Contralateral Lung Research Articles

Case Series: EGFR and ROS-1 Co-Occurrence in Advanced Non–Small Cell Lung Cancer

ABSTRACT Non–small cell lung cancer (NSCLC) is a heterogeneous disease with diverse molecular alterations. Two of the most common genetic abnormalities found in advanced NSCLC are mutations in the epidermal growth factor receptor (EGFR) and rearrangements in the ROS proto-oncogene 1 (ROS-1). Although these two alterations are typically mutually exclusive, there have been reports of their co-occurrence in a small subset of NSCLC patients. The discovery of this comutation has recently become apparent due to the increased use of more sensitive whole genome sequencing. We share our experience with two cases of coexisting EGFR and ROS-1 alterations. The first case is a 60-year-old man diagnosed with advanced adenocarcinoma of the lung with metastasis to bone and left adrenal gland. The second case is a 49-year-old woman diagnosed with stage IV lung adenocarcinoma with metastasis to the contralateral lung and diffuse abdominal lymphadenopathy. The first case was treated with osimertinib, and currently has had a stable disease on this medication for more than 3 years. The second case had a short interval of stable disease on osimertinib; then she developed progressive disease with poor response to anti–ROS-1 therapy. We believe patients with advanced NSCLC may have a higher incidence of coalterations, especially in the areas of the world with higher EGFR mutations and in the era of higher usage of whole genome sequencing. The presence of comutations will allow for a good long-term response to anti-EGFR therapy. This highlights the importance of the use of next-generation sequencing whenever possible and considers variant allele frequency as a factor in directing the therapy. There are many other unanswered questions, such as the best treatment sequencing or even the combined targeted therapy approach. This case series may add some information to the current literature.

Serial changes of 99mTc- pyrophosphate uptake in patients with hereditary transthyretin amyloid cardiomyopathy treated with tafamidis

Abstract Objective Transthyretin amyloid cardiomyopathy (ATTR-CM) arises from the deposition of amyloid in the heart, resulting in adverse outcomes. Tafamidis has demonstrated potential in slowing disease progression. Our research group, alongside others, has documented cases where decrease in cardiac tracer uptake were observed through bone scintigraphy after tafamidis treatment.[1-8] This study aims to assess the efficacy of Technetium-99m (99mTc)-pyrophosphate (PYP) scintigraphy in longitudinally monitoring tafamidis treatment for hereditary ATTR-CM over an extended follow-up period. Methods We retrospectively analyzed a prospective cohort of hereditary ATTR-CM patients treated with tafamidis (61 mg/day) retrospectively. A control group comprised hereditary ATTR-CM patients who hadn't received eplontersen, inotersen, tafamidis, or patisiran. 99mTc-PYP SPECT/CT scans were conducted at baseline and 1-3 years post-treatment, measuring visual score, planar heart to contralateral lung (H/CL) ratio, and volumetric heart to lung (H/L) ratio. Results Twenty hATTR-CM patients received tafamidis, with the other ten in the control group. After a 2-year follow-up, the tafamidis group experienced a significant decrease in volumetric heart to lung (H/L) ratio (3.817 to 3.011, p < 0.001), while the control group showed no significant change (3.775 to 3.621, p = 0.121)(Figure 1B). Significant decreases in volumetric H/L ratio were noted in the first year of tafamidis treatment (-21.71%), with minimal changes in the subsequent two years (-0.77% in the second year and -2.41% in the third year)(Figure 2B). Conclusion A significant initial reduction in 99mTc-PYP uptake was observed in hereditary ATTR-CM patients during the first year of tafamidis treatment. However, this effect was not sustained in the subsequent two years. Further investigation is warranted to comprehend the long-term efficacy of tafamidis in these patients.Changes in 99mTc-PYP uptake at 2 yearsChanges between 1st, 2nd and 3rd year

Effects of Inc parameter on quality of VMAT radiotherapy plans for right breast cancer based on dosimetric study.

This study aimed to investigate the influence of gantry angle increment (Inc) parameters on the Monaco treatment planning system for volumetric modulated arc therapy (VMAT) in right breast cancer, and to determine the optimal Inc parameters. Twenty-three patients with right breast cancer at the Sir Run Run Shaw Hospital from August 2022 to August 2023 were retrospectively selected. Four VMAT plans were generated for each patient incorporating Inc of 10°, 20° (control group), 30°, and 40°, while the other optimization parameters and constraint functions remained constant. The D98 and conformity index were lower in the Inc30 and Inc40 groups than in the Inc20 group. As Inc increased from 10° to 30°, the irradiated dose to the ipsilateral lung, including the V20, V5, and Dmax, mean dose, gradually increased. There were no statistically significant differences in the irradiated dose to the contralateral breast, contralateral lung, heart, esophagus, and brachial plexus. The number of monitor units and control points decreased with increasing Inc. Smaller Inc values can achieve higher target coverage and lower irradiated dose to the ipsilateral lung, but will reduce delivery efficiency. Considering the plan quality and delivery efficiency, an Inc of 10° or 20° is recommended for right breast cancer VMAT plans.

Use of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography in monitoring therapeutic changes of RNA interference therapeutics in patients with hereditary transthyretin amyloid cardiomyopathy

BackgroundRNA interference therapeutics reduce transthyretin production; however, their effect on hereditary transthyretin amyloid cardiomyopathy (ATTR-CA) remains unclear. We aimed to investigate alterations in technetium-99 m (99mTc)-pyrophosphate (PYP) single-photon emission computed tomography/computed tomography (SPECT/CT) outcomes in patients receiving patisiran or vutrisiran. MethodsWe retrospectively identified individuals with hereditary ATTR-CA who received patisiran or vutrisiran. First and second 99mTc-PYP SPECT/CT data, including visual grading, planar heart to contralateral lung (H/CL) ratio, and volumetric heart to lung (H/L) ratio were assessed. ResultsEight patients with hereditary ATTR-CA were enrolled. Cohort A included four patients who underwent their first 99mTc-PYP SPECT/CT imaging at the initiation of small interfering RNA (siRNA) treatment, while cohort B comprised four patients who had been receiving siRNA treatment before their first 99mTc-PYP SPECT/CT imaging (median duration 1281 days). Overall, there were numerical reductions in planar H/CL ratio (1.7 ± 0.2 to 1.6 ± 0.1, p = 0.050) and a significant improvement in volumetric H/L ratio (4.0 ± 0.9 to 3.5 ± 0.4, p = 0.035). Although without significance, subgroup analysis showed more pronounced changes in cohort A for both planar H/CL ratio and volumetric H/L ratio (−20.1 ± 12.6% and −17.1 ± 11.4%) compared to cohort B (−3.3 ± 11.2% and −4.3 ± 12.7%). ConclusionOur results demonstrated a significant decrease in volumetric H/L ratio in hereditary ATTR-CA patients receiving RNA interference therapeutics.

Dosimetric comparison of gamma knife and linear accelerator (VMAT and IMRT) plans of SBRT of Lung tumours

This study evaluates dosimetric differences in Stereotactic Body Radiation Therapy (SBRT) for lung tumors using plans of Gamma Knife, and Volumetric Modulated Arc Therapy (VMAT), Intensity-Modulated Radiation Therapy (IMRT) plans based on Linear Accelerator, aiming to inform the reader of appropriate treatment strategy selection. Ten patients with 23 lung tumor lesions treated with SBRT at Zhongshan Hospital of Dalian University were analyzed. Plans of Gamma Knife, and VMAT, IMRT plans based on Linear Accelerator were created for each lesion, totaling 18 plans per type. Lesions were treated with 30–50 Gy in 5–10 fractions. Dosimetric parameters, including gradient index (GI), heterogeneity index (HI), conformity index (CI), and doses to the plan target volumes (PTVs), the gross tumor volumes (GTVs) and organs at risk (OARs) were compared. Plans of Gamma Knife showed superior HI and GI, higher PTV and GTV doses, and reduced doses to the ipsilateral and contralateral lungs, esophagus, spinal cord, and heart compared to VMAT and IMRT plans (p < 0.05). However, Plans of Gamma Knife required longer delivery times. When comparing VMAT and IMRT plans, VMAT plans had shorter delivery times than IMRT plans, but required more monitor units (MUs). Additionally, IMRT plans delivered a lower mean dose to the ipsilateral lung compared to VMAT plans. Gamma Knife SBRT plans achieves steeper dose falloff and minimizes radiation to normal lung tissue compared to VMAT and IMRT plans, but with longer delivery times. VMAT and IMRT plans displayed similar dose distributions for lung SBRT.

Quantitative computed tomography assessment of pulmonary function and compensation after lobectomy and segmentectomy in lung cancer patients.

The effect of different surgical methods on postoperative lung function in patients with lung cancer is still inconclusive. The main objective of this study was to compare the effects of video-assisted thoracic surgery (VATS) lobectomy and segmentectomy on postoperative pulmonary function and compensatory changes in patients undergoing lung cancer surgery. A total of 120 patients (82 VATS lobectomy, 38 VATS segmentectomy) were assessed for demographic characteristics, baseline pulmonary function, tumor volume, T stage, and histological grade. Postoperative pulmonary function and compensatory changes [percentage of the well-aerated lung (WAL) total (or unilateral) lung volume (LV) (WAL%) and non-operated lung (NOL)] were measured at multiple time points up to 2 years. Logistic regression analysis identified factors associated with WAL% decline after 1 year. Both VATS lobectomy and segmentectomy led to a decrease in pulmonary function, with no significant difference in the extent of decline between the two groups (all P>0.05). Lobectomy triggered a more pronounced compensatory response, characterized by increased ipsilateral NOL volume over time. Segmentectomy induced minimal compensatory changes and had a minimal impact on pulmonary function. Factors associated with decreased pulmonary ventilation after 1 year differed between the lobectomy and segmentectomy groups. In the lobectomy group, a higher preoperative WAL% of ipsilateral NOL [odds ratio (OR) =1.073; 95% confidence interval (CI): 1.017-1.133; P=0.01] was associated with a higher risk of decline in pulmonary function, whereas in the segmentectomy group, the only influencing factor was the preoperative contralateral mean lung density (MLD) (OR =0.932; 95% CI: 0.884-0.984; P=0.01). Both lobectomy and segmentectomy after lung cancer surgery result in a decrease in WAL%, with lobectomy demonstrating a stronger pulmonary compensatory capacity. The application of quantitative computed tomography (CT) has shown significant value in predicting postoperative pulmonary function preservation and compensatory changes, providing strong support for personalized surgical decision-making.

Deep learning-based prediction of the dose-volume histograms for volumetric modulated arc therapy of left-sided breast cancer.

The advancements in artificial intelligence and computational power have made deep learning an attractive tool for radiotherapy treatment planning. Deep learning has the potential to significantly simplify the trial-and-error process involved in inverse planning required by modern treatment techniques such as volumetric modulated arc therapy (VMAT). In this study, we explore the ability of deep learning to predict organ-at-risk (OAR) dose-volume histograms (DVHs) of left-sided breast cancer patients undergoing VMAT treatment based solely on their anatomical characteristics. The predicted DVHs could be used to derive patient-specific dose constraints and dose objectives, streamlining the treatment planning process, standardizing the quality of the plans, and personalizing the treatment planning. This study aimed to develop a deep learning-based framework for the prediction of organ-specific dose-volume histograms (DVH) based on structures delineated for left-sided breast cancer treatment. We used a dataset of 249 left-sided breast cancer patients treated with tangential VMAT fields. We extracted delineated structures and dose distributions for each patient and derived slice-by-slice DVHs for planning target volume (PTV) and organs-at-risk. The patients were divided into training (70%, n=174), validation (10%, n=24), and test (20%, n=51) sets. Collected data were used to train a deep learning model for the prediction of the DVHs based on the delineated structures. The developed deep learning model comprised a modified DenseNet architecture followed by a recurrent neural network. In the independent test set (n=51), the point-wise differences in the slice-by-slice DVHs between the clinical and predicted DVHs were small; the mean squared errors were 3.53, 1.58, 2.28, 3.37, and 1.44 [×10-4] for PTV, heart, ipsilateral lung, contralateral lung, and contralateral breast, respectively. With the derived cumulative DVHs, the mean absolute difference±standard deviation of mean doses between the clinical and the predicted DVH were 0.08± 0.04Gy, 0.24± 0.22Gy, 0.73± 0.46Gy, 0.07± 0.06Gy, and 0.14± 0.14Gy for PTV, heart, ipsilateral lung, contralateral lung, and contralateral breast, respectively. The deep learning-based approach enabled automatic and reliable prediction of the DVH based on delineated structures. The predicted DVHs could potentially serve as patient-specific clinical goals used to aid treatment planning and avoid suboptimal plans or to derive optimization objectives and constraints for automated treatment planning.

Evaluation of Inverse Planned and Forward Planned Intensity Modulated Radiotherapy Techniques in Breast Cancer

Introduction: The objective of this study is to compare the dosimetric parameters of radiation to the whole breast between the two intensity-modulated radiotherapy (IP IMRT) techniques, i.e. Inverse planned IMRT (IP IMRT) and Forward Planned IMRT (FP IMRT) with regard to target coverage (PTV) and irradiation of organs at risk (OAR). Material and Methods: Plain and Contrast enhanced computed tomography (CECT) datasets were created for 41 patients treated with whole breast radiation therapy. CT simulation and treatment is performed using deep inspiratory breath hold technique (DIBH). Radiotherapy treatment Planning is done using Eclipse Treatment Planning System (version 13.7) with a prescription dose of 40 Gy in 15#. The developed treatment plans were subjected to objective comparison of PTV and OARs using dose volume histograms (DVH). Results: IP IMRT plans provided better coverage (99.5% vs 97.6%), comparable though higher maximum dose (Dmax 45.0 VS 44.1 Gy), higher hot spot (PTV105% 49.2 vs 33), lower volumes receiving 20, 25, 30 Gy (V20, V25, V30) for heart, more homogeneous (homogeneity index 0.10 vs. 0.14) and conformal dose distribution (conformity Index 1.0 vs 0.98) compared to FP IMRT. Regarding OAR dosimetry it is observed that FP IMRT showed reduced mean dose to Coronary artery (LADCA), Contralateral Lung (CL), Contralateral breast (CB) along with reduction in low dose region (V5) to all OARs under study. It was also observed that Monitor units used and planning time were lower for FP IMRT. Conclusion: On weighing different dosimetric factors, both the techniques have displayed their own advantages and disadvantages. Choosing a planning technique needs to be customized taking into consideration various factors such as breast topography, size and volumes of breast, availability of expertise planning skills and resources.

Bibliometric and knowledge map analysis of one lung ventilation.

One lung ventilation (OLV) is an essential method of lung isolation to protect the ventilated lung from soiling by the contralateral lung and obtain optimal surgical exposure in thoracic surgery. This study aims to examine the trends and developments in OLV research from 1982 to 2024 through bibliometric analysis. The literature on OLV was systematically searched in the Web of Science Core Collection database for this study. VOSviewer and CiteSpace were utilized to perform comprehensive bibliometric and visual analyses of global publication/trends, countries/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords in the field of OLV. A total of 1,682 articles and reviews on OLV research were identified, which showed an overall growing trend from 1982 to 2024. The United States was the leader in this field, accounting for the largest number of publications (n=299). Among all institutions, Yonsei University had the largest number of publications (n=23), but National Taiwan University Hospital had the highest number of cited publications (n=876). The papers related to OLV were mainly published in Journal of Cardiothoracic and Vascular Anesthesia (n=147) and the most productive author was Cheng YJ (n=15). After keywords analysis, "infants", "dexmedetomidine", "inflammation", and "airway management" were newly emergent research hotspots. Through bibliometric and visualization methods, we undertook a comprehensive analysis in the field of OLV. The United States maintained a top position in this field, the emerging hotspots of OLV changed from basic research to clinical research and the further innovation of OLV management. This study provides new ideas for scholars in their future works.

COMPARATIVE RADIATION DOSIMETRY OF WHOLE BREAST RADIOTHERAPY USING IMRT AND VMAT TECHNIQUES IN LEFT SIDED BREAST CANCER PATIENTS AFTER BREAST CONSERVING SURGERY

Background:The radiotherapy of left sided breast cancers is mandatory and integral part of treatment and challenging because of surrounding critical structures posing increased risk of complications. The main objective of this study was to quantify doses toorgan at risk(OARs) including left lung, heart, contralateral breast, spinal cord, and planning target volume (PTV) using different radiation techniques like Intensity modulated radiation therapy (IMRT)&amp;volumetric modulated arc therapy (VMAT) and comparison of radiation dosimetry. Methods: A prospective study of 30 patients of left sided breast cancer who had undergone Breast Conservative Surgery (BCS) and chemotherapy was done for adjuvant radiation. For every patient radiation planning was done by two different techniques IMRT and VMAT. Then the comparison of radiation dosimetry parameters was done for all the techniques including the parameters like PTV coverage, doses to OAR like heart, left lung, contralateral breast and spinal cord and head of humerus. The Homogenity Index (HI) were calculated. Result: The Mean age of the patient was 46.7 years. When comparing the doses delivered in IMRT and VMAT Technique for left sided breast cancer post breast conservation surgery there was significant difference in PTV Breast and axilla V95 Gy. It was 96.2±1.9% (IMRT) vs 94.8±1.71% (VMAT), (p=0.004). However significant sparing of Organs at Risk was seen. With ipsilateral lung dose mean V5 Gy was 77.86± 9.68% (IMRT) v/s 83.04± 9.86 % (VMAT), (p=0.0446). Also mean V30 Gy was 14.6±4.82% with IMRT vs 16.54±5.86% with VMAT, (p=0.0169). Heart mean dose was 8.8±1.49 Gy with IMRT and 10.98±3.7 Gy with VMAT, (p=0.0227). Further V30 Gy for Heart was 4.61±3.8% with IMRT and 6.72±4.0% with VMAT, (p=0.0132).No significant difference was seen with IMRT and VMAT technique for contralateral lung, contralateral breast and spinal cord. Conclusion: In treatment of patients with radiation with left breast cancer patients post BCS using IMRT and VMAT technique it is seen significant dose reduction with IMRT Technique for ipsilateral lung and Heart as compared to VMAT technique. Significant V95 coverage for PTV Breast and axilla with IMRT as compared to VMAT. Hence in our Study IMRT technique was found to be superior for better sparing of Organ at risk and better PTV coverage.

A novel x-Ray and γ-Ray combination strategy for radiotherapy after breast-conserving surgery in patients with right breast cancer.

Radiotherapy is a primary therapeutic approach for breast cancer following breast-conserving surgery. The TaiChiB dual-modality radiotherapy system combining X-ray and focused γ-ray, offers a new approach to reduce the radiation dose of organs at risk (OARs) and has the potential to mitigate the adverse effects of radiotherapy. Currently, there are few studies on the dosimetric characteristics of the TaiChiB dual-modality system for actual treatment plans for specific diseases. The purpose of this work is to study the dosimetric advantages of dual-modal systems for right breast patients after breast-conserving surgery. Treatment plans for 20 patients with right breast cancer were generated for a linear accelerator (LINAC) based system and the TaiChiB dual-modality system, respectively. Volumetric modulated arc therapy plans with simultaneous integrated boost (VMAT-SIB) were made for the LINAC. Focused γ-ray was used to deliver the boost dose with the dual-modality system. The dosimetric parameters of the target and OARs were evaluated and compared between the treatment plans generated for the two systems. The TaiChiB dual-modality plans exhibit a higher conformal index (CI) and lower gradient index (GI) for the PGTV and PTV compared with the LINAC-based VMAT-SIB plans. Compared to VMAT-SIB plans, the PTV Dmax, PTV Dmean, PTV V110, PGTV Dmax, and PGTV Dmean of the TaiChiB dual-modality plans are significantly lower. Meanwhile, the dose to OARs, such as the Dmean of the heart, the V5 of liver, the Dmean of ipsilateral lung, the V30 of ipsilateral lung, the V20 of ipsilateral lung, the V5 of ipsilateral lung, the Dmean of contralateral lung, Dmax of contralateral breast and the Dmean of contralateral breast are significantly reduced. Our study demonstrates the dosimetric advantages of the novel TaiChiB dual-modality radiotherapy system for the treatment of right-sided breast cancer. Overall, for the TaiChiB dual-modality radiotherapy system, the radiation dose outside the target region decreases rapidly, thereby minimizing radiation exposure to neighboring organs and ensuring the conformity of the target area. Our research confirms the potential of the TaiChiB dual-modality system for future radiotherapy.

Immunotherapy and PD-L1 Tumor Expression in Moroccan Non-Small Cell Lung Cancer Patients with Various Metastasis.

The question of whether tumor expression of PD-L1 and the presence of distant metastasis could influence the efficacy of immunotherapy represents a major challenge and needs to be further elucidated. The aim of this study is to evaluate the predictive significance of tumor expression of PD-L1 as well as the number and site of metastasis in non-small cell lung cancer (NSCLC) among Moroccan patients treated with immunotherapy. Between January 2019 and February 2023, we recruited Moroccan patients with metastatic NSCLC. All were treated with immunotherapy, either as monotherapy or in combination with chemotherapy. Immunohistochemistry was used to assess PD-L1 (clone 22C3) and ALK (clone D5F3) status. EGFR status was established by qPCR. Tumor PD-L1 expression was classified into 2 levels: TPS <1% (negative expression) and TPS ≥1% (positive expression). Statistical analysis was performed using SPSS Statistics V.21 software. The median age of patients (N=40) was 67 years (39- 92 years) and the sex ratio was 9. Disease dissemination revealed that 22.5% (N=9) of patients had a metastatic burden ≥ 3 (MB≥3). As for the sites of metastasis, the results showed that 20% (N=8), 10% (N=4), 42.5% (N=17), 22.5% (N=9), 27.5% (N=11), 45% (N=18) and 27.5% (N=11) of patients had developed lymph node, liver, bone, brain, pleural, contralateral lung and adrenal metastasis respectively. Positive PD-L1 expression was significantly associated with shorter overall survival (OS = 17.19 vs. 28.85 months, p=0.01). High metastatic burden (MB ≥ 3) was associated with lower objective response rate (ORR), shorter progression-free survival (PFS), and reduced OS, respectively (ORR = 0 vs. 58.06%, p=0.002; PFS = 10.23 vs. 25.27 months, p=0.001; and OS = 11.60 vs. 27.91 months, p=0.003). Only the presence of osseous metastasis was significantly associated with lower ORR, shorter PFS, and OS compared to other metastatic locations (ORR = 5.88 vs. 73.9%, p=0.000; PFS = 10.72 vs. 31.33 months, p=0.000; and OS = 11.39 vs. 36.17 months, p=0.000). Finally, the presence of hepatic metastasis was significantly associated with shorter PFS (10.75 months) compared to those without hepatic metastasis (22.53 months) (p=0.046). Finally, the results of the multivariate analysis revealed that the presence of bone metastasis was strongly correlated with a significant decrease in progression-free survival (p=0.001) as well as overall survival (p=0.002). Our results suggest that tumor expression of PD-L1 and metastatic burden should play a significant role in predicting the response to immunotherapy. Furthermore, it is important to note that the presence of osseous and hepatic metastasis could negatively influence the clinical outcomes of immunotherapy.

Tension hydrothorax complicating syringopleural shunt for post-traumatic syringomyelia.

Syringomyelia is a rare phenomenon that is typically associated with Chiari malformations. However, they can occur in the setting of post-traumatic spinal injury. Potential diversion treatments include syringopleural (SPS), syringoperitoneal and syringosubarachnoid shunts. Short-term complications have been reported in the literature, however, long term complications are not well documented. This case report is of a 43-year-old woman found deceased in bed. She had a history of a traumatic spinal injury following a motor vehicle accident 15 years prior to death. This was complicated by a syringomyelia/syrinx requiring a SPS insertion. Post-mortem imaging and autopsy findings demonstrated a large right tension hydrothorax with dense fibrosis of the pleural surfaces, contralateral diffuse alveolar damage lung changes histologically and a patent SPS. Her cause of death was registered as "Right tension hydrothorax and diffuse alveolar damage complicating right syringopleural shunt and thoracic syrinx".

CT features associated with contralateral recurrence of spontaneous pneumothorax.

Spontaneous pneumothorax recurs in 30 to 54% of patients without surgery. Identifying individuals likely to suffer a recurrence, who might benefit from pre-emptive surgery, is challenging. Previous meta-analysis suggested a relationship between contralateral recurrence and specific computed tomography (CT) findings. We analysed CT images and recurrence rates 243 patients seen by our tertiary referral pneumothorax service. We validated the meta-analysis observation that contralateral lung cysts are associated with a higher risk of contralateral recurrence in younger individuals. Furthermore, we observed the size of contralateral cysts to be associated with increased contralateral recurrence in younger patients. The detection of contralateral lung cysts might therefore help identify younger patients more likely to benefit from pre-emptive surgery.

A high-throughput focused collimator for OAR-sparing preclinical proton FLASH studies: commissioning and validation

Objective. To fabricate and validate a novel focused collimator designed to spare normal tissue in a murine hemithoracic irradiation model using 250 MeV protons delivered at ultra-high dose rates (UHDRs) for preclinical FLASH radiation therapy (FLASH-RT) studies. Approach. A brass collimator was developed to shape 250 MeV UHDR protons from our Varian ProBeam. Six 13 mm apertures, of equivalent size to kV x-ray fields historically used to perform hemithorax irradiations, were precisely machined to match beam divergence, allowing concurrent hemithoracic irradiation of six mice while sparing the contralateral lung and abdominal organs. The collimated field profiles were characterized by film dosimetry, and a radiation survey of neutron activation was performed to ensure the safety of staff positioning animals. Main results. The brass collimator produced 1.2 mm penumbrae radiation fields comparable to kV x-rays used in preclinical studies. The penumbrae in the six apertures are similar, with full-width half-maxima of 13.3 mm and 13.5 mm for the central and peripheral apertures, respectively. The collimator delivered a similar dose at an average rate of 52 Gy s−1 for all apertures. While neutron activation produces a high (0.2 mSv h−1) initial ambient equivalent dose rate, a parallel work-flow in which imaging and setup are performed without the collimator ensures safety to staff. Significance. Scanned protons have the greatest potential for future translation of FLASH-RT in clinical treatments due to their ability to treat deep-seated tumors with high conformality. However, the Gaussian distribution of dose in proton spots produces wider lateral penumbrae compared to other modalities. This presents a challenge in small animal pre-clinical studies, where millimeter-scale penumbrae are required to precisely target the intended volume. Offering high-throughput irradiation of mice with sharp penumbrae, our novel collimator-based platform serves as an important benchmark for enabling large-scale, cost-effective radiobiological studies of the FLASH effect in murine models.

Features and outcomes of bilateral anatomical lung resections in patients with lung cancer

The aim of this study was to evaluate the feasibility and safety of sequential bilateral anatomical lung resections performed via video-assisted thoracic surgery (VATS) or thoracotomy approaches in lung cancer patients, as well as to identify factors affecting the postoperative period. Material and Methods. Of 534 NSCLC patients undergoing anatomical lung resection in Center for Intensive Pulmonology and Thoracic Surgery from 2014 to 2022, 14 patients with consecutive bilateral anatomical lung resections were included in the retrospective study. The patients were divided into two groups depending on a surgical approach used during the first surgery: group I – 5 patients underwent thoracotomy and group II – 9 patients underwent videoassisted thoracic surgery (VATS). The groups were matched for gender, age, smoking, Charlson Comorbidity Index, lung resection, functional status and stage of the disease. Surgical treatment included anatomical lung resection and ipsilateral systematic lymph dissection. Results. There were significant differences in intraoperative blood loss between the groups. Postoperative complications after surgery on the contralateral lung were observed more often in group 1 patients than in group II patents. The overall 5-year survival rates in patients of groups 1 and 2 were 60 % and 86 %, respectively. Respiratory function indicators three months after surgery corresponded to preoperative prognosis, and their decrease did not depend on the surgical approach used. In comparison with patients who underwent standard unilateral lung resection, bilateral anatomical lung resection was not associated with increased number of “major” complications, however, an increase in the frequency of prolonged air discharge was noted (26 % vs 6 %; p&lt;0.05). Conclusion. Sequential bilateral anatomical lung resections are feasible and safe after thorough preoperative assessment of the functional reserves of the cardio-respiratory system. Mini-invasive technologies make it possible to reduce the frequency of complications in the early postoperative period. The use of the VATS approach makes it possible to safely perform anatomical resection of the contralateral lung.

An analysis of residual lung volume changes after segmentectomy based on three-dimensional computed tomography.

Based on the results of JCOG0802 and CALGB studies, segmentectomy has considered to be a standard procedure for early-stage non-small cell lung cancer (NSCLC). After lobectomy, the residual cavity is filled with mediastinal and diaphragmatic deviations, and compensatory volume changes are present in the residual lungs. In this study, we examined the efficacy of segmentectomy, a surgical procedure, by focusing on its impact on postoperative lung volume and function. We enrolled 77 patients who underwent segmentectomy as their initial surgical procedure, excluding those with additional lung resections and those who lacked postoperative computed tomography imaging. The predicted residual volume (mL) was defined as the total lung volume before surgery minus the volume of the resected area. Using the predicted residual volume (mL) and postoperative total lung volume (mL), we calculated the rate of postoperative lung volume increase [(postoperative total lung volume/predicted residual volume) × 100] (%). We also classified 52 cases with a rate of postoperative lung volume increase of ≥100% into a compensatory group, while those with a rate of <100% were classified into a non-compensatory group. The average postoperative lung volume increase was 104.6% among 77 cases. Age ≥65 years, pack year index ≥27.5, ≥3 resected segments, and use of electrocautery for intersegmental plane division were significantly associated with compensatory group classification. In 20 compensatory cases with preoperative and postoperative pulmonary function tests, postoperative vital capacity and forced expiratory volume in one second values exceeded the preoperative predictions. This study further examined the areas responsible for postoperative compensatory lung volume increase. In the compensatory group, significant expansion was observed in the ipsilateral lobes, excluding the resected segment and contralateral lung, while no significant changes were noted in the volume of the lobe, including the resected segment. Conversely, the non-compensatory group showed a significant volume decrease in the resected lobe, but no significant increase in other areas. This study emphasizes the importance of preserving lung segments in segmentectomy. The study demonstrates extensive compensatory volume changes in the ipsilateral lung and contralateral lung. There was no significant volume decrease in any residual segment. This underlines the potential of segmentectomy to maintain lung function and expand treatment options post-surgery. In addition, the compensated group included patients with a lower pack-year index and younger patients. These results suggest that postoperative compensatory lung expansion includes not only hyperinflation of the remaining lung, but also an increase in the functional lung parenchyma.

Evaluation of Dosimetric and Radiobiological Parameters for Different TPS Dose Calculation Algorithms and Plans for Lung Cancer Radiotherapy

Lung cancer presents a major public health concern in our country and around the globe. Radiotherapy is one of the main treatment modalities for lung cancer management for several years. This study aims to evaluate differences in the dosimetric and radiobiological parameters and in the dose distributions of Planning Target Volume (PTV) and organs at risk (OAR) in patients with lung tumors using different Treatment Planning System (TPS) algorithms and Volumetric Modulated Arc Therapy (VMAT) technique. This study was accomplished in a group of 19 patients with lung tumors who were treated in our clinic. In the treatment planning of the patients; Elekta-Monaco with Monte Carlo (XVMC), Pencil Beam algorithm; Varian-Eclipse with Anisotropic Analytical Algorithm (AAA), Acuros XB (AXB)algorithms and Tomo-plan Treatment Planning System with Convolution Superposition algorithm of Tomotherapy device were used. In these treatment planning systems, plans were done by 6 MV photon energy using Volumetric Arc Therapy (VMAT) techniques. The prescribed dose to the PTV was 60 Gy in 30 fractions. Statistical analysis was performed using SPSS Statistics v.29.0.2.0 programme. Statistically, significant differences were found in Dmean, Dmax, D2 and D98 values for PTV between the algorithms, while small differences were found in Dmax values of the contralateral lung, total lung and esophagus in critical organs. It is concluded that the difference between algorithms for PTV increases especially as the volume of the target tumor decreases. TPS with C/S algorithm gave closer results with XVMC. Algorithms were found to have an impact on radiobiological parameters.

Analysis of clinical characteristics of different types of lung function impaiement in TDL patients

AimThe clinical characteristics associated with pulmonary function decline in patients with Tuberculosis-destroyed lung (TDL) remain uncertain. We categorize them based on the pattern of pulmonary function impairment, distinguishing between restrictive spirometric pattern (RSP) and obstructive spirometric pattern (OSP). We aim to compare the severity of these patterns with the clinical characteristics of TDL patients and analyze their correlation.MethodWe conducted a retrospective analysis on the clinical data of TDL patients who underwent consecutive pulmonary function tests (PFT) from November 2002 to February 2023. We used the lower limit formula for normal values based on the 2012 Global Lung Function Initiative. We compared the clinical characteristics of RSP patients with those of OSP patients. The characteristics of RSP patients were analyzed using the tertiles of forced vital capacity percentage predicted (FVC% pred) decline based on PFT measurements, and the characteristics of OSP patients were analyzed using the tertiles of forced expiratory volume in 1 s percentage predicted (FEV1% pred) decline.ResultAmong the RSP patients, those in the Tertile1 group (with lower FVC% pred) were more likely to have a higher of body mass index (BMI), spinal deformities, and C-reactive protein (CRP) compared to the other two groups (P for trend < 0.001, 0.027, and 0.013, respectively). Among OSP patients, those in the Tertile1 group (with lower FEV1% pred) showed an increasing trend in cough symptoms and contralateral lung infection compared to the Tertile 2–3 group (P for trend 0.036 and 0.009, respectively).ConclusionFor TDL patients, we observed that Patients with high BMI, a higher proportion of spinal scoliosis, and abnormal elevation of CRP levels were more likely to have reduced FVC. Patients with decreased FEV1% pred have more frequent cough symptoms and a higher proportion of lung infections on the affected side.

Dosimetric analysis of six whole-breast irradiation techniques in supine and prone positions

In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and treatment positions can reduce radiation doses to normal organs and mitigate treatment-related toxicity. This study entailed a dosimetric comparison of six different external beam whole-breast irradiation techniques in both supine and prone positions. We selected fourteen breast cancer patients, generating six treatment plans in both positions per patient. We assessed target coverage and organs at risk (OAR) doses to evaluate the impact of treatment techniques and positions. Excess absolute risk was calculated to estimate potential secondary cancer risk in the contralateral breast, ipsilateral lung, and contralateral lung. Additionally, we analyzed the distance between the target volume and OARs (heart and ipsilateral lung) while considering the treatment position. The results indicate that prone positioning lowers lung exposure in X-ray radiotherapy. However, particle beam therapies (PBTs) significantly reduce the dose to the heart and ipsilateral lung regardless of the patient’s position. Notably, negligible differences were observed between arc-delivery and static-delivery PBTs in terms of target conformity and OAR sparing. This study provides critical dosimetric evidence to facilitate informed decision-making regarding treatment techniques and positions.