Evaluation of Treatment Outcomes of Prostate Cancer Patients With Lymph Node Metastasis Treated With Definitive Radiotherapy: Comparative Analysis of PSMA PET/CT and Conventional Imaging.

PURPOSE: We investigated the impact of prostate-specific membrane antigen (PSMA) PET/CT compared with conventional imaging on treatment outcomes for node-positive prostate cancer (PCa) patients who underwent androgen deprivation therapy (ADT) and external radiotherapy (RT). PATIENTS AND METHODS: A multicentric, retrospective study recruited patients with node-positive PCa patients who underwent conventional radiological evaluation or PSMA PET/CT and received ADT and RT at 3 hospitals from 2009 to 2021 were enrolled. Patients underwent prostate and pelvis RT, accompanied by a minimum of 6 months of ADT. The primary endpoints were progression-free survival (PFS) and PCa-specific survival (PCSS). Cox regression analyzed the association of survival with potential prognostic factors, whereas logistic regression identified the predictors of bone and lymph node metastasis. RESULTS: The median follow-up time was 64.0 months. The majority of patients (64.1%) underwent PSMA PET/CT for staging. The 5-year rates of PFS and PCSS were 63.7% and 83.7%, respectively. Disease progression was observed in 90 patients (36.3%). In multivariable analysis, ADT duration of less than 24 months and post-RT prostate-specific antigen (PSA) nadir were prognostic for PFS. Early clinical T stage and PSMA PET/CT predicted better PCSS. Patients staged with PSMA PET/CT had exhibited significantly higher 5-year PCSS rates than compared with those staged with conventional imaging (95.1% vs 76.9%; P = 0.01). Shorter ADT duration and higher PSA levels after RT independently predicted bone metastasis in multivariable logistic regression. Advanced T stage, shorter ADT duration, and higher PSA levels after neoadjuvant ADT predicted nonregional lymph node recurrence. CONCLUSIONS: ADT with pelvis RT is an effective treatment option for node-positive PCa patients. The PSMA PET/CT outperformed conventional imaging in PCSS, emphasizing the importance of precise clinical staging for patients undergoing definitive RT.

A Comparative Analysis of Implant-sparing Plan Versus Conventional Plans Utilizing Helical Tomotherapy in Breast Cancer Patients Undergoing Breast Reconstruction.

BACKGROUND/AIM: To compare implant sparing irradiation with conventional radiotherapy (RT) using helical (H) and TomoDirect (TD) techniques in breast cancer patients undergoing immediate breast reconstruction (IBR). PATIENTS AND METHODS: The dosimetric parameters of 40 patients with retropectoral implants receiving 50.4 Gy delivered in 28 fractions were analyzed. Three plans were created: H plan using conventional planning target volume (PTV) that included the chest wall, skin, and implant; TD plan using conventional PTV; and Hs plan using implant-sparing PTV. The H, TD, and Hs plans were compared for PTV doses, organ-at-risk (OAR) doses, and treatment times. RESULTS: Dose distribution in the Hs plan was less homogeneous and uniform than that in the H and TD plans. The TD plan had lower lung, heart, contralateral breast, spinal cord, liver, and esophagus doses than the Hs plan. Compared to the Hs plan, the H plan had lower lung volume receiving 5Gy (V5) (39.1±3.9 vs. 41.2±3.9 Gy; p<0.001), higher V20 (12.3±1.3 vs. 11.5±2.6 Gy; p=0.02), and higher V30 (7.5±1.6 vs. 4.4±1.7 Gy; p<0.001). H plan outperformed Hs plan in heart dosimetric parameters except V20. The Hs plan had significantly lower mean implant doses (43.4±2.1 Gy) than the H plan (51.4±0.5 Gy; p<0.001) and the TD plan (51.9±0.6 Gy; p<0.001). Implementing an implant sparing technique for silicone dose reduction decreases lung doses. CONCLUSION: Conventional H and TD plans outperform the implant sparing helical plan dosimetrically. Because capsular contracture during RT is unpredictable, long-term clinical outcomes are required to determine whether silicon should be spared.

The effect of dose-escalation radiotherapy with simultaneous-integrated-boost on the use of short-term androgen deprivation therapy in patients with intermediate risk prostate cancer.

PURPOSE: To compare the biochemical failure (FFBF) and prostate cancer specific survival (PCSS) rates of patients with intermediate-risk prostate cancer (IR-PC) who were treated with 6 months of androgen deprivation therapy (ADT) with 78 Gy to the prostate, those treated with ADT and focal boost (FB) of 86 Gy to intraprostatic lesion (IPL) using the simultaneous-integrated boost (SIB) technique, and those treated with SIB alone. MATERIALS AND METHODS: A retrospective analysis of 320 IR-PC patients treated between January 2012 and April 2021 was performed. Patients were divided into three groups based on their treatment arm: 78 + ADT (109 patients, 34.1%), 78/86 (102 patients, 31.8%), and 78/86 + ADT. Univariable and multivariable analyses were used to determine prognostic factors for FFBF and PCSS. RESULTS: Median follow-up was 8.8 years. The 8-year FFBF and PCSS rates were 88.6% and 99.0%. Patients who received ADT had significantly higher pretreatment PSA levels and clinical tumor stage. Disease progression occurred in 45 patients (7.3%) at a median of 41.9 months after definitive radiotherapy (RT). Younger age, positive core biopsy (PCB) ≥ 50%, and the absence of ADT were all independent predictors of poor FFBF in multivariate analysis, whereas patients with PCB < 50% who were also given ADT had better PCSS. Patients treated with 78/86 Gy alone had worse FFBF than those treated with 78 Gy and ADT (Hazard ratio [HR] = 3.39 [95% CI = 1.46-7.88]; p = 0.005), as well as than those treated with 78/86 Gy and ADT (HR = 3.21 [95% CI = 1.23-6.46]; p = 0.009). However, FB to IPL has no effect on PCSS in multivariable analysis. There was no significant difference between treatment groups in terms of acute and late Grade ≥2 genitourinary or gastrointestinal toxicity. CONCLUSIONS: Our findings demonstrated that patients who received 78/86 alone did worse than patients who received ADT with either 78 or 78/86 Gy. However, because IR-PC patients are so diverse, additional prospective trials are needed to validate our findings.

Inter-observer variation of target volume delineation for CT-guided cervical cancer brachytherapy.

Purpose: Delineation is a critical and challenging step in radiotherapy planning. Differences in delineation among observers are common, despite the presence of contouring guidelines. This study aimed to identify the inter-observer variability in the target volume delineation of computed tomography (CT)-guided brachytherapy for cervical cancer. Material and methods: Four radiation oncologists (ROs) with different expertise levels delineated high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) according to GYN GEC-ESTRO recommendations, in a blinded manner on every CT set of ten locally advanced cervical cancer cases. The most experienced RO's contours were determined as the index and used for comparison. Dice similarity coefficient (DSC) and pairwise Hausdorff distance (HD) metrics were applied to compare the overlap and gross deviations of all contours. Results: Median DSC for HR-CTV and IR-CTV were 0.73 and 0.76, respectively, and a good concordance was achieved for both in majority of contours. While there was no difference in DSC measurements for HR-CTV among the three ROs, RO-3 provided improved DSC values for IR-CTV (p = 0.01). Median HD95 was 5.02 mm and 6.83 mm, and median HDave was 1.69 mm and 2.21 mm for HR-CTV and IR-CTV, respectively. There was no significant difference among ROs in HR-CTV for HD95 or HDave; however, IR-CTV value was significantly improved according to RO-3 (p = 0.01). Case-by-case HD analysis showed no significant inter-observer variations, except for two cases. Conclusions: The inter-observer agreement is generally high for target volumes in CT-guided brachytherapy for cervical cancer. The agreement is lower for IR-CTV than HR-CTV. The individual characteristics of each case and different expertise levels of the ROs may have caused the differences. Despite the good concordance for delineation, dosimetric consequences can still be clinically significant.

Intracerebral de novo arterio-venous malformations as a side effect of bevacizumab.

INTRODUCTION: Bevacizumab is a monoclonal antibody for the vascular endothelial growth factor receptor and is utilized in the treatment of various tumors. Gastrointestinal perforation/fistula, heart failure, hemorrhage, hypertension, proteinuria/nephrotic syndrome, thromboembolism, posterior reversible encephalopathy syndrome, and necrotizing fasciitis are serious side effects of bevacizumab. Bevacizumab associated de novo brain arterio-venous malformation formation has not been documented in the literature. CASE REPORT: Here, we presented a 35-year-old female patient with recurrent high-grade glial tumor who developed multiple supra- and infratentorial de novo arterio-venous malformations after receiving the last dose of bevacizumab. MANAGEMENT & OUTCOME: Intervention options for the adverse effect were limited. In fact, there was no chance of intervention because the patient died for another reason. DISCUSSION: Based on this experience, it can be hypothesized that bevacizumab may induce de novo arterio-venous malformations in the brain as a result of arterial and venous thrombotic effects. Additional studies should be done to clarify the causal relationship between bevacizumab and arterio-venous malformations in primary brain tumors.

Every other day stereotactic radiation therapy for the treatment of uveal melanoma decreases toxicity.

BACKGROUND AND PURPOSE: To report the long-term results of stereotactic radiosurgery and fractionated stereotactic radiation therapy (SRS/FSRT) in patients with uveal melanoma (UM). MATERIALS AND METHODS: We retrospectively evaluated the results of patients treated between 2007 and 2019. The primary endpoints were local control (LC), local recurrence-free survival (LRFS), enucleation-free survival (EFS) and treatment toxicity. RESULTS: 443 patients with 445 UMs were treated via CyberKnife®. According to the COMS classification, 70% of the tumors were small/medium and 30% were large. Median total RT dose was 54 Gy, median BED10 was 151 Gy. After a median 74-months follow-up, SRS/FSRT yielded an 83% overall LC rate. The 5- and 10-year LRFS rate was 74% and 56%, respectively. Patient age and the COMS size were prognostic for all survival endpoints. An increased SRS/FSRT dose was associated with higher LRFS and EFS rates. SRS/FSRT-related toxicity was observed in 49% of the eyes. Median visual acuity (VA) significantly deteriorated after SRS/FSRT in 76% of the treated eyes. The overall eye preservation rate was 62%, and the 5- and 10-year EFS rate was 64% and 36%, respectively. The delivery of FSRT every other day resulted in a significantly lower rate of toxicity and enucleation compared to FSRT on consecutive days. CONCLUSION: A total dose of ≥45 Gy and BED10Gy ≥ 112.5 SRS/FSRT is associated with a higher LC rate in patients with UM. Despite the favorable outcomes, treatment toxicity is the major limitation of this treatment. Toxicity and enucleation can be minimized by treating the eye every other day.

Transit dosimetry of stereotactic body radiotherapy treatments with electronic portal dosimetry device in patient with spinal implant.

In recent years, the use of the Electronic Portal Imaging Device (EPID) as an in vivo dosimeter has become widespread. However, reports of EPID for stereotactic body radiotherapy (SBRT) applications is scarce. There is no data on this topic especially when there are high-density materials in the radiation field. In this study, we aimed to investigate the dose distributions of SBRT treatment plans in patients with spinal implants by transit EPID dosimetry. Implants were inserted in phantoms that mimic the vertebrae, and VMAT plans were created on the phantoms to deliver 16 Gy radiation doses to the target in 1 fraction. Transit EPID measurements were performed for each irradiation. The results were compared with the treatment planning system using the gamma analysis method. According to the gamma analysis results, while the non-implant model met the acceptance criteria with a rate of 95.4%, the implanted models did not pass the test with results between the rates of 70% to 73%. In addition, while the dose difference in the isocenter was 1.3% for the non-implanted model, this difference was observed to be between 7 and 8% in the implanted models. Our study revealed that EPID can be used as transit dosimetry for the VMAT-SBRT applications. However, unacceptable dose differences were obtained by transit EPID dosimetry in the VMAT-SBRT applications of patients with an implant. In the treatment of such patients, alternative treatment methods should be preferred in which the interaction of the implants with radiation can be prevented.

Stereotactic Radiotherapy for Adrenal Metastases: A Multi-Institutional Review of Patient Characteristics and Outcomes - Turkish Society for Radiation Oncology SBRT Group Study (Trod SBRT 10-004).

INTRODUCTION: This study aimed to report the outcomes of stereotactic body radiotherapy (SBRT) for adrenal metastasis in a retrospective multi-institutional cohort. METHODS: The outcomes of 124 patients with 146 adrenal metastases who underwent SBRT within 11 years (2008-2019) were retrospectively evaluated. Survival outcomes were analyzed by the Kaplan-Meier method. Patient, tumor, and treatment characteristics and their effects on survival, local control (LC), and toxicity outcomes were analyzed by log-rank and multivariate Cox regression methods. RESULTS: The median age was 60 years. The most frequent primary tumor site was the lung, followed by the gastrointestinal system and breast. The adrenal gland was the only metastatic site in 49 (40%) patients. Median biologically effective dose (BED)10 was 61 Gy. The overall LC rate was 83%, and it was positively correlated with the BED10 and fraction dose. The 1- and 2-year local recurrence-free survival, overall survival (OS), and progression-free survival (PFS) rate was 79% and 69%, 83% and 60%, and 31% and 12%, respectively. OS significantly improved with non-lung cancer and <4-cm lesion and PFS with a fraction dose ≥8 Gy, BED10 >65 Gy, and an isolated adrenal metastasis. Fourteen patients reported an acute toxicity, and late toxicity was observed in 3 patients, including one grade 5. CONCLUSION: A satisfactory LC rate was achieved for adrenal metastasis via SBRT. A higher BED10 and fraction dose were positive prognostic factors for tumor control. However, the main problem is DM in these patients, and systemic treatment options are needed to be improved.

Turkish translation and validation of the Xerostomia Inventory.

Objectives: The Xerostomia Inventory (XI) was developed to assess the severity of dryness in patients with xerostomia. It has a long and a short form with three- and five-point Guttman-type response options. In this study, we aimed to translate the XI into Turkish, to assess the validity and reliability of both response options in patients with head & neck cancer (HNC) or Sjögren syndrome (SS), and to select the optimal version for Turkish patients. Patients and methods: Between January 2019 and June 2019, the XI was translated into Turkish (XI-T) and applied to patients aged ≥18 years with HNC and SS. All patients were applied two tests including both the three- and five-point options. The internal consistency was assessed by Cronbach alpha and test-retest reliability by intraclass correlation coefficients (ICCs). Content validity was based on expert opinion and patient reviews. Results: A total of 186 patients (109 males, 77 females; median age: 54 years; range, 19 to 78 years) answered the XI-T. The number of patients with HNC and SS was 143 (77%) and 43 (23%), respectively. Median XI-T score was 17 for the three-point, and 24 for the five-point option, respectively. Overall internal consistency was satisfactory for both options (α=0.81 and α=0.89, respectively). Overall test-retest reliability was satisfactory and ICCs ranged between 0.71 and 0.92 for the three-point, and 0.36 and 0.94 for the five-point option, respectively. Assessments based on expert opinions and patient reviews also favored the content validity of the scale. Conclusion: The XI-T with both three- and five-point options is a valid and reliable tool to evaluate the presence and severity of dryness in patients with HNC and SS who experience xerostomia. The three-point option is more comprehensible and can be preferred over the five-point option in the Turkish population.

Radiotherapy-induced alterations in vitreous humor: A new potential critical structure.

Vitreous humor (VH) is not considered as a critical structure in the radiotherapy planning process. In the present study, an experimental animal model was performed to examine the effects of radiotherapy on VH. The right eyes of twelve New Zealand rabbits were irradiated to 60 Gy in 3 fractions in accordance with the scheme used in the treatment of uveal melanoma in our clinic, and contralateral (left) eyes were considered as control. Weekly ophthalmologic examination was performed after irradiation, for three months. At the end of the third month, enucleation and vitreous collection were conducted. The vitreous samples were subjected to metabolomic analyses, ELISA analyses, viscosity measurements, and electron microscopic examination. In control and experimental vitreous samples, 275 different metabolites were identified, and 34 were found to differ significantly between groups. In multivariate analyzes, a clear distinction was observed between control and irradiated vitreous samples. Pathway analysis revealed that nine pathways were affected, and these pathways were mainly related to amino acid metabolism. A significant decrease was observed in the expressions of type II, V, and XI collagens in protein level in the ELISA. There was a non-significant decrease in type IX collagen and viscosity. Electron microscopic examination revealed disrupted collagen fibrillar ultra-structure and dispersed collagen fragments in the experimental vitreous. An intact vitreous is essential for a healthy eye. In this study, we observed that radiation causes changes in the vitreous that may have long-term consequences.

Does Combined Fractionated Stereotactic Radiotherapy and Immunotherapy Change the Outcome of Recurrent High-Grade Gliomas?

Background Radiotherapy (RT) with immune checkpoint inhibitors (ICI) has yielded good responses in many cancers. We aimed to report the results of combined fractionated stereotactic radiotherapy (FSRT) and ICI in patients with recurrent high-grade glioma. Methodology Patients were treated with FSRT and nivolumab which were continued until progression or toxicity. The Response Assessment in Neuro-oncology and Immunotherapy Response Assessment in Neuro-oncology criteria were used to assess treatment response on magnetic resonance imaging. Treatment-related toxicity was noted in all patients. Results A total of eight patients were included. Recurrence was detected after a median of 5.8 months following the first RT, all in the treatment field. FSRT (3 × 8 Gy) was applied with neoadjuvant, concurrent, and adjuvant nivolumab. After a median follow-up of 21.3 months from diagnosis and 12.6 months from recurrence, one patient was alive and seven succumbed to the disease. The median overall survival was 20.9 months after diagnosis and 12.9 months after recurrence. The median progression-free interval was 2.3 months after FSRT. The local control (LC) rate was 62.5% with a median local recurrence-free survival of nine months. Progression in other regions of the brain was observed in four patients with a median progression-free survival of 2.1 months. Acute toxicity was not observed. ICI-related grade 3 late pneumonitis was observed in two patients, and grade 1 late thyroid toxicity in two patients. One patient with pneumonitis also developed osteoporosis and radiation necrosis. Conclusions A high LC rate was achieved with concurrent FSRT and ICI with a severe late toxicity rate of 25%. This combination can be an option in recurrent high-grade gliomas.

Parotid gland stem cells: Mini yet mighty.

BACKGROUND: Our aim was to evaluate the correlation between the radiation doses to parotid gland (PG) stem cells and xerostomia. METHODS: Patients diagnosed with head and neck cancer (HNC) were retrospectively evaluated, and xerostomia inventory (XI) was applied to these patients. PG stem cells were delineated on the treatment planning CT, and the mean doses to the PG stem cells calculated. RESULTS: The total test score and mean doses to bilateral PGs were significantly correlated (r = .34, P = .001), and the mean doses to bilateral PG stem cell niches were significantly correlated with the total test score (r = .32, P = .002). CONCLUSIONS: In this study, we found that the mean dose to PG stem cells can predict dry mouth as much as the mean dose to the PG.