A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer.
ABSTRACT: BACKGROUND:Standard therapy for stage III non-small cell lung cancer with chemotherapy and conventional radiation has suboptimal outcomes. We hypothesized that a combination of surgery followed by stereotactic body radiation therapy (SBRT) would be a safe alternative. METHODS:Patients with stage IIIA (multistation N2) or IIIB non-small cell lung cancer were enrolled from March 2013 to December 2015. The protocol included transcervical extended mediastinal lymphadenectomy (TEMLA) followed by surgical resection, 10 Gy SBRT directed to the involved mediastinum/hilar stations and/or positive surgical margins, and adjuvant systemic therapy. Patients not suitable for anatomic lung resection were treated with 30 Gy to the primary tumor. The primary efficacy end-point was the proportion of patients with grade 3 or higher adverse events (AE) or toxicities. RESULTS:Of 10 patients, 7 patients underwent neoadjuvant chemotherapy. All patients had TEMLA. Nine of 10 patients underwent surgical resection. The remaining patient had an unresectable tumor and received 30 Gy SBRT to the primary lesion. All patients had post-operative SBRT. Median follow-up was 18 months. There were no perioperative mortalities. Six patients had any grade 3 AEs with no grade 4-5 AEs. Of these, 4 were not attributable to radiation. Pulmonary-related grade 3 AEs were experienced by 2 patients. There were no failures within the 10 Gy volume. Overall survival and progression-free survival rates at 2 years were 68% (90% CI 36-86) and 40% (90% CI 16-63), respectively. CONCLUSIONS:In carefully selected patients with locally advanced non-small cell lung cancer, combining surgery with SBRT was well tolerated with no local failure. TRIAL REGISTRATION:ClinicalTrials.gov identifying number NCT01781741 . Registered February 1, 2013.
Project description:<h4>Purpose</h4>Patients with pancreatic cancer often receive radiation therapy before undergoing surgical resection. We compared the clinical outcomes differences between stereotactic body radiation therapy (SBRT) and 3-dimensional (3D)/intensity-modulated radiation therapy (IMRT).<h4>Methods and materials</h4>We retrospectively collected data from the University of Texas MD Anderson Cancer Center. Patients with borderline resectable/potentially resectable or locally advanced pancreatic cancer receiving neoadjuvant SBRT (median, 36.0 Gy/5fx), 3D conformal radiation (median, 50.4 Gy/28 fx) or IMRT (median, 50.4 Gy/28 fx) were included. Overall survival (OS) and progression-free survival were analyzed using Cox regression.<h4>Results</h4>In total, 104 patients were included in our study. Fifty-seven patients (54.8%) were treated with SBRT, and 47 patients (45.2%) were treated with 3D/IMRT. Patients in the SBRT group were slightly older (median age: 70.3 vs 62.7 in the 3D/IMRT group). Both groups had similar proportions of patients with locally advanced pancreatic cancer (SBRT: 30, 52.6%; 3D/IMRT: 24, 51.1%). All patients were treated with chemotherapy. Patients in the SBRT group underwent more surgical resection compared with the 3D/IMRT group (38.6% vs 23.4%, respectively). At a median follow-up of 22 months, a total of 60 patients (57.7%) died: 25 (25/57, 43.9%) in the SBRT group, and 35 (35/47, 74.5%) in the 3D/IMRT group. Median OS was slightly higher in the SBRT group (29.6 months vs 24.1 months in the 3D/IMRT group). On multivariable Cox regression, the choice of radiation therapy technique was not associated with differences in OS (adjusted hazard ratios [aHR] = 0.5; 95% confidence interval [CI], 0.2%-1.3%, <i>P</i> = .18). Moreover, patients that underwent surgical resection had better OS (aHR = 0.3, 95% CI, 0.1%-0.8%, <i>P</i> = .01). Furthermore, progression-free survival was also similar between patients treated with SBRT and those treated with 3D/IMRT (aHR = 0.9, 95% CI, 0.5%-1.8%, <i>P</i> = .81).<h4>Conclusions</h4>SBRT was associated with similar clinical outcomes compared with conventional radiation techniques, despite being delivered over a shorter period of time which would spare patients prolonged treatment burden. Future prospective data are still needed to better assess the role of SBRT in patients with pancreatic cancer.
Project description:Introduction:Pancreatic adenocarcinoma is an aggressive malignancy that has consistently demonstrated poor outcomes despite aggressive treatments. Despite multimodal treatment, local disease progression and local recurrence are common. Management of recurrent or progressive pancreatic carcinomas proves a further challenge. In patients previously treated with radiation therapy, stereotactic body radiation therapy (SBRT) is a promising modality capable of delivering high dose to the tumor while limiting dose to critical structures. We aimed to determine the feasibility and tolerability of SBRT for recurrent or local pancreatic cancer in patients previously treated with external beam radiation therapy (EBRT). Materials and methods:Patients treated with EBRT who developed recurrent or local pancreatic ductal adenocarcinoma treated with SBRT reirradiation at our institution, from 2004 to 2014 were reviewed. Our primary endpoints included overall survival (OS), local control, regional control, and late grade 3+ radiation toxicity. Endpoints were analyzed with the Kaplan-Meier method. The association of these survival endpoints with risk factors was studied with univariate Cox proportional hazards models. Results:We identified 38 patients with recurrent/progressive pancreatic cancer treated with SBRT following prior radiation therapy. Prior radiation was delivered to a median dose of 50.4?Gy in 28 fractions. SBRT was delivered to a median dose of 24.5?Gy in 1-3 fractions. Surgical resection was performed on 55.3% of all patients. Within a median follow-up of 24.4?months (inter-quartile range, 14.9-32.7?months), the median OS from diagnosis for the entire cohort was 26.6?months (95% CI: 20.3-29.8) with 2-year OS of 53.0%. Median survival from SBRT was 9.7?months (95% CI, 5.5-13.8). The 2-year freedom from local progression and regional progression was 58 and 82%, respectively. For the entire cohort, 18.4 and 10.5% experienced late grade 2+ and grade 3+ toxicity, respectively. Conclusion:This single institution retrospective review identified SBRT reirradiation to be a feasible and tolerable treatment strategy for patients with previous locally progressive or recurrent pancreatic adenocarcinoma.
Project description:BACKGROUND:While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. METHODS:This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. RESULTS:We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. CONCLUSIONS:These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.
Project description:Introduction:Stereotactic Body Radiation Therapy (SBRT) is a treatment option for patients with liver metastases. This study evaluated the impact of high versus low dose image-guided SBRT of hepatic metastases. Methods and materials:This is a single-center retrospective study of patients with liver metastases treated with SBRT. For analyses, patients were divided into two groups: ?100 Gy and >100 Gy near-minimum Biological Effective Doses (BED98%). The main outcomes were local control (LC), toxicity and overall survival (OS). Cox regression analyses were performed to determine prognostic variables on LC and OS. Results:Ninety patients with 97 liver metastases (77% colorectal) were included. Median follow-up was 28.6 months. The two-year LC rates in the ?100 Gy and >100 Gy BED98% group were 60% (CI: 41-80%) and 90% (CI: 80-100%), respectively (p = 0.004). Grade 3 toxicity occurred in 7% vs 2% in the ?100 Gy and >100 Gy group (p = 0.23). Two-year OS rates in the ?100 Gy and >100 Gy group were 48% (CI: 32-65%) and 85% (CI: 73-97%), respectively (p = 0.007). In multivariable Cox regression analyses, group dose and tumor volume were significantly correlated with LC (HR: 3.61; p = 0.017 and HR: 1.01; p = 0.005) and OS (HR: 2.38; p = 0.005 and HR: 1.01; p = <0.0001). Conclusion:High dose SBRT provides significantly better local control and overall survival than low dose SBRT without increasing toxicity. When surgical resection is not feasible, high dose SBRT provides an effective and safe treatment for liver metastases.
Project description:Importance:Stereotactic body radiation therapy (SBRT) has become a standard treatment for patients with medically inoperable early-stage lung cancer. However, its effectiveness in patients medically suitable for surgery is unclear. Objective:To evaluate whether noninvasive SBRT delivered on an outpatient basis can safely eradicate lung cancer and cure selected patients with operable lung cancer, obviating the need for surgical resection. Design, Setting, and Participants:Single-arm phase 2 NRG Oncology Radiation Therapy Oncology Group 0618 study enrolled patients from December 2007 to May 2010 with median follow-up of 48.1 months (range, 15.4-73.7 months). The setting was a multicenter North American academic and community practice cancer center consortium. Patients had operable biopsy-proven peripheral T1 to T2, N0, M0 non-small cell tumors no more than 5 cm in diameter, forced expiratory volume in 1 second (FEV1) and diffusing capacity greater than 35% predicted, arterial oxygen tension greater than 60 mm Hg, arterial carbon dioxide tension less than 50 mm Hg, and no severe medical problems. The data analysis was performed in October 2014. Interventions:The SBRT prescription dose was 54 Gy delivered in 3 18-Gy fractions over 1.5 to 2.0 weeks. Main Outcomes and Measures:Primary end point was primary tumor control, with survival, adverse events, and the incidence and outcome of surgical salvage as secondary end points. Results:Of 33 patients accrued, 26 were evaluable (23 T1 and 3 T2 tumors; 15 [58%] male; median age, 72.5 [range, 54-88] years). Median FEV1 and diffusing capacity of the lung for carbon monoxide at enrollment were 72.5% (range, 38%-136%) and 68% (range, 22%-96%) of predicted, respectively. Only 1 patient had a primary tumor recurrence. Involved lobe failure, the other component defining local failure, did not occur in any patient, so the estimated 4-year primary tumor control and local control rate were both 96% (95% CI, 83%-100%). As per protocol guidelines, the single patient with local recurrence underwent salvage lobectomy 1.2 years after SBRT, complicated by a grade 4 cardiac arrhythmia. The 4-year estimates of disease-free and overall survival were 57% (95% CI, 36%-74%) and 56% (95% CI, 35%-73%), respectively. Median overall survival was 55.2 months (95% CI, 37.7 months to not reached). Protocol-specified treatment-related grade 3, 4, and 5 adverse events were reported in 2 (8%; 95% CI, 0.1%-25%), 0, and 0 patients, respectively. Conclusions and Relevance:As given, SBRT appears to be associated with a high rate of primary tumor control, low treatment-related morbidity, and infrequent need for surgical salvage in patients with operable early-stage lung cancer. Trial Registration:ClinicalTrials.gov Identifier: NCT00551369.
Project description:Introduction: Pancreatic ductal adenocarcinoma (PDAC) commonly presents later in life with a median age at diagnosis of 70 years. Unfortunately, elderly patients are significantly underrepresented in clinical trials. Stereotactic body radiation therapy (SBRT) is a promising treatment modality in this population as it has demonstrated excellent local control with minimal toxicity. We aimed to determine prognostic factors associated with outcomes in elderly patients treated with SBRT. Materials and Methods: Elderly patients older than 70 treated with SBRT for PDAC at our institution, from 2004 to 2014 were included. Our primary endpoints included overall survival (OS) and local-progression-free survival (LPFS). Secondary endpoints included regional-progression-free survival (RPFS), distant-progression-free-survival (DPFS) and radiation toxicity. Endpoints were analyzed with the Kaplan-Meier method. The association of these survival endpoints with risk factors was studied with Cox proportional hazards models. Results: We identified 145 patients with 146 lesions of pancreatic adenocarcinoma with a median age at diagnosis of 79 (range, 70.1-90.3). SBRT was delivered to a median dose of 36 Gy (IQR 24-36). Surgical resection was performed on 33.8% of the total patients. Median follow-up was 12.3 months (IQR 6.0-23.3 months) and the median survival for the entire cohort 14.0 months with a 2-year OS of 27%. Multivariate analysis (MVA) demonstrated surgery [p ? 0.0001, HR 0.29 (95% CI, 0.16-0.51)] and post-SBRT CA19-9 [p = 0.009, HR 1.0004 (95% CI, 1.0002-1.0005)] significantly associated with overall survival. Recurrent lesions [p = 0.0069, HR 5.1 (95% CI, 1.56-16.64)] and post-SBRT CA19-9 levels [p = 0.0107, HR 1.0005 (95% CI, 1.0001-1.0008)] were significantly associated with local control on MVA. For the entire cohort, 4.1% experienced acute grade 2+ toxicity, and 2% experienced late grade 2+ toxicity at 2 years. Conclusion: This review demonstrates prognostic factors in elderly patients with PDAC treated with SBRT. We identified surgical resection and post-SBRT CA 19-9 as predictive of overall survival in this population. Additionally, we show low acute and late toxicity following SBRT in elderly patients.
Project description:Background:Stereotactic body radiotherapy (SBRT) is a treatment option for stage I non-small cell lung cancer (NSCLC), providing a potentially curative therapy for patients who are nonsurgical candidates. This study describes the adoption of SBRT vs other treatment options across the United States, as well as commonly used dose-fractionation regimens. Methods:We analyzed patients in the National Cancer Data Base. A total of 107?233 stage IA NSCLC patients diagnosed from 2008 to 2013 were included. We described the proportions of patients who received different surgical and radiation treatment options by year. A multivariable model was constructed to assess factors associated with patients receiving SBRT. In patients who received SBRT, we described the proportion of patients who received common dose/fractionation regimens. Results:Use of SBRT increased from 6.7% to 16.3% from 2008 to 2013, with a corresponding decrease in lobectomy/pneumonectomy (49.5% to 43.7%). The rates of wedge resection, conventional radiotherapy, and no treatment remained relatively constant. Adoption of SBRT was lowest in small community centers (8.6% of patients by 2013). On multivariable analysis, older age and treatment at larger centers were associated with higher SBRT receipt, and black race and higher comorbidity were associated with lower SBRT receipt. There was statistically significant geographic variation. Common SBRT schemes were 10?Gy × 5 (19%), 18-20?Gy × 3 (31%), and 12?Gy × 4 (16%). Conclusions:SBRT adoption has been modest over time and has not substantially replaced less curative treatments. Lack of access to this technology in smaller cancer centers may have partly contributed to the slow adoption.
Project description:After Hellman and Weichselbaum defined “Oligometastasis” in 1995, several local therapies for lung oligometastases including surgical resection and external body radiation therapy were reported that improved local control (LC) and progression-free survival, overall survival, and quality of life. This suggests that oligometastases is a potentially curable state. Modern advances in radiation therapy such as stereotactic body radiation therapy (SBRT) in which high dose coverage of target lesion without exposure of normal organ is possible, and are widely used to treat solitary or a limited number of primary lung cancer and metastases. Several reports showed that SBRT was a useful treatment method for lung oligometastases, and the LC rate of SBRT was 80–90% in 2 years and less invasive than surgical resection. SBRT is a safe and effective especially for small and peripheral lung metastases. However, if the metastatic lesion is big or centrally located, careful treatment is necessary to prevent radiation pneumonitis. After SBRT, it is sometimes difficult to differentiate local recurrence and pulmonary injury, especially in the early phase. However, it is important to detect local recurrence especially in patients who require further local therapy such as surgical resection and re-irradiation or systemic therapy. The diagnosis can be improved by determining the natural course after SBRT and local recurrence with computed tomography imaging and 18F-fluorodeoxyglucose positron emission tomography, respectively. Moreover, radiation therapy may have both local and systemic effects that are related to the enhancement of immune-response after radiation. Currently, several trials evaluating the benefits of SBRT for oligometastatic breast cancer are underway. However, the adaption of SBRT for lung metastases including other treatment strategies should be carefully discussed by the radiation oncologist and a multi-disciplinary team comprising a breast surgeon, medical oncologist, diagnostic radiologist, and radiation oncologist, among others.
Project description:<h4>Background</h4>The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes.<h4>Methods/design</h4>In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a "total neoadjuvant" therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30?Gy with simultaneous integrated boost of 50?Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10?Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting.<h4>Trial registration</h4>NCT04090463 at clinicaltrials.gov.
Project description:Purpose: To report a case series of 3 pediatric patients treated with Stereotactic Body Radiation Therapy (SBRT) for lung metastases. Patients and methods: Three patients (ages 9, 11, and 21) received SBRT for rhabdoid tumor, Ewing sarcoma, and Wilms tumor histologies, respectively. SBRT doses were 37.5-50 Gy in 3-5 fractions treating twelve lesions. Results: Three patients (ages 9, 11, and 21) received photon SBRT for pulmonary metastases. The patients were as follows: 1) 21-year-old male with favorable histology Wilms tumor and 1 lesion treated, 2) 11-year-old female with Ewing sarcoma and 1 lesion treated for relapse after previous whole lung radiation (15 Gy), and 3) 9-year-old female with rhabdoid tumor of the left thigh with 10 lesions treated over a two-year period. Median dose delivered was 40 Gy (range, 37.5-50 Gy), delivered in a median of 4 fractions (range, 4-5) of a median of 10 Gy per fraction (range, 9.4-10 Gy). Within a minimum follow-up of 1.9 years (range 1.9-4 years), local control for all 13 treated metastases is 100% without any observed acute toxicities. One possible late toxicity (grade 2 rib fracture) developed 1.3 years following SBRT for treatment of a peripheral lesion (rhabdoid tumor) in an area of disease progression and was managed conservatively. Two patients are surviving 2.9 years (Wilms tumor) and 1.9 years (Ewing sarcoma) after SBRT, and one (rhabdoid tumor) expired 2 years after her final course (4 years after initial SBRT). Two patients (rhabdoid tumor and Ewing sarcoma) suffered disease progression outside of the treated lesions and one patient (Wilms tumor) is without evidence of disease and has not required whole lung irradiation or further systemic therapy. Conclusion: SBRT appears effective and well tolerated for pediatric lung metastases, however further studies are warranted.