Constrained‐beam inverse planning for intensity‐modulated radiation therapy of prostate cancer patients with bilateral hip prostheses

Hip prostheses present a technical challenge in the planning of curative external beam radiation treatment for patients with prostate cancer. Bilateral prostheses compel planners to compromise between target coverage and avoidance of beam entry through the prostheses. Inverse planning systems given objectives to avoid dose to prostheses are overly restricted from allowing exit dose to them. We report a novel inverse planning technique for intensity‐modulated radiation therapy of patients with prostate cancer and bilateral hip prostheses, by constraining beam characteristics rather than dose in the inverse planning process.     

Novel metastatic burden‐stratified risk model in de novo metastatic hormone‐sensitive prostate cancer

The metastatic burden is a critical factor for decision‐making in the treatment of metastatic hormone‐sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low‐ and high‐burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen‐deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T‐stage were associated with poor OS in low‐burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high‐burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression‐free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden‐stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.     

局限性前列腺癌调强适形放疗联合间歇性内分泌治疗的疗效评价

目的探讨调强适形放射治疗（intensity modulated radiation therapy,IMRT）联合间歇性内分泌治疗（intermittent hormonal therapy,IHT）方法治疗局限性前列腺癌的疗效评价。方法将72例同期局限性前列腺癌患者随机分为两组,分别进行调强适形放射治疗联合间歇性内分泌治疗（37例）和单纯调强适形放射治疗（35例）,分析比较两组患者的临床症状缓解率、前列腺体积变化、血清前列腺特异性抗原（PSA）值改变、肿瘤控制率、放疗不良反应发生率及生存率。结果随访5～118个月,平均56个月,联合治疗组与单纯治疗组比较,临床症状缓解率、前列腺体积差值、血清PSA〈0．2μg/L者所占比例及治疗后1年、3年、5年和8年的PSA无进展生存率差异均有统计学意义（P〈0．05）;治疗后1年、3年两组均无死亡病例,差异无统计学意义,治疗后5年、8年的生存率和早期放疗不良反应发生率两组间差异均有统计学意义（P〈0．05）。结论调强适形放射治疗联合间歇性内分泌治疗方法治疗局限性前列腺癌可明显缓解患者的临床症状,降低血清PSA水平,提高疾病控制率及生存率,降低放疗早期不良反应发生率,疗效优于单纯调强适形放射治疗,是一种安全、有效的治疗措施。     

Dosimetric study of optimal beam number and arrangement for treatment of nasopharyngeal carcinoma with intensity‐modulated radiation therapy

The purpose of this dosimetric study was to evaluate the effect of beam number and arrangement on the dose distribution with intensity‐modulated radiation therapy in patients with nasopharyngeal cancer. Computed tomography data sets of seven patients who were treated for nasopharyngeal carcinoma at the Peter MacCallum Cancer Centre were used for the present dosimetric study. The dose planned was 70 Gy in 7 weeks for the gross nasopharyngeal and nodal disease and the biological equivalents of 60 Gy in 6 weeks for the high‐risk and 50 Gy in 5 weeks for the low‐risk nodal disease. A plan using seven fields was compared to that using nine fields in all patients. Plans were assessed on the dose to the planning target volume (PTV) and the degree of parotid sparing achieved by evaluating both dose?volume histograms (DVH) and axial slices. Seven fields (three anterior and four posterior) provide good PTV coverage and satisfactory parotid sparing in patients with localized nasopharyngeal lesions. Nine fields appear to be better for tumours with significant posterolateral parapharyngeal extension. Parotid sparing is consistently better with nine fields. Both DVH and axial slices need to be evaluated before accepting any plan.     

Health-related quality of life after intensity modulated radiation therapy for localized prostate cancer: comparison with conventional and conformal radiotherapy

OBJECTIVE: No previous studies have reported the longitudinal health-related quality of life (HRQOL) for intensity modulated radiation therapy (IMRT). We compared HRQOL after IMRT with that after conventional and after conformal radiation therapy (XRT). METHODS: A total of 110 patients underwent XRT (34 patients underwent conventional radiation therapy and 76 underwent conformal radiation therapy) and 30 underwent IMRT for clinically localized prostate cancer between 2000 and 2002. We measured the general and disease-specific HRQOL using the Medical Outcomes Study 36-Item Health Survey and University of California, Los Angeles, Prostate Cancer Index, respectively. RESULTS: There were no significant differences in the preoperative characteristics and HRQOL scores of the two groups. Repeated measure analyses of variance revealed significantly different patterns of alteration in several general HRQOL domains between XRT and the IMRT groups. In the urinary domain, there was no difference in the alteration patterns between the two groups. The XRT group suffered worse bowel function at 3 and 6 months than the IMRT group (P < 0.05). In the XRT group, sexual function decreased at 3 months and remained substantially lower than the baseline level. However, the IMRT group showed no significant difference from the baseline level at any of the observation periods. At 18 months the XRT group showed worse sexual function than the IMRT group. CONCLUSION: The two approaches showed different longitudinal profiles regarding general and disease-specific HRQOL during the first 2 years after treatment. The IMRT approach produced little impairment in bowel and sexual function.     

Intensity‐modulated radiation therapy: First reported treatment in Australasia

Intensity‐modulated radiation therapy (IMRT) is an exciting new advance in the practice of radiation oncology. It is the use of non‐uniform radiation beams to achieve conformal dose distributions. As a result of the high initial capital costs and the time and complexity of planning, IMRT is not yet a widely available clinical treatment option. We describe the process involved in applying this new technology to a case of locally advanced nasopharyngeal cancer.     

Proposing synchronous oligometastatic non–small‐cell lung cancer based on progression after first‐line systemic therapy

Despite the importance of accurate disease definitions for effective management and treatment decisions, there is currently no consensus on what constitutes oligometastatic non–small‐cell lung cancer (NSCLC). Predominant patterns of initial progressive disease (PD) after first‐line systemic therapy have been shown to be a substantial basis for local ablative therapy (LAT) for all disease sites in patients with oligometastatic NSCLC, suggesting that these patterns could be helpful in defining synchronous oligometastatic NSCLC. Therefore, this retrospective study aimed to propose a threshold number of metastases for synchronous oligometastatic NSCLC, based on the pattern of initial PD after first‐line systemic therapy. The cut‐off threshold number of metastases compatible with synchronous oligometastatic NSCLC was determined using receiver operating characteristic (ROC) curve analyses of PD at the initially involved sites alone. ROC analysis of 175 patients revealed that the presence of 1‐3 metastases before first‐line treatment (sensitivity, 85.9%; specificity, 97.3%; area under the curve, 0.91) was compatible with oligometastatic NSCLC, therefore we divided patients into oligometastatic NSCLC and non‐oligometastatic NSCLC groups. Multivariate logistic regression analyses revealed oligometastatic NSCLC to be the only independent predictor of PD at initially involved sites alone (odds ratio 165.7; P < .001). The median survival times in patients with oligometastatic or non‐oligometastatic NSCLC were 23.0 and 10.9 mo (hazard ratio, 0.51; P = .002), respectively. Based on these findings, we propose synchronous oligometastatic NSCLC as 1‐3 metastases in accordance with patterns of initial progression. The result of our study might be contributory to provide a common definition of synchronous oligometastatic NSCLC.     

Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

鼻咽癌调强放疗的剂量学研究

 【摘要】目的 分析鼻咽癌调强放疗各个靶区和周围正常组织器官的剂量学特点。方法 2005年1月-2006年6月住院的30例初治鼻咽癌进行调强放疗，将鼻咽和颈部的靶体积勾画为鼻咽大体肿瘤体积（GTVnx）、颈部大体肿瘤体积(GTVnd)、临床靶体积1（CTV1）和临床靶体积2(CTV2)，处方剂量分别为70、66、60、60Gy/30F，鼻咽和上颈部靶体积采用IMRT技术照射、下颈部靶体积采用下颈前野常规照射。研究GTV、CTV的最大、最小、平均剂量和颞叶、脑干、脊髓、视神经、晶体、眼球的最大受照剂量及腮腺、颞下颌关节的50%体积受照剂量。结果 GTVnx的最大、最小、平均剂量（均值）分别为79.2、59.5、71.9Gy, GTVnd的最大、最小、平均剂量分别为77.1、63.6、72.1Gy，CTV1、CTV2的最小剂量分别为47.6、49.7Gy，颞叶、脑干、脊髓、视神经、晶体、眼球的最大受照剂量及腮腺、颞下颌关节的50%体积受照剂量63.2、48.6、44.7、59.3、6.9、25.9Gy和34.0、36.3Gy。结论 调强放疗可以使各个靶区得到足够的、均匀的剂量分布，周围正常组织器官得到较好的保护，但是要注意CTV的低剂量区。鼻咽癌调强放疗剂量分布优于常规放疗。     

逆向计划调强适形放射治疗的质量保证

目的：通过一系列调强验证方法的研究，探讨逆向计划调强适形放射治疗（IMRT）的质量保证方法是否可行。方法：用Varian Cadplan三维治疗计划系统中Helios逆向计划系统对前列腺癌、鼻咽癌、脑瘤、胰腺癌、椎骨转移癌等设计并进行IMRT。为验证计划系统生成的各个照射野注量图与实际注量图的一致性，将剂量胶片放在平板有机玻璃体模下，使计划中的各个照射野始终垂直于体模表面；调用患者治疗数据分别单独照射，冲洗胶片后与计划得出的注量图进行比较。将剂量胶片夹在仿真体模适当的部位，调用患者治疗数据对体模进行模拟照射，由此得出轴向截面上的等剂量分布，与计划的等剂量曲线拟合比对。用电离室和水箱验证等中心和偏离点的绝对剂量。在模拟机或加速器上拍正侧位照射野验证片，与CT模拟数字重建的射线影像片比较，验证等中心位置。结果：各射线束轴垂直方向测得的注量图与计划系统计算的一致；等中心点绝对剂量测量的结果与计划计算的误差在3％以内，偏离点绝对剂量误差较大；轴向截面等剂量曲线分布的胶片测量结果与计划计算的很接近；等中心位置误差在3mm以内。结论：近一年的实践证明在IMRT中所采用的上述质量保证措施是切实可行的。     

连续加速分割逆向调强放疗治疗鼻咽癌的临床研究

目的比较鼻咽癌每周7次连续加速分割逆向调强放疗与常规逆向调强放疗的近期疗效及毒副作用。方法采用单双月分组方法将83例经病理学证实的初治鼻咽癌患者分至每周7次连续加速分割逆向调强放疗(continuous accelerated intensity modulated radiation therapy,CAIMRT)组及常规分割逆向调强放疗(intensity modulated radiation therapy,IMRT)组。总剂量70 Gy,分割剂量每次2 Gy。结果两组患者均顺利完成治疗,两组完全缓解率(complete response,CR)分别为86.8%及80%,统计学比较无明显差异(P0.05)。CAIMRT组与IMRT组比较,急性皮肤和黏膜反应出现时间提前,差异具有统计学意义(P0.05);总住院时间有所缩短,差异具有统计学意义(P0.01)。结论鼻咽癌患者采用每周7次连续加速分割逆向调强放疗,患者能够耐受,肿瘤近期局部控制率好。     

A combination of extracellular matrix‐ and interferon‐associated signatures identifies high‐grade breast cancers with poor prognosis

Breast cancer (BC) is a heterogeneous disease in which the tumor microenvironment (TME) seems to impact the clinical outcome. Here, we investigated whether a combination of gene expression signatures relating to both the structural and immune TME aspects can help predict prognosis in women with high‐grade BC (HGBC). Thus, we focused on a combined molecular biomarker variable that involved extracellular matrix (ECM)‐associated gene expression (ECM3 signature) and interferon (IFN)‐associated metagene (IFN metagene) expression. In 97 chemo‐naive HGBCs from the METABRIC dataset, the dichotomous ECM3/IFN (dECIF) variable identified a group of high‐risk patients (ECM3⁺/IFN⁻ vs other; hazard ratio = 3.2, 95% confidence interval: 1.5–6.7). Notably, ECM3⁺/IFN⁻ tumors showed low tumor‐infiltrating lymphocytes, high levels of CD33‐positive cells, absence of PD‐1 expression, or low expression of PD‐L1, as suggested by immune profiles and immune‐histochemical analysis on an independent cohort of 131 HGBCs. To make our results transferable to clinical use, we refined the dECIF biomarker using reduced ECM3 and IFN signatures; notably, the prognostic value of this reduced dECIF was comparable to that of the original dECIF. After validation in a new BC cohort, reduced dECIF was translated into a robust qPCR classifier for real‐world clinical use.     

非共面射野在鼻咽癌调强放疗中的应用

目的　通过对非共面调强放疗计划与共面调强放疗计划的比较,探讨非共面调强放疗在鼻咽癌调强放疗中的剂量学特点。方法　选择２０例经临床病理检查证实为鼻咽癌患者,其中１０例有颅底侵犯,１０例无颅底侵犯,采用ＣＭＳ逆向调强计划系统分别设计非共面调强计划（５个共面野和２个非共面野）和共面调强计划（７野共面）,同一患者两个治疗计划采取相同的物理目标函数。用剂量体积直方图（ＤＶＨ）、靶区覆盖度、靶区适形度、机器跳数、子野数目等物理参数作为计划评价指标。结果　对于剂量不均匀度、适形指数,非共面野调强均要好于共面野。对于有颅底侵犯的病例,眼球、晶体受量非共面野调强要明显低于共面野,其他正常组织无明显差别。对于无颅底侵犯病例,非共面野正常组织的受量无优势,反而可能增加眼球的受量。非共面调强和共面调强在子野数目和机器跳数均无统计学差异;与共面调强放疗计划相比,非共面调强计划并未延长治疗时间。结论　非共面射野在调强放疗计划可以改善剂量分布,提高计划优化的结果。