Brachytherapy: An overview for clinicians.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

Five-year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial.

Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone-naïve at baseline. The rate of 5-year TE-FS was 21.7% (95% confidence interval [CI]: 15.7%-28.7%) overall and 25.4% (95% CI: 18.1%-33.9%) in the hormone-naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4-5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05-2.01, p = .026), a higher baseline prostate-specific antigen (PSA) (HR = 1.06, 95% CI: 1.03-1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40-3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow-up, 18.9% (95% CI: 13.2%-25.7%) of participants were free from treatment escalation (median follow-up of 67.9 months) and two participants had an undetectable PSA level. No treatment-related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT-based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT-based MDT to standard-of-care ADT-based approaches are required to evaluate the impact of delaying ADT on survival.

Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Disease control outcomes of stereotactic body radiation therapy or moderate hypo-fractionation for prostate cancer: Real-world experience at two Canadian centers.

BACKGROUND: Advantages of using stereotactic body radiation therapy to treat prostate cancer include short treatment times, decreased costs, and limited toxicity. Randomized trial outcomes comparing 5-fraction stereotactic body radiation therapy to conventionally fractionated radiotherapy or hypo-fractionated radiation therapy are pending. OBJECTIVE: We report the 10-year experience with 5-fraction stereotactic body radiation therapy and hypo-fractionated radiation therapy at two Canadian centers. MATERIAL AND METHODS: Patients with low- or intermediate-risk prostate cancer treated with stereotactic body radiation therapy alone (35-40 Gy in 5 fractions) or hypo-fractionated radiation therapy alone (60-62 Gy in 20 fractions) in the period of July 2010 and June 2020. The biochemical relapse-free survival, PSA nadir, interval time to PSA nadir, time to biochemical recurrence (2 ng/ml above PSA nadir) and overall survival were reviewed. Outcomes between treatment groups were compared after propensity-matching by patient baseline characteristics. Kaplan-Meier curves were used to assess biochemical relapse-free survival and overall survival. RESULTS: We identified 205 and 513 patients with low or intermediate-risk prostate cancer who were treated with stereotactic body radiation therapy or hypo-fractionation, respectively. Intermediate-risk category composed 81% and 95% of the stereotactic body radiation therapy and hypo-fractionated radiation therapy cohorts, respectively. After a median follow up of 58.6 months for the stereotactic body radiation therapy cohort and 45.0 months for the hypo-fractionated cohort, biochemical relapse-free survival and overall survival were not significantly different between treatment groups. The 5-year biochemical relapse-free survival rates were 92.1% and 93.6% and overall survival rates were 96.4% and 95.0% for the stereotactic body radiation therapy and hypo-fractionated cohorts, respectively, after propensity-matching. Stereotactic body radiation therapy resulted in a significantly lower PSA nadir (0.18 ng/ml) compared to hypo-fractionated radiation therapy (0.48 ng/ml) in patients with low-risk prostate cancer. Mean time to biochemical recurrence was not different between treatment groups. CONCLUSIONS: Stereotactic body radiation therapy is an effective treatment option for low and intermediate-risk prostate cancer with encouraging biochemical relapse-free survival and overall survival rates comparable with hypo-fractionated radiation therapy.

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

A nationwide study of breast reconstruction after mastectomy in patients with breast cancer receiving postmastectomy radiotherapy: comparison of complications according to radiotherapy fractionation and reconstruction procedures.

BACKGROUND: We examined the patterns of breast reconstruction postmastectomy in breast cancer patients undergoing postmastectomy radiotherapy (PMRT) and compared complications based on radiotherapy fractionation and reconstruction procedures. METHODS: Using National Health Insurance Service (NHIS) data (2015-2020), we analysed 4669 breast cancer patients with PMRT and reconstruction. Using propensity matching, cohorts for hypofractionated fractionation (HF) and conventional fractionation (CF) were created, adjusting for relevant factors and identifying grade ≥3 complications. RESULT: Of 4,669 patients, 30.6% underwent HF and 69.4% CF. The use of HF has increased from 19.4% in 2015 to 41.0% in 2020. Immediate autologous (32.9%) and delayed two-stage implant reconstruction (33.9%) were common. Complication rates for immediate (N = 1286) and delayed two-stage (N = 784) reconstruction were similar between HF and CF groups (5.1% vs. 5.4%, P = 0.803, and 10.5% vs. 10.7%, P = 0.856, respectively) with median follow-ups of 2.5 and 2.6 years. HF showed no increased risk of complications across reconstruction methods. CONCLUSION: A nationwide cohort study revealed no significant difference in complication rates between the HF and CF groups, indicating HF for reconstructed breasts is comparable to CF. However, consultation regarding the fractionation for reconstructed breast cancer patients may still be necessary.

Effect of simultaneous integrated boost concepts on photoneutron and distant out-of-field doses in VMAT for prostate cancer.

BACKGROUND: A simultaneous integrated boost (SIB) may result in increased out-of-field (DOOF) and photoneutron (HPN) doses in volumetric modulated arc therapy (VMAT) for prostate cancer (PCA). This work therefore aimed to compare DOOF and HPN in flattened (FLAT) and flattening filter-free (FFF) 6­MV and 10-MV VMAT treatment plans with and without SIB. METHODS: Eight groups of 30 VMAT plans for PCA with 6 MV or 10 MV, with or without FF and with uniform (2 Gy) or SIB target dose (2.5/3.0 Gy) prescriptions (CONV, SIB), were generated. All 240 plans were delivered on a slab-phantom and compared with respect to measured DOOF and HPN in 61.8 cm distance from the isocenter. The 6­ and 10-MV flattened VMAT plans with conventional fractionation (6- and 10-MV FLAT CONV) served as standard reference groups. Doses were analyzed as a function of delivered monitor units (MU) and weighted equivalent square field size Aeq. Pearson's correlation coefficients between the presented quantities were determined. RESULTS: The SIB plans resulted in decreased HPN over an entire prostate RT treatment course (10-MV SIB vs. CONV -38.2%). Omission of the flattening filter yielded less HPN (10-MV CONV -17.2%; 10-MV SIB -22.5%). The SIB decreased DOOF likewise by 39% for all given scenarios, while the FFF mode reduced DOOF on average by 60%. A strong Pearson correlation was found between MU and HPN (r > 0.9) as well as DOOF (0.7 < r < 0.9). CONCLUSION: For a complete treatment, SIB reduces both photoneutron and OOF doses to almost the same extent as FFF deliveries. It is recommended to apply moderately hypofractionated 6­MV SIB FFF-VMAT when considering photoneutron or OOF doses.

Biological treatment evaluation in thermoradiotherapy: application in cervical cancer patients.

BACKGROUND: Hyperthermia treatment quality is usually evaluated by thermal (dose) parameters, though hyperthermic radiosensitization effects are also influenced by the time interval between the two modalities. This work applies biological modelling for clinical treatment evaluation of cervical cancer patients treated with radiotherapy plus hyperthermia by calculating the equivalent radiation dose (EQDRT, i.e., the dose needed for the same effect with radiation alone). Subsequent analyses evaluate the impact of logistics. METHODS: Biological treatment evaluation was performed for 58 patients treated with 23-28 fractions of 1.8-2 Gy plus 4-5 weekly hyperthermia sessions. Measured temperatures (T50) and recorded time intervals between the radiotherapy and hyperthermia sessions were used to calculate the EQDRT using an extended linear quadratic (LQ) model with hyperthermic LQ parameters based on extensive experimental data. Next, the impact of a 30-min time interval (optimized logistics) as well as a 4­h time interval (suboptimal logistics) was evaluated. RESULTS: Median average measured T50 and recorded time intervals were 41.2 °C (range 39.7-42.5 °C) and 79 min (range 34-125 min), respectively, resulting in a median total dose enhancement (D50) of 5.5 Gy (interquartile range [IQR] 4.0-6.6 Gy). For 30-min time intervals, the enhancement would increase by ~30% to 7.1 Gy (IQR 5.5-8.1 Gy; p < 0.001). In case of 4­h time intervals, an ~ 40% decrease in dose enhancement could be expected: 3.2 Gy (IQR 2.3-3.8 Gy; p < 0.001). Normal tissue enhancement was negligible (< 0.3 Gy), even for short time intervals. CONCLUSION: Biological treatment evaluation is a useful addition to standard thermal (dose) evaluation of hyperthermia treatments. Optimizing logistics to shorten time intervals seems worthwhile to improve treatment efficacy.

Dose and fractionation regimen for brachytherapy boost in cervical cancer in the US.

PURPOSE: Curative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. METHODS: We retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018-2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. RESULTS: Among the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). CONCLUSIONS: In the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes.

Hypofractionated stereotactic re-irradiation for progressive glioblastoma: twelve years' experience of a single center.

PURPOSE: We aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma. METHODS: The records of 77 previously irradiated glioblastoma patients who progressed and received second course hypofractionated SRT (1-5 fractions) between 2009 and 2022 in our department were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for all statistical analyses. RESULTS: The median time to progression from the end of initial radiotherapy was 14 months (range, 6-68 months). The most common SRT schedule was 30 Gy (range, 18-50 Gy) in 5 fractions (range, 1-5 fractions). The median follow-up after SRT was 9 months (range, 3-80 months). One-year overall (OS) and progression-free survival (PFS) rates after SRT were 46% and 35%, respectively. Re-irradiation dose and the presence of pseudoprogression were both significant independent positive prognostic factors for both OS (p = 0.009 and p = 0.04, respectively) and PFS (p = 0.008 and p = 0.04, respectively). For PFS, progression-free interval > 14 months was also a prognostic factor (p = 0.04). The treatment was well tolerated without significant acute toxicity. During follow-up, radiation necrosis was observed in 17 patients (22%), and 14 (82%) of them were asymptomatic. CONCLUSION: Hypofractionated SRT is an effective treatment approach for patients with progressive glioblastoma. Younger patients who progressed later than 14 months, received higher SRT doses, and experienced pseudoprogression following SRT had improved survival rates.

Fractionated stereotactic radiotherapy in craniopharyngiomas: A systematic review and single arm meta-analysis.

INTRODUCTION: Numerous studies have demonstrated Fractionated Stereotactic Radiotherapy's (FSRT) effectiveness in tumor control post-resection for craniopharyngiomas. Nevertheless, past literature has presented conflicting findings particularly regarding endocrine and visual function outcomes. This study aims to elucidate FSRT's efficacy and safety for this population. METHODS: Adhering to PRISMA, a systematic review and meta-analyses was conducted. Included studies had to report the effects of FSRT for treating craniopharyngiomas in a sample greater than four patients, addressing at least one of the outcomes of interest: improvement in visual acuity or field, new-onset hypopituitarism, effectiveness, and tumor progression. Relative risk with 95% confidence intervals were used to assess the outcomes. RESULTS: After retrieving a total of 1292 studies, 10 articles met the predefined criteria and thus were finally selected, amounting to a total of 256 patients. The improvement in visual acuity was estimated at 45% (95% CI: 6-83%), while the improvement in the visual field was 22% (95% CI: 0-51%). Regarding endocrine function, the new-onset hypopituitarism rate was found to be 5% (95% CI: 0-11%). Relative to FSRT effectiveness, the pooled estimate of the complete tumor response rate was 17% (95% CI: 4-30%), and the tumor progression rate was 7% (95% CI: 1-13%). Also, a 3-year progression-free survival rate of 98% (95% CI: 95-100%) was obtained. CONCLUSION: Despite limitations and risks, FSRT shows promise as a viable therapeutic option for craniopharyngiomas, offering notable benefits for visual functions and tumor control. Further research is required to better understand the associated risks, benefits, and clinical utility.

Stereotactic Body Radiotherapy: is less fractionation more effective in adrenal and renal malignant lesions?

PURPOSE: Stereotactic body radiotherapy (SBRT) has become an excellent non-invasive alternative for many patients with primary renal cell carcinoma (RCC) and adrenal malignancies (AM). The aims of this study were to analyse how tumor-, patient- and treatment-related factors may influence the outcomes and side effects of SBRT and to assess its benefits as an alternative to surgery. METHODS: This retrospective, multicenter study included 25 lesions in 23 patients treated with SBRT using different devices (LINAC, CyberKnife® and Tomotherapy®). A multivariate linear regression was used for the statistical study. RESULTS: Local control time was higher than six months in more than 87% of patients and treatment response was complete for 73.68%. There was an overall 2-year survival of 40% and none of the deaths were secondary to renal or adrenal local progression. Patients treated with lower total radiation dose (mean [m] = 55 Gy) but less fractions with more dose per fraction (> 8.5 Gy) showed better outcome. Patients with previous chemotherapy and surgery treatments also showed higher complete response and disease-free survival (> 6 months). CONCLUSIONS: This study highlights the importance of ultra-hypofractionated regimens with higher doses per session. Thus, the referral of patients with RCC and AM to Radiotherapy and Oncology departments should be encouraged supporting the role of SBRT as a minimally invasive and outpatient treatment.

Stereotactic body radiotherapy plus rucosopasem in locally advanced or borderline resectable pancreatic cancer: GRECO-2 phase II study design.

Ablative doses of stereotactic body radiotherapy (SBRT) may improve pancreatic cancer outcomes but may carry greater potential for gastrointestinal toxicity. Rucosopasem, an investigational selective dismutase mimetic that converts superoxide to hydrogen peroxide, can potentially increase tumor control of SBRT without compromising safety. GRECO-2 is a phase II, multicenter, randomized, double-blind, placebo-controlled trial of rucosopasem in combination with SBRT in locally advanced or borderline resectable pancreatic cancer. Patients will be randomized to rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT fraction (5 × 10 Gy). The primary end point is overall survival. Secondary end points include progression-free survival, locoregional control, time to metastasis, surgical resection rate, best overall response, in-field local response and acute and long-term toxicity.

The use of high doses of radiation delivered directly to tumors (stereotactic body radiation therapy [SBRT]) may improve survival compared with lower doses of radiation in patients with pancreatic cancer, but it may increase side effects. Rucosopasem, an investigational new drug being developed, can potentially improve the ability of SBRT to treat tumors without decreasing safety. In a previous study, median overall survival was improved when patients were treated with SBRT plus avasopasem, a drug that works the same way as rucosopasem. GRECO-2 is a clinical trial of rucosopasem used in combination with SBRT for treatment of localized pancreatic cancer. Patients will be randomly selected to receive either rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT treatment. The main result being studied is overall survival. Additional results include amount of time before tumors start to grow, how often patients get tumors surgically removed, best overall response and long-term safety. Clinical Trial Registration: NCT04698915 (ClinicalTrials.gov).

Early-stage hypopharyngeal squamous cell carcinoma treated with radical radiotherapy at a uniform dose of 70 Gy in 35 fractions: a single-center study.

INTRODUCTION: Hypopharyngeal squamous cell carcinoma (HSCC) is often undetected until advanced stages, which contributes to poor survival rates. Recent advances in diagnostic techniques have enhanced the feasibility of early detection, and this study evaluated the efficacy and safety of radical radiotherapy that specifically targets early stage HSCC. METHODS: This retrospective cohort study consecutively analyzed patients with clinical stage I or II HSCC between December 2008 and February 2023. These patients underwent radical radiotherapy with a uniform dose of 70 Gy delivered in 35 fractions to the primary site, followed by elective nodal irradiation. We assessed clinical outcomes, including overall survival (OS), disease-free survival (DFS), and 5-year locoregional control (LRC). Multivariate analyses were performed to identify the independent prognostic factors for OS. RESULTS: The 5-year OS rate of the entire cohort was 80.7% (95% confidence interval [CI] = 66.5-89.4%), with no significant difference between patients with clinical stage I and II HSCC. Stratified by subsite, the 5-year OS for pyriform sinus, posterior pharyngeal wall, and postcricoid region were 81.6, 68.2, and 100%, respectively. The ECOG-Performance status (PS) was identified as an independent risk factor for OS (hazard ratio [HR] = 8.457; 95% CI 1.325-53.970; p = 0.024). DFS at 5 years was 66.4%, with local recurrence being the most frequent, and LRC rate at 5 years was 79.3%. Acute and late-phase toxicities were predominantly mild to moderate, with no grade 3 or higher toxicities reported. CONCLUSION: This study supports radical radiotherapy as an effective approach for optimal tumor control in patients with early stage HSCC. Despite the limitations of this study, including its retrospective design and single-center confinement, our results revealed the effectiveness and feasibility of radical radiotherapy in the management of early stage HSCC.

Dosimetric characterization for GRID collimator-based spatially fractionated radiation therapy: Dosimetric parameter acquisition and machine interchangeability investigation.

PURPOSE: The purpose of this study is to characterize the dosimetric properties of a commercial brass GRID collimator for high energy photon beams including 15 and 10 MV. Then, the difference in dosimetric parameters of GRID beams among different energies and linacs was evaluated. METHOD: A water tank scanning system was used to acquire the dosimetric parameters, including the percentage depth dose (PDD), beam profiles, peak to valley dose ratios (PVDRs), and output factors (OFs). The profiles at various depths were measured at 100 cm source to surface distance (SSD), and field sizes of 10 × 10 cm2 and 20 × 20 cm2 on three linacs. The PVDRs and OFs were measured and compared with the treatment planning system (TPS) calculations. RESULTS: Compared with the open beam data, there were noticeable changes in PDDs of GRID fields across all the energies. The GRID fields demonstrated a maximal of 3 mm shift in dmax (Truebeam STX, 15MV, 10 × 10 cm2). The PVDR decreased as beam energy increases. The difference in PVDRs between Trilogy and Truebeam STx using 6MV and 15MV was 1.5% ± 4.0% and 2.1% ± 4.3%, respectively. However, two Truebeam linacs demonstrated less than 2% difference in PVDRs. The OF of the GRID field was dependent on the energy and field size. The measured PDDs, PVDRs, and OFs agreed with the TPS calculations within 3% difference. The TPS calculations agreed with the measurements when using 1 mm calculation resolution. CONCLUSION: The dosimetric characteristics of high-energy GRID fields, especially PVDR, significantly differ from those of low-energy GRID fields. Two Truebeam machines are interchangeable for GRID therapy, while a pronounced difference was observed between Truebeam and Trilogy. A series of empirical equations and reference look-up tables for GRID therapy can be generated to facilitate clinical applications.

Evaluating intra-fractional tumor motion in lung stereotactic radiotherapy with deep inspiration breath-hold.

PURPOSE: To evaluate the intra-fractional tumor motion in lung stereotactic body radiotherapy (SBRT) with deep inspiration breath-hold (DIBH), and to investigate the adequacy of the current planning target volume (PTV) margins. METHODS: Twenty-eight lung SBRT patients with DIBH were selected in this study. Among the lesions, twenty-three were at right or left lower lobe, two at right middle lobe, and three at right or left upper lobe. Post-treatment gated cone-beam computed tomography (CBCT) was acquired to quantify the intra-fractional tumor shift at each treatment. These obtained shifts were then used to calculate the required PTV margin, which was compared with the current applied margin of 5 mm margin in anterior-posterior (AP) and right-left (RL) directions and 8 mm in superior-inferior (SI) direction. The beam delivery time was prolonged with DIBH. The actual beam delivery time with DIBH (Tbeam_DIBH) was compared with the beam delivery time without DIBH (Tbeam_wo_DIBH) for the corresponding SBRT plan. RESULTS: A total of 113 treatments were analyzed. At six treatments (5.3%), the shifts exceeded the tolerance defined by the current PTV margin. The average shifts were 0.0 ± 1.9 mm, 0.1±1.5 mm, and -0.5 ± 3.7 mm in AP, RL, and SI directions, respectively. The required PTV margins were determined to be 4.5, 3.9, and 7.4 mm in AP, RL, and SI directions, respectively. The average Tbeam_wo_DIBH and Tbeam_DIBH were 2.4 ± 0.4 min and 3.6 ± 1.5 min, respectively. The average treatment slot for lung SBRT with DIBH was 25.3 ± 7.9 min. CONCLUSION: Intra-fractional tumor motion is the predominant source of treatment uncertainties in CBCT-guided lung SBRT with DIBH. The required PTV margin should be determined based on data specific to each institute, considering different techniques and populations. Our data indicate that our current applied PTV margin is adequate, and it is possible to reduce further in the RL direction. The time increase of Tbeam_DIBH, relative to the treatment slot, is not clinically significant.

Post-operative KEloids iRradiation (POKER): does the surgery/high-dose interventional radiotherapy association make a winning hand?

PURPOSE: To report the results involving post-operative interventional radiotherapy (POIRT) in a homogenous cohort of patients affected by keloid and treated at a single institution with the same fractionation schedule. PATIENTS AND METHODS: Inclusion criteria were: surgery with a histopathological diagnosis of keloid, subsequent high-dose rate interventional radiotherapy (HDR-IRT)-12 Gy in 4 fractions (3 Gy/fr) twice a day-and follow-up period ≥ 24 months. RESULTS: One-hundred and two patients and a total of 135 keloids were eligible for the analyses. Median follow-up was 64 [IQR: 25-103] months. Thirty-six (26.7%) recurrences were observed, 12-months and 36-months cumulative incidence of recurrence were 20.7% (95% CI 12.2-28.5) and 23.8% (95% CI 14.9-31.7) respectively. History of spontaneous keloids (HR = 7.00, 95% CI 2.79-17.6, p < 0.001), spontaneous cheloid as keloid cause (HR = 6.97, 95% CI 2.05-23.7, p = 0.002) and sternal (HR = 10.6, 95% CI 3.08-36.8, p < 0.001), ear (HR = 6.03, 95% CI 1.71-21.3, p = 0.005) or limb (HR = 18.8, 95% CI 5.14-68.7, p < 0.001) keloid sites were significantly associated to a higher risk of recurrence. CONCLUSIONS: The findings support the use of surgery and POIRT as an effective strategy for controlling keloid relapses. Further studies should focus on determining the optimal Biologically Effective Dose and on establishing a scoring system for patient selection.

Targeting the Tumor Vascular Supply to Enhance Radiation Therapy Administered in Single or Clinically Relevant Fractionated Schedules.

This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm3 murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5-20 Gy) or conventional (30 × 2 Gy) fractionation schedules. Tumor growth and control were the endpoints used. Untreated tumors had a tumor growth time (TGT5; time to grow to 5 times the original treatment volume) of around 6 days. This increased with increasing drug doses (5-100 mg/kg). However, with single-drug treatments, the maximum TGT5 was only 10 days, yet this increased to 19 days when injecting the drug on a weekly basis or as three treatments in one week. CA1P enhanced radiation response regardless of the schedule or interval between the VDA and radiation. There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice.

Predictive Factors and the Role of Conventionally Fractionated Radiation Therapy for Bone Metastasis from Renal Cell Carcinoma in the Era of Targeted Therapy.

Background and Objectives: Despite rapid advances in targeted therapies for renal cell carcinoma (RCC), bone metastases remain a major problem that significantly increases morbidity and reduces patients' quality of life. Conventional fractionated radiotherapy (CF-RT) is known to be an important local treatment option for bone metastases; however, bone metastases from RCC have traditionally been considered resistant to CF-RT. We aimed to investigate the effectiveness of CF-RT for symptomatic bone metastasis from RCC and identify the predictive factors associated with treatment outcomes in the targeted therapy era. Materials and Methods: Between January 2011 and December 2023, a total of 73 lesions in 50 patients treated with a palliative course of CF-RT for symptomatic bone metastasis from RCC were evaluated, and 62 lesions in 41 patients were included in this study. Forty-five lesions (72.6%) were treated using targeted therapy during CF-RT. The most common radiation dose fractionations were 30 gray (Gy) in 10 fractions (50%) and 39 Gy in 13 fractions (16.1%). Results: Pain relief was experienced in 51 of 62 lesions (82.3%), and the 12-month local control (LC) rate was 61.2%. Notably, 72.6% of the treatment course in this study was combined with targeted therapy. The 12-month LC rate was 74.8% in patients who received targeted therapy and only 10.9% in patients without targeted therapy (p < 0.001). Favorable Eastern Cooperative Oncology Group performance status (p = 0.026) and pain response (p < 0.001) were independent predictors of improved LC. Radiation dose escalation improved the LC in radiosensitive patients. A consistent treatment response was confirmed in patients with multiple treatment courses. Conclusions: CF-RT enhances pain relief and LC when combined with targeted therapy. Patients who responded well to initial treatment generally showed consistent responses to subsequent CF-RT for additional painful bone lesions. CF-RT could therefore be an excellent complementary local treatment modality for targeted therapy.

The Dose-Dependent Effect of Fractionated γ-Radiation on Anxiety-Like Behavior in Neonatal Mice.

High doses of ionizing radiation are the risk factor of cognitive dysfunction and anxiety disorders developing in humans and experimental animals. However, the data on the effect of low doses, especially in case of chronic or fractionated exposure, is limited and contradictory. Here we studied the effect of fractionated γ-radiation at cumulative doses of 0.1, 1, and 5 Gy on the parameters of the anxiety-like behavior in neonatal C57BL/6 mice. The anxiety was evaluated using the marble burying test and elevated plus maze. Fractionated irradiation resulted in dose-dependent changes in mouse behavior: the low dose caused an increase in anxiety, wherein the dose raise led to the decrease in anxiety-like behavior indicators compared to non-irradiated animals.