Metastatic Soft Tissue Research Articles

Characterization of A Bronchoscopically Induced Transgenic Lung Cancer Pig Model for Human Translatability.

There remains a need for animal models with human translatability in lung cancer (LC) research. Findings in pigs have high impact on humans due to similar anatomy and physiology. We present the characterization of a bronchoscopically-induced LC model in Oncopigs carrying inducible KRAS G12D and TP53 R167H mutations. Twelve Oncopigs underwent 29 injections via flexible bronchoscopy. Eighteen Adenovirus-Cre recombinase gene (AdCre) inductions were performed endobronchially (n=6) and transbronchially with a needle (n=12). Eleven control injections were performed without AdCre. Oncopigs underwent serial contrast-enhanced chest CT with clinical follow-up for 29 weeks. Following autopsy, lung and organ tissues underwent histopathology, immunohistochemistry, and RNA-sequencing with comparative analysis with The Cancer Genome Atlas (TCGA) human LC data. All 18 sites of AdCre injections had lung consolidations on CT imaging. Transbronchial injections led to histopathologic invasive cancer and/or carcinoma in situ (CIS) in 11/12 (91.7%), and invasive cancer (excluding CIS) in 8/12 (66.6%). Endobronchial inductions led to invasive cancer in 3/6 (50%). A soft tissue metastasis was observed in one Oncopig. Immunohistochemistry confirmed expression of Pan-CK+/epithelial cancer cells, with macrophages and T cells infiltration in the tumor microenvironment. Transcriptome comparison showed 54.3% overlap with human LC (TCGA), in contrast to 29.88% overlap of KRAS-mutant mouse LC with human LC. The transgenic and immunocompetent Oncopig model has a high rate of LC following bronchoscopic transbronchial induction. Overlap of the Oncopig LC transcriptome with human LC transcriptome was noted. This pig model is expected to have high clinical translatability to the human LC patient.

Laparoscopic-Assisted, Percutaneous Cryoablation: A Novel Technique for the Treatment of Abdominal Wall Soft Tissue Tumors.

Percutaneous cryoablation is a first-line therapeutic option for primary neoplasms and metastatic lesions of the musculoskeletal system. Treatment of abdominal wall tumors is challenging as surgical resection can be highly morbid and necessitate complex reconstructive surgery; the efficacy of cryoablation for abdominal wall tumors may be limited by inadequate posterior margins owing to the proximity of intra-abdominal organs. With laparoscopy and insufflation, peritoneal structures can be safely mobilized away from the abdominal wall, allowing for adequate deep margin freeze and visualization of the ice ball. We present two patients with abdominal wall soft tissue tumors treated with a novel approach of laparoscopic-assisted, percutaneous ultrasound-guided cryoablation. Patient 1 is a 65-year-old female with metastatic extraskeletal myxoid chondrosarcoma, stable on systemic therapy, who presented with a new soft tissue metastasis to the abdominal wall. Resection would have necessitated a highly morbid complex abdominal wall reconstruction with mesh. Patient 2 is a 35-year-old female with a large abdominal wall desmoid tumor, diagnosed after miscarriage. Resection was relatively contraindicated owing to the morbidity of a complex abdominal wall reconstruction and concerns regarding potential future pregnancies after surgery. Both patients underwent procedures in the outpatient setting after discussion at multidisciplinary sarcoma tumor board. Laparoscopic enterolysis was performed to mobilize the bowel away from the abdominal wall, to allow direct visualization of the peritoneal aspect of the tumor, and to confirm adequacy of the posterior margin freeze of the lesion. Laparoscopic transversus abdominus preperitoneal (TAPP) blocks with local anesthetic were performed for postoperative pain control. Interventional radiology performed an ultrasound-guided cryoablation consisting of two freeze and thaw cycles. Both patients recovered well without complications and were without radiographic evidence of persistent or recurrent disease at 12 and 18 months postoperatively, respectively. We report a novel approach of laparoscopic-assisted cryoablation for the treatment of abdominal wall soft tissue tumors. This allowed for successful minimally invasive local control of these large tumors that would have otherwise required highly morbid resections with complex abdominal wall reconstruction and mesh repair.

S2821 A Rare Case of Colon Cancer With Hepatic Metastasis and Soft Tissue Metastasis to the Breast

S2821 A Rare Case of Colon Cancer With Hepatic Metastasis and Soft Tissue Metastasis to the Breast

Long-term survival after metasectomy in patients with bone or soft-tissue metastases from renal cell carcinoma.

227 Background: Renal cell carcinoma (RCC) is reported to be associated with long-term survival, and surgical resection is now recommended in patients with metastatic lesions. This study evaluated the long-term outcome of surgery for bone or soft tissue metastases from RCC. Methods: Between 1993 and 2014, 58 patients (46 men and 12 women) underwent surgery, excluding palliative surgery, for bone or soft tissue metastatic lesions from RCC at our institution. These patients were retrospectively evaluated for factors associated with prognosis by using the log-rank test and Cox proportional hazards analysis. Results: The patients’ mean age was 60 years, and the mean follow-up period was 52 months. The surgical sites included the spine (33 patients), limb bone (10 patients), pelvis (8 patients), thoracic bone (4 patients), and soft tissue (3). The surgical procedures were total en bloc spondylectomy (TES) in 33 patients, wide excision in 13 (6 of them were also treated with prosthesis), and curettage and bone grafts in 12 (4 of them were treated with internal fixation). The 3-, 5-, 10-, and 15-year overall survival (OS) rates were 75%, 62%, 48%, and 25%, respectively. According to the surgical methods, the 5-year OS was 64% for TES, 62% for wide excision, and 46% for curettage and bone grafts. According to the surgical site, the median survival time was 127 months for the spine, 140 months for the limb bone, and 54 months for the pelvis. In multivariate analysis, preoperative lung metastasis and the pathological type, except for clear cell carcinoma, were independent risk factors for poor prognosis. However, age, performance status, Motzer classification, and abnormal blood test results were not significant risk factors. Conclusions: Our findings suggest that the surgical resection of bone and soft tissue metastatic lesions from RCC is a favorable option for improving prognosis even in patients with unfavorable conditions such as an advanced age or poor performance status. Now that treatment outcomes for renal cell carcinoma are improving, bone metastases can be treated with surgery.

45 INTerpath-004: A phase 2, randomized, double-blind study of pembrolizumab with V940 (mRNA-4157) or placebo in the adjuvant treatment of renal cell carcinoma

Abstract Background The PD-1 inhibitor pembrolizumab is approved as monotherapy for the adjuvant treatment of patients with renal cell carcinoma (RCC) who are at increased risk of recurrence following nephrectomy or nephrectomy and resection of metastatic lesions based on results from the phase 3 KEYNOTE-564 trial. Novel combination strategies could provide further clinical benefit in the adjuvant setting. V940 (mRNA-4157) is an individualized neoantigen therapy that is hypothesized to increase the antitumor activity of T cells and enhance the activity of pembrolizumab. V940 plus pembrolizumab showed improved clinical outcomes for stage III/IV melanoma compared with pembrolizumab alone in the phase 2b KEYNOTE-942 study. INTerpath-004 is a global, multicenter, randomized, double-blind, phase 2 trial (NCT06307431) designed to evaluate the efficacy and safety of adjuvant pembrolizumab with V940 or placebo in patients with RCC who have undergone nephrectomy. Methods Eligible patients are adults with histologically or cytologically confirmed RCC with clear cell or papillary histology (intermediate-high risk [pT2 Gr4, N0, M0 or pT3 Gr3/4, N0, M0], high-risk [pT4, N0, M0 or pT any stage, N1, M0], or M1 NED [solid, isolated, soft tissue metastases that can be completely resected at the time of nephrectomy or ≤2 years from nephrectomy]) with or without sarcomatoid features. Patients must have undergone nephrectomy and/or metastasectomy ≤12 weeks prior to randomization and be tumor-free as assessed by investigator. Patients must not have received prior systemic therapy ≤4 weeks or radiotherapy ≤2 weeks prior to randomization. Approximately 272 patients will be randomly assigned 1:1 to receive pembrolizumab 400 mg intravenously every 6 weeks for up to 9 cycles in combination with either V940 1 mg or placebo intramuscularly every 3 weeks for up to 9 doses or treatment discontinuation due to unacceptable toxicity, disease recurrence, patient withdrawal, or investigator decision. Randomization will be stratified by histology (clear cell vs papillary) and disease risk (intermediate-high vs high vs M1 NED). Imaging assessments (computed tomography or magnetic resonance imagery) will be performed every 12 weeks through year 2, every 16 weeks in years 3-5, and every 24 weeks in year 6 and beyond. The primary endpoint is disease-free survival by investigator assessment. Secondary endpoints include distant metastasis-free survival, overall survival, and safety parameters including adverse events (AEs), laboratory test results, and vital signs. AEs will be monitored throughout the study and for 30 days after the last dose of treatment (90 for serious AEs) and graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Efficacy will be assessed in all randomly assigned patients, and safety will be assessed in all patients who received ≥1 dose of study intervention. Recruitment is ongoing.

Clinical efficacy and prognostic factors of CT-guided radioactive iodine-125 seed implantation for the treatment of superficial soft tissue metastasis: a 12-year retrospective analysis

BackgroundSuperficial soft tissue metastasis (S-STM) of malignant tumors is uncommon and often brings great pain to patients. However, current treatment options are limited. The purpose of this study was to explore the clinical efficacy and prognostic factors of CT-guided radioactive iodine-125 (125I) seed implantation (RISI) for the treatment of S-STM.MethodsWe retrospectively evaluated 132 patients with S-STM who received RISI between June 2010 and July 2022. Local tumor progression-free survival (ltPFS), tumor response, pain control and complication were analyzed. The independent factors affecting ltPFS were screened out using a layered Cox proportional hazards model.ResultsThe median follow-up time was 8.3 months (interquartile range [IQR], 4.5–15.3 months). The objective response rate (ORR) was 81.8%. The median ltPFS was 9.1 (95% CI: 6.6, 11.6) months. The Cox proportional hazard regression model revealed that the independent factors influencing ltPFS included KPS score, primary tumor, metastases, boundary, density and postoperative D90 (All P < 0.05). After RISI, the rate of pain relief was 92.3%. 66 (84.6%) patients reported pain marked relief, and 6 (7.7%) experienced pain moderate relief. No severe adverse events associated with RISI were observed during follow-up.ConclusionsCT-guided RISI was associated with high local control and pain relief without severe adverse events and should be considered as a reliable palliative treatment modality for S-STM.Trial registrationTrial registration Retrospectively registered.

Metastatic extraneural glioblastoma diagnosed with molecular testing.

Glioblastoma, the most common malignant brain tumor in adults, is associated with a median overall survival duration of less than 2 years. Extraneural metastases occur in less than 1% of all patients with glioblastoma. The mechanism of extraneural metastasis is unclear. We present a case of extensive extraneural, extraosseous, epidural, and soft-tissue metastasis of glioblastoma. The diagnosis of metastatic glioblastoma was made only after next-generation sequencing (NGS) of the metastatic paraspinal lesions was completed. The CDK4, pTERT, PTEN, and TP53 molecular alterations seen in the initial intracranial glioblastoma were found in the paraspinal tumor, along with the addition of MYC, which is implicated in angiogenesis and epidermal-to-mesenchymal transition. Immunohistochemical stains showed that neoplastic cells were negative for GFAP. In conclusion, this case raises awareness about the role of NGS in the diagnosis of extraneural glioblastoma. This diagnosis was not possible with histology alone and only became evident after molecular profiling of the metastatic lesions and its comparison to the original tumor.

A first-in-human phase 1 trial of T cell membrane-anchored tumor targeted IL12 (ATTIL12) -T cell therapy in advanced/metastatic soft tissue and bone sarcoma.

TPS11586 Background: Interleukin-12 (IL12) is a cytokine that induces antitumor immune response and immune memory by activation of NK cells, induction of IFNg, and maturation of DC cells in the tumor microenvironment (TME). However, prior clinical experience with IL12 has been limited by toxicities including cytokine release syndrome (CRS) and hepatotoxicity. We developed a novel tumor-targeted IL12 gene (ttIL12) that encodes the p35 and p40 VNTANST fusion subunits that targets cell surface vimentin (CSV). Vimentin is expressed intracellularly in many normal and neoplastic mesenchymal cells but our group discovered that intracellular vimentin is often flipped to the cell surface (referred to as CSV) across multiple tumor types.2 Preclinical studies demonstrated efficacy and induction of long-term memory of ttIL12 against metastatic osteosarcoma with reduced toxicity in immune competent models.3 However, ttIL12 had limited efficacy in treating large volume tumors and did not completely eliminate toxic peripheral cytokines. To address this, our team generated a membrane anchored ttIL12 to arm T cells known as attIL12-T cell therapy. We hypothesize attIL12 will minimize toxic cytokines in peripheral tissues but promote induction of INFg/TNFa in the TME to decrease the toxicity and boost efficacy. Methods: This is a phase 1 trial of attIL12-T cells in patients (pts) with locally advanced or metastatic soft tissue or bone sarcomas to assess safety, maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D). Pts in part A (dose finding) will be enrolled using a Bayesian optimal interval (BOIN) design in up to 6 dose levels. Part B (dose expansion) will evaluate preliminary efficacy in 10 additional pts with osteosarcoma treated at the RP2D. Treatment:Pts will undergo leukapheresis to collect peripheral blood mononuclear cells (PBMCs) for generation of attIl12-T cells. Bridging therapy is permitted but not required. Pts will receive cyclophosphamide (Cy) IV prior to planned T cell administration. attIL12 T cells will be administered at the specified dose level IV in a single infusion (dose level 1 and 2) or 2 serial doses (dose level 3-6) on day 0 and day 14. Pts will be monitored for toxicity and response evaluation. Pts will also undergo pre-treatment/on-treatment tumor biopsies for translational and correlative analysis. Eligibility:Pts must be ≥ 12 years of age, have a confirmed diagnosis of locally advanced or metastatic sarcoma, evaluable disease, received at least 1 prior line of standard systemic therapy, ECOG PS 0-1, and adequate organ function to tolerate immune-effector cell therapy. Pts with known sensitivity to Cy, active/prior autoimmune disease, uncontrolled CNS disease, or other uncontrolled comorbidities that pose potential safety risk will be excluded. Enrollment to cohort 1 began in Dec 2023. Clinical trial information: NCT05621668 .

Early signs of efficacy in patients with anti-PD-1 naïve and anti-PD-1 resistant HNSCC treated with NBTXR3/SBRT in combination with nivolumab or pembrolizumab in the phase I trial Study 1100.

6035 Background: Overcoming resistance to immune checkpoint inhibitors (ICIs) is a major clinical challenge. NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide nanoparticles administered by a single intratumoral injection, locally amplifies radiotherapy (RT) dose without adding toxicity to surrounding healthy tissue. NBTXR3/RT enhances tumor cell death, tumor antigen release, and effectively expands T-cell repertoire in preclinical models, thus potentially triggering local and systemic immune responses to help improve ICI treatment. NBTXR3 has demonstrated favorable local control in pts with LA-HNSCC. Here we report early outcomes from the ongoing Study 1100 trial in pts with locoregionally recurrent (LRR) or metastatic (M+) head &amp; neck squamous cell carcinoma (HNSCC) who were either naïve to or who continued anti-PD-1 therapy combined with NBTRX3/RT after primary or secondary resistance to anti-PD-1 alone. Methods: A phase I dose escalation/expansion trial [NCT03589339] evaluating NBTXR3/Stereotactic Body RT (SBRT) followed by nivolumab or pembrolizumab in 3 cohorts of pts with advanced solid tumors. Pts have H&amp;N lesions either resistant to prior ICI or naïve, or lung, liver, or soft tissue metastases from ICI-resistant advanced solid tumors. SBRT doses were: HN 35 Gy/ 5 fxns; lung 45 Gy/ 5 fxns; liver 45 Gy/ 3 fxns; soft tissue as per investigator. Primary objective is safety of NBTXR3/RT/anti-PD-1 combination and its RP2D. Secondary objectives include efficacy. Results: The RP2D was 33%. There were 55 pts with HNSCC treated in the dose escalation/expansion parts. NBTXR3 injection was feasible and safe. There were 11pts (20%) who experienced G≥3 treatment related AEs, of which 3 pts experienced G≥3 AEs (5.5%) related to NBTXR3. Preliminary results of 33 pts, who were evaluable for efficacy: are reported. 6 pts with LRR disease: (2 ICI resistant, 4 naïve);. 27 pts with M+ disease (18 ICI resistant, 9 naïve). In ICI-resistant pts, objective tumor responses were observed in 25% (5/20), and the disease control rate (DCR) was 75% (15/20). In the ICI-naïve population, objective tumor responses were observed in 54% (7/13) of pts and DCR was 77% (10/13). There were observed improvements in injected lesions as well as in some noninjected target lesions. Updated efficacy data including OS in resistant and naïve pts will be presented. Conclusions: NBTXR3/RT/anti-PD-1 combination was feasible and well tolerated. Early data suggest the addition of NBTXR3/RT to ICI showed evidence of efficacy, including in patients who failed prior ICI, opening up an opportunity to further explore the ability of NBTXR3/RT to mitigate primary or secondary resistance to ICI. Clinical trial information: NCT03589339 .

First-line therapy for metastatic uveal melanoma: Experience from a single reference center.

e21514 Background: Metastatic uveal melanoma (mUM) continues to have a poor prognosis with distinct biology from cutaneous melanoma and limited effective treatment options. The main options include immunotherapy (IT, anti-PD-1+/- anti-CTLA-4, tebentafusp), chemotherapy, targeted therapy and local treatment methods for patients with isolated liver metastasis (isolated hepatic perfusion, transarterial chemoembolization, percutaneous hepatic perfusion, radiofrequency ablation). Methods: We conducted a single-center retrospective observation IRB-approved study of first-line therapy for pts age 18 and older with mUM treated at the N.N. Blokhin National Medical Research Center of Oncology from 2020 to 2023. Our objectives were to evaluate clinical outcomes in real-world settings, as well as treatment patterns, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Results: A total of 125 pts included. The mean age was 54 yrs (range: 20-74), and the median time to metastasis from primary tumor was 2 years (range: 0-21). Liver metastases were diagnosed in 92% of patients, lung metastases in 20%, bone metastases in 17%, and soft tissue metastases in 9%. Conclusions: Our data suggest that the combination of systemic and local liver-directed treatment methods may be associated with a survival benefit and higher treatment response to IT in patients with mUM. [Table: see text]

Improving assessment of lesions in longitudinal CT scans: a bi-institutional reader study on an AI-assisted registration and volumetric segmentation workflow

PurposeAI-assisted techniques for lesion registration and segmentation have the potential to make CT-based tumor follow-up assessment faster and less reader-dependent. However, empirical evidence on the advantages of AI-assisted volumetric segmentation for lymph node and soft tissue metastases in follow-up CT scans is lacking. The aim of this study was to assess the efficiency, quality, and inter-reader variability of an AI-assisted workflow for volumetric segmentation of lymph node and soft tissue metastases in follow-up CT scans. Three hypotheses were tested: (H1) Assessment time for follow-up lesion segmentation is reduced using an AI-assisted workflow. (H2) The quality of the AI-assisted segmentation is non-inferior to the quality of fully manual segmentation. (H3) The inter-reader variability of the resulting segmentations is reduced with AI assistance.Materials and methodsThe study retrospectively analyzed 126 lymph nodes and 135 soft tissue metastases from 55 patients with stage IV melanoma. Three radiologists from two institutions performed both AI-assisted and manual segmentation, and the results were statistically analyzed and compared to a manual segmentation reference standard.ResultsAI-assisted segmentation reduced user interaction time significantly by 33% (222 s vs. 336 s), achieved similar Dice scores (0.80–0.84 vs. 0.81–0.82) and decreased inter-reader variability (median Dice 0.85–1.0 vs. 0.80–0.82; ICC 0.84 vs. 0.80), compared to manual segmentation.ConclusionThe findings of this study support the use of AI-assisted registration and volumetric segmentation for lymph node and soft tissue metastases in follow-up CT scans. The AI-assisted workflow achieved significant time savings, similar segmentation quality, and reduced inter-reader variability compared to manual segmentation.

Correlations between the modification patterns mediated by pyroptosis-related genes, tumor microenvironment, and immunotherapy in soft tissue sarcoma.

Soft tissue sarcoma (STS) incidence, progression, and metastasis are tightly linked to the tumor microenvironment (TME). The modification patterns mediated by pyroptosis-related genes (PRGs) in STS are unknown regarding the immune cell infiltration landscape of TME, immunotherapy effect, and prognostic value. First, we downloaded STS samples from the Cancer Genome Atlas (TCGA) and gene-expression omnibus (GEO) databases. Based on 52 PRGs, 2 pyroptosis modification patterns were analyzed, and the associations of pyroptosis modification patterns with immune cell infiltration in the TME were elucidated systematically. To quantify PRG modification patterns in STS patients, we generated a pyroptosis scoring system using principal component analysis (PCA). We identified 2 distinct pyroptosis modification patterns in STS. Compared to PRG cluster A, the prognosis of cluster B was better. These 2 pyroptosis modification patterns corresponded to different characteristics of immune cell infiltration in the TME and biological behaviors. In the pyroptosis scoring system, a high pyroptosis score was connected to higher immune cell infiltration, stronger immune surveillance, immune-killing effects on tumor cells, and better clinical benefits. The results from 3 anti-PD1/PD-L1-treated immune cohorts demonstrated that higher pyroptosis scores are also closely connected to better immunotherapy results. We demonstrated that pyroptosis modification is essential to the STS microenvironment. Moreover, the pyroptosis score is a reliable and independent prognostic factor in STS patients, enabling a richer understanding of the STS microenvironment and the screening of immunotherapy candidates, predicting the immunotherapeutic effects for individual STS patients, and guiding the use of chemotherapy drugs.

The role of IL-1B in breast cancer bone metastasis

Interleukin-1B (IL-1B) is a potent pro-inflammatory cytokine that plays multiple, pivotal roles, in the complex interplay between breast cancer cells and the bone microenvironment. IL-1B is involved in the growth of the primary tumours, regulation of inflammation within the tumour microenvironment, promotion of epithelial to mesenchymal transition (EMT), migration and invasion. Moreover, when breast cancer cells arrive in the bone microenvironment there is an upregulation of IL-1B which promotes the creation of a conducive niche for metastatic breast cancer cells as well as stimulating initiation of the vicious cycle of bone metastasis. Pre-clinical studies have demonstrated that inhibition of IL-1 signalling reduces bone metastasis from oestrogen receptor positive/triple-negative breast cancers in various mouse models. However, effects on primary tumours and soft tissue metastasis remain controversial with some studies showing increased tumour growth in these sites, whilst others show no effects. Notably, combining anti-IL-1 therapy with standard-of-care treatments, such as chemotherapy and immunotherapy, has been demonstrated to reduce the growth of primary tumours, bone metastasis, as well as metastatic outgrowth in other organs. This review focuses on the mechanisms by which IL-1B promotes breast cancer bone metastasis.

Clinical features of patients with carcinoma soft tissue metastases as surgical indications: a retrospective cohort study

BackgroundSoft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma.MethodsIn this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed.ResultsThe primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery.ConclusionOverall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients.

Abstract PO5-20-07: A Case of Metastatic Breast Cancer to Soft Tissue of the Thigh

Abstract Breast cancer is the most diagnosed cancer in women worldwide. The predominant cause of breast cancer mortality is metastatic disease with bone, lung, liver and brain being most common sites of metastasis. After melanoma, breast cancer is the most common cancer to have cutaneous metastatic disease and this presentation represents half of all cutaneous metastases. We are presenting a case of a 70-year-old female with distant recurrence of breast cancer to the left thigh. A 70-year-old female presented to clinic with a palpable left breast mass noted July 2022. Her medical history was notable for right sided upper lobe stage IIIB squamous cell lung cancer diagnosed in 2013 treated with chemotherapy and chest radiation (RT), menopause at 25 years old following TAH/BSO for fibroids. Family history included prostate cancer and genetic testing was negative for pathogenic mutation. Diagnostic mammogram showed a lesion in the left breast at 9:00 of 1.4 cm x 1.2 cm x1.4 cm, and biopsy showed grade 3 triple negative invasive ductal carcinoma (IDC). Her nodes were clinically and radiologically negative. She opted for breast conservation. In September of 2020 the patient had a left lumpectomy with sentinel lymph node biopsy. Final pathology (path) was pT1cN0 with two foci of IDC, grade 3, measuring 1.9 × 1.9 × 1.1 cm and 0.4 × 0.2 × 0.2 cm with negative margins. Two sentinel lymph nodes were negative for carcinoma. She received 4 cycles of doxorubicin and cyclophosphamide and started paclitaxel, but only completed 5/12 planned cycles. During these treatment cycles she was admitted twice for shortness of breath and found to have an exudative pleural effusion, repeat cytology was negative for malignancy at which point fluid did not recur. There was no CT evidence of lung nodules or plural thickening. Echocardiogram showed normal ejection fraction of 45%. PET scan was negative. Chemotherapy was stopped in February of 2021. Initial pre-operative discussion with radiation oncology indicated no contraindication to adjuvant RT. However, after simulation, it was deemed by radiation oncology that the patient was no longer a candidate for RT as during her lung cancer treatment, she had received RT of 69.4 Gy including the area of the current lumpectomy cavity. She then opted for bilateral mastectomy with immediate reconstruction in June 2021. Final path from both breasts showed no carcinoma. In November of 2021 she was admitted for shortness of breath and on CT scan was noted to have a left sided lung nodule. The patient declined biopsy and underwent a left wedge resection in January of 2022. Final path showed a 2.2. cm carcinoma consistent with breast primary that was ER 0, PR 0, and Her 2 neu 1+. She was started on capecitabine with plan for 6 months of treatment but stopped taking this after one month due to severe pain in her hands and feet. In November 2022 the patient noted a left thigh mass. Exam showed a firm, palpable thigh mass without overlying skin changes and core needle biopsy showed adenocarcinoma, favoring breast primary, ER 0, PR 0, HER 2 neu 2+ and FISH negative. PET scan showed no uptake in the chest abdomen or pelvis, however a 2.6 × 2.3 × 3.1 cm round mass in the left thigh was seen with SUV max of 8.6. She was started on traztuzumab-deruxtecan by medical oncology in December of 2022. The thigh tumor shrank significantly, however, patient discontinued after two infusions, citing intolerable hand weakness. She then received RT to the thigh. She was treated using 3D technique and 6 MV photons for a total dose of 5400 cGY, from February to March of 2023. Repeat PET June 2023 showed no avid uptake in the thigh. She has declined any additional systemic therapy. Soft tissue metastasis in distant recurrent breast cancer is uncommon and little guidance exists on clinical management. In cases of metastatic disease to the skin, hormone positive lesions can be managed with hormonal therapy. Early detection and biopsy for receptor studies may help guide therapy in cases of distant soft tissue recurrence. Citation Format: Rangel Melissa, Julia Alexieva, Alison Coogan, Lily Hussein, Elizabeth Marcus, Julie Wecsler. A Case of Metastatic Breast Cancer to Soft Tissue of the Thigh [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 PO5-20-07.

2461: Palliative radiotherapy to metastases in soft tissue: patient reported outcome

2461: Palliative radiotherapy to metastases in soft tissue: patient reported outcome

MR-guided stereotactic radiotherapy of infra-diaphragmatic oligometastases: Evaluation of toxicity and dosimetric parameters

Background and purposeThe SOFT trial is a prospective, multicenter, phase 2 trial investigating magnetic resonance (MR)-guided stereotactic ablative radiotherapy (SABR) for abdominal, soft tissue metastases in patients with oligometastatic disease (OMD) (clinicaltrials.gov ID NCT04407897). We present the primary endpoint analysis of 1-year treatment-related toxicity (TRAE). Materials and methodsPatients with up to five oligometastases from non-hematological cancers were eligible for inclusion. A risk-adapted strategy prioritized fixed organs at risk (OAR) constraints over target coverage. Fractionation schemes were 45–67.5 Gy in 3–8 fractions. The primary endpoint was grade ≥ 4 TRAE within 12 months post-SABR. The association between the risk of gastrointestinal (GI) toxicity and clinical and dosimetric parameters was tested using a normal tissue complication probability model. ResultsWe included 121 patients with 147 oligometastatic targets, mainly located in the liver (41 %), lymph nodes (35 %), or adrenal glands (14 %). Nearly half of all targets (48 %, n = 71) were within 10 mm of a radiosensitive OAR. No grade 4 or 5 TRAEs, 3.5 % grade 3 TRAEs, and 43.7 % grade 2 TRAEs were reported within the first year of follow-up. We found a significant association between grade ≥ 2 GI toxicity and the parameters GI OAR D0.1cc, D1cc, and D20cc. ConclusionIn this phase II study of MR-guided SABR of oligometastases in the infra-diaphragmatic region, we found a low incidence of toxicity despite half of the lesions being within 10 mm of a radiosensitive OAR. GI OAR D0.1cc, D1cc, and D20cc were associated with grade ≥ 2 GI toxicity.

First-in-human study of PSMA-targeting agent, [18F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients.

This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients. The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software. [18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 μSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases. We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.

Oral Soft Tissue Metastasis from Breast Cancer as the Only Primary Source: Systematic Review.

Background Breast cancer is one of the most lethal neoplasms causing death. Oral cavity is the rare site of distant metastasis from breast cancer. Very little research has been conducted to date to analyze breast cancer as the sole primary source of metastasis to the oral soft tissues. The goal of this study was to examine the published cases of oral soft tissue metastasis from breast cancer as the only primary source to date. Methods An electronic search of the published literature was performed without publication year limitation in PubMed/Medline, Scopus, Google Scholar, Web of Science, Science Direct, Embase, and Research Gate databases, using mesh keywords like ("Breast cancer", OR "Breast carcinoma") AND ("Metastasis" OR "Metastases"), And ("Oral soft tissues" OR "Tongue" OR "Palate" OR "Tonsil" OR "Buccal mucosa" OR "Floor of mouth" OR "Vestibule" OR "Salivary glands"). We also searched all related journals manually. The reference list of all articles was also checked. Results Our research revealed 88 relevant papers (September 1967-September 2023) with 96 patients in total. The most predominant oral soft tissues involved were salivary glands followed by the gingiva, tonsils, tongue, and buccal mucosa. A total of 23% of patients died with an average survival time of 1 to 15 months. Conclusions Oral soft tissue metastasis from breast cancer is a rare event and has a bad prognosis. More cases need to be published to raise awareness of these lesions.

Uncharted Pathways: A Rare Case of Bony and Soft Tissue Metastasis from Cervical Carcinoma

Background: The most frequent tumors of the spine are metastases. However, we present a particular case characterized by an atypical primary origin resulting in secondary lesions in both the spinal column and adjacent soft tissues - specifically, squamous cell carcinoma of the cervix.