子野个数限值对宫颈癌固定野调强放疗计划的影响

目的:分析子野个数限值对宫颈癌固定野调强放疗（fixed-field intensity-modulated radiotherapy,ff-IMRT）计划的影响，寻求最优的子野个数限值。方法:选取10例接受ff-IMRT的宫颈癌患者，基于Monaco 5.11.03计划系统，以45 Gy/25 f处方剂量分别对同一患者设计8种ff-IMRT计划（ff-IMRT计划依据子野个数限值命名，子野个数限值分别为40、60、70、80、100、120、130、150），采用SPSS 20.0软件比较除plan100之外7个ff-IMRT计划与plan100剂量学参数、优化时间和治疗参数的差异。结果:8种ff-IMRT计划归一化后，plan40和plan60的D2%、Dmin、CI和HI均劣于plan100（P＜0.05）。8种ff-IMRT计划均能较好保护危及器官（organ at risk,OAR）和正常组织。plan40小肠V45;plan40和plan60小肠D2cc，直肠、膀胱V45、D40%，两侧股骨头V40和正常组织 V35、V40均高于plan100（P＜0.05）。plan40和plan60优化时间、治疗参数均优于plan100（P＜0.05）；plan120、plan130和plan150子野面积、子野个数（51~150 cm2和＞150 cm2）和出束时间均劣于plan100（P＜0.05）。结论:子野个数限值为70~100时，ff-IMRT计划能兼顾剂量学参数满足临床要求、优化时间和治疗参数最优化，建议在设计宫颈癌ff-IMRT计划时在该范围内设置子野个数限值。     

A systematic review of axillary nodal irradiation for the management of the axilla in patients with early-stage breast cancer

BackgroundGiven numerous publications and clinical trials regarding axillary management in breast cancer, we sought to summarize this complex literature to help clarify this field for clinicians. This systematic review focuses on the role of irradiation of the axillary nodes (locoregional nodal irradiation [LRNI]) in the management of the axilla in patients with early-stage breast cancer in various clinical settings.MethodsWe searched MEDLINE and EMBASE databases, the Cochrane library, the proceedings of the ASCO, the ASTRO, the ESMO, the ESTRO, and the San Antonio Breast Cancer Symposium (2016–2019) meetings. The quality of the studies was assessed with design-specific tools. The study was registered in PROSPERO.ResultsWe included one systematic review, one individual patient data (IPD) meta-analysis, and five randomized controlled trials (RCTs). After axillary lymph node dissection (ALND), LRNI resulted in small benefits in breast cancer specific mortality, locoregional recurrence, and distant metastases-free survival but not overall survival. After a positive sentinel node biopsy (SLNB), LRNI may provide equivalent locoregional control and disease-free survival (DFS) compared to ALND with a lower risk of lymphedema. No randomized data is available for the neoadjuvant setting.ConclusionsThe summary of the role of radiation, is relevant to radiation oncologists for choosing the correct cohort of patient requiring LRNI and to surgeons making clinical decisions regarding the timing and type of breast reconstruction offered to patients.     

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.     

新型驱动基因融合阳性非小细胞肺癌脑转移的研究进展北大核心

肺癌是我国最常见且死亡率最高的恶性肿瘤之一,随着表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)及活性氧1(ROS1)等驱动基因及其相应分子靶向药物的出现,晚期非小细胞肺癌的治疗和预后发生了革命性变化。此外,一些少见新型驱动基因融合,包括神经调节蛋白1(NRG1)、神经营养酪氨酸受体激酶(NTRK)和转染重排因子(RET),正逐渐发展成为全身性治疗选择。然而,这些罕见新型融合驱动基因在NSCLC脑转移中的作用机制,以及优化控制和预防脑转移的意义人们所知甚少。因此,本文就近几年罕见驱动基因融合在NSCLC脑转移中的研究进行综述。     

Sélection de patientes et tolérance précoce de l’irradiation mammaire selon le protocole « Fast Forward » : résultats préliminaires

PurposeModerate hypofractionated radiotherapy has become routine practice for a selected population of patients treated for early-stage breast cancer. In April 2020, the Fast Forward (FF) study was published which introduced another extreme hypofractionated radiotherapy regimen in five sessions over a week. The aim of this work is to evaluate the population of first patients in whom this regimen was used in our department, as well as the results in terms of early toxicity.Material and methodsWe retrospectively analysed all the patients treated in our department according to the Fast Forward protocol after establishing an institutional consensus regarding the selection of patients with breast cancer without indication for lymph node irradiation. All patients received breast-only irradiation at a total dose of 26 Gy in five fractions according to protocol. All patients were treated by modern conformational techniques with planning large volume coverage between 95 and 100%. Acute toxicity of the treatment was assessed using the NCI CTC v4.0 scale and the general condition was assessed according to the WHO classification.ResultsBetween August 2020 and May 2021, 30 patients were included, treated on the breast alone without complement on the tumour bed or irradiation of the lymph node areas. The median age of the patients was 80 years (range: 60–85 years) with performance status 2 in 27 cases (89%). Only one patient had metastatic disease (3%), one patient presented locally advanced and 28 (94%) patients had early stage disease. Three patients (10%) were treated in dorsal decubitus according to the “field in the field” technique and 27 patients (90%) in isocentric lateral decubitus, which made it possible to avoid the organs at risk such as the heart (average dose of less than 1 Gy) and the lungs. The early toxicity observed was grade I radio dermatitis in 8 patients (27%). No grade 2 and 3 toxicity, as well as radiation-induced pain or lymphedema were observed.ConclusionsThe results of this series of patients treated with hypofractionated radiotherapy according to the Fast Forward protocol on the breast alone with adapted techniques show that the protocol is feasible, with little early toxicity but a greater follow-up is necessary to assess long-term toxicity.     

Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.     

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.     

Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.