Absence Of Distant Metastases Research Articles

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): A prospective multicenter diagnostic cohort study in Asia.

196 Background: The benefit of standard esophagectomy in patients with clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) is disputable and the alternative of active surveillance should be studied. PreSANO study demonstrated that clinical response evaluations (CREs) are accurate to detect residual tumor after nCRT in patients with mainly adenocarcinoma, however, its applicability to esophageal squamous cell carcinoma (ESCC) is unknown. The preSINO trial (NCT03937362) aimed to assess the accuracy of CREs based on bite-on-bite biopsy, endoscopic ultrasonography with fine needle aspiration (EUS-FNA) of suspected lymph nodes, PET-CT in patients with ESCC, and to provide a basis for organ-sparing strategy of ESCC in Asia. Methods: Patients were eligible when they were planned for nCRT (CROSS regimen) followed by standard surgery. Patients received the first CRE (bite-on-bite biopsies) 4-6 weeks after completion of nCRT. Patients with locoregional residual tumor and without distant metastases underwent immediate surgery. In patients with a cCR at CRE-1, a second CRE (CRE-2) was done 10-12 weeks after completion of nCRT using PET-CT, bite-on-bite biopsies and EUS-FNA of suspicious lymph nodes. All patients underwent surgery irrespective of the outcome of CRE-2, in the absence of distant metastases. Circulating tumor DNA (ctDNA) analyses based on tumor-informed assay were performed at baseline and CREs for exploratory analysis. Primary endpoint was the accuracy of CREs for detecting TRG3-4 or TRG1-2 with ypN+ residual tumor. A false-negative rate (FNR) of 19.5% was considered acceptable according to the study protocol. Results: From Aug 20, 2019, to Jan 15, 2023, 309 patients were included of whom 250 patients underwent nCRT plus surgery. Eighteen of 133 patients with TRG3-4 or TRG1-2 with ypN+ residual tumor were not detected by bite-on-bite biopsies and EUS-FNA (FNR: 13.5%). Sensitivity, specificity, negative predictive value and positive predictive value of detecting any residual tumor were 82%, 93%, 69% and 97%, respectively. PET-CT detected interval distant metastases in 13 (5%) of 268 patients prior to surgery. Postoperative distant recurrence rate among patients with ctDNA-positive and ctDNA-negative during CREs were 15.1% (11/73) and 3.3% (2/59), respectively. Conclusions: Bite-on-bite biopsies and EUS-FNA for lymph nodes were accurate for detecting locoregional residual disease after nCRT in patients with ESCC. Post-nCRT ctDNA-positive during CREs may indicate an increased risk of long-term distant metastasis, potentially serving as a diagnostic tool to identify patients who would benefit from postponement of surgery and additional systemic therapy. The long-term follow-up results of this trial will further answer this question. Clinical trial information: NCT03937362 .

Traversing the Terrain: Potential Pitfalls within the AJCC 8th Edition Staging System for Lip and Oral Cavity Cancers.

In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

Abstract PO5-26-01: Assessing the effect of multimodal therapy in massive fungating breast cancers without distant metastasis

Abstract Background: Massive fungating breast cancers (MFBCs), which comprise exudative, foul-smelling tumors, the size of a child’s head or involve extensive ulceration are classified as locally advanced breast cancers. The National Comprehensive Cancer Network guidelines recommend preoperative neoadjuvant chemotherapy in patients with locally advanced breast cancer without distant metastases. However, limited evidence is available regarding the successful treatment of fungating breast cancers. In clinical practice, many fungating breast cancer cases are treated as stage IV tumors. This study aimed to investigate whether multimodal therapy, including surgery for giant breast cancers, can improve survival rates and whether the survival rates are comparable to those of other stage III breast cancers. Subjects and methods: Out of 1480 cases of primary breast cancer diagnosed at our hospital between June 2012 and March 2020, 123 patients with clinical stages IIIA–IIIC were chosen for analysis. Furthermore, 29 of these patients with MFBC were selected. During multimodal therapy for selected patients with fungating breast cancer, difficulties were encountered in some patients with single-stage skin suturing and closure after standard neoadjuvant chemotherapy. These patients underwent surgery with an additional skin flap or skin grafting. Furthermore, radiation therapy was added as needed. We compared the survival rates of these patients with those of patients who received drug therapy only according to the therapeutic protocol for Stage IV. Survival rates of patients with MFBC and other stage III breast cancers were also compared. Statistical analyses were conducted using the Kaplan–Meier curve and the log-rank test. Results: Of the 29 patients with MFBC, 22 (75.9%) and seven (24.1%) were treated with multimodal and palliative therapies, respectively. The median age and follow-up period of the multimodal therapy group were 62 (range: 43–94) years and 67 (range, 32–131) months, respectively. The corresponding values for the palliative therapy group were 79 (range: 42–88) years and 31 (range: 2–96) months. All patients in the palliative treatment group were hormone receptor positive and HER2 negative, and treatment with hormone therapy was initiated. The 7-year survival rate was significantly higher in the multimodal therapy group than in the palliative treatment group (92.3% vs. 68.6%, p = 0.0317). Furthermore, the 5-year distant recurrence-free rate was higher in the multimodal treatment group (79.3% vs. 63.5%). Local recurrence did not occur in any patient in the multimodal treatment group. There was no significant difference in the 7-year survival rates between patients with MFBC and those with other stage III breast cancers (86.8% vs. 75.3%; p = 0.239). Triple-negative breast cancer accounted for 20.8% (20 96) of the other stage III breast cancers, but none of these were MFBCs. Conclusions: Clinically, MFBCs are often palliatively treated as stage IV tumors, even in the absence of distant metastasis. However, the survival rate was significantly higher in the multimodal therapy group than in the palliative treatment group. Furthermore, the survival and distant recurrence-free rates for MFBC were higher than those for other stage III breast cancers. Therefore, patients with MFBCs should be actively treated using curative treatments. Citation Format: Tamaki Tamanuki, Maki Namura, Tomoyoshi Aoyagi, Haruhito Sakata, Mika Iwai, Shinichirou Shimizu, Hiroshi Matsuzaki. Assessing the effect of multimodal therapy in massive fungating breast cancers without distant metastasis [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 PO5-26-01.

Clinicopathological Findings and Treatment Outcomes of Patients with Primary Hepatobiliary Neuroendocrine Neoplasms: A Retrospective Single-institution Analysis.

Objective Primary hepatobiliary neuroendocrine neoplasms (NENs) are rare tumors exhibiting several morphological and behavioral characteristics. Considering the lack of relevant data on this topic, we evaluated the clinicopathological features and treatment outcomes of patients with primary hepatobiliary NENs. Methods/Patients We examined 43 consecutive patients treated at the National Cancer Center Hospital with pathological diagnoses of primary hepatobiliary NEN between 1980 and 2016. Results Nine patients were diagnosed with neuroendocrine tumor (NET) G1, 9 with NET G2, and 25 with neuroendocrine carcinoma (NEC) based on the World Health Organization 2019 classification. Patients with NEC had primary sites across the hepatobiliary organs, although sites in patients with NET G1 and NET G2 only included the liver and ampulla of Vater. Patients with primary extrahepatic bile duct or ampulla of Vater NENs tended to be diagnosed earlier than patients with primary gallbladder NENs. The median survival times in the NET G1, NET G2, and NEC groups were 167.9, 97.4, and 11.1 months, respectively. A good performance status, absence of distant metastases, and low tumor grade were identified as independent predictors of a favorable prognosis. Conclusion The NET-to-NEC ratio and tumor stage distribution at the diagnosis differed depending on the primary site. Patients with G1 and G2 NETs who underwent surgical resection had good prognoses, whereas those with NEC exhibited more advanced disease and poorer prognoses. The performance status, staging classification, and tumor grade are important factors to consider when devising an appropriate treatment strategy and predicting the prognoses of patients with primary hepatobiliary NEN.

Linking EMT Status of Circulating Tumor Cells to Clinical Outcomes in Lung Cancer.

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, with its prognosis influenced by complex biological factors. This study delves into the clinical relevance of circulating tumor cells (CTCs) and their Epithelial-Mesenchymal Transition (EMT) status in LC patients. We enrolled 30 newly diagnosed LC patients and utilized the CanPatrol technique for the separation and categorization of CTCs from peripheral blood samples. Immunofluorescent staining identified epithelial (CK8/18/19, EpCAM), mesenchymal (Vimentin, Twist), and leukocyte (CD45) markers in these cells. Fluorescence microscopy analyzed the slides, and RECIST 1.1 criteria assessed treatment response. Spearman's method was used to correlate CTCs' EMT states with their count and clinical characteristics. Our findings reveal three distinct CTC groups: epithelial (E-CTCs), hybrid epithelial/mesenchymal (E/M-CTCs), and mesenchymal (M-CTCs). Significant statistical differences were observed in stages III-IV vs I-II, tumor sizes T3-T4 vs T1-T2, and in the presence or absence of distant metastasis and lymph node involvement. Notably, the count of E/M-CTCs was positively correlated with TNM staging, tumor size, lymph node, and distant metastasis. Changes in M-CTC count pre- and post-treatment closely mirrored disease progression and control, showing considerable consistency with RECIST criteria. In conclusion, the EMT status of CTCs, especially E/M-CTCs, holds predictive value for LC staging, tumor size, and metastasis. Dynamic monitoring of M-CTCs can accurately reflect disease progression.

Radiotherapy can improve overall survival in patients with lymph-node positive, high-grade neuroendocrine cervical cancer: construction of two prognostic nomograms to predict treatment outcome.

To explore the beneficial subgroups after radiotherapy in high-grade neuroendocrine cervical cancer (HGNECC) and construct two survival prognosis models to quantify the efficacy of radiotherapy assessment. In this retrospective study, we included 592 eligible samples from the Surveillance, Epidemiology, and End Results (SEER) database and 56 patients with lymph-node positive HGNECC from Chongqing Medical University. Cox regression analysis was used to identify independent survival prognosis risk factors for HGNECC patients. Propensity score matching (PSM) was employed as it balances the baseline differences among grouping methods. Kaplan-Meier (K-M) curves were used to analyze survival differences among different groups. Two survival prediction nomograms were constructed separately (using the "rms" package in R software) based on whether radiotherapy was administered. The stability and accuracy of these models were assessed using receiver operating characteristic (ROC) curves and calibration curves in both the training and validation datasets. P<0.05 was considered to indicate statistically significant differences. Age, Federation of Gynecology and Obstetrics (FIGO)-stage, and treatment methods (surgery vs. chemotherapy) were independent risk factors that affected survival prognosis (P<0.05). Radiotherapy showed adverse effects on survival in patients with early tumor staging, lymph-node negative status, and absence of distant metastasis (all P<0.05). The lymph-node positive group had a beneficial response to radiotherapy (P<0.05), and patients with metastasis in the radiotherapy group showed a survival protection trend (P=0.069). In HGNECC, patients with lymph-node positive status can benefit from radiotherapy in terms of survival outcomes. We constructed two survival prediction models based on whether radiotherapy was administered, thereby offering a more scientifically guided approach to clinical treatment planning by quantifying the radiotherapy efficacy.

Automatic Detection of Distant Metastasis Mentions in Radiology Reports in Spanish.

A critical task in oncology is extracting information related to cancer metastasis from electronic health records. Metastasis-related information is crucial for planning treatment, evaluating patient prognoses, and cancer research. However, the unstructured way in which findings of distant metastasis are often written in radiology reports makes it difficult to extract information automatically. The main aim of this study was to extract distant metastasis findings from free-text imaging and nuclear medicine reports to classify the patient status according to the presence or absence of distant metastasis. We created a distant metastasis annotated corpus using positron emission tomography-computed tomography and computed tomography reports of patients with prostate, colorectal, and breast cancers. Entities were labeled M1 or M0 according to affirmative or negative metastasis descriptions. We used a named entity recognition model on the basis of a bidirectional long short-term memory model and conditional random fields to identify entities. Mentions were subsequently used to classify whole reports into M1 or M0. The model detected distant metastasis mentions with a weighted average F1 score performance of 0.84. Whole reports were classified with an F1 score of 0.92 for M0 documents and 0.90 for M1 documents. These results show the usefulness of the model in detecting distant metastasis findings in three different types of cancer and the consequent classification of reports. The relevance of this study is to generate structured distant metastasis information from free-text imaging reports in Spanish. In addition, the manually annotated corpus, annotation guidelines, and code are freely released to the research community.

An Innovative Non-Linear Prediction Model for Clinical Benefit in Women with Newly Diagnosed Breast Cancer Using Baseline FDG-PET/CT and Clinical Data.

Objectives: We aimed to develop a novel non-linear statistical model integrating primary tumor features on baseline [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), molecular subtype, and clinical data for treatment benefit prediction in women with newly diagnosed breast cancer using innovative statistical techniques, as opposed to conventional methodological approaches. Methods: In this single-center retrospective study, we conducted a comprehensive assessment of women newly diagnosed with breast cancer who had undergone a FDG-PET/CT scan for staging prior to treatment. Primary tumor (PT) volume, maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on PET/CT. Clinical data including clinical staging (TNM) but also PT anatomical site, histology, receptor status, proliferation index, and molecular subtype were obtained from the medical records. Overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) were assessed as endpoints. A logistic generalized additive model was chosen as the statistical approach to assess the impact of all listed variables on CB. Results: 70 women with newly diagnosed breast cancer (mean age 63.3 ± 15.4 years) were included. The most common location of breast cancer was the upper outer quadrant (40.0%) in the left breast (52.9%). An invasive ductal adenocarcinoma (88.6%) with a high tumor proliferation index (mean ki-67 expression 35.1 ± 24.5%) and molecular subtype B (51.4%) was by far the most detected breast tumor. Most PTs displayed on hybrid imaging a greater volume (12.8 ± 30.4 cm3) with hypermetabolism (mean ± SD of PT maximum SUVmax, SUVmean, MTV, and TLG, respectively: 8.1 ± 7.2, 4.9 ± 4.4, 12.7 ± 30.4, and 47.4 ± 80.2). Higher PT volume (p < 0.01), SUVmax (p = 0.04), SUVmean (p = 0.03), and MTV (<0.01) significantly compromised CB. A considerable majority of patients survived throughout this period (92.8%), while five women died (7.2%). In fact, the OS was 31.7 ± 14.2 months and PFS was 30.2 ± 14.1 months. A multivariate prediction model for CB with excellent accuracy could be developed using age, body mass index (BMI), T, M, PT TLG, and PT volume as predictive parameters. PT volume and PT TLG demonstrated a significant influence on CB in lower ranges; however, beyond a specific cutoff value (respectively, 29.52 cm3 for PT volume and 161.95 cm3 for PT TLG), their impact on CB only reached negligible levels. Ultimately, the absence of distant metastasis M displayed a strong positive impact on CB far ahead of the tumor size T (standardized average estimate 0.88 vs. 0.4). Conclusions: Our results emphasized the pivotal role played by FDG-PET/CT prior to treatment in forecasting treatment outcomes in women newly diagnosed with breast cancer. Nevertheless, careful consideration is required when selecting the methodological approach, as our innovative statistical techniques unveiled non-linear influences of predictive biomarkers on treatment benefit, highlighting also the importance of early breast cancer diagnosis.

How unknown is metastatic carcinoma to cervical lymph nodes from an unknown primary?

The term metastatic carcinoma to cervical lymph nodes from an unknown primary includes a small group of tumors that present themselves with metastases to the cervical nodes, and in which diagnostic methods do not reveal the primary source of these metastases. Histologically, in most cases, these are metastases of squamous cell carcinoma. Carcinomas of unknown primary metastatic to cervical nodes account for &lt; 5% of carcinomas of unknown primary and &lt; 5% of head and neck cancers. The optimal treatment has not yet been defined. In the absence of distant metastases, the intention of treatment is curative. Patients are treated mostly with combined approaches including surgery, radiotherapy, or concomitant chemoradiotherapy. Radiotherapy is part of the treatment algorithm in most of the referenced works and includes irradiation of the mucosal sites of the pharyngeal axis as a potential localization of the primary tumor and unilateral or, more often, bilateral irradiation of the neck. Due to the higher risk of late toxicities observed, individualization of irradiated volumes based on the extent of the disease or other clinical parameters is a rational way to reduce these risks. Purpose: The presented work discusses the treatment options for patients with metastatic carcinoma to cervical lymph nodes from an unknown primary. Furthermore, the work reports on the high effectiveness of curative radiotherapy in this group of tumors.

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study.

Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size. We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression. High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC. Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.

Safe and curative modified two-stage operation for T4 esophageal cancer after definitive chemoradiotherapy: a case report

BackgroundThe prognosis of esophageal cancer (EC) with organ invasion is extremely poor. In these cases, definitive chemoradiotherapy (CRT) followed by salvage surgery can be planned; however, the issue of high morbidity and mortality rates persists. Herein, we report the long-term survival of a patient with EC and T4 invasion who underwent a modified two-stage operation after definitive CRT.Case presentationA 60-year-old male presented with type 2 upper thoracic EC with tracheal invasion. First, definitive CRT was performed, which resulted in tumor shrinkage and improvement in the tracheal invasion. However, an esophagotracheal fistula subsequently developed, and the patient was treated with fasting and antibiotics. Although the fistula recovered, severe esophageal stenoses made oral intake impossible. To improve quality of life and cure the EC, a modified two-stage operation was planned. In the first surgery, an esophageal bypass was performed using a gastric tube with cervical and abdominal lymph node dissections. After confirming improved nutritional status and absence of distant metastasis, the second surgery was performed with subtotal esophagectomy, mediastinal lymph node dissection, and tracheobronchial coverage of the fistula. The patient discharged without major complications after radical resection and has been recurrence-free for 5 years since the start of treatment.ConclusionA standard curative strategy could be difficult for EC with T4 invasion due to differences in the invaded organs, presence of complications, and patient condition. Therefore, patient-tailored treatment plans are needed, including a modified two-stage operation.

Combination of CEACAM5, EpCAM and CK19 gene expressions in mediastinal lymph node micrometastasis is a prognostic factor for non-small cell lung cancer

BackgroundLung cancer is known as the most common and highly metastatic form of cancer worldwide. Tumour node metastasis (TNM) staging is the gold standard classification system for the decision-making process for appropriate treatment. Particularly N status has the most important prognostic value in the absence of distant metastasis. Traditional diagnostic methods are capable of detecting metastasis; however, they may fail to detect micrometastasis, which plays a role in disease recurrence and patients' long-term survival. Occult micrometastasis can change the tumour's TNM staging and, consequently, the patient's treatment regimen.MethodsThe median number of three lymph node tissues were collected from 30 patients who underwent surgery for non-small cell lung cancer. Lymph node tissues were collected from different lymph node stations according to the location of the patient's tumour. CK19, EpCAM and CEACAM5 gene expressions were analysed in tissues using quantitative real-time polymerase chain reaction to detect micrometastasis in distant lymph nodes.ResultsTriple positivity was seen in 26 out of 30 patients which 19 patients were upstaged from N0 to N2. While survival was not significantly affected between upstaged and non-upstaged patients, patients upstaged with multiple-station N2 had a significantly higher recurrence and lower survival compared to single-station N2.ConclusionA combination of CK19, EpCAM and CEACAM5 gene expressions in lymph nodes can be used to identify micrometastasis which postoperatively may be used as a tool to predict patients’ recurrence and survival.

Hemorrhagic Shock After Endoscopic Biopsy of Sigmoid Cancer: Pseudoaneurysm of the Rectal Superior Artery.

CASE REPORT An 86-year-old man without significant comorbidity presented with weight loss, diarrhea, and iron deficiency anemia. No signs of gastrointestinal bleeding were noticed. Colonoscopy was performed, and sigmoid cancer was suspected (a). Biopsies were obtained, which confirmed colonic adenocarcinoma. Eight hours after the endoscopy, the patient developed massive hematochezia, followed by hemodynamic instability (blood pressure 60/30 mm Hg; heart rate 120 bpm; and hemoglobin drop from 9.8 g/dL to 6.1 g/dL within 2 hours). After stabilization with intravenous fluids, norepinephrine, and transfusion of 1 unit of red blood cells, endoscopy was repeated and ruled out ongoing bleeding. A computed tomography scan confirmed a mass of the sigmoid colon, which extended along the inferior mesenteric artery and to the os sacrum. Within the sigmoid wall, extravasation of the contrast medium was seen into a structure of 2.3 × 1.7 cm. Computed tomography reconstructions suspected pseudoaneurysm of the inferior mesenteric artery (Figures B, C). In the absence of distant metastases, surgical resection was attempted urgently. However, owing to infiltration of the aortic wall, curative resection was impossible and colostomy was performed. Angiography confirmed a large pseudoaneurysm of the rectal superior artery, and embolization was performed successfully. The further course was unremarkable. Pseudoaneurysm of the inferior mesenteric artery is rare. To our knowledge, a case with hemorrhagic shock after endoscopic biopsy caused by cancer-associated pseudoaneurysm has not been reported so far. DISCLOSURES Author contributions: A. Probst: conception and design, analysis and interpretation of the data, drafting of the article. M. Ayoub, F. Sommer, and F. Schwarz: analysis and interpretation of the data. H. Messmann: critical revision of the article, final approval of the article. Financial disclosure: None to report. Informed consent was obtained for this case report.

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.

Prognostic factors in radiotherapy of anaplastic thyroid carcinoma: a single center study over 31 years

BackgroundAnaplastic thyroid carcinoma has a very poor prognosis. We analyzed the effect of surgery, radiotherapy and chemotherapy on survival time and side effects in patients with ATC.MethodsWe retrospectively analyzed all patients (n = 63) with histologically confirmed ATC who presented at our clinic between 1989 and 2020. We analyzed the survival with Kaplan–Meier curves and cox proportional hazard models and acute toxicities with logistic regression models.ResultsOut of 63 patients, 62 received radiotherapy, 74% underwent surgery and 24% received combined chemotherapy. A median radiation dose of 49 Gy (range 4–66 Gy) was applied. In 32% of the cases opposing-field technique was used, in 18% 3D-conformal, in 27% a combination of opposing field and 3D-conformal technique and 21% obtained IMRT (intensity modulated radiotherapy) or VMAT (volumetric modulated arc radiotherapy). Median overall survival (OS) was 6 months. We identified five predictive factors relevant for survival: absence of distant metastases at the time of diagnosis (OS 8 months), surgery (OS 9.8 months), resection status R0 (OS 14 months), radiation dose of 50 Gy or higher (OS 13 months) and multimodal therapy (surgery, radiotherapy and chemotherapy) with a median OS of 9.7 months.ConclusionIn spite of the dismal outcome, longer survival can be achieved in some patients with ATC using surgery and radiotherapy with a high radiation dose. Compared to our previous study, there are no significant advantages in overall survival.Trial registration Retrospectively registered.

A prospective cohort study on active surveillance after neoadjuvant chemoradiotherapy for esophageal cancer: protocol of Surgery As Needed for Oesophageal cancer-2

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is a standard treatment for potentially curable esophageal cancer. Active surveillance in patients with a clinically complete response (cCR) 12 weeks after nCRT is regarded as possible alternative to standard surgery. The aim of this study is to monitor the safety, adherence and effectiveness of active surveillance in patients outside a randomized trial.MethodsThis nationwide prospective cohort study aims to accrue operable patients with non-metastatic histologically proven adenocarcinoma or squamous cell carcinoma of the esophagus or esophagogastric junction. Patients receive nCRT and response evaluation consists of upper endoscopy with bite-on-bite biopsies, endoscopic ultrasonography plus fine-needle aspiration of suspicious lymph nodes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan. When residue or regrowth of tumor in the absence of distant metastases is detected, surgical resection is advised. Patients with cCR after nCRT are suitable to undergo active surveillance. Patients can consult an independent physician or psychologist to support decision-making. Primary endpoint is the number and severity of adverse events in patients with cCR undergoing active surveillance, defined as complications from response evaluations, delayed surgery and the development of distant metastases. Secondary endpoints include timing and quality of diagnostic modalities, overall survival, progression-free survival, fear of cancer recurrence and decisional regret.DiscussionActive surveillance after nCRT may be an alternative to standard surgery in patients with esophageal cancer. Similar to organ-sparing approaches applied in other cancer types, the safety and efficacy of active surveillance needs monitoring before data from randomized trials are available.Trial registrationThe SANO-2 study has been registered at ClinicalTrials.gov as NCT04886635 (May 14, 2021) – Retrospectively registered.

Apalutamide in the treatment of a patient with non-metastatic castration-resistant prostate cancer

The treatment of patients with prostate cancer, who do not qualify for the radical therapy is based on the use of surgical or pharmacological castration methods. The effectiveness of the so-called androgen deprivation tends to decrease over time. Even in the absence of distant metastases on imaging studies, the resistance for the hormonal castration may be developed. At this moment, the use of new generation androgen receptor inhibitors may reduce the risk of metastases or death. The paper presents a case report of a patient with prostate cancer without distant metastases who started therapy with apalutamide at the moment of developing re-sistance to the pharmacological castration.

Clinical characteristics and prognosis of anaplastic thyroid carcinoma: a 20-year single-center retrospective study

Objectives: To investigate the clinical characteristics and prognoses of patients with anaplastic thyroid carcinoma(ATC), and to explore the value of multi-modality treatment in improving overall survival(OS) of ATC patients. Methods: Medical records including clinicopathological data of patients diagnosed with ATC at Cancer Hospital, Chinese Academy of Medical Sciences between 2001 and 2020 were retrospectively analyzed. The cohort were divided into surgery-only and multi-modality subgroups, and the latter included patients treated with surgery plus radiotherapy and/or medical therapy(including chemotherapy, target therapy and immunotherapy). Univariate survival analysis was conducted through Kaplan-Meier method, and multivariate survival analysis was performed using Cox proportional hazard model. Results: A total of 47 patients were included in the study, including 24 males and 23 females, with a median age of 63 years. After a median follow-up duration of 3.37 months, 42 patients died due to tumor recurrence or progression. The median OS of the cohort was 4.33 months. Univariate survival analysis demonstrated that symptoms of recurrent laryngeal nerve(RLN) involvement, distant metastasis, leukocyte elevation, and treatment modality were significantly associated with OS (P values all<0.05). Multivariate analysis showed that symptoms of RLN involvement(HR=2.49, 95%CI: 1.16-5.32, P=0.019), distant metastasis(HR=2.33, 95%CI: 1.06-5.16, P=0.036), and leukocyte elevation(HR=2.50, 95%CI: 1.16-5.40, P=0.020) were all independent risk factors for OS, while multi-modality therapy significantly prolonged OS compared with surgery alone(HR=0.22, 95%CI: 0.10-0.47, P<0.001). Conclusions: Among ATC patients, absence of symptoms of RLN invasion, normal leukocyte level and absence of distant metastasis at initial diagnosis are all independent protective factors for OS and multi-modality treatment can help to improve the prognosis.

Comparison of clinicopathological characteristics and survival between symptomatic and asymptomatic anaplastic thyroid carcinoma

Although anaplastic thyroid carcinoma (ATC) is a fatal form of thyroid cancer with an overall survival of only a few months, there are some factors associated with longer survival. However, it remains unknown whether asymptomatic ATC differs from symptomatic ATC in terms of characteristics and overall prognosis. Therefore, we aimed to examine the clinicopathological characteristics and prognosis of asymptomatic ATC compared with those of symptomatic ATC. We retrospectively reviewed the medical records of 113 patients with ATC who were registered at our institution between November 1994 and July 2020. A total of 86 patients (59 women and 27 men; mean age, 66.9 ± 11.1 years) were enrolled for analysis. The clinicopathological characteristics of the ATC cohort were evaluated, and prognostic factors associated with disease-specific mortality were assessed. Of the 86 patients with ATC, 78 were symptomatic and eight were asymptomatic. Compared with the symptomatic group, the asymptomatic group had a younger age at diagnosis (59.3 ± 10.3 vs. 67.7 ± 11.0 years, p = 0.045), smaller tumor size (2.8 ± 1.2 vs. 5.8 ± 2.0 cm, p < 0.001), and longer survival period (37.5 ± 46.4, 9.5 ± 16.8 months, p < 0.001). However, the ATC component (%) of the tumor, sex, ultrasonographic risk category, and distant metastasis at diagnosis did not differ significantly between the two groups. In the multivariate Cox regression analysis, asymptomatic ATC (HR: 0.33, 95% CI 0.11–0.99, p = 0.045) and absence of distant metastasis (hazard ratio (HR): 0.56, 95% Confidence interval (CI) 0.35–0.88, p = 0.012) were associated with longer survival. Patients with asymptomatic ATC have a smaller tumor size, a longer survival period, and a younger age than those with symptomatic ATC. Being asymptomatic and having no distant metastasis were associated with longer survival in patients with ATC in a clinical setting.

Prognostic analysis of telangiectatic osteosarcoma of the extremities.

Telangiectatic osteosarcoma (TOS) is a rare but highly malignant subtype of osteosarcoma. Although surgical treatment is the primary treatment modality for osteosarcoma, evidence on the benefits of different surgical methods in patients with TOS is lacking. This study aimed to compare the effects of different surgical and adjuvant treatments on overall survival of TOS, and the association of patient demographics, oncological characteristics, and socioeconomic status on treatment outcomes. This retrospective study selected the most common TOS cases of the extremities registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1989 to 2019. Univariate and multivariate Cox regression models were used to analyze all prognostic factors, and Kaplan-Meier analyses were performed for disease-specific treatment factors of survival. A total of 127 patients were included in the analysis. The average age at initial diagnosis was 20.09 years. In univariate analyses, the absence of metastasis at initial diagnosis, limb-salvage surgery, adjuvant chemotherapy, and no regional lymph node dissection were associated with a lower risk of death. Multivariate analysis further showed that the presence or absence of distant metastasis and regional lymph node dissection, implementation of adjuvant chemotherapy, and choice of surgical method were independent predictors of prognosis. Distant metastasis and regional lymph node dissection are associated with poorer outcomes in TOS, and amputation has no better prognosis than limb salvage surgery. Compared with conventional chemotherapy, neoadjuvant chemotherapy did not significantly improve the prognosis of TOS.