Therapy Response Evaluation Research Articles

Initial Evaluation of Therapy Response after Adjuvant Radioiodine Therapy in Patients with Early-Stage Papillary Thyroid Cancer-Does Time Matter?

Simple SummaryIn recent years, there has been a clear trend toward personalized therapy procedures in patients with thyroid cancer with the aim to avoid unnecessary overtreatment of patients and to ensure an improved quality of life. We confirmed that early diagnostic control at 6 months after initial radioiodine therapy shows no significant disadvantages compared to a delayed control after 9 months. Further, it was observed that patients stimulated by hormone withdrawal before radioiodine therapy had significantly better outcomes compared to patients stimulated exogenously with recombinant human thyroid-stimulating hormone (rhTSH). However, early diagnostic control after TSH stimulation represents the most balanced solution for the patient, specifically regarding hypothyroidism symptoms after hormone withdrawal.Background: The aim was to assess ablation success after initial radioiodine (RAI) therapy in early-stage PTC patients and compare outcomes of first diagnostic control after 6 and 9 months (6m/9m-DC) to examine whether time could possibly avoid unnecessary overtreatment. Methods: There were 353 patients who were matched regarding age, sex, and tumor stage and divided in two groups depending on time of first DC (6m- and 9m-DC). Therapy response was defined as thyroglobulin level <0.5 ng/mL, no pathological uptake in the diagnostic I-131 whole-body scintigraphy (WBS), and no further RAI therapy courses. The 6m-DC group was further divided into endogenously and exogenously stimulated TSH before RAI therapy and compared regarding outcome. Results: No significant differences were found between 6m-DC vs. 9m-DC regarding I-131 uptake in WBS (p = n.s.), Tg levels (p = n.s.), re-therapy rates (p = n.s.), and responder rates (p = n.s.). Significantly less relevant pathological I-131 uptake was found in WBS (p = 0.006) in endogenously compared to exogenously stimulated 6m-DC patients, resulting in lower re-therapy (p = 0.028) and higher responder rates (p = 0.001). Conclusion: DC at 6 months after RAI therapy and stimulation with recombinant human thyroid-stimulating hormone (rhTSH) represent the most balanced solution. Particularly regarding quality of life and mental relief of patients, early DC with rhTSH represents sufficient and convenient assessment of ablation success.

Radiomics in sarcoma trials: a complement to RECIST for patient assessment

Radiological imaging has a critical role in the diagnosis of sarcomas and in evaluating therapy response assessment. The current gold standard for response assessment in solid tumors is the Response Evaluation Criteria in Solid Tumors, which evaluates changes in tumor size as a surrogate endpoint for therapeutic efficacy. However, tumors may undergo necrosis, changes in vascularization or become cystic in response to therapy, with no significant volume changes; thus, size assessments alone may not be adequate. Such morphological changes may give rise to radiographic phenotypes that are not easily detected by human operators. Fortunately, recent advances in high-performance computing and machine learning algorithms have enabled deep analysis of radiological images to extract features that can provide richer information about intensity, shape, size or volume, and texture of tumor phenotypes. There is growing evidence to suggest that these image-derived or “radiomic features” are sensitive to biological processes such as necrosis and glucose metabolism. Thus, radiomics could prove to be a critical tool for assessing treatment response and may present an integral complement to existing response criteria, opening new avenues for patient assessment in sarcoma trials.

Personalized medicine with drugs targeting the underlying protein defect in cystic fibrosis: is monitoring of treatment response necessary?

Cystic fibrosis (CF) is caused by two mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. In the last years, drugs targeting the underlying protein defect like lumacaftor/ivacaftor (LUM/IVA) or tezacaftor/ivacaftor (TEZ/IVA) and more recently elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) were admitted. Outcome parameters evaluating therapy response like forced expiratory pressure in 1 s (FEV1), body mass index (BMI) or the efficacy of CFTR function in sweat glands showed improvement in several cases. Other, CFTR biomarkers were analysed rarely. This prospective observational study was aimed at evaluating CFTR function in patients treated with different CFTR modulators together with common valid clinical outcome parameters at standardized appointments (day 0, week 2, 4, 16). We followed four patients with the same mutation (F508del-CFTR), sex, age and disease severity. Monitoring focused on lung function, gastrointestinal aspects and CFTR function of sweat glands, nasal and intestinal epithelium. Sweat tests were performed by pilocarpine iontophoresis. Nasal potential difference (NPD) measured transepithelial voltage in vivo and potential increased when CFTR function improved. Rectal biopsies were obtained for intestinal current measurements (ICM) ex vivo. Intestinal CFTR function was assessed by stimulating chloride secretion with different reagents. Response to CFTR modulators regarding clinical outcome parameters was rather variable. A sweat chloride reduction of 35.3 mmol/L, nasal CFTR rescue of 4.4% and fivefold higher CFTR function in the intestine was seen at week 16 post-LUM/IVA. Due to our monitoring, we identified a non-responder to LUM/IVA and TEZ/IVA. In case of ELX/TEZ/IVA, clinical parameters and CFTR bioassays improved and were concordant. Although our cohort is small, results emphasize that non-responders exist and conclusions could not be drawn if patients were not monitored. Data on CFTR function can confirm or disprove ongoing CFTR dysfunction and might be helpful selectively. Non-responders need other alternative therapy options as demonstrated with ELX/TEZ/IVA.

Muscular sarcoidosis in the eyes of 18 F-FDG PET/CT.

The aim of this study was to determine the frequency, symptoms, activity and pattern of muscle sarcoidosis, correlation with laboratory parameters, and to assess its therapy response with 18 F-FDG PET/CT. Study included 90 patients with biopsy confirmed sarcoidosis and symptoms/biochemical/imaging findings suggestive of active disease. The exclusion criteria were: presence of cancer or other diseases that resemble sarcoidosis on PET/CT (Wegener syndrome, tuberculosis, aspergillosis), and the glucose level being greater than 11 mmol/L. All patients were screened for muscle sarcoidosis with 18 F-FDG PET/CT examination. Follow-up examination was done 1 year after the baseline in order to evaluate therapy response. Disease was very rare and present in only 7/90 patients. Most of the patients had polysymptomatic disease, while muscle pain was less frequent, present only in one-third of the patients. The disease was usually present in the lower limbs, upper limbs, and skeletal striated muscles. The most common pattern of disease was nodular. Disease activity estimated with SUVmax was not in correlation with the ACE findings, creatine kinase, and aldolase levels (p > 0.05). Follow-up PET/CT revealed complete remission in one patient and partial remission in two. 18 F-FDG PET/CT can be useful in asymptomatic young patients with nodular pattern of disease, who have easily relapsing form of disease. It can help in further management of these patients and can affect prognosis of the disease, since most of the laboratory parameters in this entity are within normal limits.

Tumorous tissue characterization using integrated 18F-FDG PET/dual-energy CT in lung cancer: Combining iodine enhancement and glycolytic activity

Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) has become the method of choice for tumor staging in lung cancer patients with improved diagnostic accuracy for the evaluation of lymph node involvement and distant metastasis. Due to its spectral capabilities, dual-energy CT (DECT) employs a material decomposition algorithm enabling precise quantification of iodine concentrations in distinct tissues. This technique enhances the characterization of tumor blood supply and has demonstrated promising results for the assessment of therapy response in patients with lung cancer.Several studies have demonstrated that DECT provides additional value to the PET-based evaluation of glycolytic activity, especially for the evaluation of therapy response and follow-up of patients with lung cancer. The combination of PET and DECT in a single scanner system enables the simultaneous assessment of glycolytic activity and iodine enhancement, offering further insight to the characterization of tumorous tissues. Recently a new approach of a novel integrated PET/DECT was investigated in a pilot study on patients with non-small cell lung cancer (NSCLC). The study showed a moderate correlation between PET-based standard uptake values (SUV) and DECT-based iodine densities in the evaluation of lung tumorous tissue but with limited assessment of lymph nodes.The following review on tumorous tissue characterization using PET and DECT imaging describes the strengths and limitations of this novel technique.

18F FDG imaging – response criteria in tumors

With the progress of medical oncology, it became apparent that anatomical imaging is oftentimes insufficient for therapy response evaluation. Hybrid imaging, namely 18F-FDG PET/CT has helped to overcome these limitations. The aim of this paper is to emphasize the utility and impact in clinical use of 18F-FDG PET/CT, and to give an overview of the most important 18F-FDG PET/CT tumor response criteria.We also focus on standardization of hybrid imaging techniques as this is of outmost importance to provide reliable imaging evaluation.

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy.

Simple SummaryPatients diagnosed with pancreatic cancer have a poor prognosis at time of diagnosis, with a 5-year survival rate of merely 10%. The only treatment with curative intent is surgical resection of the tumor and adjacent tumor-containing lymph nodes. To improve surgical outcome and survival, additional (imaging) tools are needed that support complete surgical tumor resection. Firstly, more accurate monitoring of tumor response to neoadjuvant treatment and subsequent determination of resectability is needed. Secondly, an imaging tool is needed for intraoperative guidance allowing accurate identification, delineation, and complete resection of the tumor and suspected lymph nodes. Therefore, both tumor-targeted PET/CT before surgery and real time fluorescence-guidance during surgery could be helpful to improve patient outcome. This review focusses on literature considering tumor-targeted PET/CT and near-infrared fluorescence (NIRF) imaging. Several tumor-targeted agents are under clinical evaluation, and several other promising agents are currently tested preclinically, both with promising results. Their additional diagnostic value and feasibility for future implementation in standard clinical care of PDAC has yet to be established in phase III clinical trials.Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

The Prognostic Value of Total Tumor Volume Response Compared With RECIST1.1 in Patients With Initially Unresectable Colorectal Liver Metastases Undergoing Systemic Treatment.

Compare total tumor volume (TTV) response after systemic treatment to Response Evaluation Criteria in Solid Tumors (RECIST1.1) and assess the prognostic value of TTV change and RECIST1.1 for recurrence-free survival (RFS) in patients with colorectal liver-only metastases (CRLM). RECIST1.1 provides unidimensional criteria to evaluate tumor response to systemic therapy. Those criteria are accepted worldwide but are limited by interobserver variability and ignore potentially valuable information about TTV. Patients with initially unresectable CRLM receiving systemic treatment from the randomized, controlled CAIRO5 trial (NCT02162563) were included. TTV response was assessed using software specifically developed together with SAS analytics. Baseline and follow-up computed tomography (CT) scans were used to calculate RECIST1.1 and TTV response to systemic therapy. Different thresholds (10%, 20%, 40%) were used to define response of TTV as no standard currently exists. RFS was assessed in a subgroup of patients with secondarily resectable CRLM after induction treatment. A total of 420 CT scans comprising 7820 CRLM in 210 patients were evaluated. In 30% to 50% (depending on chosen TTV threshold) of patients, discordance was observed between RECIST1.1 and TTV change. A TTV decrease of >40% was observed in 47 (22%) patients who had stable disease according to RECIST1.1. In 118 patients with secondarily resectable CRLM, RFS was shorter for patients with less than 10% TTV decrease compared with patients with more than 10% TTV decrease (P = 0.015), while RECIST1.1 was not prognostic (P = 0.821). TTV response assessment shows prognostic potential in the evaluation of systemic therapy response in patients with CRLM.

Predictive role of lymphoscintigraphy undergoing lymphovenous anastomosis in patients with lower extremity lymphedema: a preliminary study

BackgroundWe investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema.Materials and methodsA total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and four types of dermal backflow patterns (absent; distal only; proximal only; whole lower limb) were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole lower limb at 3 months (early response) and 1 year (late response) was measured. Volume difference ratios (continuous variable and binary variable with a cut-off value of zero) were compared according to the lymphoscintigraphic variables.ResultsThe group with whole lower limb dermal backflow had a greater volume change than the other groups (p = 0.047). The group with dermal backflow in the whole lower limb OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p = 0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p = 0.016, p = 0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p = 0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p = 0.040).ConclusionsPreoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.

Efficacy and safety of 225Ac-DOTATATE targeted alpha therapy in metastatic paragangliomas: a pilot study.

PurposeIn this study, we aim to evaluate the efficacy and safety of 225AC-DOTATATE targeted alpha therapy in advanced-stage paragangliomas (PGLs).MethodsNine (6 males and 3 females) consecutive patients with histologically proven PGLs were treated with 225Ac-DOTATATE targeted alpha therapy (TAT) and concomitant radiosensitizer, capecitabine, at 8-weekly intervals up to a cumulative activity of ~ 74 MBq. The primary endpoint included evaluating therapy response and disease control rate (DCR) using the RECIST 1.1 criteria. Additional secondary endpoints comprised clinical response assessment using EORTC QLQ-H&N35 questionnaire, Karnofsky Performance Scale (KPS), Eastern Cooperative Oncology Group performance status (ECOG), analgesic score (AS), dose alterations of anti-hypertensive drugs (anti-HTN), and the safety and side-effect profile evaluation as per CTCAE criteria version 5.0.ResultsFollowing 225Ac-DOTATATE treatment, morphological response revealed partial response in 50%, stable disease in 37.5%, and disease progression in 12.5%, with a DCR of 87.5%. Similarly, the symptomatic response was remarkable, and anti-HTN drugs were stopped in 25% and reduced in 37.5%. Another significant finding in our study revealed a morphologic DCR of 66.6% (2/3) in patients who failed previous lutetium-177 peptide receptor radionuclide therapy (177Lu-PRRT). Regarding the KPS, ECOG, and AS performance scores, a notable improvement was observed post-225Ac-DOTATATE treatment. The QLQ-H&N35 symptom scores evaluated in seven H&N PGL patients showed significant improvement in all aspects. No improvement in sexual function was noted (P = 0.3559). Despite the significant reduction in the analgesic score post-treatment (P = 0.0031), the QLQ-H&N35 revealed only marginal significance concerning the intake of pain killers (P = 0.1723). No grade III/IV hematological, renal, and hepatological toxicities were noted.ConclusionThe evidence from this study suggests 225Ac-DOTATATE therapy is effective and safe in the treatment of advanced-stage PGLs and also reports a clear benefit even in patient’s refractory to the previous 177Lu-PRRT.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00259-021-05632-5.

Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia.

Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.

Recasted nonlinear complex diffusion method for removal of Rician noise from breast MRI images

The evolution of magnetic resonance imaging (MRI) leads to the study of the internal anatomy of the breast. It maps the physical features along with functional characteristics of selected regions. However, its mapping accuracy is affected by the presence of Rician noise. This noise limits the qualitative and quantitative measures of breast image. This paper proposes recasted nonlinear complex diffusion filter for sharpening the details and removal of Rician noise. It follows maximum likelihood estimation along with optimal parameter selection of complex diffusion where the overall functionality is balanced by regularization parameters. To make recasted nonlinear complex diffusion, the edge threshold constraint “k” of diffusion coefficient is reformed. It is replaced by the standard deviation of the image. It offers a wide range of threshold as variability present in the image with respect to edge. It also provides an automatic selection of “k” instead of user-based value. A series of evaluation has been conducted with respect to different noise ratios further quality improvement of MRI. The qualitative and quantitative assessments of evaluations are tested for the Reference Image Database to Evaluate Therapy Response (RIDER) Breast database. The proposed method is also compared with other existing methods. The quantitative assessment includes the parameters of the full-reference image, human visual system, and no-reference image. It is observed that the proposed method is capable of preserving edges, sharpening the details, and removal of Rician noise.

Tre-O1-03 - Response to brentuximab vedotin in advanced stage MF/Sézary syndrome with low CD-30 expression: “real-life” data of the German Cutaneous Lymphoma Network

Introduction and objectives: Advanced stage mycosis fungoides/Sézary syndrome (MF/SS) are difficult to treat and associated with an inferior prognosis. Brentuximab vedotin (BV) is a frequently used agent in higher stages, particularly in cases with a high expression of CD30. The ALCANZA trial, which included MF patients with a CD30 expression >10%, demonstrated high response rates and a good tolerability. However, its effectiveness in advanced stage MF/SS syndrome with low CD30-expression (<10%) still has to be systematically evaluated. Therefore, the question is whether an equally good response with BV is achievable in these CTCL cases. Material and methods: Between 2018 - 2020, 32 patients in 11 centres with predominantly advanced MF/SS and low CD-30 expression (<10%) were treated with BV in the recommended dosage, retrospective evaluation of therapy response was done according to the EORTC-ISCL criteria. Results: In all patients (n=32) at least one other systemic therapy preceded BV treatment. The median number of previous treatments was 3. Thirty patients suffering from MF (IB: 2; IIA: 1; IIB: n=18; III: 1; IV: 9; total ≥IIB: 27) and 2 SS patients were analyzed. As a result, 17 of 31 patients (OR: 54.8%) responded to therapy (CR n=4/31 12.9%, PR n=13/31 41.9%) after 6 cycles. The median progression-free interval among patients with OR was 6.4 months (range: 0.5–15.5 months, mean ± SD: 6.4±3.8, n=16). In 37.5% (n=12) the CD-30 Expression was 5-9% and in 62.5% (n=20) CD-30-Expression was <5%. Conclusions: In conclusion, with 54.8% OR, BV in MF/SS with low CD-30 expression (<10%) shows a comparable response rate compared to CTCL with CD-30 expression ≥10% (56-73%) and CR (12.9% vs. 3–35%) but with a lower PFS (6.4 vs. 11 months). In summary, based on this data the treatment of MF/SS with low CD-30 expression with BV seems to be an effective therapeutical option and justifies its use in challenging cases independent of the degree of CD30 positivity. Advanced stage mycosis fungoides/Sézary syndrome (MF/SS) are difficult to treat and associated with an inferior prognosis. Brentuximab vedotin (BV) is a frequently used agent in higher stages, particularly in cases with a high expression of CD30. The ALCANZA trial, which included MF patients with a CD30 expression >10%, demonstrated high response rates and a good tolerability. However, its effectiveness in advanced stage MF/SS syndrome with low CD30-expression (<10%) still has to be systematically evaluated. Therefore, the question is whether an equally good response with BV is achievable in these CTCL cases. Between 2018 - 2020, 32 patients in 11 centres with predominantly advanced MF/SS and low CD-30 expression (<10%) were treated with BV in the recommended dosage, retrospective evaluation of therapy response was done according to the EORTC-ISCL criteria. In all patients (n=32) at least one other systemic therapy preceded BV treatment. The median number of previous treatments was 3. Thirty patients suffering from MF (IB: 2; IIA: 1; IIB: n=18; III: 1; IV: 9; total ≥IIB: 27) and 2 SS patients were analyzed. As a result, 17 of 31 patients (OR: 54.8%) responded to therapy (CR n=4/31 12.9%, PR n=13/31 41.9%) after 6 cycles. The median progression-free interval among patients with OR was 6.4 months (range: 0.5–15.5 months, mean ± SD: 6.4±3.8, n=16). In 37.5% (n=12) the CD-30 Expression was 5-9% and in 62.5% (n=20) CD-30-Expression was <5%. In conclusion, with 54.8% OR, BV in MF/SS with low CD-30 expression (<10%) shows a comparable response rate compared to CTCL with CD-30 expression ≥10% (56-73%) and CR (12.9% vs. 3–35%) but with a lower PFS (6.4 vs. 11 months). In summary, based on this data the treatment of MF/SS with low CD-30 expression with BV seems to be an effective therapeutical option and justifies its use in challenging cases independent of the degree of CD30 positivity.

Current status of postoperative pathological diagnosis of lung cancer in China: a multicenter big data study

Objective: To reveal the current status and problem of surgical pathological diagnosis and to construct a structured pathological database of lung cancer in China, and to further improve the level of pathological standards and scientific data. Methods: Case report form (CRF) was made according to the diagnostic criteria of radical resection specimens of lung cancer, including general information, smoking history, pathological report (including molecular data), treatment and prognosis, etc. The original clinicopathological data of patients with primary lung cancer who underwent surgical resection in 23 centers from January 2013 to December 2017 were retrospectively collected. After desensitization, filtering and natural language processing, combined with domain knowledge base, and the raw data in the form of continuous text were structured. Results: A total of 153 817 non-structured pathological reports, 57 748 molecular reports and 13 295 pieces of treatment and/or follow-up information were collected. Finally, 75 941 effective structured documents (including 86 979 primary lesions) were obtained. The quality of treatment and follow-up data was not satisfactory; Number of CRF index involved showed an increasing trend with time coursing, and had no significant difference between general hospitals and cancer hospitals (P<0.05). The indexes with low use rate until 2017 were peripheral lung disease, pTNM stage, spread though air space, and pathological evaluation of neoadjuvant treatment response. The ratio of male to female was 1.2∶1.0; 8 648 cases (11.39%) had smoking history, and the ratio of smokers to non-smokers was 0.92∶1.00. Age group of the highest incidence was 60-69 years, accounting for 38.76%. The top five common pathological subtypes were adenocarcinoma (74.58%), squamous cell carcinoma (18.01%), small cell carcinoma (2.18%), adenosquamous carcinoma (1.71%) and sarcomatoid carcinoma (0.82%); histological subtypes were significantly correlated with gender, age and smoking status (P<0.05): adenocarcinoma (58.5%) and squamous cell carcinoma (31.6%) were the main pathological types in male patients, while adenocarcinoma (91.6%) and squamous cell carcinoma (3.4%) were the main pathological types in female patients; adenocarcinoma (85.6%) was the main type of non-smoking patients, adenocarcinoma and squamous cell carcinoma accounted for 50.6% and 37.7% respectively in smoking patients; the proportion of adenocarcinoma decreased with age, while squamous cell carcinoma and small cell carcinoma increased. The top five common immunohistochemical (IHC) markers were TTF1, CK7, ALK-Ventana, Napsin A and p63 and the most common panel included 7-9 IHC markers. The overall EGFR mutation rate was 51.32% (all 10 335/20 139 by PCR), the total ALK positive rate was 6.18% (2 084/33 726, PCR, FISH and IHC-Ventana platform positive rates were 3.01%, 8.93% and 6.58%, respectively), the KRAS mutation rate was 7.01% (all 662/9 441 by PCR). The positive rates of EGFR, ALK and KRAS were 58.14% (9 986/17 175), 6.59% (1 791/27 176) and 7.52% (607/8 068) in adenocarcinoma, 5.83% (113/1 939), 0.40% (1/251) and 1.76% (15/852) in squamous cell carcinoma, respectively. Due to the poor quality of prognostic data, it was difficult to obtain effective survival analysis. Conclusions: The standardization of pathological reports (including molecular detection) of lung cancer in China is generally fine, but most of the models are still in the state of unstructured continuous text. The postoperative pathological staging, pathological evaluation of neoadjuvant therapy response and high-quality prognosis data need paying more attention and improvement. Panel of IHC markers is balanced although further precision. The use of lung cancer structured report template and intelligent structured database management mode to improve the degree of the pathologic diagnosis standardization and data quality is recommended.

Tumor response evaluation in patients with malignant melanoma undergoing immune checkpoint inhibitor therapy and prognosis prediction using 18F-FDG PET/CT: multicenter study for comparison of EORTC, PERCIST, and imPERCIST

ObjectiveIn malignant melanoma patients treated with immune checkpoint inhibitor (ICI) therapy, three different FDG-PET criteria, European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), immunotherapy-modified PERCIST (imPERCIST), were compared regarding response evaluation and prognosis prediction using standardized uptake value (SUV) harmonization of results obtained with various PET/CT scanners installed at different centers.Materials and methodsMalignant melanoma patients (n = 27) underwent FDG-PET/CT examinations before and again 3 to 9 months after therapy initiation (nivolumab, n = 21; pembrolizumab, n = 6) with different PET scanners at five hospitals. EORTC, PERCIST, and imPERCIST criteria were used to evaluate therapeutic response, then concordance of the results was assessed using Cohen’s κ coefficient. Log-rank and Cox methods were employed to determine progression-free (PFS) and overall (OS) survival.ResultsComplete metabolic response (CMR)/partial metabolic response (PMR)/stable metabolic disease (SMD)/progressive metabolic disease (PMD) with harmonized EORTC, PERCIST, and imPERCIST was seen in 3/5/4/15, 4/5/3/15, and 4/5/5/13 patients, respectively. Nearly perfect concordance between each pair of criteria was noted (κ = 0.939–0.972). Twenty patients showed progression and 14 died from malignant melanoma after a median 19.2 months. Responders (CMR/PMR) showed significantly longer PFS and OS than non-responders (SMD/PMD) (harmonized EORTC: p < 0.0001 and p = 0.011; harmonized PERCIST: p < 0.0001 and p = 0.0012; harmonized imPERCIST: p < 0.0001 and p = 0.0012, respectively).ConclusionsAll harmonized FDG-PET criteria (EORTC, PERCIST, imPERCIST) showed accuracy for response evaluation of ICI therapy and prediction of malignant melanoma patient prognosis. Additional studies to determine their value in larger study populations will be necessary.

High interstudy repeatability of automatic deep learnt biventricular CMR measurements

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Wellcome Trust (UK), NIHR (UK) Introduction Cardiac magnetic resonance (CMR) measurements have significant diagnostic and prognostic value. Accurate and repeatable measurements are essential to assess disease severity, evaluate therapy response and monitor disease progression. Deep learning approaches have shown promise for automatic left ventricular (LV) segmentation on CMR, however fully automatic right ventricular (RV) segmentation remains challenging. We aimed to develop a biventricular automatic contouring model and evaluate the interstudy repeatability of the model in a prospectively recruited cohort. Methods A deep learning CMR contouring model was developed in a retrospective multi-vendor (Siemens and General Electric), multi-pathology cohort of patients, predominantly with heart failure, pulmonary hypertension and lung diseases (n = 400, ASPIRE registry). Biventricular segmentations were made on all CMR studies across cardiac phases. To test the accuracy of the automatic segmentation, 30 ASPIRE CMRs were segmented independently by two CMR experts. Each segmentation was compared to the automatic contouring with agreement assessed using the Dice similarity coefficient (DSC). A prospective validation cohort of 46 subjects (10 healthy volunteers and 36 patients with pulmonary hypertension) were recruited to assess interstudy agreement of automatic and manual CMR assessments. Two CMR studies were performed during separate sessions on the same day. Interstudy repeatability was assessed using intraclass correlation coefficient (ICC) and Bland-Altman plots. Results DSC showed high agreement (figure 1) comparing automatic and expert CMR readers, with minimal bias towards either CMR expert. The scan-scan repeatability CMR measurements were higher for all automatic RV measurements (ICC 0.89 to 0.98) compared to manual RV measurements (0.78 to 0.98). LV automatic and manual measurements were similarly repeatable (figure 2). Bland-Altman plots showed strong agreement with small mean differences between the scan-scan measurements (figure 2). Conclusion Fully automatic biventricular short-axis segmentations are comparable with expert manual segmentations, and have shown excellent interstudy repeatability.

Ga-68 DOTATATE PET/CT in the Evaluation of Therapy Response in Neuroendocrine Tumors

Ga-68 DOTATATE PET/CT in the Evaluation of Therapy Response in Neuroendocrine Tumors

Quantitative analysis of xQuant reconstruction algorithm in SPECT/CT

Standard iterative Ordered Subset Expectation Maximisation (OSEM) reconstruction is well established in SPECT/CT, but despite its wide applications in image processing it comes with limitations in image noise and quality. A novel algorithm, xQuant (developed by Siemens Healthcare), uses Ordered Subset Conjugate Gradient Maximisation (OSCGM) which enables image quantification assessment such as standardised uptake value (SUV) measurements for reliable disease detection and evaluation of therapy response. As such, xQuant allows for dosimetry measurements, staging and management of diseases, analogous to the PET/CT modality for staging cancers and chemotherapy management. This study compares the accuracy of xQuant algorithm and current OSEM, by analysing image noise, SUV quantification and varying image reconstruction parameters. Standard clinical phantoms are used for comparison of both reconstruction algorithms: xQuant SUV accuracy with various Tc99m activity and varying scan times are performed for analysis. Results indicate that SUV measurements from xQuant are similar to expected SUV, regardless of selected reconstruction parameters, varying radiation activity and delayed scan times. Image noise assessment has shown that xQuant has lesser value of coefficient of variation (CoV) compared to standard OSEM, indicating xQuant's superior noise suppression without compromising image quality. The quantifiable superiority of xQuant reconstruction algorithm supersedes the basic iterative 3D OSEM reconstruction. It shows higher resolution qualitative assessment and provides consistent quantitative analysis. The reliability and superiority of xQuant enables clinical SPECT/CT quantification to detect disease and improve therapy management.

Update of Assessment of Early Response Using PET/CT in Malignant Lymphoma.

18F-FDG PET/CT is an eminent widely used diagnostic imaging modality utilized for staging and evaluating therapy response in malignant lymphomas. The pre-eminence of 18F-FDG PET/CT over CT to recognize viable lymphomatous tissue after two cycles of chemotherapy cycles has lately directed to reconsideration of criteria of early therapy response.Numerous recent researches have also confirmed that early response assessment within early two to three chemotherapy cycles is mandatory to evaluate chemo sensitivity and may have the potential to guide additional risk-adapted treatment modalities in malignant lymphoma patients.Early response evaluation depends mostly upon quantitative Deauville criteria which may subjective dichotomous interpretation if evaluated by more than one interpreter. Therefore, assessment of therapy response might necessitate a more objective quantification methodology of 18F-FDG uptake alterations. Standardized uptake value (SUV) is currently the most regularly used semi-quantitative parameter allowing non-invasive evaluation of 18F-FDG metabolic rate.Novel Volume based parameters as MTV and TLG have recently gained researchers attention as they are considered more representative of total tumour burden than single voxel based parameter; SUV. They may have the potential for early prediction of therapy response, prognosis of clinical outcome, and tumour delineation for radiotherapy planning. However, lack of standard method for tumour segmentation hinders the routine use of more inclusive volume based parameters.

Therapy response evaluation in large-vessel vasculitis: a new role for [18F]FDG-PET/CT?

Therapy response evaluation in large-vessel vasculitis: a new role for [18F]FDG-PET/CT?