Prediction of Pleural Lavage Cytology According to Thin-Section Computed Tomography in Non-Small-Cell Lung Cancer.

BACKGROUND: Although the positive rate of preresection pleural lavage cytology (PLC) is low, it is an important indicator of poor prognosis for non-small-cell lung cancer patients with frequent pleural dissemination (PD) recurrence. Thin-section computed tomography (TSCT) can reveal relationships between a primary tumor and the pleura at 1 to 2 mm intervals, and this is associated with visceral pleural invasion (VPI). However, its association with PLC remains unclear. Therefore, we aimed to improve PLC efficiency and predict PD recurrence by understanding the relationship between PLC and preoperative TSCT findings. PATIENTS AND METHODS: Between January 2014 and December 2018, we reviewed 978 patients with non-small-cell lung cancer who underwent PLC tests during complete resection surgery. Preoperative TSCT findings were evaluated, and factors with the highest specificity (proportion of patients with radiologically to pathologically diagnosed positive PLC) were investigated. We also evaluated their relationships with VPI and PD recurrence. RESULTS: PLC positive was identified in 55 (5.6%) of the 978 patients. The two TSCT findings predicting PLC results, "the absence of pleural findings," ie, tumor not attached to pleura or without pleural tag, and "consolidation-to-tumor ratio ≤0.5", had a specificity of 100% (95% confidence interval: 90.4%-100%); additionally, all cases with these findings were VPI negative and had no PD recurrence. And 24% of the cohort had either of these findings. CONCLUSION: The absence of pleural findings and/or consolidation-to-tumor ratio ≤0.5 of primary tumor on preoperative TSCT can predict PLC negativity with very high probability; therefore, PLC can be omitted for such patients.

Real-World Data on Subsequent Therapy for First-Line Osimertinib-Induced Pneumonitis: Safety of EGFR-TKI Rechallenge (Osi-risk Study TORG-TG2101).

BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020. RESULTS: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03). CONCLUSIONS: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.

Machine learning-based computer-aided simple triage (CAST) for COVID-19 pneumonia as compared with triage by board-certified chest radiologists.

PURPOSE: Several reporting systems have been proposed for providing standardized language and diagnostic categories aiming for expressing the likelihood that lung abnormalities on CT images represent COVID-19. We developed a machine learning (ML)-based CT texture analysis software for simple triage based on the RSNA Expert Consensus Statement system. The purpose of this study was to conduct a multi-center and multi-reader study to determine the capability of ML-based computer-aided simple triage (CAST) software based on RSNA expert consensus statements for diagnosis of COVID-19 pneumonia. METHODS: For this multi-center study, 174 cases who had undergone CT and polymerase chain reaction (PCR) tests for COVID-19 were retrospectively included. Their CT data were then assessed by CAST and consensus from three board-certified chest radiologists, after which all cases were classified as either positive or negative. Diagnostic performance was then compared by McNemar's test. To determine radiological finding evaluation capability of CAST, three other board-certified chest radiologists assessed CAST results for radiological findings into five criteria. Finally, accuracies of all radiological evaluations were compared by McNemar's test. RESULTS: A comparison of diagnosis for COVID-19 pneumonia based on RT-PCR results for cases with COVID-19 pneumonia findings on CT showed no significant difference of diagnostic performance between ML-based CAST software and consensus evaluation (p > 0.05). Comparison of agreement on accuracy for all radiological finding evaluations showed that emphysema evaluation accuracy for investigator A (AC = 91.7%) was significantly lower than that for investigators B (100%, p = 0.0009) and C (100%, p = 0.0009). CONCLUSION: This multi-center study shows COVID-19 pneumonia triage by CAST can be considered at least as valid as that by chest expert radiologists and may be capable for playing as useful a complementary role for management of suspected COVID-19 pneumonia patients as well as the RT-PCR test in routine clinical practice.

Clinical and imaging features of interstitial lung disease in cancer patients treated with trastuzumab deruxtecan.

BACKGROUND: Interstitial lung disease/pneumonitis (ILD/pneumonitis) has been identified as a drug-related adverse event of special interest of trastuzumab deruxtecan (T-DXd), but there were a few reports of T-DXd-related ILD/pneumonitis in clinical practice. METHODS: Between May 25, 2020 (the launch of T-DXd in Japan) and February 24, 2022, there were 287 physician-reported potential ILD/pneumonitis cases from the Japanese post-marketing all-case surveillance. By February 27, 2022, an independent adjudication committee assessed 138 cases and adjudicated 130 cases as T-DXd-related ILD/pneumonitis. The clinical features and imaging characteristics of these cases were evaluated. RESULTS: The majority of adjudicated T-DXd-related ILD/pneumonitis cases were grade 1 or 2 (100/130, 76.9%). The most common radiological pattern types observed were organizing pneumonia patterns (63.1%), hypersensitivity pneumonitis patterns (16.9%), and diffuse alveolar damage (DAD) patterns (14.6%). Eleven cases (8.5%) from 130 resulted in death; the majority of these (8/11, 72.7%) had DAD patterns. The overall proportion of recovery (including the outcomes of recovered, recovered with sequelae, and recovering) was 76.9%, and the median time to recovery was 83.5 days (interquartile range: 42.25-143.75 days). Most cases (59/71, 83.1%) that were treated with corticosteroids were considered responsive to treatment. CONCLUSIONS: This is the first report to evaluate T-DXd-related ILD/pneumonitis cases in clinical practice. Our findings are consistent with previous reports and suggest that patients with DAD patterns have poor outcomes. Evaluation of a larger real-world dataset may further identify predictors of clinical outcome.

Creation, evolution, and future challenges of ion beam therapy from a medical physicist's viewpoint (Part 3): Chapter 3. Clinical research, Chapter 4. Future challenges, Chapter 5. Discussion, and Conclusion.

Clinical studies of ion beam therapy have been performed at the Lawrence Berkeley Laboratory (LBL), National Institute of Radiological Sciences (NIRS), Gesellschaft für Schwerionenforschung (GSI), and Deutsches Krebsforschungszentrum (DKFZ), in addition to the development of equipment, biophysical models, and treatment planning systems. Although cancers, including brain tumors and pancreatic cancer, have been treated with the Bevalac's neon-ion beam at the LBL (where the first clinical research was conducted), insufficient results were obtained owing to the limited availability of neon-ion beams and immaturity of related technologies. However, the 184-Inch Cyclotron's helium-ion beam yielded promising results for chordomas and chondrosarcomas at the base of the skull. Using carbon-ion beams, NIRS has conducted clinical trials for the treatment of common cancers for which radiotherapy is indicated. Because better results than X-ray therapy results have been obtained for lung, liver, pancreas, and prostate cancers, as well as pelvic recurrences of rectal cancer, the Japanese government recently approved the use of public medical insurance for carbon-ion radiotherapy, except for lung cancer. GSI obtained better results than LBL for bone and soft tissue tumors, owing to dose enhancement enabled by scanning irradiation. In addition, DKFZ compared treatment results of proton and carbon-ion radiotherapy for these tumors. This article summarizes a series of articles (Parts 1-3) and describes future issues of immune ion beam therapy and linear energy transfer optimization.

Creation, evolution, and future challenges of ion beam therapy from a medical physicist's viewpoint (Part 2). Chapter 2. Biophysical model, treatment planning system and image guided radiotherapy.

When an ion beam penetrates deeply into the body, its kinetic energy decreases, and its biological effect increases due to the change of the beam quality. To give a uniform biological effect to the target, it is necessary to reduce the absorbed dose with the depth. A bio-physical model estimating the relationship between ion beam quality and biological effect is necessary to determine the relative biological effectiveness (RBE) of the ion beam that changes with depth. For this reason, Lawrence Berkeley Laboratory, National Institute of Radiological Sciences (NIRS) and GSI have each developed their own model at the starting of the ion beam therapy. Also, NIRS developed a new model at the starting of the scanning irradiation. Although the Local Effect Model (LEM) at the GSI and the modified Microdosimetric Kinetic Model (MKM) at the NIRS, the both are currently used, can similarly predict radiation quality-induced changes in surviving fraction of cultured cell, the clinical RBE-weighted doses for the same absorbed dose are different. This is because the LEM uses X-rays as a reference for clinical RBE, whereas the modified MKM uses carbon ion beam as a reference and multiplies it by a clinical factor of 2.41. Therefore, both are converted through the absorbed dose. In PART 2, I will describe the development of such a bio-physical model, as well as the birth and evolution of a treatment planning system and image guided radiotherapy.

Patient dose increase caused by posteroanterior CT localizer radiographs.

INTRODUCTION: The aim of this study was to compare the output dose (volume CT dose index [ CTDIvol], and dose length product [DLP]) of automatic tube current modulation (ATCM) determined by localizer radiographs obtained in the anteroposterior (AP) and posteroanterior (PA) directions. METHODS: One hundred and twenty-four patients who underwent upper abdomen and/or chest-to-pelvis computed tomography (CT) were included. Patients underwent two series of CT examinations, and localizer radiographs were obtained in the AP and PA directions. The horizontal diameter of the localizer radiograph, scan length, CTDIvol, and DLP were measured. RESULTS: There was no significant difference in the scan length; however, all the other values were significantly higher in the PA direction. The mean horizontal diameter was 33.1 ± 2.6 cm and 35.4 ± 2.9 cm in the AP and PA directions of the localizer radiographs, respectively. The CTDIvol and DLP in the PA direction increased by approximately 7-8%. Bland-Altman plots between AP and PA localizer directions in upper abdominal CT showed a positive bias of 1.1 mGy and 30.0 mGy cm for CTDIvol and DLP, respectively. Correspondingly, chest-to-pelvic CT showed a positive bias of 0.93 mGy and 69.3 mGy cm for CTDIvol and DLP, respectively. CONCLUSION: The output dose of ATCM determined by localizer radiographs obtained in the PA direction was increased compared to the AP direction. Localizer radiographs obtained in the AP direction should be preferred for optimizing the output dose using ATCM. IMPLICATIONS FOR PRACTICE: Based on the evidence of this study, localizer radiographs obtained in the AP direction should be preferred for optimizing the output dose in CT examinations.

Clinical impact of tumour burden on the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy in non-small-cell lung cancer.

BACKGROUND: Programmed cell death 1 (PD-1)/programmed cell death ligand (PD-L1) inhibitors plus chemotherapy (ICI + Chemo) is the standard treatment for advanced non-small-cell lung cancer (NSCLC). However, the impact of tumour burden on the efficacy of ICI + Chemo remains unknown. METHODS: We retrospectively evaluated 92 patients with advanced NSCLC treated with ICI + Chemo. Tumour burden was assessed as the sum of the longest diameter of the target lesion (BSLD) and number of metastatic lesions (BNMLs). We categorised the patients into three groups based on the combined BSLD and BNML values. RESULTS: Sixty-eight patients (74%) had progressive disease or died. Forty-four patients (48%) in the low-BSLD group had a median progression-free survival (PFS) of 9.5 months, whereas patients in the high-BSLD group had a median PFS of 4.6 months (hazard ratio [HR] = 0.54, p = 0012). Twenty-five patients (27%) in the low-BNML group had a median PFS of 9.6 months, whereas patients in the high-BNML group had a median PFS of 6.5 months (HR = 0.51, p = 0.029). Low-BSLD and low-BNML were associated independently with improved PFS in multivariate analysis. Analysis of the tumour burden combined with BSLD and BNML revealed a trend towards improved PFS as the tumour burden decreased, with median PFS of 22.3, 8.7, and 3.9 months in the low- (N = 13), medium- (N = 42) and high-burden (N = 37) groups respectively. CONCLUSIONS: Our findings demonstrated that a high tumour burden negatively impacts the efficacy of ICI + Chemo in patients with advanced NSCLC.

Creation, evolution, and future challenges of ion beam therapy from a medical physicist's viewpoint (part 1). Introduction and Chapter 1. accelerator and beam delivery system.

Radiation therapy for cancer using the Bragg peak of an ion beam has been making steady progress after being proposed by Robert Wilson in 1946. At the end of 2020, 12 dedicated treatment devices existed in operation worldwide, and approximately 40,000 patients have been treated with ion beams (mostly carbon ions). To date, ion beam therapy is superior to other treatments for rare cancers in the head and neck as well as bone and soft tissues; however, most recently, evidence submitted in Japan for the 2022 revision of public health insurance shows that ion beam therapy outperforms photon therapy for intractable common cancers such as pancreatic cancer and liver cancer. This may greatly expand its indications. Lawrence Berkeley Laboratory in the United States started research of ion beam therapy, National Institute of Radiological Sciences in Japan built the first dedicated device Heavy Ion Accelerator in Chiba and started systematic clinical research, and GSI in Germany developed the scanning irradiation method and rotating gantry for the first time. This paper presents the history and future challenges of ion beam therapy in three fields: accelerator and beam delivery system, physical/biological model and treatment planning system, and clinical research. This study is divided into three parts describing the achievements and roles of the three laboratories. In Part 1, accelerator and beam delivery system are described.

Computed tomographic pulmonary angiography: Three cases of low-tube-voltage acquisition with a slow injection of contrast medium.

Acute pulmonary thromboembolism occurring during cancer treatment has been increasing with the number of cancer patients and chemotherapy cases. Computed tomographic pulmonary angiography (CTPA) for evaluating the pulmonary artery is generally performed using rapid injection of contrast medium. However, intravenous catheters for contrast medium injection might cause extravasation due to rapid injection. This case series describes three patients who underwent contrast-enhanced computed tomography combined with low-tube-voltage imaging and slow injection. Low-tube-voltage slow-injection CTPA can be an effective technique for obtaining high contrast enhancement while accommodating fragile veins and low injection rates.

Predicting the efficacy of first-line immunotherapy by combining cancer cachexia and tumor burden in advanced non-small cell lung cancer.

BACKGROUND: Cancer cachexia and tumor burden predict efficacies of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy or pembrolizumab in non-small cell lung cancer (NSCLC). There are no predictive models that simultaneously assess cancer cachexia and tumor burden. METHODS: In the present retrospective study, we reviewed the medical records of patients with advanced NSCLC who received cancer immunotherapy as first-line systemic therapy. Clinical immune predictive scores were defined according to multivariate analysis of progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 157 patients were included in the present study (75 treated with PD-1/PD-L1 inhibitors + chemotherapy; 82, pembrolizumab monotherapy). Multivariate analysis for PFS revealed that PD-L1 tumor proportion scores <50%, a total target lesion diameter ≥76 mm, and cancer cachexia were independently associated with poor PFS. Multivariate analysis for OS revealed that ≥4 metastases and cancer cachexia were significantly associated with poor OS. In the immune predictive model, the median PFS was 21.7 months in the low-risk group (N = 41); 7.6 in the medium-risk group (N = 64); and 3.0 in the high-risk group (N = 47). The median OS were not reached, 22.4 and 9.1 months respectively. Our immune predictive model was significantly associated with PFS (p < 0.001) and OS (p < 0.001). CONCLUSION: We proposed the immune predictive model, including tumor burden and cancer cachexia, which may predict the efficacy and survival outcome of first-line immunotherapy in advanced NSCLC.

[History of medical physics].

This is a review on history of medical physics in Radiological Physics and Technology published by JSRT and JSMP (https://www.jsmp.org/en/).

Validity of surgical decision based on intraoperative frozen section diagnosis for unconfirmed pulmonary nodules with previous malignancy.

OBJECTIVES: The lung is a major target organ of metastasis in several cancers. To distinguish primary lung cancer from pulmonary metastases is a clinical challenge. Small pulmonary nodules (PNs) are frequently diagnosed by frozen section diagnosis (FSD) intraoperatively after resection. Intraoperative FSD is very important to determine the extent of subsequent surgical procedures. This study aimed to know the validity of surgical decision based on FSD for preoperatively unconfirmed PN with previous malignancy. METHODS: We retrospectively evaluated 96 patients with suspected malignant PN who underwent intraoperative FSD between 2018 and 2020. Intraoperative FSD, final diagnosis, and surgical procedure data were examined. RESULTS: Surgical procedure adequacy, based on FSD for preoperatively unconfirmed PN with previous malignancy, was 91% (88/96). The overall diagnostic accuracy of FSD was 83.3% (80/96). Discrepancy was noted in two cases (2.1%), and conclusive diagnosis could not be reached intraoperatively in 14 cases (14.6%). A second surgery was required in three patients and no additional excision for primary lung cancer was performed in three patients. Conversely, there were three cases of over-surgery, namely, lobectomy for pulmonary metastasis. CONCLUSIONS: Surgical decision-making based on FSD for preoperatively unconfirmed PN in patients with previous malignancy was generally adequate. However, there were inadequate or excessive surgical procedures due to limitations in the accuracy of intraoperative FSD. Improving the accuracy of intraoperative FSD is a necessary step for obtaining adequate surgical decision-making and precision medicine.

Ultrahigh-Resolution Computed Tomography Improves Preoperative Computed Tomography Angiography for Deep Inferior Epigastric Artery Perforator Flap Reconstruction.

OBJECTIVE: The aim of the study was to compare computed tomography (CT) angiography (CTA) imaging of deep inferior epigastric artery perforator (DIEP) using the ultrahigh-resolution CT (UHRCT) and conventional multidetector CT (MDCT). METHODS: This retrospective study enrolled 20 patients who underwent CTA of DIEP flap with UHRCT and MDCT. Computed tomography values were measured at 4 large vessels (thoracic aorta, abdominal aorta, common iliac artery, and external iliac artery) and 5 peripheral vessels (proximal and distal internal thoracic artery, proximal and distal deep inferior epigastric artery, and DIEP). RESULTS: There were no significant differences in mean CT values of the major vessel between UHRCT and MDCT. Ultrahigh-resolution CT shows higher CT values of the peripheral vessels than MDCT (P < 0.05 for all). The median CT values of the DIEP in UHRCT were approximately 3 times higher than those in MDCT (P < 0.001). CONCLUSIONS: Ultrahigh-resolution CT provides higher-quality CTA of DIEP compared with MDCT.

History of medical physics.

Medical physics began with the development of safe handling of radium, such as protecting medical personnel from radiation when radium radiation is used to treat cancer. By the end of World War II, the field of medical physics had expanded to the development of safe and reliable treatments for cancer with radiation and quantification of radiation dose, which is called dosimetry that is required to evaluate the therapeutic effect. The rapid development of nuclear technology during World War II made it possible to use large amounts of radioisotopes (RI) produced in nuclear reactors, and the medical use of RI gave birth to clinical nuclear medicine. Since knowledge and skills in radiation measurement and RI handling were required for the development and clinical use of its equipment, nuclear medicine physics was added to medical physics after the war. The invention of computed tomography (CT) in 1972 had a great impact on clinical medicine, while the development of magnetic resonance imaging (MRI) began around that time. As a result, the development of CT and MRI, as well as the study of their image characteristics, which had not necessarily been regarded as the field of medical physics before, was added to that field as radiation diagnostic physics. This review outlines the history of developments in medical physics, and touches on the first medical physicists in Europe and the United States. It also briefly explains the beginning of medical physics and the world-class medical physics achievements in Japan.

Association between oligo-residual disease and patterns of failure during EGFR-TKI treatment in EGFR-mutated non-small cell lung cancer: a retrospective study.

BACKGROUND: Local ablative therapy (LAT) may be beneficial for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with oligo-residual disease after treatment with EGFR tyrosine kinase inhibitor (EGFR-TKI). However, this has not been fully established. This study aimed to evaluate the predominant progressive disease (PD) pattern limited to residual sites of disease after treatment with EGFR-TKI. METHODS: Patients with advanced EGFR-mutated NSCLC treated with EGFR-TKIs as first-line therapy were retrospectively analysed during a 7-year period. Oligo-residual disease was defined as the presence of 1 - 4 lesions (including the primary site) at 3 months from the start of EGFR-TKI treatment. The predictive factors of PD patterns after EGFR-TKI treatment were evaluated. RESULTS: A total of 207 patients were included. Three months after the start of EGFR-TKI treatment, 66 patients (32%) had oligo-residual disease. A total of 191 patients had PD, 60 with oligo-residual disease and 131 with non-oligo-residual disease. Regarding the pattern, 44 patients (73%) with oligo-residual disease and 37 patients (28%) with non-oligo-residual disease had PD limited to the residual sites. Multivariate logistic regression analysis at 3 months from the start of EGFR-TKI treatment revealed that oligo-residual disease (P < 0.001), the lack of residual central nervous system metastases (P = 0.032), and initial treatment with osimertinib (P = 0.028) were independent predictors of PD limited to residual disease sites. CONCLUSIONS: This study provided a rationale for LAT to all sites of residual disease in patients with oligo-residual disease during EGFR-TKI treatment.