What information can we gain from performing adaptive radiotherapy of head and neck cancer patients from the past 10 years?

The aim of the review was to present the current literature status about replanning regarding anatomical and dosimetric changes in the target and OARs in the head and neck region during radiotherapy, to discuss and to analyze factors influencing the decision for adaptive radiotherapy of head and neck cancer patients. Significant progress has been made in head and neck patients’ evaluation and qualification for adapted radiotherapy over the past ten years. Many factors leading to anatomical and dosimetric changes during treatment have been identified. Based on the literature, the most common factors triggering re-plan are weight loss, tumor and nodal changes, and parotid glands shrinkage. The fluctuations in dose distribution in the clinical area are significant predictive factors for patients’ quality of life and the possibility of recovery. It has been shown that re-planning influence clinical outcomes: local control, disease free survival and overall survival. Regarding literature studies, it seems that adaptive radiotherapy would be the most beneficial for tumors of immense volume or those in the nearest proximity of the OARs. All researchers agree that the timing of re-planning is a crucial challenge, and there are still no clear consensus guidelines for time or criteria of re-planning. Nowadays, thanks to significant technological progress, the decision is mostly made based on observation and supported with IGRT verification. Although further research is still needed, adaptive strategies are evolving and now became the state of the art of modern radiotherapy.     

Evaluation of prime and prime-boost immunization strategies in BALB/c mice inoculated with Leishmania infantum transfected with toxic plasmids

The etiologic agents of visceral leishmaniasis are Leishmania infantum and Leishmania donovani. Despite the variety of drugs available to treat leishmaniasis, most lead to serious adverse effects, and resistance to these drugs has been reported. Currently, no leishmaniasis vaccine is available for humans. That is why the group developed transgenic L. infantum promastigote lines, which express toxic proteins after differentiation into amastigotes. That is why group developed the pFL-AMA plasmid and transfected it into L. Infantum promastigotes. This plasmid was expressed only in the amastigote form of the parasite. Sequences encoding toxic proteins (active bovine trypsin and egg avidin) were inserted in this plasmid, and the transfected parasites died after the differentiation process. In this study, two immunization protocols were performed in BALB/c mice: prime and prime-boost immunization prior to challenge with the wild-type L. infantum (WT). The parasite burdens in the spleen, liver, and bone marrow were evaluated to verify immunological protection. Histopathological analysis of the spleen and liver and the humoral immune response were also performed. The data showed that the parasite burden was reduced in prime-boosted mice in the spleen, liver, and bone marrow, indicating that mice immunized with two doses of the transfected parasites were satisfactorily protected. High levels of IgG, IgG1, and IgG2a antibodies were observed, as well as the presence of anti-inflammatory cytokine Interleukine-10 and pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN – γ) suggesting a Th1/Th2 mix response, in addition to the presence of multinucleated giant cells in the spleen and lymphocyte infiltration in the liver. Therefore, L. infantum transfected with a toxic plasmid is an excellent vaccine candidate against visceral leishmaniasis and the application of a boost before the challenge promotes greater protection against WT L. infantum infection.     

右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响

目的 探讨右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响。方法 选择择期行腔镜手术治疗的老年恶性肿瘤患者90例，随机均分为3组：对照组（C组）、体温保护组（T组）和体温保护联合右美托咪定组（T-D组），每组30例。C组常规体温保护，T组和T-D组综合体温保护；T-D组麻醉诱导前10 min泵注右美托咪定0.5 μg/kg。记录3组患者麻醉诱导开始时（T₀）、手术开始30 min（T₁）、60 min（T₂）、90 min（T₃）、120 min（T₄）以及手术结束时（T₅）的鼻咽温度；于T₀、术后2 h（T₆）、24 h（T₇）和48 h（T₈）时抽取静脉血标本，测定T淋巴细胞亚群（CD3⁺、CD4⁺和CD8⁺）和自然杀伤细胞（NK cell）水平；记录患者术中麻醉药物用量及苏醒期质量指标。结果 与T₀比较，C组T₂～T₅时点鼻咽温度均明显降低（P < 0.05）；与C组比较，T组和T-D组T₂～T₅时点鼻咽温度明显升高（P < 0.05）。与T₀时点比较，C组、T组和T-D组T₆、T₇和T₈时点CD3⁺和NK cell活性均明显降低（P < 0.05）；C组在T₆、T₇和T₈时点，T组和T-D组在T₆和T₇时点，CD4⁺活性均明显降低（P < 0.05）。与C组比较，T组和T-D组T₆和T₇时点CD3⁺细胞活性均明显升高（P < 0.05）；T组在T₇时点，T-D组在T₆和T₇时点，CD4⁺细胞活性均明显升高（P < 0.05）；T组在T₇时点，T-D组在T₆、T₇和T₈时点，NK cell活性均明显升高（P < 0.05）。结论 采用体温保护措施联合右美托咪定能够维持老年恶性肿瘤患者的体温稳定，减少围手术期意外低体温（IPH）的发生，并有效提高患者苏醒期质量，减轻免疫抑制程度，加速患者早期恢复。     

Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

胶质瘤复发与放射性脑损伤的MRI鉴别诊断探讨

目的:讨论胶质瘤复发与放射性脑损伤的MRI鉴别诊断。方法:回顾性分析2018年1月~2020年2月本院收治的68例胶质瘤术后患者,对所有患者进行MRI平扫、增强以及灌注加权成像(PWI)扫描,记录影像学特征,对脑血容量中位数最大值(rCBV_max)、表观扩散系数(ADC_mean、ADC_min)指标进行对比。结果:有15例患者复发,其胶质瘤复发率为22.06%,其放射性脑损伤的发生率为8.82%(6例);胶质瘤复发与放射性脑损伤患者rCBV_max、ADC_min值有明显差异(P<0.05),ADC_mean比较无明显差异(P>0.05)。结论:进行MRI检查临床效果较好,可准确鉴别胶质瘤复发与反射性脑损伤。     

脾脏ARFI弹性联合血小板计数预测乙肝肝硬化食管静脉曲张的价值

目的 本研究应用声辐射力脉冲成像(Acoustic Radiation Force Impulse ARFI)技术对慢性乙型肝炎肝硬化患者进行脾脏弹性检测和分析,探讨和对比脾脏ARFI弹性及脾脏ARFI弹性联合血小板计数(Platelet Count PC)在预测乙肝肝硬化食道静脉曲张的临床应用价值。方法 对232例慢性乙型肝炎肝硬化患者应用ARFI技术检测脾脏实时超声弹性,并测量PC,所有患者均于检测前后一周内行胃镜检查明确食管静脉曲张情况,以胃镜结果为金标准,应用受试者工作特征(receiver operating characteristic, ROC)曲线比较脾脏ARFI弹性、PC、及脾ARFI弹性联合PC诊断肝硬化食管静脉曲张的临床价值。结果 食道静脉曲张组脾脏ARFI弹性和PC分别为3.52(3.16-3.87)m/s 和62(41-88.25),无食道静脉曲张组脾脏ARFI弹性和PC分别为2.91(2.35-3.35)m/s和129.5(87.25-196.25)。脾脏ARFI弹性和PC在两组间比较的差异均具有统计学意义(P＜0.001 )。单独脾脏ARFI弹性及脾脏ARFI弹性联合PC的ROC曲线下面积分别为0.76和0.83,差异具有统计学意义(P = 0.0021)。结论 脾脏ARFI弹性测值联合PC较单纯脾脏ARFI弹性能更准确的无创预测慢性乙型肝炎肝硬化食管静脉曲张的存在,具有良好的临床应用前景。     

Predictors of survival following surgical resection of limited-stage small cell lung cancer

BackgroundAdjuvant chemotherapy, postoperative radiation (PORT), and prophylactic cranial irradiation (PCI) have been individually examined in limited-stage small cell lung cancer (SCLC). There is a paucity of data on the effectiveness of each adjuvant treatment modality when used in combination after surgical resection of SCLC.MethodsData were collected from 5 cancer centers on all patients with limited-stage SCLC who underwent surgical resection between 1986 and 2019. Univariate and multivariable models were conducted to identify predictors of long-term outcomes, focusing on freedom from recurrence and survival benefit of adjuvant chemotherapy, PORT, and PCI.ResultsA total of 164 patients were analyzed. Multivariable Cox regression analysis did not identify any adjuvant therapies to significantly influence recurrence in this cohort. Specifically, PORT was not associated with a significant influence on locoregional recurrence and PCI was not significantly associated with intracranial outcomes. Adjuvant chemotherapy improved survival in all stage I through III disease (hazard ratio, 0.49; 95% confidence interval, 0.29-0.81; P = .005) and even in pathologically node negative patients (hazard ratio, 0.49; 95% confidence interval, 0.27-0.91; P = .024). Although PCI was found to improve survival in univariate analysis, it was not significant in a multivariable model. PORT was not found to affect survival on either univariate or multivariable analysis.ConclusionsThis is among the largest multi-institutional studies on surgically resected limited-stage SCLC. Our results highlight survival benefit of adjuvant chemotherapy, but did not identify a statistically significant influence from mediastinal PORT or PCI in our cohort. Larger prospective studies are needed to determine the benefit of PORT or PCI in a surgically resected limited-stage SCLC population.     

Anti-aging effect of DL-β-hydroxybutyrate against hepatic cellular senescence induced by D-galactose or γ-irradiation via autophagic flux stimulation in male rats

The present study aims to shed new light on anti-aging effect of DL-β-hydroxybutyrate (βOHB) against hepatic cellular senescence induced by d-galactose or γ-irradiation. The rats divided into 6 groups. Group 1, control, group 2, exposed to γ-ray (5 GY), group 3, injected by d-galactose (150 mg/kg) daily for consecutive 6 weeks, which regarded to induce the aging, group 4, injected intraperitoneal by β-hydroxybutyrate (βOHB) (72.8 mg/kg) daily for consecutive 14 days, group 5, exposed to γ-ray then treated with βOHB daily for consecutive 14 days, group 6, injected daily with d-galactose for consecutive 6 weeks, then treated with βOHB daily at the last two weeks of d-galactose. Aspartate amino transferase (AST), alanine amino transferase (ALT), Insulin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were estimated in serum. Moreover, protein expression of Microtubule-associated proteins 1A/1B light chain 3B (LC3-II/LC3-I) ratio, mechanistic target of rapamycin (mTOR), pAMPK, mRNA gene expression of 5′ AMP-activated protein kinase (AMPK), Nucleoporin p62 (p62), cyclin-dependent kinase inhibitor 1(P21^CIP1), cyclin-dependent kinase inhibitor 2A (p16^INK4a) and DNA fragmentation percentage were measured in liver tissue as a biomarker of cellular senescence. The results confirmed that βOHB modulated serum level of AST, ALT, insulin, IL-6 and TNF-α, protein expression of mTOR and LC3-II/LC3-I ratio, pAMPK and p62 in liver aging model induced by d-galactose or γ-irradiation. Histopathological examination results of liver tissue indicated coincidence with those recorded by molecular biochemical inspection. Taken together, these findings suggest that βOHB may be useful in combating hepatic cellular senescence induced by d-galactose or γ-irradiation via autophagy dependent mechanisms.     

Radiation Dose Reduction in Kidney Stone CT: A Randomized,Facility-Based Intervention

ObjectiveKidney stones are common, tend to recur, and afflict a young population. Despite evidence and recommendations, adoption of reduced-radiation dose CT (RDCT) for kidney stone CT (KSCT) is slow. We sought to design and test an intervention to improve adoption of RDCT protocols for KSCT using a randomized facility-based intervention.MethodsFacilities contributing at least 40 KSCTs to the American College of Radiology dose index registry (DIR) during calendar year 2015 were randomized to intervention or control groups. The Dose Optimization for Stone Evaluation intervention included customized CME modules, personalized consultation, and protocol recommendations for RDCT. Dose length product (DLP) of all KSCTs was recorded at baseline (2015) and compared with 2017, 2018, and 2019. Change in mean DLP was compared between facilities that participated (intervened-on), facilities randomized to intervention that did not participate (intervened-off), and control facilities. Difference-in-difference between intervened-on and control facilities is reported before and after intervention.ResultsOf 314 eligible facilities, 155 were randomized to intervention and 159 to control. There were 25 intervened-on facilities, 71 intervened-off facilities, and 96 control facilities. From 2015 to 2017, there was a drop of 110 mGy ∙ cm (a 16% reduction) in the mean DLP in the intervened-on group, which was significantly lower compared with the control group (P < .05). The proportion of RDCTs increased for each year in the intervened-on group relative to the other groups for all 3 years (P < .01).DiscussionThe Dose Optimization for Stone Evaluation intervention resulted in a significant (P < .05) and persistent reduction in mean radiation doses for engaged facilities performing KSCTs.