Pretreatment SUVmax predicts progression-free survival in early-stage non-small cell lung cancer treated with stereotactic body radiation therapy Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer: An updated retrospective study on local failure and survival rates Stereotactic Body Radiation Therapy for Unbiopsied Early-stage Lung Cancer: A Multi-Institutional Analysis Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable Stage I/II non-small-cell lung cancer. Stereotactic body radiation therapy for early-stage non-small-cell lung carcinoma: four-year results of a prospective phase II study. CyberKnife radiosurgery for inoperable stage IA non-small cell lung cancer: 18F-fluorodeoxyglucose positron emission tomography/computed tomography serial tumor response assessment Clinical outcome and predictors of survival and pneumonitis after stereotactic ablative radiotherapy for stage I non-small cell lung cancer CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Stage I Non-Small Cell Lung Cancer A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer: NRG Oncology RTOG 0915 (NCCTG N0927). The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Video‐assisted thoracoscopic lobectomy is associated with greater recurrence‐free survival than stereotactic body radiotherapy for clinical stage I lung cancer Clinical Staging of Stage I Non-Small Cell Lung Cancer in the Netherlands-Need for Improvement in an Era With Expanding Nonsurgical Treatment Options: Data From the Dutch Lung Surgery Audit. Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Phase II Trial of SBRT for Stage I NSCLC: Survival, Local Control, and Lung Function at 36 Months Stereotactic body radiation therapy for inoperable early stage lung cancer. Positron emission tomography combined with diagnostic chest computed tomography enhances detection of regional recurrence after stereotactic body radiation therapy for early stage non-small cell lung cancer. Outcomes of stereotactic ablative radiotherapy in patients with potentially operable stage I non-small cell lung cancer. A phase II study on stereotactic body radiotherapy for stage I non-small cell lung cancer. Patient reported outcomes following stereotactic ablative radiotherapy or surgery for stage IA non-small-cell lung cancer: Results from the ROSEL multicenter randomized trial. Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403. Stereotactic body radiotherapy using a radiobiology‐based regimen for stage I nonsmall cell lung cancer Stereotactic body radiation therapy versus surgical resection for stage I non-small cell lung cancer.
Background This retrospective study aims to assess the usefulness of SUVmax from FDG-PET imaging as a prognosticator for primary biopsy-proven stage I NSCLC treated with SBRT .  Methods This study includes 95 patients of median age 77 years , with primary , biopsy-confirmed peripheral stage IA/IB NSCLC . All patients were treated with 60Gy in 3 fractions with a median treatment time of six days . Local , regional , and distant failures were evaluated independently according to the terms of RTOG1021 . Local , regional , and distant control , overall- and progression-free survival were estimated by the Kaplan-Meier method . Cox proportional hazards regression was performed to determine whether SUVmax , age , KPS , gender , tumor size/T stage , or smoking history influenced outcomes . SUVmax was evaluated as both a continuous and as a dichotomous variable using a cutoff of < 5 and ≥5 . Results Median follow-up for the cohort was 16 months . Median OS and PFS were 25.3 and 40.3 months , respectively . SUV with a cutoff value of 5 predicted for OS and PFS ( p = .024 for each ) but did not achieve significance for LC ( p = .256 ) . On Cox univariate regression analysis , SUV as a dichotomous variable predicted for both OS and PFS ( p = .027 and p = .030 , respectively ) . Defined as a continuous variable , SUVmax continued to predict for OS and PFS ( p = .032 and p = .003 ) , but also predicted LC ( p = .045 ) and trended toward significance for DC ( p = .059).SUVmax did not predict for OS as a dichotomous or continuous variable . It did , however , predict for PFS as a continuous variable ( p = .008 ) , neared significance for local control ( p = .057 ) and trended towards , significance for distant control ( p = .092 ) . Conclusions SUVmax appears to be a statistically and clinical ly significant independent prognostic marker for progression-free survival in patients with stage I NSCLC treated with SBRT .  Prospect i ve studies to more accurately define the role of tumor FDG uptake in the prognosis of NSCLC are warranted Abstract Introduction . Stereotactic body radiation therapy ( SBRT ) for early stage non-small cell lung cancer ( NSCLC ) is now an accepted and patient friendly treatment , but still controversy exists about its comparability to conventional radiation therapy ( RT ) . The purpose of this single-institutional report is to describe survival outcome for medically inoperable patients with early stage NSCLC treated with SBRT compared with high dose conventional RT . Material and methods . From August 2005 to June 2012 , 100 medically inoperable patients were treated with SBRT at Odense University Hospital . The thoracic RT consisted of 3 fractions ( F ) of 15–22 Gy delivered in nine days . For comparison a group of 32 medically inoperable patients treated with conventional RT with 80 Gy/35–40  F ( 5 F/week ) in the period of July 1998 to August 2011 were analyzed . All tumors had histological or cytological proven NSCLC T1 - 2N0M0 . Results . The median overall survival was 36.1 months versus 24.4 months for SBRT and conventional RT , respectively ( p = 0.015 ) . Local failure-free survival rates at one year were in SBRT group 93 % versus 89 % in the conventional RT group and at five years 69 % versus 66 % , SBRT and conventional RT respectively ( p = 0.99 ) . On multivariate analysis , female gender and performance status of 0–1 and SBRT predicted improved prognosis . Conclusion . In a cohort of patients with NSCLC there was a significant difference in overall survival  favoring SBRT . Performance status of 0–1 , female gender and SBRT predicted improved prognosis . However , staging procedure , confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes . However , SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients Objectives : Medically inoperable lung cancer patients often have comorbidities that preclude pathologic diagnosis from being attained . We perform a multi-institutional analysis to determine if unbiopsied early-stage lung carcinoma can be safely and effectively treated with stereotactic body radiation therapy ( SBRT ) . Material s and Methods : Thirty-four patients with unbiopsied lung cancer were treated with SBRT at the University of Louisville or University of Virginia . Patients had computed tomography ( CT ) and positron emission tomography ( PET ) imaging clinical ly consistent with lung malignancy . Median SBRT dose was 50 Gy ( range , 30 to 55 Gy ) in a median of 5 fractions ( range , 3 to 10 fractions ) with static field SBRT or volumetric modulated arc therapy . Results : Median follow-up is 16.7 months . Primary tumors had a median longest dimension on the original CT of 1.6 cm ( range , 0.5 to 3.3 cm ) and posttreatment CT scan of 1.25 cm ( range , 0.0 to 4.5 cm ) ( P=0.025 ) . Median pretreatment st and ard uptake value on initial PET scan is 4.6 mg/mL ( range , 0.0 to 16.2 mg/mL ) , and at a median of 7.6 months after SBRT , decreased to 2.25 mg/mL ( range , 0.0 to 10.9 mg/mL ) on posttreatment PET ( P=0.002 ) . Crude local control is 97.1 % . The estimated 2-year regional control is 80 % , distant control 85 % , and overall survival 85 % . There were no grade 3 or greater acute toxicities and only 3 grade 3 chronic treatment-related toxicitities . Discussion : In medically inoperable patients with unbiopsied lung cancer , local control can be achieved with minimal toxicity with the use of SBRT . The use of SBRT for unbiopsied early-stage lung cancer patients should be performed in a multidisciplinary setting and after detailed discussion with the patient about the risks and benefits of SBRT PURPOSE To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy in patients with Stage I/II non-small-cell lung cancer . METHODS AND MATERIAL S Forty-three patients with inoperable Stage I/II non-small-cell lung cancer underwent treatment prospect ively using the stereotactic gamma-ray whole-body therapeutic system ( body gamma-knife radiosurgery ) with 30 rotary conical-surface Co(60 ) sources focused on the target volume . Low-speed computed tomography simulation was conducted , which was followed by three-dimensional conformal radiotherapy planning . A total dose of 50 Gy was delivered at 5 Gy/fraction to the 50 % isodose line covering the planning target volume , whereas a total dose of 70 Gy was delivered at 7 Gy/fraction to the gross target volume . The median follow-up duration was 27 months . RESULTS Three to 6 months after treatment , the complete response rate for body-gamma knife radiosurgery was 63 % , and the overall response rate was 95 % . The 1-year , 2-year , and 3-year local control rates were all 95 % in all patients . The 1-year , 2-year , and 3-year overall survival rates were 100 % , 91 % , and 91 % , respectively , in patients with Stage I disease and 73 % , 64 % , and 64 % , respectively , in those with Stage II disease . Only 2.3 % ( 1/43 ) of the patients had Grade 3 pneumonitis . CONCLUSION Our highly focused stereotactic body radiotherapy method result ed in promising local control and survival with minimal toxicity PURPOSE The 50-month results of a prospect i ve Phase II trial of stereotactic body radiation therapy ( SBRT ) in medically inoperable patients are reported . METHODS AND MATERIAL S A total of 70 medically inoperable patients had clinical ly staged T1 ( 34 patients ) or T2 ( 36 patients ) ( < or = 7 cm ) , N0 , M0 , biopsy-confirmed non-small-cell lung carcinoma ( NSCLC ) and received SBRT as per our previously published reports . The SBRT treatment dose of 60 - 66 Gy was prescribed to the 80 % isodose volume in three fractions . RESULTS Median follow-up was 50.2 months ( range , 1.4 - 64.8 months ) . Kaplan-Meier local control at 3 years was 88.1 % . Regional ( nodal ) and distant recurrence occurred in 6 ( 8.6 % ) and 9 ( 12.9 % ) patients , respectively . Median survival ( MS ) was 32.4 months and 3-year overall survival ( OS ) was 42.7 % ( 95 % confidence interval [ 95 % CI ] , 31.1 - 54.3 % ) . Cancer-specific survival at 3 years was 81.7 % ( 95 % CI , 70.0 - 93.4 % ) . For patients with T1 tumors , MS was 38.7 months ( 95 % CI , 25.3 - 50.2 ) and for T2 tumors MS was 24.5 months ( 95 % CI , 18.5 - 37.4 ) ( p = 0.194 ) . Tumor volume ( < or = 5 cc , 5 - 10 cc , 10 - 20 cc , > 20 cc ) did not significantly impact survival : MS was 36.9 months ( 95 % CI , 18.1 - 42.9 ) , 34.0 ( 95 % CI , 16.9 - 57.1 ) , 32.8 ( 95 % CI , 21.3 - 57.8 ) , and 21.4 months ( 95 % CI , 17.8 - 41.6 ) , respectively ( p = 0.712 ) . There was no significant survival difference between patients with peripheral vs. central tumors ( MS 33.2 vs. 24.4 months , p = 0.697 ) . Grade 3 to 5 toxicity occurred in 5 of 48 patients with peripheral lung tumors ( 10.4 % ) and in 6 of 22 patients ( 27.3 % ) with central tumors ( Fisher 's exact test , p = 0.088 ) . CONCLUSION Based on our study results , use of SBRT results in high rates of local control in medically inoperable patients with Stage I NSCLC Objective To report serial 18F-fluorodeoxyglucose ( 18F-FDG ) positron emission tomography (PET)/computed tomography ( CT ) tumor response following CyberKnife radiosurgery for stage IA non-small cell lung cancer ( NSCLC ) . Methods Patients with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved study . Targeting was based on 3 - 5 gold fiducial markers implanted in or near tumors . Gross tumor volumes ( GTVs ) were contoured using lung windows ; margins were exp and ed by 5 mm to establish the planning treatment volumes ( PTVs ) . Doses ranged from 42 - 60 Gy in 3 equal fractions . 18F-FDG PET/CT was performed prior to and at 3 - 6-month , 9 - 15 months and 18 - 24 months following treatment . The tumor maximum st and ardized uptake value ( SUVmax ) was recorded for each time point . Results Twenty patients with an average maximum tumor diameter of 2.2 cm were treated over a 3-year period . A mean dose of 51 Gy was delivered to the PTV in 3 to 11 days ( mean , 7 days ) . The 30-Gy isodose contour extended an average of 2 cm from the GTV . At a median follow-up of 43 months , the 2-year Kaplan-Meier overall survival estimate was 90 % and the local control estimate was 95 % . Mean tumor SUVmax before treatment was 6.2 ( range , 2.0 to 10.7 ) . During early follow-up the mean tumor SUVmax remained at 2.3 ( range , 1.0 to 5.7 ) , despite transient elevations in individual tumor SUVmax levels attributed to peritumoral radiation-induced pneumonitis visible on CT imaging . At 18 - 24 months the mean tumor SUVmax for controlled tumors was 2.0 , witha narrow range of values ( range , 1.5 to 2.8 ) . A single local failure was confirmed at 24 months in a patient with an elevated tumor SUVmax of 8.4 . Conclusion Local control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional . Early transient increases in tumor SUVmax are likely related to radiation-induced pneumonitis . Tumor SUVmaxvalues return to background levels at 18 - 24 months , enhancing 18F-FDG PET/CT detection of local failure . The value of 18F-FDG PET/CT imaging for surveillance following lung SBRT deserves further study Background Stereotactic ablative radiotherapy ( SABR ) can achieve excellent local control rates in early-stage non-small cell lung cancer ( NSCLC ) and has emerged as a st and ard treatment option for patients who can not undergo surgery or those with isolated recurrences . However , factors that may predict toxicity or survival are largely unknown . We sought here to identify predictors of survival and pneumonitis after SABR for NSCLC in a relatively large single-institution series . Methods Subjects were 130 patients with stage I NSCLC treated with four-dimensional computed tomography ( 4D CT ) –planned , on-board volumetric image – guided SABR to 50 Gy in 4 fractions . Disease was staged by positron emission tomography/computed tomography ( PET/CT ) and scans were obtained again at the second follow-up after SABR . Results At a median follow-up time of 26 months , the 2-year local control rate was 98.5 % . The median overall survival ( OS ) time was 60 months , and OS rates were 93.0 % at 1 year , 78.2 % at 2 years , and 65.3 % at 3 years . No patient experienced grade 4–5 toxicity ; 15 had radiation pneumonitis ( 12 [ 9.3 % ] grade 2 and 3 [ 2.3 % ] grade 3 ) . Performance status , st and ardized uptake value (SUV)max on staging PET/CT , tumor histology , and disease operability were associated with OS on univariate analysis , but only staging SUVmax was independently predictive on multivariate analysis ( P = 0.034 ) . Dosimetric factors were associated with radiation pneumonitis on univariate analysis , but only mean ipsilateral lung dose ≥9.14 Gy was significant on multivariate analysis ( P = 0.005 ) . Conclusions OS and radiation pneumonitis after SABR for stage I NSCLC can be predicted by staging PET SUVmax and ipsilateral mean lung dose , respectively Published data suggests that wedge resection for stage I non-small cell lung cancer ( NSCLC ) is associated with improved overall survival compared to stereotactic body radiation therapy . We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC .  PET/CT imaging was completed for staging . Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references . Gross tumor volumes ( GTVs ) were contoured using lung windows ; the margins were exp and ed by 5 mm to establish the planning treatment volume ( PTV ) . Treatment plans were design ed using a mean of 156 pencil beams . Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions . The 30 Gy isodose contour extended at least 1 cm from the GTV to eradicate microscopic disease . Treatments were delivered using the CyberKnife system with tumor tracking . Examination and PET/CT imaging occurred at 3 month follow-up intervals . Forty patients ( median age 76 ) with a median maximum tumor diameter of 2.6 cm ( range , 1.4–5.0 cm ) and a mean post-bronchodilator percent predicted forced expiratory volume in 1 s ( FEV1 ) of 57 % ( range , 21–111 % ) were treated . A median dose of 48 Gy was delivered to the PTV over 3–13 days ( median , 7 days ) . The 30 Gy isodose contour extended a mean 1.9 cm from the GTV . At a median 44 months ( range , 12–72 months ) follow-up , the 3 year Kaplan – Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91 and 75 % , respectively . CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection , eradicating tumors with 1–2 cm margins in order to preserve lung function . Prospect i ve r and omized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence PURPOSE To compare 2 stereotactic body radiation therapy ( SBRT ) schedules for medically inoperable early-stage lung cancer to determine which produces the lowest rate of grade ≥3 protocol -specified adverse events ( psAEs ) at 1 year . METHODS AND MATERIAL S Patients with biopsy-proven peripheral ( ≥2 cm from the central bronchial tree ) T1 or T2 , N0 ( clinical ly node negative by positron emission tomography ) , M0 tumors were eligible . Patients were r and omized to receive either 34 Gy in 1 fraction ( arm 1 ) or 48 Gy in 4 consecutive daily fractions ( arm 2 ) . Rigorous central accreditation and quality assurance confirmed treatment per protocol guidelines . This study was design ed to detect a psAEs rate > 17 % at a 10 % significance level ( 1-sided ) and 90 % power . Secondary endpoints included rates of primary tumor control ( PC ) , overall survival ( OS ) , and disease-free survival ( DFS ) at 1 year . Design ating the better of the 2 regimens was based on prespecified rules of psAEs and PC for each arm . RESULTS Ninety-four patients were accrued between September 2009 and March 2011 . The median follow-up time was 30.2 months . Of 84 analyzable patients , 39 were in arm 1 and 45 in arm 2 . Patient and tumor characteristics were balanced between arms . Four ( 10.3 % ) patients on arm 1 ( 95 % confidence interval [ CI ] 2.9%-24.2 % ) and 6 ( 13.3 % ) patients on arm 2 ( 95 % CI 5.1%-26.8 % ) experienced psAEs . The 2-year OS rate was 61.3 % ( 95 % CI 44.2%-74.6 % ) for arm 1 patients and 77.7 % ( 95 % CI 62.5%-87.3 % ) for arm 2 . The 2-year DFS was 56.4 % ( 95 % CI 39.6%-70.2 % ) for arm 1 and 71.1 % ( 95 % CI 55.5%-82.1 % ) for arm 2 . The 1-year PC rate was 97.0 % ( 95 % CI 84.2%-99.9 % ) for arm 1 and 92.7 % ( 95 % CI 80.1%-98.5 % ) for arm 2 . CONCLUSIONS 34 Gy in 1 fraction met the prespecified criteria and , of the 2 schedules , warrants further clinical research BACKGROUND A clinical prediction model to identify malignant nodules based on clinical data and radiological characteristics of lung nodules was derived using logistic regression from a r and om sample of patients ( n = 419 ) and tested on data from a separate group of patients ( n = 210 ) . OBJECTIVE To use multivariate logistic regression to estimate the probability of malignancy in radiologically indeterminate solitary pulmonary nodules ( SPNs ) in a clinical ly relevant subset of patients with SPNs that measured between 4 and 30 mm in diameter . PATIENTS AND METHODS A retrospective cohort study at a multispecialty group practice included 629 patients ( 320 men , 309 women ) with newly discovered ( between January 1 , 1984 , and May 1 , 1986 ) 4- to 30-mm radiologically indeterminate SPNs on chest radiography . Patients with a diagnosis of cancer within 5 years prior to the discovery of the nodule were excluded . Clinical data included age , sex , cigarette-smoking status , and history of extrathoracic malignant neoplasm , asbestos exposure , and chronic interstitial or obstructive lung disease ; chest radiological data included the diameter , location , edge characteristics ( eg , lobulation , spiculation , and shagginess ) , and other characteristics ( eg , cavitation ) of the SPNs . Predictors were identified in a r and om sample of two thirds of the patients and tested in the remaining one third . RESULTS Sixty-five percent of the nodules were benign , 23 % were malignant , and 12 % were indeterminate . Three clinical characteristics ( age , cigarette-smoking status , and history of cancer [ diagnosis , > or = 5 years ago ] ) and 3 radiological characteristics ( diameter , spiculation , and upper lobe location of the SPNs ) were independent predictors of malignancy . The area ( + /-SE ) under the evaluated receiver operating characteristic curve was 0.8328 + /- 0.0226 . CONCLUSION Three clinical and 3 radiographic characteristics predicted the malignancy in radiologically indeterminate SPNs Objective Stereotactic body radiotherapy is the st and ard treatment for medically inoperable early‐stage non – small cell lung cancer . Recent data suggest that in operable patients , stereotactic body radiotherapy produces outcomes comparable to those of surgical resection . In veterans with early non – small cell lung cancer , we compared the outcomes of stereotactic body radiotherapy and video‐assisted thoracoscopic lobectomy . Methods We retrospectively review ed data from 183 patients ( 94.0 % male ) with clinical stage I non – small cell lung cancer who underwent stereotactic body radiotherapy ( n = 56 ) or video‐assisted thoracoscopic lobectomy ( n = 127 ) from 2009 to 2014 . Propensity matching was used to produce more comparable groups . Primary end points were tumor control and overall , recurrence‐free , and lung‐cancer – specific survival , as estimated by Kaplan – Meier actuarial analysis . Multivariable analysis was used to identify independent predictors . Results In the overall cohort , the patients who received stereotactic body radiotherapy were older than the patients who received video‐assisted thoracoscopic lobectomy  ( median age , 79.5 vs 64 years ) and had more comorbidities . In the 37 propensity‐matched pairs , the 3‐year actuarial tumor control rate was 54.3 % after stereotactic body radiotherapy and 90.6 % after video‐assisted thoracoscopic lobectomy ( P = .0038 ) . Actuarial lung cancer – specific 3‐year survival was 78.1 % ( stereotactic body radiotherapy ) versus 93.6 % ( video‐assisted thoracoscopic lobectomy ) ( P = .055 ) . One‐year overall , 3‐year overall , and 3‐year recurrence‐free survivals were 89.2 % , 52.9 % , and 38.5 % after stereotactic body radiotherapy and 94.6 % , 85.7 % , and 82.8 % after video‐assisted thoracoscopic lobectomy ( P < .005 for all ) , respectively . In multivariable analysis , stereotactic body radiotherapy independently predicted recurrence and poorer survival . Conclusions In veteran patients with early‐stage non – small cell lung cancer , video‐assisted thoracoscopic lobectomy result ed in better disease control and survival than stereotactic body radiotherapy . Although prior reports suggest that stereotactic body radiotherapy is a suitable alternative to surgery in early‐stage lung cancer , a prospect i ve r and omized trial is needed . Nevertheless , stereotactic body radiotherapy remains a suitable option for medically inoperable patients BACKGROUND The clinical stage of non-small cell lung cancer ( NSCLC ) determines the initial treatment , whereas the pathologic stage best determines prognosis and the need for adjuvant treatment . In an era in which stereotactic ablative radiotherapy ( SABR ) has become an alternative modality to surgical intervention , clinical staging is even more important , because pathologic staging is omitted in the case of SABR . The objective of this study was to determine the concordance between clinical and pathologic stage in routine clinical practice for patients with early-stage NSCLC . METHODS Prospect i ve data were derived from the Dutch Lung Surgery Audit ( DLSA ) in 2013 and 2014 . Patients with clinical stage I NSCLC who underwent surgical resection and had a positron emission tomography-computed tomography ( PET-CT ) scan in their clinical workup were selected .  Clinical and pathologic TNM ( cTNM and pTNM ) stages were compared . RESULTS From a total of 1,790 patients with clinical stage I , 1,555 ( 87 % ) patients were included in this analysis . Concordance between cTNM and pTNM was 59.9 % . Of the patients with clinical stage I , 22.6 % were upstaged to pathologic stage II or higher . In total , 14.9 % of all patients with clinical stage I had nodal metastases , and 5.5 % of all patients had unforeseen N2 disease . In patients with clinical stage T2a tumors , 21.3 % had nodal metastases , 14.5 % being N1 and 6.7 % being N2 disease . CONCLUSIONS Concordance between clinical and pathologic stage is 59.9 % . In patients with clinical stage I NSCLC , 22.6 % were upstaged to pathologic stage II or higher , which is an indication for adjuvant chemotherapy . Improvement in accuracy of staging is thus needed , particularly for these patients PURPOSE The impact of stereotactic body radiotherapy ( SBRT ) on 3-year progression-free survival of medically inoperable patients with stage I non-small-cell lung cancer ( NSCLC ) was analyzed in a prospect i ve phase II study . PATIENTS AND METHODS Fifty-seven patients with T1NOMO ( 70 % ) and T2N0M0 ( 30 % ) were included between August 2003 and September 2005 at seven different centers in Sweden , Norway , and Denmark and observed up to 36 months . SBRT was delivered with 15 Gy times three at the 67 % isodose of the planning target volume . RESULTS Progression-free survival at 3 years was 52 % . Overall- and cancer-specific survival at 1 , 2 , and 3 years was 86 % , 65 % , 60 % , and 93 % , 88 % , 88 % , respectively . There was no statistically significant difference in survival between patients with T1 or T2 tumors . At a median follow-up of 35 months ( range , 4 to 47 months ) , 27 patients ( 47 % ) were deceased , seven as a result of lung cancer and 20 as a result of concurrent disease . Kaplan-Meier estimated local control at 3 years was 92 % . Local relapse was observed in four patients ( 7 % ) . Regional relapse was observed in three patients ( 5 % ) . Nine patients ( 16 % ) developed distant metastases . The estimated risk of all failure ( local , regional , or distant metastases ) was increased in patients with T2 ( 41 % ) compared with those with T1 ( 18 % ) tumors ( P = .027 ) . CONCLUSION With a 3-year local tumor control rate higher than 90 % with limited toxicity , SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances BACKGROUND The st and ard of care for operable , stage I , non-small-cell lung cancer ( NSCLC ) is lobectomy with mediastinal lymph node dissection or sampling . Stereotactic ablative radiotherapy ( SABR ) for inoperable stage I NSCLC has shown promising results , but two independent , r and omised , phase 3 trials of SABR in patients with operable stage I NSCLC ( STARS and ROSEL ) closed early due to slow accrual . We aim ed to assess overall survival for SABR versus surgery by pooling data from these trials . METHODS Eligible patients in the STARS and ROSEL studies were those with clinical T1 - 2a ( < 4 cm ) , N0M0 , operable NSCLC . Patients were r and omly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling . We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint . Both trials are registered with Clinical Trials.gov ( STARS : NCT00840749 ; ROSEL : NCT00687986 ) . FINDINGS 58 patients were enrolled and r and omly assigned ( 31 to SABR and 27 to surgery ) . Median follow-up was 40·2 months ( IQR 23·0 - 47·3 ) for the SABR group and 35·4 months ( 18·9 - 40·7 ) for the surgery group . Six patients in the surgery group died compared with one patient in the SABR group . Estimated overall survival at 3 years was 95 % ( 95 % CI 85 - 100 ) in the SABR group compared with 79 % ( 64 - 97 ) in the surgery group ( hazard ratio [ HR ] 0·14 [ 95 % CI 0·017 - 1·190 ] , log-rank p=0·037 ) . Recurrence-free survival at 3 years was 86 % ( 95 % CI 74 - 100 ) in the SABR group and 80 % ( 65 - 97 ) in the surgery group ( HR 0·69 [ 95 % CI 0·21 - 2·29 ] , log-rank p=0·54 ) . In the surgery group , one patient had regional nodal recurrence and two had distant metastases ; in the SABR group , one patient had local recurrence , four had regional nodal recurrence , and one had distant metastases . Three ( 10 % ) patients in the SABR  group had grade 3 treatment-related adverse events ( three [ 10 % ] chest wall pain , two [ 6 % ] dyspnoea or cough , and one [ 3 % ] fatigue and rib fracture ) . No patients given SABR  had grade 4 events or treatment-related death . In the surgery group , one ( 4 % ) patient died of surgical complications and 12 ( 44 % ) patients had grade 3 - 4 treatment-related adverse events . Grade 3 events occurring in more than one patient in the surgery group were dyspnoea ( four [ 15 % ] patients ) , chest pain ( four [ 15 % ] patients ) , and lung infections ( two [ 7 % ] ) . INTERPRETATION SABR could be an option for treating operable stage I NSCLC . Because of the small patient sample size and short follow-up , additional r and omised studies comparing SABR with surgery in operable patients are warranted . FUNDING Accuray Inc , Netherl and s Organisation for Health Research and Development , NCI Cancer Center Support , NCI Clinical and Translational Science Award Objectives : The long‐term impact of stereotactic body radiotherapy ( SBRT ) on respiratory function in patients with inoperable non – small cell lung cancer ( NSCLC ) has not been well studied . The aim of this phase II trial was to assess local control , survival , and lung function at 36 months after treatment . Methods : From July 2008 to February 2012 , 42 patients in whom inoperable NSCLC with peripheral lesions was diagnosed were consecutively enrolled . Lung function testing included measurement of forced expiratory vital capacity , forced expiratory volume in 1 second , and diffusing capacity for carbon monoxide . All lung function parameters were registered at baseline and evaluated prospect ively after SBRT every 6 months for 2 years and annually thereafter . Results : Of the 42 initial patients , four were excluded . At 36 months after SBRT , 22 patients were still evaluable ( 12 deaths and four patients lost to follow‐up ) . At 36 months , the rate of local control was 94 % . At 1 , 2 , and 3 years , respectively , overall survival rates were 92 % , 75 % , and 66 % . Median overall survival was 57 months . Grade ( G ) 3 acute toxicity was observed in four patients ( 10 % ) . Chronic G1 toxicity was observed in all 38 cases ( 100 % ) , with the most common type being pneumonitis ( 26 patients [ 68 % ] ) . The mean lung function parameters at baseline and at 36 months after treatment were as follows : forced expiratory vital capacity 83 % versus 79 % ; forced expiratory volume in 1 second 62 % versus 57 % ; and diffusing capacity for carbon monoxide 54 % versus 54 % . These changes were not significant . Conclusions : In this trial , local control and survival rates  after SBRT were very good . Treatment with SBRT had no significant impact on lung function at 36 months . These findings provide further support for the use of SBRT as a radical treatment for NSCLC . Lung toxicity is minimal , even in patients with poor pulmonary function before treatment CONTEXT Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control ( 30%-40 % ) and a high rate of mortality ( 3-year survival , 20%-35 % ) with current management . OBJECTIVE To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer . DESIGN , SETTING , AND PATIENTS Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non-small cell tumors ( measuring < 5 cm in diameter ) and medical conditions precluding surgical treatment . The prescription dose was 18 Gy per fraction x 3 fractions ( 54 Gy total ) with entire treatment lasting between 1(1/2 ) and 2 weeks . The study opened May 26 , 2004 , and closed October 13 , 2006 ; data were analyzed through August 31 , 2009 . MAIN OUTCOME MEASURES The primary end point was 2-year actuarial primary tumor control ; secondary end points were disease-free survival ( ie , primary tumor , involved lobe , regional , and disseminated recurrence ) , treatment-related toxicity , and overall survival . RESULTS A total of 59 patients accrued , of which 55 were evaluable ( 44 patients with T1 tumors and 11 patients with T2 tumors ) with a median follow-up of 34.4 months ( range , 4.8 - 49.9 months ) . Only 1 patient had a primary tumor failure ; the estimated 3-year primary tumor control rate was 97.6 % ( 95 % confidence interval [ CI ] , 84.3%-99.7 % ) . Three patients had recurrence within the involved lobe ; the 3-year primary tumor and involved lobe ( local ) control rate was 90.6 % ( 95 % CI , 76.0%-96.5 % ) . Two patients experienced regional failure ; the local-regional control rate was 87.2 % ( 95 % CI , 71.0%-94.7 % ) . Eleven patients experienced disseminated recurrence ; the 3-year rate of disseminated failure was 22.1 % ( 95 % CI , 12.3%-37.8 % ) . The rates for disease-free survival and overall survival at 3 years were 48.3 % ( 95 % CI , 34.4%-60.8 % ) and 55.8 % ( 95 % CI , 41.6%-67.9 % ) , respectively . The median overall survival was 48.1 months ( 95 % CI , 29.6 months to not reached ) . Protocol -specified treatment-related grade 3 adverse events were reported in 7 patients ( 12.7 % ; 95 % CI , 9.6%-15.8 % ) ; grade 4 adverse events were reported in 2 patients ( 3.6 % ; 95 % CI , 2.7%-4.5 % ) . No grade 5 adverse events were reported . CONCLUSION Patients with inoperable non-small cell lung cancer who received stereotactic body radiation therapy had a survival rate of 55.8 % at 3 years , high rates of local tumor control , and moderate treatment-related morbidity OBJECTIVE ( S ) Recommendations for surveillance after stereotactic body radiation therapy ( SBRT ) for early stage non-small cell lung cancer ( NSCLC ) are not well defined . Prospect i ve studies evaluating the efficacy of SBRT have used interval posttreatment imaging with computed tomography ( CT ) . We set out to determine whether positron emission tomography ( PET ) combined with diagnostic chest CT ( PET/d-chest ) can enhance detection of potentially salvageable recurrence after SBRT . METHODS We performed a retrospective analysis of posttreatment imaging for 35 patients consecutively treated with SBRT for biopsy-proven early-stage NSCLC .  PET/d-chest was generally performed every 3 months after treatment . A board-certified radiologist who did not have access to the PET results retrospectively interpreted the CT scans . CT results were reported according to response criteria used in Radiation Therapy Oncology Group 0236 and compared with PET/d-chest readings . Local and regional recurrence-free survival was compared using the Mantle-Cox ( log-rank ) test . RESULTS Median follow-up was 12.8 months . Twenty-four patients had stage IA , 7 stage IB , 3 stage IIA , and 1 stage IIB biopsy-proven NSCLC .  Two-year overall survival was 62 % . CT scans indicated no regional recurrences .  PET/d-chest indicated 10 regional recurrences . The 1-year rate of regional recurrence-free survival as evaluated by CT and PET/d-chest was 100 % and 69.4 % , respectively ( P = .0045 ) . Four of 10 patients with a diagnosis of regional recurrence underwent salvage treatment with definitive chemoradiotherapy . CONCLUSIONS PET/d-chest enhances the detection of regional progression of NSCLC after SBRT over currently recommended practice s. In patients who are fit for salvage treatment , where early detection of recurrence can increase the likelihood of successful treatment , PET/d-chest appears critical for follow-up BACKGROUND Approximately two-thirds of patients with early-stage non-small-cell lung cancer ( NSCLC ) in The Netherl and s currently undergo surgical resection . As an increasing number of fit patients have elected to undergo stereotactic ablative radiotherapy ( SABR ) in recent years , we studied outcomes after SABR in patients with potentially operable stage I NSCLC . METHODS AND MATERIAL S In an institutional prospect i ve data base collected since 2003 , 25 % of lung SABR cases ( n = 177 patients ) were found to be potentially operable when the following patients were excluded : those with ( 1 ) synchronous lung tumors or other malignancy , ( 2 ) prior high-dose radiotherapy/pneumonectomy , ( 3 ) chronic obstructive pulmonary disease with a severity score of 3 - 4 according to the Global initiative for Obstructive Lung Disease classification . ( 4 ) a performance score of ≥3 , and ( 5 ) other comorbidity precluding surgery . Study patients included 101 males and 76 females , with a median age of 76 years old , 60 % of whom were staged as T1 and 40 % of whom were T2 . Median Charlson comorbidity score was 2 ( range , 0 - 5 ) . A SABR dose of 60 Gy was delivered using a risk-adapted scheme in 3 , 5 , or 8 fractions , depending on tumor size and location . Follow-up chest computed tomography scans were obtained at 3 , 6 , and 12 months and yearly thereafter . RESULTS Median follow-up was 31.5 months ; and median overall survival ( OS ) was 61.5 months , with 1- and 3-year survival rates of 94.7 % and 84.7 % , respectively . OS rates at 3 years in patients with ( n = 59 ) and without ( n = 118 ) histological diagnosis did not differ significantly ( 96 % versus 81 % , respectively , p = 0.39 ) . Post-SABR 30-day mortality was 0 % , while predicted 30-day mortality for a lobectomy , derived using the Thoracoscore predictive model ( Falcoz PE et al. J Thorac Cardiovasc Surg 2007;133:325 - 332 ) , would have been 2.6 % . Local control rates at 1 and 3 years were 98 % and 93 % , respectively . Regional and distant failure rates at 3 years were each 9.7 % . Toxicity was mild , with grade ≥3 radiation pneumonitis and rib fractures in 2 % and 3 % , respectively . CONCLUSIONS Patients with potentially operable disease who underwent primary SABR had a median OS that exceeded 5 years . This finding supports ongoing r and omized clinical trials comparing surgery and SABR in cases of operable stage I NSCLC BACKGROUND AND PURPOSE The outcome of stage I non-small cell lung cancer ( NSCLC ) patients treated with conventional radiotherapy is inferior to that of patients treated surgically . We aim ed to evaluate the clinical outcome of stereotactic body radiotherapy ( SBRT ) in the treatment of stage I NSCLC . MATERIAL S AND METHODS We 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 . RESULTS The 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 > or = grade 2 . CONCLUSIONS SBRT is safe and effective for stage I NSCLC patients . However , a more intensive treatment regimen should be considered for T2 tumours We report quality of life and indirect costs from patient reported outcomes from the ROSEL r and omized control trial comparing stereotactic ablative radiotherapy ( SABR , also known as stereotactic body radiotherapy or SBRT ) versus surgical resection for medically operable stage IA non-small cell lung cancer . ROSEL closed prematurely after accruing and r and omizing 22 patients . This exploratory analysis found the global health related quality of life and indirect costs to be significantly favorable and cheaper , with SABR PURPOSE To evaluate , in Japan Clinical Oncology Group study 0403 , the safety and efficacy of stereotactic body radiation therapy ( SBRT ) in patients with T1N0M0 non-small cell lung cancer ( NSCLC ) . METHODS AND MATERIAL S Eligibility criteria included histologically or cytologically proven NSCLC , clinical T1N0M0 . Prescribed dose was 48 Gy at the isocenter in 4 fractions . The primary endpoint was the percent ( % ) 3-year overall survival . The threshold % 3-year survival to be rejected was set at 35 % for inoperable patients , whereas the expected % 3-year survival was 80 % for operable patients . RESULTS Between July 2004 and November 2008 , 169 patients from 15 institutions were registered . One hundred inoperable and 64 operable patients ( total 164 ) were eligible . Patients ' characteristics were 122 male , 47 female ; median age 78 years ( range , 50 - 91 years ) ; adenocarcinomas , 90 ; squamous cell carcinomas , 61 ; others , 18 . Of the 100 inoperable patients , the % 3-year OS was 59.9 % ( 95 % confidence interval 49.6%-68.8 % ) . Grade 3 and 4 toxicities were observed in 10 and 2 patients , respectively . No grade 5 toxicity was observed . Of the 64 operable patients , the % 3-year OS was 76.5 % ( 95 % confidence interval 64.0%-85.1 % ) . Grade 3 toxicities were observed in 5 patients . No grade 4 and 5 toxicities were observed . CONCLUSIONS Stereotactic body radiation therapy for stage I NSCLC is effective , with low incidences of severe toxicity . This treatment can be considered a st and ard treatment for inoperable stage I NSCLC . This treatment is promising as an alternative to surgery for operable stage I NSCLC The most common regimen of stereotactic body radiotherapy ( SBRT ) for stage I nonsmall cell lung cancer in Japan is 48 grays ( Gy ) in 4 fractions over 4 days . Radiobiologically , however , higher doses are necessary to control larger tumors , and interfraction intervals should be > 24 hours to take advantage of reoxygenation . In this study , the authors tested the following regimen : For tumors that measured < 1.5 cm , 1.5 to 3.0 cm , and > 3.0 cm in greatest dimension , radiation doses of 44 Gy , 48 Gy , and 52 Gy , respectively , were given in 4 fractions with interfraction intervals of ≥3 days OBJECTIVES Stereotactic body radiation therapy has been proposed as an alternative local treatment option for high-risk patients with early-stage lung cancer . A direct comparison of outcomes between stereotactic body radiation therapy and surgical resection has not been reported . This study compares short-term outcomes between stereotactic body radiation therapy and surgical treatment of non-small cell lung cancer . METHODS We compared all patients treated with surgery ( January 2000-December 2006 ) or stereotactic body radiation therapy ( February 2004-May 2007 ) with clinical stage IA/B non-small cell lung cancer staged by computed tomography and positron emission tomography . Comorbidity scores were recorded prospect ively using the Adult Co-Morbidity Evaluation scoring system . Charts were review ed to determine local tumor recurrence , disease-specific survival , and overall survival . A propensity score matching analysis was used to adjust estimated treatment hazard ratios for confounding effects of patient age , comorbidity index , and clinical stage . RESULTS A total of 462 patients underwent surgery and 76 received stereotactic body radiation therapy .  Overall , surgical patients were younger ( P < .001 ) , had lower comorbidity scores ( P < .001 ) , and better pulmonary function ( forced expiratory volume in 1 second and carbon monoxide diffusion in the lung ) ( P < .001 ) . Among the surgical and stereotactic body radiation therapy groups , 62.6 % ( 291/462 ) and 78.9 % ( 60/76 ) were in clinical stage IA , respectively . Final pathology upstaged 35 % ( 161/462 ) of the surgery patients . In an unmatched comparison , overall 5-year survival was 55 % with surgery , and the 3-year survival was 32 % with radiation therapy . Among patients with clinical stage IA disease , 3-year local tumor control was 89 % with radiation therapy and 96 % with surgery ( P = .04 ) . There was no difference in local tumor control in stage IB disease ( P = .89 ) . No disease-specific survival differences were found in patients with 1A ( P = .33 ) or IB disease ( P = .69 ) . Propensity analysis matched 57 high-risk surgical patients to 57 patients undergoing stereotactic body radiation therapy . In the matched comparison of this subgroup , there was no difference in freedom from local recurrence ( 88 % vs 90 % ) , disease-free survival ( 77 % vs 86 % ) , and overall survival ( 54 % vs 38 % ) at 3 years . CONCLUSIONS In an unmatched comparison of clinical stage IA disease , surgical patients were healthier and had better local tumor control compared with those receiving stereotactic body radiation therapy . Propensity analysis in clinical stage IA/B non-small cell lung cancer revealed similar rates of local recurrence and disease-specific survival in patients treated with surgery compared with stereotactic body radiation therapy
Introduction : Stereotactic body radiation therapy ( SBRT ) is a promising curative treatment for early‐stage NSCLC .
It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients .
In this systematic review and meta‐ analysis , we assess survival outcomes after SBRT in studies with patients with clinical ly diagnosed versus biopsy‐proven early‐stage NSCLC .