Node Lesions Research Articles

Utility of Intraoperative Neuromonitoring to Protect against Adjacent Nerve Injury in Musculoskeletal and Lymph Nodal Cryoablation

PurposeTo demonstrate the utility of intraoperative neuromonitoring (IONM) as an effective method of passive thermoprotection against cryogenic injury to neural structures during musculoskeletal and lymph node cryoablation. Material and MethodsTwenty-nine patients (16 men; mean age among men, 68.6 years [range, 45–90 years]; mean age among women, 62.6 years [range, 28–88 years]) underwent 33 cryoablations of musculoskeletal and lymph node lesions. Transcranial electrical motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SSEPs) of target nerves were recorded throughout the ablations. Significant change was defined as waveform amplitude reduction greater than 30% (MEP) and 50% (SSEP). The primary outcomes of this study were immediate postprocedural neurologic deficits and frequency of significant MEP and SSEP amplitude reductions. ResultsSignificant amplitude reductions were detected in 54.5% (18/33) of MEP tracings and 0% (0/33) of SSEP tracings. Following each occurrence of significant amplitude reductions, freeze cycles were promptly terminated. Intraprocedurally, 13 patients had full recovery of amplitudes to baseline, 11 of whom had additional freeze cycles completed. In 5 of 33 (15.2%) cryoablations, there were immediate postprocedural neurologic deficits (moderate adverse events). Unrecovered MEPs conferred a relative risk for neurologic sequela of 23.2 (95% CI, 3.22–167.21; P < .001) versus those with recovered MEPs. All 5 patients had complete neurologic recovery by 12 months. ConclusionsIONM (with MEP but not SSEP) is a reliable and safe method of passive thermoprotection of neurologic structures during cryoablation. It provides early detection of changes in nerve conduction, which when addressed quickly, may result in complete restoration of MEP signals within the procedure and minimize risk of cryogenic neural injury.

Cladribine in the Treatment of Multifocal Multisystem Langerhans Cell Histiocytosis in a Patient with a Poor Prognosis. A Case Report

Langerhans cell histiocytosis is a hematologic clonal disease. The treatment of localized histiocytosis includes local methods such as radiotherapy or surgery. In cases of disseminated lesions with multiple system damage, chemotherapy is administered, which provides recovery in some patients. The present paper is a case report of multifocal multisystem Langerhans cell histiocytosis with bone, liver, spleen, abdominal lymph node and pituitary lesions in a 40-year-old patient. The diagnosis was verified by histology and immunohistochemistry of bone biopsy specimens. Polymerase chain reaction revealed no V600E mutation in the BRAF gene in tumor tissue. Persistent antitumor response was achieved after 6 chemotherapy cycles with cladribine monoregimen. This drug was well tolerated by the patient. By the time of this publication, the patient had preserved the persistent response for 38 months.

Stereotactic Body Radiotherapy for Oligoprogression in Castration-Resistant Prostate Cancer: Early Toxicity Analysis of the TRAP Trial

AimsTo assess toxicity and patient quality of life after stereotactic body radiotherapy (SBRT) to oligoprogressive disease (OPD) in patients with metastatic castrate-resistant prostate cancer (CRPC) on androgen receptor targeted agents (ARTA). Material and methodsThis phase II trial enrolled patients with metastatic CRPC with ≤ 2 oligoprogressive lesions in bone, lymph node, lung, or prostate. All patients were receiving systemic treatment with abiraterone or enzalutamide at the time of oligoprogression. All patients received SBRT to the OPD site(s) and continued the current ARTA. Patients received 30 Gy in 5 fractions (alternate days) to the OPD site. The primary endpoint of the trial is to assess if SBRT to OPD sites results in progression free survival of >6 months. The primary endpoint for this toxicity analysis is the rate of grade 3 or higher adverse events at any timepoint up to 6 months after SBRT. Secondary endpoints included comparing pre- and post-SBRT patient-related outcomes reported using visual analogue scale scores and EQ-5D health questionnaire. ResultsForty enrolled patients had at least 6 months of follow-up at the time of analysis. Grade 3 or higher toxicity from any cause recorded using common terminology criteria for adverse events and radiation therapy oncology group was found in 8/40 (20%) of patients, but only 1/40 (2.5%) was deemed possibly related to SBRT. There was no significant difference in mean EQ5D visual analogue scale score from baseline to each timepoint after SBRT (p = 0.449). ConclusionIn this prospective phase II clinical trial for OPD whilst on ARTA in the CRPC setting, we report low grade ≥ 3 toxicity after SBRT. There is no discernible change in patient-reported quality of life due to SBRT treatment. The final results of progression-free survival and toxicity of SBRT treatment will be reported once further follow-up is complete.

Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.

Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NOTA-LM3 and head-to-head comparison with [68Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial.

18F-labelled somatostatin receptor (SSTR) analogs offer several advantages over 68Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [18F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs. Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120min after [18F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [68Ga]Ga-DOTATATE and [18F]AlF-NOTA-LM3 was compared. [18F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [18F]AlF-NOTA-LM3 was significantly lower than that of [68Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [18F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [68Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [18F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [18F]ALF-NOTA-LM3 were significantly smaller than those detected on [68Ga]Ga-DOTATATE. [18F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [68Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [68Ga]Ga-DOTATATE. ClinicalTrials.gov identifier NCT06056362.

Pulmonary presentation and coil marcation of dirofilaria lung coin nodes - case report.

Clinicians face significant diagnostic challenges when dealing with nodal lesions of the lung. The majority of lung nodules are benign; however, asignificant number can be cancerous. Dirofilaria infestation should also be considered in the differential diagnosis of nodal lung lesions. Most patients with Dirofilaria infestation are asymptomatic. To determine the etiology of nodal lung infiltrations, procedures like radiological imaging, bronchoscopy, endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA), transthoracic biopsy (TTB), tumor markers, nonspecific serological tests, or surgical removal of the lung coin lesions can be performed. Coil marking of the smaller lung lesions under computed tomography (CT) guidance is ahelpful tool in determining the position and localization of the nodal lung lesions. Video-assisted thoracoscopic surgery (VATS) or robot-assisted thoracoscopic surgery (RATS) wedge resection is adiagnostic and therapeutic method of choice. No additional treatment of Dirofilaria other than wedge resection of the lung is necessary.

Dosimetry of lutetium-177-PSMA-I&amp;T radioligand therapy in recurrent/metastatic adenoid cystic carcinoma.

6093 Background: There is a high unmet need for effective systemic therapies for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (AdCC), as no standard-of-care exists. AdCC frequently expresses prostate-specific membrane antigen (PSMA), providing rationale for PSMA-targeted therapies, which have demonstrated significant efficacy in prostate cancer. In our phase 2 pilot trial (EudraCT 2019-003857-27), we assessed the safety, efficacy and feasibility of lutetium-177 (177Lu)-PSMA-I&amp;T in R/M AdCC patients. Despite well-tolerated, the efficacy was limited. To gain further insight into causes of the limited efficacy, we measured absorbed 177Lu-PSMA-I&amp;T radiation doses in tumors and organs at risk. Methods: Dosimetry was feasible and was performed in all 10 enrolled AdCC patients. They received 177Lu-PSMA-I&amp;T with a median activity of 7.40 (range 6.78-7.49) GBq and a median of 4 (range 1-4) cycles. For bone marrow dosimetry, blood samples were collected during cycle 1. Single-photon emission CT/CT (SPECT/CT) was performed at 1, 24, 48, 72 and 168 hours after 177Lu-PSMA-I&amp;T injection at cycle 1. Tumors &gt;1 cm were categorized based on gallium-68 (68Ga)-PSMA PET mean standardized uptake value (SUVmean): above, at (±10%), and below liver SUVmean. Per site, up to 3 index lesions per category were selected. Volumes of interest with ~1 cm margin were drawn on SPECT/CT. Background correction was applied. Salivary gland and bone lesion volume were determined by iterative thresholding on 68Ga-PSMA PET. Other tumor volumes were determined on CT. Hermes dosimetry software and Olinda 2.2 software were used to estimate doses according to the Medical Internal Radiation Dose scheme. Results were reported as the absorbed dose at cycle 1 (Gy). Results: In total, 66 tumor lesions were analyzed. Tumor sites included lung (n=35), pleura (n=16), liver (n=5), bone (n=4), lymph node (n=3), local recurrence (n=2) and thoracic wall (n=1). The median 68Ga-PSMA PET tumor/liver SUVmean ratio was 0.94 (range 0.33-2.62). The median tumor-absorbed dose was 0.47 (range, 0.01-4.66) Gy. Highest median doses by tumor site were 1.84 (range, 0.76-2.92) Gy in local recurrences and 1.35 (range, 0.33-2.62) Gy in bone lesions. Lowest median doses by tumor site were 0.18 (range, 0.14-0.27) Gy in lymph node lesions and 0.21 (range, 0.12-0.79) Gy in liver lesions. In organs at risk, the absorbed dose was highest in the kidneys, followed by the salivary glands, with mean values of 6.29 (standard deviation [SD], 2.32) Gy and 5.07 (SD, 2.47) Gy, respectively. The mean bone marrow absorbed dose was 0.53 (SD, 0.14) Gy. Conclusions: Tumor-absorbed radiation doses in our AdCC patient cohort receiving 177Lu-PSMA-I&amp;T were significantly lower than in prostate cancer (~10-40 Gy per cycle), likely due to lower and heterogeneous PSMA expression. This could explain the limited efficacy. Organ-absorbed doses aligned with studies in prostate cancer. Clinical trial information: NCT04291300 .

Receptor expression testing of the synchronous axillary nodal metastasis in early-stage breast cancer: Comparison of primary tumor and its draining nodes.

e12542 Background: Early stage (Stage I-III) human epidermal receptor -2 (HER2) positive and triple negative breast cancers (TNBC) tend to behave more aggressively than hormone positive breast cancers with higher and earlier incidences of recurrences. Oftentimes, testing for receptor subtypes is done only on the primary tumor and not on the synchronous axillary metastasis, with the assumption that the axillary metastasis is congruous to the primary lesion. Current guidelines also do not specify a requisite to do this testing. Information about the receptor expression types is fundamental for the treatment of breast cancer. We aimed to determine if there is significant discordance between the primary and ipsilateral axillary metastasis in early-stage breast cancer. Methods: We conducted a retrospective analysis via electronic medical record review of a large institutional database from 2008 to 2020. Sample for this study included all patients with a diagnosis of early-stage breast cancer (Stage I - III) with triple negative or HER2 positive tumors. Data on demographics, comorbidities, receptor status, staging, and mortality were collected. Results: Electronic charts from 448 patients were reviewed. 140 patients had axillary node positive disease. 40 (29%) of the 140 patients underwent testing for receptors subtypes on both primary and axillary nodal metastasis. 8 (20%) of the 40 patients had discordance in their receptor subtype expressed in their respective axillary nodal metastasis. 32 (80%) of the 40 patients had axillary receptor expression congruous to the primary tumor. At the time of our review, there was no statistically significant mortality between discordant compared to concordant group (13% vs 20%; p=0.54). 2 patients were lost to follow up. Conclusions: Our data suggests that one in every five axillary metastatic breast cancers can have receptor subtypes discordant compared to the receptors expressed on the primary tumor. Knowledge about any such discordance between the primary and respective axillary metastasis has a consequential impact on the treatment approach for early-stage breast cancer. This is especially true if the patient’s nodal metastatic lesions indeed prove HER2 receptor positivity or do not express any receptors (TNBC). Consequently, patients may be being deprived of benefits from advances in treatment of these cancers, such as targeted therapies towards HER2 receptor, hormonal treatments when indicated, or the utilization of neoadjuvant chemotherapy. A strong case can be thus made to revise current standards to include receptor testing on all primary and synchronous axillary metastasis. Further testing is needed to validate our findings.

PERIO-02: Phase 1b pressure enabled regional immuno-oncology trial of nelitolimod (SD-101), a class C TLR9 agonist, delivered via hepatic artery infusion +/- checkpoint inhibition in intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

2622 Background: Immunotherapy (ICI) has shown limited survival benefit in patients (pts) with advanced HCC and intrahepatic cholangiocarcinoma (ICC). Nelitolimod (SD-101), a Class C toll-like receptor-9 (TLR-9 agonist), depletes MDSCs while broadly stimulating the tumor microenvironment. Given safety challenges with IV infusion and distribution limitations of needle injection, we studied hepatic arterial infusion (HAI) of nelitolimod with Pressure-Enabled Drug Delivery (PEDD) to enhance ICI responsiveness. Methods: Pts with advanced HCC or ICC were enrolled. Nelitolimod was dose-escalated without ICI (Cohort A), with pembrolizumab (Cohort B), or with nivolumab + ipilimumab (Cohort C). Nelitolimod administered with HAI for 2 cycles, with 3 weekly doses per cycle using the TriNav device. Primary endpoints included safety and optimal dose determination. Immune cells were examined in blood and tumor tissue using multiplex IF, flow cytometry, and Nanostring. Results: At data cutoff, 29 pts [70% ICC, 30% HCC] were enrolled, 23 received at least one dose of nelitolimod: 3 in Cohort A (4 mg), 8 in Cohort B (2 and 4 mg) and 12 in Cohort C (2 and 4 mg). Median age was 64.5. Only 1 pt was treatment-naïve; 4, 2L (17%); 5, 3L (22%); 14, &gt; 4L (61%). 26% pts had &gt; 10 liver tumors. 3 pts (13%) experienced serious treatment-related adverse events (AE); 1 pt dose-limiting toxicity. Five pts experienced LFT elevations, most G1 with 2 reported as G3. In cohort A, 1 of 3 evaluable pts had SD as best on-treatment response. In cohort B, 1 of 4 evaluable pts had SD as best on-treatment response, others experienced PD by RECIST 1.1. In cohort C 2 mg, 2 of 5 had SD reported at Day 53. At 4 mg dose in cohort C, 3 of 3 pts had disease control, with one CR in the liver (5L ICC) and 2 SD. Decreases were noted in the target liver lesion (31.3 to 17.5 mm), non-target liver lesion, and extra-hepatic lymph nodes on days 53 and 84 with complete response of target liver lesions and stability of extra hepatic nodal lesions reported on Day 154. Median PFS in the Cohort C 4 mg dose level is &gt;120 days. Median OS for this group has not reached (range 120-170 days). Immune effects in cohort C 4 mg pts included increases in liver tumor CD4+ and CD8+ T cells, along with a decrease in the MDSC:CD8+ T cell ratio. Gene expression changes in cohort C 4 mg pts revealed increased Th1 programming in tumor tissue, with increased interferon, cytokine, TLR, Th1, and lymphocyte activation signals in surrounding normal liver. Changes among blood immune cells included increased IFNg and IL2-R expression, with decreased IL17A and VEGFA. Conclusions: HAI of nelitolimod has been well tolerated and associated with encouraging immunologic activity in HCC and ICC. Clinical and biologic activity in cohort C at 4mg is supportive of further enrollment in this cohort. Clinical trial information: NCT05220722 .

Options to apply national developments in the assessment of sentinel lymph node involvement in breast cancer

Background. Breast cancer is the leading oncopathology of women. The routine radical surgery performed in this pathology includes lymph node dissection, which provokes development of postmastectomy syndrome. However, the removal of non-metastatic lymph nodes is not rational according to the subsequent disability of the patients. This can be avoided by using a sentinel lymph node (SLN) biopsy procedure. At this stage of oncology development, there are several ways to visualize SLN. The fluorescent method is among the most promising. This technique has been used for many years. However, it is not sufficiently implemented in clinical practice. There are still several questions about the procedure for its performance. In addition, it requires the introduction and improvement of domestic developments, including reducing financial costs.Aim. To study the use of indocyanine green of domestic production (LLC Firm “FERMENT”, Russia) and the IC-GOR detection system (LLC “MedKomplekt”, Russia) for SLN biopsy in patients with early breast cancer.Materials and methods. From February to September 2023, biopsy of SLN using indocyanine green (LLC Firm “FERMENT”, Russia) was performed in 53 patients with early breast cancer without clinically detectable lesion of regional lymph nodes. In all cases, according to the clinical examination, the patients had an operable stage of breast cancer (cT1–3N0M0). 5 mg of indocyanine green, dissolved in 4 ml of water for injection, was administered after sanitizing of the surgical field intradermally and subcutaneously at 2 points in the upper-outer quadrant of the breast along the edge of the areola in 40 patients (75.5 %) or paratumorally in 13 patients (24.5 %). An incision in the axilla about 4 cm long was made no earlier than 10–15 minutes after injection of indocyanine green (when visualizing the track 1 cm beyond its distal end to avoid crossing the lymph duct, after which the drug can flow into the wound). After imaging, all detected lymph nodes were removed for planned morphological examination. Standard lymph node dissection of 1 and 2 level was performed in all patients. Middle age of patients was 64.5 years (from 37 to 85 year). In 40 patients (75.5 %) modified radical mastectomy was performed, breast conserving surgery was done in 13 cases (24.5 %).Results. SLN were visualized in 51 patients out of 53 (96.2 %). After the final morphological examination, the majority of patients in the group were ranged in the IA and IIA stages of the disease – 15 (28.3 %) and 28 (52.8 %), respectively. Metastasis in the SLN were found in 9 patients (17.0 %). Besides, in 3 cases (5.7 %) metastasis in the lymph nodes were found after lymph node dissection. In 4 cases (7.6 %) metastasis were found during lymph node dissection but were not detected in the removed SLN. Thus, in the study group 13 (24.5 %) patients had metastatic lymph node lesion despite negative clinical status. The total number of removed SLN in the study group was 169 (from 1 to 6), the average number of removed lymph nodes was 3.3. Any negative events, allergic and general reactions to indocyanine were not reported.Conclusion. Our technique of contrasting SLN with indocyanine green is adequate and reproducible. The frequency of detection of SLN with this method is 96.2 %, with an acceptable level of false negative results is 7.6 %. Indocyanine green (LLC Firm “FERMENT”, Russia) and the LED fluoroscopic cancer detector IC-GOR (LLC “MedKomplekt”, Russia) can be recommended for performing a SLN biopsy.

Pattern of recurrence after stereotactic body radiotherapy of nodal lesions: a single-institution analysis.

Stereotactic body radiotherapy (SBRT) and/or single fraction stereotactic body radiosurgery (SRS) are effective treatment options for the treatment of oligometastatic disease of lymph nodes. Despite the encouraging local control rate, progression-free survival remains unfair due to relapses that might occur in the same district or at other sites. The recurrence pattern analysis after nodal local ablative RT (laRT) in oligometastatic patients is presented in this study. The pattern of failure of patients with nodal metastases who were recruited and treated with SBRT in the Destroy-1 or SRS in the Destroy-2 trials was investigated in this single-institution, retrospective analysis. The different relapsed sites following laRT were recorded. Data on 190 patients who received SBRT or SRS on 269 nodal lesions were reviewed. A relapse rate of 57.2% (154 out of 269 nodal lesions) was registered. The pattern of failure was distant in 88 (57.4%) and loco-regional in 66 (42.6%) patients, respectively. The most frequent primary malignancies among patients experiencing loco-regional failure were genitourinary and gynaecological cancers. Furthermore, the predominant site of loco-regional relapse (62%) was the pelvic area. Only 26% of locoregional relapses occurred contra laterally, with 74% occurring ipsilaterally. The recurrence rates after laRT for nodal disease were more frequent in distant regions compared to locoregional sites. The most common scenarios for locoregional relapse appear to be genitourinary cancer and the pelvic site. In addition, recurrences often occur in the same nodal station or in a nodal station contiguous to the irradiated nodal site. Local ablative radiotherapy is an effective treatment in managing nodal oligometastasis. Despite the high local control rate, the progression free survival remains dismal with recurrences that can occur both loco-regionally or at distance. To understand the pattern of failure could aid the physicians to choose the best treatment strategy. This is the first study that reports the recurrence pattern of a significant number of nodal lesions treated with laRT.

Controversies in minimally invasive surgery for invasive cervical cancer

Background. Determination of the feasibility of performing minimally invasive surgery for invasive cervical cancer and identification of criteria for optimal surgical access that ensures safety, effectiveness, and satisfactory immediate and long-term results remain challenging in gynecological oncology. The aim of the study was to evaluate the immediate and long-term treatment outcomes in patients with invasive cervical cancer who underwent radical hysterectomy via laparotomy compared to those who underwent minimally invasive surgery. Material and methods. Treatment outcomes of 91 patients with invasive carvical cancer were analyzed. The assessment of the objective tumor response to neoadjuvant chemotherapy using the RECIST scale (Response Evaluation Criteria in Solid Tumors) was confirmed by clinical, ultrasound and CT/ MRI findings. The Kaplan-Maier curves and the log-rank criterion were used to compare the time of relapse-free and overall survivals. Statistical analysis and visualization of the analysis results were performed using prism 9.5.1 (GraphPad, USA). Results. The presence of parametrial lymphovascular space invasion and the frequency of lymphadenopathy were comparable for both groups of patients. there were no statistically significant differences in the number of the resected lymph nodes, but there was a statistically significant difference in volume of blood loss and the duration of surgery between the groups (p=0.0001). Every third patient was diagnosed with stage IIIC after surgery (pelvic lymph node lesion). Intraoperative complications were significantly lower in the laparoscopy group than in the laparotomy group (6.7 % vs 13 %). No significant differences in the proportion of relapses of the disease between the groups were found (9.6 % in the laparotomy group vs 11.7 % in the laparoscopy group). There were no significant differences in overall and relapse-free survival between the groups. Conclusion. Minimally invasive surgery is a promising and adequate surgical technique for the treatment of cervical cancer. However, additional studies are needed to determine the indications for these surgeries.

Necrosis plays a role in the concentration of mycobacterial antigens in granulomas from Mycobacterium bovis naturally infected cattle

The dynamics that develop between cells and molecules in the host against infection by Mycobacterium bovis, leads to the formation of granulomas mainly present in the lungs and regional lymph nodes in cattle. Cell death is one of the main features in granuloma organization, however, it has not been characterized in granulomatous lesions caused by M. bovis. In this study we aimed to identify the profiles of cell death in the granuloma stages and its relationship with the accumulation of bacteria. We identified necrosis, activated caspase-3, LC3B/p62 using immunohistochemistry and digital pathology analysis on 484 granulomatous lesions in mediastinal lymph nodes from 23 naturally infected cattle. Conclusions: greater amounts of mycobacterial antigens were identified in granulomas from calves compared with adult cattle. The highest percentage of necrosis and quantity of mycobacterial antigens were identified in granuloma stages (III/IV) from adults. The LC3B/p62 profile was heterogeneous in granulomas between adults and calves. Our data suggest that necrosis is associated with a higher amount of mycobacterial antigens in the late stages of granuloma and the development of autophagy appears to play an heterogeneous effector response against infection in adults and calves. These results represent one of the first approaches in the identification of cell death in the four stages of granulomas in bovine tuberculosis.

Abstract PS05-04: [89Zr]Trastuzumab-PET/MRI to Characterize HER2+ Breast Cancer: A Quantitative Approach on Tumor Heterogeneity

Abstract Introduction: Molecular imaging of human epidermal receptor 2 (HER2) aims to overcome limitations of traditional HER2 assessment through biopsy, including invasiveness and inability to detect intra and inter-tumoral spatial heterogeneity. Prior human studies suggest that [89Zr]Trastuzumab-positron emission tomography (PET) imaging can effectively differentiate HER2 lesions (Dehdashti et al, Breast Cancer Res. Treat. 2018). Commonly, CT complements PET for anatomical reference, however, integrating MRI enables the sensitivity of soft-tissue contrast required for anatomic and morphological breast imaging and can provide for quantitative multiparametric characterization. Diffusion weighted-MRI (DW-MRI) contributes to tumor characterization by assessing intratumoral cellularity via the apparent diffusion coefficient (ADC), and can be combined with molecular expression from HER2-PET. We present preliminary results in 13 patients with HER2 PET/MRI to define tumor and normal tissue imaging metrics. Methods: A phase II clinical trial assessing the feasibility of [89Zr]trastuzumab-PET with simultaneous quantitative DW-MRI to enhance understanding of tumor heterogeneity in patients with HER2-positive metastatic breast cancer. 13 patients (ages 40-70; mean 60) with HER2-positive breast cancer based on prior biopsy underwent whole-body [89Zr]trastuzumab-PET/MR imaging (5 ± 1 days post-injection of radiopharmaceutical) during the course of HER2-directed therapy. Normal organ and tumor regions of interest (ROI) were identified on concurrently acquired whole-body T1-weighted MRI for ADC (cellularity) and standardized uptake value (SUV, PET uptake) mean quantification. Tumor presence was confirmed via bone scintigraphy, FDG-PET/CT, or contrast-enhanced MRI. Non-parametric T-tests compared lesions to normal organs. Lesions greater than 30 mm in diameter underwent multiparametric intratumoral habitat analysis. Using the median HER2 values, tumors were evaluated for heterogeneity of high and low HER2 expression in conjunction with ADC. Long-term treatment response evaluation is ongoing. Results: Mean [89Zr]trastuzumab uptake, SUV, and ADC values for normal tissue were summarized in Table 1. All tumors demonstrated higher overall uptake of [89Zr]trastuzumab (bone: p=0.019, brain: p=0.014, breast: p=0.069, juxtapulmonary: p=0.026) and increased ADCmean values (bone: p=0.002, brain: p=0.5, breast: p=0.03, juxtapulmonary: p=0.037), in comparison to matched normal organs. Notably, one of five patients with a breast lesion, who completely responded to HER2 targeted therapy, exhibited the highest breast lesion SUVmean. Brain and lymph node lesions demonstrated intratumoral heterogeneity of HER2 expression. Conclusion: Our study demonstrates the potential value of quantitative MRI along with molecular imaging to characterize metastatic HER2+ breast cancer and evaluate intratumoral heterogeneity. We underscore the importance of standardizing processing techniques and contribute to this effort by summarizing [89Zr]trastuzumab uptake and cellularity values of normal physiological uptake. Higher SUVmean and ADC mean values observed in lesions, compared to normal tissue, highlight their potential roles in intratumoral classification. While studies have shown the utility of [89 Zr]trastuzumab-PET/CT, our findings demonstrate that integrated DW-MRI can aid in tumor classification. Table 1: Physiological 89Zr-Trastuzumab Uptake (SUVmean) and Apparent Diffusion Coefficient (ADCmean) in Healthy Tissues Citation Format: Ameer Mansur, Moozhan Nikpanah, Johnathan McConathy, Erica Stringer-Reasor, Gabrielle Rocque, Ahmed Elkhanany, Katia Khoury, Nusrat Jahan, Suzanne Lapi, Anna Sorace. [89Zr]Trastuzumab-PET/MRI to Characterize HER2+ Breast Cancer: A Quantitative Approach on Tumor Heterogeneity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-04.

New classifications of malignant lymphomas - What changes are relevant for practice?

An internationally uniform lymphoma classification is of fundamental importance for the comparability of clinical studies. There are currently 2 parallel classifications: the "International Consensus Classification" and the WHO-classification. Follicular lymphoma 3B is classified separately as follicular large cell lymphoma in WHO-HAEM5. The diagnostic criteria of lymphoplasmocytic lymphoma (LPL) have been adjusted, both classifications recommend molecular testing for MYD88 and CXCR4 mutations. There are no significant diagnostic changes in aggressive B-cell lymphomas. The ICC classify NLPBL and THRLBCL into the group of large B-cell lymphomas (LBCL). NLPHL/NLPBL-specific therapy must be considered, which differs greatly from the therapy of DLBCL, especially in the early stages. Peripheral T-cell lymphomas are a group of nodal T-cell lymphomas with a TFH phenotype and frequent mutations; peripheral T-cell lymphoma (NOS) is therefore a diagnosis of exclusion. Indolent T-cell lymphomas/lymphoproliferations of the GI tract are rare but must be differentiated from aggressive T-cell lymphomas. The WHO-HAEM5 also includes reactive/non-neoplastic lymph node lesions classified according to B or T cell predominance.

The Utilisation of Fine Needle Aspiration Cytology for Diagnosis of Head and Neck Lesions in Paediatric Age Group

The Utilisation of Fine Needle Aspiration Cytology for Diagnosis of Head and Neck Lesions in Paediatric Age Group

APPLICATION VALUE OF CT INDEXES COMBINED WITH TUMOR MARKERS AND 7-TAAB IN THE DIAGNOSIS OF INVASIVE LUNG CANCER BASED ON IMPROVED ARTIFICIAL INTELLIGENCE TECHNOLOGY

Objective: To investigate the efficacy of artificially intelligent CT metrics combined with tumor markers and 7-TAABs in predicting the infiltrative nature of mixed ground-glass nodules in the lungs to provide a basis for rational clinical decision-making. Materials and Methods: The clinical data of patients admitted to Changshu Hospital affiliated with Soochow University (Hospital 1) and the Eighth People’s Hospital of Tongzhou District, Nantong City (Hospital 2) from January 2022 to June 2023 were retrospectively analyzed, and a total of 427 cases were included in the study based on the nadir criteria. Three hundred twenty cases from Hospital 1 were randomly grouped into a training set ([Formula: see text]) and an internal validation set ([Formula: see text]), and 107 cases from Hospital 2 were used for the external validation set. The correlations between patients’ clinicoradiological characteristics, tumor markers, and seven tumor autoantibodies (7-TAABs) were analyzed by the Mantel test and further by univariate and multivariate logistic regression analyses to screen the risk factors for the development of infiltrative tumors in the ground-glass nodes and to establish a joint model, which was combined with the clinicoradiological model and the model of the serological indexes in the internal and external validation sets were performed to compare the subject work characteristics (ROC) curves, clinical calibration curves, and clinical decision curves to evaluate their predictive efficacy and clinical utility. Results: Of the 427 cases included, 174 were in the noninfiltrating group, and 253 were in the infiltrating group. There was a significant relationship between tumor markers, seven tumor autoantibodies, and lung cancer infiltrability, and after multifactorial logistic regression analysis, a bronchial air sign, probability of malignancy, nodule diameter, percentage of solidity, VEGF, proGRP, GAGE7, and 7-TAABs were the risk factors for determining the development of infiltrative lesions in early-stage lung nodules. The clinicoradiological model was superior to the serological index model on both internal and external validation sets (AUC values were: 0.926 versus 0.839, [Formula: see text]; 0.895 versus 0.751, [Formula: see text]), and the combined model was slightly superior to the clinicoradiological model on both internal and external validation sets (AUC values were: 0.928 versus 0.926, [Formula: see text]; 0.914 versus 0.895, [Formula: see text]). The combined model performed optimally in terms of calibration accuracy and net clinical benefit, suggesting that a model constructed based on AI CT metrics combined with tumor markers and 7-TAABs would be beneficial to clinicians in predicting the infiltrative nature of early-stage lung cancer. Conclusion: The column-line diagram model built based on CT indexes improved by artificial intelligence technology combined with tumor markers and 7-TAAB can better predict the infiltration of lung tumors, which has specific clinical application value.

Third national surgical consensus conference of the Italian Association of Breast Surgeons (ANISC) on management after neoadjuvant chemotherapy: The difficulty in reaching a consensus

IntroductionNeoadjuvant chemotherapy (NAC) has a profound impact on surgical management of breast cancer. For this reason, the Italian Association of Breast Surgeons (ANISC) promoted the third national Consensus Conference on this subject, open to multidisciplinary specialists. Materials and methodsThe Consensus Conference was held on-line in November 2022, and after an introductory session with five core-team experts, participants were asked to vote on eleven controversial issues, while results were collected in real-time with a polling system. ResultsA total of 164 dedicated specialists from 74 Breast Centers participated. Consensus was reached for only three of the eleven issues, including: 1) the indication to assess the response with Magnetic Resonance Imaging (79 %); 2) the need to re-assess the biological factors of the residual tumor if present (96 %); 3) the possibility of omitting a formal axillary node dissection for cN1 patients if a pathologic Complete Response (pCR) was confirmed with analysis of one or more sentinel lymph nodes (82 %). The majority voted in favor of mapping both the breast and nodal lesions pre-NAC (59 %), and against the omission of sentinel lymph node biopsy in cN0 patients in the case of pathologic or clinical Complete Response (69 %). In cases of cT3/cN1+ tumors with pCR, only 8 % of participants considered appropriate the omission of Post-Mastectomy Radiation Therapy. ConclusionThere is still a wide variability in surgical approaches after NAC in the “real world”. As NAC is increasingly used, multidisciplinary teams should be attuned to conforming their procedures to the rapid advances in this field.

RECIST 1.1 versus clinico-radiological response assessment for locally advanced cervical cancer: implications on interpreting survival outcomes of future trials

OBJECTIVETo investigate differences in standard clinico-radiological evaluation versus Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for reporting survival outcomes in patients with locally advanced cervical cancer treated with chemoradiation...

Enhancements in Radiological Detection of Metastatic Lymph Nodes Utilizing AI-Assisted Ultrasound Imaging Data and the Lymph Node Reporting and Data System Scale.

The paper presents a novel approach for the automatic detection of neoplastic lesions in lymph nodes (LNs). It leverages the latest advances in machine learning (ML) with the LN Reporting and Data System (LN-RADS) scale. By integrating diverse datasets and network structures, the research investigates the effectiveness of ML algorithms in improving diagnostic accuracy and automation potential. Both Multinominal Logistic Regression (MLR)-integrated and fully connected neuron layers are included in the analysis. The methods were trained using three variants of combinations of histopathological data and LN-RADS scale labels to assess their utility. The findings demonstrate that the LN-RADS scale improves prediction accuracy. MLR integration is shown to achieve higher accuracy, while the fully connected neuron approach excels in AUC performance. All of the above suggests a possibility for significant improvement in the early detection and prognosis of cancer using AI techniques. The study underlines the importance of further exploration into combined datasets and network architectures, which could potentially lead to even greater improvements in the diagnostic process.