Metastatic Sites Research Articles

Elacestrant in ER+, HER2- Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups.

Elacestrant significantly prolonged progression-free survival (PFS) with manageable safety versus standard-of-care (SOC) endocrine therapy (ET) in patients with estrogen receptor-positive (ER+), HER2- metastatic breast cancer and tumors harboring estrogen receptor 1 (ESR1) mutation following ET plus a cyclin-dependent kinase 4/6 inhibitor (ET+CDK4/6i). In patients with ESR1-mutated tumors, we evaluated the efficacy and safety of elacestrant versus SOC based on prior ET+CDK4/6i duration and in clinical subgroups with prior ET+CDK4/6i ≥12 months. EMERALD, an open-label phase III trial, randomly assigned patients with ER+, HER2- metastatic breast cancer who had received 1-2 prior lines of ET, mandatory CDK4/6i, and ≤1 chemotherapy to elacestrant (345 mg daily) or SOC (aromatase inhibitor or fulvestrant). PFS was assessed across subgroups in post hoc exploratory analyses without adjustment for multiple testing. In patients with ESR1-mutated tumors and prior ET+CDK4/6i ≥12 months, the median PFS for elacestrant versus SOC was 8.6 versus 1.9 months (HR, 0.41; 95% confidence interval, 0.26-0.63). In this population, the median PFS (in months) for elacestrant versus SOC was 9.1 versus 1.9 (bone metastases), 7.3 versus 1.9 (liver and/or lung metastases), 9.0 versus 1.9 (<3 metastatic sites), 10.8 versus 1.8 (≥3 metastatic sites), 5.5 versus 1.9 (PIK3 catalytic subunit α mutation), 8.6 versus 1.9 (tumor protein p53 gene mutation), 9.0 versus 1.9 (HER2-low), 9.0 versus 1.9 (ESR1D538G-mutated tumors), and 9.0 versus 1.9 (ESR1Y537S/N-mutated tumors). Subgroup safety was consistent with the overall population. The duration of prior ET+CDK4/6i ≥12 months in metastatic breast cancer was associated with a clinically meaningful improvement in PFS for elacestrant compared with SOC and was consistent across all subgroups evaluated in patients with ER+, HER2-, ESR1-mutated tumors.

Management of de novo Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) and the role of Radiation Therapy: A Consensus by the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Prostate cancer treatments paradigms are in continuous evolution, especially in metastatic setting. In this context, the Genito-Urinary (GU) Group of Italian Association of Radiotherapy and Clinical Oncology (AIRO) aimed to create a Consensus on radiotherapy indication in de novo metastatic hormone sensitive prostate cancer both on primary tumour and metastatic sites. A panel of experts, involved in clinical management of prostate cancer, through the estimate-talk-estimate (ETE) method, developed a list of items and correspondent statements on the identified topic. Seven conclusive items were identified with 12 statements about the chosen topic, radiotherapy in metastatic hormone sensitive prostate cancer on primary tumour and metastatic sites. This consensus might help clinicians in prostate cancer managing in daily clinical practice.

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.

EP.03G.01 Comparison of Tumor Immune Microenvironments Between Primary and Metastatic Sites in Non-Small Cell Lung Cancer

EP.03G.01 Comparison of Tumor Immune Microenvironments Between Primary and Metastatic Sites in Non-Small Cell Lung Cancer

A study on direct metastasis to levels III, IV in oral tongue squamous cell carcinoma

ObjectiveThis study aimed to determine the frequency and specific metastatic patterns of direct metastasis to levels III and IV in oral tongue squamous cell carcinoma (OTSCC) among Japanese individuals. MethodsWe conducted neck dissections on 319 patients at our department from January 2001 to December 2020. Of these, 220 patients with histopathological evidence of lymph node metastasis were included in the study. Lymph node metastases were categorized by level to elucidate the metastatic patterns. Additionally, metastatic sites within level III were identified as either anterior or posterior to the internal jugular vein, and these findings were compared between the direct metastatic group and the non-direct metastatic group. ResultsAmong the patients, 13 experienced direct metastases to level III or IV. Specifically, 12 patients had metastases at level III, and one patient had metastases at both levels III and IV, constituting 5.9% (13/220) of those with cervical lymph node metastasis in OTSCC. No patients exhibited direct metastases solely to level IV. Within level III, the direct metastasis group showed a significantly higher incidence of metastasis anterior to the internal jugular vein (p = 0.03). ConclusionsDirect metastasis to levels III and/or IV occurred in 5.9% of the cases. Although elective neck dissection up to level III is generally sufficient, metastasis to level IV, while infrequent, can occur. Therefore, vigilant follow-up with attention to the lower neck regions is crucial.

Rapid Autopsy to Define Dendritic Cell Spatial Distribution and T Cell Association in Lung Adenocarcinoma.

Immunotherapy response is associated with the presence of conventional dendritic cells (cDCs). cDC type 1 (cDC1) is critically important for CD8+ T cell activation, cDC type 2 (cDC2) regulates CD4+ T cell responses, and mature regulatory cDCs may dampen T cell responses in the tumor microenvironment (TME). However, we lack a clear understanding of cDC distribution in the human TME, cDC prevalence in metastatic sites, and cDC differences in early- versus late-stage disease. Rapid autopsy specimens of 10 patients with lung adenocarcinoma were evaluated to detect cDCs and immune cells via multiplex immunofluorescence using 18 markers and 42 tumors. First, we found that T cells, cDC1, and cDC2 were confined to stroma, whereas mature regulatory DCs were enriched in tumor, suggesting unique localization-specific functions. Second, lung and lymph node tumors were more enriched in T cells and cDCs than liver tumors, underscoring differences in the TME of metastatic sites. Third, although the proportion of T cells and cDC1 did not differ in different stages, an increase in the proportion of cDC2 and macrophages in late stage suggests potential differences in regulation of T cell responses in different stages. Collectively, these findings provide new, to our knowledge, insights into cDC biology in human cancer that may have important therapeutic implications.

LNMAC Promotes Cervical Squamous Cell Carcinoma Lymphatic Metastasis via Epigenetic Regulation of FGF2-Induced Lymphangiogenesis.

The lymph node is the most common site of distant metastasis of cervical squamous cell carcinoma (CSCC), which elicits dismal prognosis and limited efficiency for treatment. Elucidation of the mechanisms underlying CSCC lymphatic metastasis would provide potential therapeutic strategies for nodal metastatic of CSCC. Here, based on in vivo lymphatic metastasis screening model, a circular RNA is identified that is termed as lymph node metastasis associated circRNA (LNMAC), is markedly upregulated in lymphatic metastatic CSCC and correlated with lymph node metastasis. Overexpression of LNMAC dramatically augments the metastatic capability of CSCC cells to the lymph node via inducing lymphangiogenesis. Mechanistically, LNMAC epigenetically upregulates fibroblast growth factor 2 (FGF2) expression by directly associating with histone acacetylase 1 (HDAC1), preventing Importin α6/8-mediated nuclear translocation of HDAC1 and eliciting histone H3K27ac-induced FGF2 transcriptional activation. Treatment with 3F12E7, an anti-FGF2 monoclonal antibody, effectively inhibits LNMAC-induced CSCC lymphatic metastasis. Taken together, these findings indicate that LNMAC plays a crucial role in FGF2-mediated lymphangiogenesis and lymphatic metastasis, highlighting that LNMAC might be a therapeutic target for lymph node metastasis in CSCC patients.

Brain metastases in newly diagnosed lung cancer: epidemiology and conditional survival.

The brain serves as the primary site for metastasis in patients with both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The presence of lung cancer with brain metastasis (LCBM) is a debilitating condition associated with considerable morbidity and mortality. The objective of this study was to assess the incidence and survival rates of LCBM in the United States population. We analyzed a total of 9,212 patients diagnosed with LCBM between 2010 and 2015, extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis assessed the incidence, relative survival, and conditional survival (CS) of LCBM. We utilized the Kaplan-Meier method to estimate overall survival and determine CS at year y+x after x years of survival, following the formula CS(y|x) = CS(y+x)/CS(x). Prognostic factor selection was performed using the least absolute shrinkage and selection operator (LASSO) regression approach, and multivariate Cox regression was employed to demonstrate the impact of these predictors on outcomes and construct a CS-based nomogram. The overall age-adjusted incidence rate of LCBM was 5.82 cases per 100,000, with a slight decline observed during our study period. Patient relative survival showed a continuous decline with increasing age. CS analysis revealed that the 5-year CS rate for patients initially diagnosed with LCBM adjusted from 3% to 13%, 28%, 52%, and 73% over successive years of survival (1-4 years). Identified predictors included age at diagnosis, sex, race, tumor size, tumor grade, surgery, radiotherapy, and chemotherapy. These predictors, along with the CS formula, were employed to develop a CS-based nomogram for real-time prognosis prediction. Calibration curve, area under the time-dependent receiver operating characteristic (ROC) curve, concordance index (c-index), and decision curve analysis (DCA) demonstrated the model's strong predictive capabilities. This study deepened our understanding of LCBM patients, summarizing their epidemiological characteristics and CS patterns. We successfully developed a novel CS-based nomogram model for dynamic survival estimation, offering real-time and personalized prognostic information that is clinically valuable.

Male breast cancer: a 32-year retrospective analysis in radiation therapy referral center in northern Iran

Background: Breast cancer commonly occurs in women, and male breast cancer makes up less than 1% of all cases of breast cancer. The limited prevalence of male breast cancer has led to decreased attention being paid to this condition, resulting in its diagnosis occurring at later ages and at more severe disease stages. Objectives: This study evaluates the demographic and clinicopathological characteristics of male patients diagnosed with breast cancer who visited the northern region of Iran from 1992 to 2023. Methods: This descriptive study reviewed data from 58 cases of male breast cancer between 1992 and 2023. The study aimed to examine and describe the information connected to these patients. The data were analyzed with SPSS.22 set at P value less than 0.05. Results: The mean age of the patients examined was 62.10±13.40 years, while their mean BMI was 27.08±4.95. The study found no statistically significant correlation between BMI with stage and kinds of recurrence, including metastasis and local recurrence (P&gt;0.05). The right and left breast involvement rates were equal (48.28%) in 28 cases, and 2 cases (3.40%) had bilateral involvement. The bone was the predominant site of metastasis, accounting for 69.23% of cases. The analysis revealed no significant correlation between stage and metastasis (P=1.000) or local recurrence (P=0.543). Most metastasis and all the local recurrence were observed in stages 3 and 4. Conclusion: Male breast cancer mainly occurs in older age and is diagnosed in the advanced stages of the disease. Therefore, it is recommended to inform men and develop suitable screening programs, especially in high-risk families.

Case Series Analysis of Diagnosis and Treatment of Gastrointestinal Metastasis in Lung Cancer Patients.

This study was designed to investigate the clinical, pathological, endoscopic, and imaging characteristics of gastrointestinal metastasis in patients with lung cancer. The clinical data of 20 patients with primary lung cancer with gastrointestinal metastasis. This study included sixteen men and four women, ranging in age from 31 to 75 years. The time interval from the diagnosis of lung cancer to the detection of gastrointestinal metastasis ranged from 13 to 142 months. The most common sites of metastasis were the small intestine (eight cases), colon (four cases), and upper gastrointestinal tract (eight cases). The major symptoms included obstruction, perforation, abdominal pain, abdominal distension, anorexia, and anemia. The predominant pathological type was poorly differentiated adenocarcinoma (seventeen cases). A single ulcer was mostly seen on endoscopy, and some cases showed a slight depression of the intestinal wall. The CT and PET-CT scan revealed bowel wall thickening, intraluminal polypoid masses, and intestinal perforation. Gastrointestinal metastasis of lung cancer is mainly observed in the small intestine, colon, and stomach, and is often detected when severe complications such as gastrointestinal obstruction and perforation occurred. Regular evaluation of gastrointestinal conditions during lung cancer diagnosis and treatment is recommended to improve the diagnostic accuracy and prevent misdiagnosis.

Overview and management of sacral tumors

Sacral tumors can range from benign to malignant. The sacrum is a common site of metastases however surgical intervention is not common for sacral metastases unless there is neurological compromise. Benign aggressive tumors such giant cell tumors, osteoblastomas and aneurysmal bone cysts (ABC) can be found in the sacrum. Malignant primary tumors including chordoma, chondrosarcomas and osteosarcomas can affect the sacrum. Management depends on the tumor histology including debulking and stabilization for metastatic spine lesions. For benign tumors such as ABCs, intralesional resection is an option. For primary spine tumors partial or total sacrectomies are an option and morbidity is dependent on the level of sacral resection.

Contrast-Enhanced Ultrasound-Based Radiomics for the Prediction of Axillary Lymph Nodes Status in Breast Cancer.

Breast cancer is the leading cause of cancer-related deaths in the female population. Axillary lymph nodes (ALN) are a group of the most common metastatic sites of breast cancer. Timely assessment of ALN status is of paramount clinical importance for medical decision making. To utilize contrast-enhanced ultrasound (CEUS)-based radiomics models for noninvasive pretreatment prediction of ALN status. Clinical data and pretreatment CEUS images of primary breast tumors were retrospectively studied to build radiomics signatures for pretreatment prediction of nodal status between May 2015 and July 2021. The cases were divided into the training cohorts and test cohorts in a 9:1 ratio. The mRMR approach and stepwise forward logistic regression technique were used for feature selection, followed by the multivariate logistic regression technique for building radiomics signatures in the training cohort. The confusion matrix and receiver operating characteristic (ROC) analysis were used for accessing the prediction efficacy of the radiomics models. The radiomics models, which consist of six features, achieved predictive accuracy with the area under the ROC curve (AUC) of 0.713 in the test set for predicting lymph node metastasis. The CEUS-based radiomics is promising to be developed as a reliable noninvasive tool for predicting ALN status.

Near-infrared photoimmunotherapy for osteosarcoma targeting epidermal growth factor receptor

Osteosarcoma is the most common bone tumor, and it possesses high metastatic propensity. Although systemic chemotherapy has improved its prognosis, improvements in survival rates have stalled in recent years. Moreover, the prognosis of patients with metastatic osteosarcoma remains poor. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer therapy that induces immunogenic cell death (ICD), and the therapeutic effects spread to distant metastatic sites. Therefore, NIR-PIT could be useful in both primary and metastatic osteosarcoma treatment. In this study, we investigated the efficacy of NIR-PIT targeting epidermal growth factor receptor (EGFR) in osteosarcoma. The cytotoxic effects of NIR-PIT in osteosarcoma cell lines with different EGFR expression levels (MG63; high, Saos-2; low) were evaluated. NIR-PIT–induced cell death was dependent on the EGFR expression level. After NIR-PIT, swelling and bleb formation, the characteristic morphological changes induced by NIR-PIT associated with necrosis caused by the influx of extracellular fluid, were observed. In addition, the release of the ICD markers lactate dehydrogenase and ATP was detected after NIT-PIT. NIR-PIT significantly suppressed tumor growth in tumor-bearing mice. This study revealed that NIR-PIT targeting EGFR has therapeutic effects and induces ICD in osteosarcoma; thus, it is potentially a novel therapeutic strategy for primary and metastatic osteosarcoma.

Clinical management of a patient with non-triple-negative breast cancer who converts to a triple-negative subtype at recurrence.

The management of patients with advanced breast cancer is becoming increasingly complex compared to the past, mainly due to numerous therapeutic innovations introduced in the current therapeutic scenario. At the time of metastatic disease diagnosis, as indicated by the guidelines, it is important to perform a biopsy of the metastatic sites to optimize choices and expand therapeutic options. Approximately 25-45% of patients who experience a recurrence of the primary tumor lose hormone receptor expression: in this context, solid data comes from a subanalysis of the randomized clinical trial ASCENT, in which the benefit of a treatment with antibody-drug conjugate sacituzumab govitecan is also confirmed in case of non-triple negative breast cancer at diagnosis that subsequently convert to a triple negative subtype. The case reported below is representative of this clinical situation.

Weekly carboplatin plus paclitaxel chemotherapy in advanced melanoma patients resistant to anti-PD-1 inhibitors: a retrospective, monocentric experience

Immunotherapy with anti-PD-1 antibodies significantly improved the prognosis in advanced melanoma patients, but most of them develop primary or secondary resistance to the treatment. In this study, we evaluated efficacy and safety of a chemotherapy regimen with weekly carboplatin plus paclitaxel (wCP) in patients previously treated with anti-PD-1 antibodies. We retrospectively identified 30 patients with advanced melanoma treated at our Institute over the last eight years with wCP. The co-primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). In addition, we evaluated treatment tolerability. For this patient cohort, median PFS and OS were 3.25 and 7.69 months, respectively. All included patients had previously received anti-PD-1 immunotherapy, most of them had ECOG PS 0–1, and only 5 patients had a BRAF V600 mutation. In univariable analysis, we observed shorter OS in patients with > 2 involved metastatic sites, superficial spreading histology, and serum lactate dehydrogenase (LDH) values above the median. Liver metastases were associated with worse outcomes, while radiotherapy treatment of brain metastases was associated with improved OS. However, in a multivariable Cox regression model, only LDH above the median, superficial spreading histology, and female sex were significantly associated with worse OS. We reported grade 3 and 4 treatment-related toxicities in 4 and 0 patients, respectively. In conclusion, chemotherapy with wCP is a valid palliative treatment in advanced melanoma who progressed with anti-PD-1 antibodies.

Bilan d’extension du cancer bronchique

The management of lung cancer patients requires a definitive diagnosis and a precise assessment of the disease extent. Pathological examination performed on tissue or cytological samples taken from the tumor, associated lymphadenopathy or an accessible metastatic site answers the first question while a set of staging techniques ensures the second. Guidelines for each technique have been issued in order to maximize diagnostic yield and allow immunohistochemical and molecular biology analyzes which impact the therapeutic strategy. The aim of this article is to discuss the different diagnostic and staging methods and to propose solutions for optimizing the diagnosis and the assessment of the anatomic extent of lung cancers. In this context, the indications and limits of the different modalities are discussed. The size of the tumor, its pleural, parietal, endobronchial and direct mediastinal extension must be specified as well as lymph node and distant extension. The clinical examination remains essential. Contrast enhanced Chest CT is systematic, unless contraindicated. 18FDG PET-CT is not always indicated but is essential in patients potentially eligible for curative treatment. Brain imaging is indicated, even in asymptomatic patients. Compliance with recommendations and adequate organization optimize patient care.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Inducible CCR2+ nonclassical monocytes mediate the regression of cancer metastasis.

A major limitation of immunotherapy is the development of resistance resulting from cancer-mediated inhibition of host lymphocytes. Cancer cells release CCL2 to recruit classical monocytes expressing its receptor CCR2 for the promotion of metastasis and resistance to immunosurveillance. In the circulation, some CCR2-expressing classical monocytes lose CCR2 and differentiate into intravascular nonclassical monocytes that have anticancer properties but are unable to access extravascular tumor sites. We found that in mice and humans, an ontogenetically distinct subset of naturally underrepresented CCR2-expressing nonclassical monocytes was expanded during inflammatory states such as organ transplant and COVID-19 infection. These cells could be induced during health by treatment of classical monocytes with small-molecule activators of NOD2. The presence of CCR2 enabled these inducible nonclassical monocytes to infiltrate both intra- and extravascular metastatic sites of melanoma, lung, breast, and colon cancer in murine models, and they reversed the increased susceptibility of Nod2-/- mutant mice to cancer metastasis. Within the tumor colonies, CCR2+ nonclassical monocytes secreted CCL6 to recruit NK cells that mediated tumor regression, independent of T and B lymphocytes. Hence, pharmacological induction of CCR2+ nonclassical monocytes might be useful for immunotherapy-resistant cancers.

Outcome of radiotherapy for metastatic neuroblastoma

Background. Neuroblastoma (NB) is a prevalent solid extracranial tumor that primarily affects children. It is the third most common type of cancer in children, following leukemia and brain tumors. Aim. The study aimed to discuss the clinical outcomes after adjuvant radiotherapy to the primary site in case of metastatic NB after good response to chemotherapy. Methods. A retrospective clinical-dosimetric study of 25 patients metastatic NB treated with radiotherapy at Baghdad Radiotherapy and Nuclear Medicine Center, at Baghdad Medical City Complex, Baghdad, Iraq. Data collection begin from December 2023 and March 2024. Data were collected retrospectively with review of records. The following variables were studied: sex, age, date of diagnosis, site of primary tumor, site of metastasis, chemotherapy, surgery, RT, RT sites, doses of RT, fractions of RT, recurrence sites, date of relapse and survival outcome for each patient. Follow-up period include look up to metastasis, site of metastasis, recurrence, site of recurrence and survival rates. Results. In relation to sex, males (14, 56%) were more than females (11, 44%). The mean age of NB cases was 45.64±17.6 months. In NB, suprarenal masses were the most common site of primary in 21 (84%) of patients. The most common site of metastasis of NB was bone marrow in 12 (48). The multi sites of recurrence was the commonest presentation in 48%. The relapse-free survival (RFS) was 22.38 months. 5 out of 25 patients were alive whereas 20 (80%) of cases were dead. The median follow-up time was 6 years, and the OS of NB in this study after optimal treatment was 2.46 years (95%CI= 1.705-3.21) for survivors. The MS was 4.84 years. The OS was 6 yrs for those diagnosed at 2017, 2 yrs for those diagnosed at 2018, 1.5 yrs for those diagnosed at 2019, 1.75 yrs for those diagnosed at 2020, 3 yrs for those diagnosed at 2021 and 1.5 yrs for those diagnosed at 2022. There was a significant difference among doses (Log Rank (Mantel-Cox)= 11.425, p=0.044). Conclusions. This study is the first study in Iraq that examines the clinical results of radiotherapy on the primary site in cases of metastatic neuroblastoma following induction chemotherapy. The suprarenal masses of neuroblastoma are the most often occurring main site. The primary sites of metastases for neuroblastoma (NB) are the bone marrow and bones. Timely detection and proactive treatment of NB can improve overall results. Reoccurrence of skeletal issues and the infiltration of bone marrow are frequently observed. There were no significant differences observed in terms of relapse-free survival and overall survival based on factors such as sex, age, location of the main tumor, chemotherapy, radiation treatment, surgery, and radiation therapy dosages.

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.

Single-Cell Analysis of Bone-Marrow-Disseminated Tumour Cells

Metastasis frequently targets bones, where cancer cells from the primary tumour migrate to the bone marrow, initiating new tumour growth. Not only is bone the most common site for metastasis, but it also often marks the first site of metastatic recurrence. Despite causing over 90% of cancer-related deaths, effective treatments for bone metastasis are lacking, with current approaches mainly focusing on palliative care. Circulating tumour cells (CTCs) are pivotal in metastasis, originating from primary tumours and circulating in the bloodstream. They facilitate metastasis through molecular interactions with the bone marrow environment, involving direct cell-to-cell contacts and signalling molecules. CTCs infiltrate the bone marrow, transforming into disseminated tumour cells (DTCs). While some DTCs remain dormant, others become activated, leading to metastatic growth. The presence of DTCs in the bone marrow strongly correlates with future bone and visceral metastases. Research on CTCs in peripheral blood has shed light on their release mechanisms, yet investigations into bone marrow DTCs have been limited. Challenges include the invasiveness of bone marrow aspiration and the rarity of DTCs, complicating their isolation. However, advancements in single-cell analysis have facilitated insights into these elusive cells. This review will summarize recent advancements in understanding bone marrow DTCs using single-cell analysis techniques.