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Simple Summary: Patients who have undergone solid-organ transplant are at higher risk of developing aggressive cutaneous squamous cell carcinoma (CSCC), which is associated with increased morbidity and mortality. There has been a major shift in the management landscape of locally advanced and metastatic CSCC with the introduction of immunotherapy. Despite this, the management of patients with a history of immunosuppression including solid-organ transplant recipients (SOTRs) remains challenging due to safety and efficacy concerns. This review addresses the unique aspects of biology and clinical care of this patient population and highlights recent advances. The management of advanced cutaneous squamous cell carcinoma (CSCC) has been revolutionized by the introduction of immunotherapy. Yet, successful treatment with immunotherapy relies on an adequate antitumor immune response. Patients who are solid-organ transplant recipients (SOTRs) have a higher incidence of CSCC compared to the general population. This review discusses the current knowledge of epidemiology, pathophysiology, and management of patients with CSCC who are immunocompromised because of their chronic exposure to immunosuppressive medications to prevent allograft rejection. First, we discuss the prognostic impact of immunosuppression in patients with CSCC. Next, we review the risk of CSCC development in immunosuppressed patients due to SOT. In addition, we provide an overview of the biological immune disruption present in transplanted immunosuppressed CSCC patients. We discuss the available evidence on the use of immunotherapy and provide a framework for the management approach with SOTRs with CSCC. Finally, we discuss potential novel approaches that are being investigated for the management of immunosuppressed patients with CSCC. [ABSTRACT FROM AUTHOR]

Purpose: There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities. Materials and Methods: Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed. Results: A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies. Conclusion Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed. [ABSTRACT FROM AUTHOR]

The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PDL1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with nonmetastatic renal cancer who are not candidates for surgical resection or decline nephrectomy. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed to summarize the clinical outcomes of patients with metastatic melanoma who received high‐dose radiation prior to or during systemic therapy at a single academic institution. Methods: We identified patients with metastatic melanoma who underwent high‐dose radiation therapy (HDRT) for extracranial metastases prior to or during systemic therapy from 2010 to 2018. Treatment indications included oligometastases, oligoprogression, and local control. Using the Kaplan‐Meier method, we plotted overall survival (OS), progression‐free survival‐1 (PFS1), and PFS2. Competing risk analysis determined the cumulative incidence of local failure (LF) and the time to start or change systemic therapy (SCST). Univariate and multivariable analyses were used to identify predictive factors. Results: We analyzed 34 patients with 79 lesions, with a median follow‐up of 17.4 months. Sixty‐eight percent of patients received systemic therapy after the first HDRT. The median OS was 22 months, with brain metastases before HDRT being a significant predictor in multivariable analysis. The median PFS1 for first‐line HDRT was 4.1 months, and the median PFS2 was 3.9 months. Rates of LF were 10.3% at 12 months and 11.7% at 24 months. The incidence of SCST following HDRT was 59.8% at 12 months and 76.1% at 24 months, with radiation targeted at the lung associated with a lower incidence of SCST. Conclusion: HDRT for treating metastatic lesions in melanoma demonstrated excellent local control and may play a role in delaying SCST. Additional courses of HDRT may provide cumulative benefits. [ABSTRACT FROM AUTHOR]

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast MRI is a valuable imaging modality that plays a critical role in the detection, diagnosis, and treatment of breast cancer. The superior sensitivity of breast MRI allows for more accurate evaluation of the extent of disease for breast cancer, which is important in an era where de-escalation of treatment is being considered and offered. In this review, we provided a detailed overview of breast MRI and its clinical utility in the management of breast cancer as a foundation for its use in the field of radiation oncology. Specifically, we describe breast MRI technique, anatomy, common breast MR imaging findings, and the role of breast MRI in assessing extent of disease and tumor response to neoadjuvant therapy. There has been increased interest in the use of MRI during radiotherapy treatment planning and delivery for patients with early-stage breast cancer as it may allow for more personalized radiotherapy. Contrast-enhanced breast MRI has an established role in aiding in the detection, evaluation, and management of breast cancer. This article discusses MRI sequences, the clinical utility of MRI, and how MRI has been evaluated for use in breast radiotherapy treatment planning. We highlight the contribution of MRI in the decision-making regarding selecting appropriate candidates for breast conservation therapy and review the emerging role of MRI-guided breast radiotherapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Ultra-central (UC) lung tumors are defined as those abutting the proximal bronchial tree. Stereotactic body radiation therapy (SBRT) for UC tumors is difficult because of concerns about severe toxicities. Therefore, we report the safety and efficacy of moderate-intensity SBRT for UC tumors at our institution. Materials and Methods: From January 2017 to May 2021, we treated 20 patients with UC tumors with SBRT at a dose of 45–60 Gy in 10 fractions. The primary endpoints were local control (LC) and overall survival (OS). Results: The median follow-up time was 15.8 months (range: 2.7–53.8 months). Ten of the 20 patients (50.0%) showed a complete response, five (25.0%) had a partial response, two (10.0%) had stable disease, and three (15.0%) showed progressive disease (PD). The response and disease control rates were 75.0% and 85.0%, respectively. Patients with PD showed local progression at median 8.3 months (range: 6.8–19.1 months) after SBRT. One-year and 2-year OS rates were 79.4% and 62.4%, respectively. One-year and 2-year LC rates are 87.1% and 76.2%, respectively. Eight patients died due to a non-radiation therapy related cause. One patient experienced grade 5 massive hemoptysis 6 months after SBRT, resulting in death. One patient experienced grade 2 esophageal pain and two experienced grade 2 radiation pneumonitis. Otherwise, no grade 3 or higher toxicities were reported. Conclusions: Moderate-intensity SBRT offers effective control of UC tumors and is a well-tolerated treatment for such tumors. [ABSTRACT FROM AUTHOR]

Objective response rate (ORR) and disease control rate (DCR) were 60% and 100%, respectively. The median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI) 5.6– 14.1 months], and the median overall survival (OS) was 18.5 months (95% CI 14.2– 22.8 months). We further confirmed that higher baseline lymphocyte-C-reactive protein ratio (LCR) (≥ 2361.11) was positively related to both longer PFS (12.0 vs 4.3 months, P = 0.002) and OS (21.9 vs 11.4 months, P = 0.022). Moreover, patients with diabetes and higher alpha-fetoprotein (AFP) (≥ 400 ng/mL) were also found to be associated with worse OS. The most common hepatotoxicity was elevated gamma-glutamyl transferase (GGT) (84.0%). Conclusion: In conclusion, for patients with inoperable HCC, SBRT resulted in satisfactory local control, survival benefits, and acceptable liver toxicity. Pre-radiotherapy LCR might be an independent and readily available predictor for survival, which facilitates us to find the most appropriate treatment options. [ABSTRACT FROM AUTHOR]

Radiotherapy for ultracentral lung tumors represents a treatment challenge, considering the high rates of high-grade treatment-related toxicities with stereotactic body radiation therapy (SBRT) or hypofractionated schedules. Accelerated hypofractionated magnetic resonance-guided adaptive radiation therapy (MRgART) emerged as a potential game-changer for tumors in these challenging locations, in close proximity to central organs at risk, such as the trachea, proximal bronchial tree, and esophagus. In this series, 13 consecutive patients, predominantly male (n = 9), with a median age of 71 (range (R): 46–85), underwent 195 MRgART fractions (all 60 Gy in 15 fractions) to metastatic (n = 12) or primary ultra-central lung tumors (n = 1). The median gross tumor volumes (GTVs) and planning target volumes (PTVs) were 20.72 cc (R: 0.54–121.65 cc) and 61.53 cc (R: 3.87–211.81 cc), respectively. The median beam-on time per fraction was 14 min. Adapted treatment plans were generated for all fractions, and indications included GTV/PTV undercoverage, OARs exceeding tolerance doses, or both indications in 46%, 18%, and 36% of fractions, respectively. Eight patients received concurrent systemic therapies, including immunotherapy (four), chemotherapy (two), and targeted therapy (two). The crude in-field loco-regional control rate was 92.3%. No CTCAE grade 3+ toxicities were observed. Our results offer promising insights, suggesting that MRgART has the potential to mitigate toxicities, enhance treatment precision, and improve overall patient care in the context of ultracentral lung tumors. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic body radiotherapy (SBRT) has been found to be an effective and safe modality with excellent oncological outcome in medically inoperable primary renal cell carcinoma (RCC) and oligometastases. There is scarcity of data on the synchronous delivery of SBRT to primary and oligometastatic RCC in patients unfit for nephrectomy. Here, we report the findings of a retrospective study of prospectively collected data on "total ablative SBRT." Methods: Oligometastatic RCC patients with intact primary tumors were enrolled between May 2021 and June 2022. SBRT was synchronously delivered to the primary tumor and metastases. Demographics, treatment, oncologic outcomes, and toxicity were assessed. Kaplan--Meier estimates were generated for oncologic outcomes. The primary endpoint of this study was feasibility and tolerability. Results: Eleven patients were enrolled between May 2021 and June 2022. One patient died at 2 months after SBRT due to viral pneumonitis (possibly COVID pneumonia). Nine patients (82%) had metastatic disease, while 2 (18%) were stage II. The average maximal diameter of primary was 68.7 mm (range, 23--128 mm). The SBRT doses for primary and metastasis ranged from 40 to 55 Gray (Gy) in 5 to 7 fractions and 22 to 40Gy in 2 to 5 fractions, respectively. The median follow-up period was 10.5 months (Range: 4--15 months). Response assessment was available for ten patients. Local control, marginal control, regional control and initial oligometastatic control (OMC) rates were 100%. OMC declined to 87.5% as one patient had recurrence in irradiated subcarinal lymphnode at 7 months. The metastatic control rate was 80% and loco-regional progression-free survival was 8 months (range, 4--15 months). Toxicities were minimal and manageable. At the last follow--up, 7 of 11 patients were alive with an overall survival of 63.5%. Six patients received systemic therapy after SBRT. Conclusions: Synchronous delivery of SBRT to primary and oligometastatic sites in patients unfit for nephrectomy was feasible and tolerable with good locoregional control. The total ablative SBRT strategy needs to be explored in similar cohorts. [ABSTRACT FROM AUTHOR]

Over the past two decades, it has been established that cancer patients with oligometastases, i.e., only a few detectable metastases confined to one or a few organs, may benefit from an aggressive local treatment approach such as the application of high-precision stereotactic body radiotherapy (SBRT). Specifically, some studies have indicated that achieving long-term local tumor control of oligometastases is associated with prolonged overall survival. This motivates investigations into which factors may modify the dose-response relationship of SBRT by making metastases more or less radioresistant. One such factor relates to the uptake of the positron emission tomography tracer 2-deoxy-2-[18F]fluoro-D-glucose (FDG) which reflects the extent of tumor cell glycolysis or the Warburg effect, respectively. Here we review the biological mechanisms how the Warburg effect drives tumor cell radioresistance and metastasis and draw connections to clinical studies reporting associations between high FDG uptake and worse clinical outcomes after SBRT for oligometastases. We further review the evidence for distinct metabolic phenotypes of metastases preferentially seeding to specific organs and their possible translation into distinct radioresistance. Finally, evidence that obesity and hyperglycemia also affect outcomes after SBRT will be presented. While delivered dose is the main determinant of a high local tumor control probability, there might be clinical scenarios when metabolic targeting could make the difference between achieving local control or not, for example when doses have to be compromised in order to spare neighboring high-risk organs, or when tumors are expected to be highly therapy-resistant due to heavy pretreatment such as chemotherapy and/or radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Patients with oligo-metastatic disease (OMD) can be safely treated with Stereotactic Radiation Therapy (SRT). Further disease progression is common in these patients. In most cases, patients relapse again with oligo-metastases, however some can experience a poly-progression after a local ablative treatment (LAT). The purpose of this study was to retrospectively identify factors associated with poly-progression in patients receiving SRT for OMD. Methods: Data from a monocentric database were retrospectively analyzed. Patients treated with SRT for OMD and who developed progression after LAT were selected. Patients were categorized as oligo- or poly-progressive according to the number of new/progressing metastases (≤ or > 5). Herein, we analyzed data about patients' characteristics, oligo-metastatic presentation and radiation treatment characteristics to evaluate their relationship with progression type. Results: From 2013 to 2021, data on 700 patients progressing after LAT were analyzed. Among them, 227 patients (32.4%) experienced a poly-progression; the median time to poly-progression was 7.72 months (range 1–79.6). Five variables associated with poly-progression were found to be statistically significant in the univariate analysis: performance status (p < 0.001), site of the primary tumor (p = 0.016), ablative dose (p = 0.002), treated site (p = 0.002), single or double organ (p = 0.03). Of those, all but the number of involved organs retained their significant predictive value on the multivariate analysis. Conclusion: Our study identified four independent factors associated with poly-progression in patients with OMD receiving SRT. Our data may support comprehensive characterization of OMD, better understanding of factors associated with progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with localized renal cell carcinoma often have medical comorbidities limiting their surgical candidacy, thus necessitating less invasive treatment options. Stereotactic ablative radiotherapy has emerged as a safe and effective management option with a growing body of evidence supporting its use. This article discusses recent advances in the use of stereotactic ablation radiotherapy for localized renal cell carcinoma, while guiding providers on practical points for patient selection and clinical application. Localized renal cell carcinoma is primarily managed surgically, but this disease commonly presents in highly comorbid patients who are poor operative candidates. Less invasive techniques, such as cryoablation and radiofrequency ablation, are effective, but require percutaneous or laparoscopic access, while generally being limited to cT1a tumors without proximity to the renal pelvis or ureter. Active surveillance is another management option for small renal masses, but many patients desire treatment or are poor candidates for active surveillance. For poor surgical candidates, a growing body of evidence supports stereotactic ablative radiotherapy (SABR) as a safe and effective non-invasive treatment modality. For example, a recent multi-institution individual patient data meta-analysis of 190 patients managed with SABR estimated a 5.5% five-year cumulative incidence of local failure with one patient experiencing grade 4 toxicity, and no other grade ≥3 toxic events. Here, we discuss the recent developments in SABR for the management of localized renal cell carcinoma, highlighting key concepts of appropriate patient selection, treatment design, treatment delivery, and response assessment. [ABSTRACT FROM AUTHOR]

At present, surgery is still the gold standard for the local treatment of renal cancer. Nonetheless, in several clinical scenarios, stereotactic body radiation therapy (SBRT) also known as stereotactic ablative body radiotherapy (SABR) is emerging as a highly effective ablative technique in fragile patients and those with significant comorbidities, as well as in cases where percutaneous therapy (cryoablation or radiofrequency) is not viable. However, considering the intrinsic radioresistance of renal tumors, the optimal treatment schemes have not been established. In oligometastatic patients, it has been reported that the control of the oligometastases can be a potentially curable approach. Being a technique than can be administered exclusively or in combination with systemic therapy, treatment individualization based on patient characteristics is key. Another scenario under investigation is oligoprogression, where SBRT offers the possibility of delaying further lines of systemic therapy by eliminating subclones of resistant tumor with ablative doses, with the additional opportunity of stimulating the immune system (immunomodulatory role). In this review, we have conducted an analysis of recently published studies that test the role of this technique in different clinical scenarios of this disease. We have found promising results that make SBRT a potent therapeutic approach with low toxicity. We also comment on ongoing studies that will generate the necessary evidence needed for the implementation of this technique in our daily clinical practice. [ABSTRACT FROM AUTHOR]

Advances in radiotherapy technologies have enabled more precise target guidance, improved treatment verification, and greater control and versatility in radiation delivery. Amongst the recent novel technologies, Magnetic Resonance Imaging (MRI) guided radiotherapy (MRgRT) may hold the greatest potential to improve the therapeutic gains of image-guided delivery of radiation dose. The ability of the MRI linear accelerator (LINAC) to image tumors and organs with ontable MRI, to manage organ motion and dose delivery in real-time, and to adapt the radiotherapy plan on the day of treatment while the patient is on the table are major advances relative to current conventional radiation treatments. These advanced techniques demand efficient coordination and communication between members of the treatment team. MRgRT could fundamentally transform the radiotherapy delivery process within radiation oncology centers through the reorganization of the patient and treatment team workflow process. However, the MRgRT technology currently is limited by accessibility due to the cost of capital investment and the time and personnel allocation needed for each fractional treatment and the unclear clinical benefit compared to conventional radiotherapy platforms. As the technology evolves and becomes more widely available, we present the case that MRgRT has the potential to become a widely utilized treatment platform and transform the radiation oncology treatment process just as earlier disruptive radiation therapy technologies have done. [ABSTRACT FROM AUTHOR]

Purpose: Spontaneous rib fracture (SRF) is a common late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF. Methods: We retrospectively reviewed 2204 patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose–volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2). Results: Most of the patients with SRF (87.3%) were asymptomatic, and the remaining symptomatic patients complained of mild tenderness or chest wall discomfort; these symptoms all resolved within 6 months without any treatment. Ipsilateral SRF occurred in 14.5% of patients 3 years after RT. The median time to develop ipsilateral SRF was 15 months. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cut-off value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF. Conclusion: Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. In addition, our results suggest that patients who received RT with exceeding rib dose cut-off value and had ipsilateral SRF on bone scan be recommended routine follow-up without additional imaging tests. [ABSTRACT FROM AUTHOR]

Opinion Statement: Radiation therapy is becoming an increasingly important part of non-small cell lung cancer (NSCLC) management. Approximately 60% of all cancer patients require radiation therapy (RT) as part of their treatment. For lung cancer, this number is even higher, reaching approximately 77% of all patients, from radical to palliative modalities of RT. This percentage may even be underestimated, as it may not account for the more recent use of RT in oligometastatic lung cancer patients. Thus, we can estimate that each year there will be approximately 21,890 new lung cancer patients in the USA requiring RT. These numbers are expected to continue to rise, as lung cancer radiation techniques continue to improve. There is growing interest in determining the best treatment options for early-stage NSCLC patients. There is well-established data showing the benefit of RT for inoperable patients, and more recent encouraging data even in operable patients. [ABSTRACT FROM AUTHOR]

Simple Summary: As the superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) for painful non-spine bone metastases remains controversial, we conducted propensity score-matched analysis. Our results showed that the 3-month pain response rate after SBRT was significantly higher than that after cEBRT. Therefore, these findings suggest that large-scale randomized controlled trials are warranted to compare SBRT with cEBRT for painful bone metastases not involving the spine. (1) Background: The superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) in terms of pain palliation for bone metastases remains controversial. (2) Methods: This propensity score-matched study compared the overall pain response (OR) 3 months after radiotherapy among patients with painful (≥2 points on a 0-to-10 scale) non-spine bone metastases. Patients with lesions that were treated with SBRT or cEBRT and whose pain scores were evaluated 3 months after radiotherapy were included in this study. Pain response was evaluated according to the International Consensus Criteria. (3) Results: A total of 234 lesions (SBRT, n = 129; cEBRT, n = 105) were identified in our institutional database. To reduce the confounding effects, 162 patients were selected using a propensity score-matched analysis (n = 81 for each treatment). The OR rate at 3 months after SBRT was significantly higher than that after cEBRT (76.5% vs. 56.8%; p = 0.012). A noteworthy finding of our study is that the same trend was observed even after 6 months (75.9% vs. 50.0%; p = 0.011). The 1-year local failure rates after SBRT and cEBRT were 10.2% and 33.3% (p < 0.001), respectively. (4) Conclusions: Our findings suggest that SBRT is superior to cEBRT for pain palliation in patients with non-spine bone metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypofractionated image-guided radiotherapy (HIGRT) is a common method in which high doses of radiation are delivered to treat oligometastatic disease. We have previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Both SIB and MA irradiation of oligometastases achieved high rates of tumor metastases control and similar pain control. Further investigation of this technique with prospective trials is warranted. Purpose: We previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Methods: Oligometastatic patients with ≤5 active metastases treated with either SIB or MA radiation at two institutions from 2013 to 2019 were analyzed retrospectively for treatment-related toxicity, pain control, and recurrence patterns. Tumor metastasis control (TMC) was defined as an absence of progression in the high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside the elective PTV but within the adjacent bone or nodal basin. Distant recurrence (DR) was defined as any recurrence that is not within the PTV or surrounding bone or nodal basin. The outcome rates were estimated using the Kaplan–Meier method and compared between the two techniques using the log-rank test. Results: 101 patients were treated via an SIB to 90 sites (58% nodal and 42% osseous) and via MA radiation to 46 sites (22% nodal and 78% osseous). The median follow-up among surviving patients was 24.6 months (range 1.4–71.0). Of the patients treated to MA, the doses ranged from 18 Gy in one fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with an SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No acute grade ≥3 toxicities occurred in either cohort. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis and two vertebral body compression), all related to the high dose PTV and not the elective volume. There was similar crude pain relief between cohorts. The MR-free survival rate at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (p = 0.07). The crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences in DR-free survival (65% (95% CI: 55–74%; p = 0.24)), disease-free survival (60% (95% CI: 40–75%; p = 0.40)), or overall survival (88% (95% CI: 73–95%; p = 0.26)), between the MA and SIB cohorts. Conclusion: Both SIB and MA irradiation of oligometastases achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for oligometastases treated with an SIB. Further investigation of this technique with prospective trials is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: In this clinical trial, 63 patients with a total of 89 prostate cancer metastases identified on PSMA-PET were included, none of them undergoing androgen deprivation therapy. We showed that local ablative radiotherapy controls >90% of the metastases, but progression at other sites is common after two years. Local ablative radiotherapy may be an option to at least temporarily avoid systemic therapy in selected patients. Progression of prostate-specific antigen (PSA) values after curative treatment of prostate cancer patients is common. Prostate-specific membrane antigen (PSMA-) PET imaging can identify patients with metachronous oligometastatic disease even at low PSA levels. Metastases-directed local ablative radiotherapy (aRT) has been shown to be a safe treatment option. In this prospective clinical trial, we evaluated local control and the pattern of tumor progression. Between 2014 and 2018, 63 patients received aRT of 89 metastases (MET) (68 lymph node (LN-)MET and 21 bony (OSS-)MET) with one of two radiation treatment schedules: 50 Gy in 2 Gy fractions in 34 MET or 30 Gy in 10 Gy fractions in 55 MET. The mean gross tumor volume and planning target volume were 2.2 and 14.9 mL, respectively. The median follow-up time was 40.7 months. Local progression occurred in seven MET, resulting in a local control rate of 93.5% after three years. Neither treatment schedule, target volume, nor type of lesion was associated with local progression. Regional progression in the proximity to the LN-MET was observed in 19 of 47 patients with at least one LN-MET (actuarial 59.3% free of regional progression after 3 years). In 33 patients (52%), a distant progression was reported. The median time to first tumor-related clinical event was 16.6 months, and 22.2% of patients had no tumor-related clinical event after three years. A total of 14 patients (22%) had another aRT. In conclusion, local ablative radiotherapy in patients with PSMA-PET staged oligometastatic prostate cancer may achieve local control, but regional or distant progression is common. Further studies are warranted, e.g., to define the optimal target volume coverage in LN-MET and OSS-MET. [ABSTRACT FROM AUTHOR]

Simple Summary: Nodal and distant metastases of cutaneous squamous cell carcinomas are very rare and lead to dismal prognoses. Immunotherapy is approved only for cutaneous squamous cell carcinoma patients not amenable to surgery or curative radiation therapy. Radiation therapy has a clear role as an adjuvant treatment for locally advanced disease. Radiation therapy may also have an important role in inoperable and metastatic disease. Oligometastatic disease is a condition that needs to be defined for this carcinoma. This review aims to offer to the readers a comprehensive overview of studies about the role of radiotherapy in the management of advanced or metastatic cutaneous squamous cell carcinomas, also assuming possible further developments in the light of the recent discoveries about tumor biology. The present paper has the merit of re-focusing great attention on the efficacy and cost-effectiveness of radiotherapy in these not yet properly explored scenarios. Radiation therapy (RT) is an effective therapeutic option for small localized cutaneous squamous cell carcinoma (cSCC) among patients who are not eligible for or refuse surgery. RT also has a defined role as an adjuvant treatment in cases of adverse features that predispose to tumor recurrence after local excision. Since the development of cSCC is often a late consequence of chronic sun exposure, its occurrence is more common among elderly patients whose comorbidities may contraindicate surgical procedures. These could be impeded not only by frail medical conditions but also by technical issues. Indeed, an aggressive locoregional behavior of cSCC may culminate in unresectability due to widespread invasion of neighboring tissues. Moreover, cSCC could develop distant metastases. Both locally advanced and metastatic cSCCs carry a poor prognosis. In these scenarios, recent discoveries of tumor molecular targets are promoting the use of promising systemic therapies, especially immunotherapy, over RT. However, the results from using immunotherapy and, even more so, of chemotherapy are still not optimal. By contrast, advances in radiation delivery equipment can safely treat even large and complex-shaped cSCC targets in challenging body sites. In addition, RT could also have a role in metastatic cSCC settings by enhancing the effectiveness of concomitant immunotherapy. The aim of this review is to summarize and comment on the body of literature about the use of radiotherapy for operable and inoperable locally advanced cSCCs and for metastatic ones in an attempt to define its current and future role. [ABSTRACT FROM AUTHOR]

Approximately 60%–70% of patients with malignant tumours require radiotherapy. The clinical application of immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1, has revolutionized cancer treatment and greatly improved the outcome of a variety of cancers by boosting host immunity.However, radiotherapy is a double-edged sword for PD-1/PD-L immunotherapy. Research on how to improve radiotherapy efficacy using PD-1/PD-L1 inhibitor is gaining momentum. Various studies have reported the survival benefits of the combined application of radiotherapy and PD-1/PD-L1 inhibitor. To fully exerts the immune activation effect of radiotherapy, while avoiding the immunosuppressive effect of radiotherapy as much as possible, the dose selection, segmentation mode, treatment timing and the number of treatment sites of radiotherapy play a role. Therefore, we aim to review the effect of radiotherapy combined with anti-PD-1/PD-L1 on the immune system and its optimization. [ABSTRACT FROM AUTHOR]

Background: Treatment indication for bone metastases is influenced by patient prognosis. Single-fraction radiotherapy (SFRT) was proven equally effective as multiple fractionation regimens (MFRT) but continues to be underused. Objective: Primary objectives: (a) to identify prognostic factors for overall survival and (b) to analyze treatment patterns of palliative radiotherapy (proportion of SFRT indication and predictive factors of radiotherapy regimen) for bone metastases. Methods: 582 patients with bone metastases who underwent conventional radiotherapy between January 1st 2014–31 December 2017 were analyzed. The Cox proportional hazard model was used to identify predictors of overall survival. For the treatment pattern analysis, 677 radiotherapy courses were evaluated. The logistic regression model was used to identify potential predictors of radiotherapy regimen. Results: The 3-year overall survival was 15%. Prognostic factors associated with poor overall survival were multiple bone metastases [hazard ratio (HR = 5.4)], poor performance status (HR = 1.5) and brain metastases (HR = 1.37). SFRT prescription increased from 41% in 2017 to 51% in 2017. Predictors of SFRT prescription were a poor performance status [odds ratio (OR = 0.55)], lung (OR = 0.49) and urologic primaries (OR = 0.33) and the half-body lower site of irradiation (OR = 0.59). Spinal metastases were more likely to receive MFRT (OR = 2.09). Conclusions: Based on the prognostic factors we identified, a selection protocol for patients candidates for palliative radiotherapy to bone metastases could be established, in order to further increase SFRT prescription in our institution. [ABSTRACT FROM AUTHOR]

Incurable head and neck cancer has a poor prognosis and impairs a patient's health-related quality of life. Palliative radiotherapy may improve or stabilize health-related quality of life and symptoms, best measured by patient-reported outcomes. There is no systematic analysis if palliative radiotherapy for head and neck cancer improves or stabilizes health-related quality of life or symptoms as validly measured by patient-reported outcomes. Therefore, the primary objective of this systematic review (PROSPERO-ID: CRD42020166434) was to assess the effect of palliative radiotherapy for head and neck cancer on patient-reported outcomes. The secondary objective was to assess the rate and quality of use of patient-reported outcomes in relevant studies claiming a "palliative effect" of radiotherapy. The databases MEDLINE/PubMed, EMBASE, Cochrane CENTRAL, " ClinicalTrials.gov " were searched. Concerning the primary objective, four studies were eligible to assess the effectiveness of palliative radiotherapy as measured by patient-reported outcomes. A narrative synthesis suggests a favorable impact of palliative radiotherapy on health-related quality of life and symptom burden. The risk of bias, however, is considerable and the overall quality of evidence low. Concerning the secondary objective, over 90% of studies claiming a "palliative effect" of palliative radiotherapy did either not use patient-reported outcomes or did so by limited quality. In conclusion, implementation of patient-reported outcomes in studies assessing palliative radiotherapy for head and neck cancer should be fostered. Palliative radiotherapy remains an option for head and neck cancer patients, although more studies focusing on patient-reported outcomes are needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD42020166434 [ABSTRACT FROM AUTHOR]

Evidence regarding postoperative radiation therapy (PORT) for metastases to the long bones is lacking. Characterizing the current practice patterns and identifying factors that influence dose-fractionation schedules are essential for future clinical trials. An internet-based survey of the palliative RT subgroup of the Japanese Radiation Oncology Study Group was performed in 2017 to collect data regarding PORT prescription practices and dose-fractionation schedules. Responders were also asked to recommend dose-fractionation schedules for four hypothetical cases that involved a patient with impending pathological fractures and one of four clinical features (poor prognosis, solitary metastasis, radio-resistant primary tumor or expected long-term survival). Responders were asked to indicate their preferred irradiation fields and the reasons for the dose fractionation schedule they chose. Responses were obtained from 89 radiation oncologists (67 institutions and 151 RT plans) who used 22 dose-fractionation schedules, with the most commonly used and recommended schedule being 30 Gy in 10 fractions. Local control was the most common reason for preferring longer-course RT. High-dose fractionated schedules were preferred for oligometastasis, and low-dose regimens were preferred for patients with a poor prognosis; however, single-fraction RT was not preferred. Most respondents recommended targeting the entire orthopedic prosthesis. These results indicated that PORT using 30 Gy in 10 fractions to the entire orthopedic prosthesis is preferred in current Japanese practice and that single-fraction RT was not preferred. Oligometastasis and poor prognosis influenced the selection of high- or low-dose regimens. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiation therapy (SBRT) is an established therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). Many elderly patients are medically inoperable owing to comorbidities. Therefore, SBRT may be a useful therapy for elderly patients. However, the application of SBRT for patients aged ≥ 80 years has not been completely elucidated. Therefore, this study aimed to assess the clinical utility of SBRT for elderly patients aged ≥ 80 years with pathologically proven early-stage NSCLC.Methods: We retrospectively evaluated the data of patients aged ≥ 80 years with pathologically proven primary NSCLC who underwent SBRT at our institution between January 2009 and March 2020. Treatment outcomes and toxicities were analyzed. We used the Kaplan-Meier method to estimate survival curves and the log-rank test to compare the survival curves. We performed univariate and multivariate Cox regression analyses. p-values < 0.05 were regarded significant.Results: Sixty-four patients (65 lesions) were included, and the median follow-up period was 38.7 (range 3.5-95.7) months. The median age was 82.9 (range 80.0-94.8) years. Sixteen patients were medically operable, and 48 patients were medically inoperable. The prescribed dose of SBRT was either 48 Gy in four fractions or 60 Gy in 10 fractions. The median survival time was 60.0 months (95% confidence interval, 43.5-71.1). The 1-, 3-, and 5-year local control, cancer-specific survival, progression-free survival, and overall survival rates were 98.4%, 98.4%, 81.0%, and 88.9%; 90.1%, 93.7%, 58.9%, and 68.3%; and 87.4%, 83.5%, 38.2%, and 47.5%, respectively. Multivariate analysis revealed that inoperability and solid nodules were the predictors of poor overall survival after SBRT in elderly patients. Two patients (3.1%) had grade 3 radiation pneumonitis, and one patient (1.6%) had grade 5 radiation pneumonitis.Conclusions: SBRT was feasible in patients aged ≥ 80 years with NSCLC. It achieved good local control with minimal toxicity. SBRT may be beneficial in elderly patients with early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Background: Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone.Methods: This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis.Discussion: The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts.Trials Registration: ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study. [ABSTRACT FROM AUTHOR]

Metastatic lesions of the heart are rare but have the potential to cause significant morbidity. We describe the case of a patient with renal cell carcinoma who presented with shortness of breath and palpitations and was found to have a metastatic myocardial lesion causing arrythmia. He received stereotactic body radiation therapy (SBRT) to alleviate symptoms and provide local control. SBRT planning was executed using a four-dimensional computed tomography (4DCT) scan to account for respiratory and cardiac motion. Images from a planning magnetic resonance imaging (MRI) scan and a gated diagnostic MRI scan of the heart were fused with the 4DCT to assist with delineating the tumour. A dose of 30 Gy in five fractions was delivered without incident. The patient's cardiac MRI at two months post-treatment showed stability of his cardiac lesion. He subsequently died of distant disease progression, without any recurrence of his cardiac symptoms. SBRT may be considered for patients who present with a symptomatic metastatic cardiac lesion. [ABSTRACT FROM AUTHOR]

Background/Aim: This multi-institutional study aimed to investigate the efficacy and feasibility of proton beam therapy (PBT) for renal cell carcinoma (RCC) in Japan. Patients and Methods: The survival, local control, and toxicities in 22 RCC patients treated between 2001 and 2016 at 6 Japanese PBT institutes were analyzed. Results: The 22 patients comprised 20 men and had a median age of 67 (range=42-88) years. The total irradiation dose was 60-79.6 Gy (relative biological effectiveness). Over a median follow-up of 37 months, the 3-year overall and disease-specific survival rates were 95% and 100%, respectively, and no recurrence occurred. No patient experienced grade 3 or higher adverse events. The serum blood urea nitrogen (p=0.25) and creatinine levels (p=0.95) were not significantly affected, although the mean estimated glomerular filtration rate was reduced by 7.1±11.2 ml/min/1.73 m². Conclusion: Despite the small number of patients, high-dose PBT can control RCC while maintaining their renal function with high probability, and could be and alternative curative therapy especially for inoperable patients. [ABSTRACT FROM AUTHOR]

Background: This study compares the outcomes of stereotactic body radiation therapy (SBRT) for sacral and thoracolumbar spine metastases. Methods: This analysis considered each sacral spine SBRT treatment at a single institution and a cohort of consecutive thoracolumbar treatments. Results: 28 patients with 35 sacral treatments and 41 patients with 49 thoracolumbar treatments were included. Local control was 63% and 90%, respectively. The sacral cohort contained more lesions with =2 vertebrae and epidural and paraspinal involvement. Sacral patients had larger treatment volumes, increased rates of subsequent SBRT, decreased propensity for pain improvement, and decreased local control (p=0.02 on Kaplan-Meier analysis). Multivariate analysis demonstrated that PTV > 50 cc and epidural involvement were correlated with decreased local control. No cases had grade =3 toxicity. Conclusion: SBRT for sacral spine metastases is a distinct disease process than metastases to the thoracolumbar spine, resulting in lower rates of local control and pain improvement. [ABSTRACT FROM AUTHOR]

Sources of residual setup error after image guidance include image localization accuracy, errors associated with image registration, and inability of some treatment couches to correct submillimeter translational errors and/or pitch and roll errors. The purpose of this experimental study was to measure setup error after image‐guided correction of the canine intracranial region, using a four degrees‐of‐freedom couch capable of 1 mm translational moves. Six cadaver dogs were positioned 45 times as for clinical treatment using a vacuum deformable body cushion, a customizable head cushion, a thermoplastic mask and an indexed maxillary plate with a dental mould. The location of five fiducial markers in the skull bones was compared between the reference position and after megavoltage (MV), kilovoltage (kV) and cone‐beam computed tomography (CBCT)‐guided correction using orthogonal kV images. The mean three‐dimensional distance vectors (3DDV) after MV, kV and CBCT‐guided correction were 1.7, 1.5 and 2.2 mm, respectively. All values were significantly different (P <.01). The 95th percentiles of the 3DDV after online MV, kV and CBCT‐guided correction were 2.8, 2.6 and 3.6 mm, respectively. Residual setup error in the clinical scenario examined was on the order of millimetres and should be considered when choosing PTV margins for image‐guided radiation therapy of the canine intracranial region. [ABSTRACT FROM AUTHOR]

Background: The number of hemodialysis (HD) patients is increasing worldwide, and they are at a higher risk of cancer than the general population. Because HD patients are more likely to have inflammation, radiotherapy (RT)-induced adverse effects (AEs) are theoretically expected to be worse for HD patients. Since only a few reports have been published on this subject, we aimed to evaluate the tolerability of RT in HD patients. Methods: We retrospectively analyzed AEs related to RT for HD patients. Our study included patients from three institutions treated between January 2007 and July 2017. The patient eligibility criteria were (i) receipt of maintenance HD 2–3 times per week for end-stage renal disease prior to the start of RT and (ii) pathologically confirmed malignancies. The endpoints were acute and late non-hematologic AEs. Results: The study included 56 patients. The most common histology was head and neck cancer (23%), followed by lung cancer (14%) and prostate cancer (11%). The median radiation dose was 60 (range, 12–93.8) Gy at an equivalent dose in 2-Gy fractions (EQD2). The RT completion rate was 96%. Patients had a median follow-up period after RT of 9.1 (range 0.5–98.1) months. Grade 3 or worse acute and late AEs were noted in 6 (11%) and 3 (7%) patients, respectively. In the acute phase, 2 patients had grade 5 AEs, both of which were infections. Conclusion: Our results suggest that RT for HD patients is clinically tolerable. However, some patients can experience severe infections related to treatment. [ABSTRACT FROM AUTHOR]

Background: For stereotactic body radiotherapy (SBRT) to central (C) and ultracentral (UC) lung tumors, our provincial practice has been to prioritize organs at risk (OARs) constraints by compromising target volume coverage if needed. The objectives are to report the treatment's efficacy and safety.Methods: We conducted a retrospective analysis of all provincial patients who underwent SBRT at 60Gy in 8 fractions to C and UC lung tumors, from 2013 to 2017.Results: Ninety-eight lesions were treated, 57 (58.2%) C and 41 (41.8%) UC. The median follow-up was 22.9 months (range 2.5-64.8 months). The 1- and 3-year local control (LC) was 97.8 and 84.5% respectively, with no differences between C and UC groups (p = 0.662). Fifty-three (54.1%) cases had optimal dose coverage (V60Gy ITV&PTV > 95%), 29 (29.6%) had compromised PTV coverage (V60Gy ITV > 95%/PTV < 95%), and 16 (16.3%) had both compromised ITV and PTV coverage (V60Gy ITV&PTV < 95%). No significant difference in LC was detected at 2 years between the 3 groups (95.6, 91.8 and 90.9%, p = 0.717). There were 3 episodes of grade 3 toxicity in the C group (2 dyspnea, 1 pneumonitis) and 2 in the UC group (1 dyspnea, 1 hemoptysis). There were no gr4/5 toxicities. On multivariable Cox regression analysis, ITV size was found to be a predictor for LC (p = 0.001).Conclusions: SBRT at 60Gy in 8 fractions achieves high rates of LC with low risks of significant toxicities, even if target volume coverage is reduced to meet OARs constraints. [ABSTRACT FROM AUTHOR]

Magnetic resonance-guided radiation therapy (MRgRT) is a promising approach to improving clinical outcomes for patients treated with radiation therapy. The roles of image guidance, adaptive planning and magnetic resonance imaging in radiation therapy have been increasing over the last two decades. Technical advances have led to the feasible combination of magnetic resonance imaging and radiation therapy technologies, leading to improved soft-tissue visualisation, assessment of inter- and intrafraction motion, motion management, online adaptive radiation therapy and the incorporation of functional information into treatment. MRgRT can potentially transform radiation oncology by improving tumour control and quality of life after radiation therapy and increasing convenience of treatment by shortening treatment courses for patients. Multiple groups have developed clinical implementations of MRgRT predominantly in the abdomen and pelvis, with patients having been treated since 2014. While studies of MRgRT have primarily been dosimetric so far, an increasing number of trials are underway examining the potential clinical benefits of MRgRT, with coordinated efforts to rigorously evaluate the benefits of the promising technology. This review discusses the current implementations, studies, potential benefits and challenges of MRgRT. [ABSTRACT FROM AUTHOR]

Bone metastases are a frequent and important source of morbidity in cancer patients. Stereotactic body radiation therapy (SBRT) is an established treatment option for local control and pain relief of bone metastases, and it is increasingly used as upfront treatment, postoperative consolidation or salvage treatment after prior RT. However, heterogeneity of dose schedules described in literature represents a severe limitation in the definition of the role of SBRT as a standard of care. No consensus is available on the use of single versus multiple fraction SBRT for bone metastases. Advantages of single-fraction SBRT include shorter overall duration of treatment, absence of inter-fraction uncertainty, improved compliance, theoretical increased efficacy, and lower costs. However, caution has been advised due to reports of severe late toxicities, in particular, vertebral collapse fracture (VCF). The aim of this paper is to review dose fractionation and indications for the management of bone metastases using SBRT. [ABSTRACT FROM AUTHOR]

The recent advancements in radiotherapy technologies have made delivery of the highly conformal dose to the target volume possible. With the increasing popularity of delivering high dose per fraction in modern radiotherapy schemes such as in stereotactic body radiotherapy and stereotactic body ablative therapy, high degree of treatment precision is essential. In order to achieve this, we have to overcome the potential difficulties caused by patient instability due to immobilization problems; patient anxiety and random motion due to prolonged treatment time; tumor deformation and baseline shift during a treatment course. This is even challenging for patients receiving radiotherapy in the chest and abdominal regions because it is affected by the patient's respiration which inevitably leads to tumor motion. Therefore, monitoring of intrafractional motion has become increasingly important in modern radiotherapy. Major intrafractional motion management strategies including integration of respiratory motion in treatment planning; breath-hold technique; forced shallow breathing with abdominal compression; respiratory gating and dynamic real-time tumor tracking have been developed. Successful intrafractional motion management is able to reduce the planning target margin and ensures planned dose delivery to the target and organs at risk. Meanwhile, the emergency of MRI-linear accelerator has facilitated radiation-free real-time monitoring of soft tissue during treatment and could be the future modality in motion management. This review article summarizes the various approaches that deal with intrafractional target, organs or patient motion with discussion of their advantages and limitations. In addition, the potential future advancements including MRI-based tumor tracking are also discussed. [ABSTRACT FROM AUTHOR]

To report treatment outcomes of stereotactic ablative radiation therapy (SABR) for non-spinal bone metastases in a single institution, and to compare assessments of Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 and the University of Texas MD Anderson Cancer Center (MDA) criteria. From July 2011 to January 2017, 33 patients with 38 non-spinal bone metastatic lesions were treated using SABR. Treatment intent was categorized as follows: single metastasis or oligo-metastases; oligo-progression; and dominant areas of progression. Tumor responses were evaluated according to the RECIST and MDA criteria. Local control (LC) was defined as lesions that were not classified as progressive disease on both criteria. The median follow-up period was 10.4 months (range, 2.5–47.4). Both 1- and 2 year LC rates were 94.2 %. The median overall survival (OS) was 20.2 months, and the median progression-free survival (PFS) was 6.9 months. Treatment intent was a significant factor for OS in multivariate analysis. The 1 year OS rates for single metastasis or oligo-metastasis, for oligo-progression, and for dominant areas of progression were 84.2%, 66.7%, and 0.0%, respectively (p < 0.001). Overall response rate was 86.8 % according to MDA criteria, and 75.7 % according to RECIST criteria. When using MDA criteria, there appeared to be significant associations both between response and PFS (median 7.6 months for responders vs 2.5 months for non-responders; p = 0.036) and between response and OS. In contrast, when using RECIST criteria, the associations were significant neither between response and PFS (median 5.8 months for responders vs 9.3 months for non-responders; p = 0.522) nor between response and OS (25.7 months for responders vs 18.5 months for non-responders; p = 0.811). SABR for non-spinal bone metastases demonstrated high LC rates with acceptable toxicity. The MDA criteria demonstrated advantages in predicting survival outcomes. SABR for non-spinal bone metastases is a promising treatment option to achieve good local control. The MDA criteria, which is a newly proposed response evaluation criteria for bone metastases, has advantages in predicting survival outcomes compared to other established criteria. [ABSTRACT FROM AUTHOR]

Purpose: To perform a multi-institutional analysis following treatment of limited osseous and/or nodal metastases in patients using a novel hypofractionated image-guided radiotherapy with simultaneous-integrated boost (HIGRT-SIB) technique. Methods: Consecutive patients treated with HIGRT-SIB for ≤5 active metastases at Duke University Medical Center or Durham Veterans' Affairs Medical Center between 2013 and 2018 were analyzed to determine toxicities and recurrence patterns following treatment. Most patients received 50 Gy to the PTVboost and 30 Gy to the PTVelect simultaneously in 10 fractions. High-dose treatment volume recurrence (HDTVR) and low-dose treatment volume recurrence (LDTVR) were defined as recurrences within PTVboost and PTVelect, respectively. Marginal recurrence (MR) was defined as recurrence outside PTVelect, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as recurrences not meeting HDTVR, LDTVR, or MR criteria. Freedom from pain recurrence (FFPR) was calculated in patients with painful osseous metastases prior to HIGRT-SIB. Outcome rates were estimated at 12 months using the Kaplan-Meier method. Results: Forty-two patients met inclusion criteria with 59 sites treated with HIGRT-SIB (53% nodal and 47% osseous). Median time from diagnosis to first metastasis was 31 months and the median age at HIGRT-SIB was 69 years. The most common primary tumors were prostate (36%), gastrointestinal (24%), and lung (24%). Median follow-up was 11 months. One acute grade ≥3 toxicity (febrile neutropenia) occurred after docetaxel administration immediately following HIGRT-SIB. Four patients developed late grade ≥3 toxicities: two ipsilateral vocal cord paralyzes and two vertebral compression fractures. The overall pain response rate was 94% and the estimated FFPR at 12 months was 72%. The estimated 12 month rate of HDTVR, LDTVR, MR, and DR was 3.6, 6.2, 7.6, and 55.8%, respectively. DR preceded MR, HDTVR, or LDTVR in each instance. The estimated 12 month probability of in-field and marginal control was 90.0%. Conclusion: Targeting areas at high-risk for occult disease with a lower radiation dose, while simultaneously boosting gross disease with HIGRT in patients with limited osseous and/or nodal metastases, has a high rate of treated metastasis control, a low rate of MR, acceptable toxicity, and high rate of pain palliation. Further investigation with prospective trials is warranted. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy. Methods and study design: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics. Results: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5–10 Gy (8/13) using schedules of 3–5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT. Conclusions: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC. [ABSTRACT FROM AUTHOR]

In head and neck imaging, the difference in neck flexion between diagnostic imaging and radiation therapy imaging can make the RIR process challenging, and translation of structures between the imaging modalities is difficult. Image registration algorithms generally operate in 3D, and 2D imaging, angle of slice plane, slice gaps and large slice thickness used in diagnostic imaging can impair RIR and DIR. The major sources of error in RIR and DIR stem from the positional and internal anatomical variations between diagnostic and radiation therapy imaging. [Extracted from the article]

Background: Palliative radiotherapy to patients with head and neck cancer is often necessary, but there is a substantial variation in the treatment regimens reported in the literature, and consensus on the most appropriate schedules does not exist. In order to minimize acute toxicity while at the same time trying to achieve prolonged tumor control, a long hypofractionated regimen has been used routinely in Denmark. In the current retrospective study, we investigated the outcome in patients intended for palliative radiotherapy with this regimen. Materials and methods: Patients with newly diagnosed head and neck cancer treated with palliative radiotherapy of 52-56 Gy in 13-14 fractions twice weekly from 2009 to 2014 were included. Patients were excluded if they had previously received radiotherapy. Data on disease location, stage, patient performance status (PS), treatment response, acute skin and mucosal toxicity, and late fibrosis were collected prospectively and supplemented with information from medical records. Results: 77 patients were included in the study. Fifty-eight patients (75%) completed the intended treatment. Loco-regional tumor response (complete or partial) was evaluated 2 months posttreatment and observed in 45% of the entire population corresponding to 71% of patients alive. PS had a significant influence on survival (p = 0.007) and on not completing the intended treatment. Grade III or IV acute mucositis were observed in 25%, and grade III or IV acute dermatitis observed in 15%. Conclusion: Palliative hypofractionated radiotherapy with 52-56 Gy in 13-14 fractions shows good tumor response and tolerability in a vulnerable patient population. However, it may not be suited for patients in poor PS. [ABSTRACT FROM AUTHOR]

Introduction: The optimal delivery of stereotactic radiotherapy for kidney tumours requires an effective motion management strategy. This study assessed the effectiveness of a pneumatic abdominal compression belt in reducing kidney motion during free breathing.Methods: Thirteen patients, with four-dimensional computed tomography (4DCT) of the abdomen in free breathing with and without a pneumatic abdominal compression belt, were retrospectively reviewed. Points of Interest (POI) were placed on each kidney to determine the greatest magnitude of displacement in all directions.Results: Without compression, all patients had >5.0 mm motion in the craniocaudal (CC) direction in at least one kidney. Median CC excursion of the left superior pole was reduced with compression from 8.0 mm (range 2.0 mm-18.0 mm) to 4.0 mm (range 2.0 mm-10.0 mm, P = 0.047) and right superior pole from 10.0 mm (range 4.0 mm-16.0 mm) to 6.0 mm (range 2.0 mm-10.0 mm, P=value 0.051). A benefit was less evident for the left and right inferior poles with median CC excursion of 6.0 mm versus 4.0 mm and 5.0 mm versus 4.0 mm without and with compression, respectively. Median displacement in the anteroposterior direction (≤3.2 mm) and lateral directions (≤1.3 mm) was similar for left and right kidneys and not significantly altered by compression. Overall, seven patients had kidney motion reduced by >5.0 mm with two reduced by 10.0 mm.Conclusion: A pneumatic abdominal compression belt reduced kidney motion by >5.0 mm in seven of thirteen patients. The relative benefit is patient and location specific and should be assessed on an individual basis. [ABSTRACT FROM AUTHOR]

Radiotherapy is considered the treatment of choice for painful bone metastases. However, novel modalities of radiotherapy have emerged in the concept of oligometastasic disease. In addition, the increase of overall survival of patients with bone metastatic disease in the last decades due to systemic treatments has issued the silent topic of re-irradiation. The aim of this manuscript was to present a current thorough search of relevant literature. Originally, 6,087 articles revealed from PubMed database related to radiotherapy and bone metastases. The first objective was to identify prospective randomised phase III studies dealing with bone metastases and which treated primary with radiotherapy. Abstracts and non-English citations were excluded. Twenty-three phase III clinical trials, 17 prospective studies and eight meta-analysis/systemic reviews matching with these criteria, were identified. Eleven randomised studies were comparing single dose fraction to multi-fraction schedules of radiotherapy. The overall response rates and complete response rates were not significant between the two arms. Re-irradiations rates were significantly higher for the single dose fraction arms. Stereotactic radiotherapy showed excellent tumour control rates more than 80%. All trials showed the equivalence of either single or multi-fractionated radiotherapy for metastatic bone lesions. Stereotactic irradiation is feasible and safe for oligometastatic disease. However, it seems that the single fraction of 8 Gy is superior to 4 Gy, in terms of efficacy. [ABSTRACT FROM AUTHOR]

Purpose Hypofractionated partial breast irradiation ( HPBI) involves treatment to the breast tumor using high doses per fraction. Recent advances in MRI-Linac solutions have potential in being applied to HPBI due to gains in the soft tissue contrast of MRI; however, there are potentially deleterious effects of the magnetic field on the dose distribution. The purpose of this work is to determine the effects of the magnetic field on the dose distribution for HPBI tumors using a tangential beam arrangement ( TAN), 5-beam intensity-modulated radiation therapy ( IMRT), and volumetric modulated arc therapy ( VMAT). Methods Five patients who have received HPBI were selected with two patients having bilateral disease resulting in a total of two tumors in this study. Six planning configurations were created using a treatment planning system capable of modeling magnetic field dose effects: TAN, IMRT and VMAT beam geometries, each of these optimized with and without a transverse magnetic field of 1.5 T. Results The heart and lung doses were not statistically significant when comparing plan configurations. The magnetic field had a demonstrated effect on skin dose: for VMAT plans, the skin (defined to a depth of 3 mm) D1cc was elevated by +11% and the V30 by +146%; for IMRT plans, the skin D1cc was increased by +18% and the V30 by +149%. Increasing the number of beam angles (e.g., going from IMRT to VMAT) with the magnetic field on reduced the skin dose. Conclusion The impact of a magnetic field on HPBI dose distributions was analyzed. The heart and lung doses had clinically negligible effects caused by the magnetic field. The magnetic field increases the skin dose; however, this can be mitigated by increasing the number of beam angles. [ABSTRACT FROM AUTHOR]

Aims To report the outcomes of a cohort of patients with renal cell carcinoma (RCC) treated using stereotactic ablative body radiotherapy (SABR). Materials and methods Patients treated with SABR for primary RCC from 1 January 2012 to 1 April 2015 were retrospectively reviewed. Patients were non-surgical candidates treated with doses ranging from 30 to 40 Gy in five fractions. The tumour sizes and serum creatinine were compared between the pre-treatment assessment and subsequent follow-up assessments. The worst acute and late grade ≥2 toxicity rates were recorded. Results In total, 16 patients were included in this study. The median follow-up was 19 months (range 7–30). Eleven patients had stable disease, four had partial responses and none had progressive disease, indicating a local control rate of 100%. One patient had grade 2 acute nausea and two patients had grade 4 renal toxicities (two patients with pre-existing stage 4–5 chronic kidney disease required dialysis following SABR). Four of four patients with pre-SABR symptoms (pain and/or haematuria) had symptomatic relief after SABR. Conclusion SABR for RCC is safe, the toxicities are minimal, and the local control is excellent at early follow-up. This technique should be further evaluated in prospective clinical trials. [ABSTRACT FROM AUTHOR]