Giuseppe Iatì

Usefulness of four dimensional (4D) PET/CT imaging in the evaluation of thoracic lesions and in radiotherapy planning: Review of the literature

In the past decade, Positron Emission Tomography (PET) has become a routinely used methodology for the assessment of solid tumors, which can detect functional abnormalities even before they become morphologically evident on conventional imaging. PET imaging has been reported to be useful in characterizing solitary pulmonary nodules, guiding biopsy, improving lung cancer staging, guiding therapy, monitoring treatment response and predicting outcome. This review focuses on the most relevant and recent literature findings, highlighting the current role of PET/CT and the evaluation of 4D-PET/CT modality for radiation therapy planning applications. Current evidence suggests that gross tumor volume delineation based on 4D-PET/CT information may be the best approach currently available for its delineation in thoracic cancers (lung and non-lung lesions). In our opinion, its use in this clinical setting is strongly encouraged, as it may improve patient treatment outcome in the setting of radiation therapy for cancers of the thoracic region, not only involving lung, but also lymph nodes and esophageal tissue. Literature results warrants further investigation in future prospective studies, especially in the setting of dose escalation.

Frameless stereotactic radiosurgery for the treatment of multiple sclerosis-related trigeminal neuralgia

BACKGROUND Trigeminal neuralgia (TN) affects 7% of patients with multiple sclerosis (MS). In such patients, TN is difficult to manage either pharmacologically and surgically. Radiosurgical rhizotomy is an effective treatment option. The nonisocentric geometry of radiation beams of CyberKnife introduces new concepts in the treatment of TN. Its efficacy for MS-related TN has not yet been demonstrated. METHODS Twenty-seven patients with refractory TN and MS were treated. A nonisocentric beams distribution was chosen; the maximal target dose was 72.5 Gy. The maximal dose to the brainstem was <12 Gy. Effects on pain, medications, sensory disturbance, rate, and time of pain recurrence were analyzed. RESULTS Median follow-up was 37 (18-72) months. Barrow Neurological Institute pain scale score I-III was achieved in 23/27 patients (85%) within 45 days. Prescription isodose line (80%) accounting for a dose of 58 Gy incorporated an average of 4.85 mm (4-6 mm) of the nerve and mean nerve volume of 26.4 mm3 (range 20-38 mm3). Seven out of 27 patients (26%) had mild, not bothersome, facial numbness (Barrow Neurological Institute numbness score II). The rate of pain control decreased progressively after the first year, and only 44% of patients retained pain control 4 years later. CONCLUSIONS Frameless radiosurgery can be effectively used to perform retrogasserian rhizotomy. Pain relief was satisfactory and, with our dose/volume constraints, no sensory complications were recorded. Nonetheless, long-term pain control was possible in less than half of the patients. This is a limitation that CyberKnife radiosurgery shares with other techniques in MS patients.

Post-Treatment Edema after Meningioma Radiosurgery is a Predictable Complication.

Symptomatic post-treatment edema (PTE) causing seizures, focal deficits, and intracranial hypertension is a rather common complication of meningioma radiosurgery. Factors associated to the occurrence of PTE still needs to be clarified. We retrospectively analyzed our patients’ data to identify factors associated with the development of symptomatic PTE. Supposed risk factors were systematically analyzed. Between July 2007 and March 2014, 245 meningiomas in 229 patients were treated by a single fraction or multisession radiosurgery (2-5 fractions) or hypofractionated stereotactic radiotherapy (6-15 fractions) using the CyberKnife system (Accuray Inc., Sunnyvale, CA) at the University Hospital of Messina, Italy. Local tumor control was achieved in 200 of 212 patients with World Health Organization (WHO) Grade I meningiomas (94%) at a mean follow-up of 62 months. Symptomatic PTE on MRI was diagnosed in 19 patients (8.3%) causing seizure (n=17, 89%), aggravating headache (n=12, 63%), or focal deficits (n=13, 68%). Four variables were found to be associated with the likelihood of edema development, including tumor volume > 4.5 mL, non-basal tumor location, tight brain/tumor interface, and atypical histology. Nonetheless, when multivariate logistic regression analysis was performed, only tumor volume and brain-tumor interface turned out to be independent predictors of PTE development. Our results suggest that the factor associated with the risk of developing PTE is associated to characteristics of meningioma rather than to the treatment modality used. Accordingly, an appropriate patient selection is the way to achieve safe treatment and long-term disease control.

High-Dose Robotic Stereotactic Body Radiotherapy in the Treatment of Patients With Prostate Cancer Preliminary Results in 26 Patients

Background: Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in patients with localized prostate cancer (LpC). The primary end point was the evaluation of both acute and late toxicities; secondary end point was the observation of prostate-specific antigen (PSA) nadir. Patients and Methods: Patients with LpC having prostate volume ≤90 cm3 were enrolled in the present study. Patients were treated with SBRT alone or in combined modality (SBRT + EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated, Sunnyvale, California) and fiducial tracking system. Results: From February 2008 to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled. Androgen deprivation therapy (ADT) was administered in 16 of the 26 patients. The median pretreatment PSA was 9.4 (range, 4.5-14.3) ng/mL. All patients completed the planned therapy. Acute Grade 1 toxicity was observed in 18 patients, genitourinary (GU) in 12 / 26 patients, and gastrointestinal (GI) in 6 / 26 patients. Acute Grade 2 GU toxicity was reported in 1 / 26 patients, and Grade 2 GI toxicity was observed in 2 / 26 patients. The median PSA nadir was 0.15 (range, 0.02 = 1.4) ng/mL. Late toxicities were observed in 5 / 26 patients: Grade 1 GU (3 of 26), Grade 2 GU (1 of 26), and Grade 1 GI (1 of 26). Median follow-up was 21.5 (range, 8-65) months. Conclusions: Our preliminary results of SBRT “simulating” HDR for LpC confirm a minimal toxicity and an optimal PSA response. The PSA nadirs appear comparable with HDR-BRT.

3D-Printing of Arteriovenous Malformations for Radiosurgical Treatment: Pushing Anatomy Understanding to Real Boundaries.

Radiosurgery of arteriovenous malformations (AVMs) is a challenging procedure. Accuracy of target volume contouring is one major issue to achieve AVM obliteration while avoiding disastrous complications due to suboptimal treatment. We describe a technique to improve the understanding of the complex AVM angioarchitecture by 3D prototyping of individual lesions. Arteriovenous malformations of ten patients were prototyped by 3D printing using 3D rotational angiography (3DRA) as a template. A target volume was obtained using the 3DRA; a second volume was obtained, without awareness of the first volume, using 3DRA and the 3D-printed model. The two volumes were superimposed and the conjoint and disjoint volumes were measured. We also calculated the time needed to perform contouring and assessed the confidence of the surgeons in the definition of the target volumes using a six-point scale. The time required for the contouring of the target lesion was shorter when the surgeons used the 3D-printed model of the AVM (p=0.001). The average volume contoured without the 3D model was 5.6 ± 3 mL whereas it was 5.2 ± 2.9 mL with the 3D-printed model (p=0.003). The 3D prototypes proved to be spatially reliable. Surgeons were absolutely confident or very confident in all cases that the volume contoured using the 3D-printed model was plausible and corresponded to the real boundaries of the lesion. The total cost for each case was 50 euros whereas the cost of the 3D printer was 1600 euros. 3D prototyping of AVMs is a simple, affordable, and spatially reliable procedure that can be beneficial for radiosurgery treatment planning. According to our preliminary data, individual prototyping of the brain circulation provides an intuitive comprehension of the 3D anatomy of the lesion that can be rapidly and reliably translated into the target volume.

Stereotactic Radiotherapy in the Retreatment of Recurrent Cervical Cancers, Assessment of Toxicity, and Treatment Response Initial Results and Literature Review

Aim: To evaluate the role of stereotactic body radiation therapy in the retreatment of locally recurrent cervical cancers. Brachytherapy is the main choice to treat gynecologic cancers. Methods: Patients with recurrent cervical cancer, previously submitted to radiotherapy, were treated with stereotactic body radiation therapy using a CyberKnife system (Accuray Incorporated, Sunnyvale, California) with a fiducial tracking system. Results: From August 2011 to October 2014, 5 patients have been treated. Median age was 81 years (range, 70-84 years). Two patients were diagnosed with adenocarcinoma endometrioid and 3 with squamous cell carcinoma. Toxicity was scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. After a median follow-up of 12 months (range, 8-34 months), no severe (>grade 3) acute/late genitourinary or low gastrointestinal toxicity was observed. Conclusion: Our preliminary results of stereotactic body radiation therapy “simulating” high dose rate for recurrent cervical cancers confirm a minimal toxicity and an optimal outcome. The stereotactic body radiation therapy is an alternative to high dose rate brachytherapy for gynecologic tumors.

Evaluation of the dose perturbation around gold and steel fiducial markers in a medical linac through Geant4 Monte Carlo simulation

OBJECTIVE Purpose of this work was to study the dose perturbation within the target volume of a external MV radiation therapy when using metal fiducials. METHODS We developed a Monte Carlo simulation in Geant4 of a cylindrical fiducial made either of gold or of steel and simulated the photon irradiation beam originating from a medical Linac operating at 6, 10 or 15 MV. For each energy, two different irradiation schemes were simulated: a single 5 × 5-cm square field in the -x direction, and five 5 × 5-cm fields at 0°, 80°, 165°, 195° and 280°. RESULTS In a single beam irradiation scheme, we observed a dose reduction behind fiducials varying from -20% for gold at 6 MV to -5% for steel at 15 MV, and a dose increment in front of the fiducial ranging from +33% for gold at 15 MV to +10% for steel at 6 MV. When five beams were employed, a dose increment ranging from +28% to +46% has been found around gold. Around a steel fiducial, an average increment of +17% was found, irrespective of the photon energy. CONCLUSIONS When using a single beam, the decrement of dose behind both steel and gold markers increases with the photon energy. This effect vanishes when a multifield treatment is delivered; in this instance there is a dose increment around fiducials, according to both fiducial material and photon energy, with lower values for steel and 6 MV. This energy represents the best choice when fiducial markers are present inside the irradiated volume.

Comments on: “Clinical implementation of a new electronic brachytherapy system for skin brachytherapy”

To the Editor: We have read with an interest the article of Olga Pons-Llanas et al. [1] published in the Journal about the use of electronic brachytherapy (EBT) in non-melanoma skin cancer (NMSC). However, we noticed the exclusion criteria for the following tumors: lesions with a diameter greater than 20 mm, invasion of more than 4 mm, irregular anatomic areas. Besides, there are limits linked to the use of circular collimators and the daily set-up position. NMSC often have irregular shapes and diameter longer than 2 cm; besides, in most cases, NMSC are recurrent and located in periorbital area (i.e. inner canthus). In these instances, both EBT and brachytherapy are difficult and/or inadequate to treat safely most of patients. Among the new technologies, stereotactic ablative radiation therapy could be a valid therapeutic option treating “difficult NMSC”. In a recent paper [2], we reported our experience with Stereotactic Body Radiation Therapy (SBRT) in a patient with recurrent and complicated NMSC using Cyberknife System (CKS). In fact, the CKS is a possible alternative to surgery and brachytherapy in patients with recurrent NMSC located in irregular anatomical areas close to critical organs (i.e. eyes). The SBRT with image guided exceeds the limits of the set-up for relocation; the inverse planning allows to cover irregular volumes greater than 20 mm. The use of the photons X-6 MV permits to treat the lesions with invasion more than 4 mm. Do Olga Pons-Llanas et al. have experience and/or data on the use of brachytherapy in “difficult areas”? In fact, in daily clinical practice many patients have “irregular and difficult” NMSC and it is important that Radiation Oncologists have more therapeutic options in these instances. We think that it is important for the authors to comment on these issues and perhaps reply within the context of this journal.

Levetiracetam-induced radiation recall dermatitis in a patient undergoing stereotactic radiotherapy.

homozygous substitution c.28T>C (p.Arg10Ter). These causative mutations in GPP have already been reported in the published work. Pregnant patients with GPP have limited treatment choices and the safety of treatment has not been established yet. Only two cases of GPP in pregnancy have been reported to be successfully treated with infliximab. This is the first report of pregnant GPP patient bearing IL36RN mutation successfully treated with infliximab. Our case demonstrated the usefulness and safety of infliximab for a pregnant GPP patient.

Comments on "Lymph Node Ratio as a Risk Factor for Locoregional Recurrence in Breast Cancer Patients"

http://ejbc.kr | pISSN 1738-6756 eISSN 2092-9900 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. To the Editor, We read the paper by Kim et al. [1], which appeared in the latest issue of this journal, with great interest. The study investigated the association between lymph node ratio (LNR) and locoregional control (LRC) in 234 breast cancer patients with ≥ 10 involved axillary lymph nodes who underwent multimodality treatment. In our opinion, the paper by Kim et al. [1] raises some interesting and relevant points that we have already addressed in our previous paper [2]. While some methodological aspects are similar, others are different. In particular, in their study, Kim et al. [1] reviewed the medical records of all breast cancer patients with ≥ 10 involved nodes, and all patients received multimodality treatment with radical surgery (n= 169) or breast conserving surgery (BCS; n= 65) with axillary lymph node dissection, adjuvant chemotherapy, and radiotherapy. The cutoff value of LNR was set at 0.7. On the other hand, in our study, 195 women with pT1-2 pN2-3 breast cancer treated by BCS with axillary lymph node dissection (levels I-II and/or III) followed by whole breast and nodal irradiation (excluding internal mammary nodes), chemotherapy, and/or hormonal therapy were included [3,4]. Patients with ectopic breast cancers were excluded [5]. Additionally, a categorization of breast cancer subtype on the basis of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status was used: (1) luminal A (ER-positive or PR-positive, HER2negative, and Ki-67-low); (2) luminal B (ER-positive or PRnegative, HER2-negative, and Ki-67-high); (3) HER2-positive or non-luminal (ER-negative, PR-negative, and HER2 overexpression or amplified); and basal-like or triple-negative (ERnegative, PR-negative, and HER2-negative). We set a cutoff value of LNR at 0.65. In the study of Kim et al. [1], locoregional recurrence (LRR) was observed in 30 patients (12.8%) and the 5-year LRC rate was 88.8%. LNR ≥ 0.7 and pathologic state (T3–T4) were noted to have an association with LRC with borderline significance (p= 0.06 and p= 0.07, respectively). Age, menopausal status, nuclear grade, resection margins, molecular subtype, and the use of taxane chemotherapy were found to not be significantly associated with LRC. Interestingly, in the multivariate analysis, LNR ≥ 0.7 was identified as the only independent factor for LRC. On the contrary, in our series [2], even though the 5-year LRC rate was similar to that reported in the study of Kim et al. [1], older age was significantly associated with a shorter overall survival (p= 0.027) and a Ki-67 value of ≥ 50% was significantly associated with time to recurrence (p = 0.049); moreover, both HER2 (3+) overexpression and pN3 status were associated with a shorter overall survival with borderline significance (p = 0.062 and p = 0.067, respectively). Similar to the study of Kim et al. [1], in our series NR > 0.65 showed a significant association with a shorter overall survival (p= 0.033) [2]. In conclusion, Kim et al. [1] suggested that an aggressive multimodal treatment approach permitted a favorable locoregional outcome in patients with ≥ 10 involved axillary lymph nodes; however, patients with a high LNR ≥ 0.7 had an increased risk for LRR, including those who received local treatment. Similarly, we have demonstrated that the LNR value in patients with more than three positive axillary nodes undergoing BCS and regional irradiation may represent an imporComments on “Lymph Node Ratio as a Risk Factor for Locoregional Recurrence in Breast Cancer Patients”