Outcomes for patients with perineal and perianal rhabdomyosarcoma: A report from the Children's Oncology Group Soft Tissue Sarcoma Committee.

PURPOSE: To describe clinical features, risk factors, and outcomes of patients with perineal and perianal rhabdomyosarcoma. METHODS: The records of 51 patients (38 perineal and 13 perianal) enrolled on Children's Oncology Group clinical trials between 1997 and 2012 were reviewed. RESULTS: At presentation, 53% were female, 65% were older than 10 years of age, 76% were alveolar histology, 76% were more than 5 cm, 84% were invasive, 65% were regional node positive by imaging, 49% were metastatic, only 16% were grossly resected upfront, and 25% of patients had a delayed excision. At a median follow-up of 6.13 years, estimated 5-year event-free survival (EFS) was 38% [22.17%-53.38%], and overall survival (OS) was 42% [26.66%-58.21%]. The rates of local, regional, and distant failure were 15.6%, 13.7%, 43.1%, respectively; all failures ultimately died. By univariate analysis, only age more than 10 years negatively impacted 5-year EFS (p = .023) and OS (p = .09), and IRS Group also impacted OS (p = .043). In Cox proportional hazards model, neither of these variables were significant after adjusting for other factors. CONCLUSION: Patients with perineal and perianal rhabdomyosarcoma have a poor overall prognosis, probably related to poor patient and disease characteristics at presentation.

Retrospective Analysis of Efficacy and Toxicity of Stereotactic Body Radiotherapy and Surgical Resection of Adrenal Metastases from Solid Tumors.

BACKGROUND: This single-center retrospective study aimed to evaluate the efficacy and toxicity profiles of stereotactic body radiotherapy (SBRT) and surgical resection in patients with adrenal metastases originating from solid tumors. METHODS/MATERIALS: Patients with advanced tumor conditions or comorbidities typically received SBRT, whereas those considered physically fit underwent standard surgical treatment. Endpoints included local control (LC), progression free survival (PFS), overall survival (OS), and complication rates (CR). RESULTS: 41 patients with 48 adrenal metastases were included, with 27 (65.9%) patients receiving SBRT and 14 (34.1%) patients undergoing adrenalectomy. One- and two-year LC values were 100% for both periods after adrenalectomy, and 70.0% and 52.5% after SBRT (p = 0.001). PFS showed values of 40.2% and 32.1% at one and two years after adrenalectomy and of 10.6% for both periods after SBRT (p = 0.223). OS was 83.3% both one and two years after surgery and 67.0% and 40.2% after SBRT (p = 0.031). There was no statistically significant difference between the two groups regarding acute complications (p = 0.123). CONCLUSION: Despite potential confounders, adrenalectomy exhibited statistically significant superior LC and OS compared to SBRT in managing adrenal metastases, while both treatment methods displayed acceptable toxicity profiles. However, patient selection bias must be taken into account when directly comparing the two therapy modalities. Nevertheless, the study provides new and important results for the scientific and medical communities regarding oncological outcomes after SBRT or surgical resection of adrenal metastases.

Consideration of Optimal Evaluation Metrics for Internal Gross Tumor Dose Relevant to Tumor Response in Multi-fraction Stereotactic Radiosurgery of Brain Metastasis.

Introduction In stereotactic radiosurgery (SRS) for brain metastasis (BM), the target dose inhomogeneity remains highly variable among modalities, irradiation techniques, and facilities, which can affect tumor response during and after multi-fraction SRS. Volumetric-modulated arcs (VMAs) can provide a concentrically-layered steep dose increase inside a gross tumor volume (GTV) boundary compared to dynamic conformal arcs. This study was conducted to review the optimal evaluation method for the internal GTV doses relevant to maximal response and local control, specifically to examine the significance of the doses 2 mm and 4 mm inside the GTV boundary in VMA-based SRS. Materials and methods This was a planning study for the clinical scenario of a single BM and targeted 25 GTVs of >0.50 cc, including eight spherical models with diameters of 10-45 mm and 17 clinical BMs (GTV: 0.72-44.33 cc). SRS plans were generated for each GTV using VMA with a 5-mm leaf-width multileaf collimator and the optimization that prioritized the steepness of the dose gradient outside the GTV boundary without any internal dose constraints. The dose prescription and evaluation were based on the GTV D V-0.01 cc, a minimum dose of GTV minus 0.01 cc. Two planning systems were compared for the GTV - 2 mm and GTV - 4 mm structures that were generated by equally reducing 2 mm and 4 mm from the GTV surface. The D eIIVs, a minimum dose of the irradiated isodose volume equivalent to the GTV - 2 mm and GTV - 4 mm, were compared to other common metrics. Results The GTV - 2 mm and GTV - 4 mm volumes differed significantly between the systems. In the spherical GTVs, the irradiated isodose surfaces of GTV D 80% and D 50% corresponded to 0.4-1.6 mm (<2 mm) and 1.0-4.6 mm inside the GTV boundary, respectively. In the 25 GTVs, the GTV - 2 mm coverage with the D eIIV varied from 83.7% to 98.2% (95-98% in 68% of the cases), while the GTV coverage with the GTV - 2 mm D eIIV was 20.2-75.9%. In the 23 GTVs of ≥1.26 cc, the GTV coverage with the GTV - 4 mm D eIIV varied from 1.9% to 55.6% (<50% in 87% of the cases). No significant difference was observed between the GTV D 50% and the GTV - 2 mm D eIIV, while the GTV - 4 mm D eIIV was significantly higher than the GTV D 50%. No significant correlations were observed between the GTV D 50% and the D eIIVs of the GTV - 2 mm and GTV - 4 mm. Conclusions The doses 2 mm and 4 mm inside a GTV have low correlations with the GTV D 50% and may be more relevant to maximal response and local control for SRS of BM. The D eIIV instead of the minimum dose of a fixed % coverage (e.g. D 98%) is suitable for reporting the doses 2 mm and 4 mm inside the GTV boundary in terms of avoiding the over- or under-coverage, with consideration to substantial variability in minus margin addition functions among planning systems. In VMA-based SRS with a steep dose gradient, the doses 2-4 mm inside a GTV decrease significantly as the GTV increases, which can attenuate the excessive dose exposure to the surrounding brain in a large BM due to the GTV shrinkage during multi-fraction SRS.

Clinicogenomic predictors of survival and intracranial progression after stereotactic radiosurgery for colorectal cancer brain metastases.

OBJECTIVE: Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS). METHODS: Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk. RESULTS: This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01). CONCLUSIONS: The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.

[Comparative analysis of combined treatment methods for patients with single brain lesions]. / Sravnitel'nyi analiz kombinirovannykh metodov lecheniya patsientov s odinochnym metastaticheskim porazheniem golovnogo mozga.

Primary brain metastases are common in oncology. Preoperative stereotactic radiosurgery followed by surgical resection is a perspective approach. OBJECTIVE: To evaluate own experience of preoperative radiosurgery followed by surgical resection (RS+S) of metastasis regarding local control, leptomeningeal progression, surgical and radiation-induced complications; to compare treatment outcomes with surgical resection and subsequent radiotherapy (S+SRT). MATERIAL AND METHODS. A: Retrospective study included 66 patients with solitary brain metastasis. Two groups of patients were distinguished: group 1 (n=34) - postoperative irradiation, group 2 (n=32) - preoperative irradiation. The median age was 49.5 years (range 36-75). RESULTS: Local 3-, 6- and 12-month control among patients with postoperative irradiation was 88.2%, 79.4% and 42.9%, in the group of preoperative irradiation - 100%, 93.3% and 66.7%, respectively (p=0.021). Leptomeningeal progression developed in 11 patients (8 and 3 ones, respectively). The one-year survival rate was 73.5% and 84.4%, respectively (p=0.33). Long-term surgical and radiation-induced complications occurred in 12 (18.2%) patients. CONCLUSION: Preoperative radiosurgery with subsequent resection provides higher local control and lower incidence of leptomeningeal progression in patients with single brain metastases.

Local relapse patterns after preoperative radiotherapy of limb and trunk wall soft tissue sarcomas: Prognostic role of imaging and pathologic response factors.

Purpose: To retrospectively identify clinical, pathologic, or imaging factors predictive of local relapse (LR) after preoperative radiotherapy (RT) for soft tissue sarcomas (STS). Methods and Materials: This is a retrospective multicenter study of patients who underwent preoperative RT and surgery for limb or trunk wall STS between 2007 and 2018 in French Sarcoma Group centers and were enrolled in the "Conticabase". Patterns of LR were investigated taking into account the multimodal response after preoperative RT. Diagnostic and surgical samples were compared after systematic review by expert pathologists and patients were stratified by tumor grade. Log-rank tests and Cox models were used to identify prognostic factors for radiation response and LR. Results: 257 patients were included; 17 % had low-grade (LG), 72.5 % had high-grade (HG) sarcomas. In HG group, tumors were larger, mostly undifferentiated, and displayed more necrosis and perilesional edema after RT. Median follow-up was 32 months. Five-year cumulative incidence of LR was 20.3 % in the HG group versus 9.7 % in the LG group (p = 0.026). In multivariate analysis, trunk wall location (HR 6.79, p = 0.012) and proportion of viable tumor cellularity ≥ 20 % (HR 3.15, p = 0.018) were associated with LR. After adjusting for tumor location, combination of histotype and cellularity rate significantly correlated with LR. We described three prognostic subgroups for HG sarcomas, listed from the highest to lowest risk: undifferentiated sarcoma (US) with cellularity rates ≥ 20 %; non-US (NUS) with cellularity rates ≥ 20 % or US with cellularity rates < 20 %; and NUS with cellularity rates < 20 %, which shared similar prognostic risks with LG sarcomas. Conclusions: HG and LG tumors have different morphological and biological behaviors in response to RT. Combination of cellularity rate with histotype could be a major prognostic for LR. Patients with undifferentiated HG sarcomas with cellularity rates ≥ 20 % after preoperative RT had the highest risk of LR and disease-specific death.

Cost-Outcome of Radiotherapy for Local Control and Overall Survival Benefits in Breast Cancer.

PURPOSE: Radiotherapy (RT) is an integral component in the treatment of breast cancer. The aims of this study were to estimate the cost per 5-year Local Control (LC) and Overall Survival (OS) benefits of the first course of RT, based on breast cancer stage, and the potential cost savings with adoption of the FAST-Forward protocol. METHODS AND MATERIALS: All RT activities for breast cancer RT July 2017-June 2020 and their associated costs were consolidated together. The average cost of treatment course was calculated (average cost per fraction X average no. of fractions). Cost per outcome was estimated based on published gains in 5-year LC and OS with optimal use of radiotherapy. RESULTS: 481 patients with breast cancer were analysed. The average cost per fraction was $285 AUD (£148 GBP) for all stages. The average costs for 5-year LC and OS gain were $31,483 AUD (£16 392 GBP) and $235,435 AUD (£122 566 GBP) respectively for all stages. The estimated costs for 5-year LC outcomes were $29,675 AUD (£15 450 GBP), $34,675 AUD (£18 053 GBP) and $32,478 AUD (£16 910 GBP) for Stage I-III respectively. The estimated costs for 5-year OS were $455,909 AUD (£237 378 GBP), $532,727 AUD (£ 277 375 GBP) and $60,717 AUD (£31 614 GBP) for Stage I-III respectively. 266 patients had characteristics that made them eligible for the FAST-Forward protocol. A cost saving of $2592-3864 AUD (£1350-2012 GBP) per patient was estimated had these patients been treated with the protocol. CONCLUSIONS: The cost of RT for LC outcome is similar across stages. The greatest value for OS outcome was seen in patients with Stage III breast cancer, due to the greater survival benefit with RT in these patients compared with Stage I-II breast cancer. Significant cost savings can be made by implementing the FAST-Forward protocol.

Clinical benefits of combining oral cytotoxic chemotherapeutic agents with radiotherapy in patients with T2N0 glottic squamous cell carcinoma based on the reports of the Head and Neck Cancer Registry of Japan.

BACKGROUND: T2N0 glottic squamous cell carcinoma (SCC) typically responds well to radiotherapy (RT); however, achieving local control remains challenging. In cases of RT failure, total laryngectomy may be necessary. Improved local control and preservation of the larynx directly enhances patients' quality of life. Our retrospective analysis using the Japan Head and Neck Cancer Registry (JHNCR) aimed to compare the clinical benefits of RT and chemoradiotherapy (CRT) in patients with T2N0 glottic SCC. METHODS: Using data from the JHNCR (2011-2015), we included 1,231 patients with T2N0 glottic SCC. Among them, 346 received curative RT and 425 underwent curative CRT. The CRT group was further divided into the oral CRT (Oral CRT, N=120) and intravenous CRT (DIV CRT, N=305) groups. This study assessed local control rate (LCR), progression-free survival (PFS), and overall survival (OS). A 1:1 propensity score-matching analysis was used to adjust for patient characteristics. RESULTS: After matching, 105 pairs compared RT with Oral CRT, and 224 pairs compared RT with DIV CRT. The variables were well-balanced in the matched populations. In the matched populations, the Oral CRT group had significantly better 5-year LCR and PFS than the RT group (LCR, 89.4 % vs. 80.6 %, P=0.043; and PFS, 85.5 % vs. 72.3 %, P=0.025, respectively), while the DIV RT group had significantly better 5-year PFS than the RT group (80.1 % vs. 68.6 %, P=0.026). CONCLUSIONS: The clinical benefits of better local and disease controls were observed when oral chemotherapy was added to RT in patients with T2N0 glottic SCC. Thus, the significance of adding oral chemotherapeutic agents to RT in the treatment of T2N0 glottic SCC requires further prospective investigation.

Treatment outcomes of surgery followed by short-course every other day radiotherapy in keloid.

BACKGROUND: Postoperative radiotherapy can significantly reduce keloid recurrence. However, consensus on the optimal radiotherapy dose and treatment schedule remains elusive. This study aims to evaluate the effectiveness of surgery followed by a short-course of radiotherapy administered every other day for keloid treatment. MATERIALS/METHODS: We conducted a retrospective analysis of 498 patients with keloids treated at our institution between January 2010 and December 2017. All patients underwent electron beam irradiation at a dose of 16 Gy, delivered in four fractions every other day, starting within 24 h post-surgery. The primary endpoint of the study was the local control rate. RESULTS: A total of 130 (26.5%) keloids recurred after a median follow-up of 68.1months (42.6-129.9 months). The local control rates at 1 year, 3 years and 5 years for all patients were 89.5%, 82.5% and 81%, respectively. The highest recurrence rate was observed in keloids located in the chest region (50.8%), followed by the suprapubic (47.8%), head and neck (38.8%), limbs (33.3%) and ear (14%). Both multivariate and univariate analyses identified the presence of pain and or pruritus as an independently prognostic factor for keloid recurrence (p<0.0001). The local control rates at 1-year, 3-years and 5-years for patients with or without symptom of pain or pruritus were 45% vs. 98.8%, 12.5% vs. 95.9%, and 8.8% vs. 95%, respectively (HR:37.829, 95%CI: 24.385-58.686, p<0.001). In the ear keloid subgroup, the 1-year, 3-year and 5-year local control rates for patients with pruritus were significantly lower than those without pain or pruritus (60.0% vs. 97.9%, 26.7% vs. 94.7%, 26.7% vs. 94.3%, HR:30.209, 95% CI:14.793-61.69, p<0.001). The same results were found in other location(p<0.001). During treatment and follow-up, two patients experienced infections, and one patient developed a cutaneous fibroblastoma. CONCLUSION: This study suggests that a combination of surgery followed by short-course, every-other-day radiotherapy can yield satisfactory local control rates for keloids. Pain and or pruritus symptom was an independently prognostic factors for recurrence of keloid. To further validate these results, a prospective randomized controlled trial is recommended.

The Impact of Local Control on Overall Survival after Y-90 Selective Internal Radiotherapy of Liver Metastases in Oligometastatic Cancer: A Retrospective Analysis.

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Association of increasing gross tumor volume dose with tumor volume reduction and local control in fractionated stereotactic radiosurgery for unresected brain metastases.

BACKGROUND: Fractionated stereotactic radiosurgery (fSRS) is an important treatment strategy for unresected brain metastases. We previously reported that a good volumetric response 6 months after fSRS can be the first step for local control. Few studies have reported the association between gross tumor volume (GTV) dose, volumetric response, and local control in patients treated with the same number of fractions. Therefore, in this study, we aimed to investigate the GTV dose and volumetric response 6 months after fSRS in five daily fractions and identify the predictive GTV dose for local failure (LF) for unresected brain metastasis. METHODS: This retrospective study included 115 patients with 241 unresected brain metastases treated using fSRS in five daily fractions at our hospital between January 2013 and April 2022. The median prescription dose was 35 Gy (range, 30-35 Gy) in five fractions. The median follow-up time after fSRS was 16 months (range, 7-66 months). RESULTS: GTV D80 > 42 Gy and GTV D98 > 39 Gy were prognostic factors for over 65% volume reduction (odds ratio, 3.68, p < 0.01; odds ratio, 4.68, p < 0.01, respectively). GTV D80 > 42 Gy was also a prognostic factor for LF (hazard ratio, 0.37; p = 0.01). CONCLUSIONS: GTV D80 > 42 Gy in five fractions led to better volume reduction and local control. The goal of planning an inhomogeneous dose distribution for fSRS in brain metastases may be to increase the GTV D80 and GTV D98. Further studies on inhomogeneous dose distributions are required.

Survival outcomes and failure patterns for oropharyngeal cancers treated with simultaneous integrated boost in intensity modulated radiotherapy (SIB-IMRT) and concurrent chemotherapy.

BACKGROUND: Intensity modulated radiotherapy (IMRT) has become a standard radiotherapy treatment delivery option owing to the advantages it offers in terms of target coverage and organ sparing. Furthermore, the ability to introduce different fractionation for different targets lets us deliver higher doses to the high-risk areas and lower doses to the elective volumes at the same sitting, referred to as simultaneous integrated boost (SIB). In the current study, we intended to retrospectively analyze the clinical outcomes and patterns of the failure of oropharyngeal cancers treated with SIB-IMRT and concurrent chemotherapy at our centre and analyze the factors contributing to poorer outcomes. MATERIAL AND METHODS: Data of oropharyngeal cancer patients treated with SIB-IMRT and concurrent chemotherapy were retrieved from the institutional database. Patient demographic details, histopathological features, staging, treatment details, failure patterns and outcomes were documented. All potential factors were evaluated for outcomes. Radiation was delivered by using the SIB-IMRT technique. High-risk planning target volume (PTV) received 66 Gy in 2.2 Gy/fraction, intermediate and low-risk PTV received 60 Gy and 54 Gy, respectively. Primary endpoint was to assess local control (LC), regional control (RC) and loco-regional control (LRC) rates and secondary end point was to evaluate the survival outcomes - overall survival (OS) and cancer-specific mortality. All survival analyzes were performed using the Kaplan-Meier method. RESULTS: A total of 169 cases were included in the final analysis. The median age was 55 years (range 20-78) with 95.3% males. The base of tongue was the most common primary site. Around 54% cases were node negative with 38% patients having stage IV disease. The local control rates for N0 vs. N+ cases were 74.1 vs. 62.3% (P = 0.046), respectively. Similarly, the 4-year RC rates for N0 vs. N+ cases were 94.4 vs. 83.5% (P = 0.024), respectively. On multivariate analysis, only 4-year RC rates showed significant difference between the two (P = 0.039). No differences were found between T stages in LRC and OS. The 4-year LRC rates for stages 1, 2 vs. 3, 4 were non-significant (69.2 vs. 66.3%; P = 0.178). The 4-year OS rate was 81.3%. The 4-year LC and LRC rates were 67.8 and 89.5%, respectively. There were 54 local and 17 regional failures. The median time to failure was 13 months (range 3.6-82.9). CONCLUSION: SIB-IMRT provides comparable outcomes for oropharyngeal cancers. OS and loco-regional recurrences were significantly worse for nodal positive disease.

Stereotactic ablative radiotherapy for locally advanced non-small cell lung cancer: A systematic review and meta-analysis.

INTRODUCTION: To evaluate the feasibility, efficacy and safety of stereotactic ablative radiotherapy (SABR) to the primary tumor and lymph nodes in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who are ineligible for or refused concomitant chemoradiation. MATERIALS AND METHODS: In accordance with the PRISMA and MOOSE guidelines, a systematic review with meta-analysis was conducted. The study included reports that assessed the outcomes of SABR treatment in patients with LA-NSCLC. Studies evaluating SBRT as a boost following primary radiotherapy were excluded. The primary outcomes measured were local control (LC) and overall survival (OS). The secondary endpoint was the incidence of severe toxicity (grades 3-5). A meta-regression analysis was performed to explore the relationship between LC, OS, and severe toxicity. The Biologically Effective Dose (BED) was analyzed as a continuous variable. Statistical significance was defined as a p-value < 0.05. RESULTS: A total of seven studies (3 prospective and 4 retrospective studies) involving 268 patients (SBRT to primary and lymph nodes) were included in the analysis. The pooled 1-year LC rate was 80 % (95 % CI: 63-94 %), and the factors significantly associated with LC were BEDGy10 (p = 0.005) and neoadjuvant chemotherapy (p = 0.005). The 1-year and 2-year OS rates were 74 % (95 % CI: 58-90 %) and 55 % (95 % CI: 34-76 %), respectively. Meta-regression analysis indicated a linear relationship between OS and LC, with a 0.7 % increase in OS for each 1 % improvement in LC (p = 0.005). The pooled rate of grade 3 acute toxicity was 5 % (95 % CI: 1-10 %), and the rate of grade 5 toxicity was 1.7 % (95 % CI: 0-3 %). CONCLUSION: Promising results (LC and OS) with limited toxicity (feasibility) using SABR in LA-NSCLC warrant further research, emphasizing the need for larger, well-designed trials for further validation of the approach.

Stereotactic Body Radiation Therapy for Symptomatic Pancreatic Insulinoma: Two-Case Report and Literature Review.

Insulinoma is the most common functional neuroendocrine tumor of the pancreas, with the main clinical symptom being hypoglycemia. The standard treatment is surgery, but some patients are not eligible for surgery, while in those operated on, the risk of perioperative complications is up to 30%. Diazoxide treatment to prevent hypoglycemia is effective only in 50% of patients. To prevent tumor growth and hormonal excess, stereotactic radiotherapy may be an alternative to surgical treatment. In our paper, we present two cases of patients with insulinoma treated successfully with stereotactic body radiation therapy (SBRT).

Factors associated with the local control of brain metastases: a systematic search and machine learning application.

BACKGROUND: Enhancing Local Control (LC) of brain metastases is pivotal for improving overall survival, which makes the prediction of local treatment failure a crucial aspect of treatment planning. Understanding the factors that influence LC of brain metastases is imperative for optimizing treatment strategies and subsequently extending overall survival. Machine learning algorithms may help to identify factors that predict outcomes. METHODS: This paper systematically reviews these factors associated with LC to select candidate predictor features for a practical application of predictive modeling. A systematic literature search was conducted to identify studies in which the LC of brain metastases is assessed for adult patients. EMBASE, PubMed, Web-of-Science, and the Cochrane Database were searched up to December 24, 2020. All studies investigating the LC of brain metastases as one of the endpoints were included, regardless of primary tumor type or treatment type. We first grouped studies based on primary tumor types resulting in lung, breast, and melanoma groups. Studies that did not focus on a specific primary cancer type were grouped based on treatment types resulting in surgery, SRT, and whole-brain radiotherapy groups. For each group, significant factors associated with LC were identified and discussed. As a second project, we assessed the practical importance of selected features in predicting LC after Stereotactic Radiotherapy (SRT) with a Random Forest machine learning model. Accuracy and Area Under the Curve (AUC) of the Random Forest model, trained with the list of factors that were found to be associated with LC for the SRT treatment group, were reported. RESULTS: The systematic literature search identified 6270 unique records. After screening titles and abstracts, 410 full texts were considered, and ultimately 159 studies were included for review. Most of the studies focused on the LC of the brain metastases for a specific primary tumor type or after a specific treatment type. Higher SRT radiation dose was found to be associated with better LC in lung cancer, breast cancer, and melanoma groups. Also, a higher dose was associated with better LC in the SRT group, while higher tumor volume was associated with worse LC in this group. The Random Forest model predicted the LC of brain metastases with an accuracy of 80% and an AUC of 0.84. CONCLUSION: This paper thoroughly examines factors associated with LC in brain metastases and highlights the translational value of our findings for selecting variables to predict LC in a sample of patients who underwent SRT. The prediction model holds great promise for clinicians, offering a valuable tool to predict personalized treatment outcomes and foresee the impact of changes in treatment characteristics such as radiation dose.

Stereotactic Body Radiotherapy as a Curative Treatment for De Novo Mucosal Carcinoma of the Head and Neck: A Feasible Alternative Option for Fragile Patients with Small Lesion: A Systematic Review.

Stereotactic body radiotherapy (SBRT) is characterized by a high dose per fraction, well-defined small targets, superior dose conformity, and a steep off-target dose gradient. A literature search was conducted to examine the experience with SBRT as a curative treatment for newly diagnosed mucosal carcinoma of the head and neck (MCHN). Four retrospective case series and one prospective phase I clinical trial published between 2012 and 2020 described 124 patients. SBRT was mainly performed in older patients with different tumor sites. The median size of the planning target volumes ranged from 5.3 to 41 cm3. Different approaches were used to create margins. In two studies, limited elective nodal irradiation was performed. The equivalent doses used were 60-83.33 Gy delivered in five fractions. Considerable heterogeneity was observed in the radiation dose specification. The incidence of grade ≥3 late toxicity was 0-8.3%, with local and regional control ranging from 73% to 100%. Improved or stable quality of life after SBRT was reported in two studies. Curative-intent SBRT for de novo MCHN appears to be an effective and relatively safe treatment for small tumor targets, preferably without concomitant elective tissue irradiation. Standardization of SBRT practice and well-designed prospective clinical trials are needed to better define the role of SBRT in this setting.

Total dose, fraction dose and respiratory motion management impact adrenal SBRT outcome.

Purpose/Objectives: Stereotactic body radiotherapy (SBRT) is an effective treatment for oligometastatic disease in multiple sites. However, the optimal radiation dose for long-term local control of adrenal metastases has yet to be determined. The aim of this study is to evaluate outcomes of adrenal SBRT and to evaluate factors that correlate with local control. Materials/Methods: After IRB approval, a retrospective data review of patients treated with SBRT for adrenal metastases at a medical center in Israel between 2015 and 2021 was conducted. A biological effective dose was calculated using an alpha beta ratio of 10. Kaplan Meier and Cox regression were calculated using SPSS software to describe the hazard ratio for local control and survival. Results: 83 cases of adrenal SBRT were identified. The average age was 67 (range 42-92 years old). Non-small cell lung cancer was the primary site in 44 % of patients. A total of 70 % of the patients had oligometastatic disease (less than five lesions), and the rest were polymetastatic, responding to systemic therapy with oligo progression in the adrenal. The average gross tumor volume (GTV) was 42 ml. Respiratory control was applied in 88 % of cases; 49.3 % used 4-D/ITV, and 38.5 % used breath-hold or continuous positive airway pressure (CPAP) with free breathing. On multivariable analysis, Dose above 75 Gy (biological effective Dose) (HR = 0.41, p = 0.031), Dose above 8 Gy per fraction (HR = 0.53p = 0.038), and breath-holds or CPAP (HR = 0.65, p = 0.047) were significant for local control. From multivariable analysis, we computed a predicted nomogram curve using seven clinical parameters to evaluate local control odds. Conclusion: In this single institution series reported to date, we found unilateral adrenal SBRT safe, yet bilateral treatment harbors a risk of adrenal insufficiency. Biological effective Dose > 75 Gy (BED), motion management with breath-hold or CPAP, and Dose per fraction > 8 Gy were the enhanced local controls. We propose a nomogram to help in decision-making regarding total Dose and Dose per fraction when treating adrenal SBRT.

The impact of loco-regional treatment modality on the outcomes in breast cancer patients younger than forty years of age.

PURPOSE: To determine the impact of the loco-regional treatment modality, on the loco-regional recurrence (LRR) rates and overall survival (OS) in breast cancer patients younger than 40 years. METHODS: Data of 623 breast cancer patients younger than 40 years of age were retrospectively reviewed. Patients were stratified according to the locoregional treatment approach into three groups: the mastectomy group (M), the mastectomy followed by radiation therapy group (MRX) and the breast conservative therapy group (BCT). RESULTS: Median follow-up was 72 months (range, 6-180). Two hundred and nine patients were treated with BCT, 86 with MRM and 328 with MRX. The 10-year rate LRR rates according to treatment modality were: 13.4% for BCT, 15.1% for MRM and 8.5% for MRX (p 0.106). On univariate analysis, T stage (p 0.009), AJCC stage (p 0.047) and Her 2 status (p 0.001) were associated with LRR. Ten-year overall survival (OS) was 72.7% (78.5% in the BCT group, 69.8% in the MRM group and 69.8% in the MRX group, p 0.072). On Univariate analysis, age < 35 (p 0.032), grade III (p 0.001), N3 stage (p 0.001), AJCC stage III (p 0.005), ER negative status (0.04), Her 2-status positive (0.006) and lack of chemotherapy administration (p 0.02) were all predictors of increased mortality. CONCLUSION: For patients younger than 40 years of age, similar LRR and overall survival outcomes were achieved using BCT, M or MRX. Young age at diagnosis should not be used alone in recommending one loco-regional treatment approach over the others.

Stereotactic radiosurgery for brain metastasis from cholangiocarcinoma.

OBJECTIVE: Accounting for approximately 15% of primary liver cancers and 3% of gastrointestinal malignancies, cholangiocarcinoma (CCA) poses a serious health concern given its high mortality rate. Managing brain metastases (BMs) from CCA is challenging because of their rarity and poor prognosis, with little guidance on treatment from the literature. In this study, the authors aimed to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in managing BMs from CCA. METHODS: This multicenter retrospective study included 13 CCA patients with 41 BMs treated with SRS from October 2006 to April 2022 at eight institutions affiliated with the International Radiosurgery Research Foundation. Inclusion criteria were a CCA diagnosis, an age over 18 years, no other malignancies, single-fraction SRS treatment for BMs, and at least one follow-up image. Data on demographics, tumor characteristics, treatment details, and outcomes were collected. The primary endpoints were local control (LC), intracranial progression-free survival (PFS), and overall survival (OS). The secondary endpoint was the development of adverse radiation effects (AREs). RESULTS: The median radiological follow-up was 5 months (range 1-18 months). At the last follow-up, LC was achieved in 39 (95.1%) of 41 BMs. New distant metastases were observed in 3 patients (23.1%), and the mean intracranial PFS was 9.4 months (95% CI 6.5-12.3 months). Six-month and 1-year OS rates were 38.5% and 11.5%, respectively, and the median OS was 6 months (95% CI 4.9-7.2 months). Concurrent immunotherapy was associated with a high risk of local failure (HR 29.665, 95% CI 1.799-489.206, p = 0.018), and the absence of systemic chemotherapy before SRS was linked to reduced OS (HR 6.658, 95% CI 1.173-37.776, p = 0.032). Regarding AREs, only 1 patient (7.7%) experienced right hemiparesis and was treated with corticosteroid therapy. CONCLUSIONS: SRS is an effective option for managing BMs in CCA patients, showing promise in LC and a high safety profile.

Early outcomes of MR-guided SBRT for patients with recurrent pancreatic adenocarcinoma.

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC. METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5. RESULTS: Fifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8-26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50-83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5-52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2-27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3-6.7 mos). Grade 1-2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted. CONCLUSIONS: This is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated. TRIAL REGISTRATION: Jefferson IRB#20976, approved 2/17/21.