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Frontiers in Oncology 2023Pseudoprogression is rarely mentioned after radiotherapy except for central nervous system tumors. With the widespread of immunotherapy, the incidence of...
Pseudoprogression is rarely mentioned after radiotherapy except for central nervous system tumors. With the widespread of immunotherapy, the incidence of pseudoprogression of thoracic tumor after radiotherapy is increasing. This study summarized the clinical features of pseudoprogression in 4 patients who had underwent thoracic radiotherapy after and/or followed by immunotherapy. All of them had received chemotherapy and immunotherapy before thoracic radiotherapy. After radiotherapy, pseudoprogression occurred within 3 months after initiation of immune consolidation/rechallenge therapy. At least a 20% increase in the sum of the longest diameter of target lesions were measured on their chest image. During this period, patients' ECOG PS scores remained stable, specific serum tumor markers did not increase significantly. Treatment strategies did not change after pseudoprogression. The causes of radiographic pseudoprogression in this case series may be attributed to disturbances such as pneumonitis, atelectasis, mucus blockages and infection. In the era of immunotherapy, pseudoprogression of thoracic tumors after chest radiotherapy might become a common phenomenon. It is important for us to identify pseudoprogression based on patient's general status, radiological changes, and laboratory tests.
PubMed: 37576884
DOI: 10.3389/fonc.2023.1021253 -
Cancers Aug 2023Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic...
BACKGROUND
Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic resonance imaging (MRI) following the Response Assessment in Neuro-Oncology (RANO) criteria. However, early assessment is hindered by phenomena such as pseudoprogression and pseudoresponse. Magnetic resonance spectroscopy (MRS/MRSI) provides metabolomics information but is underutilised due to a lack of familiarity and standardisation.
METHODS
This study explores the potential of spectroscopic imaging (MRSI) in combination with several machine learning approaches, including one-dimensional convolutional neural networks (1D-CNNs), to improve therapy response assessment. Preclinical GB (GL261-bearing mice) were studied for method optimisation and validation.
RESULTS
The proposed 1D-CNN models successfully identify different regions of tumours sampled by MRSI, i.e., normal brain (N), control/unresponsive tumour (T), and tumour responding to treatment (R). Class activation maps using Grad-CAM enabled the study of the key areas relevant to the models, providing model explainability. The generated colour-coded maps showing the N, T and R regions were highly accurate (according to Dice scores) when compared against ground truth and outperformed our previous method.
CONCLUSIONS
The proposed methodology may provide new and better opportunities for therapy response assessment, potentially providing earlier hints of tumour relapsing stages.
PubMed: 37568818
DOI: 10.3390/cancers15154002 -
European Journal of Nuclear Medicine... Nov 2023The O-(2-[F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient...
Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.
PURPOSE
The O-(2-[F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation.
METHODS
Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBR), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBR/TBR) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]).
RESULTS
Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBR, and TBR were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement.
CONCLUSION
The FIG study credentialing program has increased expertise across study sites. TBR and TBR were robust, with considerable variability in BTV delineation and image interpretation observed.
Topics: Humans; Glioblastoma; Ficus; Brain Neoplasms; Nuclear Medicine; Prospective Studies; Australia; Positron-Emission Tomography; Tyrosine; Magnetic Resonance Imaging
PubMed: 37563351
DOI: 10.1007/s00259-023-06371-5 -
Internal Medicine (Tokyo, Japan) Apr 2024Nivolumab plus ipilimumab is one of the first-line treatments for advanced non-small-cell lung cancer (NSCLC), but the safety and efficacy in patients on hemodialysis...
PD-L1-negative Non-small-cell Lung Cancer Treated with Nivolumab Plus Ipilimumab during Maintenance Hemodialysis Results in Rapid Initial Progression Followed by a Long-lasting Response.
Nivolumab plus ipilimumab is one of the first-line treatments for advanced non-small-cell lung cancer (NSCLC), but the safety and efficacy in patients on hemodialysis (HD) is unclear. We herein report a patient with NSCLC on HD in whom nivolumab and ipilimumab were initiated. We observed general deterioration and enlarged lesions, followed by a long-term response. The patient developed secondary hypoadrenocorticism, an immune-related adverse event that was easily controlled. Nivolumab plus ipilimumab can be used safely for patients with NSCLC on HD. Long-term effectiveness can be observed after initial progression, so we should carefully assess the response.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Nivolumab; Ipilimumab; B7-H1 Antigen; Lung Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37558475
DOI: 10.2169/internalmedicine.2270-23 -
Oncology Letters Aug 2023Brain metastases (BMs) usually develop in patients with non-small cell lung cancer. In addition to systemic therapy, radiation therapy and surgery, anti-programmed cell...
Radionecrosis mimicking pseudo‑progression in a patient with lung cancer and brain metastasis following the combination of anti‑PD‑1 therapy and stereotactic radiosurgery: A case report.
Brain metastases (BMs) usually develop in patients with non-small cell lung cancer. In addition to systemic therapy, radiation therapy and surgery, anti-programmed cell death-ligand 1 (PD-L1) therapy is another promising clinical anticancer treatment modality. However, the optimal timing and drug-drug interactions of anti-PD-L1 therapy with other combined treatments remain to be elucidated. Treatment with anti-PD-L1 therapy is associated with an increased risk of radionecrosis (RN) regardless of tumor histology. The present study described a case of RN in a patient with lung adenocarcinoma and with BM who received anti-PD-L1 therapy. Before anti-PD-L1 treatment, the patient received whole brain radiotherapy. During durvalumab treatment, the intracranial metastases regressed. The progression of intracranial lesions 9 months later prompted a second-line of therapy with PD-L1 inhibitor durvalumab and stereotactic radiotherapy (SRT). Despite stereotactic irradiation, the lesions progressed further, leading to surgical resection. On examination, RN was detected, but there was no evidence of metastatic lung cancer. The aim of the present study was to present the longitudinal change in magnetic resonance imaging in RN following STR and anti-PD-L1 combined therapy. The atypical image of RN is conditionally important for making an accurate preoperative diagnosis.
PubMed: 37545620
DOI: 10.3892/ol.2023.13947 -
The American Journal of Case Reports Aug 2023BACKGROUND Melanoma is an aggressive skin cancer that can be difficult to manage. Its treatment has been transformed by immunotherapy. Melanoma cells frequently have...
BACKGROUND Melanoma is an aggressive skin cancer that can be difficult to manage. Its treatment has been transformed by immunotherapy. Melanoma cells frequently have mutations that make them vulnerable to attack by the immune system, and this is how immunotherapy can fight this cancer. Immunotherapy with checkpoint inhibitors targets mechanisms that malignant cells use to evade immune system detection, blocking proteins produced by the tumor, and allowing the immune system to identify and attack cancerous cells. CASE REPORT A 74-year-old woman presented with a lump on the right side of her chest. Tests revealed a metastatic malignant tumor with melanocytic differentiation. Stage IV melanoma was diagnosed, and the patient started therapy with nivolumab/ipilimumab for palliative intent, which she tolerated without adverse effects. However, she was hospitalized for Clostridioides difficile colitis after 3 treatment cycles, and computed tomography (CT) scan findings suggested disease progression. Positron emission tomography (PET)-CT obtained after her discharge from the hospital showed a complete metabolic response at all disease sites, indicating the initial progression was most likely a pseudo-progression from the use of immunotherapy. The patient continued with nivolumab as a single agent and has been doing well. CONCLUSIONS This case highlights the importance of careful evaluation of immunotherapy response in patients with melanoma. The initial progression noted in this patient was most likely pseudo-progression, which resolved with further immunotherapy. Clinicians should consider PET-CT imaging in cases of suspected pseudo-progression to avoid unnecessary changes in therapy. Patient response to immunotherapy demonstrates the effectiveness of immunotherapy in treating advanced melanoma.
Topics: Female; Humans; Aged; Nivolumab; Ipilimumab; Positron Emission Tomography Computed Tomography; Antineoplastic Agents, Immunological; Melanoma
PubMed: 37545116
DOI: 10.12659/AJCR.940954 -
Medicine Aug 2023In the last few years, treatment of head and neck squamous cell carcinoma (HNSCC) has been enhanced by the emergence of immunotherapy. A biological phenomenon unique to...
RATIONALE
In the last few years, treatment of head and neck squamous cell carcinoma (HNSCC) has been enhanced by the emergence of immunotherapy. A biological phenomenon unique to immunotherapy is pseudoprogression, an increase in tumor burden or the appearance of a new lesion subsequently followed by tumor regression.
PATIENT CONCERNS
A 78-year-old man complaining of a lump (6*4 cm) gradually swelling on the right side of his neck with recurrent buccal mucosa squamous cell carcinoma presented to our institution. Two months prior, he received resection of the buccal lesion but refused suggested adjuvant chemoradiotherapy after the operation.
DIAGNOSES
Recurrent buccal mucosa squamous cell carcinoma.
INTERVENTIONS
Induction immunotherapy was initiated, followed by a new node appearing on the surface of the neck mass. We considered the presence of pseudoprogression and continued with immunotherapy. The patient received immunotherapy combined with chemotherapy and intensity-modulated radiation therapy (IMRT) consecutively.
OUTCOMES
The patient experienced an excellent recovery with the disappearance of pain and the lump, along with return of a healthy appetite, weight gain and positive outlook. Complete response (CR) was also noted by magnetic resonance imaging (MRI) scan, with the upper right neck mass significantly retreated to unclear display. The patient is still alive with stable, asymptomatic disease at the time of this writing.
LESSONS
These results provide confidence in the safety and efficacy of radical chemo-radio-immunotherapy for the treatment of recurrent, unresectable or metastatic HNSCC.
Topics: Male; Humans; Aged; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Immunotherapy; Chemoradiotherapy
PubMed: 37543761
DOI: 10.1097/MD.0000000000033797 -
BMJ Open Aug 2023Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and...
INTRODUCTION
Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and postoperative radiotherapy with concurrent and adjuvant temozolomide-based chemotherapy, tumours inevitably recur. Imaging with O-(2-[F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) has the potential to impact adjuvant radiotherapy (RT) planning, distinguish between treatment-induced pseudoprogression versus tumour progression as well as prognostication.
METHODS AND ANALYSIS
The FET-PET in Glioblastoma (FIG) study is a prospective, multicentre, non-randomised, phase II study across 10 Australian sites and will enrol up to 210 adults aged ≥18 years with newly diagnosed glioblastoma. FET-PET will be performed at up to three time points: (1) following initial surgery and prior to commencement of chemoradiation (FET-PET1); (2) 4 weeks following concurrent chemoradiation (FET-PET2); and (3) within 14 days of suspected clinical and/or radiological progression on MRI (performed at the time of clinical suspicion of tumour recurrence) (FET-PET3). The co-primary outcomes are: (1) to investigate how FET-PET versus standard MRI impacts RT volume delineation and (2) to determine the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumour progression. The secondary outcomes are: (1) to investigate the relationships between FET-PET parameters (including dynamic uptake, tumour to background ratio, metabolic tumour volume) and progression-free survival and overall survival; (2) to assess the change in blood and tissue biomarkers determined by serum assay when comparing FET-PET data acquired prior to chemoradiation with other prognostic markers, looking at the relationships of FET-PET versus MRI-determined site/s of progressive disease post chemotherapy treatment with MRI and FET-PET imaging; and (3) to estimate the health economic impact of incorporating FET-PET into glioblastoma management and in the assessment of post-treatment pseudoprogression or recurrence/true progression. Exploratory outcomes include the correlation of multimodal imaging, blood and tumour biomarker analyses with patterns of failure and survival.
ETHICS AND DISSEMINATION
The study protocol V.2.0 dated 20 November 2020 has been approved by a lead Human Research Ethics Committee (Austin Health, Victoria). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results of the FIG study (TROG 18.06) will be disseminated via relevant scientific and consumer forums and peer-reviewed publications.
TRIAL REGISTRATION NUMBER
ANZCTR ACTRN12619001735145.
Topics: Adult; Humans; Adolescent; Glioblastoma; Positron Emission Tomography Computed Tomography; Ficus; Tyrosine; Prospective Studies; Brain Neoplasms; Neoplasm Recurrence, Local; Australia; Positron-Emission Tomography; Magnetic Resonance Imaging; Clinical Trials, Phase II as Topic; Multicenter Studies as Topic
PubMed: 37541751
DOI: 10.1136/bmjopen-2022-071327 -
Journal of Cellular and Molecular... Jul 2023Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are... (Review)
Review
Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.
PubMed: 37525480
DOI: 10.1111/jcmm.17895 -
BMC Cancer Jul 2023In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory...
BACKGROUND
In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab.
METHODS
Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive.
RESULTS
This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available.
CONCLUSIONS
The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort.
TRIAL REGISTRATION
Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).
Topics: Adolescent; Humans; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Neoplasm Recurrence, Local; Nivolumab
PubMed: 37507657
DOI: 10.1186/s12885-023-11153-1