STK11 Inactivation Predicts Rapid Recurrence in Inoperable Early-Stage Non-Small-Cell Lung Cancer.

PURPOSE: Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC. MATERIALS AND METHODS: This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling. A second cohort of ES-NSCLC treated with RT (Stanford, n = 39) was included to power clinical analyses. Prognostic gene alterations were identified and correlated with clinical variables. The primary clinical end point was the correlation of prognostic genes with the cumulative incidence of relapse, disease-free survival, and overall survival (OS) in a pooled RT cohort from the two institutions (N = 62). RESULTS: Although the surgery cohort exhibited lower rates of relapse, the RT cohort was highly enriched for somatic STK11 mutations (43% v 6.7%). Receiving supplemental oxygen (odds ratio [OR] = 5.5), 20+ pack-years of tobacco smoking (OR = 6.1), and Black race (OR = 4.3) were associated with increased frequency of STK11 mutations. In the pooled RT cohort (N = 62), STK11 mutation was strongly associated with inferior oncologic outcomes: 2-year incidence of relapse was 62% versus 20% and 2-year OS was 52% versus 85%, remaining independently prognostic on multivariable analyses (relapse: subdistribution hazard ratio = 4.0, P = .0041; disease-free survival: hazard ratio, 6.8, P = .0002; OS: hazard ratio, 6.0, P = .022). STK11 mutations were predominantly associated with distant failure, rather than local. CONCLUSION: In this cohort of ES-NSCLC, STK11 inactivation was associated with poor oncologic outcomes after RT and demonstrated a novel association with clinical hypoxia, which may underlie its correlation with medical inoperability. Further validation in larger cohorts and investigation of effective adjuvant systemic therapies may be warranted.

Effectiveness of Tibolone in Relieving Postmenopausal Symptoms for a Short-Term Period in Indian Women.

Background: Tibolone is an alternative to conventional estrogen and progesterone in relieving post-menopausal symptoms in Indian women. Material and Methods: A prospective short-term observational study was done at a tertiary care teaching hospital in New Delhi from November 2019 to September 2021. Fifty-three women, less than 60 years of age, presenting with moderate to severe intensity of menopausal symptoms as assessed by measuring menopausal rating score (MRS > 8) were enrolled and given Tibolone 2.5 mg daily for 3 months. Improvements in symptoms were seen at 1 month and 3 months. Side effects were also noted. Results: Marked improvement was seen as reduction in scores of psychological, somatic and genitourinary symptoms was noted. The psychological symptoms reduced from 8.92 ± 1.959 to 2.905 ± 1.042, the somatic symptoms decreased from 8.33 ± 2.299 to 3.4 ± 1.167, and genitourinary symptoms decreased from 3.64 ± 1.42 to 2.150 ± 0.948 after 3 months of treatment with Tibolone. Only 3 patients (5.6%) experienced vaginal spotting with no major side effects. Conclusions: Tibolone is a highly effective and well accepted drug to reduce moderate to severe menopausal symptoms, especially psychological symptoms including depression.

Correlation of Menopausal Symptoms with Serum Estradiol: A Study in Urban Indian Postmenopausal Women.

Background: Menopause is a hypoestrogenic state. Menopausal symptoms like hot flushes, depression, joint pains and urinary symptoms all correlate with falling estrogen levels. Material and Methods: Four hundred postmenopausal women who underwent natural menopause were included in the study conducted from Nov 2018 to March 2020. Surgical menopause, premature menopause and those on hormone replacement were excluded. Serum estradiol was measured and assessment of severity of menopausal symptoms was done using MRS questionnaire. MRS score of 0-4, 5-8, 9-15 and more than 16 were taken as none/minimal, mild, moderate and severe postmenopausal symptoms, respectively. Correlation between serum estradiol and symptoms was analyzed statistically. Results: Mean age of menopause in our study population was found to be 47.2 ± 3.96 years. Somatic symptoms were found maximum out of all 3 subscales in study population. Psychological subscale which included depression and mood changes was found to have the strongest correlation with serum estradiol level compared to other two subscales (somatic and genito-urinary). Discussion: Psychological symptoms, somatic symptoms and genitor urinary symptoms at menopause show correlation with falling estrogen levels. We found maximum correlation of psychological symptoms with low serum estradiol level. Conclusion: There is an inverse correlation of serum estradiol value with menopausal symptoms, with psychological symptoms (depression, anxiety, mood changes) showing highest correlation with low estrogen levels.

CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer.

Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02-2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21-3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

Role of Dienogest in Endometriosis in Young Women.

INTRODUCTION: Endometriosis associated pelvic pain (EAPP) is the most common complaint of patients with endometriosis. Nearly, 70% of females with endometriosis present with EAPP while endometriomas are found in 17-44% of patients. MATERIAL AND METHODS: A short-term single centre study was carried out in 56 patients in the age group of 15-35 years with complaints of pain and diagnosed as endometriosis either by imaging studies and/or by laparoscopy was given dienogest 2 mg OD, and effect of treatment was seen as improvement of pain score over a period of 3 months. The effect of dienogest was also seen on size of endometrioma. Patients were followed up at 1 and 3 months. RESULTS AND DISCUSSION: Out of 56 patients, 38 (67.8%) patients reported their pain relief within 2-5 days after starting dienogest. Out of 41 patients (73%) who had severe pain at enrollment, only 1 patient (1.79%) complained of severe pain at the end of 1 month with dienogest. Successful reduction in endometriotic cyst size (>50%) was seen in 3 patients (5.3%) at the end of 1 month with dienogest. Out of 56 patients, 41 patients (73.2%) had significant pain relief (>30%) at three months of treatment. At the end of 3 months, seven patients (12.5%) had significant cyst size reduction (>50%) with dienogest. No major side effects were noted. CONCLUSION: Dienogest is well tolerated drug for endometriosis showing significant relief of pain. However, it was seen that though endometriomas did not grow during treatment, significant regression was uncommon.

Measurement of Angle of Descent (AOD) by Transperineal Ultrasound in Labour to Predict Successful Vaginal Delivery.

INTRODUCTION: Non-progress of labour forms the largest indication caesarean section. The diagnosis of failure of descent using serial digital examination is objective, poor reproducibility, carries the risk of infection and is painful to the labouring patient. There is a need if not an alternative, adjunctive to digital vaginal examination. Measuring angle of descent (AOD) to predict vaginal birth in late labour by transperineal ultrasound provides an alternative without any of the above-mentioned drawbacks. MATERIALS AND METHODS: A prospective observational study in 64 patients in the late first stage and second stage of labour with cephalic presentation was carried out, from September 2017 to December 2018, in PGIMER and DR. RML Hospital. Angle of descent was measured by transperineal ultrasound. Angle of descent is the angle between the longitudinal axis of pubic bone and a line joining the lowest edge of the pubis to the lowest convexity of the foetal skull. Time of assessment of AOD1 was noted, and if patient did not deliver within 2 h, another AOD2 was recorded. Eighty-five readings were obtained, and AOD predicting successful vaginal delivery was calculated. RESULTS AND DISCUSSION: AOD of 116° and more resulted in vaginal delivery, spontaneous or instrumental. As the angle of descent increased, there was a decrease in time interval to vaginal delivery with correlation coefficient of - 0.939. CONCLUSION: The use of intrapartum transperineal ultrasound and measurement of angle of descent can prove to be a valuable adjunct in management of labour, especially in cases of prolonged first and second stages of labour in predicting successful vaginal delivery. AOD of 116° or more can predict successful vaginal delivery within 2 h. AOD can be used in centres having facilities of intrapartum ultrasound. The authors recommend the use of ultrasound in labour room as it is non-invasive and can provide a lot of information. This method is currently useful for tertiary centres or medical colleges.

Heart V5 predicts cardiac events in unresectable lung cancer patients undergoing chemoradiation.

BACKGROUND: Recent studies incorporating dose escalated radiation identified heart dose as a predictor of cardiac toxicity in unresectable lung cancer patients. Whether conventionally dosed radiation impacts cardiac events remains unclear. METHODS: Stage III lung cancer patients undergoing definitive chemoradiation to 60-70 Gy were analyzed. Clinical and dosimetric factors (mean heart dose, heart V5-60 in 5 Gy increments) were analyzed against freedom from ≥ grade 3 cardiac events and overall survival (OS) by log-rank test. Multivariable analysis (MVA) for factors significant on univariate analysis was performed by Cox proportional hazards. RESULTS: A total of 108 patients were identified. Median follow-up was 18.0 months. One- and two-year OS were 79% and 61%, respectively. On MVA, gross tumor volume (GTV) ≥98.6 cm3 [hazard ratio (HR): 2.11, 95% confidence interval (CI): 1.15-3.93, P=0.02] and female gender (HR: 2.01, 95% CI: 1.09-3.73, P=0.03) predicted for worse survival. Twelve patients (11%) developed ≥ grade 3 cardiac events. One- and two-year freedom from cardiac events (FFCE) was 94% and 84% respectively. On MVA, heart V5 ≥49% predicted for cardiac events (HR: 11.44, 95% CI: 1.31-111.60, P=0.03) while female gender was nearly significant (HR: 3.49, 95% CI: 0.97-16.80, P=0.06). Females presented with similar comorbidity scores, GTVs, and relapse rates but experienced higher heart doses than their male counterparts. CONCLUSIONS: Heart V5 ≥49% predicted for cardiac events after chemoradiation. However, cardiac dosimetry was not associated with survival. Rather, female gender and GTV ≥98.6 cm3 led to worse survival. This study corroborates emerging data that low-dose radiation to the heart impacts cardiac toxicity.

Effect of Endoscopic Bronchial Ultrasound on Outcomes for Stage I Non-Small-Cell Lung Cancer Patients Receiving Hypofractionated Radiotherapy.

BACKGROUND: In this study we sought to determine if staging endoscopic bronchial ultrasound (EBUS) improves outcomes in stage I non-small-cell lung cancer (NSCLC) patients who received hypofractionated radiation therapy (HFRT). PATIENTS AND METHODS: Patients with stage I NSCLC treated with HFRT from 2008 to 2015 were retrospectively identified from 3 affiliated institutions. All patients underwent positron emission tomography/computed tomography staging and a subset of patients received pretreatment EBUS. Patients with and without pre-radiation therapy EBUS were compared for baseline characteristics. The log rank test was used to compare Kaplan-Meier estimates. Univariate analysis (UVA) and multivariable analysis (MVA) were used to analyze the effect of factors on disease-free survival (DFS) and overall survival (OS). RESULTS: Ninety-two patients met study criteria. Median follow-up for the entire cohort was 21 months. Two-year DFS and OS were 63% and 81%, respectively. Two-year freedom from local, regional, and distant failure were 93%, 87%, and 87%, respectively. Thirty-seven of 92 patients (40%) received pretreatment EBUS. There were no statistically significant differences in 2-year freedom from regional failure rates, DFS, or OS for EBUS-staged versus non-EBUS-staged patients. On UVA, smaller tumor size (P = .03) and higher performance status (P = .05) were associated with improved OS. On MVA, tumor size retained significance for improved OS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.19-0.97; P = .04) and higher performance status showed a trend toward improved OS (HR, 0.51; 95% CI, 0.23-1.11; P = .09). CONCLUSION: In this retrospective series, we did not detect a difference in regional failure or survival outcomes among stage I NSCLC patients who received invasive staging with EBUS before HFRT.

Association between intensity modulated radiotherapy and survival in patients with stage III non-small cell lung cancer treated with chemoradiotherapy.

PURPOSE: To determine the effect of radiotherapy (RT) technique on treatment compliance and overall survival (OS) in patients with stage III non-small lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT). METHODS AND MATERIALS: This study included patients with stage III NSCLC in the National Cancer Database treated between 2003 and 2011 with definitive CRT to 60-63 Gray (Gy). Radiation treatment interruption (RTI) was defined as a break of ≥4 days. Treatment technique was dichotomized as intensity modulated (IMRT) or non-IMRT techniques. RESULTS: Out of the cohort of 7492, 35% had a RTI and 10% received IMRT. With a median follow-up of surviving patients of 32 months, the median survival for those with non-IMRT vs. IMRT was 18.2 months vs. 20 months (p<0.0001). Median survival for those with and without an RTI≥4 days was 16.1 months vs. 19.8 months (p<0.0001). Use of IMRT predicted for a decreased likelihood of RTI (odds ratio, 0.84, p=0.04). On multivariable analysis for OS, IMRT had a HR of 0.89 (95% CI: 0.80-0.98, p=0.01) and RTI had a HR of 1.2 (95% confidence interval (CI): 1.14-1.27, p=0.001). CONCLUSIONS: IMRT was associated with small but significant survival advantage for patients with stage III NSCLC treated with CRT. A RTI led to inferior survival, and both IMRT and RTI were independently associated with OS. Additional research should investigate whether improved tolerability, reduced normal tissue exposure, or superior coverage drives the association between IMRT and improved survival.

Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy.

PURPOSE/OBJECTIVES: Patients receiving stereotactic body radiotherapy for stage I non-small cell lung cancer are typically staged clinically with positron emission tomography-computed tomography. Currently, limited data exist for the detection of occult hilar/peribronchial (N1) disease. We hypothesize that positron emission tomography-computed tomography underestimates spread of cancer to N1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of N1 nodal stations in addition to N2 nodes. MATERIALS/METHODS: A retrospective study was performed of all patients with clinical stage I (T1-2aN0) non-small cell lung cancer (American Joint Committee on Cancer, 7th edition) by positron emission tomography-computed tomography at our institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Findings on positron emission tomography-computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography-computed tomography for the detection of N1 nodal disease. An analysis was conducted to identify predictors of occult spread. RESULTS: A total of 105 patients with clinical stage I non-small cell lung cancer were included in this study, of which 8 (7.6%) patients were found to have occult N1 metastasis on pathologic review yielding a negative predictive value for N1 disease of 92.4%. No patients had occult mediastinal nodes. The negative predictive value for positron emission tomography-computed tomography in patients with clinical stage T1 versus T2 tumors was 72 (96%) of 75 versus 25 (83%) of 30, respectively ( P = .03), and for peripheral versus central tumor location was 77 (98%) of 78 versus 20 (74%) of 27, respectively ( P = .0001). The negative predictive values for peripheral T1 and T2 tumors were 98% and 100%, respectively; while for central T1 and T2 tumors, the rates were 85% and 64%, respectively. Occult lymph node involvement was not associated with primary tumor maximum standard uptake value, histology, grade, or interval between positron emission tomography-computed tomography and surgery. CONCLUSION: Our results support pathologic assessment of N1 lymph nodes in patients with stage Inon-small cell lung cancer considered for stereotactic body radiotherapy, with the greatest benefit in patients with central and T2 tumors. Diagnostic evaluation with endoscopic bronchial ultrasound should be considered in the evaluation of stereotactic body radiotherapy candidates.

Comprehensive genetic testing identifies targetable genomic alterations in most patients with non-small cell lung cancer, specifically adenocarcinoma, single institute investigation.

This study reviews extensive genetic analysis in advanced non-small cell lung cancer (NSCLC) patients in order to: describe how targetable mutation genes interrelate with the genes identified as variants of unknown significance; assess the percentage of patients with a potentially targetable genetic alterations; evaluate the percentage of patients who had concurrent alterations, previously considered to be mutually exclusive; and characterize the molecular subset of KRAS. Thoracic Oncology Research Program Databases at the University of Chicago provided patient demographics, pathology, and results of genetic testing. 364 patients including 289 adenocarcinoma underwent genotype testing by various platforms such as FoundationOne, Caris Molecular Intelligence, and Response Genetics Inc. For the entire adenocarcinoma cohort, 25% of patients were African Americans; 90% of KRAS mutations were detected in smokers, including current and former smokers; 46% of EGFR and 61% of ALK alterations were detected in never smokers. 99.4% of patients, whose samples were analyzed by next-generation sequencing (NGS), had genetic alterations identified with an average of 10.8 alterations/tumor throughout different tumor subtypes. However, mutations were not mutually exclusive. NGS in this study identified potentially targetable genetic alterations in the majority of patients tested, detected concurrent alterations and provided information on variants of unknown significance at this time but potentially targetable in the future.

Prevalence and Predictors of Inappropriate Delivery of Palliative Thoracic Radiotherapy for Metastatic Lung Cancer.

BACKGROUND: High-level evidence has established well-recognized standard treatment regimens for patients undergoing palliative chest radiotherapy (RT) for stage IV non-small cell lung cancer (NSCLC), including treating with fewer than 15 fractions of RT, and not delivering concurrent chemoradiation (CRT) because of its increased toxicity and limited efficacy in the palliative setting. METHODS: The study included patients in the National Cancer Database from 2004 to 2012 with stage IV lung cancer who received palliative chest radiation therapy. Logistic regression was performed to determine predictors of standard vs nonstandard regimens (>15 fractions or CRT). All statistical tests were two-sided. RESULTS: There were 46 803 patients in the analysis and 49% received radiotherapy for longer than 15 fractions, and 28% received greater than 25 fractions. Approximately 19% received CRT. The strongest independent predictors of long-course RT were private insurance (odds ratio [OR] = 1.40 vs uninsured, 95% confidence interval [CI] = 1.28 to 1.53) and treatment in community cancer programs (OR = 1.49, 95% CI = 1.38 to 1.58) compared with academic research programs. The strongest factors that predicted for concurrent chemoradiotherapy were private insurance (OR = 1.38 95% CI = 1.23 to 1.54) compared with uninsured patients and treatment in community cancer programs (OR = 1.44, 95% CI = 1.33 to 1.56) compared with academic programs. CONCLUSIONS: Approximately half of all patients with metastatic lung cancer received a higher number of radiation fractions than recommended. Patients with private insurance and treated in community cancer centers were more likely to receive longer courses of RT or CRT. This demonstrates that a substantial number of patients requiring palliative thoracic radiotherapy are overtreated and further work is necessary to ensure these patients are treated according to evidenced-based guidelines.

Comparative effectiveness of aggressive thoracic radiation therapy and concurrent chemoradiation therapy in metastatic lung cancer.

PURPOSE: We aimed to determine the comparative effectiveness of radiation dose escalation and concurrent chemoradiation therapy (CCRT) in a population-based cohort of patients with stage IV non-small cell lung cancer who underwent palliative thoracic radiation therapy (RT). METHODS AND MATERIALS: The cohort consisted of 27,063 patients in the National Cancer Database with stage IV non-small cell lung cancer treated with thoracic RT between 20 and 55 Gy in 2004 to 2011. High- versus intermediate- vs low-dose (HD vs ID vs LD, respectively) RT was defined as biologically effective dose above 50 Gy, between 35 and 50 Gy, and below 35 Gy, respectively. Among patients who received any chemotherapy, separate analyses were performed to examine the impact of CCRT on overall survival (OS). RESULTS: The median follow-up was 3.9 months for the entire cohort and 18 months for surviving patients. The 5 most common treatment schemes were 30/10 (Gy/fraction, 23% of entire cohort), 35/14 (8%), 37.5/15 (7%), 40/20 (3%), and 50/20 (3%). On multivariable analysis, the survival hazard ratios (HRs) for HD and ID compared with LD RT were 0.37 and 0.51, respectively (P < .0001). Propensity score matching found a superior survival benefit for ID and HD (HR, 0.41 and 0.57 for HD and ID RT, respectively, vs LD, P < .0001). Among those who received any chemotherapy (59% of total), the median OS for patients treated with CCRT (19% of total) was 5.3 versus 5.6 months (P = .667). On multivariable analysis, the HR for CCRT was 1.01 (P = .46). CONCLUSIONS: The delivery of higher-dose RT but not concurrent chemotherapy was associated with a significant improvement of OS. This population-based study supports higher-dose palliative regimens and motivates prospective study of escalation beyond a biologically effective dose of 35 Gy.

Comparison of Two Deformable Registration Algorithms in the Presence of Radiologic Change Between Serial Lung CT Scans.

We evaluated the image registration accuracy achieved using two deformable registration algorithms when radiation-induced normal tissue changes were present between serial computed tomography (CT) scans. Two thoracic CT scans were collected for each of 24 patients who underwent radiation therapy (RT) treatment for lung cancer, eight of whom experienced radiologically evident normal tissue damage between pre- and post-RT scan acquisition. For each patient, 100 landmark point pairs were manually placed in anatomically corresponding locations between each pre- and post-RT scan. Each post-RT scan was then registered to the pre-RT scan using (1) the Plastimatch demons algorithm and (2) the Fraunhofer MEVIS algorithm. The registration accuracy for each scan pair was evaluated by comparing the distance between landmark points that were manually placed in the post-RT scans and points that were automatically mapped from pre- to post-RT scans using the displacement vector fields output by the two registration algorithms. For both algorithms, the registration accuracy was significantly decreased when normal tissue damage was present in the post-RT scan. Using the Plastimatch algorithm, registration accuracy was 2.4 mm, on average, in the absence of radiation-induced damage and 4.6 mm, on average, in the presence of damage. When the Fraunhofer MEVIS algorithm was instead used, registration errors decreased to 1.3 mm, on average, in the absence of damage and 2.5 mm, on average, when damage was present. This work demonstrated that the presence of lung tissue changes introduced following RT treatment for lung cancer can significantly decrease the registration accuracy achieved using deformable registration.

Increasing radiation therapy dose is associated with improved survival in patients undergoing stereotactic body radiation therapy for stage I non-small-cell lung cancer.

PURPOSE: To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage non-small-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. METHODS AND MATERIALS: The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an α/ß ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods and Cox proportional hazard regression. RESULTS: The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy × 3 (34%), 12 Gy × 4 (16%), 18 Gy × 3 (10%), 15 Gy × 3 (10%), and 16 Gy × 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log-rank P=.03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=.9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=.01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=.01), T2 tumor (HR 1.99, P=.0001), and HD (HR 0.68, P=.001). CONCLUSIONS: This comparative effectiveness analysis of SBRT dose for patients with stage I non-small-cell lung cancer suggests that higher doses (>150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors.

Stereotactic body radiotherapy and treatment at a high volume facility is associated with improved survival in patients with inoperable stage I non-small cell lung cancer.

BACKGROUND: This study examined the comparative effectiveness of no treatment (NoTx), conventional fractionated radiotherapy (ConvRT), and stereotactic body radiotherapy (SBRT) in patients with inoperable stage I non-small cell lung cancer. This population based cohort also allowed us to examine what facility level characteristics contributed to improved outcomes. METHODS: We included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=13,036). Overall survival (OS) was estimated using Kaplan-Meier methods and Cox proportional hazard regression. RESULTS: The median follow up was 68months (interquartile range: 35-83months) in surviving patients. Among the cohort, 52% received NoTx, 41% received ConvRT and 6% received SBRT. The 3-year OS was 28% for NoTx, 36% for ConvRT radiotherapy, and 48% for the SBRT cohort (p<0.0001). On multivariate analysis, the hazard ratio for SBRT and ConvRT were 0.67 and 0.77, respectively, as compared to NoTx (1.0 ref) (p<0.0001). Patients treated at a high volume facility vs. low volume facility had a hazard ratio of 0.94 vs. 1.0 (p=0.01). CONCLUSIONS: Patients with early stage inoperable lung cancer treated with SBRT and at a high volume facility had a survival benefit compared to patients treated with ConvRT or NoTx or to those treated at a low volume facility.

Effect of deformable registration on the dose calculated in radiation therapy planning CT scans of lung cancer patients.

PURPOSE: To characterize the effects of deformable image registration of serial computed tomography (CT) scans on the radiation dose calculated from a treatment planning scan. METHODS: Eighteen patients who received curative doses (≥ 60 Gy, 2 Gy/fraction) of photon radiation therapy for lung cancer treatment were retrospectively identified. For each patient, a diagnostic-quality pretherapy (4-75 days) CT scan and a treatment planning scan with an associated dose map were collected. To establish correspondence between scan pairs, a researcher manually identified anatomically corresponding landmark point pairs between the two scans. Pretherapy scans then were coregistered with planning scans (and associated dose maps) using the demons deformable registration algorithm and two variants of the Fraunhofer MEVIS algorithm ("Fast" and "EMPIRE10"). Landmark points in each pretherapy scan were automatically mapped to the planning scan using the displacement vector field output from each of the three algorithms. The Euclidean distance between manually and automatically mapped landmark points (dE) and the absolute difference in planned dose (|ΔD|) were calculated. Using regression modeling, |ΔD| was modeled as a function of dE, dose (D), dose standard deviation (SD(dose)) in an eight-pixel neighborhood, and the registration algorithm used. RESULTS: Over 1400 landmark point pairs were identified, with 58-93 (median: 84) points identified per patient. Average |ΔD| across patients was 3.5 Gy (range: 0.9-10.6 Gy). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, with an average dE across patients of 5.2 mm (compared with >7 mm for the other two algorithms). Consequently, average |ΔD| was also lowest using the Fraunhofer MEVIS EMPIRE10 algorithm. |ΔD| increased significantly as a function of dE (0.42 Gy/mm), D (0.05 Gy/Gy), SD(dose) (1.4 Gy/Gy), and the algorithm used (≤ 1 Gy). CONCLUSIONS: An average error of <4 Gy in radiation dose was introduced when points were mapped between CT scan pairs using deformable registration, with the majority of points yielding dose-mapping error <2 Gy (approximately 3% of the total prescribed dose). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, resulting in the smallest errors in mapped dose. Dose differences following registration increased significantly with increasing spatial registration errors, dose, and dose gradient (i.e., SDdose). This model provides a measurement of the uncertainty in the radiation dose when points are mapped between serial CT scans through deformable registration.