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Patients with nonresectable breast cancer liver metastasis (BCLM) face a dismal prognosis. Despite liver transplantation (LT) for metastatic liver tumors having recently shown good results, BCLM represents an absolute contraindication. This study aimed to investigate the potential for long-term survival after LT for BCLMs in a patient experiencing end-stage liver disease, following multiple oncologic treatments. In July 2019, we performed a deceased donor LT on a 41-year-old female with BCLM controlled with human epidermal growth factor receptor 2 targeted therapy, who developed liver failure following multiple locoregional liver-directed treatments. The primary tumor was treated with surgical resection and adjuvant chemoradiation in 2000. The procedure was performed under a protocol approved by the local ethical committee, and by the Italian National Transplant Center. A 12-month treatment with trastuzumab was performed immediately after LT. Immunosuppression following transplantation was undertaken without steroids, and with everolimus. The patient completed 12 months of follow-up without recurrence. Trastuzumab was then withdrawn. Fifteen months after LT, a liver recurrence occurred that was treated with chemotherapy. In October 2021, she developed 2 brain lesions that were treated with stereotactic radiation. The patient is still alive, with a positron emission tomography/computed tomography performed in January 2024 showing no disease. LT for this patient with BCLM of extreme selectivity showed a good clinical outcome. Perioperative systemic treatment and tumor control are necessary. A specific protocol should be discussed within a multidisciplinary team, and with local and national authorities. Even if tumor recurrence occurs, multimodal therapy can control the disease.
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Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2- advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs' impact, and toxicities of abemaciclib combined with endocrine therapy in a real-world setting. Patients from 12 referral Italian hospitals with HR+/HER2- aBC who received abemaciclib were included. Clinical data about comorbidities, concurrent medications, outcomes, and adverse events (AE) were collected. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. The software was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow, and red) for each patient. Univariate and multivariate analyses were performed to identify predictors of patients' PFS or toxicity. One hundred seventy-three patients were included. 13% of patients had >75years. The overall response rate (ORR) was 63%. The general population's median PFS (mPFS) was 22 months (mo), while mOS were not reached. Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively. The most common toxicities were diarrhea, asthenia, and neutropenia detected in 63%,49%, and 49% of patients. The number of concomitant medications and comorbidities were not associated with survival outcomes (22 vs 17 mo, p = 0.068, p = 0.99). Drug-PIN tier from dark yellow to red and Drug-PIN score >12 were associated with shorter PFS compared to no/low-risk DDIs and score <12 (15 vs 23, p = 0.005, p = 0.0017). Drug interaction was confirmed as an independent biomarker in a multivariate model (p = 0.02). No difference in any grade AE, severe toxicities, and diarrhea were detected among different age subgroups. No association was found between Drug-PIN score or Drug-PIN tier and overall toxicity (p = 0.44), severe AEs (p = 0.11), or drug reduction (p = 0.27). The efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in the elderly population and patients with comorbidities. Evaluation of DDIs with Drug-PIN appears to be an independent predictor of PFS.
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BACKGROUND: Bilateral testicular germ cell tumours (B-GCT) are rare, with an incidence of 2-5%, and can be classified as synchronous (sB-GCT) or metachronous (mB-GCT). Our study aimed to identify clinical, biochemical, and radiological risk factors for mB-GCT in a cohort of patients with GCT at a single tertiary referral centre. METHODS: This retrospective case-control study included patients with GCT referred to Policlinico Umberto I-Sapienza University of Rome, from 2005 to 2023. We evaluated clinical history, testicular ultrasound features, hormone levels, semen analysis, histological characteristics, staging, and treatments. mB-GCTs were compared with unilateral GCT patients with a follow-up longer than the median time-to-onset of the second tumour. RESULTS: Of 319 patients, 52 experienced B-GCT, with a median time-to-onset of the second tumour of 62 months (range: 8-229). The mB-GCT group showed higher gonadotropin levels (FSH 13.6mUI/mL vs. 7.4mUI/mL, p < 0.001; LH 6.6mUI/mL vs. 3.9mUI/mL, p = 0.004), lower sperm concentration (27 × 106/ejaculate vs. 78 × 106/ejaculate, p = 0.009), smaller residual testis volume (10.4 mL vs. 16.3 mL, p < 0.001), more inhomogeneous echotexture [57.5% vs. 14%, p < 0.001], and presence of microlithiasis (75% vs. 19.5%, p < 0.001). Kaplan-Meier curves confirmed that ultrasound features of the residual testis increased the cumulative risk of developing a second tumour. Microlithiasis was a strong independent predictor (OR 30.712, 95% CI 3.357-280.942, p = 0.002). CONCLUSIONS: Histological features of the first tumour or its treatment do not influence the onset of a second tumour. However, low residual testis volume, inhomogeneous echotexture, and microlithiasis significantly increase this risk. A comprehensive evaluation of the residual testis at baseline is essential for developing a personalised surveillance programme in GCT survivors, with regular ultrasound follow-up recommended beyond the conventional 5-year limit.
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Cancer patients (CPs), being immunosuppressed due to the treatment received or to the disease itself, are more susceptible to infections and their potential complications, showing therefore an increased risk of developing severe COVID-19 compared to the general population. We evaluated the immune responses to anti-SARS-CoV-2 vaccination in patients with solid tumors one year after the administration of the third dose and the effect of cancer treatment on vaccine immunogenicity was assessed. Healthy donors (HDs) were enrolled. Binding and neutralizing antibody (Ab) titers were evaluated using chemiluminescence immunoassay (CLIA) and Plaque Reduction Neutralization Test (PRNT) respectively. T-cell response was analyzed using multiparametric flow cytometry. CPs who were administered three vaccine doses showed lower Ab titers than CPs with four doses and HDs. Overall, a lower cell-mediated response was found in CPs, with a predominance of monofunctional T-cells producing TNFα. Lower Ab titers and a weaker T-cell response were observed in CPs without prior SARS-CoV-2 infection when compared to those with a previous infection. While no differences in the humoral response were found comparing immunotherapy and non-immunotherapy patients, a stronger T-cell response in CPs treated with immunotherapy was observed. Our results emphasize the need of booster doses in cancer patients to achieve a level of protection similar to that observed in healthy donors and underlines the importance of considering the treatment received to reach a proper immune response.
Subject(s)
COVID-19 , Neoplasms , Humans , COVID-19 Vaccines , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , Neoplasms/therapy , Antibodies, Viral , Antibodies, NeutralizingABSTRACT
The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade > = 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Neoadjuvant Therapy , Platinum/therapeutic use , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of tumors. Natural killer (NK) cells can play an important role in cancer immune surveillance. The aim of this prospective observational study was to analyze peripheral blood mononuclear cells (PBMCs) in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICIs in order to identify predictive factors for better survival outcomes. METHODS: Forty-seven stage IV NSCLC patients were enrolled. Patients underwent baseline (T0) and longitudinal (T1) evaluations after ICIs. Peripheral immune blood cell counts were analyzed using flow cytometry. RESULTS: Basal levels of CD3-CD56+ NK cells were higher in patients with controlled disease (DC) compared to progression disease (PD) patients (127 cells/µL vs. 27.8 cells/µL, p < 0.001). Lower NK cell values were independent prognostic factors for shorter overall survival (OS) (HR 0.992; 95% CI 0.987-0.997, p < 0.001) and progression-free survival (PFS) (HR 0.988; 95% CI 0.981-0.994, p < 0.001). During the longitudinal evaluation, CD3-CD56+ NK cells (138.1 cells/µL vs. 127 cells/µL, p = 0.025) and CD56bright NK cells (27.4 cells/µL vs. 18.1 cells/µL, p = 0.034) significantly increased in the DC group. Finally, lower values of CD3-CD56+ NK cells (28.3 cells/µL vs. 114.6 cells/µL, p = 0.004) and CD56dim NK cells (13.2 cells/µL vs. 89.4 cells/µL, p < 0.001) were found in sarcopenic patients compared to patients without sarcopenia. CONCLUSIONS: Peripheral NK cells could represent a non-invasive and useful tool to predict ICI therapy response in NSCLC patients, and the association of low NK cell levels with sarcopenia deserves even more attention in clinical evaluation.
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No evidence exists as to whether body mass index (BMI) impairs clinical outcomes from ALK inhibitors (ALKi) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). Retrospective data of patients affected by metastatic ALK-rearranged NSCLC treated with ALKi were collected. We divided patients into "low- BMI" (≤25 kg/m2) and "high- BMI" (>25 kg/m2) categories and correlated them with overall survival (OS) and progression-free survival (PFS). We included 40 patients treated with ALKi. We observed a 3-year OS of 81.5% in high-BMI vs. 49.6% in low-BMI categories (p = 0.049); the 3-year first-line PFS was superior in high-BMI vs. low-BMI patients (47% vs. 19%, p = 0.019). As expected, patients treated with Alectinib had a 55.6% 3-year PFS vs. 7.1% for others treated with ALKi (p = 0.025). High-BMI was associated with a 100% 3-year PFS rate vs. 25.4% in low-BMI Alectinib patients (p = 0.03). BMI was independently correlated with first-line PFS and OS at multivariate analysis with PS (HR 0.39, CI 95% 0.16-0.96, p = 0.042; HR 0.18, CI 95% 0.05-0.61, p = 0.006). High-BMI was associated with higher efficacy in ALK-rearranged patients. These results are particularly exciting for Alectinib and could be correlated to mechanisms that should be investigated in subsequent prospective studies.
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BACKGROUND: Abscopal effect (AE) describes the ability of radiotherapy (RT) to induce immune-mediated responses in nonirradiated distant metastasis. Bone represents the third most frequent site of metastasis and an immunologically favorable environment for the proliferation of cancer cells. We revised the literature, searching documented cases of AE involving bone metastases (BMs) and evaluated the incidence of AE involving BMs in patients requiring palliative RT on BMs or non-BMs treated at our department. METHODS: Articles published in the PubMed/MEDLINE database were selected using the following search criteria: ((abscopal effect)) AND ((metastases)). Patients with BMs, who underwent performed bone scintigraphy before and at least 2-3 months after RT, were selected and screened between January 2015 and July 2022. AE was defined as an objective response according to the scan bone index for at least one nonirradiated metastasis at a distance > 10 cm from the irradiated lesion. The primary endpoint was the rate of AE on BMs. RESULTS: Ten cases experiencing AE of BMs were identified from the literature and eight among our patients. CONCLUSIONS: The analysis performed here suggests the use of hypofractionated radiotherapy as the only triggering factor for AE of BMs through the activation of the immune response.
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BACKGROUND: A large amount of evidence from clinical studies has demonstrated that circulating tumor cells are strong predictors of outcomes in many cancers. However, the clinical significance of CTC enumeration in metastatic colorectal cancer is still questioned. The aim of this study was to evaluate the clinical value of CTC dynamics in mCRC patients receiving first-line treatments. MATERIALS AND METHODS: Serial CTC data from 218 patients were used to identify CTC trajectory patterns during the course of treatment. CTCs were evaluated at baseline, at a first-time point check and at the radiological progression of the disease. CTC dynamics were correlated with clinical endpoints. RESULTS: Using a cut-off of ≥1 CTC/7.5 mL, four prognostic trajectories were outlined. The best prognosis was obtained for patients with no evidence of CTCs at any timepoints, with a significant difference compared to all other groups. Lower PFS and OS were recognized in group 4 (CTCs always positive) at 7 and 16 months, respectively. CONCLUSIONS: We confirmed the clinical value of CTC positivity, even with only one cell detected. CTC trajectories are better prognostic indicators than CTC enumeration at baseline. The reported prognostic groups might help to improve risk stratification, providing potential biomarkers to monitor first-line treatments.
Subject(s)
Colorectal Neoplasms , Neoplastic Cells, Circulating , Humans , Neoplastic Cells, Circulating/pathology , Prognosis , Biomarkers, Tumor , Disease-Free Survival , Colorectal Neoplasms/pathologyABSTRACT
Background: The term "neo-RAS wild-type" refers to the switch to RAS wild-type disease in plasma circulating tumor DNA (ctDNA) from originally RAS mutant colorectal cancers. Consistently, the hypothesis to re-determine RAS mutational status in ctDNA at disease progression in RAS mutant mCRC opened to a new perspective for clinically-based selection of patients to be treated with EGFR inhibitors. Currently, the genomic landscape of "neo-RAS wild-type" is unknown. This is a prospective study aimed to investigate clinical and genomic features associated with RAS mutation clearance in a large cohort of RAS mutant mCRC patients who converted to RAS wild- type in liquid biopsy at failure of first-line treatments. Secondary aim was to investigate the long term prognostic significance of "true neo-RAS wild- type". Patients and methods: 70 patients with stage IV RAS mutant colorectal cancer were prospectively enrolled. Plasma samples were collected at progression from first-line treatment. RAS/BRAF mutations in plasma were assessed by RT-PCR. In RAS/BRAF wild-type samples, ctDNA was used to generate libraries using a 17 genes panel whose alteration has clinical relevance. To investigate the prognostic significance of RAS mutation clearance, test curves for PFS and OS were represented by Kaplan-Meier estimator plot and Log-rank test. Results: The most commonly detected actionable mutations in "neo-RAS wild-type" were: PIK3CA (35.7%); RET (11.9%); IDH1 (9.5%); KIT (7%); EGFR (7%); MET (4.7%); ERBB2 (4.7%); FGFR3 (4.7%). Both OS and post-progression survival were longer in patients with "neo-RAS wild-type" compared to those who remained RAS mutant (p<0.001 for both). Conclusions: De-novo-targetable mutations occured in a large percentage of "neo-RAS wild-type", being PIK3CA the most commonly detected. RAS mutation clearance in ctDNA is associated with long- term improvement of overall survival.
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Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.
Subject(s)
Brachytherapy , Colorectal Neoplasms , Radiosurgery , Humans , Radiosurgery/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapy , Colorectal Neoplasms/pathologyABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development. METHODS: A prospective, multicenter study evaluating the immune profile (IP) of 79 patients with advanced cancer and treated with anti-programmed cell death protein 1 (anti-PD-1) drugs as a first- or second-line setting was performed. The results were then correlated with irAEs onset. The IP was studied by means of multiplex assay, evaluating circulating concentration of 12 cytokines, 5 chemokines, 13 soluble immune checkpoints and 3 adhesion molecules. Indoleamine 2, 3-dioxygenase (IDO) activity was measured through a modified liquid chromatography-tandem mass spectrometry using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. A connectivity heatmap was obtained by calculating Spearman correlation coefficients. Two different networks of connectivity were constructed, based on the toxicity profile. RESULTS: Toxicity was predominantly of low/moderate grade. High-grade irAEs were relatively rare, while cumulative toxicity was high (35%). Positive and statistically significant correlations between the cumulative toxicity and IP10 and IL8, sLAG3, sPD-L2, sHVEM, sCD137, sCD27 and sICAM-1 serum concentration were found. Moreover, patients who experienced irAEs had a markedly different connectivity pattern, characterized by disruption of most of the paired connections between cytokines, chemokines and connections of sCD137, sCD27 and sCD28, while sPDL-2 pair-wise connectivity values seemed to be intensified. Network connectivity analysis identified a total of 187 statistically significant interactions in patients without toxicity and a total of 126 statistically significant interactions in patients with toxicity. Ninety-eight interactions were common to both networks, while 29 were specifically observed in patients who experienced toxicity. CONCLUSIONS: A particular, common pattern of immune dysregulation was defined in patients developing irAEs. This immune serological profile, if confirmed in a larger patient population, could lead to the design of a personalized therapeutic strategy in order to prevent, monitor and treat irAEs at an early stage.
Subject(s)
Antineoplastic Agents, Immunological , Neoplasms , Humans , Prospective Studies , Tandem Mass Spectrometry , Antineoplastic Agents, Immunological/therapeutic use , Neoplasms/drug therapy , Cytokines , Retrospective StudiesABSTRACT
Non-metastatic castration resistant prostate cancer (nmCRPC) is a clinical setting defined as confirmed rising levels of PSA in patients treated with ADT but without detectable metastases on conventional imaging with computerized tomography (CT) and technetium-99 m scintigraphy. Men with nmCRPC and a PSA doubling time (PSADT) ≤ 10 months are considered at high risk of rapidly developing metastases with a consequent possible impact on survival. Three recent phase III trials have demonstrated, in this setting, the efficacy of adding a next-generation androgen receptor targeted agent (ARTA) to ADT in respect to ADT only, in delaying the development of metastases (metastasis-free survival, MFS) and prolong overall survival. The magnitude of clinical benefit of these agents was even more meaningful if considering the low incidence of drug related adverse events. Our review described the latest advances in the management of nmCRPC, deriving from the pivotal clinical trials, SPARTAN, PROSPER and ARAMIS, in order to support clinicians to optimally manage these patients. Of note, the emergence of novel, more accurate, next-generation imaging techniques (including Ga PSMA-PET/CT), as well as eventual future tumor biomarkers, is modifying the entity and definition of the nmCRPC setting, with a consequent impact on patient's diagnosis and management.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Male , Humans , Prostatic Neoplasms, Castration-Resistant/drug therapy , Androgen Receptor Antagonists/therapeutic use , Prostate-Specific Antigen/therapeutic use , Positron Emission Tomography Computed Tomography , Treatment Outcome , Androgen Antagonists/therapeutic useABSTRACT
Nutritional issues, including malnutrition, low muscle mass, sarcopenia (i.e., low muscle mass and strength), and cachexia (i.e., weight loss characterized by a continuous decline in skeletal muscle mass, with or without fat loss), are commonly experienced by patients with cancer at all stages of disease. Cancer cachexia may be associated with poor nutritional status and can compromise a patient's ability to tolerate antineoplastic therapy, increase the likelihood of post-surgical complications, and impact long-term outcomes including survival, quality of life, and function. One of the primary nutritional problems these patients experience is malnutrition, of which muscle depletion represents a clinically relevant feature. There have been recent calls for nutritional screening, assessment, treatment, and monitoring as a consistent component of care for all patients diagnosed with cancer. To achieve this, there is a need for a standardized approach to enable oncologists to identify patients commencing and undergoing antineoplastic therapy who are or who may be at risk of malnutrition and/or muscle depletion. This approach should not replace existing tools used in the dietitian's role, but rather give the oncologist a simple nutritional protocol for optimization of the patient care pathway where this is needed. Given the considerable time constraints in day-to-day oncology practice, any such approach must be simple and quick to implement so that oncologists can flag individual patients for further evaluation and follow-up with appropriate members of the multidisciplinary care team. To enable the rapid and routine identification of patients with or at risk of malnutrition and/or muscle depletion, an expert panel of nutrition specialists and practicing oncologists developed the PROtocol for NuTritional risk in Oncology (PRONTO). The protocol enables the rapid identification of patients with or at risk of malnutrition and/or muscle depletion and provides guidance on next steps. The protocol is adaptable to multiple settings and countries, which makes implementation feasible by oncologists and may optimize patient outcomes. We advise the use of this protocol in countries/clinical scenarios where a specialized approach to nutrition assessment and care is not available.
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BACKGROUND/AIM: We conducted a retrospective analysis in our center (Umberto I Polyclinic) in collaboration with Campus Biomedico Polyclinic to assess the results of the REFLECT study, which was the first study that demonstrated the non-inferiority of Lenvatinib to Sorafenib. PATIENTS AND METHODS: We identified 21 patients affected by advanced hepatocellular carcinoma during the last 3 years who were treated in our centers. They were subdivided according to the treatment administered (Lenvatinib or Sorafenib). Progression-free survival (PFS) and overall survival (OS) were calculated, and subgroups were compared using the log-rank test. Specific predictive and prognostic factors were identified. The safety profile of the two drugs and the collateral effects were evaluated. RESULTS: The OS in patients in the Lenvatinib arm was 19 (months and 12.5 months in the Sorafenib arm. PFS in patients in the Lenvatinib arm was 6 months and 2.5 months in the Sorafenib arm. OS and PFS in patients treated with Lenvatinib were higher in any subcategory analyzed whereas no positive predictors of response to Sorafenib were found. Based on data from literature, the albumin bilirubin index (ALBI) grade was found to be a key prognostic factor. Patients treated with Sorafenib had more adverse events than those treated with Lenvatinib (100% versus 81.8%, respectively). Patients treated with Sorafenib had more frequently hand-foot syndromes, diarrhea, and nausea whereas patients treated with Lenvatinib commonly had hypertension, proteinuria, and weight loss. CONCLUSION: Lenvatinib was found to be better than Sorafenib in terms of both survival and toxicity, in advanced hepatic cell carcinoma patients.
Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Sorafenib/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/chemically induced , Antineoplastic Agents/adverse effects , Retrospective Studies , Treatment Outcome , Phenylurea Compounds/adverse effects , Liver Neoplasms/drug therapy , HepatocytesABSTRACT
OBJECTIVE: To investigate the predictive role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC). METHODS: In this single-center retrospective study, patients with LARC who underwent staging MRI and TNT were enrolled. MRI-based staging, tumor volume, and DWI-ADC values were analyzed. Patients were classified as complete responders (pCR) and non-complete responders (non-pCR), according to post-surgical outcome. Pre-treatment ADC values were compared to pathological outcome, post-treatment downstaging, and reduction of tumor volume. The diagnostic accuracy of DWI-ADC in differentiating between pCR and non-pCR groups was calculated with receiver operating characteristic (ROC) analysis. RESULTS: A total of 36 patients were evaluated (pCR, n = 20; non-pCR, n = 16). Pre-treatment ADC values were significantly different between the two groups (p = 0.034), while no association was found between pre-TNT tumor volume and pathological response. ADC values showed significant correlations with loco-regional downstaging after therapy (r = -0.537, p = 0.022), and with the reduction of tumor volume (r = -0.480, p = 0.044). ADC values were able to differentiate pCR from non-pCR patients with a sensitivity of 75% and specificity of 70%. CONCLUSIONS: ADC values on pre-treatment MRI were strongly associated with the outcome in patients with LARC, both in terms of pathological response and in loco-regional downstaging after TNT, suggesting the use of DW-MRI as a potential predictive tool of response to therapy. KEY POINTS: ⢠ADC values of pre-TNT MRI examinations of patients with LARC were significantly associated with a pathological complete response (pCR) and with post-treatment regression of TNM staging. ⢠An ADC value of 1.042 ×10-3 mm2/s was found to be the optimal cutoff value for discriminating between pCR and non-pCR patients, with a sensitivity of 75% and specificity of 70%. ⢠DW-MRI proved to have a potential predictive role in the assessment of response to therapy in patients with LARC, throughout the analysis of ADC map values.
Subject(s)
Diffusion Magnetic Resonance Imaging , Rectal Neoplasms , Humans , Diffusion Magnetic Resonance Imaging/methods , Neoadjuvant Therapy , Retrospective Studies , Rectal Neoplasms/therapy , Rectal Neoplasms/drug therapy , Magnetic Resonance Imaging , Chemoradiotherapy , Treatment OutcomeABSTRACT
The aim of this study was to combine breast MRI-derived biomarkers with clinical-pathological parameters to identify patients who truly need an Oncotype DX Breast Recurrence Score® (ODXRS) genomic assay, currently used to predict the benefit of adjuvant chemotherapy in ER-positive/HER2-negative early breast cancer, with the ultimate goal of customizing therapeutic decisions while reducing healthcare costs. Patients who underwent a preoperative multiparametric MRI of the breast and ODXRS tumor profiling were retrospectively included in this study. Imaging sets were evaluated independently by two breast radiologists and classified according to the 2013 American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) lexicon. In a second step of the study, a combined oncologic and radiologic assessment based on clinical-pathological and radiological data was performed, in order to identify patients who may need adjuvant chemotherapy. Results were correlated with risk levels expressed by ODXRS, using the decision made on the basis of the ODXRS test as a gold standard. The χ2 test was used to evaluate associations between categorical variables, and significant ones were further investigated using logistic regression analyses. A total of 58 luminal-like, early-stage breast cancers were included. A positive correlation was found between ODXRS and tumor size (p = 0.003), staging (p = 0.001) and grading (p = 0.005), and between BI-RADS categories and ODXRS (p < 0.05 for both readers), the latter being confirmed at multivariate regression analysis. Moreover, BI-RADS categories proved to be positive predictors of the therapeutic decision taken after performing an ODXRS assay. A statistically significant association was also found between the therapeutic decision based on the ODXRS and the results of combined onco-radiologic assessment (p < 0.001). Our study suggests that there is a correlation between BI-RADS categories at MRI and ODXRS and that a combined onco-radiological assessment may predict the decision made on the basis of the results of ODXRS genomic test.
ABSTRACT
Background: Despite the efficacy of immunotherapy, only a small percentage of patients achieves a long-term benefit in terms of overall survival. The aim of this study was to define an immune profile predicting the response to immune checkpoint inhibitors (ICIs). Methods: Patients with advanced solid tumors, who underwent ICI treatment were enrolled in this prospective study. Blood samples were collected at the baseline. Thirteen soluble immune checkpoints, 3 soluble adhesion molecules, 5 chemokines and 11 cytokines were analyzed. The results were associated with oncological outcomes. Results: Regardless of tumor type, patients with values of sTIM3, IFNα, IFNγ, IL1ß, IL1α, IL12p70, MIP1ß, IL13, sCD28, sGITR, sPDL1, IL10 and TNFα below the median had longer overall survival (p<0.05). By using cluster analysis and grouping the patients according to the trend of the molecules, two clusters were found. Cluster A had a significantly higher mean progression free survival (Cluster A=11.9 months vs Cluster B=3.5 months, p<0.01), a higher percentage of disease stability (Cluster A=34.5% vs. Cluster B=0%, p<0.05) and a lower percentage of disease progression (Cluster A=55.2% vs. Cluster B = 94.4%, p=0.04). Conclusion: The combined evaluation of soluble molecules, rather than a single circulating factor, may be more suitable to represent the fitness of the immune system status in each patient and could allow to identify two different prognostic and predictive outcome profiles.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Prospective Studies , Immunotherapy/methods , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/pathology , Immune Checkpoint InhibitorsABSTRACT
Combining EGFR-tyrosine kinase inhibitors (TKIs) to whole brain radiation therapy (WBRT) has been shown to be more effective than EGFR-TKIs or WBRT alone in treating brain metastases (BMs) from EGFR-mutated Non Small-Cell Lung Cancer (NSCLC). However, despite the combination results well tolerated, EGFR-TKIs are often discontinued before WBRT, to reduce the risk of possible side effects, potentially resulting in reduced treatment efficacy and possible progression of intra- and extra-cranial disease. Afatinib, an irreversible inhibitor of EGFR-TK, has been shown to radiosensitize NSCLC in pre-clinical models and, compared to the other EGFR-TKIs, more efficiently penetrates the blood-brain barrier. However, nowadays, only two case reports describe the therapeutic efficiency and safety of combining afatinib with WBRT. Herein, we report on a 58-year-old woman patient with symptomatic BMs from NSLCL, treated with afatinib and concomitant WBRT, 30 Gy in 10 fractions. Treatment induced a remarkable and persistent radiological regression of BMs and the disappearance of neurological symptoms. However, the patient experienced severe skin toxicity of G3, corresponding to the irradiation area. Toxicity was successfully treated pharmacologically, and the patient did not experience any BMs-related symptoms for the next 10 months. She died of COVID-19-related respiratory failure. The association of afatinib with WBRT appears to be a successful strategy in the control of BMs from EGFR-mutated NSCLC. However, it should be considered that the combination could be responsible for serious dermatological toxicity.