Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage non-small-cell lung cancer

Purpose: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. Materials and Methods: We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. Results: The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ≤90 Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. Conclusion: Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT. © 2013. The Korean Society for Radiation Oncology.

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer

Purpose: To identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). Materials and methods: Among 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. Results: Median follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). Conclusion: Three prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended. (C) 2020 Elsevier B.V. All rights reserved.

Comparison of treatment plans between IMRT with MR-linac and VMAT for lung SABR

Background The aim of this study was to compare the plan quality of magnetic-resonance image-based intensity modulated radiation therapy (MRI-based-IMRT) with the MRIdian Linac system to that of volumetric modulated arc therapy (VMAT) with the TrueBeam STx system for lung stereotactic ablative radiotherapy (SABR). Methods A total of 22 patients with tumors located in the lower lobe were retrospectively selected for the study. For each patient, both the MRI-based-IMRT and VMAT plans were generated using an identical CT image set and identical structures with the exception of the planning target volume (PTV). The PTVs of the MRI-based-IMRT were generated by adding an isotropic margin of 3 mm from the gross tumor volume, whereas those of VMAT were generated by adding an isotropic margin of 5 mm from the internal target volume. For both the MRI-based-IMRT and VMAT, the prescription doses to the PTVs were 60 Gy in four fractions. Results The average PTV volume of the MRI-based-IMRT was approximately 4-times smaller than that of VMAT (p <  0.001). The maximum dose to the bronchi for the MRI-based-IMRT was smaller than that for the VMAT (20.4 Gy versus 24.2 Gy, p <  0.001). In addition, V40Gy of the rib for the MRI-based-IMRT was smaller than that for the VMAT (1.8 cm3 versus 7.7 cm3, p = 0.008). However, the maximum doses to the skin and spinal cord for the MRI-based-IMRT (33.0 Gy and 14.5 Gy, respectively) were larger than those for the VMAT (27.8 Gy and 11.0 Gy, respectively) showing p values of less than 0.02. For the ipsilateral lung, the mean dose, V20Gy, V10Gy, and V5Gy for the MRI-based-IMRT were smaller than those for the VMAT (all with p <  0.05). For the contralateral lung, V5Gy, V10Gy, D1500cc, and D1000cc for the MRI-based-IMRT were larger than those for the VMAT (all with p <  0.05). The mean dose and V50% of the whole body for the MRI-based-IMRT were smaller than those for the VMAT (0.9 Gy versus 1.2 Gy, and 78.7 cm3 versus 103.5 cm3, respectively, all at p <  0.001). Conclusions The MRI-based-IMRT using the MRIdian Linac system could reduce doses to bronchi, rib, ipsilateral lung, and whole body compared to VMAT for lung SABR when the tumor was located in the lower lobe.This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2017M2A2A7A02020640, 2017M2A2A7A02020641, and 2017M2A2A7A02020643)

Treatment outcomes of re-irradiation using stereotactic ablative radiotherapy to lung: a propensity score matching analysis

Background The purpose of this study was to compare the treatment efficacy and safety of re-irradiation (re-RT) using stereotactic ablative radiotherapy (SABR) and initial SABR for primary, recurrent lung cancer or metastatic lung tumor. Methods A retrospective review of the medical records of 336 patients who underwent lung SABR was performed. Re-RT was defined as the overlap of the 70% isodose line of second-course SABR with that of the initial radiotherapy, and 20 patients were classified as the re-RT group. The median dose of re-RT using SABR was 54Gy (range 48–60Gy), and the median fraction number was 4 (range 4–6). One-to-three case-matched analysis with propensity score matching was used, and 60 patients were included in the initial SABR group of the matched cohort. Results The 1- and 2-year local control rates for the re-RT group were 73.9% and 63.3% and those for the initial SABR group in the matched cohort were 92.9% and 87.7%, respectively (P = 0.013). There was no difference in distant metastasis-free, progression-free, and overall survival rates. The crude grade ≥ 2 toxicity rates were 40.0% for the re-RT group and 25.0% for the initial SABR group (P = 0.318). Re-RT group had higher acute grade ≥ 2 toxicity rates (25.0% vs 5.0%, P = 0.031). One incident of grade 3 toxicity (pulmonary) was reported in the re-RT group; there was no grade 4‒5 toxicity. Conclusions The local control rate of the in-field re-RT SABR was lower than that of the initial SABR without compromising the survival rates. The toxicity of re-RT using SABR was acceptable

Effect of changes in monitor unit rate and energy on dose rate of total marrow irradiation based on Linac volumetric arc therapy

Background This study set out to evaluate the effect of dose rate on normal tissues (the lung, in particular) and the variation in the treatment efficiency as determined by the monitor unit (MU) and energy applied in Linac-based volumetric arc therapy (VMAT) total marrow irradiation (TMI). Methods Linac-based VMAT plans were generated for the TMI for six patients. The planning target volume (PTV) was divided into six sub-volumes, each of which had their own isocenter. To examine the effect of the dose rate and energy, a range of MU rates (40, 60, 80, 100, 300, and 600 MU/min) were selected for 6, 10, and 15 MV. All the plans were verified by portal dosimetry. Results The dosimetric parameters for the target and normal tissue were consistent in terms of the energy and MU rate. The beam-on time was changed from 59.6 to 6 min for 40 and 600 MU/min. When 40 MU/min was set for the lung, the dose rate delivered to the lung was less than 6 cGy/min (that is, 90%), while the beam-on time was approximately 10 min. The percentage volume of the lung receiving 20 cGy/min was 1.47, 3.94, and 6.22% at 6, 10, and 15 MV, respectively. However, for 600 MU/min, the total lung volume received over 6 cGy/min regardless of the energy, and over 20 cGy/min for 10 and 15 MV (i.e., 54.4% for 6 MV). Conclusions In TMI treatment, reducing the dose rate administered to the lung can decrease the incidence of pulmonary toxicity. To reduce the probability of normal tissue complications, the selection of the lowest MU rate is recommended for fields including the lung. To minimize the total treatment time, the maximum MU rate can be applied to other fields.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (no. 2017M2A2A7A02020641) and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (no. HA 16C0025)

Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: A role in organ preservation

Background/Aims: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. Methods: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. Results: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). Conclusions: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.

Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Triple-negative breast cancer (TNBC) shows aggressive clinical behavior, but the treatment options are limited due to lack of a specific target. TNBC shares many clinical and pathological similarities with BRCA-deficient breast cancer, for which poly(ADP-ribose) polymerase (PARP) inhibitor is effective, but PARP inhibitor alone failed to show clinical effects in patients with sporadic TNBC. Radiation induces DNA double-strand breaks, and the phosphoinositide 3-kinase (PI3K) signaling pathway has been known to regulate steady-state levels of homologous recombination. A recent preclinical study showed that PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient TNBC to PARP inhibition. Therefore, we assessed the radiosensitizing effect, and the underlying mechanism of combination treatment with PARP inhibitor olaparib and PI3K inhibitor PI-103 in BRCA-proficient TNBC cells. Methods MDA-MB-435S cells were divided into four treatment groups, irradiation (IR) alone, olaparib plus IR, PI-103 plus IR, and olaparib plus PI-103 plus IR. Cells were exposed to the drugs for 2 hours prior to irradiation, and the cell survival curve was obtained using a clonogenic assay. Western blotting and immunofluorescent detection of γH2AX foci were performed. Xenograft and bioluminescence imaging were carried out to assess in vivo radiosensitivity. Results Combined use of olaparib and PI-103 enhanced radiation-induced death of MDA-MB-435S (sensitizer enhancement ratio[SER]0.05,1.7) and MDA-MB-231-BR (SER0.05,2.1) cells and significantly reduced tumor volume in a xenograft models (P < 0.001). Treatment with PI-103 showed persistent γH2AX foci, indicating delayed repair of DNA strand breaks. PI-103 alone increased levels of poly(ADP-ribose) and phosphorylated extracellular signal-regulated kinase, and downregulated BRCA1. Conclusions Combined use of olaparib and PI-103 enhanced radiation-induced cell death in BRCA-proficient MDA-MB-435S and MDA-MB-231-BR cells and xenografts. TNBC patients have high incidences of locoregional relapse and distant metastasis, and radiation therapy targets both locoregional control and treatment of distant recurrences such as brain metastasis or other oligometastasis. Targeting of the PI3K signaling pathway combined with PARP inhibition maybe a feasible approach to enhance effects of radiation in BRCA-proficient TNBC

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO