Spinal metastases: From conventional fractionated radiotherapy to single-dose SBRT

AimTo review the recent evolution of spine SBRT with emphasis on single dose treatments.BackgroundRadiation treatment of spine metastases represents a challenging problem in clinical oncology, because of the high risk of inflicting damage to the spinal cord. While conventional fractionated radiation therapy still constitutes the most commonly used modality for palliative treatment, notwithstanding its efficacy in terms of palliation of pain, local tumor control has been approximately 60%. This limited effectiveness is due to previous lack of technology to precisely target the tumor while avoiding the radiosensitive spinal cord, which constitutes a dose-limiting barrier to tumor cure.Materials and methodsA thorough review of the available literature on spine SBRT has been carried out and critically assessed.ResultsStereotactic body radiotherapy (SBRT) emerges as an alternative, non-invasive high-precision approach, which allows escalation of tumor dose, while effectively sparing adjacent uninvolved organs at risk. Engaging technological advances, such as on-line Cone Beam Computed Tomography (CBCT), coupled with Dynamic Multi-Leaf Collimation (DMLC) and rapid intensity-modulated (IMRT) beam delivery, have promoted an interactive image-guided (IGRT) approach that precisely conforms treatment onto a defined target volume with a rapid dose fall-off to collateral non-target tissues, such as the spinal cord. Recent technological developments allow the use of the high-dose per fraction mode of hypofractionated SBRT for spinal oligometastatic cancer, even if only a few millimeters away from the tumor.ConclusionSingle-dose spine SBRT, now increasingly implemented, yields unprecedented outcomes of local tumor ablation and safety, provided that advanced technology is employed.     

Stereotactic radiotherapy for early lung cancer: Evidence-based approach and future directions

AimTo review key studies evaluating stereotactic radiotherapy in the setting of early-stage non-small cell lung cancer (NSCLC) for inoperable or high-risk patients, and discuss areas of ongoing research and clinical trials.BackgroundThe use of stereotactic radiotherapy for the treatment of early stage non-small cell lung cancer (NSCLC) has increased rapidly over the past decade. Numerous studies have reported outcomes for patients treated with SBRT who are unfit for surgical resection, or at high risk of surgical complications.Materials and methodsA narrative review.ResultsThe preponderance of evidence suggests that SBRT is associated with excellent local control (∼90% at 3 years) and a favorable toxicity profile. In patients with higher operative risks, such as the elderly and patients with severe COPD, SBRT may provide a less-toxic treatment than surgery with similar oncologic outcomes. Ongoing studies are evaluating the use of SBRT for locally advanced or oligometastatic NSCLC.ConclusionsA large body of evidence now exists to support the use of SBRT for early-stage NSCLC. Decisions regarding the optimal choice of treatment should be individualized, and made in the context of a multidisciplinary team.     

Re-irradiation after stereotactic body radiotherapy for spine metastases from hepatocellular carcinoma: a case report

Modern radiotherapy machines with refinements in planning software and image-guidance apparatuses have made stereotactic body radiotherapy (SBRT) more widely available as an effective tool in the management of spine metastases. In conventional palliative radiotherapy, the aim has traditionally been pain relief and short-term local control. In contrast, SBRT aims to deliver an ablative dose to enhance local control, with a smaller number of fractions while sparing the organs at risk (OAR), especially the spinal cord. Recently, trials have asserted the role of spine SBRT as an effective modality for durable local control, in addition to achieving pain relief. The quality of evidence for spine SBRT data is maturing, while prospective published trials on re-irradiation SBRT in spine remain sparse. The purpose of the present case report is to share the challenges faced while salvaging a dorsal spine metastasis and ablating a new right adrenal metastatic lesion in proximity of the transplanted liver.     

Successful Implantation of Transvenous Pacing System via Persistent Left Superior Vena Cava and Coronary Sinus in Small Children

Transvenous pacemaker implantation tends to be difficult in the setting of a persistent left superior vena cava (SVC) and an absent or inaccessible right SVC. We report two small children in whom transvenous pacing leads were successfully inserted via a persistent left SVC. This technique was safe in our cases; however, favorable long-term result has yet to be demonstrated.     

非小细胞肺癌体部寡转移的立体定向放射治疗

非小细胞肺癌(Non-small cell lung cancer, NSCLC)寡转移是NSCLC转移过程中的一种中间状态,是肿瘤生物侵袭过程中较温和的一个阶段,它介于原发灶与远处广泛转移之间,转移瘤数目≦5个,受累器官≦2个,此时肿瘤细胞尚不具备全身播散的倾向。晚期恶性肿瘤患者很大部分处于寡转移状态,而约30%的非小细胞肺癌(NSCLC)患者死于寡转移,目前对于寡转移的治疗以局部治疗为主(包括手术、放疗以及射频消融)。治疗隐匿性转移灶、寡转移灶及全身化学治疗结束后清除残留局部病灶成为治疗寡转移的关键,越来越得到专家共识。在无法手术或者拒绝手术的患者中,局部放放射治疗凸显巨大优势,尤其是体部立体定向放射治疗(Stereotactic Body Radiation Therapy, SBRT),大量临床研究结果显示体部立体定向放射治疗NSCLC寡转移是安全有效的,并能提高转移灶的局部控制率。本文旨在对SBRT治疗非小细胞肺癌寡转移的临床进展做一综述。     

Successful Implantation of Transvenous Pacing System via Persistent Left Superior Vena Cava and Coronary Sinus in Small Children

Transvenous pacemaker implantation tends to be difficult in the setting of a persistent left superior vena cava (SVC) and an absent or inaccessible right SVC. We report two small children in whom transvenous pacing leads were successfully inserted via a persistent left SVC. This technique was safe in our cases; however, favorable long-term result has yet to be demonstrated.     

Extracranial stereotactic body radiotherapy. Review of main SBRT features and indications in primary tumors

Aim

Review of main SBRT features and indications in primary tumors.

Background

Stereotactic body radiotherapy has been developed in the last few years. SBRT allows the hypofractionated treatment of extra cranial tumors, using either a single or limited number of dose fractions, and resulting in the delivery of a high biological effective dose with low toxicity.

Material and methods

SBRT requires a high level of accuracy for all phases of the treatment process: effective patient immobilization, precise target localization, highly conformed dosimetry and image guided systems for treatment verification. The implementation of SBRT in routine requires a careful considering of organ motion. Gating and tracking are effective ways to do so, and less invasive technologies “fiducials free” have been developed. Due to the hypofractionated scheme, the physician must pay attention to new dosimetric constraints in organ at risk and new radiobiological models are needed to assess the optimal fractionation and dose schemes.

Results

Currently, SBRT is safe and effective to treat primary tumors, which are otherwise untreatable with conventional radiotherapy or surgery. SBRT has quickly developed because of its excellent results in terms of tolerance and its high locoregional control rates. SBRT indications in primary tumors, such as lung primary tumors, have become a standard of care for inoperable patients. SBRT seems to be effective in many others indications in curative or palliative intent such as liver primary tumors, and novel indications and strategies are currently emerging in prostate cancer, head and neck tumor recurrences or pelvis reirradiations.

Conclusion

Currently, SBRT is mainly used when there is no other therapeutic alternative for the patient. This is due to the lack of randomized trials in these settings. However, the results shown in retrospective studies let us hope to impose SBRT as a new standard of care for many patients in the next few years.     

In vivo dosimetry for lung radiotherapy including SBRT

SBRT for lung cancer is being rapidly adopted as a treatment option in modern radiotherapy centres. This treatment is one of the most complex in common clinical use, requiring significant expertise and resources. It delivers a high dose per fraction (typically ∼6–30 Gy/fraction) over few fractions. The complexity and high dose delivered in only a few fractions make powerful arguments for the application of in vivo dosimetry methods for these treatments to enhance patient safety. In vivo dosimetry is a group of techniques with a common objective – to estimate the dose delivered to the patient through a direct measurement of the treatment beam(s). In particular, methods employing an electronic portal imaging device have been intensely investigated over the past two decades. Treatment verification using in vivo dosimetry approaches has been shown to identify errors that would have been missed with other common quality assurance methods. With the addition of in vivo dosimetry to verify treatments, medical physicists and clinicians have a higher degree of confidence that the dose has been delivered to the patient as intended.In this review, the technical aspects and challenges of in vivo dosimetry for lung SBRT will be presented, focusing on transit dosimetry applications using electronic portal imaging devices (EPIDs). Currently available solutions will be discussed and published clinical experiences, which are very limited to date, will be highlighted.     

β-Adrenergic stimulation induces pro-arrhythmic activity in the caval vein myocardial tissue

Electrical activity of the right superior vena cava (SVC) is considered as a source of the atrial fibrillation. We have shown that bioelectrical properties of the SVC myocardium differ from those of the working atrial myocardium. Electrically evoked action potential duration in SVC is significantly shorter, the resting membrane potential in both stimulated and quiescent SVC preparations is significantly more positive than in atria. Activation of β-adrenoreceptors in SVC myocardium leads to a series of action potentials, and this process depends on protein kinase A. Probably, β-adrenergic stimulation enhances SVC arrhythmogenesis in vivo.     

Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS)

We have reviewed the studies on radiation-induced vascular changes in human and experimental tumors reported in the last several decades. Although the reported results are inconsistent, they can be generalized as follows. In the human tumors treated with conventional fractionated radiotherapy, the morphological and functional status of the vasculature is preserved, if not improved, during the early part of a treatment course and then decreases toward the end of treatment. Irradiation of human tumor xenografts or rodent tumors with 5-10 Gy in a single dose causes relatively mild vascular damages, but increasing the radiation dose to higher than 10 Gy/fraction induces severe vascular damage resulting in reduced blood perfusion. Little is known about the vascular changes in human tumors treated with high-dose hypofractionated radiation such as stereotactic body radiotherapy (SBRT) or stereotactic radiosurgery (SRS). However, the results for experimental tumors strongly indicate that SBRT or SRS of human tumors with doses higher than about 10 Gy/fraction is likely to induce considerable vascular damages and thereby damages the intratumor microenvironment, leading to indirect tumor cell death. Vascular damage may play an important role in the response of human tumors to high-dose hypofractionated SBRT or SRS.     

Left superior vena cava, a remnant of embryological development

A 46-year-old Brugada syndrome patient underwent insertion of a dual-chamber implantable cardioverter- defibrillator (ICD), revealing a left-sided superior vena cava (SVC), (figure 1), running, characteristically, left from the sternum and flowing into the great cardiac vein. Following this course, the atrial lead was placed in the right atrium (RA) (figure 2, arrow, note dorsal position). The ventricular lead was inserted through the connecting anonymous vein between left and right SVC (figure 1, double arrow), into the right SVC and right ventricle (RV). The presence of a left superior vena cava results from the persistence of the embryonic left anterior cardinal vein. This anomaly is present in approximately 0.5% of the general population and in 3 to 5% of persons with other congenital heart defects, as established by autopsy.     

Stereotactic Radiosurgery for Gynecologic Cancer

Stereotactic body radiotherapy (SBRT) distinguishes itself by necessitating more rigid patient immobilization, accounting for respiratory motion, intricate treatment planning, on-board imaging, and reduced number of ablative radiation doses to cancer targets usually refractory to chemotherapy and conventional radiation. Steep SBRT radiation dose drop-off permits narrow ''pencil beam'' treatment fields to be used for ablative radiation treatment condensed into 1 to 3 treatments.Treating physicians must appreciate that SBRT comes at a bigger danger of normal tissue injury and chance of geographic tumor miss. Both must be tackled by immobilization of cancer targets and by high-precision treatment delivery. Cancer target immobilization has been achieved through use of indexed customized Styrofoam casts, evacuated bean bags, or body-fix molds with patient-independent abdominal compression.^1-3 Intrafraction motion of cancer targets due to breathing now can be reduced by patient-responsive breath hold techniques,⁴ patient mouthpiece active breathing coordination,⁵ respiration-correlated computed tomography,⁶ or image-guided tracking of fiducials implanted within and around a moving tumor.^7-9 The Cyberknife system (Accuray [Sunnyvale, CA]) utilizes a radiation linear accelerator mounted on a industrial robotic arm that accurately follows patient respiratory motion by a camera-tracked set of light-emitting diodes (LED) impregnated on a vest fitted to a patient.¹⁰ Substantial reductions in radiation therapy margins can be achieved by motion tracking, ultimately rendering a smaller planning target volumes that are irradiated with submillimeter accuracy.^11-13Cancer targets treated by SBRT are irradiated by converging, tightly collimated beams. Resultant radiation dose to cancer target volume histograms have a more pronounced radiation "shoulder" indicating high percentage target coverage and a small high-dose radiation "tail." Thus, increased target conformality comes at the expense of decreased dose uniformity in the SBRT cancer target. This may have implications for both subsequent tumor control in the SBRT target and normal tissue tolerance of organs at-risk. Due to the sharp dose falloff in SBRT, the possibility of occult disease escaping ablative radiation dose occurs when cancer targets are not fully recognized and inadequate SBRT dose margins are applied. Clinical target volume (CTV) expansion by 0.5 cm, resulting in a larger planning target volume (PTV), is associated with increased target control without undue normal tissue injury.^7,8 Further reduction in the probability of geographic miss may be achieved by incorporation of 2-[¹⁸F]fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography (PET).⁸ Use of ¹⁸F-FDG PET/CT in SBRT treatment planning is only the beginning of attempts to discover new imaging target molecular signatures for gynecologic cancers.     

Treatment of Pacemaker-Induced Superior Vena Cava Syndrome by Balloon Angioplasty and Stenting

Superior vena cava (SVC) syndrome is a rare but serious complication after pacemaker implantation. This report describes three cases of SVC syndrome treated with venoplasty and venous stenting, with an average follow-up of 30.7 (±3.1) months. These cases illustrate that the definitive diagnosis, and the extent and location of venous obstruction, can only be determined by venography.     

Radiofrequency Ablation Of Typical Atrial Flutter Via Right Subclavian/jugular Vein Access In A Patient With Implanted Filter In The Inferior Vena Cava

Radiofrequency ablation of Cavotricuspid Isthmus-dependent Atrial Flutter (CTI AFL), a usual and safe therapeutic procedure in interventional electrophysiology with a high success rate, aiming to induce permanent block of conduction over CTI, is normally performed via the femoral access, which allows practical access to the CTI through the inferior vena cava (IVC). In rare cases of obstruction of IVC, ablation of CTI can be performed only through the superior vena cava (SVC) access. We present a case of typical atrial flutter that was ablated through the right subclavian/jugular veins because of iatrogenic obstruction of the IVC due to a previously implanted thrombus filter. Furthermore we discuss about how we resolved access-related problems of instability during catheter ablation on CTI.     

All is not lost, when lead goes in the wrong direction

Left sided superior vena cava (SVC) is an uncommon anomaly noted in the general population. It adds complexity to the procedure, when attempting to place pacing or defibrillator devices into the heart. Here we report a case where the leads were placed through the left sided SVC into the right sided chambers giving an interesting X-ray appearance.     

Geometrical and dosimetrical uncertainties in hypofractionated radiotherapy of the lung: A review

The application of high precision hypofractionated regimes (a.k.a. stereotactic body radiotherapy (SBRT)) to the treatment of lung cancer is a ‘success story’ of radiotherapy. From the technical perspective, lung SBRT is a challenging technique as all aspects of the treatment workflow, from imaging to dose calculation to treatment delivery, should be carefully handled in order to ensure consistency between planned and delivered dose.In this review such technical aspects are presented and discussed, looking at what has been developed over the years.The use of imaging techniques such as slow-CT, breath-hold CT, four-dimensional CT and mid-ventilation is reviewed, presenting the main characteristics of each approach but not necessarily to single out ‘the best’ solution.Concerning dose calculation, a number of studies clearly separate dose algorithms that should be considered inadequate for lung SBRT (e.g. simple pencil beam algorithms) from approaches such as convolution algorithms, Monte Carlo, and solution of the transport equation, that are much better at handling the combination of small fields and heterogenenous geometries that make dose calculation not trivial.Patient positioning and management of intrafraction motion have been two areas of significant developments, to the point where it is difficult to identify which solution represents the best compromise between technical complexity and clinical effectiveness. The review analyses several of these methods, outlining the residual uncertainties associated with each of them.Last but not least, two subjects are discussed, adaptive therapy and particle therapy, that may represent in the near future additional tools for the technical improvement of lung SBRT.     

MRI-guided lung SBRT: Present and future developments

Stereotactic body radiotherapy (SBRT) is rapidly becoming an alternative to surgery for the treatment of early-stage non-small cell lung cancer patients. Lung SBRT is administered in a hypo-fractionated, conformal manner, delivering high doses to the target. To avoid normal-tissue toxicity, it is crucial to limit the exposure of nearby healthy organs-at-risk (OAR).Current image-guided radiotherapy strategies for lung SBRT are mostly based on X-ray imaging modalities. Although still in its infancy, magnetic resonance imaging (MRI) guidance for lung SBRT is not exposure-limited and MRI promises to improve crucial soft-tissue contrast. Looking beyond anatomical imaging, functional MRI is expected to inform treatment decisions and adaptations in the future.This review summarises and discusses how MRI could be advantageous to the different links of the radiotherapy treatment chain for lung SBRT: diagnosis and staging, tumour and OAR delineation, treatment planning, and inter- or intrafractional motion management. Special emphasis is placed on a new generation of hybrid MRI treatment devices and their potential for real-time adaptive radiotherapy.     

Refractoriness of the sheep superior vena cava myocardial sleeve

The cardiomyocytes in the superior vena cava (SVC) myocardial sleeve have distinct action potentials and ionic current profiles, but the refractoriness of these cells has not been reported. Using standard intracellular microelectrode techniques, we demonstrated in sheep that the effective refractory period (ERP) of the cardiomyocytes in the SVC (114.7 +/- 6.5 ms) is shorter than that in the inferior vena cava (IVC) (166.7 +/- 6.2 ms), right atrial free wall (RAFW) (201.0 +/- 6.0 ms) and right atrial appendage (RAA) (203.1 +/- 5.8 ms) (P < 0.05). The right atrial cardiomyocyte ERP was heterogeneously shortened by acetylcholine, a muscarinic type 2 receptor (M(2)R) agonist. After perfusion with 15 microM acetylcholine, the shortest ERP occurred in the SVC (the ERP in the SVC, IVC, RAFW and RAA was 53.6 +/- 2.7, 98.9 +/- 2.2, 121.8 +/- 6.0 and 109.7 +/- 5.1 ms, respectively; P < 0.05). Carbachol (1 microM), another M(2)R agonist, produced a similar effect as acetylcholine. Furthermore, we used methoctramine, a M(2)R blocker, 4-DAMP, a muscarinic type 3 receptor (M(3)R) blocker, and tropicamide, a muscarinic type 4 receptor (M(4)R) blocker to inhibit the acetylcholine-induced ERP shortening of SVC cardiomyocytes, and found that the 50% inhibitory concentration for methoctramine, 4-DAMP and tropicamide was 5.91, 45.72 and 80.34 nM, respectively. Therefore, we conclude that the sheep SVC myocardial sleeve is a unique electrophysiological region of the right atrium with the shortest ERP both under physiological condition and under cholinergic agonist stimulation. M(2)R might play a major role in the response of the SVC myocardial sleeve to parasympathetic nerve tone. The association between the distinct refractoriness in SVC and atrial fibrillation originating from the region deserves further investigation.     

4:2:1 conduction of an AF initiating trigger

A 44 year old male with idiopathic dilated cardiomyopathy was undergoing persistent atrial fibrillation (AF) ablation. Following antral ablation, AF terminated into a regular narrow complex rhythm. Earliest activation was mapped to a focus in the superior vena cava (SVC) which was conducted in a 2:1 ratio to the atria which in turn was conducted with 2:1 ratio to the ventricles, resulting in an unusual 4:2:1 conduction of the SVC tachycardia. 1:1 conduction of the SVC tachycardia to the atrium preceded initiation of AF. During AF, SVC tachycardia continued unperturbed. Sinus rhythm was restored following catheter ablation of the focus.     

The characteristics of action potential and nonselec-tive cation current of cardiomyocytes in rabbit superior vena cava

As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may in-crease or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can in-crease or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyo-cytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.