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Introduction: Surgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis. Material and methods: Patients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups. Results: CT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT. Conclusions: CT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies. [ABSTRACT FROM AUTHOR]

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F] NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0-20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%-34% for non-tumour bone in each dose level. [ABSTRACT FROM AUTHOR]

IntroductionSurgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis.Material and methodsPatients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups.ResultsCT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT.ConclusionsCT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies.

For patients with locally recurrent rectal cancer (LRRC), the response rate to chemoradiotherapy is 40%-50%. Additionally, only approximately 40%-50% of patients with recurrent rectal cancer are able to undergo R0 resection. Recent studies in locally advanced rectal cancer (LARC) have shown promising synergistic effects when combining immunotherapy (PD-1/PD-L1 antibodies) with neoadjuvant chemoradiotherapy (nCRT). Therefore, incorporating immunotherapy into the treatment regimen for LRRC patients has the potential to further improve response rates and prognosis. To investigate this, the TORCH-R trial was conducted. This prospective, single-arm, two-cohort, phase II trial focuses on the use of hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients without or with oligometastases. The trial will include two cohorts: cohort A consists of rectal cancer patients who are treatment-naive for local recurrence, and cohort B includes patients with progressive disease after first-line chemotherapy. Cohort A and cohort B patients will receive 25-40 Gy/5 Fx irradiation or 15-30 Gy/5 Fx reirradiation for pelvic recurrence, respectively. Subsequently, they will undergo 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. Decisions regarding follow-up of complete response (CR), radical surgery, sustained treatment of non-resection, or exiting the trial are made by a multidisciplinary team (MDT). The primary endpoint of this study is the local objective response rate (ORR). The secondary endpoints include the extrapelvic response rate, duration of response, local recurrence R0 resection rate, progression-free survival (PFS), overall survival (OS), and safety and tolerability. Notably, this trial represents the first clinical exploration of inducing hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients. [ABSTRACT FROM AUTHOR]

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F]NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0–20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%–34% for non-tumour bone in each dose level.

Background: The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking. Methods: A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS. Results: Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%. Conclusions: SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: To determine the MRI-Linac added value over conventional imageguided radiation therapy (IGRT) in liver tumors Stereotactic ablative radiation therapy (SABR). Materials and methods: We retrospectively compared the Planning Target Volumes (PTVs), the spared healthy liver parenchyma volumes, the Treatment Planning System (TPS) and machine performances, and the patients' outcomes when using either a conventional accelerator (Versa HD®, Elekta, Utrecht, NL) with Cone Beam CT as the IGRT tool or an MR-Linac system (MRIdian®, ViewRay, CA). Results: From November 2014 to February 2020, 59 patients received a SABR treatment (45 and 19 patients in the Linac and MR-Linac group, respectively) for 64 primary or secondary liver tumors. The mean tumor size was superior in the MR-Linac group (37,91cc vs. 20.86cc). PTV margins led to a median 74%- and 60% increase in target volume in Linac-based and MRI-Linac-based treatments, respectively. Liver tumor boundaries were visible in 0% and 72% of the cases when using CBCT and MRI as IGRT tools, respectively. The mean prescribed dose was similar in the two patient groups. Local tumor control was 76.6%, whereas 23.4% of patients experienced local progression (24.4% and 21.1% of patients treated on the conventional Linac and the MRIdian system, respectively). SABR was well tolerated in both groups, and margins reduction and the use of gating prevented ulcerous disease occurrence. Conclusion: The use of MRI as IGRT allows for the reduction of the amount of healthy liver parenchyma irradiated without any decrease of the tumor control rate, which would be helpful for dose escalation or subsequent liver tumor irradiation if needed. [ABSTRACT FROM AUTHOR]

BackgroundThe role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking.MethodsA prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS.ResultsOverall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age

ObjectiveTo determine the MRI-Linac added value over conventional image-guided radiation therapy (IGRT) in liver tumors Stereotactic ablative radiation therapy (SABR).Materials and methodsWe retrospectively compared the Planning Target Volumes (PTVs), the spared healthy liver parenchyma volumes, the Treatment Planning System (TPS) and machine performances, and the patients’ outcomes when using either a conventional accelerator (Versa HD®, Elekta, Utrecht, NL) with Cone Beam CT as the IGRT tool or an MR-Linac system (MRIdian®, ViewRay, CA).ResultsFrom November 2014 to February 2020, 59 patients received a SABR treatment (45 and 19 patients in the Linac and MR-Linac group, respectively) for 64 primary or secondary liver tumors. The mean tumor size was superior in the MR-Linac group (37,91cc vs. 20.86cc). PTV margins led to a median 74%- and 60% increase in target volume in Linac-based and MRI-Linac-based treatments, respectively. Liver tumor boundaries were visible in 0% and 72% of the cases when using CBCT and MRI as IGRT tools, respectively. The mean prescribed dose was similar in the two patient groups. Local tumor control was 76.6%, whereas 23.4% of patients experienced local progression (24.4% and 21.1% of patients treated on the conventional Linac and the MRIdian system, respectively). SABR was well tolerated in both groups, and margins reduction and the use of gating prevented ulcerous disease occurrence.ConclusionThe use of MRI as IGRT allows for the reduction of the amount of healthy liver parenchyma irradiated without any decrease of the tumor control rate, which would be helpful for dose escalation or subsequent liver tumor irradiation if needed.

The advent of targeted therapy has transformed the treatment paradigm and survival of patients with metastatic non-small cell lung cancer (NSCLC) with driver mutations. The development of acquired resistances during treatment with tyrosine kinase inhibitors (TKIs) impedes a prolonged survival in many patients. This fact is leading to the use of locally ablative therapies such as stereotactic ablative radiotherapy (SABR) to counter these resistances. SABR is a non-invasive treatment that can be delivered in multiple locations and has already proven effective in oligometastatic disease. Clinical evidence suggests that the combination of SABR with TKIs prolongs progression-free survival (PFS) in metastatic NSCLC patients with mutations in epidermal growth factor receptor (EGFR), with international guidelines recommending their use in unfavorable scenarios such as oligoprogressive disease. In this publication, we have reviewed the available evidence on EGFR-TKIs resistance mechanisms and the combination of SABR with TKI in metastatic NSCLC with EGFR mutations. We also describe the utility and clinical recommendations of this combination in oligometastatic and oligoprogressive disease. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: Magnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children. Materials/Methods: All patients treated with MRgRT since inception at our institution between 4/2018 and 4/2022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonanceguided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments. Results: Between 4/2018 and 4/2022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a nonadaptive workflow. Two patients received fractionated MRgRT for an ALKrearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumor/cystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments. Conclusions: In four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracic/abdominal/pelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing. [ABSTRACT FROM AUTHOR]

Purpose/ObjectivesMagnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children.Materials/MethodsAll patients treated with MRgRT since inception at our institution between 4/2018 and 4/2022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonance-guided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments.ResultsBetween 4/2018 and 4/2022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a non-adaptive workflow. Two patients received fractionated MRgRT for an ALK-rearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumor/cystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments.ConclusionsIn four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracic/abdominal/pelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing.

The advent of targeted therapy has transformed the treatment paradigm and survival of patients with metastatic non-small cell lung cancer (NSCLC) with driver mutations. The development of acquired resistances during treatment with tyrosine kinase inhibitors (TKIs) impedes a prolonged survival in many patients. This fact is leading to the use of locally ablative therapies such as stereotactic ablative radiotherapy (SABR) to counter these resistances. SABR is a non-invasive treatment that can be delivered in multiple locations and has already proven effective in oligometastatic disease. Clinical evidence suggests that the combination of SABR with TKIs prolongs progression-free survival (PFS) in metastatic NSCLC patients with mutations in epidermal growth factor receptor (EGFR), with international guidelines recommending their use in unfavorable scenarios such as oligoprogressive disease. In this publication, we have reviewed the available evidence on EGFR-TKIs resistance mechanisms and the combination of SABR with TKI in metastatic NSCLC with EGFR mutations. We also describe the utility and clinical recommendations of this combination in oligometastatic and oligoprogressive disease.

Background: radiotherapy is one of the major treatments for lung cancer and has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer radiotherapy. Method: On August 31, 2022, the authors identified 9868 articles on lung cancer radiotherapy by the Web of Science (Science Citation Indexing Expanded database) and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top-papers) as well as top-journals on lung cancer radiotherapy. After that, the authors analyzed the recent research hotspots based on the latest publications in top-journals. Results: These 9868 papers were cited a total of 268,068 times. "Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer" published in 2017 by Antonia et al. was the most cited article (2110 citations). Among the journals, New England Journal of Medicine was most influential. Moreover, J. Clin. Oncol. and Int. J. Radiat. Oncol. Biol. Phys. was both influential and productive. Corresponding authors represented the USA (2610 articles) and China mainland (2060 articles) took part in most publications and articles with corresponding authors from Netherlands were most cited (46.12 citations per paper). Chemoradiotherapy was the hottest research area, and stereotactic body radiotherapy has become a research hotspot since 2006. Radiotherapy plus immunotherapy has been highly focused since 2019. Conclusions: This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on 9868 relevant articles, and further suggests future research directions. The researchers can benefit in selecting journals and in finding potential collaborators. This study can help researchers gain a comprehensive picture of the research landscape, historical development, and recent hotspots in lung cancer radiotherapy and can provide inspiration for future research. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether prostate motion mitigation using the rectal distension-mediated technique is safe and effective in stereotactic ablative radiation therapy (SABR) salvage treatment of intraprostatic cancer recurrences following initial radiotherapy for primary prostate cancer. Materials and methods: Between July 2013 and December 2020, 30 patients received salvage SABR for 68Ga- PSMA-11 PET/CT-detected intra-prostatic relapses. Median time from primary RT to salvage reirradiation was 70.2 (IQR, 51.3-116.0) months. Median PSA at retreatment was 3.6 ng/mL (IQR, 1.9-6.2). Rectal distension-mediated SABR was achieved with a 150-cm³ air-inflated endorectal balloon and a Foley catheter loaded with 3 beacon transponders was used for urethra visualization and on-line tracking. MRI-based planning employed a 2-mm expansion around the planned target volume (PTV), reduced to 0-mm at the interface with critical organs at risk (OARs). Volumetric Modulated Arc Therapy (VMAT) permitted a 20% dose reduction of the urethra. VMAT simultaneous integrated boost (SIB) of the dominant intraprostatic lesion was deployed when indicated. Median SABR dose was 35 Gy (7 Gy per fraction over 5 consecutive days; range 35-40 Gy). Toxicity assessment used CTCAE v.4 criteria. Results: Median follow-up was 44 months (IQR, 18-60). The actuarial 3- and 4- year biochemical relapse free survival was 53.4% and 47.5%, respectively. Intraprostatic post-salvage relapse by PSMA PET/CT was 53.3%. Acute grade 2 and 3 genitourinary (GU) toxicities were 20% and 0%, respectively. There were no instances of acute grade ≥2 rectal (GI) toxicity. Late grade 2 and 3 GU toxicities occurred in 13.3% and 0% of patients, respectively. There were no instances of grade ≥2 late rectal toxicity. Patient-reported QOL measures showed an acute transient deterioration in the urinary domain 1 month after treatment but returned to baseline values at 3 months. The median IPSS scores rose over baseline (≥5 points in 53% of patients) between month 6 and 12 posttreatment as a result of urinary symptoms flare, eventually receding at 18 months. The bowel domain metrics had no appreciable changes over time. Conclusion: Pursuit of local control in intraprostatic failures is feasible and can be achieved with an acceptably low toxicity profile associated with effective OAR sparing. [ABSTRACT FROM AUTHOR]

PurposeTo explore whether prostate motion mitigation using the rectal distension-mediated technique is safe and effective in stereotactic ablative radiation therapy (SABR) salvage treatment of intraprostatic cancer recurrences following initial radiotherapy for primary prostate cancer.Materials and methodsBetween July 2013 and December 2020, 30 patients received salvage SABR for 68Ga- PSMA-11 PET/CT-detected intra-prostatic relapses. Median time from primary RT to salvage reirradiation was 70.2 (IQR, 51.3-116.0) months. Median PSA at retreatment was 3.6 ng/mL (IQR, 1.9-6.2). Rectal distension-mediated SABR was achieved with a 150-cm3 air-inflated endorectal balloon and a Foley catheter loaded with 3 beacon transponders was used for urethra visualization and on-line tracking. MRI-based planning employed a 2-mm expansion around the planned target volume (PTV), reduced to 0-mm at the interface with critical organs at risk (OARs). Volumetric Modulated Arc Therapy (VMAT) permitted a 20% dose reduction of the urethra. VMAT simultaneous integrated boost (SIB) of the dominant intraprostatic lesion was deployed when indicated. Median SABR dose was 35 Gy (7 Gy per fraction over 5 consecutive days; range 35-40 Gy). Toxicity assessment used CTCAE v.4 criteria.ResultsMedian follow-up was 44 months (IQR, 18-60). The actuarial 3- and 4-year biochemical relapse free survival was 53.4% and 47.5%, respectively. Intraprostatic post-salvage relapse by PSMA PET/CT was 53.3%. Acute grade 2 and 3 genitourinary (GU) toxicities were 20% and 0%, respectively. There were no instances of acute grade ≥2 rectal (GI) toxicity. Late grade 2 and 3 GU toxicities occurred in 13.3% and 0% of patients, respectively. There were no instances of grade ≥2 late rectal toxicity. Patient-reported QOL measures showed an acute transient deterioration in the urinary domain 1 month after treatment but returned to baseline values at 3 months. The median IPSS scores rose over baseline (≥5 points in 53% of patients) between month 6 and 12 post-treatment as a result of urinary symptoms flare, eventually receding at 18 months. The bowel domain metrics had no appreciable changes over time.ConclusionPursuit of local control in intraprostatic failures is feasible and can be achieved with an acceptably low toxicity profile associated with effective OAR sparing.

Purpose: The oligometastatic stage is an intermediate stage of cancer between the localized stage and polymetastatic stage. The prognosis of patients in this stage also appears to be intermediate. Lung stereotactic body radiotherapy is a possible tool for treating oligometastatic lung sites. The objective of our study was to evaluate the clinical outcomes in terms of local control, progressionfree survival, overall survival, and toxicity of SBRT in oligometastatic patients with lung metastases from any solid primary tumor. Materials and methods: Clinical records of consecutive lung oligometastatic patients treated between January 2010 and December 2020 for lung SBRT at 60 Gy in 3-or 8-fraction schedules and a controlled primary tumor were retrospectively analyzed. Results: After a median follow-up of 20.3 months, local failure occurred for 14 lesions, 57 patients experienced lung progression, and 64 patients experienced disease progression. Overall survival rates at 1 and 2 years were 85.6 and 69.7%, respectively. Fifty-two patients experienced radiation pneumonitis, but only 2 patients were symptomatic and presented grade 2 late pneumonitis. No grade 3-4 toxicity was observed. ECOG 0 was the only prognostic factor for overall survival (HR = 3.5; 95% CI 3.2-3.8; p < 0.01). Conclusion: SBRT with a 60-Gy schedule in 8 fractions is an effective and welltolerated treatment for patients with lung oligometastases from any solid primary tumor. [ABSTRACT FROM AUTHOR]

PurposeThe oligometastatic stage is an intermediate stage of cancer between the localized stage and polymetastatic stage. The prognosis of patients in this stage also appears to be intermediate. Lung stereotactic body radiotherapy is a possible tool for treating oligometastatic lung sites. The objective of our study was to evaluate the clinical outcomes in terms of local control, progression-free survival, overall survival, and toxicity of SBRT in oligometastatic patients with lung metastases from any solid primary tumor.Materials and methodsClinical records of consecutive lung oligometastatic patients treated between January 2010 and December 2020 for lung SBRT at 60 Gy in 3- or 8-fraction schedules and a controlled primary tumor were retrospectively analyzed.ResultsAfter a median follow-up of 20.3 months, local failure occurred for 14 lesions, 57 patients experienced lung progression, and 64 patients experienced disease progression. Overall survival rates at 1 and 2 years were 85.6 and 69.7%, respectively. Fifty-two patients experienced radiation pneumonitis, but only 2 patients were symptomatic and presented grade 2 late pneumonitis. No grade 3-4 toxicity was observed. ECOG 0 was the only prognostic factor for overall survival (HR = 3.5; 95% CI 3.2-3.8; p < 0.01).ConclusionSBRT with a 60-Gy schedule in 8 fractions is an effective and well-tolerated treatment for patients with lung oligometastases from any solid primary tumor.

Purpose: To explore whether the rectal distension-mediated technique, harnessing human physiology to achieve intrafractional prostate motion mitigation, enables urethra sparing by inverse dose painting, thus promoting dose escalation with extreme hypofractionated stereotactic ablative radiotherapy (SABR) in prostate cancer. Materials and Methods: Between June 2013 and December 2018, 444 patients received 5 × 9 Gy SABR over 5 consecutive days. Rectal distension-mediated SABR was employed via insertion of a 150-cm3 air-inflated endorectal balloon. A Foley catheter loaded with 3 beacon transponders was used for urethra visualization and online tracking. MRI-based planning using Volume Modulates Arc Therapy - Image Guided Radiotherapy (VMAT-IGRT) with inverse dose painting was employed in delivering the planning target volume (PTV) dose and in sculpting exposure of organs at risk (OARs). A 2-mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. All plans fulfilled Dmean ≤45 Gy. Target motion ≤2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of the planned dose delivery. Results: Patient compliance to the rectal distension-mediated immobilization protocol was excellent, achieving reproducible daily prostate localization at a patient-specific retropubic niche. Online tracking recorded ≤1-mm intrafractional target deviations in 95% of treatment sessions, while target realignment in ≤2-mm deviations enabled treatment completion as scheduled in all cases. The cumulative incidence rates of late grade ≤2 genitourinary (GU) and gastrointestinal (GI) toxicities were 5.3% and 1.1%, respectively. The favorable toxicity profile was corroborated by patient-reported quality of life (QOL) outcomes. Median prostate-specific antigen (PSA) nadir by 5 years was 0.19 ng/ml. The cumulative incidence rate of biochemical failure using the Phoenix definition was 2%, 16.6%, and 27.2% for the combined low/favorable–intermediate, unfavorable intermediate, and high-risk categories, respectively. Patients with a PSA failure underwent a 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) scan showing a 20.2% cumulative incidence of intraprostatic relapses in biopsy International Society of Urological Pathology (ISUP) grade ≤3. Conclusion: The rectal distension-mediated technique is feasible and well tolerated. Dose escalation to 45 Gy with urethra-sparing results in excellent toxicity profiles and PSA relapse rates similar to those reported by other dose-escalated regimens. The existence of intraprostatic recurrences in patients with high-risk features confirms the notion of a high α/β ratio in these phenotypes resulting in diminished effectiveness with hypofractionated dose escalation. [ABSTRACT FROM AUTHOR]

PurposeTo explore whether the rectal distension-mediated technique, harnessing human physiology to achieve intrafractional prostate motion mitigation, enables urethra sparing by inverse dose painting, thus promoting dose escalation with extreme hypofractionated stereotactic ablative radiotherapy (SABR) in prostate cancer.Materials and MethodsBetween June 2013 and December 2018, 444 patients received 5 × 9 Gy SABR over 5 consecutive days. Rectal distension-mediated SABR was employed via insertion of a 150-cm3 air-inflated endorectal balloon. A Foley catheter loaded with 3 beacon transponders was used for urethra visualization and online tracking. MRI-based planning using Volumetric Modulated Arc Therapy - Image Guided Radiotherapy (VMAT-IGRT) with inverse dose painting was employed in delivering the planning target volume (PTV) dose and in sculpting exposure of organs at risk (OARs). A 2-mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. All plans fulfilled Dmean ≥45 Gy. Target motion ≥2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of the planned dose delivery.ResultsPatient compliance to the rectal distension-mediated immobilization protocol was excellent, achieving reproducible daily prostate localization at a patient-specific retropubic niche. Online tracking recorded ≤1-mm intrafractional target deviations in 95% of treatment sessions, while target realignment in ≥2-mm deviations enabled treatment completion as scheduled in all cases. The cumulative incidence rates of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicities were 5.3% and 1.1%, respectively. The favorable toxicity profile was corroborated by patient-reported quality of life (QOL) outcomes. Median prostate-specific antigen (PSA) nadir by 5 years was 0.19 ng/ml. The cumulative incidence rate of biochemical failure using the Phoenix definition was 2%, 16.6%, and 27.2% for the combined low/favorable–intermediate, unfavorable intermediate, and high-risk categories, respectively. Patients with a PSA failure underwent a 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) scan showing a 20.2% cumulative incidence of intraprostatic relapses in biopsy International Society of Urological Pathology (ISUP) grade ≥3.ConclusionThe rectal distension-mediated technique is feasible and well tolerated. Dose escalation to 45 Gy with urethra-sparing results in excellent toxicity profiles and PSA relapse rates similar to those reported by other dose-escalated regimens. The existence of intraprostatic recurrences in patients with high-risk features confirms the notion of a high α/β ratio in these phenotypes resulting in diminished effectiveness with hypofractionated dose escalation.

Herein, we report the first case presentation of paraneoplastic myelofibrosis associated with cancer. Paraneoplastic syndromes occur in some patients with thoracic malignancies; however, myelofibrosis is not commonly seen in non-small cell lung cancer (NSCLC). We report a case of myelofibrosis in a patient with a new diagnosis of NSCLC that resolved after stereotactic ablative radiotherapy (SABR). In conclusion, NSCLC may evoke unexpected systemic effects that resolve with treatment.

In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward an “immunological radiation plan”, i.e., radiation scheduling with abscopal effect as a vital endpoint as well. The literature review of part A enumerates the advantages of the intermediate dose of SBRT 6–10 Gy per fraction, appropriate use of dose painting, proper timing with immunotherapy, and the potential of immunoadjuvants to maximize cell kill in the irradiated lesions, found to have improved the abscopal effects. Part B summarizes part A, primarily the findings of animal trials, forming the basis of the tenets of the proposed model given in part C to realize the true abscopal potential of the SBRT tumor cell kill of the index lesions. Part C proposes a theoretical model highlighting tumor vasculature integrity as the central theme for converting “abscopal effect by chance” to “abscopal effect by design” using a harmonized combinatorial approach. The proposed model principally deals with the use of SBRT in strategizing increased cell kill in irradiated index tumors along with immunomodulators as a basis for improving the consistency of the abscopal effect. Included is the possible role of integrating immunotherapy just after SBRT, “cyclical” antiangiogenics, and immunoadjuvants/immune metabolites as abscopal effect enhancers of SBRT tumor cell kill. The proposed model suggests convergence research in adopting existing numerous SBRT abscopal enhancing strategies around the central point of sustained vascular integrity to develop decisive clinical trial protocols in the future.

Herein, we report the first case presentation of paraneoplastic myelofibrosis associated with cancer. Paraneoplastic syndromes occur in some patients with thoracic malignancies; however, myelofibrosis is not commonly seen in non-small cell lung cancer (NSCLC). We report a case of myelofibrosis in a patient with a new diagnosis of NSCLC that resolved after stereotactic ablative radiotherapy (SABR). In conclusion, NSCLC may evoke unexpected systemic effects that resolve with treatment. [ABSTRACT FROM AUTHOR]

In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward an "immunological radiation plan", i.e., radiation scheduling with abscopal effect as a vital endpoint as well. The literature review of part A enumerates the advantages of the intermediate dose of SBRT 6–10 Gy per fraction, appropriate use of dose painting, proper timing with immunotherapy, and the potential of immunoadjuvants to maximize cell kill in the irradiated lesions, found to have improved the abscopal effects. Part B summarizes part A, primarily the findings of animal trials, forming the basis of the tenets of the proposed model given in part C to realize the true abscopal potential of the SBRT tumor cell kill of the index lesions. Part C proposes a theoretical model highlighting tumor vasculature integrity as the central theme for converting "abscopal effect by chance" to "abscopal effect by design" using a harmonized combinatorial approach. The proposed model principally deals with the use of SBRT in strategizing increased cell kill in irradiated index tumors along with immunomodulators as a basis for improving the consistency of the abscopal effect. Included is the possible role of integrating immunotherapy just after SBRT, "cyclical" antiangiogenics, and immunoadjuvants/immune metabolites as abscopal effect enhancers of SBRT tumor cell kill. The proposed model suggests convergence research in adopting existing numerous SBRT abscopal enhancing strategies around the central point of sustained vascular integrity to develop decisive clinical trial protocols in the future. [ABSTRACT FROM AUTHOR]

BackgroundIn certain malignancies, patients with oligometastatic disease benefit from radical ablative or surgical treatment. The SABR-COMET trial demonstrated a survival benefit for oligometastatic patients randomized to local stereotactic ablative radiation (SABR) compared to patients receiving standard care (SC) alone. Our aim was to determine the cost-effectiveness of SABR.Materials and MethodsA decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY) associated with both strategies in a United States setting from a health care perspective. Analyses were performed over the trial duration of six years as well as a long-term horizon of 16 years. Model input parameters were based on the SABR-COMET trial data as well as best available and most recent data provided in the published literature. An annual discount of 3% for costs was implemented in the analysis. All costs were adjusted to 2019 US Dollars according to the United States Consumer Price Index. SABR costs were reported with an average of $11,700 per treatment. Deterministic and probabilistic sensitivity analyses were performed. Incremental costs, effectiveness, and cost-effectiveness ratios (ICER) were calculated. The willingness-to-pay (WTP) threshold was set to $100,000/QALY.ResultsBased on increased overall and progression-free survival, the SABR group showed 0.78 incremental QALYs over the trial duration and 1.34 incremental QALYs over the long-term analysis. Treatment with SABR led to a marginal increase in costs compared to SC alone (SABR: $304,656; SC: $303,523 for 6 years; ICER $1,446/QALY and SABR: $402,888; SC: $350,708 for long-term analysis; ICER $38,874/QALY). Therapy with SABR remained cost-effective until treatment costs of $88,969 over the trial duration (i.e. 7.6 times the average cost). Sensitivity analysis identified a strong model impact for ongoing annual costs of oligo- and polymetastatic disease states.ConclusionOur analysis suggests that local treatment with SABR adds QALYs for patients with certain oligometastatic cancers and represents an intermediate- and long-term cost-effective treatment strategy.

Background: In certain malignancies, patients with oligometastatic disease benefit from radical ablative or surgical treatment. The SABR-COMET trial demonstrated a survival benefit for oligometastatic patients randomized to local stereotactic ablative radiation (SABR) compared to patients receiving standard care (SC) alone. Our aim was to determine the cost-effectiveness of SABR. Materials and Methods: A decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY) associated with both strategies in a United States setting from a health care perspective. Analyses were performed over the trial duration of six years as well as a long-term horizon of 16 years. Model input parameters were based on the SABR-COMET trial data as well as best available and most recent data provided in the published literature. An annual discount of 3% for costs was implemented in the analysis. All costs were adjusted to 2019 US Dollars according to the United States Consumer Price Index. SABR costs were reported with an average of $11,700 per treatment. Deterministic and probabilistic sensitivity analyses were performed. Incremental costs, effectiveness, and cost-effectiveness ratios (ICER) were calculated. The willingness-to-pay (WTP) threshold was set to $100,000/QALY. Results: Based on increased overall and progression-free survival, the SABR group showed 0.78 incremental QALYs over the trial duration and 1.34 incremental QALYs over the long-term analysis. Treatment with SABR led to a marginal increase in costs compared to SC alone (SABR: $304,656; SC: $303,523 for 6 years; ICER $1,446/QALY and SABR: $402,888; SC: $350,708 for long-term analysis; ICER $38,874/QALY). Therapy with SABR remained cost-effective until treatment costs of $88,969 over the trial duration (i.e. 7.6 times the average cost). Sensitivity analysis identified a strong model impact for ongoing annual costs of oligo- and polymetastatic disease states. Conclusion: Our analysis suggests that local treatment with SABR adds QALYs for patients with certain oligometastatic cancers and represents an intermediate- and long-term cost-effective treatment strategy. [ABSTRACT FROM AUTHOR]

Background and ObjectiveTo assess the efficacy of a Risk-Adapted Ablative Radiotherapy (RAdAR) approach, after intensive induction chemotherapy, in patients with locally advanced pancreatic cancer (LAPC).Material and MethodsPatients with LAPC who received RAdAR following induction chemotherapy from January 2017 to December 2019 were included in this observational study. The RAdAR approach consisted of an anatomy- and simultaneous integrated boost (SIB)-based dose prescription strategy. RAdAR was delivered with stereotactic ablative radiation therapy (SAbR), administering 30 Gy in 5 fractions to the tumor volume (PTVt) and 50 Gy SIB (BED10 100 Gy) to the vascular involvement, or with (hypo-)fractionated ablative radiotherapy (HART) prescribing 50.4 Gy in 28 fractions to the PTVt, with a vascular SIB of 78.4 Gy (BED10 100 Gy). Primary end points were freedom from local progression (FFLP), overall survival (OS), and progression-free survival (PFS).ResultsSixty-four LAPC patients were included. Induction chemotherapy consisted of gemcitabine/nab-paclitaxel in 60.9% and FOLFIRINOX in 39.1% of cases. SAbR was used in 52 (81.2%) patients, and HART in 12 (18.8%). After RAdAR, surgery was performed in 17 (26.6%) patients. Median follow-up was 16.1 months. Overall local control (LC) rate was 78.1%, with no difference between resected and non-resected patients (2-year FFLP 75.3% vs 56.4%; p = 0.112). Median OS and PFS were 29.7 months and 8.7 months, respectively, for the entire cohort. Resected patients had a better median OS (not reached versus 26.1 months; p = 0.0001) and PFS (19 versus 5.6 months; p < 0.0001) compared to non-resected patients. In non-resected patients, no significant difference was found between SAbR and HART for median FFLP (28.1 versus 18.5 months; p = 0.614), OS (27.4 versus 25.3 months; p = 0.624), and PFS (5.7 versus 4.3 months; p = 0.486). One patient (1.6%) experienced acute grade 4 gastro-intestinal bleeding. No other acute or late grade ≥ 3 toxicities were observed.ConclusionsThe RAdAR approach, following intensive induction chemotherapy, is an effective radiation treatment strategy for selected LAPC patients, representing a promising therapeutic option in a multimodality treatment regimen.

Background and Objective: To assess the efficacy of a Risk-Adapted Ablative Radiotherapy (RAdAR) approach, after intensive induction chemotherapy, in patients with locally advanced pancreatic cancer (LAPC). Material and Methods: Patients with LAPC who received RAdAR following induction chemotherapy from January 2017 to December 2019 were included in this observational study. The RAdAR approach consisted of an anatomy- and simultaneous integrated boost (SIB)-based dose prescription strategy. RAdAR was delivered with stereotactic ablative radiation therapy (SAbR), administering 30 Gy in 5 fractions to the tumor volume (PTVt) and 50 Gy SIB (BED10 100 Gy) to the vascular involvement, or with (hypo-)fractionated ablative radiotherapy (HART) prescribing 50.4 Gy in 28 fractions to the PTVt, with a vascular SIB of 78.4 Gy (BED10 100 Gy). Primary end points were freedom from local progression (FFLP), overall survival (OS), and progression-free survival (PFS). Results: Sixty-four LAPC patients were included. Induction chemotherapy consisted of gemcitabine/nab-paclitaxel in 60.9% and FOLFIRINOX in 39.1% of cases. SAbR was used in 52 (81.2%) patients, and HART in 12 (18.8%). After RAdAR, surgery was performed in 17 (26.6%) patients. Median follow-up was 16.1 months. Overall local control (LC) rate was 78.1%, with no difference between resected and non-resected patients (2-year FFLP 75.3% vs 56.4%; p = 0.112). Median OS and PFS were 29.7 months and 8.7 months, respectively, for the entire cohort. Resected patients had a better median OS (not reached versus 26.1 months; p = 0.0001) and PFS (19 versus 5.6 months; p < 0.0001) compared to non-resected patients. In non-resected patients, no significant difference was found between SAbR and HART for median FFLP (28.1 versus 18.5 months; p = 0.614), OS (27.4 versus 25.3 months; p = 0.624), and PFS (5.7 versus 4.3 months; p = 0.486). One patient (1.6%) experienced acute grade 4 gastro-intestinal bleeding. No other acute or late grade ≥ 3 toxicities were observed. Conclusions: The RAdAR approach, following intensive induction chemotherapy, is an effective radiation treatment strategy for selected LAPC patients, representing a promising therapeutic option in a multimodality treatment regimen. [ABSTRACT FROM AUTHOR]

Purpose: To present a retrospective analysis of the efficacy, toxicity, and quality of life (QoL) of patients treated with OARExtreme-sparing stereotactic body radiotherapy (SBRT) in previously-irradiated head and neck cancer.Materials/Methods: From 11/2012 to 7/2015, 60 patients with in-field recurrence of head and neck cancer underwent re-irradiation with SBRT. Retreatment sites included the aerodigestive tract (43%), lateral neck (22%), and skull base (35%). The median prior RT dose was 63.6 Gy with a median time from prior irradiation of 16.5 months. The median volume treated was 61.0 cc. Patients were treated with 40 Gy in the definitive setting or 35 Gy in the post-operative setting in five fractions. Dose constraints to the OARExtreme were calculated with a BED calculator using an alpha/beta ratio of 3 to reduce the risk of late toxicities. QoL data was collected from patients at the time of consultation and at subsequent follow up appointments using the MD Anderson Dysphagia Inventory (MDADI) and Symptom Inventory (MDASI).Results: The 1- and 2- year rates of local, regional, and distant control and overall survival were 79/79, 74/70, 74/71, and 59/45%, respectively. Late grade 3 toxicities were seen in 3% in the group treated to the aerodigestive tract and 1% in the group treated to the skull base. No grade 4 or 5 toxicities were observed. Patients with skull base re-irradiation maintained a stable QoL score after radiation treatment, while patients treated to the aerodigestive tract demonstrated a slight impairment associated with worsening dysphagia, compared to their pretreatment baseline. All groups experienced an increase in xerostomia.Conclusions: OARExtreme-sparing SBRT is able to achieve excellent tumor coverage while protecting the organs at highest risk of re-irradiation-related complications. The potential for lower toxicities and maintained QoL with this treatment makes it a promising option for salvage of recurrent head and neck cancer.SummaryLocal control and overall survival rates for recurrent head and neck cancer remain poor, despite the use of local therapy. In addition, re-irradiation with conventional radiation therapy confers a high rate of grade 3 and higher late toxicities. SBRT appears to improve the therapeutic ratio in this patient population, and treatment planning with a focus on sparing OARExtreme may further decrease the rates of morbidity in these patients.

Purpose: The oligometastatic state is a proposed entity between localized cancer and widely metastatic disease, comprising an intermediate subset of metastatic cancer patients. Most data to support locally-directed treatment, such as stereotactic ablative radiotherapy (SABR), for oligometastases are from retrospective institutional reports. Following the success of a recently completed and reported phase II trial demonstrating important clinical outcomes, herein we review the current landscape of ongoing clinical trials in this context.Materials and methods: A review of currently activated and registered clinical trials was performed using the clinicaltrials.gov database from inception to February 2019. A search of actively recruiting trials, using the key words oligometastases, SABR, and various related terms was performed. Search results were independently reviewed by two investigators, with discrepancies settled by a third. Data abstracted from identified studies included study type, primary disease site, oncologic endpoints, and inclusion/exclusion criteria.Results: Of the initial 216 entries identified, 64 met our review eligibility criteria after full-text review. The most common study type was a phase II clinical trial (n = 35, 55%) with other study designs ranging from observational registry trials to phase III randomized controlled trials (RCTs). A minority of trials were randomized in design (n = 17, 27%). While most studies allowed for metastases from multiple primary disease sites (n = 22, 34%), the most common was prostate (n = 13, 15%), followed by breast, gastrointestinal, non-small cell lung cancer (NSCLC), and renal (n = 6, 9% each). In studies with a solitary target site, the most common was liver (n = 6, 9%) followed by lung (n = 3, 5%). The most common primary endpoints were progression-free survival (PFS) (n = 20, 31%) and toxicity (n = 10, 16%). A combined strategy of systemic therapy and SABR was an emerging theme (n = 23, 36%), with more recent studies specifically evaluating SABR and immunotherapy (n = 9, 14%).Conclusion: The safety and efficacy of SABR as oligometastasis-directed treatment is increasingly being evaluated within prospective clinical trials. These data are awaited to compliment the abundance of existing observational studies and to guide clinical decision-making.

Aim: Lung metastases from an extra-pulmonary origin occasionally present with a limited metastatic disease burden. In cases where metastatectomy is not feasible, stereotactic body radiation therapy (SBRT) represents a non-invasive, efficacious option. We report the outcomes of patients treated with lung SBRT in cases of limited metastatic disease.Methods: We retrospectively reviewed outcomes in 44 patients with 50 lung nodules from various extra-pulmonary malignancies treated with SBRT. Fifty percent of the patients were male and median age was 64. The median number of nodules was 1 and 90% of patients had oligometastatic disease. Thirty-four percent of patients had extra-thoracic disease.Results: Fifty lung nodules were treated with SBRT in 44 patients. Median dose was 48 Gy in 5 fractions with a median biological effective dose (BED) of 100 Gy10. Follow-up imaging was available for review in 96% of nodules. Median follow-up was 17.5 months. One year local control was 82%. BED >72 Gy10 predicted improved local control (90 vs. 57% at 1 year). One year overall survival following SBRT was 66%. There was no difference in overall survival if patients had extra-thoracic disease.Conclusion: Lung SBRT is a safe, effective tool for treatment of limited lung metastases. Dose selection remains important for local control.

Purpose: To present a retrospective analysis of the efficacy, toxicity, and quality of life (QoL) of patients treated with OAR Extreme -sparing stereotactic body radiotherapy (SBRT) in previously-irradiated head and neck cancer. Materials/Methods: From 11/2012 to 7/2015, 60 patients with in-field recurrence of head and neck cancer underwent re-irradiation with SBRT. Retreatment sites included the aerodigestive tract (43%), lateral neck (22%), and skull base (35%). The median prior RT dose was 63.6 Gy with a median time from prior irradiation of 16.5 months. The median volume treated was 61.0 cc. Patients were treated with 40 Gy in the definitive setting or 35 Gy in the post-operative setting in five fractions. Dose constraints to the OAR Extreme were calculated with a BED calculator using an alpha/beta ratio of 3 to reduce the risk of late toxicities. QoL data was collected from patients at the time of consultation and at subsequent follow up appointments using the MD Anderson Dysphagia Inventory (MDADI) and Symptom Inventory (MDASI). Results: The 1- and 2- year rates of local, regional, and distant control and overall survival were 79/79, 74/70, 74/71, and 59/45%, respectively. Late grade 3 toxicities were seen in 3% in the group treated to the aerodigestive tract and 1% in the group treated to the skull base. No grade 4 or 5 toxicities were observed. Patients with skull base re-irradiation maintained a stable QoL score after radiation treatment, while patients treated to the aerodigestive tract demonstrated a slight impairment associated with worsening dysphagia, compared to their pretreatment baseline. All groups experienced an increase in xerostomia. Conclusions: OAR Extreme -sparing SBRT is able to achieve excellent tumor coverage while protecting the organs at highest risk of re-irradiation-related complications. The potential for lower toxicities and maintained QoL with this treatment makes it a promising option for salvage of recurrent head and neck cancer. Summary: Local control and overall survival rates for recurrent head and neck cancer remain poor, despite the use of local therapy. In addition, re-irradiation with conventional radiation therapy confers a high rate of grade 3 and higher late toxicities. SBRT appears to improve the therapeutic ratio in this patient population, and treatment planning with a focus on sparing OAR Extreme may further decrease the rates of morbidity in these patients. [ABSTRACT FROM AUTHOR]

Purpose: The oligometastatic state is a proposed entity between localized cancer and widely metastatic disease, comprising an intermediate subset of metastatic cancer patients. Most data to support locally-directed treatment, such as stereotactic ablative radiotherapy (SABR), for oligometastases are from retrospective institutional reports. Following the success of a recently completed and reported phase II trial demonstrating important clinical outcomes, herein we review the current landscape of ongoing clinical trials in this context. Materials and methods: A review of currently activated and registered clinical trials was performed using the clinicaltrials.gov database from inception to February 2019. A search of actively recruiting trials, using the key words oligometastases, SABR, and various related terms was performed. Search results were independently reviewed by two investigators, with discrepancies settled by a third. Data abstracted from identified studies included study type, primary disease site, oncologic endpoints, and inclusion/exclusion criteria. Results: Of the initial 216 entries identified, 64 met our review eligibility criteria after full-text review. The most common study type was a phase II clinical trial (n = 35, 55%) with other study designs ranging from observational registry trials to phase III randomized controlled trials (RCTs). A minority of trials were randomized in design (n = 17, 27%). While most studies allowed for metastases from multiple primary disease sites (n = 22, 34%), the most common was prostate (n = 13, 15%), followed by breast, gastrointestinal, non-small cell lung cancer (NSCLC), and renal (n = 6, 9% each). In studies with a solitary target site, the most common was liver (n = 6, 9%) followed by lung (n = 3, 5%). The most common primary endpoints were progression-free survival (PFS) (n = 20, 31%) and toxicity (n = 10, 16%). A combined strategy of systemic therapy and SABR was an emerging theme (n = 23, 36%), with more recent studies specifically evaluating SABR and immunotherapy (n = 9, 14%). Conclusion: The safety and efficacy of SABR as oligometastasis-directed treatment is increasingly being evaluated within prospective clinical trials. These data are awaited to compliment the abundance of existing observational studies and to guide clinical decision-making. [ABSTRACT FROM AUTHOR]

Aim: Lung metastases from an extra-pulmonary origin occasionally present with a limited metastatic disease burden. In cases where metastatectomy is not feasible, stereotactic body radiation therapy (SBRT) represents a non-invasive, efficacious option. We report the outcomes of patients treated with lung SBRT in cases of limited metastatic disease. Methods: We retrospectively reviewed outcomes in 44 patients with 50 lung nodules from various extra-pulmonary malignancies treated with SBRT. Fifty percent of the patients were male and median age was 64. The median number of nodules was 1 and 90% of patients had oligometastatic disease. Thirty-four percent of patients had extra-thoracic disease. Results: Fifty lung nodules were treated with SBRT in 44 patients. Median dose was 48 Gy in 5 fractions with a median biological effective dose (BED) of 100 Gy10. Follow-up imaging was available for review in 96% of nodules. Median follow-up was 17.5 months. One year local control was 82%. BED >72 Gy10 predicted improved local control (90 vs. 57% at 1 year). One year overall survival following SBRT was 66%. There was no difference in overall survival if patients had extra-thoracic disease. Conclusion: Lung SBRT is a safe, effective tool for treatment of limited lung metastases. Dose selection remains important for local control. [ABSTRACT FROM AUTHOR]

Traditionally, the ability to deliver large doses of ionizing radiation to a tumor has been limited by radiation induced toxicity to normal surrounding tissues. This was the initial impetus for the development of conventionally fractionated radiation therapy, where large volumes of healthy tissue received radiation and were allowed the time to repair the radiation damage. However, advances in radiation delivery techniques and image guidance have allowed for more ablative doses of radiation to be delivered in a very accurate, conformal and safe manner with shortened fractionation schemes. Hypofractionated regimens with photons have already transformed how certain tumor types are treated with radiation therapy. Additionally, hypofractionation is able to deliver a complete course of ablative radiation therapy over a shorter period of time compared to conventional fractionation regimens making treatment more convenient to the patient and potentially more cost-effective. Recently there has been an increased interest in proton therapy because of the potential further improvement in dose distributions achievable due to their unique physical characteristics. Furthermore, with heavier ions the dose conformality is increased and in addition there is potentially a higher biological effectiveness compared to protons and photons. Due to the properties mentioned above, charged particle therapy has already become an attractive modality to further investigate the role of hypofractionation in the treatment of various tumors. This review will discuss the rationale and evolution of hypofractionated radiation therapy, the reported clinical success with initially photon and then charged particle modalities, and further potential implementation into treatment regimens going forward.

IntroductionSABR provides a superior NSCLC treatment option when compared to conventional radiotherapy for patients deemed inoperable or refusing surgery. This study retrospectively analyzed the rates of tumor control and toxicity following SABR treatment (Cyberknife system) of primary early-stage NSCLC in a community setting.MethodsOne hundred patients were treated between 2007 and 2011. Patients with T3-4 or N1-3 disease, metastasis, recurrent local disease, or a non-lung primary were excluded from analysis. All patients had biopsy proven disease. Staging included CT or FDGPET scan. Median dose was 54Gy (45-60); 18Gy (10-20) per fraction. Median PTV expansion was 8mm (2-10). Median BED was 151.2. Tumors were tracked via Synchrony, X-Sight Lung, or X-Sight Spine. Patients were evaluated for local control, overall survival, and toxicity. All local failures were determined by evaluating post treatment PET/CT.ResultsWith a median follow up of 27.5 months, the 1-, 2-, and 3-year local control rates were 100%, 93.55%, and 84.33%, respectively. Median survival was 2.29 years; actuarial 3- year survival was 37.20%. Grade-3 toxicity was observed in 2% of patients (pneumonia within two months of treatment, n=1; chronic pneumonitis requiring hospital admission, n=1). No patients demonstrated toxicity above Grade-3. Multivariate analysis did not show T-stage as an independent predictor of OS, though it did trend toward significance.ConclusionIn a community-center setting, definitive treatment of NSCLC with SABR for nonsurgical candidates and those who choose to forego surgery result in excellent and comparable rates of local control and toxicity compared to published series from large academic centers.

Purpose: Stereotactic ablative radiotherapy (SABR) is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival and toxicities in SABR for the treatment of malignant skull base tumors. Methods and Materials: A total of 31 patients and 40 locally-advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013 were retrospectively reviewed. The local control rate (LC), progression-free survival rate (PFS), overall survival rate (OS) and toxicities were reported.Results: The median follow-up time of all patients was 11.4 months (range: 0.6-67.2 months). The median tumor volume was 27 cm3 (range: 2.4-205 cm3). All patients received prior EBRT with a median radiation dose of 64 Gy (range: 24-75.6 Gy) delivered in 12 to 42 fractions. 20 patients had surgeries prior to SABR. 19 patients received chemotherapy. Specifically, 8 patients received concurrent cetuximab (ErbituxTM) with SABR. The median time-to-progression (TTP) was 3.3 months (range: 0-16.9 months). For the 29 patients (93.5%) who died, the median time from the end of first SABR to death was 10.3 months (range: 0.5-41.4 months). The estimated 1-year overall survival (OS) rate was 35%. The estimated 2-year OS rate was 12%. Treatment was well-tolerated without grade 4 or 5 treatment-related toxicities.Conclusions: SABR has been shown to achieve low toxicities in locally-advanced or recurrent, previously irradiated head and neck malignancies invading the skull base.

Even though there is extensive research carried out in radiation oncology, most of the clinical studies focus on the effects of radiation on the local tumor tissue and deal with normal tissue side effects. The influence of dose fractionation and timing particularly with regard to immune activation is not satisfactorily investigated so far. This review, therefore, summarizes current knowledge on concepts of modern radiotherapy (RT) and evaluates the potential of RT for immune activation. Focus is set on radiation-induced forms of tumor cell death and consecutively the immunogenicity of the tumor cells. The so-called non-targeted, abscopal effects can contribute to anti-tumor responses in a specific and systemic manner and possess the ability to target relapsing tumor cells as well as metastases. The impact of distinct RT concepts on immune activation is outlined and pre-clinical evidence and clinical observations on RT-induced immunity will be discussed. Knowledge on the radiosensitivity of immune cells as well as clinical evidence for enhanced immunity after RT will be considered. While stereotactic ablative body radiotherapy seem to have a beneficial outcome over classical RT fractionation in pre-clinical animal models, in vitro model systems suggest an advantage for classical fractionated RT for immune activation. Furthermore, the optimal approach may differ based on the tumor site and/or genetic signature. These facts highlight that clinical trials are urgently needed to identify whether high-dose RT is superior to induce anti-tumor immune responses compared to classical fractionated RT and in particular how the outcome is when RT is combined with immunotherapy in selected tumor entities. [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): Herein, we report the results of an IRB-approved phase II trial of Varian Trilogy/TrueBeam-based SABR monotherapy for low-risk prostate cancer using the Calypso® System to provide real-time electromagnetic tracking of the prostate’s position during treatment delivery. Materials/Methods: A total of 102 low-risk patients completed protocol treatment between January 2007 and May 2009. A total dose of 40.0 Gy in 5 every-other-day fractions of 8.0 Gy was prescribed to the planning target volume. Target setup and tracking procedures were as follows: (1) the Calypso® System was used to achieve target setup prior to each fraction; (2) conebeam CT imaging was then used for correction of setup error and for assessment of target and Organs-at-Risk (OAR) deformations; (3) after treatment delivery was initiated, the Calypso® System then provided real-time intrafractional target tracking. The NCI CTCAE v3.0 was used to assess urinary and rectal toxicity during treatment and at defined followup time points. Biochemical response and quality of life measurements were made at concurrent followup points.Results: Urinary toxicities were most common. At 6 months, 19.6%, 2.9% and 4.9% of patients reported grades 1 – 2 urinary frequency, dysuria and retention, respectively. Rectal toxicities were uncommon. By 12 months, 2.9% of patients reported painless rectal bleeding with subsequent symptom resolution without requiring invasive interventions. Quality of life measurements demonstrated a significant decline over baseline in urinary irritative/obstructive scores at 1 month following SABR but otherwise did not demonstrate any difference for bowel, bladder and sexual function scores at any other followup time point. One patient suffered biochemical recurrence at 6 years following SABR.Conclusions: At five years minimum followup for this favorable patient cohort, prostate SABR resulted in favorable toxicity, quality of life and biochemical outcomes.

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) has been shown to have increased local control and overall survival relative to conventional external beam radiation therapy in patients with medically inoperable stage I non-small cell lung cancer (NSCLC). Excellent rates of local control have been demonstrated both in clinical trials as well as in single-center studies at large academic institutions. However, there is limited data on the experiences of small academic hospitals with SBRT for Stage I NSCLC. The purpose of this study is to report the local control and overall survival rates in patients treated with SBRT for Stage I NSCLC at Winthrop-University Hospital (WUH), a small academic hospital. Materials/Methods: This is a retrospective review of 78 Stage I central and peripheral NSCLC tumors treated between December 2006 and July 2012 with SBRT at WUH. Treatment was given utilizing fiducials and a respiratory tracking system. If the fiducials were not trackable, a spine tracking system was used for tumor localization. CT-based planning was performed using the ray trace algorithm. Treatment was delivered over 4 consecutive days for central tumors to a dose of 4800 cGy delivered in 4 fractions. Peripheral tumors were treated to a dose of 6000 cGy in 3 consecutive fractions. The Kaplan-Meier method was used to calculate local control and overall survival. Results: The median age was 78.5 years. 54% of the patient population was female. 67% of the tumors were Stage IA, and 33% of the tumors were Stage IB. 53% of the tumors were adenocarcinomas and 29% were squamous cell carcinomas, with the remainder being of unknown histology or NSCLC, not otherwise specified The 2-year local control rate was 87%, and the two-year overall survival was 68%. Conclusions: Our findings support that local control and overall survival at a small academic hospital are comparable to that of larger academic institutions' published experiences with SBRT for Stage I NSCLC.

Image guidance allows delivery of very high doses of radiation over a few fractions, known as stereotactic ablative radiotherapy (SABR). This treatment is associated with excellent outcome for early stage non-small cell lung cancer and metastases to the lungs. In the delivery of SABR, central location constantly poses a challenge due to the difficulty of adequately sparing critical thoracic structures that are immediately adjacent to the tumor if an ablative dose of radiation is to be delivered to the tumor target. As of current, various respiratory motion management and image guidance strategies can be used to ensure accurate tumor target localization prior and/ or during daily treatment, which allows for maximal and safe reduction of set up margins. The incorporation of both may lead to the most optimal normal tissue sparing and the most accurate SABR delivery. Here, the clinical outcome, treatment related toxicities, and the pertinent respiratory motion management/image guidance strategies reported in the current literature on SABR for central lung tumors are reviewed.

Purpose: Stereotactic ablative radiotherapy (SABR) is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival, and toxicities in SABR for the treatment of previously irradiated malignant skull base tumors. Materials and methods: A total of 31 patients and 40 locally advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen, which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013, were retrospectively reviewed. The local control rate (LC), progression-free survival rate, overall survival (OS) rate, and toxicities were reported. Results: The median follow-up time of all patients was 11.4 months (range: 0.6-67.2 months). The median tumor volume was 27 cm3 (range: 2.4-205 cm3). All patients received prior external beam radiation therapy with a median radiation dose of 64 Gy (range: 24-75.6 Gy) delivered in 12-42 fractions. Twenty patients had surgeries prior to SABR. Nineteen patients received chemotherapy. Specifically, eight patients received concurrent cetuximab (Erbitux™) with SABR. The median time-to-progression (TTP) was 3.3 months (range: 0-16.9 months). For the 29 patients (93.5%) who died, the median time from the end of first SABR to death was 10.3 months (range: 0.5-41.4 months).The estimated 1-year OS rate was 35%. The estimated 2-year OS rate was 12%. Treatment was well-tolerated without grade 4 or 5 treatment-related toxicities. Conclusion: Stereotactic ablative radiotherapy has been shown to achieve low toxicities in locally advanced or recurrent, previously irradiated head and neck malignancies invading the skull base. [ABSTRACT FROM AUTHOR]

Introduction: Prostate-specific antigen (PSA) bounce after brachytherapy has been well-documented. This phenomenon has also been identified in patients undergoing stereotactic body radiation therapy (SBRT). While the parameters that predict PSA bounce have been extensively studied in prostate brachytherapy patients, this study is the first to analyze the clinical and pathologic predictors of PSA bounce in prostate SBRT patients. Materials and Methods: Our institution has maintained a prospective database of patients undergoing SBRT for prostate cancer since 2006. Our study population includes patients between May 2006 and November 2011 who have at least 18 months of follow-up. All patients were treated using the CyberKnife treatment system. The prescription dose was 3500-3625cGy in 5 fractions.Results: 120 patients were included in our study. Median PSA follow-up was 24 months (range 18-78 months). 34 (28%) patients had a PSA bounce. The median time to PSA bounce was 9 months, and the median bounce size was 0.50ng/mL. On univariate analysis, only younger age (p = .011) was shown to be associated with an increased incidence of PSA bounce. Other patient factors, including race, prostate size, prior treatment by hormones, and family history of prostate cancer, did not predict PSA bounces. None of the tumor characteristics studied, including Gleason score, pre-treatment PSA, T-stage, or risk classification by NCCN guidelines, was associated with increased incidence of PSA bounces. Younger age was the only statistically significant predictor of PSA bounce on multivariate analysis (OR = 0.937, p = 0.009).Conclusion: PSA bounce, which has been reported after prostate brachytherapy, is also seen in a significant percentage of patients after CyberKnife SBRT. Close observation rather than biopsy can be considered for these patients. Younger age was the only factor that predicted PSA bounce.

Purpose/Objective(s): Herein, we report the results of an IRB-approved phase II trial of VarianTrilogy/TrueBeam-based stereotactic ablative body radiotherapy (SABR) monotherapy for low-risk prostate cancer using the Calypso® System to provide real-time electromagnetic tracking of the prostate's position during treatment delivery. Materials/Methods: A total of 102 low-risk patients completed protocol treatment between January 2007 and May 2009. A total dose of 40.0 Gy in 5 every-other-day fractions of 8.0 Gy was prescribed to the planning target volume. Target setup and tracking procedures were as follows: (1) the Calypso® System was used to achieve target setup prior to each fraction; (2) conebeam CT imaging was then used for correction of setup error and for assessment of target and organs-at-risk deformations; (3) after treatment delivery was initiated, the Calypso® System then provided real-time intrafractional target tracking. The NCI CTCAE v3.0 was used to assess urinary and rectal toxicity during treatment and at defined follow-up time points. Biochemical response and quality of life measurements were made at concurrent follow-up points. Results: Urinary toxicities were most common. At 6 months, 19.6, 2.9, and 4.9% of patients reported grades 1-2 urinary frequency, dysuria, and retention, respectively. Rectal toxicities were uncommon. By 12 months, 2.9% of patients reported painless rectal bleeding with subsequent symptom resolution without requiring invasive interventions. Quality of life measurements demonstrated a significant decline over baseline in urinary irritative/obstructive scores at 1 month following SABR but otherwise did not demonstrate any difference for bowel, bladder, and sexual function scores at any other follow-up time point. One patient suffered biochemical recurrence at 6 years following SABR. Conclusion: At 5 years, minimum follow-up for this favorable patient cohort, prostate SABR resulted in favorable toxicity, quality of life, and biochemical outcomes. [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) has been shown to have increased local control and overall survival relative to conventional external beam radiation therapy in patients with medically inoperable stage I non-small cell lung cancer (NSCLC). Excellent rates of local control have been demonstrated both in clinical trials and in single-center studies at large academic institutions. However, there is limited data on the experiences of small academic hospitals with SBRT for stage I NSCLC. The purpose of this study is to report the local control and overall survival rates in patients treated with SBRT for stage I NSCLC at Winthrop-University Hospital (WUH), a small academic hospital. Materials/Methods: This is a retrospective review of 78 stage I central and peripheral NSCLC tumors treated between December 2006 and July 2012 with SBRT at WUH. Treatment was given utilizing fiducials and a respiratory tracking system. If the fiducials were not trackable, a spine tracking system was used for tumor localization. CT-based planning was performed using the ray trace algorithm. Treatment was delivered over consecutive days to a median dose of 4800 cGy delivered in four fractions. The Kaplan-Meier method was used to calculate local control and overall survival. Results: The median age was 78.5 years. Fifty-four percent of the patient population was female. Sixty seven percent of the tumors were stage IA, and 33% of the tumors were stage IB. Fifty-three percent of the tumors were adenocarcinomas and 29% were squamous cell carcinomas, with the remainder being of unknown histology or NSCLC, not otherwise specified The 2-year local control rate was 87%, and the 2-year overall survival was 68%. Conclusion: Our findings support that local control and overall survival at a small academic hospital are comparable to that of larger academic institutions' published experiences with SBRT for stage I NSCLC. [ABSTRACT FROM AUTHOR]

Image guidance allows delivery of very high doses of radiation over a few fractions, known as stereotactic ablative radiotherapy (SABR). This treatment is associated with excellent outcome for early stage non-small cell lung cancer and metastases to the lungs. In the delivery of SABR, central location constantly poses a challenge due to the difficulty of adequately sparing critical thoracic structures that are immediately adjacent to the tumor if an ablative dose of radiation is to be delivered to the tumor target. As of current, various respiratory motion management and image guidance strategies can be used to ensure accurate tumor target localization prior and/or during daily treatment, which allows for maximal and safe reduction of set up margins. The incorporation of both may lead to the most optimal normal tissue sparing and the most accurate SABR delivery. Here, the clinical outcome, treatment related toxicities, and the pertinent respiratory motion management/ image guidance strategies reported in the current literature on SABR for central lung tumors are reviewed. [ABSTRACT FROM AUTHOR]

Abstract:Purpose: Standard chemoradiation therapy for Stage III non-small cell lung cancer results in suboptimal outcomes with a high rate of local failure and poor overall survival. We hypothesize that dose escalation using stereotactic body radiotherapy (SBRT) boost could improve upon these results. We present here a study evaluating the dosimetric feasibility of such an approach.Methods: Anonymized CT data sets from 3 randomly selected patients with stage III NSCLCa undergoing definitive chemoradiation therapy in our department with disease volumes appropriate for SBRT boost were selected. 3D-CRT plans to 50.4 Gy in 28 fractions were generated follow by SBRT plans to two dose levels, 16 Gy in 2 fractions and 28 Gy in 2 fractions. SBRT plans and total composite (3D-CRT and SBRT) were optimized and evaluated for target coverage and dose to critical structures; lung, esophagus, cord, and heart.Results: All three plans met predetermined target coverage and normal tissue dose constraints. PTV V95 was equal to or greater than 95% in all cases. The cumulative lung V20 and V5 of the combined 3D-CRT and SBRT plans were less than or equal to 30% and 55%, respectively. The 5cc esophageal dose was less than 12 Gy for all low and high dose SBRT plans. The cumulative dose to the esophagus was also acceptable with less than 10% of the esophagus receiving doses in excess of 50 Gy. The cumulative spinal cord dose was less than 33 Gy and heart V25 was less than 5%.Conclusion: The combination of chemoradiation to 50.4 Gy followed by SBRT boost to gross disease at the primary tumor and involved regional lymph nodes is feasible with respect to normal tissue dose constraints in this dosimetric pilot study. A phase I/II trial to evaluate the clinical safety and efficacy of this approach is being undertaken.

Introduction: Prostate-specific antigen (PSA) bounce after brachytherapy has been welldocumented. This phenomenon has also been identified in patients undergoing stereotactic body radiation therapy (SBRT). While the parameters that predict PSA bounce have been extensively studied in prostate brachytherapy patients, this study is the first to analyze the clinical and pathologic predictors of PSA bounce in prostate SBRT patients. Materials and Methods: Our institution has maintained a prospective database of patients undergoing SBRT for prostate cancer since 2006. Our study population includes patients between May 2006 and November 2011 who have at least 18 months of follow-up. All patients were treated using the CyberKnife treatment system. The prescription dose was 35-36.25 Gy in five fractions. Results: One hundred twenty patients were included in our study. Median PSA follow-up was 24 months (range 18-78 months). Thirty-four (28%) patients had a PSA bounce. The median time to PSA bounce was 9 months, and the median bounce size was 0.50 ng/mL. On univariate analysis, only younger age (p =0.011) was shown to be associated with an increased incidence of PSA bounce. Other patient factors, including race, prostate size, prior treatment by hormones, and family history of prostate cancer, did not predict PSA bounces. None of the tumor characteristics studied, including Gleason score, pre-treatment PSA,T-stage, or risk classification by NCCN guidelines,were associated with increased incidence of PSA bounces. Younger age was the only statistically significant predictor of PSA bounce on multivariate analysis (OR=0.937, p =0.009). Conclusion: PSA bounce, which has been reported after prostate brachytherapy, is also seen in a significant percentage of patients after CyberKnife SBRT. Close observation rather than biopsy can be considered for these patients. Younger age was the only factor that predicted PSA bounce [ABSTRACT FROM AUTHOR]

Purpose: Standard chemoradiation therapy for stage III non-small cell lung cancer (NSCLCa) results in suboptimal outcomes with a high rate of local failure and poor overall survival. We hypothesize that dose escalation using stereotactic body radiotherapy (SBRT) boost could improve upon these results. We present here a study evaluating the dosimetric feasibility of such an approach. Methods: Anonymized CT data sets from five randomly selected patients with stage III NSCLCa undergoing definitive chemoradiation therapy in our department with disease volumes appropriate for SBRT boost were selected. Three-dimensional conformal radiation therapy (3D-CRT) plans to 50.4 Gy in 28 fractions were generated follow by SBRT plans to two dose levels, 16 Gy in two fractions and 28 Gy in two fractions. SBRT plans and total composite (3D-CRT and SBRT) were optimized and evaluated for target coverage and dose to critical structures; lung, esophagus, cord, and heart. Results: All five plans met predetermined target coverage and normal tissue dose constraints. PTV V95 was equal to or greater than 95% in all cases. The cumulative lung V20 and V5 of the combined 3D-CRT and SBRT plans were less than or equal to 30 and 55%, respectively. The 5 cc esophageal dose was less than 12 Gy for all low and high dose SBRT plans. The cumulative dose to the esophagus was also acceptable with less than 10% of the esophagus receiving doses in excess of 50 Gy. The cumulative spinal cord dose was less than 33 Gy and heart V25 was less than 5%. Conclusion: The combination of chemoradiation to 50.4 Gy followed by SBRT boost to gross disease at the primary tumor and involved regional lymph nodes is feasible with respect to normal tissue dose constraints in this dosimetric pilot study. A phase I/II trial to evaluate the clinical safety and efficacy of this approach is being undertaken. [ABSTRACT FROM AUTHOR]