Interim PET-guided ABVD or ABVD/escalated BEACOPP for newly diagnosed advanced-stage classic Hodgkin lymphoma (JCOG1305).

This single-arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)-guided therapy for newly diagnosed advanced-stage classic Hodgkin lymphoma (cHL). Patients aged 16-60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five-point Deauville scale. PET2-negative patients continued an additional four cycles of ABVD, whereas PET2-positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co-primary endpoints were 2-year progression-free survival (PFS) among all eligible and PET2-positive patients. Ninety-three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28-48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2-positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2-negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow-up period of 41.1 months, the 2-year PFS of 92 eligible patients and 19 PET2-positive patients were 84.8% (80% confidence interval [CI], 79.2-88.9) and 84.2% (80% CI, 69.7-92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET-guided therapy is a useful treatment option for younger patients with newly diagnosed advanced-stage cHL. Registration number: jRCTs031180218.

Ringlike Peripheral Increased Iodine Concentration for the Differentiation of Primary Lung Cancer and Pulmonary Metastases on Contrast-Enhanced Dual-Energy CT.

BACKGROUND. Differentiation of primary lung cancers and pulmonary metastases may present a diagnostic dilemma given overlapping CT findings. OBJECTIVE. The purpose of this study was to compare the utility of ringlike peripheral increased iodine concentration and conventional findings for differentiating primary lung cancers from pulmonary metastases on dual-energy CT (DECT). METHODS. This retrospective study included 93 patients (64 men, 29 women; median age, 70 years) who underwent resection of a primary lung cancer (n = 68) or pulmonary metastasis (n = 25) corresponding to a solid lesion on preoperative contrast-enhanced DECT performed between April 2020 and March 2021. Venous phase 120-keV single-energy images, equilibrium phase 66-keV virtual monoenergetic images, and iodine concentration maps were reconstructed. Two radiologists independently assessed lesions for spiculated margins, air bronchograms, rim enhancement, and thin ringlike peripheral high iodine concentration; differences were resolved by consensus. Inter-reader agreement and diagnostic performance were assessed. Multivariable logistic regression analysis incorporated additional patient and lesion characteristics. RESULTS. Interobserver agreement, expressed as kappa, was 0.26 for spiculated margins, 0.60 for air bronchograms, 0.56 for rim enhancement, and 0.80 for ringlike peripheral high iodine concentration. Pulmonary metastases, compared with primary lung cancers, exhibited significantly higher frequency of ringlike peripheral high iodine concentration (52% vs 19%; p = .004) but no significant difference in frequency of spiculated margins (49% vs 32%; p = .17), air bronchograms (36% vs 51%; p = .24), or rim enhancement (4% vs 4%; p > .99). Sensitivity and specificity for diagnosing pulmonary metastasis were 68% and 49% for absence of spiculated margins, 64% and 51% for absence of air bronchograms, 4% and 96% for presence of rim enhancement, and 52% and 81% for presence of ringlike peripheral high iodine concentration. In multivariable analysis including smoking history, lesion diameter, multiple resected lesions, and ringlike peripheral high iodine concentration, the only independent significant predictor of pulmonary metastasis was ringlike peripheral high iodine concentration (OR, 7.81 [95% CI, 2.28-29.60); p = .001). CONCLUSION. Ringlike peripheral high iodine concentration had excellent interobserver agreement and high specificity (albeit poor sensitivity) for differentiating pulmonary metastasis from primary lung cancer and was independently predictive of pulmonary metastasis. CLINICAL IMPACT. Ringlike peripheral high iodine concentration could help guide management of patients with known cancer and an indeterminate solitary nodule.

Reproducibility of the principal component analysis (PCA)-based data-driven respiratory gating on texture features in non-small cell lung cancer patients with 18 F-FDG PET/CT.

OBJECTIVE: Texture analysis is one of the lung cancer countermeasures in the field of radiomics. Even though image quality affects texture features, the reproducibility of principal component analysis (PCA)-based data-driven respiratory gating (DDG) on texture features remains poorly understood. Hence, this study aimed to clarify the reproducibility of PCA-based DDG on texture features in non-small cell lung cancer (NSCLC) patients with 18 F-Fluorodeoxyglucose (18 F-FDG) Positron emission tomography/computed tomography (PET/CT). METHODS: Twenty patients with NSCLC who underwent 18 F-FDG PET/CT in routine clinical practice were retrospectively analyzed. Each patient's PET data were reconstructed in two PET groups of no gating (NG-PET) and PCA-based DDG gating (DDG-PET). Forty-six image features were analyzed using LIFEx software. Reproducibility was evaluated using Lin's concordance correlation coefficient ( ρ c ${\rho _c}$ ) and percentage difference (%Diff). Non-reproducibility was defined as having unacceptable strength ( ρ c $({\rho _c}$  < 0.8) and a %Diff of >10%. NG-PET and DDG-PET were compared using the Wilcoxon signed-rank test. RESULTS: A total of 3/46 (6.5%) image features had unacceptable strength, and 9/46 (19.6%) image features had a %Diff of >10%. Significant differences between the NG-PET and DDG-PET groups were confirmed in only 4/46 (8.7%) of the high %Diff image features. CONCLUSION: Although the DDG application affected several texture features, most image features had adequate reproducibility. PCA-based DDG-PET can be routinely used as interchangeable images for texture feature extraction from NSCLC patients.

Determination of a reliable assessment for occupational eye lens dose in nuclear medicine.

The most recent statement published by the International Commission on Radiological Protection describes a reduction in the maximum allowable occupational eye lens dose from 150 to 20 mSv/year (averaged over 5-year periods). Exposing the eye lens to radiation is a concern for nuclear medicine staff who handle radionuclide tracers with various levels of photon energy. This study aimed to define the optimal dosimeter and means of measuring the amount of exposure to which the eye lens is exposed during a routine nuclear medicine practice. A RANDO human phantom attached to Glass Badge and Luminess Badge for body or neck, DOSIRIS and VISION for eyes, and nanoDot for body, neck, and eyes was exposed to 99m Tc, 123 I, and 18 F radionuclides. Sealed syringe sources of each radionuclide were positioned 30 cm from the abdomen of the phantom. Estimated exposure based on measurement conditions (i.e., air kerma rate constants, conversion coefficient, distance, activity, and exposure time) was compared measured dose equivalent of each dosimeter. Differences in body, neck, and eye lens dosimeters were statistically analyzed. The 10-mm dose equivalent significantly differed between the Glass Badge and Luminess Badge for the neck, but these were almost equivalent at the body. The 0.07-mm dose equivalent for the nanoDot dosimeters was greatly overestimated compared to the estimated exposure of 99m Tc and 123 I radionuclides. Measured dose equivalents of exposure significantly differed between the body and eye lens dosimeters with respect to 18 F. Although accurately measuring radiation exposure to the eye lenses of nuclear medicine staff is conventionally monitored using dosimeters worn on the chest or abdomen, eye lens dosimeters that provide a 3-mm dose equivalent near the eye would be a more reliable means of assessing radiation doses in the mixed radiation environment of nuclear medicine.

Alectinib for relapsed or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma: An open-label phase II trial.

Anaplastic lymphoma kinase (ALK) inhibition is expected to be a promising therapeutic strategy for ALK-positive malignancies. We aimed to examine the efficacy and safety of alectinib, a second-generation ALK inhibitor, in patients with relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL). This open-label, phase II trial included patients (aged 6 years or older) with relapsed or refractory ALK-positive ALCL. Alectinib 300 mg was given orally twice a day (600 mg/d) for 16 cycles, and the duration of each cycle was 21 days. Patients who weighed less than 35 kg were given a reduced dose of alectinib of 150 mg twice a day (300 mg/d). Ten patients were enrolled, and the median age was 19.5 years (range, 6-70 years). Objective responses were documented in eight of 10 patients (80%; 90% confidence interval, 56.2-95.9), with six complete responses. The 1-year progression-free survival, event-free survival, and overall survival rates were 58.3%, 70.0%, and 70.0%, respectively. The median duration of therapy was 340 days. No unexpected adverse events occurred. The most common grade 3 and higher adverse event was a decrease in neutrophil count in two patients. Alectinib showed favorable clinical activity and was well tolerated in patients with ALK-positive ALCL who had progressed on standard chemotherapy. Based on the results of the current study, the Ministry of Health, Labour and Welfare of Japan approved alectinib for the treatment of recurrent or refractory ALK-positive ALCL in February 2020.

Cardiac overload resolved by resection of a large plexiform neurofibroma on both the buttocks and upper posterior thighs in a patient with neurofibromatosis type I: a case report.

BACKGROUND: A large plexiform neurofibroma in patients with neurofibromatosis type I can be life threatening due to possible massive bleeding within the lesion. Although the literature includes many reports that describe the plexiform neurofibroma size and weight or strategies for their surgical treatment, few have discussed their possible physical or mental benefits, such as reducing cardiac stress. In addition, resection of these large tumors can result in impaired wound healing, partly due to massive blood loss during surgery. CASE PRESENTATION: A 24-year-old man was diagnosed with neurofibromatosis type I and burdened with a large plexiform neurofibroma on the buttocks and upper posterior thighs. The patient was 159 cm in height and 70.0 kg in weight at the first visit. Cardiac overload was indicated by an echocardiography before surgery. His cardiac output was 5.2 L/min with mild tricuspid regurgitation. After embolism of the arteries feeding the tumor, the patient underwent surgery to remove the neurofibroma, followed by skin grafting. Follow-up echocardiography, performed 6 months after the final surgery, indicated a decreased cardiac output (3.6 L/min) with improvement of tricuspid regurgitation. Because the blood loss during the first surgery was over 3.8 L, malnutrition with albuminemia was induced and half of the skin graft did not attach. Nutritional support to improve the albuminemia produced better results following a second surgery to repair the skin wound. CONCLUSION: Cardiac overload may be latent in patients with neurofibromatosis type I with large plexiform neurofibromas. As in pregnancy, the body may compensate for this burden. In these patients, one stage total excision may improve quality of life and reduce cardiac overload. In addition, nutritional support is likely needed following a major surgery that results in either an extensive skin wound or excessive blood loss during treatment.

Revised staging system for malignant lymphoma based on the Lugano classification.

The Lugano classification was published in 2014 to form the basis for revising the recommendations regarding anatomic staging and evaluation of disease before and after therapy. This staging system was adopted by the eighth edition of the Cancer Staging Manual of the American Joint Committee on Cancer. In this review, we aimed to discuss this updated staging system for malignant lymphomas. The most important change was that fluorodeoxyglucose positron emission tomography/computed tomography became the new standard imaging technique for staging of all fluorodeoxyglucose-avid histologies. Due to the introduction of fluorodeoxyglucose positron emission tomography/computed tomography for staging, the evaluation of not only lymph node involvement but also organ involvement, including liver or spleen, has become simplified. Furthermore, it is possible to eliminate bone marrow biopsies in patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. Although patients were grouped according to the absence (A) or presence (B) of disease-related symptoms based on the previous classification, only the patients with Hodgkin lymphoma need to be assigned the designations A or B in this revision. Hopefully, these revised recommendations will improve patient management and the conduct of clinical trials.

[Administration Accuracy of Automated Infusion Device for PET Using Improved Disposable Kit].

PURPOSE: The AI-300 automated infusion device (Sumitomo Heavy Industries, Ltd., Tokyo, Japan) is subject to administration error as a function of smaller volumes of 18F-FDG dispensed via a three-way cock supplied with a disposable kit. The present study aimed to validate the administration accuracy of the AI-300 using an improved disposable kit for quantitative positron emission tomography (PET) assessment. METHODS: We determined administration accuracy between the improved and previous disposable kits by measuring variations in dispensed volumes and radioactive concentrations of 18F-FDG according to the criteria of the Japanese Society of Nuclear Medicine. A reference value was generated by measuring radioactivity using a standard dose calibrator. RESULTS: The values obtained using the previous kit deviated from the reference values by a maximum of -10.6%, and the deviation depended on dispensed volumes of 18F-FDG<0.25 mL. In contrast, the values were relatively stable when using the improved kit with dispensed 18F-FDG volumes < 0.25 mL. Variations in radioactive concentrations were relatively stable using the improved kit, whereas that of the previous kit was slightly unstable at high radioactive concentrations. CONCLUSION: The administration accuracy of the AI-300 using the previous kit varied considerably according to smaller dispensed volumes, but the improved kit might alleviate this problem. The present results indicated that the improved disposal kit should be immediately implemented to eliminate uncertainty surrounding quantitative PET findings.

Prognosis of patients with peripheral T cell lymphoma who achieve complete response after CHOP/CHOP-like chemotherapy without autologous stem cell transplantation as an initial treatment.

Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy has been mostly applied to patients with untreated peripheral T cell lymphoma (PTCL). Because the long-term outcome of patients with PTCL, especially those achieving complete response (CR), has not been fully elucidated, we retrospectively analyzed 78 consecutive patients initially treated with CHOP/CHOP-like chemotherapy, without high-dose chemotherapy followed by autologous stem cell transplantation (HDC/auto-SCT). Median overall and progression-free survivals in all 78 patients were 44 and 17 months, respectively, with a median follow-up of 62 months. In the 53 patients achieving CR, the median relapse-free survival (RFS) was 21 months, and 2-, 3-, and 5-year RFSs were 46, 45, and 36%, respectively. Although our results showed an unfavorable outcome for PTCL as a whole, those who achieved CR following CHOP/CHOP-like chemotherapy did not always have a poor outcome without the consolidation of HDC/auto-SCT; in particular, 45% of the 65 years or younger patients were alive without disease at 5 years.

Validation of Cross-calibration Schemes for Quantitative Bone SPECT/CT Using Different Sources under Various Geometric Conditions.

PURPOSE: Several cross-calibration schemes have been proposed to produce quantitative values in bone SPECT imaging. Differences in the radionuclide sources and geometric conditions can decrease the accuracy of cross-calibration factor (CCF). The present study aimed to validate the effects of calibration schemes using different sources under various geometric conditions. METHODS: Temporal variations as well as variations in acquisition counts and the shapes of 57Co standard and 99mTc point sources and a 99mTc disk source were determined. The effects of the geometric conditions of the source-to-camera distance (SCD) and lateral distance on the CCF were investigated by moving the camera or source away from the origin. The system planar sensitivity of NEMA incorporated into a Symbia Intevo SPECT/CT device (Siemens®) was defined as reference values. RESULTS: The temporal variation in CCF using the 57Co source was relatively stable within the range of 0.7% to 2.3%, whereas the 99mTc source ranged from 2.7% to 7.3%. In terms of source shape, the 57Co standard point source was the most stable. Both SCD and lateral distance decreased as a function of distance from the origin. Errors in the geometric condition were higher for the 57Co standard point source than the 99mTc disk source. CONCLUSIONS: Different calibration schemes influenced the reliability of quantitative values. The 57Co standard point source was stable over a long period, and this helped to maintain the quality of quantitative SPECT/CT imaging data. The CCF accuracy of the 99mTc source decreased depending on the preparative method. The method of calibration for quantitative SPECT should be immediately standardized to eliminate uncertainty.

Calculation Accuracy of Gross Tumor Volume at the Diaphragm Boundary Evaluated Using Respiratory-gated PET/CT.

OBJECTIVE: The present study aimed to clarify gross tumor volume (GTV) contouring accuracy at the diaphragm boundary using respiratory-gated PET/CT. METHODS: The lung/diaphragm boundary was simulated using a phantom containing 18F solution (10.6 kBq/mL). Tumors were simulated using spheres (diameter, 11-38 mm) containing 18F and located at the positions of the lungs and liver. The tumor background ratios (TBR) were 2, 4, and 8. The phantom was moved from the superior to inferior direction with a 20-mm motion displacement at 3.6 s intervals. The recovery coefficient (RC), volume RC (VRC), and standardized uptake value (SUV) threshold were calculated using stationary, non-gated (3D), and gated (4D) PET/CT. RESULTS: In lung cancer simulation, RC and VRC in 3D PET images were, respectively, underestimated and overestimated in smaller tumors, whereas both improved in 4D PET images regardless of tumor size and TBR. The optimal SUV threshold was about 30% in 4D PET images. In liver cancer simulation, RC and VRC were, respectively, underestimated and overestimated in smaller tumors, and when the TBR was lower, but both improved in 4D PET images when tumors were >17 mm and the TBR was >4. The optimal SUV threshold tended to depend on the TBR. CONCLUSIONS: The contouring accuracy of GTV was improved by considering TBR and using an optimal SUV threshold acquired from 4D PET images.

Prognostic implications of diffusion-weighted magnetic resonance imaging in patients with superior sulcus tumors receiving induction chemoradiation therapy.

OBJECTIVE: The aim of this study was to evaluate a diffusion-weighted magnetic resonance imaging to represent therapeutic response of induction chemoradiation and outcome in patients with non-small cell lung cancer of the superior sulcus. METHODS: Seventeen patients with non-small cell lung cancer of the superior sulcus (median age, 57 years; range, 44-70 years) received induction chemoradiation, followed by surgery. Diffusion-weighted magnetic resonance imaging of the lesion using b values of 0 and 800 s/mm(2) was acquired before treatment and after induction chemoradiation. Changes in tumoral apparent diffusion coefficient were compared with clinical and histopathological response. Cumulative disease-free survival and proportion of surviving were estimated by the Kaplan-Meier method. Survival of diffusion responders and non-responders were compared by log-rank test. RESULTS: A significant correlation was observed between changes of diffusion response after induction chemoradiation and overall survival. Using a defined threshold of percent increase in mean apparent diffusion coefficient, nine out of 17 patients (53%) were classified as diffusion responders and had a mean increase in mean apparent diffusion coefficient of 40.7 ± 11.2%, while eight diffusion non-responding patients (47%) had a mean increase of 11.0 ± 15.5% (P < 0.0001). Significant difference was found in overall survival between diffusion responders and diffusion non-responders (88.9 months versus 20.3 months, P = 0.002). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging represented therapeutic effect and prognosis after induction chemoradiation in patients with non-small cell lung cancer of the superior sulcus.

Update on the use of FDG-PET/CT in malignant lymphoma.

This article aims to explain the current status of FDG-PET/CT in malignant lymphoma management by reviewing the new recommendations for evaluation, staging, and response assessment in patients with malignant lymphoma, published as the Lugano Classification in 2014. FDG-PET/CT was formally incorporated into standard staging for FDG-avid lymphoma in this new classification. Nearly all subtypes of malignant lymphoma are FDG-avid. In staging, the increased FDG uptake compatible with lymphoma is considered to represent involvement of lymphoma, regardless of size, and the FDG-avid lesion is potentially a good biopsy target. FDG-PET/CT is more sensitive than bone marrow biopsy in diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). Location, size and FDG uptake, based on a 5 point scale (compared to hepatic uptake and mediastinal blood pool) for the residual lesion, constitute useful information for response assessment. Routine surveillance scans after remission are discouraged, especially for DLBCL and HL. Interim PET is regarded as a promising biomarker for stratifying treatments of malignant lymphoma, although its usefulness remains controversial.

Prognostic significance of metabolic tumor burden by positron emission tomography/computed tomography in patients with relapsed/refractory diffuse large B-cell lymphoma.

The aim of the present study was to investigate the feasibility of measuring metabolic tumor burden using [F-18] fluorodeoxyglucose ((18) F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with bendamustine-rituximab. Because the standardized uptake value is a critical parameter of tumor characterization, we carried out a phantom study of (18) F-FDG PET/CT to ensure quality control for 28 machines in the 24 institutions (Japan, 17 institutions; Korea, 7 institutions) participating in our clinical study. Fifty-five patients with relapsed or refractory DLBCL were enrolled. The (18) F-FDG PET/CT was acquired before treatment, after two cycles, and after the last treatment cycle. Treatment response was assessed after two cycles and after the last cycle using the Lugano classification. Using this classification, remission was complete in 15 patients (27%) and incomplete in 40 patients (73%) after two cycles of therapy, and remission was complete in 32 patients (58%) and incomplete in 23 patients (42%) after the last treatment cycle. The percentage change in all PET/CT parameters except for the area under the curve of the cumulative standardized uptake value-volume histogram was significantly greater in complete response patients than in non-complete response patients after two cycles and the last cycle. The Cox proportional hazard model and best subset selection method revealed that the percentage change of the sum of total lesion glycolysis after the last cycle (relative risk, 5.24; P = 0.003) was an independent predictor of progression-free survival. The percent change of sum of total lesion glycolysis, calculated from PET/CT, can be used to quantify the response to treatment and can predict progression-free survival after the last treatment cycle in patients with relapsed or refractory DLBCL treated with bendamustine-rituximab.

A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.

Although initial rituximab-containing chemotherapies achieve high response rates, indolent B-cell non-Hodgkin lymphoma (B-NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B-NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21-d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression-free survival (PFS). Fifty-six eligible patients were enrolled; 50 patients (39 with FL, seven with other B-NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab-containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted.

[Imaging examinations in lymphoma].

Imaging examinations are necessary in the various clinical situations of malignant tumors including lymphoma, which are differential diagnosis, staging, evaluation of response to treatment, prognosis prediction or early diagnosis of relapse. Generally morphologic imaging(such as CT, MRI and US) and functional imaging(such as gallium scintigraphy and FDG-PET) are used for malignant lymphoma. Especially, CT and FDG-PET have quite important roles for multicenter studies of treatment according to the response criteria of lymphoma. In this chapter, the features of each imaging examinations in lymphoma were explained. In addition, interim PET was mentioned at the end, which is considered as a promising biomarker for stratifying treatment of lymphoma.

Evaluation of two-dimensional total bone uptake (2D-TBU) and bone scan index (BSI) extracted from active bone metastatic burden on the bone scintigraphy in patients with radium-223 treatment.

OBJECTIVE: Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223. METHODS: Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed. RESULTS: Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15). CONCLUSIONS: The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions.

Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.

BACKGROUND: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer. METHODS: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021. MRI exams were evaluated independently by two radiologists. Final histopathological diagnosis for malignant lesions were obtained from surgical specimen. RESULTS: A total of 16 patients included TP53, CDH1, PALB2, ATM pathogenic variants and 3 variant of unknown significance. 2 patients with TP53 pathogenic variants were detected breast cancer by annual MRI surveillance. The rate of cancer detection was 12.5% (2/16). One patient was detected synchronous bilateral breast cancer and unilateral multiple breast cancers (3 lesions in 1 patient), so there were 4 malignant lesions in total. Surgical pathology of 4 lesions were 2 ductal carcinoma in situ, 1 invasive lobular carcinoma, and 1 invasive ductal carcinoma. MRI findings of 4 malignant lesions were detected as 2 non mass enhancement, 1 focus and 1 small mass. All of 2 patients with PALB2 pathogenic variants had previously developed breast cancer. CONCLUSIONS: Germline TP53 and PALB2 were strongly associated with breast cancer, suggesting that MRI surveillance is essential for breast cancer-related hereditary predisposition.

Mucinous tumors arising from ovarian teratomas as another source of pseudomyxoma peritoneii: MR findings comparison with ovarian metastases from appendiceal mucinous tumors.

Objective: The origin of pseudomyxoma peritoneii (PMP) has been established as low-grade appendiceal mucinous tumors (AMT). However, intestinal-type ovarian mucinous tumors are known as another source of PMP. Recently, it is advocated that ovarian mucinous tumors causing PMP originates from teratomas. However, AMTs are often too small to detect on imaging; then, differentiating metastatic ovarian tumors of AMT from ovarian teratoma-associated mucinous tumors (OTAMT) is important. Therefore, this study investigates the MR characteristics of OTAMT compared to the ovarian metastasis of AMT. Methods: MR findings of six pathologically confirmed OTAMT were retrospectively analyzed compared to ovarian metastases of low-grade appendiceal mucinous neoplasms (LAMN). We studied the existence of PMP, uni- or bilateral disease, the maximum diameter of ovarian masses, the number of loculi, a variety of sizes and signal intensity of each content, the existence of the solid part, fat, calcification within the mass, and appendiceal diameters. All the findings were statistically analyzed using the Mann-Whitney test. Results: Four of the six OTAMT showed PMP. OTAMT showed unilateral disease, had a larger diameter, more frequent intratumoral fat, smaller appendiceal diameter than those in AMT, and they were statistically significant (p < .05). On the other hand, the number, variety of size, signal intensity of loculi, and the solid part, calcification within the mass did not differ from each other. Conclusion: Both OTAMT and ovarian metastasis of AMT appeared as multilocular cystic masses with relatively uniform signal and size of loculi. However, a larger unilateral disease with intratumoral fat and smaller size of the appendix may suggest OTAMT. Advances in knowledge: OTAMT can be another source of PMP, as AMT. MR characteristics of OTAMT were very similar to ovarian metastases of AMT; however, in cases with PMP combined with fat-containing multilocular cystic ovarian mass, we can diagnose them as OTAMT, not PMP caused by AMT.

Bone metastases with "false negative" findings on 18F-FDG PET/CT in patients with angiosarcoma: A case series with literature review.

RATIONALE: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is considered a reliable and indispensable imaging method when evaluating distant metastases and clinical staging of angiosarcomas. Here, we report 2 cases of angiosarcoma with bone metastases with "false negative" findings on 18F-FDG PET/CT. PATIENT CONCERNS: Case 1, a 39-year-old woman, who had undergone mastectomy for primary angiosarcoma 2 years prior, presented with a 5-month history of right coxalgia. Case 2 was a 37-year-old woman, who had undergone mastectomy for primary angiosarcoma 4 months prior. During postoperative follow-up, multiple bone lesions were detected on magnetic resonance imaging (MRI). DIAGNOSES: Based on the histopathological findings, both cases were diagnosed with bone metastases of angiosarcoma. Although MRI showed multiple bone metastatic lesions, 18F-FDG PET/CT showed no uptake or osteolytic destruction in both cases. INTERVENTIONS: Weekly paclitaxel was initiated as a salvage chemotherapy in both cases. OUTCOMES: No uptake or osteolytic lesions were observed on 18F-FDG PET/CT, despite multiple bone metastases detected on MRI. LESSONS: False-negative findings on 18F-FDG PET/CT should be considered when evaluating bone metastases of angiosarcoma. Even with negative findings on 18F-FDG PET/CT, open biopsy should be performed if MRI indicates bone metastases.