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Inversion-recovery ultrashort-echo-time (IR-UTE) MRI-based detection of radiation dose heterogeneity in gynecologic cancer patients treated with HDR brachytherapy. 基于反相恢复超短波回波时间(IR-UTE)磁共振成像检测接受 HDR 近距离放射治疗的妇科癌症患者的放射剂量异质性。
IF 3.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-06 DOI: 10.1186/s13014-024-02499-2
Khadija Sheikh, Bruce L Daniel, Michael Roumeliotis, Junghoon Lee, William T Hrinivich, Thomas Benkert, Himanshu Bhat, Ravi T Seethamraju, Akila N Viswanathan, Ehud J Schmidt

Purpose: To evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT).

Methods: Seven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3-6 months post-BT. Diffuse-fibrosis (FDiffuse) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (FDense) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting FDiffuse and FDense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean FDiffuse and FDense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT FDiffuse and FDense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT FDense across IDLs was determined using paired t-tests with Bonferroni correction.

Results: FDense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. FDense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in FDense post-BT (n = 5, r = .89, p = .04). Post-BT FDiffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL.

Conclusions: Results suggest that FDense SI 3-6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether FDiffuse and FDense are accurate biomarkers of fibrotic radiation response.

目的:评估接受高剂量率近距离放射治疗(HDR)的妇科癌症患者的放射线(RT)与RT后反转恢复超回波时间(IR-UTE)MRI信号强度(SI)之间的关系:七名患者接受了全骨盆 RT(WPRT)治疗,随后在高风险临床靶区(HR-CTV)进行了 BT 治疗。在三个时间点采集了 MR 图像:RT 前、WPRT 后/BT 前和 BT 后 3-6 个月。弥漫性纤维化(FDiffuse)采用非对比双回波 IR(反转时间 [TI] = 60 ms)UTE 研究应用成像,对后一回波进行图像减影,仅保留超短回波 SI。致密纤维化(FDense)成像采用单回波晚期钆增强 IR-UTE,在注射加达维斯特后 15 分钟采集。结果显示的 FDiffuse 和 FDense SI 与相应的臀肌 SI 一致。根据正常组织的解剖结构,在时间点之间对图像进行变形注册。使用多参数 MRI 对两个时间点的残余肿瘤进行分割。创建了与处方 BT 剂量的 50%、100%、150% 和 200% 等剂量线 (IDL) 相对应的等值线。计算(i)每个 IDL 等值线和(ii)残余肿瘤内的平均 FDiffuse 和 FDense SI。BT 后 FDiffuse 和 FDense SI 与处方 BT 剂量相关。为了确定 BT 剂量和 IR-UTE SI 之间的关系,使用配对 t 检验和 Bonferroni 校正确定了 BT 后 FDense 在不同 IDL 之间的差异:结果:6/7 例患者的 FDense 在剂量较高的区域较高,100% 和 50% IDL 的平均值(± SD)分别为 357 ± 103% 和 331 ± 97% (p = .03)。在有反应的区域,较高剂量区域的 FDense 较高,150% 和 50% IDL 的平均值(± SD)分别为 380 ± 122% 和 356 ± 135% (p = .03)。在分段残余肿瘤内,处方剂量的增加与 BT 后 FDense 的增加相关(n = 5,r = .89,p = .04)。在100% IDL内,BT后FDiffuse与BT处方剂量成反比(n = 7,r = -.83,p = .02):结果表明,BT 后 3-6 个月的 FDense SI 是衡量组织对异质 BT 放射剂量反应的敏感指标。未来的研究将验证 FDiffuse 和 FDense 是否是纤维化辐射反应的准确生物标记。
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引用次数: 0
Advances in breast cancer treatment: a systematic review of preoperative stereotactic body radiotherapy (SBRT) for breast cancer. 乳腺癌治疗进展:乳腺癌术前立体定向体放射治疗 (SBRT) 系统综述。
IF 3.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-02 DOI: 10.1186/s13014-024-02497-4
Mateusz Bilski, Katarzyna Konat-Bąska, Maria Alessia Zerella, Stefanie Corradini, Marcin Hetnał, Maria Cristina Leonardi, Martyna Gruba, Aleksandra Grzywacz, Patrycja Hatala, Barbara Alicja Jereczek-Fossa, Jacek Fijuth, Łukasz Kuncman

Breast conserving treatment typically involves surgical excision of tumor and adjuvant radiotherapy targeting the breast area or tumor bed. Accurately defining the tumor bed is challenging and lead to irradiation of greater volume of healthy tissues. Preoperative stereotactic body radiotherapy (SBRT) which target tumor may solves that issues. We conducted a systematic literature review to evaluates the early toxicity and cosmetic outcomes of this promising treatment approach. Secondary we reviewed pathological complete response (pCR) rates, late toxicity, patient selection criteria and radiotherapy protocols. We retrieved literature from PubMed, Scopus, Web of Science, Cochrane, ScienceDirect, and ClinicalTrials.gov. The study adhered to the PRISMA 2020 guidelines. Ten prospective clinical trials (7 phase II, 3 phase I), encompassing 188 patients (aged 18-75 years, cT1-T3 cN0-N3 cM0, primarily with ER/PgR-positive, HER2-negative status,), were analyzed. Median follow-up was 15 months (range 3-30). Treatment involved single-fraction SBRT (15-21Gy) in five studies and fractionated (19.5-31.5Gy in 3 fractions) in the rest. Time interval from SBRT to surgery was 9.5 weeks (range 1-28). Acute and late G2 toxicity occurred in 0-17% and 0-19% of patients, respectively, G3 toxicity was rarely observed. The cosmetic outcome was excellent in 85-100%, fair in 0-10% and poor in only 1 patient. pCR varied, showing higher rates (up to 42%) with longer intervals between SBRT and surgery and when combined with neoadjuvant systemic therapy (up to 90%). Preoperative SBRT significantly reduce overall treatment time, enabling to minimalize volumes. Early results indicate excellent cosmetic effects and low toxicity.

保乳治疗通常包括手术切除肿瘤和针对乳房区域或肿瘤床的辅助放疗。准确界定肿瘤床具有挑战性,会导致更大体积的健康组织受到照射。针对肿瘤的术前立体定向体放射治疗(SBRT)可以解决这一问题。我们进行了一项系统性文献回顾,以评估这种前景广阔的治疗方法的早期毒性和美容效果。其次,我们回顾了病理完全反应率(pCR)、晚期毒性、患者选择标准和放疗方案。我们从 PubMed、Scopus、Web of Science、Cochrane、ScienceDirect 和 ClinicalTrials.gov 检索文献。研究遵循了 PRISMA 2020 指南。研究分析了 10 项前瞻性临床试验(7 项 II 期,3 项 I 期),包括 188 名患者(年龄 18-75 岁,cT1-T3 cN0-N3 cM0,主要为 ER/PgR 阳性、HER2 阴性)。中位随访时间为 15 个月(3-30 个月)。五项研究采用单次分次SBRT治疗(15-21Gy),其余研究采用分次治疗(19.5-31.5Gy,3次分次)。从SBRT到手术的时间间隔为9.5周(1-28周)。急性和晚期G2毒性发生率分别为0-17%和0-19%,很少观察到G3毒性。85%-100%的患者美容效果极佳,0%-10%的患者美容效果一般,仅有1名患者美容效果较差。pCR的情况各不相同,SBRT与手术间隔时间越长,pCR率越高(高达42%),与新辅助系统疗法联合使用时,pCR率高达90%。术前 SBRT 大大缩短了整体治疗时间,使治疗量最小化。早期结果表明,SBRT 具有良好的美容效果和低毒性。
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引用次数: 0
Effect of dose to parotid ducts on Sticky Saliva and Xerostomia in radiotherapy of head and neck squamous cell carcinoma. 腮腺导管剂量对头颈部鳞状细胞癌放疗中粘稠唾液和口臭的影响
IF 3.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-02 DOI: 10.1186/s13014-024-02495-6
Daniel H Schanne, Dominik U Alder, Jana Lippmann, Daniel M Aebersold, Olgun Elicin

Background: Radiotherapy (RT) in head and neck squamous cell cancer (HNSCC) often leads to sticky saliva and xerostomia (SSX). Dose sparing of salivary glands (SG) reduces occurrence of SSX but few studies investigated the relationship between RT dose to SG substructures and SSX. We therefore investigated this hypothesis, focusing on the parotid duct (PD).

Methods: Retrospective data was collected from 99 HNSCC patients treated at our center with (chemo-)radiotherapy (CRT). PD and other organs-at-risk (OAR) were (re-)contoured and DVHs were generated without re-planning. SSX was graded according to CTCAE v.4.03 and evaluated at acute, subacute, and two late timepoints.

Results: Most patients presented with loco-regionally advanced disease. In 47% of patients, up-front neck dissection preceded CRT. Weighted mean dose was 28.6 Gy for bilateral parotid glands (PG), and 32.0 Gy for PD. Acute SSX presented as grades 0 (35.3%), I (41.4%), II (21.2%) and III (2.0%). There was no association of OARs and SSX ≥ grade 2 in univariable logistic regression (LR). Multivariable LR showed statistically significant relationship of acute SSX with: PG weighted mean dose (OR 0.84, p = 0.004), contralateral PG mean dose (OR 1.14, p = 0.02) and contralateral PD planning OAR (PD PRV) mean dose (OR 1.84, p = 0.03).

Conclusions: There was an association of acute SSX with dose exposure of PD PRV in multivariable regression, only. Due to statistical uncertainties and the retrospective nature of this analysis, further studies are required to confirm or reject the hypothesis.

背景:头颈部鳞状细胞癌(HNSCC)的放疗(RT)经常导致唾液粘稠和口干症(SSX)。唾液腺(SG)的剂量疏导可减少唾液粘稠和口臭的发生,但很少有研究调查唾液腺下结构的 RT 剂量与唾液粘稠和口臭之间的关系。因此,我们对这一假设进行了研究,重点是腮腺导管(PD):我们从本中心接受(化疗)放疗(CRT)的 99 例 HNSCC 患者中收集了回顾性数据。对腮腺导管和其他危险器官(OAR)进行(重新)轮廓描绘,并在不重新规划的情况下生成 DVH。根据 CTCAE v.4.03 对 SSX 进行分级,并在急性、亚急性和两个晚期时间点进行评估:结果:大多数患者为局部区域晚期疾病。47%的患者在接受 CRT 治疗前进行了颈部切除术。双侧腮腺(PG)的加权平均剂量为28.6 Gy,PD为32.0 Gy。急性 SSX 分为 0 级(35.3%)、I 级(41.4%)、II 级(21.2%)和 III 级(2.0%)。在单变量逻辑回归(LR)中,OAR 与≥ 2 级的 SSX 没有关联。多变量 LR 显示急性 SSX 与以下因素有显著的统计学关系:PG加权平均剂量(OR 0.84,p = 0.004)、对侧PG平均剂量(OR 1.14,p = 0.02)和对侧PD计划OAR(PD PRV)平均剂量(OR 1.84,p = 0.03):结论:仅在多变量回归中,急性SSX与PD PRV的剂量暴露有关。由于统计学上的不确定性和该分析的回顾性,需要进一步研究来证实或否定该假设。
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引用次数: 0
Prostate radiotherapy may cause fertility issues: a retrospective analysis of testicular dose following modern radiotherapy techniques 前列腺放疗可能导致生育问题:现代放疗技术后睾丸剂量的回顾性分析
IF 3.6 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.1186/s13014-024-02498-3
M. Kissel, M. Terlizzi, N. Giraud, A. Alexis, M. Cheve, J. Vautier, A. Bossi, P. Morice, P. Blanchard
Prostate cancer in younger men is rare but not exceptional. Radiotherapy is a cornerstone of prostate cancer treatment and yet, its impact on fertility is scarcely reported in literature. Given the radiosensitivity of testicular tissue, this study aimed to determine the testicular dose using modern radiotherapy techniques for definitive prostate irradiation. One hundred radiotherapy plans were reviewed. Testicles were contoured retrospectively without dosimetric optimization on testicles. The median testicular dose was 0.58 Gy: 0.18 Gy in stereotactic plans, 0.62 Gy in Volumetric Modulated Arc Therapy plans and 1.50 Gy in Tomotherapy plans (p < 0.001). Pelvic nodal irradiation increased the median testicular dose to 1.18 Gy versus 0.26 Gy without nodal irradiation (p < 0.001). Weight and BMI were inversely associated with testicular dose (p < 0.005). 65% of patients reached the theoretical dose threshold for transient azoospermia, and 10% received more than 2 Gy, likely causing definitive azoospermia. Despite being probably lower than doses from older techniques, the testicular dose delivered with modern prostate radiotherapy is not negligible and is often underestimated because the contribution of daily repositioning imaging is not taken into account and most Treatment Planning Systems underestimate the out of field dose. Radiation oncologists should consider the impact on fertility and gonadal endocrine function, counseling men on sperm preservation if they wish to maintain fertility. Trial registration: retrospectively registered.
年轻男性患前列腺癌的情况虽然罕见,但并非绝无仅有。放疗是前列腺癌治疗的基石,但文献中却很少报道放疗对生育能力的影响。考虑到睾丸组织的放射敏感性,本研究旨在利用现代放射治疗技术确定前列腺照射时的睾丸剂量。研究回顾了 100 例放射治疗计划。在未对睾丸进行剂量学优化的情况下,对睾丸进行了轮廓回溯。睾丸剂量中位数为 0.58 Gy:立体定向计划为0.18 Gy,体积调制弧线治疗计划为0.62 Gy,断层治疗计划为1.50 Gy(p < 0.001)。盆腔结节照射使睾丸的中位剂量增至 1.18 Gy,而无结节照射时为 0.26 Gy(p < 0.001)。体重和体重指数与睾丸剂量成反比(p < 0.005)。65%的患者达到了一过性无精子症的理论剂量阈值,10%的患者接受了超过2 Gy的照射,很可能导致明确的无精子症。尽管现代前列腺放疗的睾丸剂量可能低于旧技术的剂量,但也不容忽视,而且经常被低估,因为日常重新定位成像的贡献没有考虑在内,而且大多数治疗计划系统都低估了场外剂量。放射肿瘤专家应考虑对生育能力和性腺内分泌功能的影响,如果男性希望保持生育能力,应指导他们保存精子。试验登记:回顾性登记。
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引用次数: 0
Treatment outcome of localized prostate cancer using transperineal ultrasound image-guided radiotherapy 经会阴超声图像引导放射治疗局部前列腺癌的疗效
IF 3.6 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.1186/s13014-024-02490-x
Kenji Takai, Ryota Watanabe, Ken-ichi Hyogo, Yuri Ito, Nobuko Minagawa, Yusuke Sato, Yoshikazu Matsuda, Kenji Nemoto
We report the results of a retrospective analysis of localized prostate cancer (LPCa) treated with transperineal ultrasound image-guided radiotherapy (TPUS-IGRT). A total of 124 patients (median age: 74 y, 46–84 y) with LPCa who underwent TPUS-IGRT (Clarity Autoscan system; CAS, Elekta; Stockholm, Sweden) between April 2016 and October 2021 for curative/after hormone induction were enrolled. The number of patients by risk (National Comprehensive Cancer Network 2019) was 7, 25, 42, and 50 for low (LR), good intermediate (good IR), poor intermediate (poor IR), and high (HR)/very high (VHR), respectively. Ninety-five patients were given neoadjuvant hormonal therapy. The planning target volume margin setting was 3 mm for rectal in most cases, 5–7 mm for superior/inferior, and 5 mm for anterior/right/left. The principle prescribed dose is 74 Gy (LR), 76 Gy (good IR), and 76–78 Gy (poor IR or above). CAS was equipped with a real-time prostate intrafraction monitoring (RTPIFM) system. When a displacement of 2–3 mm or more was detected, irradiation was paused, and the patients were placed on standby for prostate reinstatement/recorrection. Of the 3135 fractions in 85 patients for whom RTPIFM was performed, 1008 fractions (32.1%) were recorrected at least once after starting irradiation. A total of 123 patients completed the radiotherapy course. The 5-year overall survival rate was 95.9%. The 5-year biological prostate-specific antigen relapse-free survival rate (bPFS) was 100% for LR, 92.9% for intermediate IR, and 93.2% for HR/VHR (Phoenix method). The 5-year late toxicity rate of Grade 2+ was 7.4% for genitourinary (GU) and 6.5% for gastrointestinal (GI) organs. Comparing the ≤ 76 Gy group to the 78 Gy group for both GU and GI organs, the incidence was higher in the 78 Gy group for both groups. These results suggest that TPUS-IGRT is well tolerated, as the bPFS and incidence of late toxicity are almost comparable to those reported by other sources of image-guided radiotherapy.
我们报告了对采用经会阴超声图像引导放疗(TPUS-IGRT)治疗局部前列腺癌(LPCa)的回顾性分析结果。2016年4月至2021年10月期间,共有124名LPCa患者(中位年龄:74岁,46-84岁)接受了TPUS-IGRT(Clarity Autoscan系统;CAS,Elekta;瑞典斯德哥尔摩)治疗/激素诱导后治疗。按风险(美国国立综合癌症网络 2019)划分,低风险(LR)、良好中间风险(良好 IR)、较差中间风险(较差 IR)和高风险(HR)/极高风险(VHR)的患者人数分别为 7、25、42 和 50 人。95名患者接受了新辅助激素治疗。大多数病例的计划目标体积边缘设置为直肠3毫米,上/下5-7毫米,前/右/左5毫米。处方剂量原则上为 74 Gy(LR)、76 Gy(良好 IR)和 76-78 Gy(不良 IR 或以上)。CAS 配备了实时前列腺腔内分量监测(RTPIFM)系统。当检测到2-3毫米或更大的移位时,就会暂停照射,让患者处于前列腺复位/校正待命状态。在 85 位接受 RTPIFM 治疗的患者的 3135 个分段中,有 1008 个分段(32.1%)在开始照射后至少进行了一次重新校正。共有123名患者完成了放疗疗程。5年总生存率为95.9%。LR患者的5年生物前列腺特异抗原无复发生存率(bPFS)为100%,中期IR患者为92.9%,HR/VHR患者为93.2%(凤凰法)。泌尿生殖系统(GU)和胃肠道(GI)器官的5年晚期2级以上毒性率分别为7.4%和6.5%。在泌尿生殖器官和消化道器官方面,≤76 Gy 组与 78 Gy 组相比,78 Gy 组的发生率均较高。这些结果表明,TPUS-IGRT 的耐受性良好,因为其 bPFS 和晚期毒性发生率几乎与其他影像引导放疗的报道相当。
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引用次数: 0
Clinical outcomes and risk stratification in unresectable biliary tract cancers undergoing radiation therapy 接受放射治疗的不可切除胆道癌症的临床结果和风险分层
IF 3.6 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.1186/s13014-024-02481-y
Uri Amit, Misra Shagun, John P. Plastaras, James M. Metz, Thomas B. Karasic, Maryanne J. Lubas, Edgar Ben-Josef
Biliary tract cancers (BTC) are rare and aggressive malignancies originating from intrahepatic and extrahepatic bile ducts and the gallbladder. Surgery is the only curative option, but due to late-stage diagnosis, is frequently not feasible, leaving chemotherapy as the primary treatment. Radiotherapy (RT) can be an effective alternative for patients with unresectable, non-metastatic BTC despite the generally poor prognosis and significant variability. To help manage patients with unresectable BTC who receive RT, we aimed to identify prognostic markers that could aid in predicting overall survival (OS). A retrospective cohort study was conducted at the University of Pennsylvania, involving seventy-eight patients with unresectable BTC treated with definitive intent RT. Comprehensive demographic, clinical, and treatment-related data were extracted from the electronic medical records. Univariate and multivariate Cox regressions were employed to identify predictors of OS after RT. A biomarker model was developed for refined survival prediction. The cohort primarily comprised patients with good performance status without significant hepatic dysfunction at presentation. The predominant treatment approach involved hypofractionated RT or concurrent 5FU-based chemoRT. Median OS after RT was 12.3 months, and 20 patients (15.6%) experienced local progression with a median time of 30.1 months. Univariate and multivariate analyses identified CA19-9 (above median) and higher albumin-bilirubin (ALBI) grades at presentation as significant predictors of poor OS. Median OS after RT was 24 months for patients with no risk factors and 6.3 months for those with both. Our study demonstrates generally poor but significantly heterogeneous OS in patients with unresectable BTC treated with RT. We have developed a biomarker model based on CA19-9 and ALBI grade at presentation that can distinguish sub-populations with markedly diverse prognoses. This model can aid the clinical management of this challenging disease.
胆道癌(BTC)是一种罕见的侵袭性恶性肿瘤,起源于肝内、肝外胆管和胆囊。手术是唯一的根治选择,但由于诊断较晚,往往不可行,因此化疗成为主要治疗手段。放疗(RT)是不可切除、非转移性 BTC 患者的有效替代疗法,尽管其预后普遍较差且存在很大的变异性。为了帮助管理接受 RT 治疗的不可切除 BTC 患者,我们旨在找出有助于预测总生存期(OS)的预后标志物。宾夕法尼亚大学开展了一项回顾性队列研究,共有 78 名接受确定性 RT 治疗的不可切除 BTC 患者参与。研究人员从电子病历中提取了全面的人口统计学、临床和治疗相关数据。采用单变量和多变量 Cox 回归来确定 RT 术后 OS 的预测因素。还开发了一个生物标志物模型,用于完善生存预测。队列中的患者主要表现良好,发病时无明显肝功能障碍。主要的治疗方法包括低分次RT或同时进行基于5FU的化疗RT。RT 后的中位 OS 为 12.3 个月,20 例患者(15.6%)出现局部进展,中位时间为 30.1 个月。通过单变量和多变量分析发现,CA19-9(高于中位数)和发病时白蛋白-胆红素(ALBI)分级较高是不良OS的重要预测因素。无危险因素的患者 RT 后的中位生存期为 24 个月,有危险因素的患者为 6.3 个月。我们的研究表明,接受 RT 治疗的不可切除 BTC 患者的 OS 普遍较差,但存在明显的异质性。我们开发了一种基于 CA19-9 和 ALBI 分级的生物标志物模型,该模型可以区分预后明显不同的亚群。该模型可帮助临床治疗这种具有挑战性的疾病。
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引用次数: 0
Factors influencing pathological complete response and tumor regression in neoadjuvant radiotherapy and chemotherapy for high-risk breast cancer. 影响高危乳腺癌新辅助放化疗病理完全反应和肿瘤消退的因素。
IF 3.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-07-31 DOI: 10.1186/s13014-024-02450-5
Jan Haussmann, Wilfried Budach, Carolin Nestle-Krämling, Sylvia Wollandt, Danny Jazmati, Bálint Tamaskovics, Stefanie Corradini, Edwin Bölke, Alexander Haussmann, Werner Audretsch, Christiane Matuschek

Background: Pathological complete response (pCR) is a well-established prognostic factor in breast cancer treated with neoadjuvant systemic therapy (naST). The determining factors of pCR are known to be intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage as well as type of systemic therapy. The addition of neoadjuvant radiotherapy (naRT) to this paradigm might improve response, freedom from disease, toxicity and cosmetic outcome compared to adjuvant radiotherapy. The factors for pCR and primary tumor regression when neoadjuvant radiation therapy is added to chemotherapy have not been thoroughly described.

Methods: We performed a retrospective analysis of 341 patients (cT1-cT4/cN0-N+) treated with naRT and naST between 1990 and 2003. Patients underwent naRT to the breast and mostly to the supra-/infraclavicular lymph nodes combined with an electron or brachytherapy boost. NaST was given either sequentially or simultaneously to naRT using different regimens. We used the univariate and multivariate regression analysis to estimate the effect of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) as well as complete primary tumor response (ypT0/Tis; bpCR) in our cohort. Receiver operating characteristic (ROC) analysis was performed to evaluate the interval between radiotherapy (RT) and resection (Rx) as well as radiotherapy dose.

Results: Out of 341 patients, pCR and pbCR were achieved in 31% and 39%, respectively. pCR rate was influenced by resection type, breast cancer subtype, primary tumor stage and interval from radiation to surgery in the multivariate analysis. Univariate analysis of bpCR showed age, resection type, breast cancer subtype, clinical tumor stage and grading as significant factors. Resection type, subtype and clinical tumor stage remained significant in multivariate analysis. Radiation dose to the tumor and interval from radiation to surgery were not significant factors for pCR. However, when treatment factors were added to the model, a longer interval from radiotherapy to resection was a significant predictor for pCR.

Conclusions: The factors associated with pCR following naST and naRT are similar to known factors after naST alone. Longer interval to surgery might to be associated with higher pCR rates. Dose escalation beyond 60 Gy did not result in higher response rates.

背景:病理完全缓解(pCR)是乳腺癌新辅助全身治疗(naST)的一个公认的预后因素。病理完全反应的决定因素包括内在亚型、增殖指数、分级、临床肿瘤和结节分期以及全身治疗类型。与辅助放疗相比,在这一模式中加入新辅助放疗(naRT)可能会改善反应、免于疾病、毒性和美容效果。在化疗中加入新辅助放疗时,pCR 和原发肿瘤消退的因素尚未得到充分说明:我们对 1990 年至 2003 年间接受 naRT 和 naST 治疗的 341 例患者(cT1-cT4/cN0-N+)进行了回顾性分析。患者接受了乳腺和大部分锁骨上/锁骨下淋巴结的naRT治疗,同时接受了电子或近距离放射治疗。NaST是在naRT的基础上采用不同的治疗方案先后或同时进行的。我们使用单变量和多变量回归分析来估计不同亚组和治疗方式对我们队列中的 pCR(ypT0/Tis 和 ypN0)以及完全原发肿瘤反应(ypT0/Tis;bpCR)的影响。对放疗(RT)和切除(Rx)之间的间隔时间以及放疗剂量进行了接收者操作特征(ROC)分析:在多变量分析中,pCR 率受切除类型、乳腺癌亚型、原发肿瘤分期和放疗至手术时间间隔的影响。bpCR 的单变量分析显示,年龄、切除类型、乳腺癌亚型、临床肿瘤分期和分级是重要的影响因素。在多变量分析中,切除类型、亚型和临床肿瘤分期仍然重要。肿瘤的放射剂量和从放射到手术的时间间隔对 pCR 无显著影响。然而,当治疗因素被加入到模型中时,从放疗到切除的时间间隔更长是预测pCR的重要因素:结论:naST和naRT治疗后与pCR相关的因素与单独naST治疗后的已知因素相似。较长的手术间隔可能与较高的 pCR 率有关。超过60 Gy的剂量升级不会导致更高的反应率。
{"title":"Factors influencing pathological complete response and tumor regression in neoadjuvant radiotherapy and chemotherapy for high-risk breast cancer.","authors":"Jan Haussmann, Wilfried Budach, Carolin Nestle-Krämling, Sylvia Wollandt, Danny Jazmati, Bálint Tamaskovics, Stefanie Corradini, Edwin Bölke, Alexander Haussmann, Werner Audretsch, Christiane Matuschek","doi":"10.1186/s13014-024-02450-5","DOIUrl":"10.1186/s13014-024-02450-5","url":null,"abstract":"<p><strong>Background: </strong>Pathological complete response (pCR) is a well-established prognostic factor in breast cancer treated with neoadjuvant systemic therapy (naST). The determining factors of pCR are known to be intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage as well as type of systemic therapy. The addition of neoadjuvant radiotherapy (naRT) to this paradigm might improve response, freedom from disease, toxicity and cosmetic outcome compared to adjuvant radiotherapy. The factors for pCR and primary tumor regression when neoadjuvant radiation therapy is added to chemotherapy have not been thoroughly described.</p><p><strong>Methods: </strong>We performed a retrospective analysis of 341 patients (cT1-cT4/cN0-N+) treated with naRT and naST between 1990 and 2003. Patients underwent naRT to the breast and mostly to the supra-/infraclavicular lymph nodes combined with an electron or brachytherapy boost. NaST was given either sequentially or simultaneously to naRT using different regimens. We used the univariate and multivariate regression analysis to estimate the effect of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) as well as complete primary tumor response (ypT0/Tis; bpCR) in our cohort. Receiver operating characteristic (ROC) analysis was performed to evaluate the interval between radiotherapy (RT) and resection (Rx) as well as radiotherapy dose.</p><p><strong>Results: </strong>Out of 341 patients, pCR and pbCR were achieved in 31% and 39%, respectively. pCR rate was influenced by resection type, breast cancer subtype, primary tumor stage and interval from radiation to surgery in the multivariate analysis. Univariate analysis of bpCR showed age, resection type, breast cancer subtype, clinical tumor stage and grading as significant factors. Resection type, subtype and clinical tumor stage remained significant in multivariate analysis. Radiation dose to the tumor and interval from radiation to surgery were not significant factors for pCR. However, when treatment factors were added to the model, a longer interval from radiotherapy to resection was a significant predictor for pCR.</p><p><strong>Conclusions: </strong>The factors associated with pCR following naST and naRT are similar to known factors after naST alone. Longer interval to surgery might to be associated with higher pCR rates. Dose escalation beyond 60 Gy did not result in higher response rates.</p>","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"19 1","pages":"99"},"PeriodicalIF":3.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Improving the performance of deep learning models in predicting and classifying gamma passing rates with discriminative features and a class balancing technique: a retrospective cohort study. 利用判别特征和类平衡技术提高深度学习模型在预测和分类伽马通过率方面的性能:一项回顾性队列研究。
IF 3.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-07-31 DOI: 10.1186/s13014-024-02496-5
Wei Song, Wen Shang, Chunying Li, Xinyu Bian, Hong Lu, Jun Ma, Dahai Yu

Background: The purpose of this study was to improve the deep learning (DL) model performance in predicting and classifying IMRT gamma passing rate (GPR) by using input features related to machine parameters and a class balancing technique.

Methods: A total of 2348 fields from 204 IMRT plans for patients with nasopharyngeal carcinoma were retrospectively collected to form a dataset. Input feature maps, including fluence, leaf gap, leaf speed of both banks, and corresponding errors, were constructed from the dynamic log files. The SHAP framework was employed to compute the impact of each feature on the model output for recursive feature elimination. A series of UNet++ based models were trained on the obtained eight feature sets with three fine-tuning methods including the standard mean squared error (MSE) loss, a re-sampling technique, and a proposed weighted MSE loss (WMSE). Differences in mean absolute error, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared between the different models.

Results: The models trained with feature sets including leaf speed and leaf gap features predicted GPR for failed fields more accurately than the other models (F(7, 147) = 5.378, p < 0.001). The WMSE loss had the highest accuracy in predicting GPR for failed fields among the three fine-tuning methods (F(2, 42) = 14.149, p < 0.001), while an opposite trend was observed in predicting GPR for passed fields (F(2, 730) = 9.907, p < 0.001). The WMSE_FS5 model achieved a superior AUC (0.92) and more balanced sensitivity (0.77) and specificity (0.89) compared to the other models.

Conclusions: Machine parameters can provide discriminative input features for GPR prediction in DL. The novel weighted loss function demonstrates the ability to balance the prediction and classification accuracy between the passed and failed fields. The proposed approach is able to improve the DL model performance in predicting and classifying GPR, and can potentially be integrated into the plan optimization process to generate higher deliverability plans.

Trial registration: This clinical trial was registered in the Chinese Clinical Trial Registry on March 26th, 2020 (registration number: ChiCTR2000031276). https://clinicaltrials.gov/ct2/show/ChiCTR2000031276.

背景:本研究的目的是通过使用与机器参数相关的输入特征和类平衡技术,提高深度学习(DL)模型在预测和分类 IMRT 伽马通过率(GPR)方面的性能:回顾性收集了鼻咽癌患者的 204 个 IMRT 计划中的 2348 个场,形成数据集。从动态日志文件中构建了输入特征图,包括通量、叶间隙、两组叶速度以及相应的误差。采用 SHAP 框架计算每个特征对模型输出的影响,以进行递归特征消除。利用三种微调方法,包括标准均方误差 (MSE) 损失、重新采样技术和建议的加权 MSE 损失 (WMSE),对获得的八个特征集进行了一系列基于 UNet++ 的模型训练。比较了不同模型在平均绝对误差、接收器工作特征曲线下面积(AUC)、灵敏度和特异性方面的差异:结果:使用包括叶片速度和叶片间隙特征在内的特征集训练的模型比其他模型更准确地预测了失败田块的 GPR(F(7, 147) = 5.378, p 结论:机器参数可提供判别输入特征的能力:机器参数可为 DL 的 GPR 预测提供具有区分性的输入特征。新颖的加权损失函数证明了在通过和失败区域之间平衡预测和分类准确性的能力。所提出的方法能够提高 DL 模型在预测和分类 GPR 方面的性能,并有可能集成到计划优化流程中,以生成更高的交付计划:本临床试验于 2020 年 3 月 26 日在中国临床试验注册中心注册(注册号:ChiCTR2000031276)。https://clinicaltrials.gov/ct2/show/ChiCTR2000031276。
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引用次数: 0
Quantitative PSMA-PET parameters in localized prostate cancer: prognostic and potential predictive value. 局部前列腺癌的 PSMA-PET 定量参数:预后和潜在预测价值。
IF 3.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-07-29 DOI: 10.1186/s13014-024-02483-w
Stephanie Bela Andela, Holger Amthauer, Christian Furth, Julian M Rogasch, Marcus Beck, Felix Mehrhof, Pirus Ghadjar, Jörg van den Hoff, Tobias Klatte, Rana Tahbaz, Daniel Zips, Frank Hofheinz, Sebastian Zschaeck

Background: PSMA-PET is increasingly used for staging prostate cancer (PCA) patients. However, it is not clear if quantitative imaging parameters of positron emission tomography (PET) have an impact on disease progression and are thus important for the prognosis of localized PCA.

Methods: This is a monocenter retrospective analysis of 86 consecutive patients with localized intermediate or high-risk PCA and PSMA-PET before treatment The quantitative PET parameters maximum standardized uptake value (SUVmax), tumor asphericity (ASP), PSMA tumor volume (PSMA-TV), and PSMA total lesion uptake (PSMA-TLU = PSMA-TV × SUVmean) were assessed for their prognostic significance in patients with radiotherapy or surgery. Cox regression analyses were performed for biochemical recurrence-free survival, overall survival (OS), local control, and loco-regional control (LRC).

Results: 67% of patients had high-risk disease, 51 patients were treated with radiotherapy, and 35 with surgery. Analysis of metric PET parameters in the whole cohort revealed a significant association of PSMA-TV (p = 0.003), PSMA-TLU (p = 0.004), and ASP (p < 0.001) with OS. Upon binarization of PET parameters, several other parameters showed a significant association with clinical outcome. When analyzing high-risk patients according to the primary treatment approach, a previously published cut-off for SUVmax (8.6) showed a significant association with LRC in surgically treated (p = 0.048), but not in primary irradiated (p = 0.34) patients. In addition, PSMA-TLU (p = 0.016) seemed to be a very promising biomarker to stratify surgical patients.

Conclusion: Our data confirm one previous publication on the prognostic impact of SUVmax in surgically treated patients with high-risk PCA. Our exploratory analysis indicates that PSMA-TLU might be even better suited. The missing association with primary irradiated patients needs prospective validation with a larger sample size to conclude a predictive potential. Trial registration Due to the retrospective nature of this research, no registration was carried out.

背景:PSMA-PET越来越多地被用于前列腺癌(PCA)患者的分期。然而,尚不清楚正电子发射断层扫描(PET)的定量成像参数是否对疾病进展有影响,因而对局部 PCA 的预后是否重要:方法:这是一项单中心回顾性分析,研究对象为连续86例局部中危或高危PCA患者,治疗前进行了PSMA-PET检查。评估了PET定量参数最大标准化摄取值(SUVmax)、肿瘤非球面度(ASP)、PSMA肿瘤体积(PSMA-TV)和PSMA总病灶摄取量(PSMA-TLU = PSMA-TV × SUVmean)对放疗或手术患者的预后意义。对无生化复发生存率、总生存率(OS)、局部控制率和局部区域控制率(LRC)进行了Cox回归分析:67%的患者患有高危疾病,51名患者接受了放疗,35名患者接受了手术治疗。对整个队列的PET指标进行分析后发现,PSMA-TV(p = 0.003)、PSMA-TLU(p = 0.004)和ASP(p max (8.6))与手术治疗患者的LRC有显著相关性(p = 0.048),但与原发性放疗患者的LRC无显著相关性(p = 0.34)。此外,PSMA-TLU(p = 0.016)似乎是对手术患者进行分层的一个非常有前景的生物标志物:我们的数据证实了之前发表的一篇关于 SUVmax 对接受手术治疗的高危 PCA 患者预后影响的文章。我们的探索性分析表明,PSMA-TLU 可能更适合。与原发性照射患者的关联缺失需要更大样本量的前瞻性验证,才能得出预测潜力的结论。试验注册 由于该研究具有回顾性,因此没有进行注册。
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引用次数: 0
Comparison of data fusion strategies for automated prostate lesion detection using mpMRI correlated with whole mount histology. 比较利用 mpMRI 与整装组织学相关联的数据融合策略自动检测前列腺病变。
IF 3.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-07-29 DOI: 10.1186/s13014-024-02471-0
Deepa Darshini Gunashekar, Lars Bielak, Benedict Oerther, Matthias Benndorf, Andrea Nedelcu, Samantha Hickey, Constantinos Zamboglou, Anca-Ligia Grosu, Michael Bock

Background: In this work, we compare input level, feature level and decision level data fusion techniques for automatic detection of clinically significant prostate lesions (csPCa).

Methods: Multiple deep learning CNN architectures were developed using the Unet as the baseline. The CNNs use both multiparametric MRI images (T2W, ADC, and High b-value) and quantitative clinical data (prostate specific antigen (PSA), PSA density (PSAD), prostate gland volume & gross tumor volume (GTV)), and only mp-MRI images (n = 118), as input. In addition, co-registered ground truth data from whole mount histopathology images (n = 22) were used as a test set for evaluation.

Results: The CNNs achieved for early/intermediate / late level fusion a precision of 0.41/0.51/0.61, recall value of 0.18/0.22/0.25, an average precision of 0.13 / 0.19 / 0.27, and F scores of 0.55/0.67/ 0.76. Dice Sorensen Coefficient (DSC) was used to evaluate the influence of combining mpMRI with parametric clinical data for the detection of csPCa. We compared the DSC between the predictions of CNN's trained with mpMRI and parametric clinical and the CNN's trained with only mpMRI images as input with the ground truth. We obtained a DSC of data 0.30/0.34/0.36 and 0.26/0.33/0.34 respectively. Additionally, we evaluated the influence of each mpMRI input channel for the task of csPCa detection and obtained a DSC of 0.14 / 0.25 / 0.28.

Conclusion: The results show that the decision level fusion network performs better for the task of prostate lesion detection. Combining mpMRI data with quantitative clinical data does not show significant differences between these networks (p = 0.26/0.62/0.85). The results show that CNNs trained with all mpMRI data outperform CNNs with less input channels which is consistent with current clinical protocols where the same input is used for PI-RADS lesion scoring.

Trial registration: The trial was registered retrospectively at the German Register for Clinical Studies (DRKS) under proposal number Nr. 476/14 & 476/19.

背景:在这项工作中,我们比较了用于临床重大前列腺病变(csPCa)自动检测的输入级、特征级和决策级数据融合技术:在这项工作中,我们比较了用于自动检测有临床意义的前列腺病变(csPCa)的输入级、特征级和决策级数据融合技术:方法:以 Unet 为基线,开发了多种深度学习 CNN 架构。CNN 使用多参数 MRI 图像(T2W、ADC 和高 b 值)和定量临床数据(前列腺特异性抗原 (PSA)、前列腺特异性抗原密度 (PSAD)、前列腺腺体体积和肿瘤总体积 (GTV)),并仅将 mp-MRI 图像(n = 118)作为输入。此外,全装载组织病理学图像(n = 22)的共注册地面真实数据也被用作评估测试集:结果:CNN 的早期/中期/晚期融合精确度为 0.41/0.51/0.61,召回值为 0.18/0.22/0.25,平均精确度为 0.13 / 0.19 / 0.27,F 分数为 0.55/0.67/ 0.76。戴斯-索伦森系数(DSC)用于评估 mpMRI 与参数临床数据相结合对检测 csPCa 的影响。我们比较了使用 mpMRI 和临床参数训练的 CNN 预测结果与仅使用 mpMRI 图像作为输入的 CNN 预测结果之间的 DSC 差异。我们得到的 DSC 数据分别为 0.30/0.34/0.36 和 0.26/0.33/0.34。此外,我们还评估了每个 mpMRI 输入通道对 csPCa 检测任务的影响,得到的 DSC 分别为 0.14 / 0.25 / 0.28:结果表明,决策层融合网络在前列腺病变检测任务中表现更佳。将 mpMRI 数据与定量临床数据相结合,并未发现这些网络之间存在显著差异(p = 0.26/0.62/0.85)。结果表明,使用所有 mpMRI 数据训练的 CNN 优于使用较少输入通道的 CNN,这与当前的临床方案一致,即使用相同的输入进行 PI-RADS 病变评分:该试验在德国临床研究注册中心(DRKS)进行了回顾性注册,注册号为476/14和476/19。
{"title":"Comparison of data fusion strategies for automated prostate lesion detection using mpMRI correlated with whole mount histology.","authors":"Deepa Darshini Gunashekar, Lars Bielak, Benedict Oerther, Matthias Benndorf, Andrea Nedelcu, Samantha Hickey, Constantinos Zamboglou, Anca-Ligia Grosu, Michael Bock","doi":"10.1186/s13014-024-02471-0","DOIUrl":"10.1186/s13014-024-02471-0","url":null,"abstract":"<p><strong>Background: </strong>In this work, we compare input level, feature level and decision level data fusion techniques for automatic detection of clinically significant prostate lesions (csPCa).</p><p><strong>Methods: </strong>Multiple deep learning CNN architectures were developed using the Unet as the baseline. The CNNs use both multiparametric MRI images (T2W, ADC, and High b-value) and quantitative clinical data (prostate specific antigen (PSA), PSA density (PSAD), prostate gland volume & gross tumor volume (GTV)), and only mp-MRI images (n = 118), as input. In addition, co-registered ground truth data from whole mount histopathology images (n = 22) were used as a test set for evaluation.</p><p><strong>Results: </strong>The CNNs achieved for early/intermediate / late level fusion a precision of 0.41/0.51/0.61, recall value of 0.18/0.22/0.25, an average precision of 0.13 / 0.19 / 0.27, and F scores of 0.55/0.67/ 0.76. Dice Sorensen Coefficient (DSC) was used to evaluate the influence of combining mpMRI with parametric clinical data for the detection of csPCa. We compared the DSC between the predictions of CNN's trained with mpMRI and parametric clinical and the CNN's trained with only mpMRI images as input with the ground truth. We obtained a DSC of data 0.30/0.34/0.36 and 0.26/0.33/0.34 respectively. Additionally, we evaluated the influence of each mpMRI input channel for the task of csPCa detection and obtained a DSC of 0.14 / 0.25 / 0.28.</p><p><strong>Conclusion: </strong>The results show that the decision level fusion network performs better for the task of prostate lesion detection. Combining mpMRI data with quantitative clinical data does not show significant differences between these networks (p = 0.26/0.62/0.85). The results show that CNNs trained with all mpMRI data outperform CNNs with less input channels which is consistent with current clinical protocols where the same input is used for PI-RADS lesion scoring.</p><p><strong>Trial registration: </strong>The trial was registered retrospectively at the German Register for Clinical Studies (DRKS) under proposal number Nr. 476/14 & 476/19.</p>","PeriodicalId":49639,"journal":{"name":"Radiation Oncology","volume":"19 1","pages":"96"},"PeriodicalIF":3.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Radiation Oncology
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