Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK

AimsIn response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I–III lung cancer from April to October 2020.Materials and methodsLung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I–III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression.ResultsIn total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease.ConclusionsThe COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.     

Locally advanced cervical carcinoma patients treated with chemoradiation followed by radical surgery: clinical response and oncological outcomes according to histotype after propensity score analysis

IntroductionThe aims of this study were to analyze the pathological response, and survival outcomes of adenocarcinoma/adenosquamous (AC/ASC) versus squamous cell carcinoma (SCC) in patients with locally advanced cervical cancer (LACC) managed by chemoradiotherapy followed by radical surgery.MethodsRetrospective, multicenter, observational study, including patients with SCC and AC/ACS LACC patients treated with preoperative CT/RT followed by tailored radical surgery (RS) between 06/2002 and 05/2017. Clinical-pathological characteristics were compared between patients with SCC versus AC/ASC. A 1:3 ratio propensity score (PS) matching was applied to remove the variables imbalance between the two groups.ResultsAfter PS, 320 patients were included, of which 240 (75.0%) in the SCC group, and 80 (25.0%) in the AC/ASC group. Clinico-pathological and surgical baseline characteristics were balanced between the two study groups. Percentage of pathologic complete response was 47.5% in SCC patients versus 22.4% of AC/ASC ones (p < 0.001). With a median follow-up of 51 months (range:1–199), there were 54/240 (22.5%) recurrences in SCC versus 28/80 (35.0%) in AC/ASC patients (p = 0.027). AC/ASC patients experienced worse disease free (DFS), and overall survival (OS) compared to SCC patients (p = 0.019, and p = 0.048, respectively). In multivariate analysis, AC/ACS histotype, and FIGO stage were associated with worse DFS and OS.ConclusionIn LACC patients treated with CT/RT followed by RS, AC/ASC histology was associated with lower pathological complete response to CT/RT, and higher risk of recurrence and death compared with SCC patients. This highlights the need for specific therapeutic strategies based on molecular characterization to identify targets and develop novel treatments.     

基于自动勾画和快速蒙特卡罗计算的放射治疗全身器官剂量数据库平台的可行性研究

目的:探讨建立一种放射治疗全身器官剂量数据库平台的可行性。方法:使用基于深度学习的自动勾画软件DeepViewer?1例食管癌患者的全身CT上勾画全身器官，然后利用基于GPU加速的蒙特卡罗软件ARCHER计算相应的器官剂量分布，最后利用Lyman-Kutcher-Burman（LKB）模型评估放疗患者正常组织并发症概率（NTCP）。结果:针对该病例，成功建立基于DeepViewer?ARCHER和LKB模型的全身器官剂量数据库，发现距离靶区越近的器官剂量越大，其中心脏与靶区间距离最小，剂量为14.11 Gy，但因其模型参数特殊，通过LKB模型计算的NTCP为0.00%；左、右肺的剂量分别为3.19和1.16 Gy，但是NTCP值却很大，分别为2.13%和1.60%。对于距离靶区较远的头颈部器官（视交叉、视神经和眼）和腹部器官（直肠、膀胱和股骨头）剂量分别约为9和2 mGy，并且NTCP均近似为0.00%。结论:研究结果证明通过自动勾画软件DeepViewer?蒙特卡罗软件ARCHER和LKB模型建立全身器官剂量数据库的可行性。     

肺鳞癌治疗新靶点FGFR的研究进展

肺癌是目前全球发病率和死亡率均居前列的恶性肿瘤，其中肺鳞癌经手术、放化疗等综合治疗后，其疗效仍不满意。随着分子靶向治疗在肺腺癌中取得了令人瞩目的成果，而肺鳞癌患者中EGFR基因突变及ALK融合基因少见，急需探索新的靶点指导肺鳞癌患者的临床治疗。研究表明，FGFR家族（FGFR1-4）是肺鳞癌中突变频率较高的基因，FGFR基因的激活突变和扩增与肺鳞癌的发生和发展密切相关，同时许多小分子 FGFR 抑制剂在临床应用中已经取得较好的治疗效果。目前，许多FGFR抑制剂治疗肺鳞癌的临床试验也正在进行研究，针对FGFR靶点的基因治疗可为肺鳞癌的治疗提供一种新的策略。本文就FGFR在肺鳞癌的靶向治疗中的最新研究进展进行综述。     

Assessment of the uterine dose in digital mammography and digital breast tomosynthesis

IntroductionDigital Mammography (DM-2D) and more recently Digital Breast Tomosynthesis (DBT), are two of the most effective imaging modalities for breast cancer detection, often used in screening programmes. It may happen that exams using these two imaging modalities are inadvertently performed to pregnant women. The objective of this study is to assess the dose in the uterus due to DM-2D and DBT exams, according to two main irradiation scenarios: in the 1st scenario the exposure parameters were pre-selected directly by the imaging system, while in the 2nd scenario, the maximum exposure parameters were chosen.MethodsThe mammography equipment used was a Siemens Mammomat Inspiration. A physical anthropomorphic phantom, PMMA plates (simulating a breast thickness of 6 cm) and thermoluminescent dosimeters (TLDs) were used to measure entrance air kerma values on the phantom's breast and abdomen in order to successively estimate the mean glandular dose (MGD) and the dose in the uterus. For the two irradiation scenarios chosen, two-breast imaging modalities were selected: 1) DBT in Cranio-Caudal (CC) view (with 28 kV and 160 mAs as exposure parameters), 2) DBT and DM in Medio Lateral-Oblique (MLO) and CC views (with 34 kV and 250 mAs as exposure parameters).ResultsIn the 1st scenario, the TLD measurements did not detect significant dose values in the abdomen whereas the MGD estimated using the D.R. Dance model was in close agreement with data available in the literature. In the 2nd scenario, there was no significant difference in MGD estimation between the different views, whereas the air kerma values in the abdomen (in DBT mode, CC and MLO) were 0.049 mGy and 0.004 mGy respectively. In CC DM-2D mode the abdomen air kerma value was 0.026 mGy, with no significant detected value in MLO view.ConclusionsFor the dose in the uterus, the obtained values seem to indicate that DM-2D and DBT examinations inadvertently performed during pregnancy do not pose a significant radiological risk, even considering the case of overexposure in both breasts.Implications for practiceThe accurate knowledge of the doses in DM-2D and DBT will contribute to raise the awareness among medical practitioners involved in breast imaging empowering them to provide accurate information about dose levels in the uterus, improving their radiation risk communication skills and consequently helping to reduce the anxiety of pregnant women undergoing this type of examinations.     

Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region

IntroductionInherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer.MethodsWe conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer.ResultsWe detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722–0.820; p value 5.31 × 10^-16), rs380286 (OR: 0.770, 95% CI: 0.723–0.820; p value 4.32 × 10^-16), and rs4975616 (OR: 0.778, 95% CI: 0.730–0.829; p value 1.04 × 10^-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.ConclusionsWe found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.     

Anticoagulation Strategies in Patients With Cancer: JACC Review Topic of the Week

Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.     

Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer – A Nationwide Cohort Study

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death

Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser⁴⁷³, increased inhibitory phosphorylation of proapoptotic BAD on Ser¹³⁶, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death.