A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions

BACKGROUND: It is hypothesized that oligometastatic disease represents a state of potentially curable, limited metastases. Stereotactic body radiation therapy (SBRT) is an option for patients who are not amenable to or do not want resection. METHODS: From 2001 to 2006, 121 patients with < or =5 detectable metastases were enrolled in 2 prospective studies that used curative-intent SBRT. Most patients were treated with 10 fractions of 5 Gray. Stereotactic radiosurgery was offered to patients with brain metastases. RESULTS: The 2-year overall survival (OS), progression-free survival (PFS), local control (LC), and distant control (DC) rates were 50%, 26%, 67%, and 34%, respectively; and the respective 4-year rates values were 28%, 20%, 60%, and 25%. A greater net tumor volume predicted significantly worse OS, PFS, LC, and DC. Patients with breast cancer fared significantly better with respect to OS, PFS, LC, and DC; and patients with adrenal metastases had significantly worse OS, PFS, and DC despite the small number of such patients enrolled. Neither the number of metastatic lesions nor the number of organs involved was a significant predictor of outcome. Among 45 patients who remained alive at the last follow-up, 29 patients had no evidence of disease, including 23 patients with > or =2 years of follow-up. CONCLUSIONS: Oligometastatic disease is a potentially curable state of distant cancer spread. In this hypothesis-generating analysis, patients with less volume burden of their metastatic disease and those with primary breast cancer fared better. SBRT delivered with curative intent in patients with limited metastases should be investigated further. The Southwest Oncology Group is developing a prospective protocol to treat women who have limited breast cancer metastases with SBRT.     

Use of stereotactic body radiation therapy for oligometastatic recurrent prostate cancer: A systematic review

The purpose of this study is to evaluate the effectiveness and safety of stereotactic body radiation therapy (SBRT) in the management of oligometastatic recurrent prostate cancer (PCa) by means of a systematic review. Six databases were searched (CENTRAL, Embase, LILACS, PubMed, Scopus and Web of Science). Additionally, hand‐searching and grey literature search were performed. The main outcomes were progression‐free survival (PFS) and toxicity rates. Androgen deprivation therapy‐free survival (ADT‐FS), local control, pattern of recurrence, cancer‐specific survival and overall survival were also assessed. Risk of bias and quality of evidence were judged with the aid of specific tools. Fourteen studies were included, involving 661 patients and 899 lesions (561 nodal, 336 bone, 2 liver). Median PFS and ADT‐FS were around 1 to 3 years. Local control rates varied from 82 to 100% among researches with low risk of bias. Acute and late grade 2 toxicity was observed in 2.4% and 1.1% of the patients, respectively. One case of acute and two cases of late grade 3 toxicity were registered. Only one randomized study addresses this topic. Although it does not meet all the eligibility criteria, it is useful for the discussion. A quantitative analysis was not possible, nor were subgroup analyses, due to the significant heterogeneity of the interventions and outcomes reported. Longer follow‐up period is required. SBRT seems to be a safe approach to metastatic lesions that might provide disease control and defer androgen deprivation therapy (ADT). Local control is better when higher radiation doses are employed.     

A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins

The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one‐third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology‐based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82 and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78 and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence.     

Cushing's disease: Pituitary imaging

Fourteen patients with adrenocorticotropic hormone (ACTH)-dependent hypercortisolism underwent pituitary scanning with computed axial tomography (CT) and magnetic resonance imaging (MRI). Computed tomography revealed pituitary macroadenomas in two patients, pituitary hyperplasia in one and a suspicion of pituitary microadenoma in one. Thirteen patients underwent MRI. One with a macroadenoma diagnosed on CT did not undergo MRI. The MRI revealed a pituitary macroadenoma in one, microadenoma in three and hyperplasia in two cases. Magnetic resonance imaging following gadolinium diethylene triamine penta acetic acid (gd-DTPA) enhancement revealed four more pituitary microadenomas. All patients who had pituitary adenomas (micro and macro) and hyperplasia underwent trans-sphenoidal pituitary surgery. One of the two patients, who had an enlarged pituitary on imaging but no demonstrable adenoma, was found to have a microadenoma at surgery. Patients with ACTH-dependent hypercortisolism should undergo MRI of the pituitary gland to identify/localize corticotroph pituitary adenomas. The study should include gd-DTPA enhancement in cases where the scan is normal.     

核医学分子影像在分化型甲状腺癌中的应用现状与进展

分化型甲状腺癌因其发病率逐年升高而引人关注,核医学诊疗是其诊疗过程中重要的一环。随着新型示踪剂的发展,核医学分子影像检查对于在体显示甲状腺癌特定的分子特征及表达水平有重要价值,并可实现基于在体分子特征评估指导下的精准靶向治疗。现就核医学分子影像在评估分化型甲状腺癌分化表型特征和非分化表型特征两方面的应用与进展进行综述。     

An alternative approach to histopathological validation of PET imaging for radiation therapy image-guidance: A proof of concept

Purpose

In radiotherapy, PET images can be used to guide the delivery of selectively escalated doses to biologically relevant tumour subvolumes. Validation of PET for such applications requires demonstration of spatial coincidence between PET tracer uptake pattern and the histopathologically confirmed target. This study introduces a novel approach to histopathological validation of PET image segmentation for radiotherapy guidance.

Methods and materials

Sequential tissue sections from surgically excised whole-tumour specimens were used to acquire full 3D-sets of both histopathological images (microscopy) and PET tracer distribution images (autoradiography). After these datasets were accurately registered, a full 3D autoradiographic distribution of PET tracer was reconstructed and used to obtain synthetic PET images (sPET) by simulating the image deterioration induced by processes involved in PET image formation. To illustrate the method, sPET images were used in this study to investigate spatial coincidence between high FDG uptake areas and the distribution of viable tissue in two small animal tumour models.

Results

The reconstructed 3D autoradiographic distribution of the PET tracer was spatially coherent, as indicated by the high average value of the normalised pixel-by-pixel correlation of intensities between successive slices (0.84 ± 0.05 and 0.94 ± 0.02). The loss of detail in the sPET images versus the 3D autoradiography was significant as indicated by Dice coefficient values corresponding to the two tumours (0 and 0.1 at 70% threshold). The maximum overlap between the FDG segmented volumes and the extent of the viable tissue as indicated by Dice coefficient values, was 0.8 for one tumour (for the image thresholded at 22% of max intensity) and 0.88 for the other (threshold of 14% of max intensity).

Conclusion

It was demonstrated that the use of synthetic PET images for histopathological validation allows for bypassing a technically challenging and error-prone step of registering non-invasive PET images with histopathology.     

Hyperpolarized 13C magnetic resonance metabolic imaging: application to brain tumors

In order to compare in vivo metabolism between malignant gliomas and normal brain, ¹³C magnetic resonance (MR) spectroscopic imaging data were acquired from rats with human glioblastoma xenografts (U-251 MG and U-87 MG) and normal rats, following injection of hyperpolarized [1-¹³C]-pyruvate. The median signal-to-noise ratio (SNR) of lactate, pyruvate, and total observed carbon-13 resonances, as well as their relative ratios, were calculated from voxels containing Gadolinium-enhanced tissue in T₁ postcontrast images for rats with tumors and from normal brain tissue for control rats. [1-¹³C]-labeled pyruvate and its metabolic product, [1-¹³C]-lactate, demonstrated significantly higher SNR in the tumor compared with normal brain tissue. Statistical tests showed significant differences in all parameters (P < .0004) between the malignant glioma tissue and normal brain. The SNR of lactate, pyruvate, and total carbon was observed to be different between the U-251 MG and U-87 MG models, which is consistent with inherent differences in the molecular characteristics of these tumors. These results suggest that hyperpolarized MR metabolic imaging may be valuable for assessing prognosis and monitoring response to therapy for patients with brain tumors.     

18F-FDG PET imaging for identifying the dynamics of intestinal disease caused by SFTSV infection in a mouse model

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that causes fever, enteritis, thrombocytopenia, and leucopenia and can be fatal in up to 30% of cases. However, the mechanism of severe disease is not fully understood. Molecular imaging approaches, such as positron-emission tomography (PET), are functional in vivo imaging techniques that provide real-time dynamics of disease progression, assessments of pharmacokinetics, and diagnoses for disease progression. Molecular imaging also potentially provides useful approaches to explore the pathogenesis of viral infections. Thus, the purpose of this study was to image the pathological features of SFTSV infection in vivo by PET imaging. In a mouse model, we showed that ¹⁸F-FDG accumulations clearly identified the intestinal tract site as a pathological site. We also demonstrated that ¹⁸F-FDG PET imaging can assess disease progression and response to antiserum therapy within the same individual. This is the first report demonstrating a molecular imaging strategy for SFTSV infection. Our results provide potentially useful information for preclinical studies such as the elucidation of the mechanism of SFTSV infection in vivo and the assessment of drugs for SFTS treatment.     

An alternative approach to account for patient organ doses from imaging guidance procedures

Purpose

To investigate the feasibility of an alternative method of accounting for additional organ doses resulting from image guidance procedures during patient treatment planning through tabulated values based on scan protocol and scan site.

Methods and materials

Patient-specific imaging dose to 30 patients resulting from Varian OBI kV–CBCT scans using the Standard Head (17 patients), Low-dose Thorax (8 patients), and Pelvic (5 patients) scan protocols were retrospectively calculated using Monte Carlo methods. Dose dependence on scan location and patient geometry was explored. Patient organ doses were analyzed by using dose–volume histograms and expressed by the mean, minimum dose delivered to 50% of the organ volume, D50. The reported doses are dose-to-medium instead of dose-to-water.

Results

The organ doses from all patient-specific calculations show predictable and limited ranges across patients. For brain isocenters using Standard Head Scans: Bone: 0.7–1.1 cGy, Brain: 0.2–0.3 cGy, Brainstem: 0.2–0.3 cGy, Skin: 0.3–0.4 cGy, Eye: 0.03–0.3 cGy. For head and neck patients using the Standard Head Scan: Bone: 0.3–0.6 cGy, Parotids: 0.3–0.4 cGy, Spinal Cord: 0.15–0.25 cGy, Thyroid: 0.1–0.25 cGy, Skin: 0.2–0.3 cGy, Trachea–Esophagus: 0.1–0.2 cGy. For chest using Thorax Scans: Bone: 1.1–1.8 cGy, Soft tissue organs (Bowel, Lung, Heart, Kidney, Esophagus, and Spinal Cord): 0.3–0.6 cGy. For abdominal site using Pelvic Scans: Bone: 3.2–4.2 cGy. Soft tissue organs (Bladder, Bowel, Rectum, Prostate, and Skin) D50s fell between 1.2 and 2.2 cGy. Femoral Heads: 2.5–3.4 cGy.

Conclusions

It is adequate to estimate and account for organ dose by using tabulated values based on scan procedure and site because organ doses from imaging procedures are only modestly dependent upon scan location and body size. Considering the dose variation and magnitude of dose from each scan protocol in comparison to therapeutic doses, this approach provides a simple alternative to account for additional imaging guidance doses during patient treatment planning. Clinicians can use these tabulated values to make informed decisions in selecting the appropriate imaging procedures and imaging frequency during radiotherapy treatment.     

Performance of magnetic resonance imaging in pulmonary fungal disease compared to high‐resolution computed tomography

To evaluate the performance of magnetic resonance imaging (MRI) compared to computed tomography (CT) in patients diagnosed with pulmonary mycosis. We prospectively included 21 patients diagnosed with pulmonary mycosis between January 2013 and October 2014. Inclusion criteria were presence of respiratory symptoms, histopathological diagnosis of mycosis and absence of mycosis treatment. Reviewers identified one predominant imaging pattern per patient: nodular, reticular or airspace pattern. Afterwards, all CT findings were analysed separately per lobe and compared to MRI. Nodular pattern was the most common found (CT: 76.20%; MRI: 80.96%), followed by airspace pattern (CT and MRI: 9.52%) and reticular (CT: 9.52%; MRI: 4.76%). Compared to CT, MRI performance varied according to radiological finding and pulmonary region. For nodules, MRI presented high sensitivity (100% [95% CI: 93.52‐100]) and specificity (100% [95% CI: 92.00‐100]). For bronchiectasis and septal thickening, there were poorer positive predictive values (33.33% [95% CI: 1.77‐87.47]; and 83.33% [95% CI: 50.88‐97.06] respectively). As specificity and negative predictive value had superior results than sensitivity and positive predictive value, rather than for diagnosis of this condition, MRI might be more considered for the follow‐up of patients with pulmonary mycosis, an alternative to multiple radiation exposures with CT follow‐up.     

Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease

BACKGROUND:

A subset of patients with metastatic cancer in limited organs may benefit from metastasis‐directed therapy. The authors investigated whether patients with limited metastases could be safely treated with metastasis‐directed radiotherapy.

METHODS:

Patients with 1 to 5 metastatic cancer sites with a life expectancy of >3 months received escalating stereotactic body radiotherapy (SBRT) doses to all known cancer sites. Patients were followed radiographically with CT scans of the chest, abdomen, and pelvis and metabolically with fluorodeoxyglucose‐positron emission tomography, 1 month after treatment, and then every 3 months. Acute toxicities were scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0, and late toxicities were scored using the Radiation Therapy Oncology Group late toxicity scoring system.

RESULTS:

Sixty‐one patients with 113 metastases were enrolled from November 2004 to November 2009 on a prospective radiation dose escalation study. Median follow‐up was 20.9 months. Patients tolerated treatment well; the maximal tolerated dose was not reached in any cohort. Eleven patients (18.3%) have not progressed. One and 2‐year progression‐free survival are 33.3% (95% confidence interval [CI], 22.8‐46.1) and 22.0% (95% CI, 12.8‐34.4); 1‐year and 2‐year overall survival are 81.5% (95% CI, 71.1‐91.1) and 56.7% (95% CI, 43.9‐68.9). Seventy‐two percent of patients whose tumors progressed did so in limited (1‐3) metastatic sites.

CONCLUSIONS:

Patients with 1 to 5 metastases can be safely treated to multiple body sites and may benefit from SBRT. Further investigation should focus on patient selection. Cancer 2011;. © 2011 American Cancer Society.     

介入分子影像学研究现状与进展*

随着介入放射学与分子影像学的发展、延伸和融合,形成了一门新的学科- 介入分子影像学。介入放射学和分子影像学协同发展,不断拓宽应用领域,提升实用性,明显提高了恶性肿瘤的早期诊断、局部治疗和治疗监测水平。一方面,介入放射学拓展了分子影像学的研究和应用领域,使其可以监测深部、微小的病变部位,同时辅助传送非靶向分子探针和药物,从而提高靶向成像与治疗的有效性。另一方面,分子影像学已融入介入放射学,可更加精准地监测与评价介入治疗疗效,进一步提高介入治疗的安全性和有效性。虽然当前的分子影像学研究大多还处于动物实验或临床前阶段,随着介入分子影像学理念和技术的不断完善,必将推动分子影像学的临床实践,提升恶性肿瘤的诊治水平。      

常规MRI联合弥散加权成像对直肠癌T分期诊断价值

目的 探讨常规核磁共振(Magnetic resonance imaging,MRI)联合弥散加权成像(Diffusion weighted imaging,DWI)在直肠癌术前T分期的诊断价值。方法 对107例经病理证实为直肠腺癌患者行回顾性分析,分别运用常规MRI序列、常规MRI联合DWI序列对直肠癌进行术前T分期,于检查后1周内行手术治疗并取得病理结果,将影像检查结果与术后病理结果对照,比较两种方法对直肠癌术前T分期诊断的准确性。结果 107例患者中,常规MRI检查诊断直肠癌T分期的准确率为84.11%(90/107),与病理T分期间一致性检验较好(Kappa=0.652,P＜0.001);常规MRI+DWI检查诊断直肠癌术前T分期的准确性为90.65%(97/107),与病理学T分期间一致性检验较好(Kappa=0.732,P＜0.001)。结论 与常规MRI序列相比,常规MRI联合DWI诊断直肠癌T分期准确性更高,可为临床提供较合理的治疗方案。     

In vivo imaging of tumor response to therapy using a dual-modality imaging strategy

In vivo assessment of the outcome of cancer therapy is hampered by the paucity of imaging probes that target tumors specifically and noninvasively. The importance of such probes increases with the continuous development of chemotherapeutics and the necessity to evaluate their effectiveness in a clinical setting. We have recently reported on a dual-modality imaging probe specifically targeting the underglycosylated mucin-1 tumor-specific antigen (uMUC-1), which is one of the early hallmarks of tumorigenesis in a wide variety of tumors. This probe consists of crosslinked superparamagnetic iron oxide nanoparticles (CLIO) for MR imaging, modified with Cy5.5 dye (for near infrared optical fluorescence imaging (NIRF)), and has peptides (EPPT), specifically recognizing uMUC-1, attached to the nanoparticle's dextran coat. In the present study, we demonstrated that this probe could not only detect orthotopically implanted preclinical models of adenocarcinomas but could also track tumor response to chemotherapy in vivo in real time. Considering the high cost associated with the development and testing of new cancer therapeutics and the need for accurate, noninvasive assessment of their effectiveness, we believe that the developed probe represents a valuable research tool relevant to clinical discovery.