Five- Versus Ten-Fraction Regimens of Stereotactic Body Radiation Therapy for Primary and Metastatic NSCLC

IntroductionAt our institution, stereotactic body radiotherapy (SBRT) has commonly been prescribed with 50 Gy in 5 fractions and in select cases, 50 Gy in 10 fractions. We sought to evaluate the impact of these 2 fractionation schedules on local control and survival outcomes.MethodsWe reviewed patients treated with SBRT with 50 Gy/5 fraction or 50 Gy/10 fraction for early-stage non–small cell lung cancer (NSCLC) and metastatic NSCLC. Cumulative incidence of local failure (LF) was estimated using competing risk methodology. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method only for patients with stage I disease.ResultsOf the 353 lesions, 300 (85%) were treated with 50 Gy in 5 fractions and 53 (15%) with 10 fractions. LFs at 3 years were 6.5% and 23.9% and Kaplan-Meier estimate of median time to LF was 17.5 months and 26.2 months, respectively. Multivariable analysis revealed increasing planning target volume (hazard ratio 1.01, P = .04) as an independent predictor of increased LF, but tumor size, ultracentral location, and 10 fractions were not. Among patients with stage I NSCLC (n = 298), overall median PFS was 35.6 months and median OS was 42.4 months. There was no difference in PFS or OS between the 2 treatment regimens for patients with stage I NSCLC. Low rates of grade 3+ toxicity were observed, with 1 patient experiencing grade 3 pneumonitis after a 5-fraction regimen of SBRT.ConclusionDose-fractionation schemes with BED₁₀ ≥ 100 Gy provide superior local control and should be offered when meeting commonly accepted constraints. If those regimens appear unsafe, 50 Gy in 10 fractions may provide acceptable compromise between tumor control and safety with relatively durable control, and minimal negative impact on long-term survival.     

Stereotactic body radiation therapy and 3-dimensional conformal radiotherapy for stage I non-small cell lung cancer: A pooled analysis of biological equivalent dose and local control

PurposeTo determine the relationship between tumor control probability (TCP) and biological effective dose (BED) for radiation therapy in medically inoperable stage I non-small cell lung cancer (NSCLC).Methods and MaterialsForty-two studies on 3-dimensional conformal radiation therapy (3D-CRT) and SBRT for stage I NSCLC were reviewed for tumor control (TC), defined as crude local control ≥ 2 years, as a function of BED. For each dose-fractionation schedule, BED was calculated at isocenter using the linear quadratic (LQ) and universal survival curve (USC) models. A scatter plot of TC versus BED was generated and fitted to the standard TCP equation for both models.ResultsA total of 2696 patients were included in this study (SBRT: 1640; 3D-CRT: 1056). Daily fraction size was 1.2-4 Gy (total dose: 48-102.9) with 3D-CRT and 6-26 (total dose: 20-66) with SBRT. Median BED was 118.6 Gy (range, 68.5-320.3) and 95.6 Gy (range, 46.1-178.1) for the LQ and USC models, respectively. According to the LQ model, BED to achieve 50% TC (TCD₅₀) was 61 Gy (95% confidence interval, 50.2-71.1). TCP as a function of BED was sigmoidal, with TCP ≥ 90% achieved with BED ≥ 159 Gy and 124 Gy for the LQ and USC models, respectively.ConclusionsDose-escalation beyond a BED 159 by LQ model likely translates into clinically insignificant gain in TCP but may result in clinically significant toxicity. When delivered with SBRT, BED of 159 Gy corresponds to a total dose of 53 Gy in 3 fractions at the isocenter.     

Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients

BackgroundStereotactic body radiotherapy (SBRT) has emerged as a treatment modality in patients presenting with oligometastatic nonsmall-cell lung cancer (NSCLC). SBRT is used as a local consolidative treatment to metastatic disease sites. The majority of patients included in SBRT trials for oligometastatic NSCLC have controlled primary tumors and brain metastases.Patients and methodsOligometastatic NSCLC patients with ≤5 metastatic lesions were included in a prospective phase II trial to evaluate efficacy and toxicity of SBRT to all disease sites, primary tumor and metastatic locations. SBRT to a dose of 50 Gy in 10 fractions was delivered. Positron emission tomography–computed tomography (PET-CT) was carried out at baseline and 3 months after SBRT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST). The progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method from start of chemotherapy or radiotherapy. Side-effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.ResultsTwenty-six patients received SBRT after induction chemotherapy (n = 17) or as a primary treatment (n = 9). Median follow-up was 16.4 months. Overall metabolic response rate was 60% with seven patients (30%) achieving a complete metabolic remission and 7 (30%) a partial metabolic response. Any acute grade 2 toxicity was observed in four patients (15%) and grade 3 pulmonary toxicity in two patients (8%). Median PFS and OS were 11.2 and 23 months. The 1-year PFS and 1-year OS rate were 45% and 67%, respectively.ConclusionSBRT to all disease sites, primary tumor and metastatic locations, in oligometastatic NSCLC patients produced an acceptable median PFS of 11.2 months.     

Stereotactic Body Radiation Therapy in the Management of Oligometastatic and Oligoprogressive Bladder Cancer and Other Urothelial Malignancies

AimsBladder cancer represents the most common type of urothelial carcinoma, with a median overall survival of 12.5–15 months in the case of metastatic disease. We evaluated the role of stereotactic body radiation therapy (SBRT) in the management oligometastatic urothelial cancer.Materials and methodsData on patients with a maximum of five metastases were collected from three institutions. Concomitant systemic therapy was allowed. End points were the local control of treated metastases, distant progression-free survival (PFS), overall PFS and overall survival.ResultsData for 82 lesions and 61 patients were included. The primary tumour was located in the bladder in 82% of patients, followed by kidney pelvis (11.5%). The most common treated site was lung (40.2%). Twenty-nine (47.5%) and 14 (23%) patients received systemic therapy before and during SBRT, respectively. The median BED10 value was 78.7 Gy. The median follow-up was 17.2 months. Rates of local control at 1 and 2 years were 92% and 88.9%, respectively, with correlation with systemic therapy before SBRT (hazard ratio 2.62, P = 0.034). Overall PFS at 1 and 2 years was 47.9% and 38.1%, respectively. The number of metastases was a predictive factor (hazard ratio 2.65, P = 0.008). The median overall survival was 25.6 months. Total dose (hazard ratio 0.93, P = 0.003) and BED10 (hazard ratio 0.97, P = 0.006) were correlated with overall survival. No grade ≥2 adverse events were reported.ConclusionsSBRT represents an effective and safe treatment in metastatic urothelial carcinoma. Prospective randomised trials are necessary to better evaluate the benefit on delaying the onset of new systemic therapies.     

Hypofractionated Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost and Simultaneous Integrated Protection in Pancreatic Ductal Adenocarcinoma

AimsTo evaluate the safety and feasibility of stereotactic body radiation therapy (SBRT) with simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma.Materials and methodsPatients receiving SBRT following induction chemotherapy from January 2017 to December 2018 were included in this observational analysis. SBRT was delivered in five consecutive daily fractions by administering 30 Gy to the planning target volume while simultaneously delivering a 50 Gy SIB to the tumour–vessel interface. SIP was created by lowering the dose to 25 Gy on the overlap area between the planning target volume and the planning organ at risk volume. The primary end point was acute and late gastrointestinal grade ≥3 toxicity. Secondary end points were freedom from local progression, overall survival and progression-free survival (PFS).ResultsFifty-nine consecutive patients (27 borderline resectable and 32 locally advanced) were included. Fifty-eight patients (98.3%) completed the SBRT planned treatment and 35 patients (59.4%) received surgical resection following SBRT. No acute or late grade ≥3 SBRT-related adverse events were observed. The median follow-up time was 15.1 months in the overall cohort and 18.1 months in censored patients. One- and 2-year freedom from local progression rates were 85% and 80% versus 79.7% and 60.6% in resected and unresected patients, respectively (P = 0.33). The median overall survival and PFS were 30.2 months and 19 months from diagnosis and 19.1 months and 10.7 months from SBRT in the entire cohort. Resected patients had improved 2-year overall survival rates (72.5% versus 49%, P = 0.012) and median PFS (13 months versus 5 months; P < 0.001) relative to unresected patients. There was no survival difference between borderline resectable and locally advanced patients.ConclusionsSBRT with SIB/SIP had an excellent toxicity profile and could be administered safely on pancreatic ductal adenocarcinoma patients, even in a total neoadjuvant setting.     

Stereotactic body radiation therapy for the treatment of locally recurrent pancreatic cancer after surgical resection

BackgroundTo report on a cohort of radiation-naïve patients with pancreatic cancer who developed isolated local recurrence following surgical resection and were subsequently treated with stereotactic body radiation therapy (SBRT).MethodsPatients with pancreatic cancer who were treated with SBRT for isolated local recurrence after surgical resection were retrospectively reviewed. Clinical outcomes were calculated from completion of SBRT and included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Univariate (UVA) analysis was performed to identify variables associated with clinical outcomes. Kaplan-Meier method was used for survival outcomes. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0.ResultsFrom September 2012 to November 2018, a total of 19 patients with localized pancreatic cancer were treated with SBRT for isolated local recurrence after initial surgical resection. No patients had prior radiation. The median biologically effective dose (BED₁₀) was 54.8 Gy (range, 37.5–54.8 Gy). Median OS was 17.1 months, with 6-month and 1-year OS rates of 94.4% and 69.6%, respectively. Nine patients (47.4%) developed local failure after SBRT. Pattern of first failure after SBRT was distant in 7 patients (46.7%), local in 5 patients (33.3%), and synchronous distant and local in 3 patients (20.0%). One patient developed local failure after developing distant disease first. Of the 9 local failures, 3 (33.3%) were out-of-field. Median LPFS was 22.2 months, with 6-month and 1-year LPFS rates of 86.9% and 63.2%, respectively. A BED₁₀ <54.8 Gy was associated with inferior LPFS (1-year, 25.0% vs. 80.2%, P<0.009). Median DMFS and PFS were 15.6 months. There was 1 case (5.3 %) of grade 3 gastric perforation. There were no cases of grade 4–5 toxicity events.ConclusionsSBRT for locally recurrent pancreatic cancer after initial curative resection is safe and feasible. A BED₁₀ <54.8 Gy was significantly associated with inferior local control. Further studies investigating dose escalation and optimal treatment volumes in the locally recurrent setting are warranted.     

Stereotactic body radiation therapy for stage I non-small cell lung cancer: The importance of treatment planning algorithm and evaluation of a tumor control probability model

Background

Stereotactic body radiation therapy (SBRT) is increasingly used to treat early-stage non-small cell lung cancer (NSCLC). A previous report introduced the term size-adjusted biologically effective dose (sBED), which accounts for tumor diameter and biologically effective dose (BED) and may be used to predict the likelihood of local control following SBRT. Here we seek to replicate those findings using a separate dataset.

Charlson comorbidity index and G8 in older old adult(≥80 years) hepatocellular carcinoma patients treated with stereotactic body radiotherapy

IntroductionHepatocellular Carcinoma (HCC) is characterized, in Western countries, by higher incidence and mortality rates in the older adult population. In frail patients, limited therapeutic resources are available due to limited expected benefit concerning the risk of treatment-related toxicity. The aim of our study is to evaluate the role of Stereotactic Body Radiotherapy (SBRT) in the clinical management of older old adults (age ≥ 80 years) HCC patients and to identify predictors of efficacy and toxicity.Material and MethodsClinical and treatment-related data of older old adults HCC patients treated with SBRT at our institution were retrospectively reviewed. Statistical analysis was carried out to identify variables correlated with impaired outcome and toxicity.ResultsForty-two patients were included, accounting for 63 treated tumors. Median age was 85 (range 80–91) years. Median Charlson Comorbidity Index (CCI) and G8 scores were 10 (range 7–16) and 11 (range 8–14), respectively. SBRT was administered to a median BED10 of 103 Gy10. Median follow-up interval was 11 (range 3–40) months. Two years Local Control (LC), Progression-Free Survival (PFS), and Overall Survival (OS) were 93%, 31%, and 43%, respectively. Acute toxicity occurred in 28% (n = 13) of treatments. A G8 score > 10 was associated with improved survival (p = 0.045), while a CCI ≥10 was correlated with increased acute toxicity (p = 0.021).ConclusionsSBRT is a safe and effective option in older old adults HCC patients. A comprehensive geriatric assessment (CGA) is advised before treatment decisions to select optimal candidates for SBRT.     

Multiagent Chemotherapy and Stereotactic Body Radiation Therapy in Patients with Unresectable Pancreatic Adenocarcinoma: A Prospective Nonrandomized Controlled Trial

PurposeIn a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes.Methods and MaterialsThis prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between 2012 and 2015 at a high-volume pancreatic cancer center. For induction CTX, most received modified FOLFIRINOX (mFFX), or gemcitabine and nab-paclitaxel (GnP) followed by 5-fraction SBRT for all. During fiducial placement, biopsies were obtained with DNA extracted for targeted sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform.ResultsMedian induction CTX duration was ≥4 months, and 31 patients received mFFX (65%). Among 44 LAPC patients, 17 (39%) were surgically explored, and 12 of 16 (75%) achieved a R0 resection. Median overall survival (mOS) was 20.2 and 14.6 months from diagnosis and SBRT, respectively. One- and 2-year OS from SBRT was 58% and 28%. The mOS after resection was 28.6 and 22.4 months from diagnosis and SBRT, respectively. Median local progression-free survival was 23.9 and 15.8 months from diagnosis and SBRT, respectively. The mOS for pre-SBRT CA 19-9 ≤180 U/mL versus >180 was 23.1 and 11.3 months, respectively (hazard ratio, 0.53; P = .04). Only 1 patient (2.1%) had late grade ≥2 gastrointestinal toxic effects attributable to SBRT. Despite significant pretreatment with chemotherapy, 88% of tumor specimens were effectively sequenced; survival outcomes were not significantly associated with specific mutational patterns. Quality of life was prospectively collected pre- and post-SBRT with the EORTC QLQ-C30 and PAN26 questionnaires showing no significant change.ConclusionsSBRT was safely administered with MA-CTX with minimal toxicity. A high proportion of LAPC patients underwent R0 resection with favorable survival outcomes.     

Cost-Effectiveness of Treatment Strategies for Spinal Metastases

PurposeWe analyzed the cost-effectiveness of standard palliative external beam radiation (EBRT, 8 Gy in 1 fraction), stereotactic body radiation therapy (SBRT, 24 Gy in 2 fractions), and radiofrequency ablation for painful spinal metastases. Single-fraction SBRT (delivering 24 Gy) was also assessed.Methods and MaterialsA Markov state transition model was constructed. Key model parameters were derived from prospective clinical trial data. Strategies were compared using the incremental cost-effectiveness ratio (ICER), with effectiveness in quality-adjusted life-years (QALYs) and a willingness-to-pay threshold of $100,000 per QALY gained. Costs included both hospital and professional costs using 2020 Medicare reimbursement.ResultsThe base case demonstrated that 2-fraction SBRT was not cost-effective compared with single-fraction EBRT, with an ICER of $194,145 per QALY gained. Radiofrequency ablation was a more costly and less effective strategy in this model. Probabilistic sensitivity analysis demonstrated that EBRT was favored in 66% of model iterations. If median survival were improved after SBRT, 2-fraction SBRT became cost-effective, with ICERs of $80,394, $57,062, and $47,038 for 3-, 6-, and 9-month improvements in survival, respectively. Because 2-fraction SBRT data reported that 18% of patients had an indeterminant pain response at 3 months and 2-fraction SBRT is infrequently used in clinical practice, single-fraction SBRT data were also assessed. Single-fraction SBRT delivering 24 Gy was cost-effective compared with single-fraction EBRT, with an ICER of $92,833 per QALY gained.ConclusionsFor appropriately chosen patients, single-fraction SBRT was more cost-effective than conventional EBRT or radiofrequency ablation. Conventional EBRT remains a cost-effective treatment for patients with poor expected survival.     

Safety of Prostate Stereotactic Body Radiation Therapy after Transurethral Resection of Prostate (TURP): A Propensity Score Matched Pair Analysis

PurposeTo determine the genitourinary (GU) toxicity outcomes in prostate cancer patients treated with stereotactic body radiation therapy (SBRT) who have undergone a prior transurethral resection of prostate (TURP) and compare it to a similar non-TURP cohort.Materials and MethodsFifty prostate cancer patients who had undergone a single TURP, had a good baseline urinary function, and had been subsequently treated with SBRT were chosen from a prospectively maintained database. These were propensity score matched to a similar non-TURP cohort treated during the same period. Matching was done for diabetes mellitus and volume of radiation therapy. Acute GU and late GU toxicity were scored using the Radiation Therapy Oncology Group (RTOG) criteria. Stricture and incontinence were scored using Common Terminology for Common Adverse Events version 4.0.ResultsMedian follow-up for the entire cohort was 26 months (non-TURP vs TURP, 30 months vs 22 months, P = .34). The median duration between TURP and start of SBRT was 10 months. There was no significant difference between non-TURP versus TURP cohort in terms of RTOG acute GU toxicities grade ≥2 (8% vs 6%, P = .45), RTOG late GU toxicities grade ≥2 (8% vs 12%, P = .10), stricture rates (4% vs 6%, P = .64), and incontinence rates (0% vs 4%, P = .15). The median duration of time to late toxicity was 16 months vs 10 months (P = .12) in non-TURP and TURP cohort, respectively.ConclusionsAlthough modestly increased as compared with non-TURP patients, GU toxicities remains low with SBRT in post-TURP patients. SBRT can be safely performed in carefully selected post-TURP prostate cancer patients.     

Re-irradiation with stereotactic body radiation therapy as a novel treatment option for isolated local recurrence of pancreatic cancer after multimodality therapy: experience from two institutions

Limited treatment options exist for isolated local recurrence of pancreatic ductal adenocarcinoma (PDA) following surgical resection accompanied by neoadjuvant or adjuvant chemoradiation therapy (CRT). While select patients are eligible for re-resection, recurrent lesions are often unresectable. Stereotactic body radiation therapy (SBRT) represents a possible minimally invasive treatment option for these patients, although published data in this setting are currently lacking. This study examines the safety, efficacy, and palliative capacity of re-irradiation with SBRT for isolated local PDA recurrence.All patients undergoing SBRT at two academic centers from 2008-2012 were retrospectively reviewed to identify those who received re-irradiation with SBRT for isolated local recurrence or progression of PDA after previous conventionally fractionated CRT. Information regarding demographics, clinicopathologic characteristics, therapies received, survival, symptom palliation, and toxicity was obtained from patient charts. Kaplan-Meier statistics were used to analyze survival and the log-rank test was used to compare survival among patient subgroups.Eighteen patients were identified. Fifteen had previously undergone resection with neoadjuvant or adjuvant CRT, while 3 received definitive CRT for locally advanced disease. Median CRT dose was 50.4 Gy [interquartile range (IQR), 45.0-50.4 Gy] in 28 fractions. All patients subsequently received gemcitabine-based maintenance chemotherapy, but developed isolated local disease recurrence or progression without evidence of distant metastasis. Locally recurrent or progressive disease was treated with SBRT to a median dose of 25.0 Gy (range, 20.0-27.0 Gy) in 5 fractions. Median survival from SBRT was 8.8 months (95% CI, 1.2-16.4 months). Despite having similar clinicopathologic disease characteristics, patients who experienced local progression greater than vs. less than 9 months after surgery/definitive CRT demonstrated superior median survival (11.3 vs. 3.4 months; P=0.019) and progression-free survival (10.6 vs. 3.2 months; P=0.030) after SBRT. Rates of freedom from local progression at 6 and 12 months after SBRT were 78% (14 of 18 patients) and 62% (5 of 8 patients), respectively. Effective symptom palliation was achieved in 4 of 7 patients (57%) who reported symptoms of abdominal or back pain prior to SBRT. Five patients (28%) experienced grade 2 acute toxicity; none experienced grade ≥3 acute toxicity. One patient (6%) experienced grade 3 late toxicity in the form of small bowel obstruction.In conclusion, re-irradiation with hypofractionated SBRT in this salvage scenario appears to be a safe and reasonable option for palliation of isolated local PDA recurrence or progression following previous conventional CRT. Patients with a progression-free interval of greater than 9 months prior to isolated local recurrence or progression may be most suitable for re-irradiation with SBRT, as they appear to have a better prognosis with survival that is long enough for local control to be of potential benefit.Key Words: Stereotactic body radiation therapy (SBRT), pancreatic cancer, local recurrence, re-irradiation     

Thoracic reirradiation with SBRT for residual/recurrent and new primary NSCLC within or immediately adjacent to a prior high-dose radiation field

Purpose

Local failure following concurrent chemoradiation and in-lobe failures following stereotactic body radiation therapy (SBRT) are common. We evaluated our institutional experience using SBRT as salvage in this setting.

Thoracic re-irradiation using stereotactic body radiotherapy (SBRT) techniques as first or second course of treatment

Background and purpose

Management for in-field failures after thoracic radiation is poorly defined. We evaluated SBRT as an initial or second course of treatment re-irradiating in a prior high dose region.

Materials and methods

Thirty-three patients were treated with re-irradiation defined by the prior 30 Gy isodose line. Kaplan–Meier estimates were performed for local (LC), regional (RC), distant control (DC), and overall survival (OS). The plans when available were summed to evaluate doses to critical structures. Patient and treatment variables were analyzed on UVA for the impact on control and survival measures.

Results

Median follow-up was 17 months. Treatment for sequential courses was as follows: (course1:course2) EBRT:SBRT (24 patients), SBRT:SBRT (7 patients), and SBRT:EBRT (3 patients). Median re-irradiation dose and fractionation was 50 Gy and 10 fractions (fx), with a median of 18 months (6–61) between treatments. Median OS was 21 months and 2 year LC 67%, yet LC for >1 fraction was 88% (p = 0.006 for single vs. multiple). 10 patients suffered chronic grade 2–3 toxicity (6 chest wall pain, 3 dyspnea, 1 esophagitis) and 1 grade 5 toxicity with aorta-esophageal fistula after 54 Gy in 3 fx for a central tumor with an estimated EQD2 to the aorta of 200 Gy.

Conclusion

Tumor control can be established with re-irradiation using SBRT techniques for in-field thoracic failures at the cost of manageable toxicity.     

Radiotherapy for hilar or mediastinal lymph node metastases after definitive treatment with stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer

PurposeManagement of regional lymph node (LN) recurrence is an important issue in definitive treatment of non-small cell lung cancer (NSCLC). We evaluated clinical outcomes of conventional radiotherapy for hilar or mediastinal LN metastases developing after stereotactic body radiotherapy (SBRT) or surgery for stage I NSCLC.Methods and MaterialsBetween 2004 and 2008, 26 patients with hilar or mediastinal LN metastases without local recurrence and distant metastasis after SBRT (n = 14) or surgery (n = 12) were treated with conventional radiotherapy. Twelve of the 14 post-SBRT patients (86%) were judged medically inoperable at the time of SBRT. All patients were treated to the hilum and mediastinum with conventional daily fractions of 2.0 Gy (n = 25) or 2.4 Gy (n = 1). The median total dose for treating metastatic LN was 60 Gy (range, 54-66 Gy) for the post-SBRT patients and 65 Gy (range, 60-66 Gy) for the post-surgery patients. Only 1 of the 14 post-SBRT patients and 8 of the 12 post-surgery patients received chemotherapy.ResultsFor all 26 patients, the overall and cause-specific survival rates at 3 years from radiation for LN metastases were 36% and 51%, respectively (14% and 39%, respectively, for the 14 post-SBRT patients and both 64% for the 12 post-surgery patients). Three of the SBRT patients were alive at 35 to 43 months with (n = 2) or without (n = 1) further recurrence, and 4 of the post-surgery patients were alive at 36 to 62 months with (n = 2) or without (n = 2) further recurrence. The incidence of ≥grade 2 pulmonary toxicity was 49% at 1 year (53% for post-SBRT patients and 44% for post-surgery patients). A grade 5 pulmonary toxicity was observed in 1 of the post-SBRT patients.ConclusionsConventional radiotherapy could successfully salvage LN relapses after SBRT as well as after surgery in 7 of 26 patients. Radiotherapy in this setting appears reasonably well tolerated.     

Long-term Follow-up and Patterns of Recurrence of Patients With Oligometastatic NSCLC Treated With Pulmonary SBRT

IntroductionThis multicenter study aims to analyze outcome as well as early versus late patterns of recurrence following pulmonary stereotactic body radiotherapy (SBRT) for patients with oligometastatic non–small-cell lung cancer (NSCLC).Materials and MethodsThis analysis included 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases. Although treatment of the primary tumor consisted of surgical resection, radiochemotherapy, and/or systemic therapy, pulmonary oligometastases were treated with SBRT.ResultsThe median follow-up time was 16.1 months, resulting in 2-year overall survival (OS), local control (LC), and distant control (DC) of 62.2%, 82.0%, and 45.2%, respectively. Multivariate analysis identified age (P = .019) and histologic subtype (P = .028), as well as number of metastatic organs (P < .001) as independent prognostic factors for OS. LC was superior for patients with favorable histologic subtype (P = .046) and SBRT with a higher biological effective dose at isocenter (P = .037), whereas DC was inferior for patients with metastases in multiple organs (P < .001) and female gender (P = .027). Early (within 24 months) local or distant progression was observed in 15.3% and 36.5% of the patients. After 24 months, the risk of late local failure was low, with 3- and 4-year local failure rates of only 4.0%, and 7.6%. In contrast, patients remained at a high risk of distant progression with 3- and 4-year failure rates of 13.3% and 24.1%, respectively, with no plateau observed.ConclusionSBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS. The dominant failure pattern is distant with a continuously high risk of disease progression for many years.     

Clinical Outcomes and Safety Profile in the Treatment of Synchronous Nonmetastatic Lung Tumors With Stereotactic Body Radiation Therapy

PurposeStereotactic body radiation therapy (SBRT) has increasingly been used to treat early-stage primary lung cancers, but its effectiveness and safety in patients with multiple synchronous primary lung tumors is not as well established. Our aim was to evaluate clinical outcomes, patterns of recurrence, and toxicities for these patients.Methods and MaterialsWe queried an institutional database of patients treated with SBRT for primary lung tumors from 2007 to 2019. Patients with known metastatic disease were excluded. Recurrences were described as new primaries (NP) if they occurred as an isolated pulmonary mass outside the previous planning target volume.ResultsWe analyzed 126 lesions from 60 consecutive patients who received SBRT synchronously to ≥2 lesions for nonmetastatic lung cancers. Median total dose per lesion was 50 Gy (range, 30-60 Gy) delivered over 3 to 5 fractions. All but 4 lesions were treated to a biologically effective dose ≥100 Gy. The median follow-up time was 47.3 months (interquartile range, 34.1-65.6). Median overall survival was 46.2 months. Two and 5-year overall survival for all patients was 70% and 48%, respectively. Median progression-free survival was 26 months (interquartile range, 7.6-32.6), and at the time of data collection 25 patients (42%) had experienced any disease progression. Median time to progression was 36 months: 9 (15%) patients experienced local failure, with 1- and 2-year local failure rates of 8% and 13%, respectively. Four patients (7%) experienced regional failure, at 3, 10, 30, and 50 months. Eleven patients (18%) experienced distant failure, with 2-year distant failure rate of 13%. Thirteen patients (21%) developed NPs, with 2-year NP rate of 15.1%. Fourteen patients (23%) experienced Common Terminology Criteria for Adverse Events grade ≥2 toxicity, and 2 patients (3%) experienced Common Terminology Criteria for Adverse Events grade ≥3 toxicity (pneumonitis and hemoptysis).ConclusionsSynchronous SBRT to biologically effective dose ≥100 Gy appears safe and effective for selected patients with synchronous primary lung tumors.     

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.     

A phase II study on stereotactic body radiotherapy for stage I non-small cell lung cancer

Background and purposeThe outcome of stage I non-small cell lung cancer (NSCLC) patients treated with conventional radiotherapy is inferior to that of patients treated surgically. We aimed to evaluate the clinical outcome of stereotactic body radiotherapy (SBRT) in the treatment of stage I NSCLC.Materials and methodsWe performed SBRT for 31 stage I NSCLC patients. Of these, 20 were medically inoperable, and 11 refused surgery. Nineteen tumours were T1-stage masses, and 12 tumours were T2. Median tumour size was 25 mm. SBRT was administered as 45 Gy/3 fractions; however, when the tumour was close to an organ at risk, 60 Gy/8 fractions were used. These doses were prescribed at the centre of the tumours.ResultsThe median duration of observation for all patients was 32 months (range, 4–87 months). In 9 of the 31 cases, local recurrence was observed. The 3-year local control rates of T1 and T2 tumours were 77.9% and 40.0%, respectively. The 3-year overall and cause-specific survival rates were 71.7% and 83.5%, respectively. Although the symptoms improved with medical treatment, 5 patients developed acute pulmonary toxicity ⩾grade 2.ConclusionsSBRT is safe and effective for stage I NSCLC patients. However, a more intensive treatment regimen should be considered for T2 tumours.