Site Of Metastatic Disease Research Articles

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Metastatic site radiation therapy for Ewing sarcoma and rhabdomyosarcoma: Consensus guidelines from the National Pediatric Cancer Foundation

BackgroundDespite the urgent need for improved outcomes in patients with metastatic Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS), it is unknown how to best approach metastatic site radiation therapy for these patients and whether such treatment provides a significant oncologic benefit that outweighs the toxicities. MethodsWe gathered a panel of pediatric radiation oncologists from academic hospitals to identify and discuss current controversies regarding the role of radiation in the management of metastatic EWS and RMS. The panel reviewed existing clinical data and ongoing trials to address five key questions: 1) the role of whole lung irradiation (WLI) in treating lung metastases 2) number of metastatic sites warranting radiotherapy and the radicality of such an approach; 3) radiation techniques, including stereotactic body radiation therapy (SBRT); 4) the timing of metastatic-site radiation therapy; and 5) the utility of metastatic site radiation therapy for relapsed metastatic disease. ResultsAfter a review of existing data, consensus recommendations were developed to support the decision-making process in metastatic-site irradiation with the goal of improving long-term disease control. Patients with pulmonary metastases should receive WLI. In patients with limited (<8 sites) metastatic disease, a comprehensive approach should be taken to treat all sites of metastatic disease diagnosed at presentation. SBRT should be considered as a preferred treatment technique. The timing of metastatic-site treatment should coincide with the end of systemic therapy. However, if there is a dosimetric advantage or improved compliance, concurrent treatment with the primary site may be preferred. ConclusionsA consensus guideline was established to address several critical questions regarding the role of radiation in the treatment of metastatic EWS and RMS. The study highlights the existing controversies, provides a structured approach, and underscores the need for future studies to further evaluate the therapeutic ratio of metastatic-site directed therapy.

Efficacy and Safety of First-Line Palliative Chemotherapy with Fluorouracil Plus Leucovorin, Oxaliplatin, and Docetaxel (FLOT) in HER2-Negative Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-Institutional Real-World Experience from Eastern India

Background Fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) is one of the preferred perioperative chemotherapy regimens in locally advanced resectable gastric cancer (GC). Till date, there are very few published data from India, regarding the outcomes of this relatively well-tolerated biweekly triplet regimen as first-line palliative chemotherapy in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Materials and Methods In the present retrospective study, we evaluated the efficacy and safety of first-line FLOT regimen in Indian patients with HER2-negative metastatic adenocarcinoma of stomach or GEJ. The primary endpoint was overall survival (OS). Progression-free survival (PFS), overall response rate (ORR), and toxicity profile were taken as secondary endpoints. Results Between January 2021 and June 2024, 88 patients were treated with FLOT. The median age was 52 years (range, 23–68); 69.3% were males and 37.5% of the patients had ≥ 3 metastatic disease sites involvement at baseline. Dose reductions due to toxicity were required in 25% of the patients. The ORR was 68.2%; median PFS and OS were 6.3 months (95% confidence interval [CI]: 5.3–7.4) and 12.5 months (95% CI: 11.3–14.2), respectively. The most frequent grade 3 to 4 adverse events were diarrhea (15.9%), fatigue (13.6%), and neutropenia (12.5%). Younger patients (aged &lt; 55 years) had much less ≥ grade 3 diarrhea (7.5%, n = 4), compared with patients aged ≥ 55 years (28.6%, n = 10). There was one toxicity-related death. Conclusion In the present study, biweekly FLOT regimen with primary prophylactic granulocyte colony-stimulating factor demonstrated encouraging efficacy with a favorable nongastrointestinal toxicity profile in Indian patients with HER2-negative metastatic gastric or GEJ adenocarcinoma. Clearly, this well-tolerated triplet regimen should be explored further through large prospective randomized trials in Asian patients.

The Role of Stereotactic Body Radiotherapy (SBRT) in Oligoprogressive Renal Cell Carcinoma (RCC) Treated with ICIs-TKIs: A Retrospective Multicentric Study.

This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine-kinase inhibitor (TKI). We retrospectively evaluated 34 pts affected by oligoprogressive RCC treated with an ICI-TKI combination between January 2020 and December 2023. SBRT was delivered to each site of oligoprogressive metastatic disease. After SBRT, pts were given follow-up clinical evaluations. 6-12-18-month local control (LC) rates and median next-line treatment-free survival (NEST-FS) were the primary endpoints. The secondary endpoints were overall response rate (ORR), clinical benefits and safety. After a median follow-up of 24 months, 6-12-18-month LC rates were 100%, 71% and 43%, respectively, and the median NEST-FS was 20 months. ORR was 90%, while clinical benefit was 100%. No > G2 adverse events related to SBRT were recorded. In our study, SBRT for oligoprogressive mRCC turned out to be a safe and useful treatment which was able to preserve current treatment. Further prospective studies are necessary to explore the effects of the ICIs-TKIs combination and SBRT upon oligoprogressive sites in mRCC.

Liver metastases and peritoneal metastases and response to checkpoint inhibitors in metastatic colorectal cancer with microsatellite instability.

There have been conflicting reports on the predictive impact of metastatic disease sites on the response to checkpoint inhibitors (CPI) in microsatellite instability (MSI) metastatic colorectal cancers (mCRC). Recent studies have highlighted peritoneal metastases, ascites, and liver metastases as possible indicators of resistance to CPI. We performed a detailed analysis of high microsatellite instability (MSI-H) mCRC treated with programmed cell death (PD-1) or PD-1/cytotoxic T-lymphocyte-associated protein 4 CPI in a single center. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and stable disease but with complete pathological response upon resection (SDcPR) were analyzed by the presence of liver metastases, peritoneal metastases, or absence of either. The impact of number and size of liver metastases on clinical outcomes were also interrogated. Thirty-five patients with MSI mCRC were included in the analysis. Patients with peritoneal metastatic disease had lower ORR and shorter PFS compared to patients without liver and peritoneal metastases. Contrary to recent reports, ORR and ORR + SDcPR rates were high in patients with liver metastases, at 58% and 66%, respectively. In the liver metastases category, a better response rate was noted for patients with<5 lesions compared to patients with more than 5 lesions. Patients who responded had a higher median tumor mutation burden than patients with progressive disease. In MSI mCRC, no single clinical characteristic was sufficient to preclude CPI response. Peritoneal metastatic disease was associated with numerically lower ORR and shorter PFS. In contrast, liver metastases do not predict poor outcome.

Collateralization of the upper extremity lymphatic system after axillary lymph node dissection.

Lymphatic drainage from the arm may be altered after axillary lymph node dissection (ALND). Understanding these alterations is important as they may change standard surgical and radiation treatment in recurrent breast cancer or upper extremity skin cancers, including melanoma. Utilizing a single-institution planar and single photon emission computed tomography/computed tomography lymphoscintigraphy database, we identified patients with a diagnosis of upper extremity cutaneous melanoma from 2008 to 2023 who previously underwent ALND for cancer treatment and did not develop upper extremity cancer-related lymphedema. ALND patients were matched to control patients presenting with cutaneous melanomas at the same anatomic sites. Sentinel lymph nodes (SLNs) were compared between both groups. Of 3628 upper extremity melanoma cutaneous patients, 934 met inclusion criteria, including 22 ALND and 912 control patients. Level I axillary SLN drainage was observed in 98% of controls and 27% of ALND patients (p < 0.001). Level II axillary SLN drainage was observed in 3% of controls and 27% of ALND patients (p < 0.001). Level III axillary SLN drainage was observed in 1% of controls and 32% of ALND patients (p < 0.001). Epitrochlear SLN drainage was observed in 9% of controls and 32% of ALND patients, respectively (p < 0.046). Brachial SLN drainage was observed in 4% of controls and 23% of ALND patients (p < 0.001). Distinct changes in functional lymphatic drainage were seen between the arms of patients who previously underwent ALND versus control patients. Levels II and III axillary, epitrochlear, and brachial nodes are possible sites of metastatic disease that should be considered in patients with a prior ALND.

Histopathological Growth Patterns Determine the Outcomes of Colorectal Cancer Liver Metastasis Following Liver Resection.

Colorectal cancer liver metastasis (CRCLM) remains a lethal diagnosis, with an overall 5-year survival rate of 5-10%. Two distinct histopathological growth patterns (HGPs) of CRCLM are known to have significantly differing rates of patient survival and response to treatment. We set out to review the results of 275 patients who underwent liver resection for CRCLM at the McGill University Health Center (MUHC) and analyze their clinical outcome, mutational burden, and pattern of cancer progression in light of their HGPs, and to consider their potential effect on surgical decision making. We performed a retrospective multivariate analysis on clinical data from patients with CRCLM (n = 275) who underwent liver resection at the McGill University Health Center (MUHC). All tumors were scored using international consensus guidelines by pathologists trained in HGP scoring. A total of 109 patients (42.2%) were classified as desmoplastic and angiogenic, whereas 149 patients (57.7%) were non-desmoplastic and vessel co-opting. The 5-year survival rates for angiogenic patients compared with vessel co-opting patients were 47.1% and 13%, respectively (p < 0.0001). Multivariate analysis showed patients with vessel co-opting CRCLM had a higher incidence of extrahepatic metastatic disease (p = 0.0215) compared with angiogenic CRCLM. Additionally, KRAS mutation status was a marker of increased likelihood of disease recurrence (p = 0.0434), as was increased number of liver tumors (p = 0.0071) and multiple sites of extrahepatic metastatic disease (p < 0.0001). Multivariate analysis identified key clinical prognostic and molecular features correlating with the two HGPs. Determining liver tumor HGPs is essential for patient prognostication and treatment optimization.

STRIvE-02: A First-in-Human Phase I Study of Systemically Administered B7-H3 Chimeric Antigen Receptor T Cells for Patients With Relapsed/Refractory Solid Tumors.

B7-H3 is an immunoregulatory protein overexpressed by many pediatric solid tumors with limited expression on critical organs, making it an attractive immunotherapy target. We present a first-in-human phase I clinical trial systemically administered B7-H3 chimeric antigen receptor (CAR) T cells for young patients with relapsed or refractory solid tumors. Patients were enrolled onto a phase I trial to examine the safety of B7-H3-specific CARs at various dose levels (DLs) using a standard 3 + 3 dose escalation design. Sixteen patients (range, 11-24 years; median, 18.5 years) were enrolled, and nine were treated at DL1 (0.5 × 106 CAR T cells/kg; n = 3) or DL2 (1 × 106 CAR T cells/kg; n = 6). There were no first infusion dose-limiting toxicities. Maximum first-infusion circulating CAR T cells detected in the peripheral blood were 4.98 cells/μL (range, 0-4.98 cells/μL) with detection of CAR T cells colocalizing with tumor cells at the site of metastatic disease in one patient. Patients were eligible for subsequent infusions. An objective partial response by PERCIST criteria was observed 28 days after a second CAR T cell infusion in a patient who did not have an objective response after the first infusion. The second infusion demonstrated marked enhancement of CAR T cell expansion to 1,590 cells/μL and was accompanied by cytokine release syndrome and dose-limiting transaminitis. Detailed peripheral blood cytokine profiling revealed elevated IL-21 levels preinfusion 2 compared with infusion 1. B7-H3 CAR T cells are tolerable and demonstrate limited antitumor activity without acute on-target, off-tumor toxicity. High levels of CAR T cell expansion may be necessary to achieve objective responses, but undefined host and tumor microenvironment factors appear to be critical (ClinicalTrials.gov identifier: NCT04483778).

529P Evaluating metastatic disease sites as a prognostic marker in patients receiving sequential treatment with regorafenib and trifluridine/tipiracil for refractory colorectal cancer: Survival outcomes from the multicenter retrospective “ReTrITA” study

529P Evaluating metastatic disease sites as a prognostic marker in patients receiving sequential treatment with regorafenib and trifluridine/tipiracil for refractory colorectal cancer: Survival outcomes from the multicenter retrospective “ReTrITA” study

Systemic treatment post curative-intent intervention based on tumor-informed circulating tumor DNA result for oligometastatic colorectal cancer.

84 Background: Local therapies potentially offer a curative approach for patients with oligometastatic colorectal cancer (CRC). The effectiveness of systemic chemotherapy following definitive local treatment in this setting is not well-defined. Tumor-informed circulating tumor DNA (ctDNA) might guide management strategies after curative-intent local treatment. Methods: This is a single institution retrospective study of patients with CRC who underwent curative-intent local therapy to an isolated site of metastatic disease and had post-intervention tumor-informed ctDNA (Signatera) testing. The study was approved by the institutional review board. Clinical characteristics, including ctDNA results, were collected and evaluated. Kaplan-Meier method and log-rank test were used to calculate and compare disease-free survival (DFS). Factors associated with DFS were analyzed using multivariate Cox proportional hazards model. Results: 45 patients were included with median age of 59 years, 62% being male, 91% white, and 53% with stage IV disease at diagnosis. 37% of the patients had RAS mutations, no patient had BRAF mutation, and 2.2% patient had mismatch repair deficient disease. Isolated liver metastases were present in 80% of patients, lung metastases in 11% and other sites in 9%. 44 patients received chemotherapy prior to definitive treatment, with a median treatment duration of 16 weeks. ctDNA tests were done prior to local therapy in 23 patients, with 14 cases (61%) testing positive. Definitive treatment included resection (58%), ablation (13%), radiotherapy (4%), and multimodality (25%). Post-definitive treatment chemotherapy was administered to 24 (53%) patients. ctDNA positivity following definitive therapy was observed in 10 patients (22%), which was associated with a poorer prognosis, with a median DFS of 5.3 months compared to 21.3 months for the ctDNA-negative group (p&lt;0.001). These findings were confirmed on multivariate analysis. In patients who had negative ctDNA after definitive local treatment, median DFS was 14.9 months for those who received post-intervention chemotherapy versus 21.3 months for those without post-intervention chemotherapy (p=0.835). Conclusions: Patients with negative ctDNA results following definitive local therapy for isolated metastatic CRC have better prognosis. Post-intervention chemotherapy in this group of patients was not associated with improved DFS. ctDNA guided omission of post-intervention chemotherapy following curative-intent local treatment of oligometastatic CRC warrants further study. [Table: see text]

Unusual “Mini-Rugby Ball” Pattern Solitary Lung Metastasis in Relapsed Ewing's Sarcoma

AbstractEwing's sarcoma (ES) is a mesenchymal origin malignant neoplasm that affects children and adolescents. It is the second most common type of bone sarcoma and accounts for approximately 1.5% of all childhood cancers with an annual incidence of 1 to 3 cases per million children under 16 years of age. In this article, we present the case of a 16-year-old adolescent girl. Lung metastasis at the initial diagnosis of ES is relatively uncommon but carries significant prognostic implications. Lung metastases in ES can vary significantly in size, ranging from small nodules (just a few millimeters in size) to the largest reported case being 15 cm. The size of the metastases impacts the choice of therapeutic strategies and the prognosis. Approximately 30% of patients with ES experience a relapse, with the lungs being a common site for metastatic disease. Relapsed lung metastasis on follow-up is a critical concern in the long-term management of ES. We describe a relapsed case of ES in a 16-year-old adolescent girl who presented with a solitary large metastatic right lung mass, with the longest dimension of 16 cm on craniocaudal measurement. The primary site of the tumor was the left distal femur, for which the patient received six cycles of neoadjuvant chemotherapy, followed by en bloc tumor excision and rotationplasty of the left distal femur, after which the patient received seven cycles of adjuvant chemotherapy. Subsequent 5 years of regular follow-up was asymptomatic. Later, the patient presented with back pain and cough, and was diagnosed with a solitary large right lung mass. Computed tomography (CT) guided biopsy of the right lung mass revealed a metastatic ES, for which she underwent chemoradiotherapy. This case highlights the large size of solitary lung metastases in relapsed ES.

Addressing disparities in health outcomes for patients with advanced pancreatic cancer and limited English proficiency.

There are significant challenges and a lack of data related to culturally and linguistically diverse (CALD) cancer patients. We compared patient characteristics, treatment patterns, and outcomes of patients with advanced pancreatic cancer that required an interpreter. Registry data was extracted for advanced pancreatic cancer patients from a single health institution with a comprehensive Transcultural and Language Service (TALS). Demographic and clinicopathologic characteristics were compared. Kaplan-Meier survival estimates with log-rank testing, and univariate and multivariable regression analysis were performed to compare the group with limited English proficiency (LEP) to theEnglish proficient (EP)group. Of 155 patients, 32.9% (n=51) required the TALS. TheLEP group had a higher mean age (71.2vs. 76.8 years; p=0.005) and received less chemotherapy (42.3%vs. 31.4%, p=0.220). Univariate analysis revealed a shorter median overall survival (OS) in the LEP group (3.6vs. 5.0 months), with a hazard ratio [HR] of 1.51 (95% confidence interval [CI]: 1.03-2.21, p=0.033). Upon multivariable analysis, adjusting for Eastern Cooperative Oncology Group (ECOG) performance scale, the number of sites of metastatic disease and chemotherapy use, the strength of association between LEP and OS reduced marginally (HR 1.42, 95% CI: 0.93-2.16), and was no longer statistically significant (p=0.103). In patients with advanced pancreatic cancer utilizing a comprehensive TALS, there was a trend to poorer survival with limited English proficiency, although this association was not statistically significant. An ongoing research commitment to the CALD experience is necessary to build a granular understanding of this population and ensure equitable outcomes.

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer.

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan-Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar's test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.

OTHR-07. LIFE THREATENING CATATONIA AND THE USE OF ELECTROCONVULSIVE THERAPY IN A PATIENT WITH RELAPSED MEDULLOBLASTOMA

Abstract Medulloblastoma is one of the most common malignant brain tumors in the pediatric population and with multimodal therapy the majority of patients will be cured, but patients experience significant morbidity related to the disease and therapy. Catatonia is a life-threatening psychomotor disorder that has rarely been described in the pediatric population and is likely under recognized. Catatonia is a treatable condition using benzodiazepines as first line with electroconvulsive therapy (ECT) used for patients who do not respond or have life threatening malignant catatonia. In the medical literature there are very few papers to inform on the safety of using ECT in patients who have received radiation in the past or are undergoing chemotherapy. We describe a patient in remission of his medulloblastoma who presented with refractory catatonia who needed lifesaving ECT, then had metastatic recurrence of his medulloblastoma. The patient was initially diagnosed with group 4 medulloblastoma at 14 – he was treated with high-risk therapy to metastatic sites of disease at diagnosis as per COG ACNS 0332 with a combination of surgery, chemotherapy and craniospinal radiation and a boost to the primary tumor and metastatic sites of disease. Approximately 18 months after the end of therapy he was diagnosed with treatment refractory catatonia and needed to be started on ECT with a good response. 6 months after presentation of catatonia, the patient unfortunately had a relapse of his medulloblastoma in his left temporal lobe and is now actively getting ECT and chemotherapy at the same time without complications. The description of this patient will add to the sparse body of evidence that it is likely safe to be able to deliver chemotherapy at the same time as ECT.

GCT-13. OUTCOMES OF INTRACRANIAL GERMINOMA TREATED AT A SINGLE UK PROTON CENTRE ACCORDING TO UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG) GUIDELINES

Abstract BACKGROUND After SIOP-CNS-GCT II closed in 2018, the CCLG recommended, with caveats, following the standard trial arms: 4 cycles of chemotherapy (Etoposide-Carboplatin alternating with Etoposide-Ifosfamide) followed by whole ventricular radiotherapy (WVRT) (24Gy/15fractions) and boost (16Gy/10fr) to the primary site(s) for localised germinoma and craniospinal irradiation (CSI) (24Gy/15fr) followed by boost (16Gy/10fr) to primary and metastatic sites for metastatic disease. Since 04/2021, the CCLG formally recommended omitting the boost for localised unifocal germinoma in complete radiological response after chemotherapy. From autumn 2022, we also omitted boosts to completely responded primary sites for localised bifocal germinoma. METHODS Retrospective reviewed of all patients referred to our proton centre 12/2018–06/2023. We collected patient, tumour and treatment factors, acute toxicities (CTCAE grade≥3), and event-free survival(EFS) from radiotherapy until 09/2023. RESULTS Forty-two patients (36M:6F) were included, 23 localised and 19 (including 3 incompletely staged) treated as metastatic. Primary sites: 21 pineal, 8 pituitary/suprasellar, 10 bifocal and 3 atypical (optic nerve, periventricular, thalamic). Diagnosis was by histopathology in 40 and bifocal disease with negative CSF and serum markers in 2. Median age was 15 years (IQR 13-16), median follow-up 13 months (IQR 6-15). Patients were treated according to CCLG guidance, apart from three patients with metastatic pure germinoma, of whom one received 2 cycles Cisplatin-Etoposide, and two received 5 and 3 cycles of Vinblastine before CSI, and one patient with metastatic germinoma plus teratoma who received 2 cycles of Cisplatin-Etoposide and non-germinoma radiotherapy doses (30Gy/20fr CSI, 24Gy/15fr cranial boosts). No patient had subsequent surgery. All remained progression free at last follow-up. Eight patients developed acute grade 3 toxicities: 3 vomiting (2 CSI, 1 WVRT), and 5 lymphopenia (all CSI). CONCLUSIONS Disease control was excellent, with no relapses to date. Proton therapy was well tolerated with low rates of acute high grade toxicities.

Predictors of pulmonary metastases on chest computed tomography in children and adolescents with osteosarcoma—tips for qualifying patients for thoracotomy

BackgroundOsteosarcoma is the most common primary malignant bone tumour in children and adolescents. Lungs are the most frequent and often the only site of metastatic disease. The presence of pulmonary metastases is a significant unfavourable prognostic factor. Thoracotomy is strongly recommended in these patients, while computed tomography (CT) remains the gold imaging standard. The purpose of our study was to create tools for the CT-based qualification for thoracotomy in osteosarcoma patients in order to reduce the rate of useless thoracotomies.MethodsSixty-four osteosarcoma paediatric patients suspected of lung metastases on CT and their first-time thoracotomies (n = 100) were included in this retrospective analysis. All CT scans were analysed using a compartmental evaluation method based on the number and size of nodules. Calcification and location of lung lesions were also analysed. Inter-observer reliability between two experienced radiologists was assessed. The CT findings were then correlated with the histopathological results of thoracotomies. Various multivariate predictive models (logistic regression, classification tree and random forest) were built and predictors of lung metastases were identified.ResultsAll applied models proved that calcified nodules on the preoperative CT scan best predict the presence of pulmonary metastases. The rating of the operated lung on the preoperative CT scan, dependent on the number and size of nodules, and the total number of nodules on this scan were also found to be important predictors. All three models achieved a relatively high sensitivity (72–92%), positive predictive value (81–90%) and accuracy (74–79%). The positive predictive value of each model was higher than of the qualification for thoracotomy performed at the time of treatment. Inter-observer reliability was at least substantial for qualitative variables and excellent for quantitative variables.ConclusionsThe multivariate models built and tested in our study may be useful in the qualification of osteosarcoma patients for metastasectomy through thoracotomy and may contribute to reducing the rate of unnecessary invasive procedures in the future.

Stereotactic radiosurgery (SRS) for non-small cell lung cancer (NSCLC) in the oncogene-addicted era: A real-world UK tertiary center experience.

e14011 Background: 30-50% of NSCLC patients develop brain metastases (BM). Re-evaluation of the role of SRS is required with evolving understanding of molecular subtypes of NSCLC and increasing intracranial efficacy of systemic agents. Methods: We conducted a retrospective analysis of NSCLC patients receiving SRS at our centre from 05/16-11/23. Primary objective was median overall survival (mOS months). Analysis was performed on Prism 10.1.1. Multivariate analysis was conducted using Cox Proportional Hazards Regression, with age, gender, KPS, BM size, total BM volume and oncogene status as predictor variables. Extraction from medical records was undertaken by authors, with local R&amp;D committee approval. Results: 237 patients were evaluable. 59% (N=139) were oncogene-addicted (oNSCLC) and 41% (N=98) non-oncogene-addicted (non-oNSCLC). Median duration of follow up was 43.3m. m OS was 11.9m overall. For oNSCLC mOS was 13.1m vs 8.8m for non-oNSCLC (HR 1.49, P=0.02). mOS was 20.7m for EGFR sensitizing NSCLC (N=48) vs 10.5m without (HR 1.40 P=0.12). mOS for ALK+ (N=22) was 29.3m vs 11.6m for non-ALK+ (HR 1.90, P=0.05). mOS for KRAS+ (N=32) was 11.6m vs 12.0m without (HR 0.91, P=0.68). Significantly inferior mOS was seen for single (N=186 [78%]) vs multiple (N=51[22%]) SRS courses (8.4m vs 38.8m, [HR 0.34 P=&lt;0.0001]). SRS at diagnosis of BM (N=118) had a mOS of 12.3m vs at nadir (N=9, not reached [HR0.44, P=0.18]), progression on 1st line TKI (N=31, 22.1m [HR 1.1, P=0.79]) and at any other time (N=157, 7.8m [HR 1.33, P=0.11 ]). There was no significant difference in survival for patients diagnosed with brain metastases at the diagnosis of metastatic disease compared to those who developed brain metastases during their disease course (12.3m vs 10.6m [HR 1.18, P=0.33]). Survival of those with 1 site of metastatic disease (18.3m) was numerically improved compared to those with 2 (10.7m, HR 1.26, P=0.25) sites, and statistically significant compared to those with 3 (10.1m, HR 1.69, P&lt;0.02) and ≥4 (4.4m, HR 4.41, P&lt;0.0001) sites. Conclusions: Median OS in oNSCLC was superior to non-oNSCLC, driven by numerically superior survival in EGFR+ and ALK+ cohorts. Significantly improved OS was observed in patients with multiple vs single SRS treatments, however this may be confounded by biases. Patients treated with SRS at nadir had numerically superior OS to those treated at other timepoints, however this must be interpreted with caution due to small sample size. Further prospective research is needed to interrogate these findings and guide local therapies in NSCLC with BM. [Table: see text]

Single institution retrospective review of patients with metastatic hormone receptor positive breast cancer receiving first line therapy of CDK4/6 inhibitors.

e13090 Background: Breast cancer continues to be the most commonly diagnosed cancer in women. The majority of these cancers are estrogen positive (ER+) and about 6% of new cases are stage 4 at time of diagnosis. The current standard of care for postmenopausal women with stage 4 ER+ breast cancer is a combination of an aromatase inhibitor (AI) with a cyclin-dependent kinase (CDK) 4/6 inhibitor. Based on Medicare data claim analysis from IQVIA, CDK 4/6 inhibitors are being used nationally in the first line setting in 56% of cases where 24% of cases were treated with AI monotherapy. The state of Kentucky currently lies below this national average by using this treatment regimen in 38% of cases where 47% of cases are treated with AI monotherapy. The reason for this discrepancy between the national average and Kentucky is currently unknown. To further understanding, we have conducted an internal review of adherence to the guidelines. Methods: This is a single center retrospective study done at University of Louisville, Brown Cancer Center. Data was collected on patients who had biopsy proven metastatic hormone positive breast cancer from July 2021 until May 2023 (n=41). Collected characteristics include age on diagnosis, tumor grade, sites of metastatic disease, first line treatment received, choice of CDK4/6 inhibitor if received, and prior exposure to chemotherapy or anti-estrogen therapy. Results: In our cohort of 41 patients, we found that 63.4% (n=26) of patients received an AI and CDK4/6 inhibitor in the first line. There were 4.88% (n=2) of patients who received AI monotherapy, 21.9% (n=9) received Fulvestrant and CDK4/6 inhibitor, 4.88 % (n=2) received AI and Fulvestrant and 4.88% (n=2) received Fulvestrant alone. In total, patients who received estrogen therapy plus CDK4/6 inhibitor totaled 85% of new patients (n=35). Conclusions: This internal review showed our institution to be compliant with endocrine therapy and CDK 4/6 inhibitor in front-line treatment for the majority of metastatic ER+ patients. Given the supportive data for use of CDK 4/6 inhibitors in front-line treatment, the compliance is expected to be much higher. We recommend continued discussion amongst oncology providers to help identify barriers to treatment and determine the causes for poor compliance in the state of Kentucky.

Randomized controlled, open-label, phase IIb/III study of lurbinectedin in combination with doxorubicin versus doxorubicin alone as first-line treatment in patients with metastatic leiomyosarcoma.

TPS11590 Background: Lurbinectedin (LUR) is a synthetic chemical entity structurally related to trabectedin that inhibits oncogenic transcription and is active in tumors addicted to transcription. Synergistic activity of the combination of LUR with Doxorubicin (DOX) was found in solid tumors. Preliminary results from two trials showed efficacy for LUR/DOX in anthracycline-naïve advanced Leiomyosarcoma (LMS) (1st or 2nd line) at different doses. In a phase 2 trial in soft tissue sarcoma (STS) patients (pts) (mostly with LMS: 12/20 pts), a combination of DOX 50 mg/m2 + LUR 2 mg/m2 Day (D)1 q3wk resulted in a response rate (RR) of 35% (4/7 LMS pts responding) and a disease control rate (DCR) at 24 wks of 40% (1). A phase 1b/2 trial in 10 advanced STS pts found a RR of 60% (5 were LMS, with 3 partial responses) treated at DOX 25 mg/m2 D1 or D1,D8 + LUR 3.2 mg/m2 D1 q3wk, (2). The promising results of these trials provide a rationale for further exploring this combination in a phase 2b/3 trial as first-line therapy for metastatic LMS (SaLuDo - NCT06088290). Methods: SaLuDo is a randomized, open-label study evaluating LUR in combination with DOX compared to DOX alone as first-line treatment of pts with metastatic LMS. The primary endpoint is progression-free survival (PFS) according to Independent Radiological committee (IRC). Secondary endpoints include overall survival, PFS according to Investigator assessment (IA), overall response rate, duration of response, and clinical benefit rate (according to IRC and IA), safety profile, patient-reported outcomes, pharmacokinetics, and exploratory pharmacogenomic analysis. Main inclusion criteria include age ≥ 18 years, confirmed diagnosis of metastatic LMS, and no prior systemic treatment for metastatic disease. Exclusion criteria include prior treatment with anthracyclines, lurbinectedin or trabectedin. The phase 2b part of the study will randomize approximately 120 pts into 3 arms (1:1:1): Control arm (DOX 75 mg/m2 D1 q3wk; experimental ARM A (DOX 50 mg/m2 D1 + LUR 2.2 mg/m2 D1 + 1ry GCSF prophylaxis q3wk), and experimental ARM B (DOX 25 mg/m2 D1 + LUR 3.2mg/m2 D1 + 1ry GCSF prophylaxis q3wk). Stratification will be done according to site of primary tumor (uterine vs. soft tissue), sites of metastatic disease (lung as unique site vs. other) and time from diagnosis to study entry (≤ 12 months vs. &gt;12 months). One of the two experimental arms will be dropped out at the end of phase 2b. The study will then enter the phase 3 part and approximately 120 pts will be randomized 1:1 between the control arm and the selected experimental arm. An Independent Data Monitoring Committee will oversee the conduct of the study. The first patient was randomized in 09/2023. The phase 2b part of the study is ongoing and recruiting patients in Europe and the USA. 1. Cote EJC 2020; 126:21-32. 2. Cote. JCO 2023; 41: Abst 11507. Clinical trial information: NCT06088290 .

Correlation of previous local vaccination site “flares” during immunotherapy for metastatic melanoma with complete responses to therapy.

e21534 Background: mRNA vaccines have been shown to stimulate T-cells targeting patient-specific tumor neoantigens. When combined with immune checkpoint inhibitors (ICI) in a randomized Phase II trial, mRNA vaccines demonstrated improvement in recurrence free survival and distant metastasis free survival compared to ICI alone. We retrospectively examined patients (pts) with advanced melanoma treated more than 5 years ago on clinical trials with adjuvant NYESO1 or mRNA vaccine therapies (VT) then ICI upon recurrence and analyzed biomarkers correlating with treatment response. Methods: This retrospective study examined 22 pts with advanced melanoma treated between 2004-2017 with adjuvant vaccine therapies (VT). 10 of the 22 pts subsequently developed recurrent disease and were treated with ICI. We evaluated disease free interval following ICI, sex, age, BRAF status, HLA type, site of primary and metastatic disease, initial vaccine treatment, vaccine toxicities, stage and sites of melanoma recurrence, ICI treatment, response and toxicities, vaccine site flares or cutaneous immune related adverse events (irAEs) following ICI. Results: Of the 22 patients (11 male, 11 female) treated with adjuvant VT, median age at first vaccine was 53 years old. HLA type was known for 11 pts. Stage at initial VT was IIB to IIIC. 14 pts recurred following adjuvant VT. Median time from vaccine initiation to melanoma recurrence was 3.2 years (range 6.5 months to 11 years). 10 pts received ICI for recurrent melanoma, 3 pts received ipilimumab, 2 anti-PD1 monotherapy, 4 ipilimumab and nivolumab, and 1 nivolumab/relatlimab. Stage at first ICI was IIIB to IV M1d. 9 pts experienced cutaneous irAEs. 7 pts experienced local vaccine site flare reactions following ICI treatment. Additionally, 2 pts experienced vitiligo, 2 with dermatologic flares (bullous pemphigoid and psoriatic rash), 2 with generalized rash that resolved with steroid cream. 1 pt did not experience rash, vaccine site flare, nor irAE dermatologic flare. Of the pts who recurred, 2 pts had BRAF V600E mutations, and 1 of these pts experienced vaccine flare, the other did not. 1 pt with a BRAF Q16L mutation did not have vaccine flare. 6 out of 7 BRAF wild type pts who recurred and received ICI experienced a localized vaccine site flare. Median disease-free interval following ICI treatment was 1.5 years (range 3 months to 9 years). All 10 pts are disease-free and off ICI being closely monitored. Conclusions: Evidence of prior localized vaccination “flare” may be a biomarker for a complete immunologic response in pts with metastatic disease treated with immunotherapy. ICI targeting CTLA-4 and/or PD-1 both triggered this localized vaccination site response, suggesting that T cell memory and immunologic activation against melanoma antigens translate into clinical responses.