Node Lesions Research Articles

Development and application of artificial intelligence to detect metastases in lymph nodes in colorectal cancer

AIM: to create a marked data set (histoscans of lymph nodes) for use in the development of medical decision support systems (based on machine learning) in pathomorphology, which will allow determining the presence of metastatic lymph node lesions in CRC.RESULTS: the dataset included 432 files with digital images and markings of 1000 lymph nodes, including lymph nodes with and without metastases. Based on the marked-up data, a neural network model was trained to determine the probability of metastatic lesion for each pixel in the area of interest - the lymph node (Dice 0.863 for the replaced tissue, Dice macro 0.923). In addition, pre- and postprocessing methods were implemented to represent input data in a form acceptable for machine learning and to represent the AI model's response in a form convenient for user perception. Additionally, a neural network model has been developed that predicts the probability of finding artifacts in digital images of lymph nodes with the possibility of forming an artifact probability map (Dice macro0.776; Dice for artifacts 0.552; IoU macro 0.725 and IoU for artifacts 0.451).CONCLUSION: the developed model is a good basis for the implementation of a full-fledged solution, on the basis of which a system can be developed to assist doctors in finding and evaluating the replacement of tissue structures and determining metastatic lymph node lesions, detecting artifacts and evaluating the quality of digital images.

Lenalidomide treatment for recurrent adult T-cell leukemia/lymphoma after allogeneic hematopoietic cell transplantation.

Patients with recurrent adult T-cell leukemia/lymphoma (ATL) after allogeneic hematopoietic cell transplantation (allo-HCT) have a dismal prognosis. We retrospectively evaluated the safety and efficacy of lenalidomide (LEN)in 11 consecutive patients with recurrent ATL after allo-HCT. The median time from allo-HCT to ATL recurrence was 111days (range, 20-1476), and that from allo-HCT to the initiation of LEN was 162days (range, 43-1560). The median initial daily dose of LEN was 10mg (range, 5-25), and the median duration of LEN treatment was 37days (range, 3-1078). Three patients (27%) achieved complete response and two (18%) achieved partial response (PR). The rates of complete or PR according to the involved site were 57% for skin and 50% for nodal or extranodal lesions. With a median follow-up of 1033days (range, 601-1465) among survivors, the 1-year probability of overall survival (OS) after ATL recurrence was 55%. Grade ≥3 toxicities included cytopenia (n=4), superficial vein thrombosis (n=1), and deep vein thrombosis (n=1). Graft-versus-host disease (GVHD) newly developed in five patients (45%) and worsened in four patients (36%). The median duration from the initiation of LEN to GVHD onset or worsening was 5days (range, 1-9). GVHD was manageable in all patients. Seven patients received mogamulizumab (MOG) for recurrent ATL before LEN treatment. The overall response rates to LEN were 57% in patients who had previously received MOG and 25% in those who had not. The 1-year probabilities of OS after recurrent ATL were 71% in patients who had previously received MOG and 25% in those who had not. Although cytopenia and GVHD are common among patients with recurrent ATL after allo-HCT, LEN may improve survival. Administering MOG before LEN may augment treatment efficacy in the allo-HCT population.

Locally advanced thyroid cancer. Issues of diagnosis and treatment

Background. From 10 to 20% of highly differentiated papillary thyroid cancer show signs of local prevalence: invasion into the surrounding fatty tissue, organs and tissues adjacent to the gland — the anterior muscles of the neck, recurrent nerve, esophagus, laryngopharynx, larynx, trachea. A tumor that has a massive spread, often with life-threatening symptoms in the form of dysphagia, stenosis of the trachea or larynx, has no alternatives to surgical treatment.Aim. Evaluation of the results of extended and extended-combined interventions for locally advanced highly differentiated thyroid cancer (immediate surgical and long-term results of treatment).Materials and methods. During the period from 2010 to 2021, 82 patients with locally advanced thyroid cancer were operated on. This cohort included patients in whom the tumor process spread not only to the neck, but also to the mediastinum: either in the region of the upper thoracic inlet, or there was a lesion of deeper parts of the mediastinum. The average age is 56.8 years. The ratio of men and women: 34 (41.5%) and 48 (58.5%), respectively. According to the prevalence of the tumor process, T4 tumors were diagnosed in 54.8% (n= 45). 37 patients had T3 (45.2%) tumors. In 57.3% (n= 47), the primary tumor was combined with the presence of a metastatic lesion in the regional lymph nodes of the neck. 34.1% (n 28) had distant metastases. In all cases it was a lesion of the lungs. Papillary thyroid cancer was verified in 89.6%. 21 patients underwent operations with resection of the larynx and trachea: in 7 cases, laryngectomy with resection of 5 to 8 rings of the trachea, in 4 cases, circular resections, in 6 cases, “shaving”, in 2 cases, “terminal” resections of the trachea with plasty of the defect of the sternum-clavicle-mastoid muscle, in 2 patients the plates of the thyroid cartilage were resected while maintaining the integrity of the organ. In 24 patients, mediastinal lymph node dissection (sternotomy) was performed; in 2 cases, mediastinal lymph node dissection was performed thoracoscopically. In 2 cases, resection of bone structures was performed — the manubrium of the sternum and sternoclavicular joints. In 33 patients, removal of the primary tumor, paratracheal, paraesophageal metastases and metastatic conglomerates from the posterior mediastinum (4 cases) was performed through the cervical approach.Results. The postoperative period in this group of patients was complicated by the development of pneumonia in 52 (63.4%) patients. Purulent mediastinitis developed in 6 (7.8%) patients, arrosive bleeding in 6% (n= 5), osteomyelitis of the sternum in 2 (2.4%) cases, gastric bleeding in 1 patient (1.5%), lymphorrhea in 2 (2.4%), parathyroid insufficiency developed in 70.7% (n 58) of observations. Postoperative mortality was 6% (n= 5).OS and disease-free survival amounted to 66.7% and 53.4%, respectively. Death from the progression of the disease occurred in all cases due to the growth of distant metastases against the background of resistance to radioactive iodine that developed during treatment or the implementation of new metastatic foci in terms of 2 to 5 years.Conclusions. This group of patients demonstrates satisfactory results of OS and disease-free survival, but requires further dynamic monitoring and evaluation of the effectiveness of drug treatment of radioiodine-resistant tumors.

The clinical significance of the features of the morphological study and immunohistochemical determination of pancytokeratin in the lymph nodes of the central zone in papillary thyroid cancer

Introduction. papillary thyroid cancer is increasingly being detected at early stages when regional and distant metastases are absent per clinical examination. However, lymph nodes of the central zone can carry hidden metastases. frequency of such metastases is 22.3–46.7 %. maximally accurate identification of hidden metastases after lymph node dissection remains an important problem.Aim. тo evaluate the effect of histological examination characteristics and immunohistochemical measurement of pancytokeratin level on frequency of detection of papillary cancer hidden metastases in regional lymph nodes of the central zone in patients with clinical stage N0 papillary cancer.Materials and methods. The main group included 50 patients with stage ст1–2N0М0 primary papillary thyroid cancer. Dissected central lymph nodes of the patients prior to formalin fixation were extracted from the sample and inserted in individual paraffin blocks. Apart from standard histological examination, pancytokeratin level was measured immunohistochemically in the lymph nodes. The control group consisted of 200 patients for whom dissected central cell tissue was sectioned into blocks after formalin fixation. The number of lymph nodes in the dissected sample was measured by a pathomorphologist.Results. In the main group, the number of lymph nodes in the sample varied between 6 and 37 with mean of 20.7 ± 6.8; in the control group the number was lower: 3–25, mean 9.8 ± 5.1 (р = 0.000). In the main group, hidden metastases were detected more frequently than in the control group: in 30 (60 %) and 68 (34 %) cases, respectively (р = 0.001). In 20 (40 %) patients, immunohistochemical examination showed new metastases. use of this method allowed to detect 1 to 7 additional metastases (mean 2.4 ± 1.5 lymph node lesions).Conclusion. use of targeted dissection with extraction of lymph nodes led to significant increase in their numbers in the samples, and immunohistochemical examination allowed to detect a large number of hidden metastases in the central lymph nodes.

Prognostic significance of the logistic regression model for assessing the risk of recurrence in patients with prostate cancer after radical prostatectomy

Purpose of the study. The study’s objective is to investigate the influence of risk factors for recurrence of prostate cancer (PCa) after radical surgical treatment on the unfavourable course of recurrence of the disease with the formation of a set of the most significant factors of a model that reflects the likelihood of relapse.Materials and methods. A retrospective analysis of clinical, pathomorphological and perioperative parameters of 803 patients with PCa after radical prostatectomy was carried out. By means of logistic regression, a model for assessing the risk of recurrence for patients with prostate cancer was built, which included 7 indicators, one of which was measured by quantity (time between biopsy and start of treatment) and six categorical ones (ISUP grade group, cT, cN+, positive surgical margin, PSA level after surgery, pN+). The construction of a logistic regression model consisted in obtaining a characteristic of the logistic function Ψ for the standard equation y = exp(ψ) / (1 + exp(ψ)).Results. Substituting the coefficients obtained for each of the indicators, we obtain Ψ to assess the risk of relapse Ψ = 0.485 × X1+ 1.937 × X2 + 0.789 × X3 + 3.229 × X4 + 0.443 × X5 + 0.880 × X6 + 0.015 × X7–6.65. In the resulting formula, each of the regression coefficients describes the size of the contribution of the corresponding factor. In our case, all regression coefficients were positive, which means that this factor increases the overall risk of relapse. The quality of the resulting model is determined by the chi-square = 284.3; p < 0.001; OR = 28.45. The sensitivity of this model was 86.6 %, specificity 81.5 %, diagnostic accuracy 82.7 %.Conclusion. This model makes it possible to obtain the probability of recurrence after radical prostatectomy depending on the severity of a specific set of predictive signs (a positive effect is predicted for y > 0.5, a negative one for y ≤ 0.5) and the degree of influence of one or a group of predictive signs on the likelihood of relapse, such as the ISUP grade group, locally advanced disease, clinically detectable lymph node lesion, positive surgical margin, PSA level of more than 0.09 ng/ml 1 month after surgery, the presence of regional metastases and the time between biopsy and the start of treatment.

Diagnosis challenges of a patient with peritoneal tuberculosis masquerading as ovarian malignancy: a case report

Background: Peritoneal tuberculosis (PTB) could mimic advanced ovarian cancer cases, making its diagnosis challenging. Comprehensive and conscientious examinations for diagnosis are needed to differentiate such cases to avoid inappropriate treatment. We report a problematic diagnosis of PTB that mimic ovarian malignancy. Case Presentation: A 20-year-old female patient with history of multiple rehospitalizations, presented with complaints of abdominal pain, nausea/vomiting, low-grade fever, and weight loss in the last five months. In the first admission, patient was suspected with malignant ovarian cyst due to clinical features of malignancy with normal chest X-ray, abdominal USG suggested ovarian cyst in both ovaries, high levels of Ca125. However abdominal CT-scan showed thickening in peritoneum which suggested PTB. The patient was planned for urgent laparotomy while waiting for GenExpert result. On the second admission, patient presented with recurrent abdominal pain, GenExpert sputum and stool showed negative result, and planned for surgery but the patient refused. On the last admission, patient diagnosed with impending bowel obstruction and underwent abdominal CT-scan with contrast showed diffuse multiloculated cystic lesion in cavum pelvic and multiple prominent mesenteric lymph nodes that suggested abdominal TB with abscess in cavum pelvic. Exploratory laparotomy revealed conglomeration, pus and tubercles in the peritoneum. A TB was confirmed based on pathology and microbiology examination from tissue biopsy and pus. Conclusion: We reported patients with PTB with unspecific clinical symptoms which suspected as ovarian malignancy. This study highlights the challenges in diagnosing PTB and therefore PTB could be considered a differential diagnosis in patients suspected of ovarian malignancy in the TB endemic countries.

SC-gtCAR19, a Non-Viral Genome Targeting Anti-CD19 CAR-T Candidate in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: Updated Results from Long-Term Follow-up

Introduction It has been made great commercial success in hematological malignancies by chimeric antigen receptor (CAR) T cell therapy. However, high rate of adverse events (AEs) still remains an issue. Non-viral Genome Targeting CAR (gtCAR) delivery technology, which uses CRISPR-Cas9 to insert CAR DNA to TRAC locus specifically in human T cells, produces moderate CAR-T cells compared with conventional ones. Earlier results of SC-gtCAR19, an anti-CD19 gtCAR-T candidate from an investigator initiated Phase I clinical trial (ChiCTR2000031942) demonstrated a favorable benefit-risk profile in relapsed/refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL) patients. Reported here are updated long-term follow-up results. Objective The primary objective is to assess safety. Secondary objective is to evaluate efficacy. Level of CAR-T cell in blood was explored. Method This is a single center, open-label and single-arm trial. Patients or allogeneic donors underwent leukapheresis and their CD3+ T cells were selected and modified by non-viral vector to produce SC-gtCAR19. A standard lymphodepletion chemotherapy was performed. The median dose was 3.89×106CAR+ cells/kg (0.58-8.31×106/kg). AEs were graded according to CTCAE v5.0. Cytokine Release Syndrome (CRS) and neurological events (NEs) were graded by ASTCT consensus grading. Relapse defined as bone marrow (BM) blast or B-ALL related mutation gene positive from nonexistence regardless of specific value, and extramedullary disease (EMD) occurrence. Result As of May 1st 2022, twenty-two r/r B-ALL patients received SC-gtCAR19 (Table 1). The median age was 29 (13-61), and the median number of previous regimen was 5 (2-16). The median baseline BM blast after preconditioning was 44.1% (0.3-99%), particularly 73% of patents with high disease burden (>25% leukemic blast). Five patients (23%) once had stem cell transplantation (SCT), and 14 (64%) have B-ALL related chromosomal and molecular abnormalities. One patient has EMD. No patient has been treated by any other CD19 related therapy before enrollment. The most common AEs of any grade were anaemia (100%), pyrexia (91%), neutrophil count decreased (91%), and white blood cell count decreased (86%) (Table 2). CRS occurred in 20 patients (91%), and 4 of them (18%) with grade 3 CRS. The median time to CRS onset was 7 days (IQR 7-14), and the median duration of any grade CRS was 3 days (IQR 2-5). Three patents developed NEs, one was grade 2 and 2 were grade 3 (temporary seizure, related to infection and patient's cerebral infarction before enrollment). No fatal or life-threatening events happened. No Tocilizumab administered, four patients used vasopressors and 2 steroids for treatment of CRS. All patients were eligible for efficacy analysis. At Day 28, the overall response rate was 100%, with 9 (41%) patients achieving complete remission (CR), ten (45%) achieving complete remission with incomplete haematological recovery (CRi), and 3 (14%) with blast-free hypoplastic. Among them, twenty patients (91%) achieved minimum residual disease (MRD) negative CR, and those 2 patients with MRD positive CR were assessed undetectable BM MRD in Day 90. Patient with EMD, the nodal lesions in her breast disappeared at Day 60. At a median follow-up of 19.9 months (4.5-26.6), nineteen patients relapsed, within which 7 (36.8%) antigen escape relapse. The median duration of remission for 19 patients achieving CR/CRi was 8 months (2.5-NE). All patients received a consolidation treatment by Lenalidomide 3 months after infusion on condition of CR status until disease progression/death, and all of them did not receive SCT afterwards before relapse. As of the data cutoff, two patients (9%) had ongoing CR with median follow-up of 22.4 months. The median relapse-free survival for 19 patients was 8.9 months (2.9-NE) (Figure 1). The median OS was 24.2 months (3.7-NE) (Figure 2). CAR T cell level measured by cell copies percentage per peripheral blood mononuclear cells peaked at median 12 days (IQR 10-13) (Figure 3). The median peak percentage of copies was 53% (IQR 26.5-72.1%). Conclusion This study is the first clinical trial applied a gtCAR-T candidate for r/r B-ALL treatment. SC-gtCAR19 has a better risk-tolerance. Despite TCR gene knocked-out, gtCAR-T cell proliferation and its function both short and long term may not be influenced. We illustrate that this novel approach is feasible in terms of manufacture and clinical application. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Interim PET-Guided ABVD or ABVD/Escalated BEACOPP for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma (JCOG1305, INNOVATE-HL study)

Introduction Interim positron-emission tomography (PET) can predict clinical outcomes in patients with classic Hodgkin lymphoma (cHL). The objective of this single-arm confirmatory study (JCOG1305, INNOVATE-HL) is to establish interim PET-guided treatment strategy for newly diagnosed advanced-stage cHL. Methods Patients aged 16-60 years with cHL received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as an induction chemotherapy, and then underwent an interim PET scan. Images were centrally reviewed with the use of a 5-point scale for PET findings for further response guided treatments. Patients with negative interim PET findings (defined as score 1 to 3) continued additional 4 cycles of ABVD, whereas those with positive interim PET findings (score 4 or 5) switched to 6 cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone). Involved site radiation therapy (ISRT) was set as a protocol treatment if patients with partial response had a single residual lesion after completion of chemotherapy. The primary endpoint were 2-year progression-free survival (PFS) among all eligible patients and among interim PET-positive patients (co-primary endpoints). We had the following hypotheses: 2-year PFS of eligible patients and interim-PET positive patients will exceed 75% and 35%, respectively, compared to a historical control with one-sided alpha of 0.1. Secondary endpoints included overall survival (OS), event-free survival (EFS), in which events were defined as death, progression or not achieving complete response at end of protocol treatment, and incidences of adverse events and secondary malignancy. This study was registered at jRCTs031180218. Results A total of 93 patients were enrolled from 35 institutions between January 2016 and December 2019. One patient was ineligible because of diagnostic error. Baseline characteristics of 92 eligible patients who underwent an interim PET scan were as follows: a median age of 35 years (interquartile range [IQR]: 28-48); 58% were male; most of patients (87 [95%]) had performance status of 0 or 1; Ann Arbor stage III and IV consisted of 40 (43%) and 43 (47%), respectively, the remaining 9 (10%) had stage IIB with bulky (10 cm or more) mediastinal lesion or nodal lesion involving directly to extranodal lesion; 51 (55%) and 15(16%) had B symptoms and bulky lesions, respectively. An interim PET scan showed 19 patients (21%) with positive findings; those patients received escalated BEACOPP; 18 completed 6 cycles of BEACOPP including one who underwent ISRT, the remaining one discontinued BEACOPP. On the other hand, 73 patients (79%) who had interim PET-negative findings continued ABVD; 70 completed additional 4 cycles of ABVD including two who underwent ISRT, the remaining 3 discontinued ABVD. Average relative dose intensity of induction ABVD, additional ABVD and escalated BEACOPP were 98.6% (±4.0), 96.7% (±5.7) and 82.2% (±9.3%), respectively. With a median follow-up of 41.1 months (IQR: 29.7-53.1), the 2-year PFS were 84.8% (80% confidence interval [CI]: 79.2-88.9) and 84.2% (80% CI: 69.7-92.1) among all 92 eligible patients and 19 interim PET-positive patients, respectively (Figure 1). The 2-year EFS were 76.1% and 68.4% among all eligible patients and interim-PET positive patients, respectively. Bleomycin lung toxicity (BLT) occurred in 9 patients, but no patients led to BLT-related death. Twelve and three patients underwent autologous and allogeneic hematopoietic stem cell transplantation (HSCT) as a salvage treatment, respectively, including one received allogeneic HSCT for relapse after autologous HSCT. The 2-year OS was 98.9%; two patients died due to interstitial pneumonia after autologous HSCT and brain hemorrhage without relapsing cHL among the interim PET-positive patients, whereas no patients died among interim PET-negative patients. Diffuse large B-cell lymphoma developed in one patient with interim PET-negative findings as a secondary malignancy 4.6 years after enrollment. Conclusions This INNOVATE-HL study demonstrated that interim PET-guided treatment strategy was useful for younger patients with newly diagnosed advanced-stage cHL. Of note, 6 cycles of escalated BEACOPP is a feasible and effective regimen for interim PET-positive cHL patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Total Metabolic Tumor Volume Is Confirmed As Independent Prognostic Factor in Treatment Naïve Follicular Lymphoma Patients and Can be Combined with FLIPI2 to Improve Prognostic Accuracy. a FOLL12 Substudy By the Fondazione Italiana Linfomi

Aim/Introduction: The prognostic role of FDG PET/CT parameters before first line therapy in patients with Follicular Lymphoma (FL) remains unclear, with conflicting data published in the literature. To this end we evaluated the prognostic value of baseline Total Metabolic Tumor Volume (TMTV) in a large cohort of treatment-naïve FL patients enrolled in the FOLL12 trial (NCT02063685). Materials and Methods: FOLL12 is a multicenter, randomized, phase III trial that compared standard (Arm A) vs response adapted maintenance (Arm B) in patients with grade 1-3a advanced stage FL who achieved complete (CR) or partial response (PR) to induction rituximab based immunochemotherapy (R-ICT). In the current study we included patients for whom baseline FDG PET/CT was available and centrally reviewed. The TMTV was obtained by expert nuclear physicians from baseline scans by summing the metabolic volumes of all individual nodal and extra nodal lesions, using the 41% SUVmax threshold method. Univariate and multivariate analyses were performed using Cox proportional hazard model. Main study endpoint was Progression Free Survival (PFS). Results: starting from the FOLL12 trial population, 692/807 patients were included in this study; 48% were older than 60 years, 89% had stage III-IV disease and 40% had a high-risk FLIPI-2 score(3-5 risk factors). Overall, the 5-year PFS was 79% (95% CI, 76 to 82%) and the median TMTV was 242 mL (IQR=446). The optimal cutoff identified for TMTV was 200ml. TMTV values were higher in association with unfavorable prognostic features (Hb <12 g/dl, LoDLIN > 6cm, elevated beta2 microglobulin and LDH, and number of nodal areas >4) whereas were similar between study arms, and ICT regimens. In univariate analysis, 5-year PFS was significantly lower for patients with high vs low TMTV (60% vs 75%; HR=1.87 [95%CI: 1.41-2.49], p<0.001). The correlation between TMTV and PFS was confirmed both in the standard maintenance arm and in the response adapted arm of the FOLL12 trial and the independent prognostic role of TMTV was confirmed when adjusted by study arm, FLIPI-2, and type of ICT. In multivariate analysis, high TMTV (HR 1.47 (1.09 - 2.00); p=0.012) and high risk FLIPI2 (3-5 RFs: HR2.05 (1.54 - 2.73) p<0.001) retained their independent prognostic role for predicting PFS. Three groups of patients were identified which were associated with different 5-year PFS rates; TMTV < 200ml and intermediate FLIPI2: N=241 (35%), 5yr PFS 78% (95% CI 71-83); TMTV > 200ml or high risk FLIPI2: N=237 (34%), 5yr PFS 68% (60-74), HR 1.53 (1.06 - 2.22); TMTV >200ml and high risk FLIPI2: N=214 (31%) 5-yr PFS 51% (43-58), HR 2.96 (2.10-4.19). The combined TMTV + FLIPI2 model was internally validated with 1000 bootstrap resampling (c-Harrel 0.616) Conclusion: Pre-treatment TMTV is confirmed as a strong independent predictor of PFS in patients with FL receiving frontline R-based ICT The combination of TMTV and FLIPI2 may contribute to improve risk stratification in guiding risk adapted therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Dissection of the VI cervical lymph collector for papillary thyroid cancer

Objective. To assess the expediency and necessity of implementing the dissection of the central cervical lymph nodes (group VI) in patients with papillary thyroid cancer.&#x0D; Materials and methods. The results of preoperative examination, surgical treatment and its follow-up were evaluated in 210 patients, who along with thyreoidectomy, underwent dissection of the central cervical lymph nodes (group VI).&#x0D; Results. It was established that for papillary thyroid cancer, a high frequency of cervical lymph node metastasis is typical. During the preoperative examination, (US and cytological study), metastases were detected in 23.5 % of patients, and while pathomorphological study of the removed central neck cellular tissue in 47.4 % more. Therefore, preventive dissection of the central cervical lymph nodes (VI group) is worthwhile.&#x0D; Though expansion of the volume of operations in patients with papillary thyroid cancer at the expense of dissecting the central cervical lymph nodes in addition to the thyroid gland, leads to insignificant elevation of the number of complications but in the remote period (35 years), volume expansion of operations has no negative impact on the indicators of physical and psychical components of the life quality.&#x0D; Conclusions. The obtained objective information regarding the presence or absence of metastatic lesion of the cervical lymph nodes permits to ground the process staging in papillary thyroid cancer and form treatment tactics.

Analysis of lymphocyte profile in lymph nodes, bronchoalveolar lavage fluid and peripheral blood in patients with stage II sarcoidosis

ObjectiveTo evaluate the lymphocyte profile (LP) in lymph node puncture fluid (LNPF) of mediastinal and hilar lymph nodes, bronchoalveolar lavage fluid (BALF), and peripheral blood (PB) involved in stage 2 sarcoidosis. MethodsAfter selection, 31 patients diagnosed with stage II sarcoidosis were finally included. Patients were further divided into symptomatic (n = 17) and asymptomatic (n = 14) groups according to the presence or absence of respiratory symptoms. The LP in lymph node puncture fluid (LNPF), bronchoalveolar lavage fluid (BALF), and peripheral blood (PB) were evaluated and compared using flow cytometry. The relationship between respiratory symptoms and LP was preliminarily analyzed. ResultsThe proportions of T cells and CD4 T cells, and CD4/CD8 ratio in BALF were significantly higher than that of LNPF with PB (all P < 0.05). The proportions of lymphocyte cells, CD8 T cells, NK cells, and CD4/CD8 ratio in LNPF and PB were significantly different (all P < 0.05). There were significant differences in CD4 T cells [72.40 (68.90,75.55) vs.46.30 (38.55,52.50), P = 0.004], CD8 T cells (9.9 ± 3.9 vs. 16.8 ± 6.8, P = 0.002), and CD4/CD8 ratio (7.9 ± 2.8 vs. 3.9 ± 1.5, P < 0.001) in BALF between the symptomatic group and asymptomatic group (all P < 0.05). The T cells (rs = 0.447, P = 0.011), CD4 (rs = 0.572, P = 0.002), and CD4/CD8 ratio (rs = 0.701, P < 0.001) in BALF were positively correlated with respiratory symptoms. ConclusionThe LP in LNPF, BALF and PB were significantly different and the main index correlated with respiratory symptoms was CD4/CD8 ratio in BALF. The difference of LP in BALF and LNPF may help to deeply understand the pathophysiological process and may reflect the different degree of lung and lymph node lesion.

A multidimensional model incorporating radiomics score and liquid biopsy for the prediction of malignant and benign pulmonary nodules.

As the lesions in pulmonary nodules (PNs) are small and the clinical manifestations lack specificity, the etiology of PNs is complex, predisposing them to misdiagnoses missed diagnoses. Thus, the diagnosis and treatment of PNs remains challenging and an important clinical problem. This study prospectively enrolled 156 patients with computed tomography (CT)-diagnosed PNs who underwent circulating genetically abnormal cell (CAC) testing between January 2020 and December 2021. We collected data on clinical features closely related to the nature of PNs, such as age, smoking history, and type of nodule. All internal regions of interest (ROIs) of PNs in this study were segmented. Radiomic feature extraction was performed on the ROIs, and a radiomics model was constructed using least absolute shrinkage and selection operator (LASSO) regression to obtain a radiomics score (Rad-score). A comprehensive model combining clinical features, Rad-score, and liquid biopsy was constructed using logistic regression analysis. The diagnostic performance of the model was evaluated using receiver operating characteristic (ROC) curves. In this study, 5 radiomics features were screened for model construction. The area under the ROC curve (AUC) of the radiomics model was 0.844 [95% confidence interval (CI): 0.766-0.915] in the training set. The Rad-score, clinical features, and CAC were further combined to construct a multidimensional analysis model. The AUC of the synthesized model was 0.943 (95% CI: 0.881-0.978) in the training set. A multidimensional model is an effective tool for the noninvasive diagnosis of malignant PNs. The validation and combination of multiple diagnostic methods is a productive avenue of research trend for the identification of malignant PNs.

18F-FDG PET–CT dual-time imaging in detection and characterization of recurrent lesions in patients with testicular cancer

BackgroundTesticular cancer is the second most frequent form of male genital tumors. Globally, testicular malignancy has risen over the last forty years. Among malignant testicular tumors, germ cell tumors represent approximately 95% of all tumors. They are classified into seminomatous and non-seminomatous tumors as they differ in clinical features, therapy, and prognosis. Despite the increasing value of whole-body fluorodeoxyglucose positron emotion tomography/computerized tomography (18FDG-PET/CT) for all malignancies, the practical function of this imaging method in testicular germ cell tumors is still unknown. We aim to assess the diagnostic performance of18FDG-PET/CT dual-time-point imaging (DTPI) in the detection and characterization of recurrent testicular cancer lesions.Results18FDG-PET/CT DTPI showed higher specificity (SP) in lesions' delectability and characterization for local, nodal, and distant lesions than the single-time-point imaging (STPI) (97.6%, 93.8%, and 97% versus 95.2%, 68.8%, and 84.8%, respectively) and higher sensitivity (SN) for nodal and distant lesions (97% and 93.8% versus 87.8% and 87.5%, respectively). The mean SUVmaxD and the RI values—not the SUVmaxE—of the malignant lesions were significantly greater than the benign lesions (p 0.001*).Conclusions18FDG-PET/CT DTPI and its related indices (SUVmaxD and the RI) are more accurate, sensitive, and specific than the STPI in the characterization of recurrent lesions in testicular cancer patients.

Clinicopathologic Analysis of Kikuchi-Fujimoto Disease and Etiologic Exploration Using Metagenomic Next-Generation Sequencing.

Kikuchi-Fujimoto lymphadenitis, also known as Kikuchi-Fujimoto disease (KFD), is a self-limited lymphoproliferative disease, with no definitive causative agent confirmed by traditional methods. To further explore the clinicopathologic features of KFD and clarify related pathogenic factors. A retrospective analysis was performed in a collection of KFD cases to review the clinical and histopathologic features, and metagenomic next-generation sequencing (mNGS) was used in 64 formalin-fixed, paraffin-embedded (FFPE) tissues from patients with KFD. One hundred five of the 170 patients with KFD (61.8%) were female; 10 patients had autoimmune diseases. Four pathologic subtypes were classified: necrotic (45.9%, 78 of 170), phagocytic (32.4%, 55 of 170), proliferative (17.1%, 29 of 170), and xanthomatous (4.7%, 8 of 170). Patients younger than 40 years with unilateral cervical lymphadenopathy and small vessel fibrinous degeneration accounted for significant differences among the 4 pathologic subtypes (P < .05). Among 64 patients with KFD, 9 had detectable bacterial or viral DNA-of 6 bacterial cases, 1 involved Chlamydia psittaci; while of 3 viral cases, 1 involved human beta herpesvirus 6B and 2 involved Epstein-Barr virus. No significant relationships were found between the pathologic subtypes and specific pathogens. Only a small proportion of patients with KFD had autoimmune diseases or infections from specific pathogens, suggesting that KFD is likely a reactive lesion of lymph nodes to various circumstances. To our knowledge, this is the first and the largest study to detect pathogens with the use of mNGS on FFPE samples in KFD. Our study also further confirms that mNGS can be used on FFPE samples to detect potentially infectious agents in clinical settings.

Establishment and evaluation of a CT-based radiomic model for AIDS-associated pulmonary cryptococcosis

BackgroundEstablish a CT-based diagnostic radiomic model for AIDS complicated with pulmonary cryptococcosis and evaluate the diagnostic efficacy of this model.MethodsThis retrospective study enrolled 98 AIDS patients with pulmonary cryptococcosis and 103 AIDS patients with other infections or neoplastic lesions, comprising a total of 699 lesions. Patients were randomly divided into a training group and test group at a ratio of 2.75:1. Features from all lesions, cavity lesions and solid nodule lesions were extracted, and two kinds of radiomic models (6 types) were established. ROC curves were drawn, and the sensitivity and specificity were calculated to compare the SVM model and LR model, radiologists’ empirical diagnoses and the combination of these empirical diagnoses with the radiomic model.ResultsThe AUCs of senior radiologist for all lesions and cavity lesions were lower than those of the SVM and LR models. The diagnostic efficacy of primary radiologist was lower than that of both of the other model types. The diagnostic efficacy of the LR model was relatively stable, with the highest diagnostic efficiency of the 3 model/radiologist groups. The AUCs of intermediate radiologist in combination with the LR radiomic model for all lesions, nodular lesions and cavity lesions were 0.88, 0.84, and 0.9, respectively, which were the highest among all models and radiologists.ConclusionsThe CT-based radiomic LR model of AIDS-associated pulmonary cryptococcosis exhibits good diagnostic performance, which was similar to that of senior radiologists and higher than that of the primary radiologist. With the help of a radiomic model, radiologists can achieve improved diagnostic accuracy compared to that when only an empirical diagnosis is used.

The diagnostic value and safety of modified needle aspiration biopsy for superficial lymphadenectasis.

To explore the safety and diagnostic value of modified needle aspiration biopsy for superficial enlarged lymph nodes. A total of 88 patients with unknown diagnosis of superficial lymphadenopathy in our hospital (Wuxi Fifth People's Hospital) from January 2018 to July 2021 were recruited and then divided into two groups using the simple random grouping method. The study group included 48 patients who were punctured via modified needle aspiration biopsy, while the control group included 40 patients who were punctured via core needle biopsy (CNB) and had a better clinical evaluation. A BARD® automatic biopsy gun with a 18 G needle was used to puncture any enlarged lymph nodes, and specimens were obtained for pathological examination. The diagnostic positive rate of the two puncture methods was then compared and the complications involved in the two methods were observed. The positive rate of definite pathological diagnosis was 79.2% (38/48) in the study group and 82.5% (33/40) in the control group. Both groups had similar diagnostic positive rates regarding tuberculosis and metastatic tumours in the lymph nodes (P > 0.05). Only slight bleeding was observed during the operations using the two puncture methods, with the bleeding rate of the study group 20.8% and that of the control group 15.0%, and the difference was not statistically significant (P > 0.05). No other complications were observed across both groups. Among the 48 patients with enlarged lymph nodes in the study group, there was no difference in the positive rate of diagnosis between enlarged lymph nodes larger than 20 mm and those smaller than 20 mm in the pathological, bacterial culture and cytology examinations (P > 0.05). The sensitivity, specificity, positive predictive values and negative prediction values of the improved lymph node lesions were 83.3%, 100%, 100% and 90.9%, respectively. The diagnostic efficacy and safety of modified needle aspiration biopsy in superficial swollen lymph nodes are equivalent to those of CNB, but the former is a more economical, simple and practical method for clinical settings and one that could be popularised in primary hospitals.

Kinetics and Patterns of PSMA PET Uptake in Prostate Cancer after Radiation Therapy: A Single Center Retrospective Study

<h3>Purpose/Objective(s)</h3> The kinetics of PSMA PET uptake in prostate cancer lesions after radiation therapy (RT) is unknown. The aim of this study was to assess the patterns of PSMA PET uptake in irradiated lesions using serial PSMA PET/CT scans. <h3>Materials/Methods</h3> This was a single-center retrospective study that included patients with prostate cancer who underwent one PSMA PET/CT scan before RT and at least one other scan after RT between November 2016 and July 2021. One reader (M.H.) analyzed the target lesions uptake by visual criteria (uptake above background) and semi-quantitative analysis. Lesions with and without residual uptake were compared for 1) time-interval after RT, 2) lesion tissue type (prostate, prostate bed, lymph node, and bone), 3) RT type (stereotactic body RT, intensity-modulated RT, three-dimensional conformal RT, and proton therapy), 4) baseline uptake intensity (SUVmax), and 5) PSMA-derived tumor volume (PSMA-TV). Lesions with residual uptake were followed-up. Diagnosis of eventual progression was made by biopsy or subsequent follow-up imaging when available. <h3>Results</h3> A total of 108 patients with available clinical and imaging data on 257 irradiated lesions (lymph node: n = 126; bone: n = 98; prostate: n = 25; prostate bed: n = 8) were included. The median time from end of RT to follow-up PET was 10.6 (range: 0.4-51.7) months. Residual uptake after RT was observed in 90/257 (35.0%) of the irradiated lesions. The mean % decrease in SUVmax of the irradiated lesions on the follow-up PET performed at <3 (n = 20), 3-6 (n = 38), 6-9 (n = 58), and 9-12 (n = 27) months post-RT were 41.4%, 53.8%, 65.6%, and 69.7% (p = 0.004). Residual uptake was more commonly seen in the prostate (prostate 68.0%; bone 40.8%; prostate bed 25.0%; lymph node 24.8%, p < 0001), and associated with higher baseline uptake and lesion size: SUVmax 9.5 vs 6.4 (p < 0.001) and PSMA-TV 1.7 vs 1.0 ml (p = 0.002) in lesions with residual uptake vs. without, respectively. RT type was not associated with the residual uptake (p = 0.17). In multivariate logistic regression analysis, shorter time after RT (OR: 0.93 [95%CI: 0.89-0.97]), higher baseline SUVmax (OR: 1.07 [1.03-1.11]), and lesion in the prostate (OR: 6.84 [2.19-21.3]) were independently associated with residual uptake. Among the lesions with residual uptake, 28/90 (31.1%) lesions were subsequently evaluated by biopsy and/or follow-up imaging, and 6/28 (21.4%) lesions were eventually showed progression. Risk factors of recurrence were a residual uptake observed after a long time-interval from the end of RT (recurrence vs non-recurrence: 15.8 vs 3.7 months, p = 0.002) in the prostate lesion (prostate 50.0%; bone 12.5%; lymph node 0.0%, p = 0.044). When using a cutoff value of >8.6 months after RT, the presence of residual uptake was diagnostic of recurrence with a sensitivity of 0.83 and specificity of 0.86 (AUC: 0.92). <h3>Conclusion</h3> The PSMA PET uptake of irradiated lesion decreases gradually over one year, while the uptake in the prostate tends to remain longer than in bone and lymph node lesions.

Lesion Segmentation Using Convolutional Neural Network for PET/CT-Guided Salvage Post-Prostatectomy Radiotherapy

<h3>Purpose/Objective(s)</h3> Molecular imaging with novel PET radiotracers has been shown to significantly impact radiotherapy decision making, target definition, and cancer control in the setting of prostate cancer (PCa) recurrent after prostatectomy. We propose a deep learning-based method to automatically segment pelvic node and prostate bed lesions on 18F-fluciclovine (anti-1-amino-3-[18F] fluorocyclobutane-1-carboxylic acid, FACBC) PET/CT images for salvage post-prostatectomy radiotherapy. <h3>Materials/Methods</h3> Our proposed method, named hierarchical activation network, consists of three main subnetworks: a fully convolutional one-stage object detection (FCOS) network, a hierarchical module, and a mask segmentation network. FCOS is employed to detect the view-of-interests (VOIs) of prostate bed and pelvic nodal lesions. Hierarchical module is used to derive activation map to boost the classification accuracy around lesion boundary. The mask segmentation network utilizes the detected VOIs obtained from FCOS network and the activation map obtained from hierarchical module to perform binary segmentation of lesions within the detected VOIs. To evaluate the proposed method, we retrospectively investigated 146 lesions from 83 prostate cancer patients who had 18F-fluciclovine PET/CT scan acquired. Each dataset has lesions contoured by physicians based on 18F-fluciclovine PET/CT scan, which were served as ground truth and training targets. The proposed method was trained and evaluated by a five-fold cross validation strategy. Quantitatively, we characterized the accuracy of the proposed method by calculating 95 percentile of Hausdorff distance (HD₉₅), the distance between the centroids of the two contours, the absolute difference of volumes, and Dice similarity coefficient (DSC). <h3>Results</h3> The average HD₉₅, centroid distance, volume difference, and DSC among all lesions is 4.09±3.75 mm, 1.84±1.77 mm, 1.44±7.21 cc, and 0.72±0.17. There is no statistically significant difference observed between ground truth (manual contour) and our proposed lesion volumes on a patient-wise basis using a paired t-test of significance (p = 0.83). Quantitative evaluations show the accuracy of the proposed method and confirm the feasibility of the proposed segmentation method. <h3>Conclusion</h3> We demonstrated the accuracy of the proposed method by evaluating the discrepancy in the centroid and volume, as well as the overlaps with ground truth. It is shown that the proposed method has great potential in improving the efficiency and mitigating the observer-dependence in pelvic and prostate bed lesion contouring for radiation therapy, and facilitating the workflow for ¹⁸F-fluciclovine PET/CT-guided salvage post-prostatectomy radiotherapy.

Longitudinal Assessment of Gross Tumor Volume in Abdominal and Pelvic Patients Undergoing MR-Guided Online Adaptive Radiotherapy as a Predictive Biomarker of Treatment Response

<h3>Purpose/Objective(s)</h3> MR-guided radiotherapy (MRgRT) provides longitudinal MR images during RT, and enables the evaluation of potential imaging biomarkers of treatment response (TR). We investigated whether interfraction tumor volumetric changes correlated with ultimate radiographic response. <h3>Materials/Methods</h3> 131 patients underwent daily adaptive MRgRT of the pancreas (n=71), adrenal (n=27), abdominal lymph node (LN) (n=19), and pelvic LN (n=14) to a median of 50 Gy/5 fractions (fxs). For each adaptive fx, the simulation GTV was compared to the daily GTV on the 0.35 T TRUFI MR. GTV change (ΔGTV) was quantified as the % difference in GTV of the adapted fx compared to simulation. To ensure robustness, a minimum ΔGTV > ±1 cc was required for TR-correlation on post-RT diagnostic MR. Patients were categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), using RECIST criteria, and TR was correlated to fx with the largest ΔGTV. <h3>Results</h3> Median follow up was 22.5 months. Numerically (not statistically significant) the largest interfraction ΔGTV for the entire cohort was observed at fx 3 (14.2%) compared to 6.8, 10.2, 8.9, and 13.1% for fxs 1, 2, 4, and 5, respectively. For pancreas, adrenal, abdominal LN, and pelvic LN, the median ΔGTV at fx 3 (ΔGTV_fx3) was -5.1, 20.8, 27.5, and 3.4%, respectively; meaning GTV increased, on average, for all sites except pancreas. ΔGTV_fx3 as a function of TR is displayed in the Table. ΔGTV_fx3 for pancreas and pelvic LN was <10%. For adrenals achieving post-RT CR, PR, SD, larger ΔGTV_fx3 were observed, with median of 23.8, 20.8, and 26.3%, respectively, with extreme case of 41% increase in a patient achieving a subsequent CR. For PD adrenal lesions, the ΔGTV_fx3 is 0. These findings putatively suggest an acute SBRT-related inflammatory response resulting in subsequent disease stability or regression. In contrast, for abdominal LN, no such significant ΔGTV_fx3 is noted for CR, PR, or SD, but for PD, the ΔGTV_fx3 increases substantially to 39.1%_. <h3>Conclusion</h3> Daily adaptive MRgRT enabled interfraction tracking of ΔGTV that was retrospectively correlated to TR. Numerically, we observed the greatest ΔGTV at fx 3. However, this change was seen primarily in adrenal and abdominal nodal lesions, and not other sites. The significance of this change is non-uniform, in that for adrenal lesions, responders were more likely to have volumetric increase, whereas for abdominal LN, progressors were more likely to have volumetric increase. These preliminary findings are being rigorously tested through a retrospective, multi-observer blinded contouring exercise, and also being extended to other disease sites, prior to formulating a clinically actionable hypothesis.

Proton SBRT for Isolated Nodal Recurrence in Gynecological Cancers

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) for isolated lymph node recurrence has been shown to have good rates of local control (LC) in gynecological cancers. However there exists the risk of toxicities to nearby organs. This single institution, retrospective outcome and dosimetric analysis assesses treatment response, associated GI and GU toxicities and associated characteristics for improved or worsened outcomes with proton based SBRT, hypothesizing that there will be low rates of toxicities while maintaining beneficial outcomes. <h3>Materials/Methods</h3> Adult patients diagnosed with primary gynecologic malignancy with isolated nodal recurrence treated with proton SBRT from 2006-2021 at a single institution were included. Toxicities were evaluated using RTOG/EORTC and CTCAE grading. Descriptive statistics were used to describe characteristics associated with local recurrence, toxicity, and survival. <h3>Results</h3> Fourteen patients with 21 nodal lesions were treated with 19 courses of proton SBRT. Median age was 64.5 (range: 47-78) years at time of initial cancer diagnosis and median of 66.0 (range: 51- 80) years at initial lymph node recurrence. Patients recurred within an average of 13.00 (range: 0.66- 31.41) months from end of initial treatment. Primary cancer sites included endometrium (n= 9), cervix (n= 2), ovary (n= 2), and vagina (n= 2). SBRT doses ranged from 30- 50 Gy (median 40 Gy) in 5-15 fractions with mean BED (alpha beta 10) of 69.93 (range: 48.00- 100.00) and mean BED (alpha beta 3) of 139.95 (range: 72.00- 216.67). Nodal locations treated included para-aortic (n= 7), pelvis (n= 5), iliacs (n= 4), and distant nodes (n= 3, supraclavicular, perirectal, periadrenal). Three pelvic and iliac lesions recurred locally at a median of 2.9 months (range 1.25-29.23) and 50% of patients developed local or distant recurrence. Local control at 3 months, 6 months, 1 year, and 2 years was 84.6%, 83.3%, 81.8%, and 70.0% respectively. Local recurrence free survival (LRFS) at 1 year and 2 years was 80.0%, 75.0% and overall survival (OS) was 54.5%, 44.4% respectively. Six patients developed grade 1 or 2 GI treatment related toxicity (Grade 1: 3, Grade 2: 3). 2 patients developed grade 1 GU toxicity. There were no GI grade 3-5 toxicities or GU grade 2-5 toxicities. Average Dmax to bladder was 14.42 Gy (median 18.62 Gy), range (0.6- 30.6). Average rectum Dmax was 15.75 Gy (range: 0.1- 34.2), median: 15.8 Gy. Median small bowel D2cc was 27 Gy (range: 10- 50.5) <h3>Conclusion</h3> Patients treated with proton SBRT had excellent rates of LC and LRFS and low rates of GI and GU toxicity. Dosimetric analysis also demonstrates low dose to nearby OARs. Based on these findings, Phase I/II trials evaluating dose escalation using proton techniques to further improve local control of isolated nodal recurrences should be considered.