Dual-tracer PET/CT protocol with [18F]FDG and [68Ga]Ga-FAPI-46 outperforms single-tracer PET/CT with [18F]FDG in different cancer types, resulting in larger functional and gross tumor volume.

PURPOSE: Fibroblast activation protein (FAP) detected by positron-emission tomography (PET) using fibroblast activation protein inhibitor (FAPI) appears to be a promising target for cancer imaging, staging, and therapy, providing added value and strength as a complement to [18F]fluorodeoxyglucose (FDG) in cancer imaging. We recently introduced a combined single-session/dual-tracer protocol with [18F]FDG and [68Ga]Ga-FAPI for cancer imaging and staging. Malignant tissue visualization and target-to-background uptake ratios (TBRs) as well as functional tumor volume (FTV) and gross tumor volume (GTV) were assessed in the present study with single-tracer [18F]FDG PET/computed tomography (CT) and with dual-tracer [18F]FDG&[68Ga]Ga-FAPI-46 PET/CT. METHODS: A total of 19 patients with head and neck and gastrointestinal cancers received initial [18F]FDG-PET/CT followed by dual-tracer PET/CT after additional injection of [68Ga]Ga-FAPI-46 during the same medical appointment (on average 13.9 ± 12.3 min after injection of [18F]FDG). Two readers visually compared detection rate of malignant tissue, TBR, FTV, and GTV for tumor and metastatic tissue in single- and dual-tracer PET/CT. RESULTS: The diagnostic performance of dual-tracer compared to single-tracer PET/CT was equal in 13 patients and superior in 6 patients. The mean TBRs of tumors and metastases in dual-tracer PET/CTs were mostly higher compared to single-tracer PET/CT using maximal count rates (CRmax). GTV and FTV were significantly larger when measured on dual-tracer compared to single-tracer PET/CT. CONCLUSION: Dual-tracer PET/CT with [18F]FDG and [68Ga]Ga-FAPI-46 showed better visualization due to a generally higher TBR and larger FTV and GTV compared to [18F]FDG-PET/CT in several tumor entities, suggesting that [68Ga]Ga-FAPI-46 provides added value in pretherapeutic staging.

Prognostic value of fibroblast activation protein expressing tumor volume calculated from [68 Ga]Ga-FAPI PET/CT in patients with esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to investigate the prognostic value of semiquantitative parameters derived from [68 Ga]Ga-fibroblast activation protein inhibitor (FAPI) PET/CT for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. METHODS: We conducted a retrospective analysis on patients from a prospective parent study (NCT04416165). A total of 45 patients with locally advanced ESCC who underwent [68 Ga]Ga-FAPI from December 2019 to March 2021 were included. The maximum standard uptake value (SUVmax), gross tumor volume (GTV), and total lesion-FAPI (TL-FAPI) of the primary tumor were calculated from the corresponding PET/CT image. Unpaired parameters were compared using Student's t test or the Mann-Whitney U test. Paired parameters were compared using the paired t test or the Wilcoxon matched-pairs signed-rank test. Kaplan-Meier curves were generated to calculate progression-free survival (PFS) and overall survival (OS) rates, and Cox regression analysis was performed to determine which PET/CT parameters were prognostic factors for PFS and/or OS. RESULTS: Thirty-four of the 45 patients met the criteria, and the median follow-up time was 24 months (16-29 months). SUVmax-FAPI, GTVFAPI, and TL-FAPI in patients with stage T4 tumors were significantly higher than those in patients with stage T2/T3 tumors (all P < 0.01). In the univariate Cox regression analysis, T stage, N stage, GTVFAPI, and TL-FAPI were associated with PFS, and T stage, GTVFAPI, and TL-FAPI were associated with OS. Upon multivariable analysis, GTVFAPI was an independent prognostic factor for both PFS (hazard ratio (HR), 5.76; 95% confidence interval (CI), 2.13-15.57, P = 0.001) and OS (HR, 4.96; 95% CI, 2.55-18.79, P = 0.001). CONCLUSION: This pilot study revealed that [68 Ga]Ga-FAPI PET/CT may have prognostic value for patients with ESCC treated with definitive chemoradiotherapy. It may aid in personalized patient management by steering treatment modifications before therapy. Prospective studies with larger samples and longer observation periods are needed.

Impact of metal artifact reduction algorithm on gross tumor volume delineation in tonsillar cancer: reducing the interobserver variation.

BACKGROUND: Patients with tonsillar cancer (TC) often have dental fillings that can significantly degrade the quality of computed tomography (CT) simulator images due to metal artifacts. We evaluated whether the use of the metal artifact reduction (MAR) algorithm reduced the interobserver variation in delineating gross tumor volume (GTV) of TC. METHODS: Eighteen patients with TC with dental fillings were enrolled in this study. Contrast-enhanced CT simulator images were reconstructed using the conventional (CTCONV) and MAR algorithm (CTMAR). Four board-certified radiation oncologists delineated the GTV of primary tumors using routine clinical data first on CTCONV image datasets (GTVCONV), followed by CTCONV and CTMAR fused image datasets (GTVMAR) at least 2 weeks apart. Intermodality differences in GTV values and Dice similarity coefficient (DSC) were compared using Wilcoxon's signed-rank test. RESULTS: GTVMAR was significantly smaller than GTVCONV for three observers. The other observer showed no significant difference between GTVCONV and GTVMAR values. For all four observers, the mean GTVCONV and GTVMAR values were 14.0 (standard deviation [SD]: 7.4) cm3 and 12.1 (SD: 6.4) cm3, respectively, with the latter significantly lower than the former (p < 0.001). The mean DSC of GTVCONV and GTVMAR was 0.74 (SD: 0.10) and 0.77 (SD: 0.10), respectively, with the latter significantly higher than that of the former (p < 0.001). CONCLUSIONS: The use of the MAR algorithm led to the delineation of smaller GTVs and reduced interobserver variations in delineating GTV of the primary tumors in patients with TC.

Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer-results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group.

BACKGROUND: In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. METHODS: A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. RESULTS: GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5-877) and GTV2 of 106.2 ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2 ml (p < 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64-0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. CONCLUSION: Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.

[F18] FDG-PET/CT for manual or semiautomated GTV delineation of the primary tumor for radiation therapy planning in patients with esophageal cancer: is it useful?

BACKGROUND: Target volume definition of the primary tumor in esophageal cancer is usually based on computed tomography (CT) supported by endoscopy and/or endoscopic ultrasound and can be difficult given the low soft-tissue contrast of CT resulting in large interobserver variability. We evaluated the value of a dedicated planning [F18] FDG-Positron emission tomography/computer tomography (PET/CT) for harmonization of gross tumor volume (GTV) delineation and the feasibility of semiautomated structures for planning purposes in a large cohort. METHODS: Patients receiving a dedicated planning [F18] FDG-PET/CT (06/2011-03/2016) were included. GTV was delineated on CT and on PET/CT (GTVCT and GTVPET/CT, respectively) by three independent radiation oncologists. Interobserver variability was evaluated by comparison of mean GTV and mean tumor lengths, and via Sørensen-Dice coefficients (DSC) for spatial overlap. Semiautomated volumes were constructed based on PET/CT using fixed standardized uptake values (SUV) thresholds (SUV30, 35, and 40) or background- and metabolically corrected PERCIST-TLG and Schaefer algorithms, and compared to manually delineated volumes. RESULTS: 45 cases were evaluated. Mean GTVCT and GTVPET/CT were 59.2/58.0 ml, 65.4/64.1 ml, and 60.4/59.2 ml for observers A-C. No significant difference between CT- and PET/CT-based delineation was found comparing the mean volumes or lengths. Mean Dice coefficients on CT and PET/CT were 0.79/0.77, 0.81/0.78, and 0.8/0.78 for observer pairs AB, AC, and BC, respectively, with no significant differences. Mean GTV volumes delineated semiautomatically with SUV30/SUV35/SUV40/Schaefer's and PERCIST-TLG threshold were 69.1/23.9/18.8/18.6 and 70.9 ml. The best concordance of a semiautomatically delineated structure with the manually delineated GTVCT/GTVPET/CT was observed for PERCIST-TLG. CONCLUSION: We were not able to show that the integration of PET/CT for GTV delineation of the primary tumor resulted in reduced interobserver variability. The PERCIST-TLG algorithm seemed most promising compared to other thresholds for further evaluation of semiautomated delineation of esophageal cancer.

Tumor regression during radiotherapy for non-small cell lung cancer patients using cone-beam computed tomography images.

PURPOSE: Previous literature has reported contradicting results regarding the relationship between tumor volume changes during radiotherapy treatment for non-small cell lung cancer (NSCLC) patients and locoregional recurrence-free rate or overall survival. The aim of this study is to validate the results from a previous study by using a different volume extraction procedure and evaluating an external validation dataset. METHODS: For two datasets of 94 and 141 NSCLC patients, gross tumor volumes were determined manually to investigate the relationship between tumor volume regression and locoregional control using Kaplan-Meier curves. For both datasets, different subgroups of patients based on histology and chemotherapy regimens were also investigated. For the first dataset (n = 94), automatically determined tumor volumes were available from a previously published study to further compare their correlation with updated clinical data. RESULTS: A total of 70 out of 94 patients were classified into the same group as in the previous publication, splitting the dataset based on median tumor regression calculated by the two volume extraction methods. Non-adenocarcinoma patients receiving concurrent chemotherapy with large tumor regression show reduced locoregional recurrence-free rates in both datasets (p < 0.05 in dataset 2). For dataset 2, the opposite behavior is observed for patients not receiving chemotherapy, which was significant for overall survival (p = 0.01) but non-significant for locoregional recurrence-free rate (p = 0.13). CONCLUSION: The tumor regression pattern observed during radiotherapy is not only influenced by irradiation but depends largely on the delivered chemotherapy schedule, so it follows that the relationship between patient outcome and the degree of tumor regression is also largely determined by the chemotherapy schedule. This analysis shows that the relationship between tumor regression and outcome is complex, and indicates factors that could explain previously reported contradicting findings. This, in turn, will help guide future studies to fully understand the relationship between tumor regression and outcome.

Radiotherapy for the treatment of pituitary adenomas: A dosimetric comparison of three planning techniques.

AIM: Our goal was to compare conformal 3D (C3D) radiotherapy (RT), modulated intensity RT (IMRT), and volumetric modulated arc therapy (VMAT) planning techniques in treating pituitary adenomas. BACKGROUND: RT is important for managing pituitary adenomas. Treatment planning advances allow for higher radiation dosing with less risk of affecting organs at risk (OAR). MATERIALS AND METHODS: We conducted a 5-year retrospective review of patients with pituitary adenoma treated with external beam radiation therapy (C3D with flattening filter, flattening filter-free [FFF], IMRT, and VMAT). We compared dose-volume histogram data. For OARs, we recorded D2%, maximum, and mean doses. For planning target volume (PTV), we registered V95%, V107%, D95%, D98%, D50%, D2%, minimum dose, conformity index (CI), and homogeneity index (HI). RESULTS: Fifty-eight patients with pituitary adenoma were included. Target-volume coverage was acceptable for all techniques. The HI values were 0.06, IMRT; 0.07, VMAT; 0.08, C3D; and 0.09, C3D FFF (p < 0.0001). VMAT and IMRT provided the best target volume conformity (CI, 0.64 and 0.74, respectively; p < 0.0001). VMAT yielded the lowest doses to the optic pathway, lens, and cochlea. The position of the neck in extreme flexion showed that it helps in planning mainly with VMAT by allowing only one arc to be used and achieving the desired conformity, decreasing the treatment time, while allowing greater protection to the organs of risk using C3D, C3DFFF. CONCLUSIONS: Our results confirmed that EBRT in pituitary adenomas using IMRT, VMAT, C3D, C3FFF provide adequate coverage to the target. VMAT with a single arc or incomplete arc had a better compliance with desired dosimetric goals, such as target coverage and normal structures dose constraints, as well as shorter treatment time. Neck extreme flexion may have benefits in treatment planning for better preservation of organs at risk. C3D with extreme neck flexion is an appropriate treatment option when other treatment techniques are not available.

Dosimetric impact on changes in target volumes during intensity-modulated radiotherapy for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To assess anatomic changes during intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine its dosimetric impact. PATIENTS AND METHODS: Twenty patients treated with IMRT for NPC were enrolled in this study. A second CT was performed at 38 Gy. Manual contouring of the macroscopic tumor volumes (GTV) and the planning target volumes (PTV) were done on the second CT. We recorded the volumes of the different structures, D98 %, the conformity, and the homogeneity indexes for each PTV. Volume percent changes were calculated. RESULTS: We observed a significant reduction in tumor volumes (58.56 % for the GTV N and 29.52 % for the GTV T). It was accompanied by a significant decrease in the D98 % for the 3 PTV (1.4 Gy for PTV H, p = 0.007; 0.3 Gy for PTV I, p = 0.03 and 1.15 Gy for PTV L, p = 0 0.0066). In addition, we observed a significant reduction in the conformity index in the order of 0.02 (p = 0.001) and 0.01 (p = 0.007) for PTV H and PTV I, respectively. The conformity variation was not significant for PTV L. Moreover, results showed a significant increase of the homogeneity index for PTV H (+ 0.03, p = 0.04) and PTV L (+ 0.04, p = 0.01). CONCLUSION: Tumor volume reduction during the IMRT of NPC was accompanied by deterioration of the dosimetric coverage for the different target volumes. It is essential that a careful adaptation of the treatment plan be considered during therapy for selected patients.

Clinical safety and efficacy of salvage reirradiation for upper abdominal malignancies.

PURPOSE: Reirradiation has the potential to provide effective local control of upper abdominal malignancies. This study aimed to evaluate the safety and efficacy of reirradiation for upper abdominal malignancies. METHODS: A total of 42 patients with a history of prior radiotherapy (RT) received reirradiation for abdominal malignancies between 2005 and 2017. Each patient's medical records, contours, and dose distribution for both RT courses were reviewed. The median dose of the prior RT was 50.0 Gy (range, 30.0-60.0 Gy) and the median dose of reirradiation was 45.0 Gy (range, 15.0-75.0 Gy). RESULTS: With a median follow-up of 10.9 months, the median infield-failure-free survival (IFFS) rate was 9.2 months. Gross tumor volume (GTV) significantly related to IFFS in both the univariate (p = 0.009) and multivariate analyses (p = 0.024), and patients with a GTV of <60.0 mL had an improved IFFS (p = 0.001). Four patients experienced ≥grade 3 late toxicities. In the retrospective dose reconstruction analysis in these patients, the cumulative dose to the most exposed 2 cc (D2cc) of the duodenum was >60.0 Gy (range, 60.1-73.7 Gy). In the univariate analysis, the D2cc of the duodenum and a preexisting duodenal ulcer identified using endoscopy prior to reirradiation significantly correlated with late severe toxicity (p = 0.021 and 0.017, respectively). CONCLUSIONS: Reirradiation for upper abdominal malignancies could be safely performed for patients without preexisting gastrointestinal morbidity unless the duodenum received excessive radiation doses. Reirradiation could also provide substantial IFFS, especially for patients with a GTV of <60.0 mL.

PET/MRI-guided GTV delineation during radiotherapy planning in patients with squamous cell carcinoma of the tongue.

PURPOSE: The aim of the study was to evaluate the usefulness and accuracy of 18-fluorine-labeled fluorodeoxyglucose (PET) and magnetic resonance imaging (MRI) hybrid in gross tumor volume (GTV) delineation during radiotherapy planning in patients with carcinoma of the tongue. METHODS: Ten patients with squamous cell carcinoma (SCC) of the tongue underwent computed tomography (CT) and PET/MRI examination. The GTV for primary tumor and lymph nodes (nGTV) were defined on CT (GTV-CT) and compared to GTVs obtained from PET (GTV-PET) and MRI (GTV-MRI) images. Two methods of GTV determination were used: visual interpretation of CT, PET (GTV-PETvis) and MRI images and quantitative automatic method (Syngovia, Siemens) based on a chosen threshold value (20%, 30%, 40%, 50%) of standardized uptake values (SUVmax) from PET examination (GTV-PET20%, GTV-PET30%, etc.). Statistical analysis of differences in GTV values obtained from CT, PET and MRI studies was performed. GTV-CT was used as a reference. RESULTS: In all, 80% of GTV-MRI and 40% of GTV-PETvis were larger than GTV-CT. Respectively, 20% of GTV-MRI and 60% of GTV-PETvis were smaller than GTV-CT. Taking into account all threshold measurements, 70% of volumes were smaller than GTV-CT. GTV-PET30% were the most closely related volumes to GTV-CT from all threshold methods in 50% of patients. GTV-PETvis generated the most similar volumes in relation to GTV-CT from all PET measurements. Statistical analysis confirmed those results. Compared to nGTV-CT, 70% of nGTV-MRI and 20% of nGTV-PETvis were larger. The remaining nGTV-MRI and nGTV-PETvis measurements were smaller than nGTV-CT. Measurements of all thresholds nGTVs were smaller than nGTV-CTV in 52.5% of cases. nGTV-PET20% were the most closely related volumes to nGTV-CT in 40% of the cases. Statistical analysis showed that nGTV-PET20% (p = 0.0468), nGTV-PETvis (p = 0.0166), and nGTV-PET50% (p = 0.0166) diverge significantly from nGTV-CT results. nGTV-MRI (p = 0.1141), nGTV-PET30% (p = 0.2845), and nGTV-PET40% (p = 0.5076) were significantly related with nGTV-CT. CONCLUSION: Combination of PET/MRI provides more information during target tumor mass delineation in radiotherapy planning of patients with SCC of the tongue than other standard imaging methods. The most frequently matching threshold value was 30% of SUVmax for primary tumor delineation and 30-40% of SUVmax for nGTV determination.

Major complications from radiotherapy following treatment for atypical meningiomas.

OBJECTIVEComplications from radiotherapy (RT), in a primary or adjuvant setting, have overall been described as uncommon, with few detailed descriptions of major complications. The authors present two cases involving significant complications and their management in their review of patients undergoing RT for treatment of atypical meningioma.METHODSThe authors conducted a retrospective review of all patients with pathologically confirmed atypical meningioma (WHO grade II) treated with primary or adjuvant RT from February 2011 through February 2019. They identified two patients with long-term, grade 3 toxicity. The cases of these patients are described in detail.RESULTSTwo patients had major complications associated with postoperative RT. Patients 1 and 2 both were treated with postoperative RT for pathologically confirmed atypical meningioma. Patient 1 experienced worsening behavioral changes, cognitive decline, and hydrocephalus following treatment. This required cerebrospinal fluid diversion. Patient 2 developed radiation necrosis with mass effect and cognitive decline. Neither patient returned to his/her initial post-RT status after steroid therapy, and each remained in need of supportive care. Both patients remained free of tumor progression at 52 and 38 months following treatment.CONCLUSIONSThe postoperative management of patients with atypical meningioma continues to be defined, with questions remaining regarding timing of RT, dose, target delineation, and fractionation. Both of the patients in this study received fractionated RT, which included a greater volume of normal brain than more focal treatment options such as would be required by stereotactic radiosurgery (SRS). Further research is needed to compare SRS and fractionated RT for the management of patients with grade II meningiomas. The more focused nature of SRS may make this a preferred option in certain cases of focal recurrence.

Impact of 68Ga-DOTATOC PET/MRI on robotic radiosurgery treatment planning in meningioma patients: first experiences in a single institution.

OBJECTIVEFor stereotactic radiosurgery (SRS) planning, precise contouring of tumor boundaries and organs at risk is of utmost importance. Correct interpretation of standard neuroimaging (i.e., CT and MRI) can be challenging after previous surgeries or in cases of skull base lesions with complex shapes. The aim of this study was to evaluate the impact of 68Ga-DOTATOC PET/MRI on treatment planning for image-guided SRS by CyberKnife.METHODSThe authors retrospectively identified 11 meningioma treatments in 10 patients who received a 68Ga-DOTATOC PET/MRI prior to SRS. The planning target volume (PTV) used for the patients' treatment was defined as the reference standard. This was contoured by a treating radiosurgeon (RS0) using fused planning CT and PET/MRI data sets. The same tumors were then contoured by another experienced radiosurgeon (RS1) and by a less-experienced radiosurgeon (RS2), both blinded to PET data sets. A comparison of target volumes with focus on volume-based metrics and distance to critical structures was performed. RS1 and RS2 also filled in a questionnaire analyzing the confidence level and the subjective need for the implementation of PET data sets for contouring.RESULTSAnalysis showed a subjective personal preference for PET/MRI in all cases for both radiosurgeons, particularly in proximity to critical structures. The analysis of the planning volumes per physician showed significantly smaller RS2-PTV in comparison to RS1-PTV and to RS0-PTV, whereas the median volumes were comparable between RS1-PTV and RS2-PTV (median: RS0: 4.3 cm3 [IQR 3.4-6.5 cm3] and RS1: 4.5 cm3 [IQR 2.7-6 cm3] vs RS2: 2.6 cm3 [IQR 2-5 cm3]; p = 0.003). This was also reflected in the best spatial congruency between the 2 experienced physicians (RS0 and RS1). The percentage of the left-out volume contoured by RS1 and RS2 compared to RS0 with PET/MRI demonstrated a relevant left-out-volume portion in both cases with greater extent for the less-experienced radiosurgeon (RS2) (RS1: 19.1% [IQR 8.5%-22%] vs RS2: 40.2% [IQR 34.2%-53%]). No significant differences were detected regarding investigated critical structures.CONCLUSIONSThis study demonstrated a relevant impact of PET/MRI on target volume delineation of meningiomas. The extent was highly dependent on the experience of the treating physician. This preliminary study supports the relevance of 68Ga-DOTATOC PET/MRI as a tool for radiosurgical treatment planning of meningiomas.

Canine meningiomas treated with three-dimensional conformal radiation therapy require magnetic resonance imaging to avoid a geographic miss.

Exact target volume definition is an essential prerequisite for modern radiotherapy treatment planning. Contouring the gross tumor volume of brain tumors on computed tomography (CT) images coregistered with magnetic resonance images is standard practice in human medicine. In this retrospective study, including only cases with an imaging diagnosis of meningioma, we hypothesized that the gross tumor volume contoured from the contrast-enhanced magnetic resonance imaging (MRI) (gross tumor volume-MRI) is larger when compared to the gross tumor volume contoured using contrast-enhanced CT (gross tumor volume-CT). A total of 22 dogs were included in the study. Interestingly, there was a significant statistical difference between the gross tumor volume-CT and the gross tumor volume-MRI (P = 0.001). The gross tumor volume-MRI was larger than the gross tumor volume-CT in all, but two cases. The mean ratio between gross tumor volume-MRI and gross tumor volume-CT was 1.43 (range 0.84-4.00). The mean overlap between gross tumor volume-CT and gross tumor volume-MRI was 68% (range 22-86%), while a mean of 26% of the composite gross tumor volume was defined only by MRI (range 4-76%) and a mean of 6% only by CT (range 0-22%). These findings suggest that CT and MRI are complementary modalities in radiation planning of meningiomas and their composite volume should be used to avoid geographical miss of neoplastic tissue. When the MRI is not available for planning, a margin of 0.3 cm around the gross tumor volume-CT could reduce the probability of a geographical miss. However, such numerical correction cannot be applied to the clinical practice until it is validated in a properly designed treatment planning study.

Peripheral nervous system injury after high-dose single-fraction image-guided stereotactic radiosurgery for spine tumors.

OBJECTIVE The object of this study was to determine the percentage of high-dose (1800-2600 cGy) single-fraction stereotactic radiosurgery (SF-SRS) treatments to the spine that result in peripheral nervous system (PNS) injury. METHODS All patients treated with SF-SRS for primary or metastatic spine tumors between January 2004 and May 2013 and referred to the Rehabilitation Medicine Service for evaluation and treatment of neuromuscular, musculoskeletal, or functional impairments or pain were retrospectively identified. RESULTS Five hundred fifty-seven SF-SRS treatments in 447 patients resulted in 14 PNS injuries in 13 patients. All injures resulted from SF-SRS delivered to the cervical or lumbosacral spine at 2400 cGy. The overall percentage of SF-SRS treatments resulting in PNS injury was 2.5%, increasing to 4.5% when the thoracic spine was excluded from analysis. The median time to symptom onset following SF-SRS was 10 months (range 4-32 months). The plexus (cervical, brachial, and/or lumbosacral) was affected clinically and/or electrophysiologically in 12 (86%) of 14 cases, the nerve root in 2 (14%) of 14, and both in 6 (43%) of 14 cases. All patients experienced pain and most (93%) developed weakness. Peripheral nervous system injuries were CTCAE Grade 1 in 14% of cases, 2 in 64%, and 3 in 21%. No dose relationship between SF-SRS dose and PNS injury was detected. CONCLUSIONS Single-fraction SRS to the spine can result in PNS injury with major implications for function and quality of life.

The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery.

OBJECTIVE An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment. METHODS All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3-6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumor's histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression. RESULTS A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2-141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7-57 months). The median prescribed dose was 2400 cGy (range 1600-2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose). CONCLUSIONS High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes.

[Effect of image fusion technology of radioactive particles implantation before and after the planning target and dosimetry].

Objective: To compare the post-implant target volumes and dosimetric evaluation with pre-plan, the gross tumor volume(GTV) by CT image fusion-based and the manual delineation of target volume in CT guided radioactive seeds implantation. Methods: A total of 10 patients treated under CT-guidance (125)I seed implantation during March 2016 to April 2016 were analyzed in Peking University Third Hospital.All patients underwent pre-operative CT simulation, pre-operative planning, implantation seeds, CT scanning after seed implantation and dosimetric evaluation of GTV.In every patient, post-implant target volumes were delineated by both two methods, and were divided into two groups. Group 1: image fusion pre-implantation simulation and post-operative CT image, then the contours of GTV were automatically performed by brachytherapy treatment planning system; Group 2: the contouring of the GTV on post-operative CT image were performed manually by three senior radiation oncologists independently. The average of three data was sets. Statistical analyses were performed using SPSS software, version 3.2.0. The paired t-test was used to compare the target volumes and D(90) parameters in two modality. Results: In Group 1, average volume of GTV in post-operation group was 12-167(73±56) cm(3). D(90) was 101-153 (142±19)Gy. In Group 2, they were 14-186(80±58)cm(3) and 96-146(122±16) Gy respectively. In both target volumes and D(90), there was no statistical difference between pre-operation and post-operation in Group 1.The D(90) was slightly lower than that of pre-plan group, but there was no statistical difference (P=0.142); in Group 2, between pre-operation and post-operation group, there was a significant statistical difference in the GTV (P=0.002). The difference of D(90) was similarly (P<0.01). Conclusion: The method of delineation of post-implant GTV through fusion pre-implantation simulation and post-operative CT scan images, the contours of GTV are automatically performed by brachytherapy treatment planning system appears to have improved more accuracy, reproducibility and convenience than manual delineation of target volume by maximum reduce the interference from artificial factor and metal artifacts. Further work and more cases are required in the future.

A Kindler syndrome-associated squamous cell carcinoma treated with radiotherapy.

Kindler syndrome1, 2 is a genetic disorder mainly characterized by increased skin fragility and photosensitivity,3, 4 making the use of treatments based on radiation difficult or even prohibited. Thus, cases reporting Kindler syndrome patients treated with radiotherapy are rare. In this study, we report clinical outcomes and care provided for a rare case of a Kindler syndrome patient submitted to radiotherapy. Diagnosed with squamous cell carcinoma involving the buccal mucosa, the patient was exclusively treated with radiotherapy, with 70 Gy delivered on the PTV with the Volumetric Modulated Arc technique. The patient's reaction regarding control of the lesion is relevant compared to patients not affected by the syndrome. We noticed acute reactions of the skin and buccal mucosa after few radiotherapy sessions, followed by a fast reduction in the tumor volume. The efficacy of radiotherapy along with multidisciplinary actions allowed treatment continuity, leading to a complete control of the lesion and life quality improvement and showed that the use of radiotherapy on Kindler syndrome patients is possible.

Comparison of patient-specific internal gross tumor volume for radiation treatment of primary esophageal cancer based separately on three-dimensional and four-dimensional computed tomography images.

To compare the target volume, position and matching index of the patient-specific internal gross tumor volume (IGTV) based on three-dimensional (3D) and four-dimensional (4D) computed tomography (CT) images for primary esophageal cancer. Twenty-nine patients with primary thoracic esophageal cancer underwent 3DCT and 4DCT scans during free breathing. IGTVs were constructed using three approaches: combining the gross target volumes from the 10 respiratory phases of the 4DCT dataset to produce IGTV10 ; IGTV2 was acquired by combining the two extreme phases; and IGTV3D was created from the 3DCT-based gross target volume by enlarging the 95th percentile of motion in each direction measured by the 4DCT. 0.16 cm lateral (LR), 0.14 cm anteroposterior (AP) and 0.29 cm superoinferior (SI) in the upper; 0.18 cm LR, 0.10 cm AP and 0.63 cm SI in the middle; and 0.40 cm LR, 0.58 cm AP and 0.82 cm in the lower thoracic esophagus could account for 95% of respiratory-induced tumor motion. The centroid position shift between IGTV10 and IGTV2 was all below 0.10 cm, and less than 0.20 cm between IGTV10 and IGTV3D . IGTV10 was bigger than IGTV2 ; the mean value of matching index for IGTV2 to IGTV10 was 0.87 ± 0.05, 0.85 ± 0.06 and 0.83 ± 0.05 for upper, middle and distal thoracic esophageal tumors, respectively, and just 0.57 ± 0.11, 0.56 ± 0.13 and 0.40 ± 0.03 between IGTV3D and IGTV10 . 4DCT-based IGTV10 is a reasonable patient-specific IGTV for primary thoracic esophageal cancer, and IGTV2 is considered as an acceptable alternative to IGTV10 . However, it seems unreasonable to use IGTV3D substitute IGTV10 .

MRI to delineate the gross tumor volume of nasopharyngeal cancers: which sequences and planes should be used?

BACKGROUND: Magnetic resonance imaging (MRI) has been found to be better than computed tomography for defining the extent of primary gross tumor volume (GTV) in advanced nasopharyngeal cancer. It is routinely applied for target delineation in planning radiotherapy. However, the specific MRI sequences/planes that should be used are unknown. METHODS: Twelve patients with nasopharyngeal cancer underwent primary GTV evaluation with gadolinium-enhanced axial T1 weighted image (T1) and T2 weighted image (T2), coronal T1, and sagittal T1 sequences. Each sequence was registered with the planning computed tomography scans. Planning target volumes (PTVs) were derived by uniform expansions of the GTVs. The volumes encompassed by the various sequences/planes, and the volumes common to all sequences/planes, were compared quantitatively and anatomically to the volume delineated by the commonly used axial T1-based dataset. RESULTS: Addition of the axial T2 sequence increased the axial T1-based GTV by 12% on average (p = 0.004), and composite evaluations that included the coronal T1 and sagittal T1 planes increased the axial T1-based GTVs by 30% on average (p = 0.003). The axial T1-based PTVs were increased by 20% by the additional sequences (p = 0.04). Each sequence/plane added unique volume extensions. The GTVs common to all the T1 planes accounted for 38% of the total volumes of all the T1 planes. Anatomically, addition of the coronal and sagittal-based GTVs extended the axial T1-based GTV caudally and cranially, notably to the base of the skull. CONCLUSIONS: Adding MRI planes and sequences to the traditional axial T1 sequence yields significant quantitative and anatomically important extensions of the GTVs and PTVs. For accurate target delineation in nasopharyngeal cancer, we recommend that GTVs be outlined in all MRI sequences/planes and registered with the planning computed tomography scans.

Exploring habitats-based spatial distributions: improving predictions of lymphovascular invasion in invasive breast cancer.

RATIONALE AND OBJECTIVES: Accurate assessment of lymphovascular invasion (LVI) in invasive breast cancer (IBC) plays a pivotal role in tailoring personalized treatment plans. This study aimed to investigate habitats-based spatial distributions to quantitatively measure tumor heterogeneity on multiparametric magnetic resonance imaging (MRI) scans and assess their predictive capability for LVI in patients with IBC. MATERIALS AND METHODS: In this retrospective cohort study, we consecutively enrolled 241 women diagnosed with IBC between July 2020 and July 2023 and who had 1.5 T/T1-weighted images, fat-suppressed T2-weighted images, and dynamic contrast-enhanced MRI. Habitats-based spatial distributions were derived from the gross tumor volume (GTV) and gross tumor volume plus peritumoral volume (GPTV). GTV_habitats and GPTV_habitats were generated through sub-region segmentation, and their performances were compared. Subsequently, a combined nomogram was developed by integrating relevant spatial distributions with the identified MR morphological characteristics. Diagnostic performance was compared using receiver operating characteristic curve analysis and decision curve analysis. Statistical significance was set at p < 0.05. RESULTS: GPTV_habitats exhibited superior performance compared to GTV_habitats. Consequently, the GPTV_habitats, diffusion-weighted imaging rim signs, and peritumoral edema were integrated to formulate the combined nomogram. This combined nomogram outperformed individual MR morphological characteristics and the GPTV_habitats index, achieving area under the curve values of 0.903 (0.847 -0.959), 0.770 (0.689 -0.852), and 0.843 (0.776 -0.910) in the training set and 0.931 (0.863 -0.999), 0.747 (0.613 -0.880), and 0.849 (0.759 -0.938) in the validation set. CONCLUSION: The combined nomogram incorporating the GPTV_habitats and identified MR morphological characteristics can effectively predict LVI in patients with IBC.