A comparison of two methodologies for radiotherapy treatment plan optimization and QA for clinical trials.

BACKGROUND AND PURPOSE: The efficacy of clinical trials and the outcome of patient treatment are dependent on the quality assurance (QA) of radiation therapy (RT) plans. There are two widely utilized approaches that include plan optimization guidance created based on patient-specific anatomy. This study examined these two techniques for dose-volume histogram predictions, RT plan optimizations, and prospective QA processes, namely the knowledge-based planning (KBP) technique and another first principle (FP) technique. METHODS: This analysis included 60, 44, and 10 RT plans from three Radiation Therapy Oncology Group (RTOG) multi-institutional trials: RTOG 0631 (Spine SRS), RTOG 1308 (NSCLC), and RTOG 0522 (H&N), respectively. Both approaches were compared in terms of dose prediction and plan optimization. The dose predictions were also compared to the original plan submitted to the trials for the QA procedure. RESULTS: For the RTOG 0631 (Spine SRS) and RTOG 0522 (H&N) plans, the dose predictions from both techniques have correlation coefficients of >0.9. The RT plans that were re-optimized based on the predictions from both techniques showed similar quality, with no statistically significant differences in target coverage or organ-at-risk sparing. The predictions of mean lung and heart doses from both methods for RTOG1308 patients, on the other hand, have a discrepancy of up to 14 Gy. CONCLUSIONS: Both methods are valuable tools for optimization guidance of RT plans for Spine SRS and Head and Neck cases, as well as for QA purposes. On the other hand, the findings suggest that KBP may be more feasible in the case of inoperable lung cancer patients who are treated with IMRT plans that have spatially unevenly distributed beam angles.

A study of positioning orientation effect on segmentation accuracy using convolutional neural networks for rectal cancer.

PURPOSE: Convolutional neural networks (CNN) have greatly improved medical image segmentation. A robust model requires training data can represent the entire dataset. One of the differing characteristics comes from variability in patient positioning (prone or supine) for radiotherapy. In this study, we investigated the effect of position orientation on segmentation using CNN. METHODS: Data of 100 patients (50 in supine and 50 in prone) with rectal cancer were collected for this study. We designed three sets of experiments for comparison: (a) segmentation using the model trained with data from the same orientation; (b) segmentation using the model trained with data from the opposite orientation; (c) segmentation using the model trained with data from both orientations. We performed fivefold cross-validation. The performance was evaluated on segmentation of the clinical target volume (CTV), bladder, and femurs with Dice similarity coefficient (DSC) and Hausdorff distance (HD). RESULTS: Compared with models trained on cases positioned in the same orientation, the models trained with cases positioned in the opposite orientation performed significantly worse (P < 0.05) on CTV and bladder segmentation, but had comparable accuracy for femurs (P > 0.05). The average DSC values were 0.74 vs 0.84, 0.85 vs 0.88, and 0.91 vs 0.91 for CTV, bladder, and femurs, respectively. The corresponding HD values (mm) were 16.6 vs 14.6, 8.4 vs 8.1, and 6.3 vs 6.3, respectively. The models trained with data from both orientations have comparable accuracy (P > 0.05), with average DSC of 0.84, 0.88, and 0.91 and HD of 14.4, 8.1, and 6.3, respectively. CONCLUSIONS: Orientation affects the accuracy for CTV and bladder, but has negligible effect on the femurs. The model trained from data combining both orientations performs as well as a model trained with data from the same orientation for all the organs. These observations can offer guidance on the choice of training data for accurate segmentation.

Atom Pairing in Optical Superlattices.

We study the pairing of fermions in a one-dimensional lattice of tunable double-well potentials using radio-frequency spectroscopy. The spectra reveal the coexistence of two types of atom pairs with different symmetries. Our measurements are in excellent quantitative agreement with a theoretical model, obtained by extending the Green's function method of Orso et al. [Phys. Rev. Lett. 95, 060402 (2005)PRLTAO0031-900710.1103/PhysRevLett.95.060402] to a bichromatic 1D lattice with nonzero harmonic radial confinement. The predicted spectra comprise hundreds of discrete transitions, with symmetry-dependent initial state populations and transition strengths. Our work provides an understanding of the elementary pairing states in a superlattice, paving the way for new studies of strongly interacting many-body systems.

Stabilization of Natural Organic Matter by Short-Range-Order Iron Hydroxides.

Dissolved organic matter (DOM) is capable of modifying the surfaces of soil minerals (e.g., Fe hydroxides) or even forming stable co-precipitates with Fe(III) in a neutral environment. The DOM/Fe co-precipitation may alter biogeochemical carbon cycling in soils if the relatively mobile DOM is sorbed by soil minerals against leaching, runoff, and biodegradation. In this study, we aimed to determine the structural development of DOM/Fe co-precipitates in relation to changes in pH and C/(C + Fe) ratios using XRD, XPS, Fe K-edge XAS, FTIR, and C-NEXAFS techniques. The results showed that in the system with bulk C/(C + Fe) molar ratios ≤0.65, the ferrihydrite-like Fe domains were precipitated as the core and covered by the C shells. When the C/(C + Fe) molar ratio ranged between 0.71 and 0.89, the emerging Fe-C bonding suggested a more substantial association between Fe domains including edge- and corner-sharing FeO6 octahedra and DOM. With C/(C + Fe) bulk molar ratios ≥0.92, only corner-sharing FeO6 octahedra along with Fe-C bonding were found. The homogeneously distributed C and Fe domains caused the enhancement of Fe and C solubilization from co-precipitates. The C/(C + Fe) ratios dominated structural compositions and stabilities of C/Fe co-precipitates and may directly affect the Fe and C cycles in soils.

Spin-imbalanced quasi-two-dimensional Fermi gases.

We measure the density profiles for a Fermi gas of (6)Li containing N(1) spin-up atoms and N(2) spin-down atoms, confined in a quasi-two-dimensional geometry. The spatial profiles are measured as a function of spin imbalance N(2)/N(1) and interaction strength, which is controlled by means of a collisional (Feshbach) resonance. The measured cloud radii and central densities are in disagreement with mean-field Bardeen-Cooper-Schrieffer theory for a true two-dimensional system. We find that the data for normal-fluid mixtures are reasonably well fit by a simple two-dimensional polaron model of the free energy. Not predicted by the model is a phase transition to a spin-balanced central core, which is observed above a critical value of N(2)/N(1). Our observations provide important benchmarks for predictions of the phase structure of quasi-two-dimensional Fermi gases.

Pencil Beam Scanning Proton Bragg Peak Conformal FLASH in Prostate Cancer Stereotactic Body Radiotherapy.

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for Dmax. For the CTV, the FLASH plans resulted in a higher Dmax than the clinical plans (116.9% vs. 103.3%). For the rectum, the V40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT.

Engineering Cathode-Electrolyte Interface of High-Voltage Spinel LiNi0.5Mn1.5O4 via Halide Solid-State Electrolyte Coating.

The high-voltage spinel LiNi0.5Mn1.5O4 (LNMO) cathode material with high energy density, low cost, and excellent rate capability has grabbed the attention of the field. However, a high-voltage platform at 4.7 V causes severe oxidative side reactions when in contact with the organic electrolyte, leading to poor electrochemical performance. Furthermore, the contact between the liquid electrolyte and LNMO leads to Mn dissolution during cycles. In this work, we applied the sol-gel method to prepare Li3InCl6-coated LNMO (LIC@LNMO) to address the mentioned problems of LNMO. By introducing a protective layer of halide-type solid-state electrolyte on LNMO, we can prevent direct contact between LNMO and electrolyte while maintaining good ionic conductivity. Thus, we could demonstrate that 5 wt % LIC@LNMO exhibited a good cycle performance with a Coulombic efficiency of 99% and a capacity retention of 80% after the 230th cycle at the 230th cycle at 1C at room temperature.

Pencil Beam Scanning Bragg Peak FLASH Technique for Ultra-High Dose Rate Intensity-Modulated Proton Therapy in Early-Stage Breast Cancer Treatment.

Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications.

Proton Bragg Peak FLASH Enables Organ Sparing and Ultra-High Dose-Rate Delivery: Proof of Principle in Recurrent Head and Neck Cancer.

Proton pencil-beam scanning (PBS) Bragg peak FLASH combines ultra-high dose rate delivery and organ-at-risk (OAR) sparing. This proof-of-principle study compared dosimetry and dose rate coverage between PBS Bragg peak FLASH and PBS transmission FLASH in head and neck reirradiation. PBS Bragg peak FLASH plans were created via the highest beam single energy, range shifter, and range compensator, and were compared to PBS transmission FLASH plans for 6 GyE/fraction and 10 GyE/fraction in eight recurrent head and neck patients originally treated with quad shot reirradiation (14.8/3.7 CGE). The 6 GyE/fraction and 10 GyE/fraction plans were also created using conventional-rate intensity-modulated proton therapy techniques. PBS Bragg peak FLASH, PBS transmission FLASH, and conventional plans were compared for OAR sparing, FLASH dose rate coverage, and target coverage. All FLASH OAR V40 Gy/s dose rate coverage was 90-100% at 6 GyE and 10 GyE for both FLASH modalities. PBS Bragg peak FLASH generated dose volume histograms (DVHs) like those of conventional therapy and demonstrated improved OAR dose sparing over PBS transmission FLASH. All the modalities had similar CTV coverage. PBS Bragg peak FLASH can deliver conformal, ultra-high dose rate FLASH with a two-millisecond delivery of the minimum MU per spot. PBS Bragg peak FLASH demonstrated similar dose rate coverage to PBS transmission FLASH with improved OAR dose-sparing, which was more pronounced in the 10 GyE/fraction than in the 6 GyE/fraction. This feasibility study generates hypotheses for the benefits of FLASH in head and neck reirradiation and developing biological models.

Factors influencing neutralizing antibody titers elicited by coronavirus disease 2019 vaccines.

The World Health Organization has highlighted the importance of an international standard (IS) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) neutralizing antibody titer detection to calibrate diagnostic techniques. We applied an IS to calibrate neutralizing antibody titers (NTs) (international units/mL) in response to coronavirus disease 2019 (COVID-19) vaccination. Moreover, the association between different factors and neutralizing antibodies was analyzed. A total of 1667 serum samples were collected from participants receiving different COVID-19 vaccines. Antibody titers were determined by a microneutralization assay using live viruses in a biosafety level 3 (BSL-3) laboratory and a commercial serological MeDiPro kit. The titer determined using the MeDiPro kit was highly correlated with the NT determined using live viruses and calibrated using IS. Fever and antipyretic analgesic treatment were related to neutralizing antibody responses in ChAdOx1-S and BNT162b2 vaccinations. Individuals with diabetes showed a low NT elicited by MVC-COV1901. Individuals with hypertension receiving the BNT162b2 vaccine had lower NTs than those without hypertension. Our study provided the international unit (IU) values of NTs in vaccinated individuals for the development of vaccines and implementation of non-inferiority trials. Correlation of the influencing factors with NTs can provide an indicator for selecting COVID-19 vaccines based on personal attributes.

Dual-Energy Computed Tomography Proton-Dose Calculation with Scripting and Modified Hounsfield Units.

PURPOSE: To describe an implementation of dual-energy computed tomography (DECT) for calculation of proton stopping-power ratios (SPRs) in a commercial treatment-planning system. The process for validation and the workflow for safe deployment of DECT is described, using single-energy computed tomography (SECT) as a safety check for DECT dose calculation. MATERIALS AND METHODS: The DECT images were acquired at 80 kVp and 140 kVp and were processed with computed tomography scanner software to derive the electron density and effective atomic number images. Reference SPRs of tissue-equivalent plugs from Gammex (Middleton, Wisconsin) and CIRS (Computerized Imaging Reference Systems, Norfolk, Virginia) electron density phantoms were used for validation and comparison of SECT versus DECT calculated through the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, California) application programming interface scripting tool. An in-house software was also used to create DECT SPR computed tomography images for comparison with the script output. In the workflow, using the Eclipse system application programming interface script, clinical plans were optimized with the SECT image set and then forward-calculated with the DECT SPR for the final dose distribution. In a second workflow, the plans were optimized using DECT SPR with reduced range-uncertainty margins. RESULTS: For the Gammex phantom, the root mean square error in SPR was 1.08% for DECT versus 2.29% for SECT for 10 tissue-surrogates, excluding the lung. For the CIRS Phantom, the corresponding results were 0.74% and 2.27%. When evaluating the head and neck plan, DECT optimization with 2% range-uncertainty margins achieved a small reduction in organ-at-risk doses compared with that of SECT plans with 3.5% range-uncertainty margins. For the liver case, DECT was used to identify and correct the lipiodol SPR in the SECT plan. CONCLUSION: It is feasible to use DECT for proton-dose calculation in a commercial treatment planning system in a safe manner. The range margins can be reduced to 2% in some sites, including the head and neck.

Redox reactions between chromium(VI) and hydroquinone: Alternative pathways for polymerization of organic molecules.

Chromium (VI) reduction by organic compounds is one of the major pathways to alleviate the toxicity and mobility of Cr(VI) in the environment. However, oxidative products of organic molecules receive less scientific concerns. In this study, hydroquinone (H2Q) was used as a representative organic compound to determine the redox reactions with Cr(VI) and the concomitant oxidative products. Spectroscopic analyses showed that Cr(III) hydroxides dominated the precipitates produced during redox reactions of Cr(VI) and H2Q. For the separated filtrates, the acidification induced the oxidative polymerization of organic molecules, accompanied with the complexation with Cr(III). The aromatic domains dominated the chemical structures of the black and fluffy organic polymers, which was different to the natural humic acids due to the shortage of aliphatic chains. Results of linear combination fitting (LCF) for Cr K-edge X-ray absorption near edge structure (XANES) spectra demonstrated that up to 90.4% of Cr inventory in precipitates derived after the acidification of filtrates was Cr(III) complexed with humic-like polymers, suggesting that Cr(III) possibly acted as a linkage among organic molecules during the polymerization processes of H2Q. This study demonstrated that Cr(VI) may lead to the polymerization of organic molecules in an acidic solution, and thus, it could raise scientific awareness that the oxidative decomposition of organic molecules may not be the only pathway while interacting with the strong oxidant of Cr(VI).

Higher Dose Volumes May Be Better for Evaluating Radiation Pneumonitis in Lung Proton Therapy Patients Compared With Traditional Photon-Based Dose Constraints.

PURPOSE: The dosimetric parameters used clinically to reduce the likelihood of radiation pneumonitis (RP) for lung cancer radiation therapy have traditionally been V20Gy ≤ 30% to 35% and mean lung dose ≤ 20 to 23 Gy; however, these parameters are derived based on studies from photon therapy. The purpose of this study is to evaluate whether such dosimetric predictors for RP are applicable for locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with proton therapy. METHODS AND MATERIALS: In the study, 160 (78 photon, 82 proton) patients with LA-NSCLC treated with chemoradiotherapy between 2011 and 2016 were retrospectively identified. Forty (20 photon, 20 proton) patients exhibited grade ≥2 RP after therapy. Dose volume histograms for the uninvolved lung were extracted for each patient. The percent lung volumes receiving above various dose levels were obtained in addition to V20Gy and Dmean. These dosimetric parameters and patient characteristics were evaluated with univariate and multivariate logistic regression tests. Receiver operating characteristic curves were generated to obtain the optimal dosimetric constraints through analyzing RP and non-RP sensitivity and specificity values. RESULTS: The multivariate analysis showed V40Gy and Dmean to be statistically significant for proton and photon patients, respectively. V35Gy to V50Gy were strongly correlated to V40Gy for proton patients. Based on the receiver operating characteristic curves, V35Gy to V50Gy had the highest area under the curve compared with other dose levels for proton patients. A potential dosimetric constraint for RP predictor in proton patients is V40Gy ≤ 23%. CONCLUSIONS: In addition to V20Gy and Dmean, the lung volume receiving higher doses, such as V40Gy, may be used as an additional indicator for RP in LA-NSCLC patients treated with proton therapy.

Dose to Highly Functional Ventilation Zones Improves Prediction of Radiation Pneumonitis for Proton and Photon Lung Cancer Radiation Therapy.

PURPOSE: We hypothesized that the radiation dose in high-ventilation portions of the lung better predicts radiation pneumonitis (RP) outcome for patients treated with proton radiation therapy (PR) and photon radiation therapy (PH). METHODS AND MATERIALS: Seventy-four patients (38 protons, 36 photons) with locally advanced non-small cell lung cancer treated with concurrent chemoradiation therapy were identified, of whom 24 exhibited RP (graded using Common Terminology Criteria for Adverse Events v4.0) after PR or PH, and 50 were negative controls. The inhale and exhale simulation computed tomography scans were deformed using Advanced Normalization Tools. The 3-dimensional lung ventilation maps were derived from the deformation matrix and partitioned into low- and high-ventilation zones for dosimetric analysis. Receiver operating curve analysis was used to study the power of relationship between RP and ventilation zones to determine an optimal ventilation cutoff. Univariate logistic regression was used to correlate dose in high- and low-ventilation zones with risk of RP. A nonparametric random forest process was used for multivariate importance assessment. RESULTS: The optimal high-ventilation zone definition was determined to be the higher 45% to 60% of the ventilation values. The parameter vV20Gy_high (high ventilation volume receiving ≥20 Gy) was found to be a significant indicator for RP (PH: P = .002, PR: P = .035) with improved areas under the curve compared with the traditional V20Gy for both photon and proton cohorts. The relationship of RP with dose to the low-ventilation zone of the lung was insignificant (PH: P = .123, PR: P = .661). Similar trends were observed for ventilation mean lung dose and ventilation V5Gy. Multivariate importance assessment determined that vV20Gy_high, vV5_high, and mean lung dose were the most significant parameters for the proton cohort with a combined area under the curve of 0.78. CONCLUSION: Dose to the high-ventilated regions of the lung can improve predictions of RP for both PH and PR.

Technical Note: More accurate and efficient segmentation of organs-at-risk in radiotherapy with convolutional neural networks cascades.

PURPOSE: Manual delineation of organs-at-risk (OARs) in radiotherapy is both time-consuming and subjective. Automated and more accurate segmentation is of the utmost importance in clinical application. The purpose of this study is to further improve the segmentation accuracy and efficiency with a novel network named convolutional neural networks (CNN) Cascades. METHODS: CNN Cascades was a two-step, coarse-to-fine approach that consisted of a simple region detector (SRD) and a fine segmentation unit (FSU). The SRD first used a relative shallow network to define the region of interest (ROI) where the organ was located, and then, the FSU took the smaller ROI as input and adopted a deep network for fine segmentation. The imaging data (14,651 slices) of 100 head-and-neck patients with segmentations were used for this study. The performance was compared with the state-of-the-art single CNN in terms of accuracy with metrics of Dice similarity coefficient (DSC) and Hausdorff distance (HD) values. RESULTS: The proposed CNN Cascades outperformed the single CNN on accuracy for each OAR. Similarly, for the average of all OARs, it was also the best with mean DSC of 0.90 (SRD: 0.86, FSU: 0.87, and U-Net: 0.85) and the mean HD of 3.0 mm (SRD: 4.0, FSU: 3.6, and U-Net: 4.4). Meanwhile, the CNN Cascades reduced the mean segmentation time per patient by 48% (FSU) and 5% (U-Net), respectively. CONCLUSIONS: The proposed two-step network demonstrated superior performance by reducing the input region. This potentially can be an effective segmentation method that provides accurate and consistent delineation with reduced clinician interventions for clinical applications as well as for quality assurance of a multicenter clinical trial.

Cascaded atrous convolution and spatial pyramid pooling for more accurate tumor target segmentation for rectal cancer radiotherapy.

Convolutional neural networks (CNNs) have become the state-of-the-art method for medical segmentation. However, repeated pooling and striding operations reduce the feature resolution, causing loss of detailed information. Additionally, tumors of different patients are of different sizes. Thus, small tumors may be ignored while big tumors may exceed the receptive fields of convolutions. The purpose of this study is to further improve the segmentation accuracy using a novel CNN (named CAC-SPP) with cascaded atrous convolution (CAC) and a spatial pyramid pooling (SPP) module. This work is the first attempt at applying SPP for segmentation in radiotherapy. We improved the network based on ResNet-101 yielding accuracy gains from a greatly increased depth. We added CAC to extract a high-resolution feature map while maintaining large receptive fields. We also adopted a parallel SPP module with different atrous rates to capture the multi-scale features. The performance was compared with the widely adopted U-Net and ResNet-101 with independent segmentation of rectal tumors for two image sets, separately: (1) 70 T2-weighted MR images and (2) 100 planning CT images. The results show that the proposed CAC-SPP outperformed the U-Net and ResNet-101 for both image sets. The Dice similarity coefficient values of CAC-SPP were 0.78 ± 0.08 and 0.85 ± 0.03, respectively, which were higher than those of U-Net (0.70 ± 0.11 and 0.82 ± 0.04) and ResNet-101 (0.76 ± 0.10 and 0.84 ± 0.03). The segmentation speed of CAC-SPP was comparable with ResNet-101, but about 36% faster than U-Net. In conclusion, the proposed CAC-SPP, which could extract high-resolution features with large receptive fields and capture multi-scale context yields, improves the accuracy of segmentation performance for rectal tumors.

Thoracic radiotherapy (TRT) improved survival in both oligo- and polymetastatic extensive stage small cell lung cancer.

There has been no previous study on the efficacy of the thoracic radiotherapy (TRT) in oligometastatic or polymetastatic extensive stage small-cell lung cancer (ES-SCLC) to the overall survival (OS). In a group of 270 ES-SCLC cases retrospective study, 78 patients (28.9%) had oligometastases and 192 (71.1%) had polymetastases, among which 51 oligometastatic patients (65.4%) and 93 polymetastatic patients (51.6%) received TRT. Propensity score matching (PSM) was utilized. The 2-year OS, progression free survival (PFS) and local control (LC) in oligometastatic and polymetastatic patients were 22.8% and 4.5% (p < 0.001), 12.0% and 3.8% (p < 0.001), and 36.7% and 6.1% (p < 0.001), respectively. The 2-year OS in oligometastatic patients with the chemotherapy + radiotherapy and chemotherapy alone were 25.2% and 12.7% (p = 0.002), in contrast to 10.0% and 6.8% (p = 0.030) in polymetastatic patients. The estimated hazard ratios for survival were 2.9 and 1.7 for both oligometastatic and polymetastatic patients with radiotherapy. The polymetastatic group has a lower LC (6.1% v.s. 36.7%, (p < 0.001)), due to polymetastases patients receiving involved-sites radiotherapy with low dose schemas. TRT improved OS of patients with oligometastases and polymetastases. Our study demonstrated that aggressive TRT might be a suitable addition of chemotherapy when treating ES-SCLC patients with oligometastases and polymetastases.

Receipt of thoracic radiation therapy and radiotherapy dose are correlated with outcomes in a retrospective study of three hundred and six patients with extensive stage small-cell lung cancer.

BACKGROUND: The importance of the thoracic radiation therapy (TRT) dose has not been clearly defined in extensive stage small-cell lung cancer (ES-SCLC) and it is unclear whether improved TRT dose translates into a survival benefit. METHODS: 306 patients with ES-SCLC were retrospectively reviewed, of which 170 received IMRT/CRT fractionation RT after ChT, and 136 received chemotherapy (ChT) alone. We adopted the time-adjusted BED (tBED) for effective dose fractionation calculation. Due to the nonrandomized nature of this study, we compared the ChT+RT with ChT groups that matched on possible confounding variables. RESULTS: Patients achieved 2-year OS, PFS and LC rates of 19.7%, 10.7% and 28.4%, respectively. After propensity score matching, (113 cases for each group), the rates of OS, PFS and LC at 2 years were 21.4%, 7.7% and 34.5% for ChT+TRT, and 10.3% (p<0.001), 4.6% (p<0.001) and 6.3% for ChT only (p<0.001), respectively. Among propensity score matching patients, 56 cases for each group received the high dose (tBED>50 Gy) TRT and received low dose (tBED≤50 Gy) TRT. Two-year OS, PFS and LC rates were 32.3%, 15.3% and 47.1% for the high dose compared with 17.0% (p<0.001), 12.9% (p=0.097) and 34.7% (p=0.029) for low dose radiotherapy. CONCLUSIONS: TRT added to ChT improved ES-SCLC patient OS. High dose TRT improved OS over lower doses. Our results suggest that high-dose thoracic radiation therapy may be a reasonable consideration in select patients with ES-SCLC.