Diagnosis Of Distant Metastasis Research Articles

Surgical Outcomes in Non-Small Cell Lung Cancer with Distant Metastasis: The Prognostic Significance of Delayed Metastasis Diagnosis.

The diagnosis of distant metastasis on preoperative examinations for non-small cell lung cancer (NSCLC) can be challenging, leading to surgery for some patients with uncertain metastasis. This study evaluated the prognostic impact of delayed diagnosis of metastasis on patients who underwent upfront surgery. The study enrolled patients who underwent lobectomy or pneumonectomy for NSCLC between June 2010 and December 2017 and evaluated the presence of distant metastasis before surgery. Overall survival (OS) for patients with stage IV cancer was compared with that for patients without metastasis, and the prognostic factors were analyzed. Of 3046 patients (mean age, 63 years; 1770 men), 100 (3.3 %) had distant metastasis, diagnosed preoperatively in 1.4 % (42/3046) and postoperatively in 1.9 % (58/3046) of the patients. The two most common metastasis sites diagnosed after surgery were contralateral lung (22/58, 37.9 %) and ipsilateral pleura (16/58, 27.6 %). The OS (median, 42.7 months) for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer (P = 0.865), whereas the OS (median OS, 91.7 months) for the patients with stage IV cancer diagnosed preoperatively was better than for the patients with stage IIIB cancer (P = 0.001). Among the patients with distant metastasis, squamous cell type (hazard ratio [HR], 3.15; P = 0.002) and systemic treatment for metastasis (HR, 2.42; P = 0.002) were independent predictors of worse OS. Among NSCLC patients undergoing upfront surgery, the OS for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer. For patients with stage IV disease, squamous cell type and systemic treatment for metastasis were prognostic factors for poorer OS.

Quality of Life of Oligometastatic and Polymetastatic Head and Neck Squamous Cell Carcinoma Patients.

Evidence suggests that distant metastasis in head and neck squamous cell carcinoma is a spectrum of disease. Previous studies show that oligometastasis has favorable survival compared with polymetastasis. The quality of life of patients with oligometastasis remains unknown. To further solidify the position of oligometastasis as a separate entity, we hypothesized that oligometastatic patients experience better quality of life than polymetastatic patients. Patients with distant metastasis were stratified into three groups: oligometastasis (≤3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site), and explosive-disseminating metastasis (spread to ≥3 anatomic sites). Quality of life was assessed every 2 months post distant metastasis diagnosis. Between January 1, 2016, and December 31, 2021, a total of 161 patients with distant metastasis were identified, with a total of 397 measurements. In this group, 57 (35.4%) patients had oligometastasis, 35 (21.7%) patients had explosive metastasis, and 69 (42.9%) patients had explosive-disseminating metastasis. Their median post-distant metastasis survivals were 8.5 months, 3.2 months, and 3.2 months respectively (p < 0.001). A significantly better overall quality of life was observed in the oligometastasis group compared with the polymetastatic groups (+0.75 out of 7, p < 0.05). Furthermore, oligometastatic patients performed better in the subdomains of "physical functioning," "fatigue," and "pain." Results from this study underscore that subgroups exist regarding quality of life and survival within distant metastasis, with polymetastatic patients performing worse than oligometastatic patients. This highlights the significance of tailored interventions that consider the unique challenges faced by each metastatic group of patients. 3, retrospective cohort study Laryngoscope, 2024.

Association of follow-up imaging frequency with temporal incidence and patterns of distant failure following (chemo) radiotherapy for HPV related oropharyngeal cancer

ObjectivesEmerging data supports radical intent therapy for oligometastatic (OM) relapsed human papilloma virus (HPV+) related oropharyngeal cancer (OPC). We assess the association of follow-up imaging frequency amongst HPV + OPC, with temporal and spatial patterns of distant relapse, to inform rationalisation of routine post-treatment imaging. Materials and methodsA retrospective single centre cohort study was carried out of consecutive HPV + OPC patients treated with radical intent (chemo)radiotherapy ((CT)RT) between 2011 and 2019. OM state was defined as ≤ 5 metastasis, none larger than 3 cm (OMs) or, if interval from last negative surveillance imaging > 6-months, then ≤ 10 metastasis, none larger than 5 cm, (OMp). Patients not meeting OMs / OMp criteria were deemed to have incurable diffuse metastatic disease (DMdiffuse). Results793 HPV-OPC patients were identified with median follow-up 3.15years (range 0.2–8.9). 52 (6.6 %) patients had radiologically identified DM at first failure and were considered for analysis. The median time to recurrence was 15.1 months (range: 2.6–63 months). 87 % of distant metastasis (DM) occurred in the first two years after treatment. Twenty-seven (52 %) patients had OM (OMs or OMp) at time of failure, with 31 % having OMs. The median time from completion of treatment to diagnosis of DMdiffuse vs OM was 22.2 months (range: 2.6–63.1 months) vs 11.6 months (range: 3.5–32.5 months). The probability of being diagnosed with OM vs DMdiffuse increased with reducing interval from last negative surveillance scan to imaging identifying DM (≤6 months 88.9 %, 7–12 months 71.4 %, 13–24 months 35 %, > 24 months 22.2 %). ConclusionWe demonstrate that a reduced interval between last negative imaging and subsequent radiological diagnosis of DM is associated with increased likelihood of identification of OM disease. Consideration of increased frequency of surveillance imaging during the first two years of follow up is supported, particularly for patients at high risk of distant failure.

Risk factors for distant metastasis of Chondrosarcoma in the middle-aged and elderly people.

Chondrosarcoma is the second most common primary bone malignancy with the highest incidence in middle-aged and elderly people, where distant metastasis (DM) still leads to poor prognosis. The purpose of this study was to construct a nomogram for studying the diagnosis of DM in middle-aged and elderly patients with chondrosarcoma. Data on chondrosarcoma patients aged ≥ 40 years diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The data were divided into a training set and an internal validation set according to a 7:3 ratio, and the training set data were screened for independent risk factors for DM in chondrosarcoma patients using univariate and multivariate logistic regression analysis. The screened independent risk factors were then used to build a nomogram. In addition, data from 144 patients with chondrosarcoma aged ≥ 40 years diagnosed in a tertiary hospital in China from 2012 to 2021 were collected as the external validation set. The results were evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis in the training set, internal validation set, and external validation set. A total of 1462 middle-aged and elderly patients with chondrosarcoma were included, and 92 (6.29%) had DM at the time of diagnosis. Independent risk factors for DM in middle-aged and elderly patients with chondrosarcoma included being married (OR: 2.119, 95% CI: 1.094-4.105), histological type of dedifferentiated chondrosarcoma (OR: 1.290, 95% CI: 1.110-1.499), high-grade tumor (OR: 1.511, 95% CI: 1.079-2.115), T3 stage (OR: 4.184, 95% CI: 1.977- 8.858), and N1 staging (OR: 5.666, 95% CI: 1.964-16.342). The area under the receiver operating characteristic curve (AUC) was 0.857, 0.820, and 0.859 in the training set, internal validation set, and external validation set, respectively. The results of the calibration curve and decision curve analysis also confirmed that the established nomogram could accurately predict DM in middle-aged and elderly patients with chondrosarcoma. Married, histological type of dedifferentiated chondrosarcoma, high-grade tumor, T3 stage, and N1 stage are independent risk factors for DM in middle-aged and elderly chondrosarcoma patients, and clinicians should see more attention.

Temporal Incidence and Patterns of Distant Failure for Human Papillomavirus (HPV) Related Oropharyngeal Cancer

HPV related oropharyngeal cancer (HPV-OPC) enjoys improved treatment outcomes relative to non-HPV related disease but suffers from similar rates of distant metastases (DM) following treatment. Emerging data supports radical intent therapy for oligometastatic relapsed HPV-OPC, suggesting early diagnosis of DM may be beneficial to outcome. We assess temporal patterns in distance relapse to investigate rationalization of post treatment imaging. A retrospective single center cohort study was carried out of consecutive HPV-OPC treated with radical intent (chemo)radiotherapy ((CT)RT) between 2011 and 2020. Electronic records were reviewed to identify location and timing of development of DM. Oligometastatic (OM) state was defined as </ = 5 metastasis in one system. A total of 793 HPV-OPC patients were identified with median follow-up 3.15 years (range 0.2-8.9). The median time to recurrence was 15.1 months (range: 2.6-63 months). 87% of DM occurred in the first two years after treatment. Pattern of failure by stage are shown in table 1. Indications for scans performed identifying DM alone were symptoms (66%), follow-up imaging based on previous radiological findings (15%), disease response assessment imaging (15%), and incidental findings (4%). Sites of distant metastasis were lung (64%), thoracic nodes (36.5%), bone (27%), visceral (23%), brain (4%) and skin (2%). The sites of visceral metastasis involvement included liver (92%), Adrenal (18%), kidney (18%), and spleen (9%). Treatment offered to patients with OM alone was best supportive care (46%), palliative chemotherapy (15.4%), palliative RT (23%), immunotherapy (8%), and one patient lost to follow up (8%). SBRT was not available during time period. Median survival following diagnosis was 17.5 months (range 4.4-85.4 months). Despite no routine imaging beyond initial treatment response assessment, we identify a small minority of HPV OPC patients with OM recurrence that is associated with better outcome and occasional long-term cure from aggressive therapy. The majority (69%) of DM occur in the thorax/upper abdomen of patients in the first two years post treatment. This finding supports the potential utility of regular imaging of thorax/upper abdomen during early follow.

Assessment of whole-body MRI including diffusion-weighted sequences in the initial staging of breast cancer patients at high risk of metastases in comparison with PET-CT: a prospective cohort study.

The aim of this study was to assess the diffusion-weighted whole-body-MRI (WBMRI) in the initial staging of breast cancer at high risk of metastases in comparison with positron emission tomography (PET)-CT. Forty-five women were prospectively enrolled. The inclusion criteria were female gender, age >18, invasive breast cancer, an initial PET-CT, and a performance status of 0-2. The exclusion criteria were contraindication to WB-MRI and breast cancer recurrence. The primary outcome was the concordance of WB-MRI and PET-CT in the diagnosis of distant metastases, whereas secondary outcomes included their concordance for the primary tumor and regional lymph nodes (LN), as well as the agreement of WB-MRI interpretation between two radiologists. The mean age was 51.2 years with a median size of the primary tumor of 30 mm. Concordance between the two modalities was almost perfect for metastases staging, all sites included (k= 0.862), with excellent interobserver agreement. The accuracy of WB-MRI for detecting regional LN, distant LN, lung, liver, or bone metastases ranged from 91 to 96%. In 2 patients, WB-MRI detected bone metastases that were overlooked by PET-CT. WB-MRI showed a substantial agreement with PET-CT for staging the primary tumor, regional LN status, and stage (k= 0.766, k= 0.756, and k= 0.785, respectively) with a high interobserver agreement. WB-MRI including DWI could be a reliable and reproducible examination in the initial staging of breast cancer patients at high risk of metastases, especially for bone metastases and therefore could be used as a surrogate to PET-CT. Whole-body-MRI including DWI is a promising technique for detecting metastases in the initial staging of breast cancer at high risk of metastases. Whole-body-MRI (WB-MRI) was effective for detecting metastases in the initial staging of 45 breast cancer patients at high risk of metastases in comparison with PET-CT. Concordance between WB-MRI and PET-CT was almost perfect for metastases staging, all sites included, with excellent interobserver agreement. The accuracy of WB-MRI for detecting bone metastases was 92%.

Patterns of distant metastases in patients with triple‐negative breast cancer—A population‐based study

AbstractThis study provided systematic insights into the patterns of triple‐negative breast cancer (TNBC) distant metastases (DM) and investigated the related elements for the prognosis prediction of TNBC patients based on a large sample. We reviewed eligible patients with TNBC from the SEER database between 2010 and 2015. We also analyzed differences in baseline characteristics among patients with diverse modes of metastasis. Meanwhile, we calculated proportional mortality ratio and expression of proportional trends in different patients. Subsequently, KM analysis was employed to investigate the survival outcomes. Finally, the predictive and prognostic factors of DM were identified. In this study, we included 24 822 TNBC patients, including 1026 DM patients and 23 796 non‐DM patients. At the time of initial diagnosis, 4.1% of patients had DM, and 36.9% had multiple metastases. According to the study, the most common sites of metastasis in DM patients were bone (251 cases) and lung (244 cases), while the least common organ of metastasis was brain (37 cases). Age, grade, T, N, and marital status were deemed as risk elements of DM. T stage, insurance status, marital status, surgery treatment, chemotherapy, number of metastatic sites, and metastatic sites also significantly affected the diagnosis of DM. Our study showed that the most common site of metastasis in TNBC patients with DM was bone and the least common site was brain. Different modes of metastasis have different survival and prognostic characteristics. Thus, our research may have important implications for the clinical practice of TNBC patients in the future.

Multimodal AI for prediction of distant metastasis in carcinoma patients.

Metastasis of cancer is directly related to death in almost all cases, however a lot is yet to be understood about this process. Despite advancements in the available radiological investigation techniques, not all cases of Distant Metastasis (DM) are diagnosed at initial clinical presentation. Also, there are currently no standard biomarkers of metastasis. Early, accurate diagnosis of DM is however crucial for clinical decision making, and planning of appropriate management strategies. Previous works have achieved little success in attempts to predict DM from either clinical, genomic, radiology, or histopathology data. In this work we attempt a multimodal approach to predict the presence of DM in cancer patients by combining gene expression data, clinical data and histopathology images. We tested a novel combination of Random Forest (RF) algorithm with an optimization technique for gene selection, and investigated if gene expression pattern in the primary tissues of three cancer types (Bladder Carcinoma, Pancreatic Adenocarcinoma, and Head and Neck Squamous Carcinoma) with DM are similar or different. Gene expression biomarkers of DM identified by our proposed method outperformed Differentially Expressed Genes (DEGs) identified by the DESeq2 software package in the task of predicting presence or absence of DM. Genes involved in DM tend to be more cancer type specific rather than general across all cancers. Our results also indicate that multimodal data is more predictive of metastasis than either of the three unimodal data tested, and genomic data provides the highest contribution by a wide margin. The results re-emphasize the importance for availability of sufficient image data when a weakly supervised training technique is used. Code is made available at: https://github.com/rit-cui-lab/Multimodal-AI-for-Prediction-of-Distant-Metastasis-in-Carcinoma-Patients.

A Novel Deep Learning Framework Based Mask-Guided Attention Mechanism for Distant Metastasis Prediction of Lung Cancer

Distant metastasis (DM) is the leading cause of death in advanced lung cancer, which is diagnosed by positron emission tomography (PET) scanning. Compared with the expensive price and nocuous contrast medium in PET, using computed tomography (CT) for DM diagnosis is more economical and convenient in clinical practice. However, most existing methods only analyze tumor regions to extract local features for DM prediction, which neglects the rich whole-lung information. To alleviate this problem, we propose a novel deep learning framework based mask-guided attention mechanism called Mask-Guided Two-stream Attention network (MGTA) for DM prediction, including a 3D pseudo-siamese feature pyramid network (PSFPN) to learn both global features in the whole lung and local features in tumor; and a deep cascaded attention module (DCAM) for further feature fusion. The proposed MGTA enjoys several merits. First, to the best of our knowledge, this is the first work to simultaneously mine tumor and whole-lung information through a mask-guided mechanism for DM prediction. Second, the proposed deep cascade attention module can effectively leverage the complementary multi-level features in PSFPN to enhance the feature recognition capacity of small tumors. Extensive experiments on a large-scale DM dataset including 2814 lung cancer patients show that the MGTA achieves good performance with area under the curve (AUC) of 0.822; sensitivity of 0.753; and specificity of 0.743, which outperforms state-of-the-art lung cancer diagnosis methods and the commonly used tumor-based methods. Furthermore, the MGTA shows large improvement especially when the training data size is small.

The pattern and treatment outcomes for rectal cancer with concurrent locoregional recurrence and distant metastases after total mesorectal excision

BackgroundTo study the pattern and treatment outcome of rectal cancer (RC) with concurrent locoregional recurrence (LR) and distant metastasis (DM) after total mesorectal excision (TME) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after concurrent LR and DM.MethodsRC patients who were diagnosed with concurrent LR and DM after TME from May 2015 to June 2019 were included in our study. All patients received single or multiple treatment modalities under the guidance of multidisciplinary team (MDT) of colorectal cancer in Fudan University Shanghai Cancer Center. The prognostic value of various clinicopathological factors for survival were calculated by Kaplan–Meier curves and Cox regression analyses.ResultsA total of 74 RC patients with concurrent LR and DM who had undergone TME with a median follow-up of 27 months were eligible for analysis. The median survival of the included patients was 34 months, and 30 patients (41%) died. Fifty-nine patients (80%) underwent comprehensive treatments. Patients with oligometastatic disease (OMD) achieved no evidence of disease (NED) status more frequently than those with multiple metastases (P = 0.003). In the univariate analysis, patients achieving NED, diagnosed with OMD and five or less peritoneal metastases tended to have longer survival after LR and DM diagnosis (P < 0.05). In the multivariate analysis, attaining NED status was the only independent factor for survival (hazard ratio (HR), 2.419; P = 0.032). Survival after concurrent LR and DM in the non-NED group was significantly shorter than that in the NED group (median survival, 32 vs. 46 months; HR, 2.7; P = 0.014).ConclusionsThe pattern and treatment outcome of RC with concurrent LR and DM after TME has changed with the development of multiple treatment modalities. Although the prognosis remains poor, pursuing NED status through comprehensive treatments may improve the survival of RC patients with concurrent LR and DM after TME.

Outcomes of Patients With Metastatic Differentiated Thyroid Cancer After Excellent Response to Treatment.

BackgroundTo evaluate the outcomes in differentiated thyroid cancer (DTC) patients who achieved excellent response to initial treatment and developed distant metastasis during follow-up.MethodsThyroid cancer patients registered in Chang Gung Memorial Hospital thyroid cancer database between January 1979 and December 2019 were assessed.ResultsAmong 1053 DTC patients with excellent response to initial therapy, 14 (1.3%) patients developed metastatic disease during follow-up, including 6 males and 8 females with median age of 50.2 years [interquartile range (IQR), 39.9-53.7]. Nine (64.3%) patients had papillary cancer, four (28.6%) had follicular cancer, and one (7.1%) had Hürthle cell cancer. Most patients (92.9%) had stage I disease at diagnosis. The sites of metastasis were lung (71.4%), bone (7.1%), mediastinum (7.1%) and multiple sites (14.3%). With a median follow-up of 18.3 years (IQR, 14.8-23.8), 2 patients had disease-specific mortality. The 5- and 10-year disease-specific survival after the diagnosis of distant metastasis was 92% and 74%, respectively. Multiple sites of metastasis was associated with increased risk of mortality (P = 0.022).ConclusionsA small proportion of DTC patients with an excellence response to initial therapy developed distant metastasis during follow-up. Multiple organ distant metastases conferred a worse disease-specific survival.

Tumor-targeted fluorescence labeling systems for cancer diagnosis and treatment.

Conventional imaging techniques are available for clinical identification of tumor sites. However, detecting metastatic tumor cells that are spreading from primary tumor sites using conventional imaging techniques remains difficult. In contrast, fluorescence‐based labeling systems are useful tools for detecting tumor cells at the single‐cell level in cancer research. The ability to detect fluorescent‐labeled tumor cells enables investigations of the biodistribution of tumor cells for the diagnosis and treatment of cancer. For example, the presence of fluorescent tumor cells in the peripheral blood of cancer patients is a predictive biomarker for early diagnosis of distant metastasis. The elimination of fluorescent tumor cells without damaging normal tissues is ideal for minimally invasive treatment of cancer. To capture fluorescent tumor cells within normal tissues, however, tumor‐specific activated target molecules are needed. This review focuses on recent advances in tumor‐targeted fluorescence labeling systems, in which indirect reporter labeling using tumor‐specific promoters is applied to fluorescence labeling of tumor cells for the diagnosis and treatment of cancer. Telomerase promoter‐dependent fluorescence labeling using replication‐competent viral vectors produces fluorescent proteins that can be used to detect and eliminate telomerase‐positive tumor cells. Tissue‐specific promoter‐dependent fluorescence labeling enables identification of specific tumor cells. Vimentin promoter‐dependent fluorescence labeling is a useful tool for identifying tumor cells that undergo epithelial–mesenchymal transition (EMT). The evaluation of tumor cells undergoing EMT is important for accurately assessing metastatic potential. Thus, tumor‐targeted fluorescence labeling systems represent novel platforms that enable the capture of tumor cells for the diagnosis and treatment of cancer.

Clinical course and outcome of differentiated thyroid cancer patients with pregnancy after diagnosis of distant metastasis.

There is no sufficient data about the clinical course and outcome in thyroid cancer patients who become pregnant after diagnosis of distant metastasis (DM). The current study was conducted to collect information regarding the clinical and reproductive characteristics, and outcomes in thyroid cancer patients who became pregnant after being diagnosed with DM. Records of 125 differentiated thyroid cancer (DTC) patients with age ≤45 years at DM diagnosis who had visited Ito Hospital from January 2005 to June 2021 were retrospectively reviewed. Among those 125 patients, 28 who became pregnant after DM diagnosis were classified as pregnancy group, and the remained 97 patients were classified as comparator group. In pregnancy group, the median age at malignancy diagnosis, DM diagnosis, and first pregnancy after DM diagnosis was 25 years (range, 4-41 years), 27 years (range, 11-41 years), and 32 years (range, 25-45 years), respectively. Fifty-five pregnancies and 40 live births were reported. Other pregnancy outcomes were miscarriage (n = 14) and induced abortion (n = 1). The 10-year progression-free survival (PFS) rates of pregnant and comparator group were 92.1% and 74.4%, respectively (p = 0.018). The multivariate analysis showed that multiple 131I treatment was independent negative prognostic factor for PFS (p = 0.046). DTC patients with age ≤45 years at DM diagnosis had good survival even though they became pregnant. Our results add to the information required for counseling thyroid cancer patients who have concerns about their fertility in the future.

Impact of 18FDG Positron Emission Tomography - Computed Tomography (PET-CT) on Management of Gallbladder Carcinoma

Background: Reports concerning the clinical usefulness 18F-FDG PET-CT for patients with gallbladder cancer are relatively scarce. The purpose of this study was to assess the diagnostic value of 18FGD- PET-CT in relation to a conventional imaging modality, multidetector row CT (MDCT), for patients with gallbladder cancer. Materials and Methods: Seventy patients with suspected gallbladder cancer who underwent both PET-CT and MDCT for initial staging were included in our study. The results of these two imaging modalities for evaluating primary tumors, regional lymph nodes and distant metastases were compared with the final diagnoses based on histopathological examination. Change in management of patients with gallbladder cancer based on PET-CT was also evaluated. Results: A maximum standardized uptake value (SUVmax) of 5.37 was taken as cutoff value for detecting a malignant tumor. PET-CT demonstrated no significant advantage over MDCT for the diagnosis of a primary tumor. PETCT showed a significantly higher accuracy (90.8 vs. 80.0%, P = 0.04) than that found for MDCT in the diagnosis of regional lymph node metastasis. PET-CT showed higher sensitivity (92.3 vs. 61.5%, P = 0.04) than that found for MDCT in the diagnosis of distant metastasis. Addition of PET-CT in preoperative staging of the disease changed management in 10 patients (14.3%). Conclusions: In patients with gallbladder carcinoma, the addition of 18FDG-PET-CT to standard staging CT may be helpful in detecting distant nodal metastasis and unsuspected metastatic disease that may preclude patients from surgical resection and result in a change of management in a significant number of patients.

The Association of Metastasis Pattern and Management of Metastatic Disease with Oncological Outcomes in Patients with Malignant Peripheral Nerve Sheath Tumors: A Multicenter Cohort Study.

Simple SummaryAround 40% of patients with MPNSTs develop distant metastasis (DM) within five years. Identification of MPNST patients more likely to develop DM and the identification of prognostic factors after DM diagnosis may guide clinical decision-making and may result in a better balance between quantity and quality of life. This study aimed to identify clinicopathologic and treatment-related factors associated with the development of DM and with overall survival (OS) after DM diagnosis. NF1, high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. This is the first study that reveals that NF1 status is also independently associated with worse survival after DM diagnosis with a median survival difference of more than 6 months between NF1 and no-NF1 patients. Purpose: This multicenter cohort study aimed to identify clinicopathologic and treatment-related factors associated with the development of distant metastasis (DM) and with overall survival (OS) after DM diagnosis in patients with malignant peripheral nerve sheath tumors (MPNST). Methods: All patients diagnosed with primary MPNST from 1988 to 2019 who were surgically treated for the primary tumor were included. Multivariable Cox regression analyses were performed to identify factors associated with DM and OS after DM diagnosis. Results: A total of 383 patients were included in this analysis, of which 150 developed metastatic disease. No differences in clinicopathologic characteristics and clinical outcome were found between patients with synchronous and metachronous DM. Neurofibromatosis type 1 (NF1), high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. NF1 and more than two metastasis sites were independently associated with worse OS after DM diagnosis. Metastasectomy, chemotherapy and the metastatic site category ‘other’ were associated with prolonged survival after DM diagnosis. Conclusions: This analysis provides important insights into clinicopathologic and treatment factors associated with outcomes in metastatic MPNST. Moreover, NF1-status is associated with a higher risk of DM; it is also independently associated with worse survival in metastatic MPNST.

Abstract PS13-41: Real-world evidence of platinum-based chemotherapy for the treatment of BRCA-positive metastatic breast cancer in a cohort of 33,878 women in the United States

Abstract Background The choice of chemotherapy for women diagnosed with metastatic breast cancer (BC) has been evolving as new agents and clinical trial results become available. Current NCCN guidelines recommend sequential single chemotherapeutic agents and combination therapy including platinum-based regimens for patients with high risk disease. Platinum-based chemotherapies are recommended for triple-negative breast cancer (TNBC) and, in particular, for a more defined population of TNBC with a BRCA mutation that may have particular sensitivity to platinum agents due to the impaired ability to repair DNA damage inherent in these patients.1 Here, we aim to leverage real world data to ascertain the use of platinum-based treatments in BRCA-mutation positive (BRCA+) metastatic BC patients, characterized by their hormonal receptor status. Methods Optum’s electronic health records (EHR) database was used to identify a cohort of women with 1) confirmed BC ICD-9/ICD-10 diagnosis between 2008 and 2018, 2) at least 12 months of history in the EHR, 3) at least one distant metastasis diagnosis (per ICD-9/ICD-10, or from physician notes), and 4) no previous diagnosis of other primary cancers in previous 12 months. BRCA-mutation status, ER, PR and HER2 test results were used to create relevant biomarker subgroups. Distinct lines of therapy (LOT) in the post-metastatic period were established using business rules, and the extent of use of platinum-based treatments, overall and of specific platinum regimens, were analyzed in various LOTs. Results Among 33,878 metastatic BC patients receiving a systemic chemotherapy, 8.7% were treated with a platinum-based regimen, while among the subgroup who were BRCA+, the proportion receiving platinum-based regimens was higher at 12.3%. In LOT2 and LOT3, the proportion receiving platinum regimens was 3.9% and 2.5% for the overall cohort, compared with 5.2% and 3.0% for the BRCA+ cohort. Within the BRCA+ cohort, the use of platinum-based regimens in TNBC patients was substantially higher than in other patients, accounting for 21.6%, 15.3% and 14.2% of patients in LOT1, LOT2 and LOT3 respectively, compared with 8.7%, 3.1% and 1.7% in ER+/PR+ patients (Table 1). The choice of specific platinum-containing combination regimens differed by biomarker cohorts; the combination of carboplatin and paclitaxel was most common in TNBC patients, while a quadruplet regimen was most used in the ER+/PR+ cohort. Conclusions Real-world evidence on use of platinum-based regimens in metastatic BC patients revealed differences across BRCA and hormonal status phenotypes. Women with TNBC had higher use of platinum agents than other subgroups across all lines of treatment. The observation that the use of platinum-based chemotherapy, including combination regimens, was highest in TNBC across lines of treatment highlights the persistent unmet need around alternative therapies for women affected with TNBC and BRCA+ disease. Table 1. Use of platinum-based regimens in women with metastatic BC in LOTs 1-3All metastatic BCBRCA+All BRCA+ER+/PR+TNBCN (treated with LOT1)33,8785,6494,228782Age at LOT1 start (in years): Median (IQR)63 (53-73)54 (46-64)54 (46-64)54 (45-62)Total proportion (%) of platinum-based regimens in LOT18.7%12.3%8.7%21.6%REGIMENCarboplatin+paclitaxel1.8%2.8%1.4%8.3%Carboplatin+docetaxel+pertuzumab+trastuzumab1.7%2.8%2.6%0.4%Carboplatin+docetaxel+trastuzumab1.2%1.9%1.8%0.3%Carboplatin+gemcitabine0.9%1.4%0.7%5.5%Carboplatin0.7%0.8%0.5%1.9%Carboplatin+docetaxel0.3%0.4%0.2%1.3%Cisplatin0.3%0.4%0.2%1.0%Other platinum-based regimens1.9%2.0%1.4%2.9%N (treated with LOT2)21,1484,1973,317495Total proportion (%) of platinum-based regimens in LOT23.9%5.2%3.1%15.3%N (treated with LOT3)13,9372,9592,523226Total proportion (%) of platinum-based regimens in LOT32.5%3.0%1.7%14.2%Footnotes1 Isakoff, SJ. Triple-Negative Breast Cancer: Role of Specific Chemotherapy Agents. Cancer J 2010;16: 53-61 Citation Format: Wendy Sebby, Alexander Liede, Debasish Mazumder, Anirban Ghosh, Eros Papademetriou, Ravi Potluri, Bruce Bach, Jerzy Tyczynski. Real-world evidence of platinum-based chemotherapy for the treatment of BRCA-positive metastatic breast cancer in a cohort of 33,878 women in the United States [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-41.

Abstract PD3-04: Prognostic role of distant disease-free interval from completion of adjuvant trastuzumab in HER2-positive early breast cancer: Analysis from the ALTTO (BIG 2-06) trial

Abstract Background: In HER2-positive breast cancer patients, timing from the end of (neo)adjuvant trastuzumab (T)-based therapy to diagnosis of metastatic breast cancer is the key factor in determining the optimal first-line treatment. There is currently lack of clear evidence to support the possible prognostic role of this interval and 12 months has been mostly empirically used. The present analysis aimed to investigate patterns of relapse, first-line choice and survival outcomes of patients with HER2-positive early breast cancer who relapsed after adjuvant T-based therapy depending on T-free interval (TFI, i.e. timing from end of adjuvant T to diagnosis of distant metastases). Methods: In ALTTO, HER2-positive early breast cancer patients were randomized to 1 year of either T alone, lapatinib (L) alone, their sequence (T–&amp;gt;L) or their combination (T+L). This exploratory analysis included only pts in the T or T+L arms who experienced a distant disease-free survival (DDFS) event. Two cohorts of patients were defined depending on TFI: group A (TFI of &amp;lt;12 months) and group B (&amp;gt;12 months). Baseline characteristics, patterns of relapse, first-line choice and overall survival (OS) were compared. OS was defined as time between date of DDFS event to death; age at diagnosis, tumor size and hormone receptor status were the variables included in the final multivariate models. Results: Out of 8,381 patients included in ALTTO, 404 patients in the T and T+L arms developed a DDFS event, of whom 201 occurred &amp;lt;12 months (group A) and 203 &amp;gt;12 months (group B) after the end of adjuvant T. Patients in group A were older (p=0.013), had larger tumors (p=0.004) and more frequently hormone receptor-negative disease (p&amp;lt;0.001). No significant difference in patterns of first DDFS event was observed (p=0.073); however, a numerically higher number of patients in group A compared to group B developed brain metastasis (26% vs. 15%). First-line anti-HER2 therapy was received by 57% of the patients. Choice of first-line anti-HER2 therapy was different between the two groups (p=0.022): the majority of patients received T in both groups (61% vs. 65% in groups A and B, respectively), while more patients in group A received L (25% vs. 11%) and less received pertuzumab (8% vs. 17%). OS survival was significantly shorter in group A compared to group B: median OS was 18.4 and 29.3 months in groups A and B, respectively (adjusted HR 0.69; 95% CI 0.54-0.89; p=0.004). Similar results were observed after the exclusion of patients treated with first-line pertuzumab-based therapy (n=29): median OS was 18.2 and 26.8 months in groups A and B, respectively (adjusted HR 0.66; 95% CI 0.51-0.86; p=0.002). Better outcomes in terms of OS for patients in group B was observed across all analyzed subgroups with no interaction according to hormone receptor status (p=0.814) nor type of adjuvant anti-HER2 treatment (p=0.233): hormone receptor-positive (adjusted HR 0.69; 95% CI 0.48-0.99), hormone receptor-negative (adjusted HR 0.68; 95% CI 0.48-0.98), T+L arm (adjusted HR 0.55; 95% CI 0.38-0.80) and T arm (adjusted HR 0.80; 95% CI 0.55-1.17). Conclusions: In the ALTTO trial, HER2-positive early breast cancer patients who experienced shorter TFI (i.e. &amp;lt;12 months vs. &amp;gt;12 months) following adjuvant T-based therapy had inferior OS after the diagnosis of distant recurrence. Given its prognostic value, TFI can help to individualize clinical recommendations and to design future trials in the metastatic setting for patients relapsing after prior exposure to anti-HER2 therapy for early disease. Citation Format: Matteo Lambertini, Dominique Agbor-Tarh, Otto Metzger-Filho, Noam Ponde, Francesca Poggio, Florentine Hilbers, Larissa A Korde, Saranya Chumsri, Olena Werner, Lucia Del Mastro, Rafael Caparica, Volker Moebus, Alvaro Moreno-Aspitia, Martine Piccart, Evandro de Azambuja. Prognostic role of distant disease-free interval from completion of adjuvant trastuzumab in HER2-positive early breast cancer: Analysis from the ALTTO (BIG 2-06) trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-04.

An analysis of distant metastasis cases from HPV-associated oropharyngeal squamous cell carcinoma

Although mostly associated with good survival outcomes, some patients with HPV-positive oropharyngeal squamous cell carcinoma develop distant metastasis and face dire prognosis. The aim of this study was to analyze distant metastatic patients in regards to survival, clinical staging, therapy approach and p16/HPV status.This retrospective single-centre study assessed patients with HPV-associated oropharyngeal cancer with distant metastasis treated in a tertiary referral center from 2005 to 2019. Overall- (OS) and survival after diagnosis of distant metastasis (OMS), clinical staging and different therapy approaches were assessed. Moreover, the overall mortality was assessed, as well as the association of different therapy approaches and p16/HPV status with the survival outcome.Out of 211 patients with HPV-associated oropharyngeal cancer that were treated in the study period, 15 developed distant metastases (7.1%). Median OS and OMS of the total group were 11 months (range 0.1–32 months) and 3 months (range 0.1–21 months), respectively. The overall mortality rate was 53.3% (n = 8). Significantly better outcome was present in patients treated with primary chemoradiotherapy (median OS 17 months vs. not reached, p = .03, median OMS 8 months vs not reached, p = .05). The OMS was significantly better in patients treated with chemotherapy initially after diagnosis (mean OMS 21 months vs 4 months; P = .001). Surgical resection after initial diagnosis was associated with a significantly shorter OMS (median OMS 3 vs. 21 months, p = .005). Interestingly, postoperative adjuvant therapy was delayed in all of these cases due to surgical site complications.Systemic treatment after initial diagnosis may be beneficial in clinical outcome of HPV associated distant metastases. Furthermore, surgical site complications should be treated with immediate care in order to avoid delay of adjuvant therapy. Further studies are warranted for validation of our results.

Performance of Long-Term CT and PET/CT Surveillance for Detection of Distant Recurrence in Patients with Resected Stage IIIA-D Melanoma.

Follow-up for patients with resected stage IIIA-D melanoma may include computed tomography (CT) or positron emission tomography (PET)/CT imaging to identify distant metastases. The aim of this study was to evaluate the test performance over follow-up time, of structured 6- and 12-monthly follow-up imaging schedules in these patients. We conducted a retrospective analysis of consecutive resected stage IIIA-D melanoma patients from Melanoma Institute Australia (2000-2017). Patients were followed until a confirmed diagnosis of distant metastasis, end of follow-up schedule, or death. Test accuracy was evaluated by cross-classifying the results of the test against a composite reference standard of histopathology, cytology, radiologic imaging, and/or clinical follow-up, and then quantified longitudinally using logistic regression models with random effects. In total, 1373 imaging tests were performed among 332 patients. Distant metastases were detected in 110 (33%) patients during a median follow-up of 61months (interquartile range 38-86), and first detected by imaging in 86 (78%) patients. 152 (68%) patients had at least one false-positive result. Sensitivity of the schedule over 5years was 79% [95% confidence interval (CI) 70-86%] and specificity was 88% (95% CI 86-90%). There was no evidence of a significant difference in test performance over follow-up time or by American Joint Committee on Cancer (AJCC) substage. The positive predictive value ranged between 33 and 48% over follow-up time, reflecting a ratio of 1:2 false-positives per true-positive finding. Regular 6- or 12-monthly surveillance imaging using CT or PET/CT has reasonable and consistent sensitivity and specificity over 5-year follow-up for resected stage IIIA-D melanoma patients. These data are useful when discussing the risks and benefits of long-term follow-up.

PCN179 Real-World Evidence on Metastatic or Relapsing Head and Neck Cancer

To evaluate the healthcare resource consumption and costs in charge of the Italian National Health System (NHS) of patients with relapsing or metastatic head and neck (H&N) cancer. From the ReS administrative database, adult patients with primary/secondary hospital diagnosis (ICD9-CM code) of H&N cancer were selected in 2015 (accrual period). At least a lymph node and/or distant metastasis diagnosis was searched in the same discharge form (index date for metastatic cancer). Incidence of metastasis was ascertained by the absence in two years before this index date. Chemo/radiotherapy in the accrual (index date for relapsing cancer) identified relapse events, if it was administered at least 6 months after the last treatment occurred in the previous period. Patients were characterized by gender, age and comorbidities of interest. Two-year hospitalizations, outpatient specialist care and healthcare costs were analysed, in the NHS perspective. One-year disease progression was identified as further chemo/radiotherapy use or newly hospital diagnosed metastasis. Out of >7 million inhabitants in 2015, 126 adults (2.0x100,000 inhabitants) had relapsing or metastatic H&N cancer. Males were the 89.7%. Mean age (±SD) was 63±11. Mainly men and elders had comorbidities: arterial hypertension was the most common one (45.2% of the cohort). During the last life month of died subjects, the NHS spent €2,668/patient. In the first follow-up year, mean overall cost per patient was €15,781, while €7,458 in the second one (n=79 subjects alive). Hospitalizations accounted for the highest expenditure. In 1-year follow-up, the disease progressed for 14 patients (11.1% of the cohort). On average, each subject with/without disease progression yearly costed €14,791/€15,904, considering the whole clinical and demographic picture. In the light of the evolving diagnostic and therapeutic options for subjects with H&N cancer, the real-world evidence at the healthcare management service can help optimize patient outcomes and clinician resources.