Dosimetric predictors of esophageal toxicity after stereotactic body radiotherapy for central lung tumors.
ABSTRACT: Stereotactic body radiotherapy (SBRT) to central lung tumors can cause esophageal toxicity, but little is known about the incidence or risk factors. We reviewed central lung SBRT patients to identify dosimetric factors predictive of esophageal toxicity.We assessed esophageal toxicity in 125 SBRT patients. Using biological equivalent doses with ?/?=10 Gy (BED??), dose-volume histogram variables for the esophagus (Dv and Vd) were assessed for correlation with grade ?2 acute toxicity.Incidence of grade ?2 acute toxicity was 12% (n=15). Highly significant logistic models were generated for D?cc and Dmax (p<0.001). To keep the complication rate <20%, the model requires that D?cc?26.3 BED??. At 2 years, the probability of complication with BED??D?cc>14.4 Gy was 24%, compared to 1.6% if ?14.4 Gy.This novel analysis provides guidelines to predict acute esophageal toxicity in lung SBRT. Dose to the hottest 5cc and Dmax of the esophagus were the best predictors of toxicity. Converting the BED?? limits to physical doses, D?cc to the esophagus should be kept less than 16.8, 18.1 and 19.0 Gy for 3, 4, and 5 fractions, respectively, to keep the acute toxicity rate <20%.
Project description:Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters.We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity.One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ? grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ? grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ?80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT ("no-fly-zone" [NFZ]) correlated with pulmonary toxicity ?grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum.Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.
Project description:BACKGROUND:This study evaluates the outcomes and toxicity of stereotactic body radiation therapy (SBRT) in ovarian cancer. METHODS:This retrospective analysis considered all patients treated with SBRT from 2009 to 2018 with a primary ovarian tumor. Follow-up included PET-CT and CT scans at 2-3?month intervals. Statistical analysis primarily consisted of univariate analysis, Cox proportional hazards analysis, and the Kaplan-Meier method. RESULTS:The study included 35 patients with 98 treatments for lymph nodes (51), local recurrence (21), and de novo solid metastases (26). Median biologically effective dose (BED), gross tumor volume, and planning target volume were 38.40?Gy, 10.41?cc, and 25.21?cc, respectively. 52 lesions showed complete radiographic response, and two-year local control was 80%. Median overall survival (OS) was 35.2?months, and two-year progression-free survival (PFS) was 12%. On univariate analysis, Eastern Cooperative Oncology Group performance status >?0 was predictive of decreased OS (p?=?0.0024) and PFS (p?=?0.044). Factors predictive of local failure included lower BED (p?=?0.016), treatment for recurrence (p?=?0.029), and higher pre-treatment SUV (p?=?0.026). Kaplan-Meier analysis showed BED ?35?Gy (p?<?0.005) and treatment for recurrence (p?=?0.01) to be predictive of local failure. On Cox proportional hazards analysis, treatment of lymph nodes was predictive of complete radiographic response (hazard ratio (HR)?=?4.95), as was higher BED (HR?=?1.03). Toxicity included 27 cases of grade?<?3 toxicity, and one grade 5 late toxicity of GI bleed from a radiation therapy-induced duodenal ulcer. CONCLUSIONS:SBRT provides durable local control with minimal toxicity in ovarian cancer, especially with BED >?35?Gy and treatment for lymph nodes.
Project description:We aim to evaluate whether different definitions of esophagus (DEs) impact on the esophageal toxicity prediction for esophageal cancer (EC) patients administered intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) vs. standard-dose IMRT (SD-IMRT). The esophagus for 21 patients diagnosed with primary EC were defined in the following four ways: the whole esophagus, including the tumor (ESOwhole); ESOwhole within the treatment field (ESOinfield); ESOinfield, excluding the tumor (ESOinfield-tumor) and ESOwhole, excluding the tumor (ESOwhole-tumor). The difference in the dose variation, acute esophageal toxicity (AET) and late esophageal toxicity (LET) of four DEs were compared. We found that the mean esophageal dose for ESOwhole, ESOinfield, ESOinfield-tumor and ESOwhole-tumor were increased by 7.2?Gy, 10.9?Gy, 4.6?Gy and 2.0?Gy, respectively, in the SIB-IMRT plans. Radiobiological models indicated that a grade???2 AET was 2.9%, 3.1%, 2.2% and 1.6% higher on average with the Kwint model and 14.6%, 13.2%, 7.2% and 3.4% higher with the Wijsman model for the four DEs. A grade???3 AET increased by 4.3%, 7.2%, 4.2% and 1.2%, respectively. Additionally, the predicted LET increased by 0.15%, 0.39%, 1.2?×?10-2% and 1.5?×?10-3%. Our study demonstrates that different DEs influence the esophageal toxicity prediction for EC patients administered SIB-IMRT vs. SD-IMRT treatment.
Project description:To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity.A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher's exact test and logistic regression. Clinical factors were correlated with toxicity.The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ?3 acute or late toxicity was 6.8% (14 patients). Fisher's exact test resulted in significant median splits for grade ?3 toxicity at V12 = 3.78 cm(3) (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm(3) (RR 13, P=.0013), V20 = 0.11 cm(3) (RR 6, P=0.01), and V22 = 0.0 cm(3) (RR 13, P=.0013). The median split for D2.5 cm(3) (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm(3). One hundred percent (n = 7) of grade ?4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus.High-dose, single-fraction paraspinal SRS has a low rate of grade ?3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are associated with development of grade ?4 toxicity.
Project description:To report overall survival and local control for patients identified in the RSSearch® Patient Registry with metastatic cancer to the lung treated with SBRT.Seven hundred two patients were identified with lung metastases in the RSSearch® Registry. Of these patients, 577 patients had SBRT dose and fractionation information available. Patients were excluded if they received prior surgery, radiation, or radiofrequency ablation to the SBRT treated area. Between April 2004-July 2015, 447 patients treated with SBRT at 30 academic and community-based centers were evaluable for overall survival (OS). Three hundred four patients with 327 lesions were evaluable for local control (LC). All doses were converted to Monte Carlo equivalents and subsequent BED Gy10 for dose response analysis.Median age was 69 years (range, 18-93 years). Median Karnofsky performance status (KPS) was 90 (range 25/75% 80-100). 49.2% of patients had prior systemic therapy. Median metastasis volume was 10.58 cc (range 25/75% 3.7-25.54 cc). Site of primary tumor included colorectal (25.7%), lung (16.6%), head and neck (11.4%), breast (9.2%), kidney (8.1%), skin (6.5%) and other (22.1%). Median dose was 50 Gy (range 25/75% 48-54) delivered in 3 fractions (range 25/75% 3-5) with a median BED of 100Gy10 (range 25/75% 81-136). Median OS for the entire group was 26 months, with actuarial 1-, 3-, and 5-year OS of 74.1%, 33.3, and 21.8%, respectively. Patients with head and neck and breast cancers had longer median OS of 37 and 32 months respectively, compared to colorectal (30 months) and lung (26 months) which corresponded to 3-year actuarial OS of 51.8 and 47.9% for head and neck and breast respectively, compared to 35.8% for colorectal and 31.2% for lung. The median LC for all patients was 53 months, with actuarial 1-, 3-, and 5-year LC rates of 80.4, 58.9, and 46.3%, respectively. There was no difference in LC by primary histologic type (p?=?0.49). Improved LC was observed for lung metastases that received SBRT doses of BED ?100Gy10 with 3-year LC rate of 77.1% compared to 45% for lung metastases treated with BED?<?100Gy10 (p?=?0.01). Smaller tumor volumes (<11 cc) had improved LC compared to tumor volumes?>?11 cc. (p?=?0.005) Two-year LC rates for tumor volumes?<?11 cc, 11-27 cc and?>?27 cc were 72.9, 64.2 and 45.6%, respectively. This correlated with improved OS with 2-year OS rates of 62.4, 60.9 and 46.2% for tumor volumes?<?11 cc, 11-27 cc and?>?27 cc, respectively (p?=?0.0023). In a subset of patients who received BED ?100Gy10, 2-year LC rates for tumor volumes?<?11 cc, 11-27 cc and?>?27 cc were 82.8, 58.9 and 68.6%, respectively (p?=?0.0244), and 2-year OS rates were 66.0, 58.8 and 28.5%, respectively (p?=?0.0081).Excellent OS and LC is achievable with SBRT utilizing BED ?100Gy10 for lung metastases according to the RSSearch® Registry data. Patients with small lung metastases (volumes?<?11 cc) had better LC and OS when using SBRT doses of BED ?100Gy10. Further studies to evaluate a difference, if any, between various tumor types will require a larger number of patients.
Project description:We present our initial experience with CyberKnife stereotactic body radiation therapy (SBRT) in a heavily pretreated group of patients with liver metastases and primary liver tumors. From October 2007 to June 2009, 48 patients were treated at the Philadelphia CyberKnife Center for liver metastases or primary liver tumors. We report on 30 patients with 41 discrete lesions (1-4 tumors per patient) who received an ablative radiation dose (BED???79.2?Gy10?=?66?Gy EQD2). The treatment goal was to achieve a high SBRT dose to the liver tumor while sparing at least 700?cc of liver from radiation doses above 15?Gy. Twenty-three patients were treated with SBRT for metastatic cancer to the liver; the remainder (n?=?7) were primary liver tumors. Eighty-seven percent of patients had prior systemic chemotherapy with a median 24?months from diagnosis to SBRT; 37% had prior liver directed therapy. Local control was assessed for 28 patients (39 tumors) with 4?months or more follow-up. At a median follow-up of 22?months (range, 10-40?months), 14/39 (36%) tumors had documented local failure. A decrease in local failure was found with higher doses of SBRT (p?=?0.0237); 55% of tumors receiving a BED???100?Gy10 (10/18) had local failure compared with 19% receiving a BED?>?100?Gy10 (4/21). The 2-year actuarial rate of local control for tumors treated with BED?>?100?Gy10 was 75% compared to 38% for those patients treated with BED???100?Gy10 (p?=?0.04). At last follow-up, 22/30 patients (73%) had distant progression of disease. Overall, seven patients remain alive with a median survival of 20?months from treatment and 57?months from diagnosis. To date, no patient experienced persistent or severe adverse effects. Despite the heavy pretreatment of these patients, SBRT was well tolerated with excellent local control rates when adequate doses (BED?>?100?Gy10) were used. Median survival was limited secondary to development of further metastatic disease in the majority of patients.
Project description:Objectives: To report the preliminary results of salvage re-irradiation in the prostatic bed after radical prostatectomy and salvage external beam radiation therapy (EBRT) using robotic stereotactic body radiation therapy (SBRT) with Cyberknife® for local recurrence of prostate cancer. Materials and Methods: Retrospective monocentric analysis was performed on patients treated with SBRT for isolated macroscopic recurrence in the prostatic bed. All patients had radical prostatectomy and salvage or adjuvant EBRT. Local recurrence was documented using magnetic resonance imaging (MRI) and positron emission tomography (PET). Biochemical recurrence was defined as 2 rises in prostate-specific antigen (PSA) of ≥ 0.2 ng/mL above nadir. Internal gold fiducials were used for the tracking of tumor motion during SBRT. The prescription dose was 36 Gy in 6 fractions for all patients. Toxicity was scored according to the CTCAE v4.0. Results: Between July 2011 and November 2017, 12 patients were treated with SBRT for prostatic bed recurrence with a median follow-up of 34.2 (range, 3.5-64.4) months. Isolated non-metastatic recurrence in the prostatic bed was seen at MRI and PET imaging. Two patients were treated with 6 months androgen deprivation therapy (ADT) concomitant with re-irradiation. The median planning target volume was 4.5 cm3 (range, 1.2-13.3). A PSA decrease after SBRT was found in 10 (83%) patients. The 1 and 2 years biochemical recurrence-free survival rates were 79 and 56%, respectively. Biochemical recurrence was observed for 6 patients (50%) after a median time of 18 (4-42) months. Toxicity showed: 3 patients (25%) with grade 1 cystitis and 1 patient (8%) with acute grade 2 proctitis at 4 months. One patient (13%) had grade 1 cystitis at 12 months. Conclusion: Re-irradiation for local recurrence in the prostatic bed using Cyberknife® after surgery and salvage or adjuvant EBRT is well-tolerated and associated with 2 years biochemical recurrence-free survival rates of 56%. Longer follow-up and larger series are necessary.
Project description:Purpose:There are limited treatment options for locally advanced, unresectable pancreatic cancer (LAPC) and no likelihood of cure without surgery. Radiation offers an option for local control, but radiation dose has previously been limited by nearby bowel toxicity. Advances in on-board imaging and treatment planning may allow for dose escalation not previously feasible and improve local control. In preparation for development of clinical trials of dose escalation in LAPC, we undertook a dosimetric study to determine the maximum possible dose escalation while maintaining known normal tissue constraints. Methods and Materials:Twenty patients treated at our institution with either SBRT or dose-escalated hypofractionated IMRT (DE-IMRT) were re-planned using dose escalated SBRT to 70 Gy in 5 fractions to the GTV and 40 Gy in 5 fractions to the PTV. Standard accepted organ at risk (OAR) constraints were used for planning. Descriptive statistics were generated for homogeneity, conformality, OAR's and GTV/PTV. Results:Mean iGTV coverage by 50 Gy was 91% (±0.07%), by 60 Gy was 61.3% (±0.08%) and by 70 Gy was 24.4% (±0.05%). Maximum PTV coverage by 70 Gy was 33%. Maximum PTV coverage by 60 Gy was 77.5%. The following organ at risk (OAR) constraints were achieved for 90% of generated plans: Duodenum V20 < 30 cc, V30 < 3 cc, V35 < 1 cc; Small Bowel V20 < 15 cc, V30 < 1 cc, V35 < 0.1 cc; Stomach V20 < 20 cc, V30 < 2 cc, V35 < 1 cc. V40 < 0.5 cc was achieved for all OAR. Conclusions:Dose escalation to 60 Gy is dosimetrically feasible with adequate GTV coverage. The identified constraints for OAR's will be used in ongoing clinical trials.
Project description:Radiotherapy is an increasingly preferred treatment option for localized prostate cancer, and stereotactic body radiation therapy (SBRT) a relatively established modality of therapeutic irradiation. The present study analyzes the toxicity and biochemical efficacy of SBRT in 100 consecutive prostate cancer patients treated with CyberKnife Robotic Radiosurgery System.One hundred patients were treated with SBRT at the Radiation Oncology department of San Bortolo Hospital, Vicenza, Italy. All patients included in this IRB-approved protocol-driven prospective study had biopsy-proven prostate cancer. Risk category was low in 41, intermediate in 42, and high in 17 patients. The patients were treated with CyberKnife-SBRT (CK-SBRT), the prescription dose was 35 Gy in five fractions, corresponding to 92 Gy in 2-Gy fractions (?/? =1.5 Gy); 29 patients also received androgen deprivation therapy (ADT).Median follow-up was 36 months (range, 6-76 months). Acute Grade 2 genitourinary and gastrointestinal toxicity occurred in respectively 12% and 18% of the patients; there were no Grade 3 or higher acute toxicities. Late Grade 1, 2, and 3 genitourinary toxicities occurred in 4%, 3%, and 1% of the patients, respectively; late Grade 1 gastrointestinal toxicity occurred in two patients and Grade 2 toxicity in one patient; no late gastrointestinal toxicities of grade 3 or 4 were observed. Median PSA nadir was 0.45 ng/ml at 36 months for all patients. In the SBRT-monotherapy group, the median PSA nadir at 36 months was 0.62 ng/ml; in the ADT-SBRT group, it was 0.18 ng/ml. Four patients had clinical recurrence: one local, two lymph nodes, and one to the bone. Ninety-six patients had no evidence of biochemical or clinical recurrence. A benign PSA bounce of median 1.08 ng/ml occurred in 12% of the 71 SBRT monotherapy patients at a mean 23 months (range, 18-30 months).In this study CK-SBRT has provided promising outcomes in localized prostate cancer with good PSA response, minimal toxicity and patient inconvenience.
Project description:Radiation technique for prostate cancer has continuously evolved over the past several decades. The aim of the present study was to describe the effects of implementing modern prostate intensity-modulated radiation therapy (M-IMRT) on dosimetry and outcome. Between January 2010 and April 2012, 48 consecutive patients were treated with conventional prostate IMRT (C-IMRT) to a dose of 81 Gy. Between May 2012 and April 2015, 50 consecutive patients were treated with M-IMRT to the entire prostate to a dose of 75.6-79.2 Gy, while using prostate magnetic resonance imaging fusion, dose-volume constraints prioritizing normal tissue avoidance above planning target volume coverage, and boosting any dominant intraprostatic masses to 79.2-81 Gy. Rectal Dmax, V75, V60, V65 and V50, bladder Dmax, V75, V70 and V65, and acute and late toxicities were compared between the C-IMRT and M-IMRT groups. The median follow-up for the C-IMRT and M-IMRT groups was 61 vs. 26 months, respectively (P<0.001). M-IMRT resulted in a significant reduction in median rectal Dmax, rectal V75, rectal V70, rectal V65, bladder Dmax, bladder V75, bladder V70 and bladder V65 (P<0.01 for all). There was no significant difference in rectal V50. The 2-year rate of late grade ≥2 rectal bleeding was 13% with C-IMRT vs. 3% with M-IMRT (P=0.03). The 2-year rate of late grade ≥2 genitourinary toxicity was 11% for C-IMRT vs. 5% for M-IMRT (P=0.21). There were no significant differences in acute toxicity, biochemical control or overall survival. Therefore, compared with C-IMRT, M-IMRT was associated with reduced rectal toxicity without compromising disease control.