Stereotactic Body Radiation Therapy Regimen Research Articles

Multi-institutional analysis of high-risk prostate cancer patients treated with stereotactic body radiotherapy.

51 Background: Stereotactic Body Radiotherapy (SBRT) delivers ablative doses of radiation (RT) over a course of five treatments and has been increasingly used as a definitive RT option for low- and intermediate-risk prostate cancer (PCa). Ongoing prospective trials are evaluating the efficacy of SBRT for high-risk PCa, but clinical outcomes reports are limited. Methods: Patients treated for high-risk PCa between 2006-2017 at any of five institutions were included. SBRT doses ranged from 35-40 Gy in 5 fractions per institutional standards, with one institution using an integrated boost approach. The Phoenix definition was used to define biochemical failure (BCR). Physician-reported genitourinary (GU) and gastrointestinal (GI) toxicity outcomes were scored using the Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events systems. Results: In total, 182 patients were included in this study with a median follow-up time of 38.4 months (mos). The median age was 72. Most patients (72%) had Gleason 8-10 disease. Sixty-eight percent of patients received androgen deprivation therapy (ADT) for a median of 9 mos (interquartile range 6-9 mos). The rate of distant metastases was 3.8%. There were no acute Grade 3 (G3) or higher GU or GI toxicities. Three patients (1.6%) experienced a late G3 GU toxicity and one patient (0.5%) experienced a late G3 GI toxicity. The incidence of BCR was significantly higher in patients who did not receive ADT (30% vs. 15%, p = 0.02 by Chi-square). Conclusions: In this multi-institutional study, SBRT demonstrated an acceptable safety profile for the treatment of high-risk PCa. Longer term follow-up is necessary to evaluate the oncologic efficacy of this approach, but given the potentially higher incidence of BCR without ADT, ADT likely has an important oncologic role even with SBRT regimens.

Single-Fraction Stereotactic Body Radiotherapy for Oligometastatic Lymph Node Relapse in Prostate Cancer

Background: Stereotactic body radiotherapy (SBRT) emerged as a treatment option in oligometastatic (≤3 metastases) patients experiencing lymph node relapse from treated prostate cancer. No recommendations are available concerning dose schedule, and available studies report the use of multiple-fraction regimens due to theoretical lower toxicity and higher cumulative dose delivered to the target. The aim of the present study was to evaluate the safety and efficacy of a dose-intensive, single-fraction SBRT regimen. Patients and Methods: Retrospective data on outcome and toxicity from 27 treatments on 23 consecutive patients were collected. Statistical analysis was performed. Results: Median follow-up was 22 months (range 6-63, interquartile range 15-28). Biochemical progression-free survival (bPFS) at 6 months, 1 year, and 2 years were 65%, 40%, and 26%, respectively. In 2 cases acute toxicity of grade 1 were observed. Conclusion: Single-fraction SBRT for lymph node relapse of oligometastatic prostate cancer resulted in promising biochemical control with minimal toxicity.

Significance of stereotactic body radiotherapy in older patients with early stage non-small cell lung cancer.

Our aim was to investigate long-term treatment outcomes in older patients with early stage non-small cell lung cancer (NSCLC) and the presence or absence of therapeutic benefits, using the G8 screening tool. We retrospectively studied 43 older patients (median age 78 years, range 65-89 years) with stage I lung tumors (T1 and T2 tumors in 34 and 9 patients, respectively), who underwent stereotactic body radiotherapy (SBRT). This study assessed outcomes in a cohort of patients who received geriatric assessments, performed between 2004 and 2011, before the start of their SBRT regimen. Any questions asked to patients before undergoing treatment were applied to the G8 screening tool. G8 scores ranged from 8 to 16 (median, 12) in all patients (n = 43), while G8 scores in the T1 and T2 groups ranged from 9 to 16 (median, 13) and 8 to 15 (median, 12), respectively. In patients with G8 scores ≤12, the 2-year and 5-year survival rates were 56.1% and 28% respectively, while the rates were 94.1% and 68.4%, respectively, in patients with G8 scores ≥13 (P = 0.0014). During long-term follow-up, 25.9% of the patients (n = 43) died of the primary disease, NSCLC, and 34.9% of patients died of other diseases or other types of cancer. SBRT may be effective, even in older adults. Regardless of age, SBRT improved the long-term survival of patients only with G8 scores ≥13. The G8 screening tool may aid in determining whether older patients with comorbidities would benefit from SBRT.

Three- Versus Five-Fraction Regimens of Stereotactic Body Radiotherapy for Peripheral Early-Stage Non–Small-Cell Lung Cancer: A Two-Institution Propensity Score–Matched Analysis

PurposeTo evaluate differences in outcomes of early-stage peripheral non–small-cell lung cancer (NSCLC) treated with either 3- or 5-fraction stereotactic body radiotherapy (SBRT) at 2 institutions. Patients and MethodsPatients diagnosed with peripherally located early-stage NSCLC who received either a median dose of 60 Gy (interquartile range [IQR], 60-60, biologically effective dose, 151-151) in 3 fractions or a median dose of 50 Gy (IQR, 50-50, biologically effective dose, 94-94) in 5 fractions were included in this study. All data were retrospectively collected and reviewed in an institutional review board–approved database. ResultsA total of 192 lesions in 192 patients were identified: 94 received 3-fraction SBRT and 98 received 5-fraction SBRT. Patients in the 5-fraction cohort had significantly smaller tumors (P = .0021). Larger tumor size was associated with worse overall survival (hazard ratio, 1.40, P = .0013) for all patients. A single grade 3 toxicity was reported in each cohort. A propensity score–matched cohort of 94 patients was constructed with a median follow-up of 29.3 months (IQR, 17.3-44.6) for the 3-fraction cohort and 31.0 months (IQR, 17.0-48.5) for the 5-fraction cohort (P = .84). There were no statistically significant differences between these 2 cohorts in overall survival (P = .33), progression-free survival (P = .40), local failure (P = .86), and nodal or distant failure (P = .57) at 2 years. ConclusionThe 3- and 5-fraction SBRT regimens for early-stage peripheral NSCLC had comparable clinical outcomes. Both regimens were well tolerated. A large tumor size was an adverse prognostic factor for worse survival.

Stereotactic body radiation therapy for palliative treatment of bone metastases: Practice patterns and survival outcomes.

242 Background: Stereotactic body radiation therapy (SBRT) is an emerging modality of treatment designed to deliver high radiation doses in few fractions. We examine practice trends in the use of SBRT for managing bone metastases in patients with breast, kidney, non-small-cell lung, melanoma, or prostate cancer. Methods: We selected patients from the National Cancer Database (2004-2013) diagnosed with bone metastases from breast, kidney, non-small-cell lung, melanoma, or prostate cancer. SBRT fractionation regimens were defined as 12-45 Gy in 1 fraction, 14-50 Gy in 2 fractions, 21-50 Gy in 3 fractions, 28-50 Gy in 4 fractions, and 30-60 Gy in 5 fractions. Standard palliative radiation fractionation regimens were defined as all other cases with 2-40 Gy in 20 fractions or fewer. Results: Patients receiving SBRT regimens made up 1454 of 57,556 total palliative cases. Bone metastases treated with SBRT primarily at the spine (65.5%), hip/pelvis (12.3%), and shoulder/extremity (11.4%). SBRT palliation regimens were used for only 2.5% of patients. Though standard palliative radiation fractionation regimens comprised the majority of treatments (97.5%), SBRT utilization is increasing, with a majority (68.4%) of SBRT cases occurring from 2009-2013. Treatment at an academic center and lack of comorbidities were positively associated with receiving SBRT regimens. Mean survival outcomes were higher for patients receiving SBRT (24.3 months) than patients receiving standard regimens (16.9 months). Conclusions: Though the vast majority of bone metastases were treated with standard palliative radiation fractionation, SBRT utilization increased from 2004-2013, with the greatest portion of SBRT cases occurring at academic institutions. Patients receiving SBRT exhibit better survival outcomes, likely as a result of patient selection practices.

Local Tumor Control After Stereotactic Body Radiation Therapy for Early Lung Cancer is Not Impacted by the Use of Intensity Modulated Radiation Therapy or Respiratory Gating

Though stereotactic body radiation therapy (SBRT) has become a standard treatment option for stage I NSCLC, the majority of published results relate to three-dimensional treatment planning (3D-CRT). Less data is available following treatment with IMRT, and there is also limited published experience using respiratory gating, where treatment is only delivered to a portion of the breathing cycle, during SBRT. Retrospective review of patients treated with SBRT for Stage I NSCLC between 2007 and 2015. All patients had a 4D simulation with the Varian RPMTM system and abdominal compression was used in the majority (81%). Respiratory gating was typically used if longitudinal tumor motion exceeded 1cm. Patient characteristics, treatment planning and delivery parameters, dosimetry information, and patient outcomes were collected and analyzed using SPSS statistical software (descriptive stats, bivariate procedures and survival analyses). A total of 297 patients (median age 71, range 43-89) with stage I NSCLC were included. Pathology was confirmed in 94.6% of patients. The majority of lesions were located in the upper lobes (60.9%) and clinical stage T1A (68%). The use of 3DCRT and IMRT planning was similar, 52% vs 48%, although an increased frequency of IMRT was noted in more recent years. Respiratory gating was employed in approximately 16% of cases (n=51). The gating cohort included 78% lower lobe tumors, while 26% of lesions treated without gating were in the lower lobes. The most common SBRT regimens were 48Gy in 4 fractions and 54-60Gy in 3 fractions. With a median follow up of 22.7 months, there were 17 local failures for a crude relapse rate of 5.7%. Local tumor relapse was similar in patients treated with 3DCRT and IMRT (6.5% vs 4.9%, p=0.962), and relapse likewise was similar with and without respiratory gating (7.8% vs 4.9%, p=0.560). In addition, T-stage, tumor size, pathology and SBRT regimen did not correlate with local tumor control. Overall survival for the entire population approximated 72% at 2 years. Treatment appeared tolerated well with 6 documented grade 3+ events, and thus there were too few events to compare toxicity amongst treatment cohorts. The utilization of respiratory gating or the use of IMRT does not appear to compromise the therapeutic ratio for patients treated with SBRT for stage I NSCLC.

Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: Preliminary Toxicity Results of a Phase 2 Trial

Stereotactic body radiotherapy (SBRT) for high-risk prostate cancer (CaP) remains investigational not only due to undetermined efficacy but also due to concerns for the potential toxicity when the treatment volumes extend beyond the prostate gland itself. Herein we present the preliminary toxicity results of a phase II trial evaluating a five fraction SBRT regimen for high-risk CaP that allows for the integration pelvic nodal radiation (RT) and androgen deprivation therapy (ADT). Men with high-risk CaP, as defined by Gleason score >= 8, clinical stage T3-T4, or initial PSA >= 20 ng/mL, were enrolled on a multicenter phase II trial and were treated with 40 Gy to prostate. Radiation to the pelvic nodes with 25 Gy in a simultaneous integrated boost plan (5 Gy per fraction) and/or a nine months neoadjuvant and concurrent androgen deprivation therapy (ADT) could be integrated with prostate SBRT at the discretion of the treating physician. Follow-up assessment was with CTCAE v4 and Expanded Prostate Composite Index (EPIC). SBRT was delivered with a linear accelerator using volumetric modulated arc therapy or with a CyberKnife system. A total of 73 patients have been treated on this protocol, with a median follow-up of 13.8 months. Forty-six (63%) received ADT and 23 (32%) received nodal RT. The median initial PSA was 8.8 ng/mL and 11% of patients had clinical T3-T4 disease; 48% and 33% had Gleason score 8 and 9-10 disease, respectively. No grade 3 or higher genitourinary (GU) or gastrointestinal (GI) toxicities were seen. For patients receiving nodal radiation, rates of acute grade 1 and 2 GU toxicities were 18.2% and 4.5%; for those not receiving nodal RT, they were 23.5% and 17.6%. Rates of acute grade 1 and 2 GI toxicities were 9.1% and 9.1% with and 11.8% and 3.9% without nodal RT. Late grade 1 and 2 GU toxicities rates with nodal RT were 27.3% and 4.5%; without nodal RT, the rates were 18.6% and 7.0%. Late grade 1 and 2 GI rates were 13.6% and 13.6% with nodal radiation and 11.6% and 4.7% without it. Mean changes in EPIC urinary and bowel domain scores at 4 months were +0.13 and -4.17 with nodal RT, and +0.79 and -2.97 without it. Mean changes in EPIC urinary and bowel domain scores at 12 months were -1.52 and -5.12 with nodal RT and -1.71 and -5.67 without it. Overall, the receipt of nodal RT had no significant association with either physician- or patient-reported toxicity profiles (p > 0.1, Fisher’s exact test). Similarly, the receipt of ADT had no significant association with any toxicity parameter. Two patients (2.7%) experienced biochemical failure; in both cases, the PSA never decreased after SBRT. SBRT regimens can be safely utilized to deliver the entire course in 5 treatment days in patients with high-risk localized CaP, with or without the integration of nodal RT and/or short-course ADT. Despite the short followup, the low rate of biochemical failure is encouraging.

A Phase 1/2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer With a Simultaneous Integrated Boost to MRI-Identified Regions of High Tumor Volume (NCT02470897)

Stereotactic body radiation therapy (SBRT) is a promising treatment option for low- and intermediate- risk prostate carcinoma. Dose escalation beyond currently standard SBRT regimens may further improve outcomes, particularly for bulkier tumors, but could be limited by adjacent organ dose constraints. However, selective dose escalation to identified regions of high tumor burden may offer a safer approach than uniform dose escalation. Therefore, this ongoing prospective study seeks to test the planning and delivery feasibilities and the tolerability of treating patients with a modest dose escalation to the entire prostate and a simultaneous integrated boost (SIB) to MRI-identified lesions. Low- or intermediate- risk prostate cancer patients (Gleason score ≤ 7, PSA ≤20, T stage ≤2b) are eligible and treated based on ability to undergo pre-treatment pelvic MRI. Patients enrolled to date undergoing MRI (n=10) received LINAC-based prostate SBRT (5 x 8.0 Gy delivered every other day) with urethral, anterior rectal wall and bladder base doses constrained to 7.25 Gy/fraction. MRI-identified PI-RADS 4 or 5 lesions received a SIB to 8.5 - 9.0 Gy/fraction. Patients not undergoing MRI imaging (n=6) received a uniform SBRT dose (5 x 7.5 Gy) with the same normal tissue constraints. Intra-fractional shifts were monitored with a repeat alignment scan after half of the fractional dose was delivered. Acute bowel and bladder toxicity was assessed using RTOG toxicity scales and the IPSS. Urinary, bowel and sexual quality of life will be assessed at regular intervals using the expanded prostate cancer index composite (EPIC-26) questionnaire. Median follow up was 8 months with a range of 2-16 months. Dosimetric evaluation of planned and delivered dose indicates that prostate SBRT including both a dose constraint applied to the urethra, anterior rectum and bladder base as well as a SIB to MRI-identified tumor subvolumes can be reproducibly planned and delivered. There were no grade 3 or 4 acute or late GI or GU toxicities and only two patients reported acute grade 2 urinary symptoms (2/16 or 12.5%). Average IPSS scores increased only modestly from pretreatment baseline scores of 8.2 to 6 week scores of 10.4 (p=0.02). This ongoing trial employs a simultaneous integrated boost to MRI-detected lesions during SBRT while constraining doses to immediately bordering normal organ subvolumes. Results to date indicate that this approach is dosimetrically feasible and deliverable, while preliminary outcomes find it to be well tolerated acutely. Additional accrual and follow up for this ongoing trial will be required to assess longer term conventional and patient reported toxicity outcomes as well as tumor control.

Survival Outcome after Stereotactic Body Radiation Therapy and Surgery for Early Stage Non-Small Cell Lung Cancer: A Meta-Analysis

ABSTRACTObjective: Treatment modalities in medically compromised patients with early-stage non-small cell lung cancer (NSCLC) are controversial. Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has been increasingly recognized as a favorable alternative to surgical resection for early-stage NSCLC. Many retrospective analyses compared the efficacy of stereotactic body radiotherapy (SBRT) with surgery for early-stage non-small cell lung cancer (NSCLC). However, the efficacy between SBRT and surgery regimens for patients with early-stage NSCLC remains unclear. This study aimed to investigate the efficacy between SBRT and surgery. Methods: Publications on comparison SBRT with Surgery in treatment of early stage non-small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Retrospective trials analyzed the summary hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), and distant control survival (DC) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. Result: A systematic literature search was conducted including14 studies. In this meta-analysis, patients with SBRT achieved inferior OS, DFS, LC, RC, LRC and DC, compared with surgery. Conclusion: In this study we found more favorable outcomes with stage I NSCLC treated with SBRT. The surgery had no obvious advantages in this meta-analysis. Although surgery has become the recommended treatment at present, SBRT has potential to be an alternative treatment as a novel non-invasive radiation therapy modality in patients with stage I-II NSCLC.

Hypo-fractionated SBRT for localized prostate cancer: a German bi-center single treatment group feasibility trial

BackgroundFor prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany.Methods/designThis German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3–5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients.DiscussionThe HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials.Study statusThe study is ongoing and currently recruiting patients.Trial registrationRegistration number: NCT02635256 (clinicaltrials.gov). Registered 8 December 2015.

Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer

Background: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for unresectable pancreatic cancer, and is postulated to be more effective and less toxic than conventionally fractionated intensity modulated radiation therapy (IMRT).Material and methods: We retrospectively reviewed unresectable stage I–III pancreatic adenocarcinoma treated from 2008 to 2016 at our institution with SBRT (five fractions, 30–33 Gy) or IMRT (25–28 fractions, 45–56 Gy with concurrent chemotherapy). Groups were compared with respect to overall survival (OS), local and distant failure, and toxicity. Log-rank test and Cox proportional hazards regression model, and competing risks methods were used for univariate and multivariate analysis.Results: SBRT patients (n = 44) were older than IMRT (n = 226) patients; otherwise there was no significant difference in baseline characteristics. There was no significant difference in OS or local or distant failure. There was no significant difference in rates of subsequent resection (IMRT =17%, SBRT =7%, p = .11). IMRT was associated with more acute grade 2+ gastrointestinal toxicity, grade 2+ fatigue, and grade 3+ hematologic toxicity (p = .008, p < .0001, p = .001, respectively).Conclusions: In this analysis, SBRT achieves similar disease control outcomes as IMRT, with less acute toxicity. This suggests SBRT is an attractive technique for pancreatic radiotherapy because of improved convenience and tolerability with equivalent efficacy. However, the lack of observed advantages in disease control with this moderate-dose SBRT regimen may suggest a role for increasing SBRT dose, if this can be accomplished without significant increase in toxicity.

A Phase 2 Randomized Study of 2 Stereotactic Body Radiation Therapy Regimens for Medically Inoperable Patients With Node-Negative, Peripheral Non–Small Cell Lung Cancer

A Phase 2 Randomized Study of 2 Stereotactic Body Radiation Therapy Regimens for Medically Inoperable Patients With Node-Negative, Peripheral Non–Small Cell Lung Cancer

Stereotactic body radiotherapy for high-risk prostate cancer (5 treatment days): Toxicity results of a phase II trial.

46 Background: Stereotactic body radiotherapy (SBRT) for high-risk prostate cancer (CaP) remains investigational not only due to undetermined efficacy but also due to concerns for the potential toxicity when the treatment volumes extend beyond the prostate gland itself. Methods: Men with high-risk CaP, as defined by Gleason score &gt; = 8, clinical stage T3-T4, or initial PSA &gt; = 20 ng/mL, were enrolled on a multicenter phase II trial and were treated with 40 Gy to prostate and 25 Gy to pelvic nodes in 5 fractions and 9 months neoadjuvant and concurrent ADT. Treatment with ADT and pelvic nodal radiation was at the discretion of the treating physician. Follow-up assessment was with CTCAE v4 and Expanded Prostate Composite Index (EPIC). Results: A total of 61 patients were treated, with a median follow-up of 12 months. Forty (64.4%) received ADT and 23 (37.1%) received nodal radiation. The median initial PSA was 8.1 ng/mL and 8% of patients had clinical T3-T4 disease; 45.9% and 39.3% had Gleason score 8 and 9-10 disease, respectively. No grade 3 or higher toxicities were seen. Rates of acute and late grade 2 genitourinary toxicities were 13.1% and 6.7%, respectively; rates of acute and late grade 2 gastrointestinal toxicities were 6.6% and 8.2%, respectively. Mean changes in EPIC urinary incontinence, urinary obstructive, and bowel domain scores at 4 months were -0.35, +1.44, and -2.38, respectively. For the 32 patients with evaluable EPIC scores at 12 months, mean changes on EPIC urinary incontinence, urinary obstructive, and bowel domain scores at 4 months were -1.04, -2.70, and -6.76, respectively. The percentages of patients with minimum clinically important change in EPIC urinary incontinence, urinary obstructive, and bowel domain scores at 4 months were 11.9%, 21.4%, and 26.2%, respectively. At 12 months, these figures were 13.9%, 30.6% and 27.8%. The receipt of ADT and/or nodal radiation had no significant effect on either physician- or patient-reported toxicity profiles (p &gt; 0.1, Fisher’s exact test). Conclusions: SBRT regimens can be safely utilized to deliver the entire course in 5 treatment days in patients with high-risk localized CaP. Clinical trial information: NCT02296229.

Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer.

353 Background: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for unresectable pancreatic cancer, and may be more effective and less toxic than intensity modulated radiation therapy (IMRT). Methods: We retrospectively reviewed unresectable stage I-III pancreatic adenocarcinoma treated with SBRT (5 fractions, 30-33Gy) or IMRT (25-28 fractions, 45-56Gy with concurrent chemotherapy) between 2008-2016 at our institution. The groups were compared with respect to overall survival (OS), local failure (LF), distant failure (DF), any failure (AF), proportion of patients becoming resectable, and incidence of acute toxicity. Competing risks methods were used for univariate (UVA) and multivariate analysis (MVA) for LF, DF and AF. All endpoints were calculated from end of RT. Results: Median follow-up for surviving patients was 12.9 months. 44 patients received SBRT and 226 patients received IMRT. Patients who received SBRT were older (45% vs 29% &gt; 70 years old, p = 0.05). Otherwise there was no significant difference in baseline characteristics, including stage and duration of induction chemotherapy. On MVA, there was no significant difference in OS, LF, DF, or AF between IMRT and SBRT (p = 0.73, 0.81, 0.44, and 0.39 respectively). Median OS was 15.7 months, and the 1-year rate of LF was 34.4% for SBRT and 30.2% for IMRT. Response to induction chemotherapy was associated with longer OS (p = 0.03). There was no significant difference in the proportion of patients who were subsequently resected between IMRT (17%) and SBRT (7%; p = 0.11). Significantly more IMRT patients experienced acute G2+ GI toxicity (24% vs. 7%, p = 0.008), G2+ fatigue (42% vs. 7%, p &lt; 0.0001), and G3+ hematologic toxicity (26% vs. 5%, p = 0.001) compared to SBRT. Conclusions: SBRT achieves similar disease control outcomes as IMRT, and is associated with less acute toxicity. This data suggests SBRT is an attractive technique for pancreatic radiotherapy because of improved convenience and tolerability with equivalent efficacy. However, the lack of observed advantages in disease control with this moderate-dose SBRT regimen suggests a role for increasing SBRT dose, if this can be accomplished without significant increase in toxicity.

Reirradiation with stereotactic body radiation therapy after prior conventional fractionation radiation for locally recurrent pancreatic adenocarcinoma

PurposeLocally recurrent pancreatic cancer after prior radiotherapy is a therapeutic challenge with limited treatment options. This study examines the safety and efficacy of stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma after prior conventional fractionation radiotherapy (CRT). Methods and materialsOutcomes from all patients treated with SBRT for locally recurrent pancreatic adenocarcinoma after prior CRT at our institution were reviewed. A total of 23 patients were identified. Prior CRT median dose was 50.4 Gy (range, 30-60 Gy). Twelve patients (52%) had previously undergone surgery and received CRT as neo- or adjuvant treatment. Nine patients (39.1%) were reirradiated with SBRT with a dose of 25 Gy in a single fraction, and 14 patients (60.8%) received a 5-fraction SBRT schedule with a median dose of 25 Gy (range, 20-33 Gy) in 5 fractions (1-5 fractions). ResultsMedian follow-up time was 28 months (range, 9-77 months). The median planning target volume was 46 cm3 (range, 14-89 cm3). Median overall survival from diagnosis and from reirradiation were 27.5 months (range, 10-77 months) and 8.5 months (range, 1 month to not reached) respectively. The cumulative incidence of local failures at the last follow-up was 19%. For the 4 patients who presented with local failure, one was treated with a single fraction of 25 Gy, and the other 3 were treated with 25 Gy in 5 fractions. Three patients presented regional failure, with a cumulative incidence of 14%, all with concurrent distant progression. The cumulative incidence of distant progression was 64% at last follow-up. After reirradiation, 6 patients (26.1%) developed a grade 2 or 3 gastrointestinal toxicity, 4 of them occurring among patients treated with a single-fraction SBRT regimen. ConclusionsOur report shows that SBRT for reirradiation of locally recurrent pancreas adenocarcinoma is a feasible option with good local control and acceptable toxicity rates, especially with a multifraction schedule.

Patients With Oligometastatic Disease Limited to the Chest Are Optimal Candidates for Lung Stereotactic Body Radiotherapy

SESSION TITLE: Advancements in Lung Cancer Diagnostics and Treatment SESSION TYPE: Original Investigation Slide PRESENTED ON: Wednesday, October 26, 2016 at 08:45 AM - 10:00 AM PURPOSE: The aim of this study was to identify patients with pulmonary metastases who would be most likely to benefit from lung stereotactic body radiotherapy (SBRT). METHODS: After institutional review board approval, we retrospectively identified 92 patients with 111 pulmonary metastases from any primary site treated with SBRT at our institution between 2008 and 2015. Gross tumor volume (GTV) was non-uniformly expanded to create an internal target volume (ITV) to encompass tumor motion. A 5 mm uniform expansion of the ITV was applied to create the planning target volume (PTV). Cone beam CT was used for daily image-guidance. The most common SBRT regimen was 48 Gy/4 fractions for peripheral lesions, and 50 Gy/5 fractions for central lesions. Toxicities were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Survival curves were calculated from the time of SBRT using the Kaplan-Meier method. RESULTS: The median follow-up was 17 months (range: 3-74 months). Median PTV was 29 cm3. There were 51 men and 41 women included, with a median age of 70 years (range: 37-90). The most common primary tumors were lung (n=30), colorectal (n=14), melanoma (n=13), and head & neck (n=12). 44 patients had solitary lung lesions, 31 patients had >1 lung lesions with no extrathoracic disease, and 17 patients had additional sites of oligometastatic disease outside of the thorax. Median time to next treatment event was 18 months in patients with metastatic disease confined to the lungs versus 5 months with extrathoracic oligometastatic disease present (p=0.01). For patients with a solitary lesion, time to next treatment was 28 months. The median, 1, 2, and 3 year survival (OS) was 33 months, 79%, 68%, and 48%, respectively. There was no significant difference in OS among patients with metastatic disease confined to the lung versus patients with additional extrathoracic oligometastatic disease (OS 37 vs 25 months, respectively; p=0.093). Primary disease site was not associated with disease outcome. Local failure occurred in 8/111 lesions for a 2-year local control rate of 85%. Grade 3 pneumonitis was reported in two (2%) of patients. There was no grade 4-5 toxicity. CONCLUSIONS: This is one of the largest experiences with lung SBRT for metastatic disease. Lung SBRT provides excellent local control with acceptable toxicity. Properly selected oligometastatic patients have excellent long-term survival with the addition of SBRT into their management. Patients with oligometastatic disease confined to the lung do especially well, while patients with extrathoracic disease progress rapidly. These findings provide guidance for optimal patient selection and counseling. CLINICAL IMPLICATIONS: Patients with limited oligometastatic disease confined to the chest are the most likely to benefit from stereotactic body radiotherapy. Time to next treatment is a clinically meaningful endpoint and helps guide decision making in patients with limited oligometastatic lung disease. DISCLOSURE: The following authors have nothing to disclose: Rebecca Fega, Uma Goyal, Helen Ross, Dawn Jaroszewski, Harshita Paripati, Kosiorek Heidi, Thomas Daniels, William Rule, Steven Schild, Sujay Vora, Jonathan Ashman No Product/Research Disclosure Information

The significance of PTV dose coverage on cancer control outcomes in early stage non-small cell lung cancer patients treated with highly ablative stereotactic body radiation therapy.

We evaluated whether patients with early-stage non-small-cell lung cancers (NSCLCs) treated with stereotactic body radiation therapy (SBRT) without full prescription dose coverage of the planning target volume (PTV) had inferior outcomes. The SBRT regimen was 54 Gy in three fractions. Dosimetric constraints were as per the Radiation Therapy Oncology Group 0236 guidelines. All patients underwent four-dimensional CT (4D-CT) simulation. The internal target volume (ITV) was defined using 4D-CT, and the PTV was defined as a 6-mm longitudinal and a 3-mm axial expansion from the ITV. If normal tissue constraints were beyond tolerance, ITV-based dosing was employed where priority was made for full ITV coverage at the expense of PTV coverage. Patients with and without full PTV dose coverage were compared, and control rates were estimated using Kaplan-Meier analysis. 120 NSCLC cases were evaluated with 81% having adequate PTV dose coverage. ITV and PTV were significantly larger in the cohort with inadequate PTV dose coverage (p = 0.0085 and p = 0.0038, respectively), and the mean ITV and PTV doses were higher in patients with adequate PTV dose coverage (p = 0.002 and p < 0.0001, respectively). The 3-year local control rate was 100% for both cohorts. There was no difference in 3-year regional control (p = 0.36), disease-specific survival (p = 0.79) or overall survival (p = 0.73). When delivering a highly ablative SBRT regimen for early-stage NSCLC, full-dose coverage of the ITV is sufficient for local control. Our data are among the first to evaluate the utility of PTV margins in a highly ablative SBRT regimen and suggest that when dosing constraints cannot be met, full tumouricidal dose coverage of the ITV is sufficient for local control.

Local control rates of metastatic renal cell carcinoma (RCC) to the bone using stereotactic body radiation therapy: Is RCC truly radioresistant?

PurposeWe report the radiographic and clinical response rate of stereotactic body radiation therapy (SBRT) compared with conventional fractionated external beam radiation therapy (CF-EBRT) for renal cell carcinoma (RCC) bone lesions treated at our institution. Methods and materialsForty-six consecutive patients were included in the study, with 95 total lesions treated (50 SBRT, 45 CF-EBRT). We included patients who had histologic confirmation of primary RCC and radiographic evidence of metastatic bone lesions. The most common SBRT regimen used was 27 Gy in 3 fractions. ResultsMedian follow-up was 10 months (range, 1-64 months). Median time to symptom control between SBRT and CF-EBRT were 2 (range, 0-6 weeks) and 4 weeks (range, 0-7 weeks), respectively. Symptom control rates with SBRT and CF-EBRT were significantly different (P = .020) with control rates at 10, 12, and 24 months of 74.9% versus 44.1%, 74.9% versus 39.9%, and 74.9% versus 35.7%, respectively. The median time to radiographic failure and unadjusted pain progression was 7 months in both groups. When controlling for gross tumor volume, dose per fraction, smoking, and the use of systemic therapy, biologically effective dose ≥80 Gy was significant for clinical response (hazard ratio [HR], 0.204; 95% confidence interval [CI], 0.043-0.963; P = .046) and radiographic (HR, 0.075; 95% CI, 0.013-0.430; P = .004). When controlling for gross tumor volume and total dose, biologically effective dose ≥80 Gy was again predictive of clinical local control (HR, 0.140; 95% CI, 0.025-0.787; P = .026). Toxicity rates were low and equivalent in both groups, with no grade 4 or 5 toxicity reported. ConclusionsSBRT is both safe and effective for treating RCC bone metastases, with rapid improvement in symptoms after treatment and more durable clinical and radiographic response rate. Future prospective trials are needed to further define efficacy and toxicity of treatment, especially in the setting of targeted agents.

Pelvic Nodal Dosing With Registration to the Prostate: Implications for High-Risk Prostate Cancer Patients Receiving Stereotactic Body Radiation Therapy

To determine whether image guidance with rigid registration (RR) to intraprostatic markers (IPMs) yields acceptable coverage of the pelvic lymph nodes in the context of a stereotactic body radiation therapy (SBRT) regimen. Four to seven kilovoltage cone-beam CTs (CBCTs) from 12 patients with high-risk prostate cancer were analyzed, allowing approximation of an SBRT regimen. The nodal clinical target volume (CTV(N)) and bladder were contoured on all kilovoltage CBCTs. The V100 CTV(N), expressed as a ratio to the same parameter on the initial plan, and the magnitude of translational shift between RR to the IPMs versus RR to the pelvic bones, were computed. The ability of a multimodality bladder filling protocol to minimize bladder height variation was assessed in a separate cohort of 4 patients. Sixty-five CBCTs were assessed. The average V100 CTV(N) was 92.6%, but for a subset of 3 patients the average was 80.0%, compared with 97.8% for the others (P<.0001). The average overall and superior-inferior axis magnitudes of the bony-to-fiducial translations were significantly larger in the subgroup with suboptimal nodal coverage (8.1 vs 3.9 mm and 5.8 vs 2.4 mm, respectively; P<.0001). Relative bladder height changes were also significantly larger in the subgroup with suboptimal nodal coverage (42.9% vs 18.5%; P<.05). Use of a multimodality bladder-filling protocol minimized bladder height variation (P<.001). A majority of patients had acceptable nodal coverage after RR to IPMs, even when approximating SBRT. However, a subset of patients had suboptimal nodal coverage. These patients had large bony-to-fiducial translations and large variations in bladder height. Nodal coverage should be excellent if the superior-inferior axis bony-to-fiducial translation and the relative bladder height change (both easily measured on CBCT) are kept to a minimum. Implementation of a strict bladder filling protocol may achieve this goal.

Incidental Mediastinal Dose Does Not Explain Low Mediastinal Node Recurrence Rates in Patients With Early-Stage NSCLC Treated With Stereotactic Body Radiotherapy

BackgroundPatients with stage I non–small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) do not undergo a staging mediastinoscopy, yet reported mediastinal recurrence rates appear lower than in patients undergoing surgical resection. We determined incidental SBRT doses to assess whether this could account for the low rates of recurrence. Patients and MethodsBetween March 2009 and September 2012, we reviewed cases of patients with inoperable lung tumors (n = 136) treated with SBRT at our institution. The SBRT regimen was 54 Gy in 3 fractions with positron emission tomography/computed tomography (PET/CT) staging. Incidental doses to the mediastinal lymph node stations (MLNSs), primary tumor control, locoregional (LR), distant control (DC), and overall survival (OS) rates were determined. ResultsForty-six patients with stage I NSCLC met the inclusion criteria. The calculated median incidental SBRT dose to all MLNSs was < 5 Gy for the majority of patients (75%). At a median follow-up of 16.8 months (0.6-38.9 months), the 1- and 2-year primary tumor control, LR, OS, and DC rates were 100% and 95.5%, 97.4% and 81.7%, 88.1% and 81%, and 96.9% and 86.9%, respectively. Only 2 patients (4.9%) had mediastinal recurrence, with incidental SBRT doses to MLNSs that were similar to the rest of patients (P > .05). ConclusionLow mediastinal recurrence rates in stage I NSCLC treated with SBRT validates the omission of staging mediastinoscopy. The low incidental dose to MLNSs does not seem to explain the low mediastinal recurrence in the majority of patients. Our findings also confirm that prophylactic radiation to the mediastinum is not necessary and support the hypothesis that local ablation of the primary lesion could indirectly affect subclinical nodal disease through unknown mechanisms.