-
Journal of Neuro-oncology May 2024There remains no standard of care for patients with recurrent and chemorefractory glioblastoma. Re-irradiation (reRT) provides an additional management option. However,...
Hypofractionated re-irradiation with bevacizumab for relapsed chemorefractory glioblastoma after prior high dose radiotherapy: a feasible option for patients with large-volume relapse.
PURPOSE
There remains no standard of care for patients with recurrent and chemorefractory glioblastoma. Re-irradiation (reRT) provides an additional management option. However, published series predominantly focus on small reRT volumes utilizing stereotactic hypofractionated regimens. Concerns regarding toxicity have limited utilisation of reRT for larger recurrences, however this may be mitigated with use of bevacizumab (BEV).
METHODS AND MATERIALS
A prospective database of patients managed with the EORTC-NCIC (Stupp) protocol 60 Gy chemoradiotherapy protocol for glioblastoma between 2007 and 2021 was reviewed for those patients receiving reRT for chemorefractory relapse. Serial MRI and PET were used to establish true progression and exclude patients with pseudoprogression or radionecrosis from reRT. The primary endpoint was overall survival (OS) from date of reRT. Prognostic factors were also assessed.
RESULTS
447 patients managed for glioblastoma under the Stupp protocol were identified, of which 372 had relapsed and were thus eligible for reRT. 71 patients underwent reRT. Median relapse-free survival from diagnosis for the reRT and overall cohorts were similar at 11.6 months (95%CI:9.4-14.2) and 11.8 months (95%CI:9.4-14.2) respectively. 60/71 (85%) reRT patients had received BEV prior to reRT and continued concurrent BEV during reRT. Of the 11 patients not managed with BEV during reRT, 10 required subsequent salvage BEV. ReRT patients were younger (median 53 vs. 59 years, p < 0.001), had better performance status (86% vs. 69% ECOG 0-1, p = 0.002) and more commonly had MGMT promoter-methylated tumours (54% vs. 40%, p = 0.083) compared to non-reRT patients. Median reRT PTV volume was 135cm (IQR: 69-207cm). Median OS from reRT to death was 7.1 months (95%CI:6.3-7.9). Patients aged < 50, 50-70 and > 70 years had post-reRT median OS of 7.7, 6.4 and 6.0 months respectively (p = 0.021). Median post-reRT survival was longer for patients with ECOG performance status 0-1 compared to 2-3 (8.1 vs. 6.3 months, p = 0.039). PTV volume, site of relapse, MGMT promoter-methylation status and extent of initial surgical resection were not associated with post-reRT survival. ReRT was well-tolerated. Out of the 6 patients (8%) admitted to hospital after reRT, only one was for reRT toxicity. This was a CTCAE grade 3 radiation necrosis event in a patient managed without prior BEV.
CONCLUSION
Patients with recurrent glioblastoma who have been previously treated with 60 Gy radiotherapy have a meaningful survival benefit from large volume re-irradiation which is well tolerated. ReRT should not be ignored as a salvage treatment option in patients with chemorefractory progressive disease.
Topics: Humans; Glioblastoma; Bevacizumab; Female; Male; Middle Aged; Brain Neoplasms; Neoplasm Recurrence, Local; Re-Irradiation; Aged; Radiation Dose Hypofractionation; Antineoplastic Agents, Immunological; Adult; Prospective Studies; Salvage Therapy; Retrospective Studies; Prognosis; Chemoradiotherapy; Follow-Up Studies; Survival Rate
PubMed: 38551747
DOI: 10.1007/s11060-024-04643-0 -
Neurosurgery Mar 2024
PubMed: 38529998
DOI: 10.1227/neu.0000000000002932 -
Neurosurgery Mar 2024
PubMed: 38529995
DOI: 10.1227/neu.0000000000002931 -
Cancer Imaging : the Official... Mar 2024Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new...
BACKGROUND
Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system.
METHODS
This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints (< 5 months, 5-10 months, > 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT).
RESULTS
Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2-59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen's Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT.
CONCLUSIONS
PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS.
Topics: Humans; Male; Aged; Female; Skin Neoplasms; Carcinoma, Squamous Cell; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Tomography, X-Ray Computed; Australia; Retrospective Studies; Immunotherapy
PubMed: 38500235
DOI: 10.1186/s40644-024-00678-8 -
Translational Lung Cancer Research Feb 2024Programmed cell death protein-1/programmed cell death protein-ligand 1 (PD-1/PD-L1) inhibitor and chemotherapy are the standard treatment for advanced non-small cell...
BACKGROUND
Programmed cell death protein-1/programmed cell death protein-ligand 1 (PD-1/PD-L1) inhibitor and chemotherapy are the standard treatment for advanced non-small cell lung cancer (NSCLC) without sensitizing mutations. However, patients with untreated, symptomatic or recently-irradiated brain metastases (BMs) are mostly excluded from immunochemotherapy trials. This study aims to evaluate the intracranial response pattern, tolerability and biomarkers of tislelizumab plus chemotherapy in NSCLC with untreated, symptomatic or recently-irradiated BM.
METHODS
This multicenter, single-arm, phase 2 trial enrolled patients with treatment-naïve, brain-metastasized NSCLC. BM could be untreated or irradiated. Symptomatic or recently-irradiated BMs that were deemed clinically stable were allowed. Patients received tislelizumab (200 mg) plus pemetrexed (500 mg/m) and carboplatin (AUC =5) on day 1 every 3 weeks for 4 cycles, followed by maintenance with tislelizumab plus pemetrexed. Primary endpoint was 1-year progression-free survival (PFS) rate. Secondary endpoints included intracranial efficacy and tolerability. PD-L1 expression, tumor mutational burden (TMB) and genomic alterations were evaluated as potential biomarkers.
RESULTS
A total of 36 patients were enrolled, 19.2% had prior brain radiotherapy, 8.3% had symptomatic BMs that required corticosteroids ≤10 mg/d or antiepileptics. Confirmed systemic and intracranial ORR (iORR) was 43.8% and 46.7%, respectively. One-year systematic PFS rate and One-year iPFS rate was 36.8% and 55.8%, respectively. About 41.7% patients had neurological adverse events, 90% patients had concordant intracranial-extracranial responses. No intracranial pseudoprogression or hyperprogression occurred. Patients with prior brain radiation trended towards higher systemic (83.3% . 34.6%) and iORR (75.0% . 42.3%). Similar intracranial efficacy was observed in tumors with different PD-L1 and TMB levels, while alterations in cytokine receptors pathway predicted higher iORR (P=0.081), prolonged systematic PFS [hazard ratio (HR) =0.16, P=0.021] and overall survival (OS) (HR =0.71, P=0.029).
CONCLUSIONS
Untreated or irradiated BMs in NSCLC follows a conventional response and progression pattern under immunochemotherapy with altered cytokine receptors pathway being a potential biomarker for systemic and intracranial outcomes.
PubMed: 38496686
DOI: 10.21037/tlcr-23-687 -
Cancers Feb 2024The activity of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma is often monitored using fluorine-18-fluorodeoxyglucose-positron emission...
Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression.
The activity of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma is often monitored using fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans. However, distinguishing disease progression (PD) from pseudoprogression (PsPD), where increased FDG uptake might reflect immune cell activity rather than tumor growth, remains a challenge. This prospective study compared the efficacy of dual-time point (DTP) FDG-PET/CT with modified response criteria (PERCIMT) in differentiating PsPD from PD. From July 2017-January 2021, 41 patients suspected to have PsPD on an evaluation scan were prospectively included (29 evaluable). A subsequent DTP FDG-PET/CT scan was conducted within 14 days, followed by a confirmatory FDG-PET/CT scan. Additionally, PERCIMT were applied. DTP FDG-PET/CT identified 24% with PsPD and 76% with PD. Applying PERCIMT criteria, 69% showed PsPD, while 31% had PD. On follow-up, 10 patients (34%) demonstrated confirmed PsPD, while 19 (66%) exhibited PD. The sensitivity and specificity of DTP FDG-PET/CT were 20% and 74%, respectively, and for PERCIMT this was 80% and 37%, respectively. Our findings suggest limited efficacy of DTP FDG-PET/CT in distinguishing PsPD from PD in ICI-treated patients with metastatic melanoma. The use of PERCIMT could complement clinical assessment and be incorporated in multidisciplinary team conferences for enhanced decision-making.
PubMed: 38473325
DOI: 10.3390/cancers16050964 -
Cancer Treatment and Research... 2024Colorectal cancer (CRC) continues to be one of the most prevalent and lethal cancers worldwide. Over the past decades, immune checkpoint inhibitors (ICIs) have shown to... (Review)
Review
Colorectal cancer (CRC) continues to be one of the most prevalent and lethal cancers worldwide. Over the past decades, immune checkpoint inhibitors (ICIs) have shown to significantly improve patient outcomes in mismatch repair-deficient metastasized CRC. However, widening the scope of this novel treatment modality has been the object of growing interest. This article will review several landmark trials, while exploring various aspects of this rapidly evolving field, including potential neoadjuvant (or even entirely nonsurgical) and adjuvant indications in localized disease. We will also discuss differences between management of rectal and colon cancer, current and expected challenges (eg. resistance, toxicities, pseudoprogression, biomarkers) and other future opportunities including combinations with other therapeutic agents and the role of ICIs in the treatment of both deficient as well as proficient mismatch repair (dMMR and pMMR respectively) CRC.
Topics: Humans; Colorectal Neoplasms; DNA Mismatch Repair; Immune Checkpoint Inhibitors; Immunotherapy; Neoadjuvant Therapy
PubMed: 38461691
DOI: 10.1016/j.ctarc.2024.100807 -
Journal of Neuro-oncology Apr 2024We aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma.
PURPOSE
We aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma.
METHODS
The records of 77 previously irradiated glioblastoma patients who progressed and received second course hypofractionated SRT (1-5 fractions) between 2009 and 2022 in our department were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for all statistical analyses.
RESULTS
The median time to progression from the end of initial radiotherapy was 14 months (range, 6-68 months). The most common SRT schedule was 30 Gy (range, 18-50 Gy) in 5 fractions (range, 1-5 fractions). The median follow-up after SRT was 9 months (range, 3-80 months). One-year overall (OS) and progression-free survival (PFS) rates after SRT were 46% and 35%, respectively. Re-irradiation dose and the presence of pseudoprogression were both significant independent positive prognostic factors for both OS (p = 0.009 and p = 0.04, respectively) and PFS (p = 0.008 and p = 0.04, respectively). For PFS, progression-free interval > 14 months was also a prognostic factor (p = 0.04). The treatment was well tolerated without significant acute toxicity. During follow-up, radiation necrosis was observed in 17 patients (22%), and 14 (82%) of them were asymptomatic.
CONCLUSION
Hypofractionated SRT is an effective treatment approach for patients with progressive glioblastoma. Younger patients who progressed later than 14 months, received higher SRT doses, and experienced pseudoprogression following SRT had improved survival rates.
Topics: Humans; Glioblastoma; Brain Neoplasms; Retrospective Studies; Re-Irradiation; Neoplasm Recurrence, Local; Dose Fractionation, Radiation; Radiosurgery
PubMed: 38383875
DOI: 10.1007/s11060-024-04607-4 -
Oncoimmunology 2024This study aimed to develop a computed tomography (CT)-based radiomics model capable of precisely predicting hyperprogression and pseudoprogression (PP) in patients with...
Noninvasive radiomic biomarkers for predicting pseudoprogression and hyperprogression in patients with non-small cell lung cancer treated with immune checkpoint inhibition.
This study aimed to develop a computed tomography (CT)-based radiomics model capable of precisely predicting hyperprogression and pseudoprogression (PP) in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy. We retrospectively analyzed 105 patients with NSCLC, from three institutions, treated with immune checkpoint inhibitors (ICIs) and categorized them into training and independent testing set. Subsequently, we processed CT scans with a series of image-preprocessing techniques, and 6008 radiomic features capturing intra- and peritumoral texture patterns were extracted. We used the least absolute shrinkage and selection operator logistic regression model to select radiomic features and construct machine learning models. To further differentiate between progressive disease (PD) and hyperprogressive disease (HPD), we developed a new radiomics model. The logistic regression (LR) model showed optimal performance in distinguishing PP from HPD, with areas under the receiver operating characteristic curve (AUC) of 0.95 (95% confidence interval [CI]: 0.91-0.99) and 0.88 (95% CI: 0.66-1) in the training and testing sets, respectively. Additionally, the support vector machine model showed optimal performance in distinguishing PD from HPD, with AUC of 0.97 (95% CI: 0.93-1) and 0.87 (95% CI: 0.72-1) in the training and testing sets, respectively. Kaplan‒Meier survival curves showed clear stratification between PP predicted by the radiomics model and true progression (HPD and PD) (hazard ratio = 0.337, 95% CI: 0.200-0.568, < 0.01) in overall survival. Our study demonstrates that radiomic features extracted from baseline CT scans are effective in predicting PP and HPD in patients with NSCLC treated with ICIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Radiomics; Retrospective Studies; Disease Progression; Biomarkers
PubMed: 38343749
DOI: 10.1080/2162402X.2024.2312628 -
Seminars in Nuclear Medicine Mar 2024Following the previous part of the narrative review on artificial intelligence (AI) applications in positron emission tomography (PET) using tracers rather than... (Review)
Review
Application of Artificial Intelligence in Oncologic Molecular PET-Imaging: A Narrative Review on Beyond [F]F-FDG Tracers Part II. [F]F-FLT, [F]F-FET, [C]C-MET and Other Less-Commonly Used Radiotracers.
Following the previous part of the narrative review on artificial intelligence (AI) applications in positron emission tomography (PET) using tracers rather than F-fluorodeoxyglucose ([F]F-FDG), in this part we review the impact of PET-derived radiomics data on the diagnostic performance of other PET radiotracers, F-O-(2-fluoroethyl)-L-tyrosine ([F]F-FET), F-Fluorothymidine ([F]F-FLT) and C-Methionine ([C]C-MET). [F]F-FET-PET, using an artificial amino acid taken up into upregulated tumoral cells, showed potential in lesion detection and tumor characterization, especially with its ability to reflect glioma heterogeneity. [F]F-FET-PET-derived textural features appeared to have the potential to reveal considerable information for accurate delineation for guiding biopsy and treatment, differentiate between low-grade and high-grade glioma and related wild-type genotypes, and distinguish pseudoprogression from true progression. In addition, models built using clinical parameters and [F]F-FET-PET-derived radiomics features showed acceptable results for survival stratification of glioblastoma patients. [F]F-FLT-PET-based characteristics also showed potential in evaluating glioma patients, correlating with Ki-67 and patient prognosis. AI-based PET-volumetry using this radiotracer as a proliferation marker also revealed promising preliminary results in terms of guide-targeting bone marrow-preserving adaptive radiation therapy. Similar to [F]F-FET, the other amino acid tracer which reflects cellular proliferation, [C]C-MET, has also shown acceptable performance in predicting tumor grade, distinguishing brain tumor recurrence from radiation necrosis, and treatment monitoring by PET-derived radiomics models. In addition, PET-derived radiomics features of various radiotracers such as [F]F-DOPA, [F]F-FACBC, [F]F-NaF, [Ga]Ga-CXCR-4 and [F]F-FMISO may also provide useful information for tumor characterization and predict of disease outcome. In conclusion, AI using tracers beyond [F]F-FDG could improve the diagnostic performance of PET-imaging for specific indications and help clinicians in their daily routine by providing features that are often not detectable by the naked eye.
Topics: Humans; Fluorodeoxyglucose F18; Artificial Intelligence; Neoplasm Recurrence, Local; Positron-Emission Tomography; Brain Neoplasms; Glioma; Amino Acids
PubMed: 38331629
DOI: 10.1053/j.semnuclmed.2024.01.002