Long-term expression after infection by the hybrid vector AdLTR-luc is from integrated transgene

The novel adenoretroviral vector, AdLTR-luc, infects dividing and nondividing cells, and mediates long-term transgene expression(Zheng, C., Baum, B. J., Iadarola, M. J., and O'Connell, B. C., Nat. Biotech. 18, 176-180, 2000). To determine the source of this expression we examined two epithelial cell lines. One, HSG, permits E1(-) recombinant adenoviral replication, while the other, A5, does not. An HSG clone, that expressed luciferase stably for > 6 months, was obtained following infection at approximately 0.2 AdLTR-luc particles/cell. Southern and PCR analyses showed that luciferase cDNA present was integrated. A5 cells were infected with AdLTR-luc at approximately 1000 particles/cell, and colonies were obtained by limiting dilution. Eight clones showed stable luciferase activity for > 9 months. High molecular weight DNA extracts from clones were positive for genomic integration by Southern, PCR, and quantitative PCR analyses. Similar analyses of low molecular weight DNA extracts indicated the absence of intact extrachromosomal vector. These data demonstrate that long-term luciferase expression after infection by AdLTR-luc is derived from the integrated cDNA.     

Inhibition of protein phosphatase 2A with the small molecule LB100 overcomes cell cycle arrest in osteosarcoma after cisplatin treatment

Osteosarcoma is the most common primary malignant bone tumor and affects a significant portion of pediatric oncology patients. Although surgery and adjuvant chemotherapy confer significant survival benefits, many patients go on to develop metastatic disease, particularly to the lungs, secondary to development of drug resistance. Inhibition of protein phosphatase 2A with the small molecule, LB100, has demonstrated potent chemo- and radio-sensitizing properties in numerous pre-clinical tumor models. In this study, we showed that LB100 overcame DNA repair mechanisms in osteosarcoma cells treated with cisplatin, in vitro, and recapitulated these findings in an in vivo xenograft model. Notably, the addition of LB100 to cisplatin prevented development of pulmonary metastases in the majority of treated animals. Our data indicated the mechanism of chemo-sensitization by LB100 involved abrogation of the ATM/ATR-activated DNA damage response, leading to hyperphosphorylation of Chk proteins and persistent cyclin activity. In addition, LB100 exposure suppressed Akt signaling, leading to Mdm2-mediated proteasomal degradation of functional p53. Taken together, LB100 prevented repair of cisplatin-induced DNA damage, resulting in mitotic catastrophe and cell death.     

Rural patients are at risk for increased stage at presentation and diminished overall survival in osteosarcoma

BackgroundThere is an undefined relationship between access to regional referral centers and whether the eventual oncologic outcomes are influenced by distance, travel time, or residence in a rural community.MethodsWe used the Surveillance, Epidemiology and End Results (SEER) Program Database to capture all cases of high-grade osteosarcoma from 1990 to 2014 in Iowa, Utah, and New Mexico. Using univariate, Kaplan Meier survival analysis, and multivariate Cox proportional hazards modeling we analyzed patient and tumor characteristics.ResultsA total of 476 patients met the study criteria. There was an increased incidence of metastases for patients residing in a county with a greater than 2 -h drive to the nearest comprehensive cancer center (p = 0.021). Individuals residing in “rural” counties and “very rural” counties showed decreased 5-year survival (p = 0.007 and 0.003, respectively) when compared to those living in areas of higher population density. A multivariate regression analysis showed that the presence of metastasis (HR = 2.78 [95% CI: 1.88–4.10], p < 0.0001) and rural status (HR = 1.58 [95% CI: 1.03–2.43], p = 0.037) were risk factors for mortality when controlling for size of the tumor.ConclusionThe travel time to the nearest comprehensive center was associated with an increased incidence of metastasis on presentation in patients with osteosarcoma. Metastasis and rural status were independent risk factors for mortality. This investigation suggests that individuals living in rural counties may experience barriers to presentation, treatment, or surveillance that are not present in areas with a higher population density.     

Apoptotic and mitotic activity in squamous cell carcinoma cells after combined modality treatment with gamma-irradiation and dibromodulcitol.

A-431 squamous cell carcinoma cells were treated in vitro with either 4 Gy radiation of 15 (or 45) microg/ml dibromodulcitol (DBD), as well as with combined 4 Gy irradiation and DBD, with the latter as either a pretreatment or post-treatment. DBD alone or in combination with radiation had a greater effect on cell proliferation than the effect of radiation alone. The difference is due to a higher level of apoptosis induced by DBD, especially in conjunction with radiation. Such a combination may therefore be useful in the treatment of squamous cell carcinoma, which in general responds poorly to radiation therapy.     

Variations of dose and electrode spacing for rat breast cancer electrochemical treatment

Electrochemical treatment (EChT) with direct current delivered through implanted electrodes has been used for local control of solid tumors in humans. This study tested the hypothesis that rat breast cancer responses to EChT are dependent on electrode spacing and dose, and explored suitable parameters for treating breast cancers with EChT. Rat breast cancers were initiated by injecting 1 x 10(6) MTF-7 cells to the right mammary gland fat pad of Fisher 344 female rats. The rats were randomly divided into designated experimental groups when the tumors grew to approximately 2 x 2 x 2 cm. One hundred and thirty rats were used for a survival study and 129 for a pathology study. A 4-channel EChT machine was used to administer coulometric doses. The survival study indicated that local tumor control rate is less than 40% in the 40 coulomb (C) and 60 C groups and more than 70% in the 80 and 100 C groups. Sixty six rats died of primary tumors, including all 10 rats in the control group. Once a rat's primary tumor was controlled, no recurrence was found. The main reason for terminating the primary tumor-free rats (51) was lymph node metastasis. Thirteen tumor-free rats survived for more than 6 months. The pathology study showed a significant dose effect on EChT induced tumor necrosis. At 10, 20, 40, and 80 C, the fraction showing necrosis were 39.7, 52.3, 62, and 77.7%, respectively (P 相似文献   

Tailor-made treatment combined with proton beam therapy for children with genitourinary/pelvic rhabdomyosarcoma

Background

Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas among children. Patients who developed genitourinary/pelvic rhabdomyosarcoma (GU/P-RMS) have a higher complication ratio and relatively poorer event free survival, with local therapy being very important. While proton beam therapy (PBT) is expected to reduce co-morbidity, especially for children, this lacks firm evidence and analysis. We analyzed GU/P-RMS children who had undergone multimodal therapy combined with PBT at a single institution.

Method

We retrospectively reviewed charts of children with GU/P-RMS treated from January 2007 to May 2013 at the University of Tsukuba Hospital who had undergone multimodal therapy with PBT.

Results

There were 5 children and their median age at diagnosis was 2.8 years (0.6–4.4 years). Primary sites were the bladder (2) and the prostate (3). All received neo-adjuvant chemotherapy and 3 underwent chemotherapy during PBT (Group Cx). All patients of Group Cx developed leukocytopenia (WBC <1000/μL). The median dose of PBT was 47.7 GyE (41.4–50.4 GyE). All patients survived by their last hospital visit (median, 36 months).

Conclusions

We analyzed multimodal treatment combined with PBT applied for GU/P-RMS. PBT was well tolerated and could be a plausible choice instead of photon therapy for this population.     

阿奇霉素联合布地奈德治疗小儿支原体肺炎的临床疗效分析

目的 探讨阿奇霉素联合布地奈德治疗小儿支原体肺炎的临床疗效。方法 选取90例支原体肺炎患者,随机分为对照组和观察组（每组45例）,两组均常规给予药物进行对症治疗,在此基础上,对照组采用阿奇霉素序贯疗法进行治疗,观察组采用阿奇霉素序贯疗法联用布地奈德混悬液雾化吸入治疗,两组均连续治疗14天,观察两组患者主要指标变化时间,临床疗效及不良反应等。结果 治疗后,观察组的临床总有效率为95.6%,显著高于对照组的80.0%;观察组的体温复常时间、咳嗽消失时间、症状好转时间及住院时间分别为（2.1±0.9）、（10.1±2.3）、（6.9±1.6）和（12.1±2.4）天,对照组分别为（4.6±1.6）、（12.3±3.1）、（8.4±2.4）和（15.8±3.7）天,两组比较,差异均有统计学意义（P＜0.05）;两组不良反应比较,差异无统计学意义（P>0.05）。结论 阿奇霉素联合布地奈德用于治疗小儿支原体肺炎,可显著缩短主要指标复常时间,提高临床疗效,且安全性较好。