Browsing by Author "Lautenschlaeger, Tim"

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    Baseline Karnofsky performance status is independently predictive of death within 30 days of intracranial radiation therapy completion for metastatic disease
    (Elsevier, 2020) McClelland, Shearwood, III.; Agrawal, Namita; Elbanna, May F.; Shiue, Kevin; Bartlett, Gregory K.; Lautenschlaeger, Tim; Zellars, Richard C.; Watson, Gordon A.; Ellsworth, Susannah G.; Radiation Oncology, School of Medicine
    Introduction: For patients with brain metastases, palliative radiation therapy (RT) has long been a standard of care for improving quality of life and optimizing intracranial disease control. The duration of time between completion of palliative RT and patient death has rarely been evaluated. Methods: A compilation of two prospective institutional databases encompassing April 2015 through December 2018 was used to identify patients who received palliative intracranial radiation therapy. A multivariate logistic regression model characterized patients adjusting for age, sex, admission status (inpatient versus outpatient), Karnofsky Performance Status (KPS), and radiation therapy indication. Results: 136 consecutive patients received intracranial palliative radiation therapy. Patients with baseline KPS <70 (OR = 2.2; 95%CI = 1.6-3.1; p < 0.0001) were significantly more likely to die within 30 days of treatment. Intracranial palliative radiation therapy was most commonly delivered to provide local control (66% of patients) or alleviate neurologic symptoms (32% of patients), and was most commonly delivered via whole brain radiation therapy in 10 fractions to 30 Gy (38% of patients). Of the 42 patients who died within 30 days of RT, 31 (74%) received at least 10 fractions. Conclusions: Our findings indicate that baseline KPS <70 is independently predictive of death within 30 days of palliative intracranial RT, and that a large majority of patients who died within 30 days received at least 10 fractions. These results indicate that for poor performance status patients requiring palliative intracranial radiation, hypofractionated RT courses should be strongly considered.
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    Blood-based biomarkers for precision medicine in lung cancer: precision radiation therapy
    (2017-12) De Ruysscher, Dirk; Jin, Jianyue; Lautenschlaeger, Tim; She, Jin-Xiong; Liao, Zhongxing; Kong, Feng-Ming (Spring); Medicine, School of Medicine
    Both tumors and patients are complex and models that determine survival and toxicity of radiotherapy or any other treatment ideally must take into account this variability as well as its dynamic state. The genetic features of the tumor and the host, and increasingly also the epi-genetic and proteomic characteristics, are being unraveled. Multiple techniques, including histological examination, blood sampling, measurement of circulating tumor cells (CTCs), and functional and molecular imaging, can be used for this purpose. However, the effects of radiation on the tumor and on organs at risk (OARs) are also influenced by the applied dose and volume of irradiated tissues. Combining all these biological, clinical, imaging, and dosimetric parameters in a validated prognostic or predictive model poses a major challenge. Here we aimed to provide an objective review of the potential of blood markers to guide high precision radiation therapy. A combined biological-mathematical approach opens new doors beyond prognostication of patients, as it allows truly precise oncological treatment. Indeed, the core for individualized and precision medicine is not only selection of patients, but even more the optimization of the therapeutic window on an individual basis. A holistic model will allow for determination of an individual dose-response relationship for each organ at risk for each tumor in each individual patient for the complete oncological treatment package. This includes, but is not limited to, radiotherapy alone. Individualized dose-response curves will allow for consideration of different doses of radiation and combinations with other drugs to plan for both optimal toxicity and complete response. Insights into the interactions between a multitude of parameters will lead to the discovery of new pathways and networks that will fuel new biological research on target discovery.
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    Brainstem metastases treated with Gamma Knife stereotactic radiosurgery: the Indiana University Health experience
    (Future Medicine:, 2018-01) Patel, Ajay; Mohammadi, Homan; Dong, Tuo; Shiue, Kevin Ren-Yeh; Frye, Douglas; Le, Yi; Ansari, Shaheryar; Watson, Gordon A.; Miller, James C.; Lautenschlaeger, Tim; Medicine, School of Medicine
    Brainstem metastases offer a unique challenge in cancer treatment, yet stereotactic radiosurgery (SRS) has proven to be an effective modality in treating these tumors. This report discusses the clinical outcomes of patients with brainstem metastases treated at Indiana University with Gamma Knife (GK) radiosurgery from 2008 to 2016. 19 brainstem metastases from 14 patients who had follow-up brain imaging were identified. Median tumor volume was 0.04 cc (range: 0.01-2.0 cc). Median prescribed dose was 17.5 Gy to the 50% isodose line (range: 14-22 Gy). Median survival after GK SRS treatment to brainstem lesion was 17.2 months (range: 2.8-45.6 months). The experience at Indiana University confirms the safety and efficacy of range of GK SRS prescription doses (14-22 Gy) to brainstem metastases.
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    Chemoradiotherapy versus chemotherapy alone for unresected intrahepatic cholangiocarcinoma: practice patterns and outcomes from the national cancer data base
    (AME Publishing Company, 2018-06) Verma, Vivek; Appiah, Adams Kusi; Lautenschlaeger, Tim; Adeberg, Sebastian; Simone, Charles B., II; Lin, Chi; Radiation Oncology, School of Medicine
    Background: Current guidelines recommend chemotherapy (CT) with or without radiotherapy (RT) for unresected intrahepatic cholangiocarcinoma (IC). Although there is currently lack of consensus, previous smaller studies have illustrated the efficacy of local therapy for this population. This investigation evaluated outcomes of chemoradiotherapy (CRT) versus CT alone in unresected IC using a large, contemporary national database. Methods: The National Cancer Data Base (NCDB) was queried for primary IC cases (2004-2013) receiving CT alone or CRT. Patients undergoing resection or not receiving CT were excluded, as were those with M1 disease or unknown M classification. Logistic regression analysis ascertained factors associated with CRT administration. Kaplan-Meier analysis evaluated overall survival (OS) between both groups. Cox proportional hazards modeling assessed variables associated with OS. Results: In total, 2,842 patients were analyzed [n=666 (23%) CRT, n=2,176 (77%) CT]. CRT was less likely delivered at community centers, in more recent time periods (2009-2013), to older patients, and in certain geographic locations. Median OS in the CRT and CT groups were 13.6 vs. 10.5 months, respectively (P<0.001). On multivariate analysis, poorer OS was associated with age, male gender, increased comorbidities, treatment at a community center, and treatment at earlier time periods (2004-2008) (P<0.05 for all). Notably, receipt of CRT independently predicted for improved OS (P<0.001). Conclusions: As compared to CT alone, CRT was independently associated with improved survival in unresected IC. These findings support a randomized trial evaluating this question that is currently accruing.
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    Discovery of increased number or interval growth of brain metastases on same-day GammaKnife™ planning MRI: Predicting factors and patient outcomes
    (Old City Publishing, 2022) Mereniuk, Todd R.; Burney, Heather N.; Lautenschlaeger, Tim; Watson, Gordon A.; Rhome, Ryan M.; Radiation Oncology, School of Medicine
    Purpose: To determine factors associated with increased risk of finding new and/or enlarged brain metastases (BM) on GammaKnife™ (GK) MRI and their impact on patient outcomes. Results: 43.9% of patients showed BM growth, 32.9% had additional brain metastases (aBM), and 18.1 % had both. Initial brain metastasis velocity (iBMV) was associated with finding aBM. Time between diagnostic MRI (dMRI) and GK MRI was associated with interval growth and each day increased this risk by 2%. Prior brain metastasectomy and greater time between either dMRI or latest extracranial RT and GK MRI predicted both aBM and BM growth. aBM and/or BM growth led to management change in 1.8% of cases and were not associated with OS or incidence of distant intracranial failure. Conclusions: Number of metastases seen on dMRI and iBMV predicted both aBM and/or BM growth, however, these factors did not significantly affect survival or incidence of distant intracranial failure.
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    Effects of Proton Center Closure on Pediatric Case Volume and Resident Education at an Academic Cancer Center
    (Elsevier, 2018-03) Galle, James O.; Long, David E.; Lautenschlaeger, Tim; Zellars, Richard C.; Watson, Gordon A.; Ellsworth, Susannah G.; Radiation Oncology, School of Medicine
    Purpose To analyze effects of closure of an academic proton treatment center (PTC) on pediatric case volume, distribution, and resident education. Methods and Materials This was a review of 412 consecutive pediatric (age ≤18 years) cases treated at a single institution from 2012 to 2016. Residents' Accreditation Council for Graduate Medical Education case logs for the same years were also analyzed. Characteristics of the patient population and resident case volumes before and after closure of the PTC are reported. Results Overall pediatric new starts declined by approximately 50%, from 35 to 70 per 6 months in 2012 to 2014 to 22 to 30 per 6 months in 2015 to 2016. Central nervous system (CNS) case volume declined sharply, from 121 patients treated in 2012 to 2015 to 18 patients in 2015 to 2016. In 2012 to 2014 our institution treated 36, 24, and 17 patients for medulloblastoma/intracranial primitive neuroectodermal tumor, ependymoma, and low-grade glioma, respectively, compared with 0, 1, and 1 patient(s) in 2015 to 2016. Forty-nine patients were treated with craniospinal radiation (CSI) from 2012 to 2014, whereas only 2 patients underwent CSI between 2015 and 2016. Hematologic malignancy patient volume and use of total body irradiation remained relatively stable. Patients treated when the PTC was open were significantly younger (9.1 vs 10.7 years, P=.010) and their radiation courses were longer (35.4 vs 20.9 days, P<.0001) than those treated after its closure. Resident case logs showed only a small decline in total pediatric cases, because the percentage of pediatric cases covered by residents increased after PTC closure; however, residents logged fewer CNS cases after PTC closure versus before. Conclusions Overall pediatric case volume decreased after PTC closure, as did the number of patients treated for potentially curable CNS tumors. Our findings raise important questions regarding resident training in pediatric radiation oncology as these cases become increasingly concentrated at specialized centers.
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    First report of pulmonary large cell neuroendocrine carcinoma treated with stereotactic body radiation therapy
    (Elsevier, 2019-11) McClelland, Shearwood; Durm, Gregory A.; Birdas, Thomas J.; Musto, Paul M.; Lautenschlaeger, Tim; Medicine, School of Medicine
    Introduction: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a very rare disease, comprising approximately 3% of lung cancers. Even for Stage I disease, recurrence after resection is common, with a poor five-year overall survival. We present the first report of stereotactic body radiotherapy (SBRT) for pulmonary LCNEC. Methods: A 54-year-old woman with a left upper lobe pulmonary nodule underwent a wedge resection with thoracoscopic mediastinal lymph node dissection, revealing a 2.3 cm pT1b N0 LCNEC. Approximately one year later, surveillance imaging demonstrated a new left upper lobe PET-avid nodule, resulting in completion left upper lobectomy revealing LCNEC, with 0/6 involved lymph nodes and negative staging studies. The patient subsequently chose surveillance over adjuvant chemotherapy; unfortunately 23 months later imaging revealed an enlarging 0.7 cm nodule adjacent to the previous resection site, despite the patient remaining in good health (KPS = 90). Subsequent restaging demonstrated no evidence of metastatic disease. Due to the morbidity of a third operation in this region, and based on the safety of SBRT for Stage I non small-cell lung cancer, the consensus decision from our thoracic oncology team was to proceed with SBRT as preferred management for presumptive second recurrence of LCNEC. The patient shortly thereafter underwent SBRT (50 Gy in 10 Gy/fraction) to this new nodule, 41 months following initial LCNEC diagnosis. Results: Four months following SBRT, the patient remains in excellent clinical condition (KPS 90), with no evidence of disease spread on surveillance studies. The nodule itself demonstrated no evidence of growth following SBRT. Conclusions: This first report of SBRT for pulmonary LCNEC demonstrates that SBRT is a feasible modality for this rare disease. A multidisciplinary thoracic oncology approach involving medical oncology, thoracic surgery, radiation oncology and pulmonology is strongly recommended to ensure proper patient selection for receipt of SBRT.
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    Genetic Variations in the Transforming Growth Factor-β1 Pathway May Improve Predictive Power for Overall Survival in Non-small Cell Lung Cancer
    (Frontiers Media, 2021-07-07) Zhang, Hong; Wang, Weili; Pi, Wenhu; Bi, Nan; DesRosiers, Colleen; Kong, Fengchong; Cheng, Monica; Monica, Li; Yang, Li; Lautenschlaeger, Tim; Jolly, Shruti; Jin, Jianyue; Kong, Feng-Ming (Spring); Radiation Oncology, School of Medicine
    Purpose: Transforming growth factor-β1 (TGF-β1), a known immune suppressor, plays an important role in tumor progression and overall survival (OS) in many types of cancers. We hypothesized that genetic variations of single nucleotide polymorphisms (SNPs) in the TGF-β1 pathway can predict survival in patients with non-small cell lung cancer (NSCLC) after radiation therapy. Materials and Methods: Fourteen functional SNPs in the TGF-β1 pathway were measured in 166 patients with NSCLC enrolled in a multi-center clinical trial. Clinical factors, including age, gender, ethnicity, smoking status, stage group, histology, Karnofsky Performance Status, equivalent dose at 2 Gy fractions (EQD2), and the use of chemotherapy, were first tested under the univariate Cox's proportional hazards model. All significant clinical predictors were combined as a group of predictors named "Clinical." The significant SNPs under the Cox proportional hazards model were combined as a group of predictors named "SNP." The predictive powers of models using Clinical and Clinical + SNP were compared with the cross-validation concordance index (C-index) of random forest models. Results: Age, gender, stage group, smoking, histology, and EQD2 were identified as significant clinical predictors: Clinical. Among 14 SNPs, BMP2:rs235756 (HR = 0.63; 95% CI:0.42-0.93; p = 0.022), SMAD9:rs7333607 (HR = 2.79; 95% CI 1.22-6.41; p = 0.015), SMAD3:rs12102171 (HR = 0.68; 95% CI: 0.46-1.00; p = 0.050), and SMAD4: rs12456284 (HR = 0.63; 95% CI: 0.43-0.92; p = 0.016) were identified as powerful predictors of SNP. After adding SNP, the C-index of the model increased from 84.1 to 87.6% at 24 months and from 79.4 to 84.4% at 36 months. Conclusion: Genetic variations in the TGF-β1 pathway have the potential to improve the prediction accuracy for OS in patients with NSCLC.
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    Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy
    (Elsevier, 2018) Shiue, Kevin; Cerra-Franco, Alberto; Shapiro, Ronald; Estabrook, Neil; Mannina, Edward M.; Deig, Christopher R.; Althouse, Sandra; Liu, Sheng; Wan, Jun; Zang, Yong; Agrawal, Namita; Ioannides, Pericles; Liu, Yongmei; Zhang, Chen; DesRosiers, Colleen; Bartlett, Greg; Ewing, Marvene; Langer, Mark P.; Watson, Gordon; Zellars, Richard; Kong, Feng-Ming; Lautenschlaeger, Tim; Radiation Oncology, School of Medicine
    Introduction It remains unclear if histology should be independently considered when choosing stereotactic ablative body radiotherapy dose prescriptions for NSCLC. Methods The study population included 508 patients with 561 lesions between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. Eligible patients had histologically or clinically diagnosed early-stage NSCLC and were treated with 3 to 5 fractions. The primary endpoint was in-field tumor control censored by either death or progression. Involved lobe control was also assessed. Results At 6.7 years median follow-up, 3-year in-field control, involved lobe control, overall survival, and progression-free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p = 0.0225) were independently associated with involved lobe failure. GTV (HR = 1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose with α/β = 10 [BED10], HR = 2.380, p = 0.0084) were independently associated with in-field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in-field control (12 Gy × 4 or 10 Gy × 5 versus 18 Gy or 20 Gy × 3: HR = 3.530, p = 0.0447, confirmed by propensity score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence interval: 1.005–1.022, p = 0.0012). For adenocarcinomas, there were no differences in in-field control observed using the above dose groupings (p = 0.12 and p = 0.31, respectively). Conclusions In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.
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    Impact of Lung Parenchymal-Only Failure on Overall Survival in Early-Stage Lung Cancer Patients Treated With Stereotactic Ablative Radiotherapy
    (Elsevier, 2021) Elbanna, May; Shiue, Kevin; Edwards, Donna; Cerra-Franco, Alberto; Agrawal, Namita; Hinton, Jason; Mereniuk, Todd; Huang, Christina; Ryan, Joshua L.; Smith, Jessica; Aaron, Vasantha D.; Burney, Heather; Zang, Yong; Holmes, Jordan; Langer, Mark; Zellars, Richard; Lautenschlaeger, Tim; Radiation Oncology, School of Medicine
    Introduction: The impact of lung parenchymal-only failure on patient survival after stereotactic ablative body radiotherapy (SABR) for early-stage non-small-cell lung cancer (NSCLC) remains unclear. Patients and methods: The study population included 481 patients with early-stage NSCLC who were treated with 3- to 5-fraction SABR between 2000 and 2016. The primary study objective was to assess the impact of out-of-field lung parenchymal-only failure (OLPF) on overall survival (OS). Results: At a median follow-up of 5.9 years, the median OS was 2.7 years for all patients. Patients with OLPF did not have a significantly different OS compared to patients without failure (P = .0952, median OS 4.1 years with failure vs. 2.6 years never failure). Analysis in a 1:1 propensity score-matched cohort for Karnofsky performance status, comorbidity score, and smoking status showed no differences in OS between patients without failure and those with OLPF (P = .8). In subgroup analyses exploring the impact of time of failure on OS, patients with OLPF 6 months or more after diagnosis did not have significantly different OS compared to those without failure, when accounting for immortal time bias (P = .3, median OS 4.3 years vs. 3.5 years never failure). Only 7 patients in our data set experienced failure within 6 months of treatment, of which only 4 were confirmed to be true failures; therefore, limited data are available in our cohort on the impact of OLPF for ≤ 6 months on OS. Conclusion: OLPF after SABR for early-stage NSCLC does not appear to adversely affect OS, especially if occurring at least 6 months after SABR. More studies are needed to understand if OLPF within 6 months of SABR is associated with adverse OS. These data are useful when discussing prognosis of lung parenchymal failures after initial SABR.