-
Journal of Clinical Medicine May 2024Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly...
Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral ( = 4) or Non-alcoholic steatohepatitis, NASH ( = 2). Tumor focality was multifocal ( = 4) and unifocal ( = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab ( = 4), nivolumab/ipilimumab ( = 1), and nivolumab as monotherapy ( = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.
PubMed: 38892779
DOI: 10.3390/jcm13113068 -
JAMA Network Open Jun 2024Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small... (Observational Study)
Observational Study
IMPORTANCE
Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.
OBJECTIVE
To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.
DESIGN, SETTING, AND PARTICIPANTS
This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.
EXPOSURES
Preoperative chemotherapy (with or without radiotherapy) followed by resection.
MAIN OUTCOMES AND MEASURES
The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.
RESULTS
Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).
CONCLUSIONS AND RELEVANCE
This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
Topics: Humans; Pancreatic Neoplasms; Male; Middle Aged; Female; Adenocarcinoma; Aged; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Cohort Studies; Oxaliplatin; Pancreatectomy
PubMed: 38888920
DOI: 10.1001/jamanetworkopen.2024.17625 -
PloS One 2024The inflammatory response is a key factor in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI), and anti-inflammatory interventions may offer a promising...
BACKGROUND
The inflammatory response is a key factor in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI), and anti-inflammatory interventions may offer a promising therapeutic strategy. Forsythoside B (FB) is a phenylethanoid glycoside isolated from Forsythiae fructus, which has been reported to have anti-inflammatory effects. However, the mechanism of the neuroprotective effect of FB on CIRI remains unclear.
METHODS
Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R). FB was administered intraperitoneally for 3 days prior to MCAO/R. Cerebral infarct volume and neurological deficit score were used as indices to evaluate MCAO/R injury. The serum levels of inflammatory factors and antioxidant enzymes were measured. The activation of silent information regulator 2 homolog 1 (Sirt1) and the inhibition of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) pathway were assessed through western blot and immunohistochemistry analysis. Furthermore, the rats were treated with Sirt1 shRNA 3 days before MCAO/R by stereotactical injection into the ipsilateral hemispheric region to assess the impact of Sirt1 knockdown on the protection of FB during MCAO/R.
RESULTS
FB reduced cerebral infarct volume and neurological deficit score in MCAO/R rats. FB reduced pathological changes and cell apoptosis in the hippocampal CA1 region and cortex on the ischemic side of rats. FB inhibited the serum levels of inflammatory factors and increased the activities of antioxidant enzymes. Further study showed that FB inhibited the activation of the NLRP3 pathway and induced Sirt1 activation.
CONCLUSION
FB demonstrated neuroprotective and anti-inflammatory effects by inhibiting the NLRP3 pathway through Sirt1 activation in CIRI.
Topics: Animals; Sirtuin 1; NLR Family, Pyrin Domain-Containing 3 Protein; Reperfusion Injury; Male; Rats, Sprague-Dawley; Inflammasomes; Rats; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Brain Ischemia; Caffeic Acids; Glucosides
PubMed: 38885233
DOI: 10.1371/journal.pone.0305541 -
Radiation Oncology (London, England) Jun 2024Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates,...
Stereotactic body radiation therapy is beneficial for a subgroup of patients with urothelial cancer and solitary metastatic disease: a single institution real-world experience.
BACKGROUND
Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population.
METHODS
All patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT.
RESULTS
In total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81-9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT.
CONCLUSIONS
SBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC.
Topics: Humans; Radiosurgery; Male; Female; Aged; Middle Aged; Retrospective Studies; Aged, 80 and over; Survival Rate; Urologic Neoplasms; Neoplasm Metastasis; Adult; Urinary Bladder Neoplasms
PubMed: 38880908
DOI: 10.1186/s13014-024-02465-y -
Oncology Reports Jul 2024Immunotherapy, particularly immune checkpoint inhibitors (ICIs), is undoubtedly one of the major breakthroughs in lung cancer research. Patient survival and prognosis... (Review)
Review
Immunotherapy, particularly immune checkpoint inhibitors (ICIs), is undoubtedly one of the major breakthroughs in lung cancer research. Patient survival and prognosis have all been improved as a result, although numerous patients do not respond to immunotherapy due to various immune escape mechanisms of the tumor cells. Recent preclinical and clinical evidence has shown that stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy, has a prominent immune priming effect that could elicit antitumor immunity against specific tumor antigens and destroy distant tumor cells, thereby achieving the elusive abscopal effect, with the resulting immuno‑active tumor environment also being more conducive to ICIs. Some landmark trials have already demonstrated the survival benefit of the dynamic duo of SBRT plus immunotherapy in metastatic non‑small‑cell lung cancer, while others such as PEMBRO‑RT further suggest that the addition of SBRT to immunotherapy could expand the current indication to those who have historically responded poorly to ICIs. In the present review, the biological mechanisms that drive the synergistic effect of SBRT and immunotherapy were first briefly outlined; then, the current understanding from clinical trials was summarized and new insight into the evolving role of immunotherapy and SBRT synergy in lung cancer treatment was provided. Finally, novel avenues for discovery were highlighted. The innovation of the present review lies in the inclusion of non‑ICI immunotherapy in the discussion, which provides a more comprehensive view on the current development and future trend of SBRT + immunotherapy synergy.
Topics: Humans; Radiosurgery; Lung Neoplasms; Immunotherapy; Combined Modality Therapy; Immune Checkpoint Inhibitors; Carcinoma, Non-Small-Cell Lung
PubMed: 38874014
DOI: 10.3892/or.2024.8755 -
Cureus May 2024Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in...
Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in the English literature as of January 31, 2024. Nevertheless, physicians need to be vigilant in recognizing this condition, as its progression impacts the quality of life (QOL) of affected patients. In Case 1, a 60-year-old male with a medical history of papillary RCC experienced a deterioration in visual acuity (VA) and was diagnosed with solitary choroidal metastasis. Subsequently, multiple metastases were identified, prompting the initiation of a combination therapy regimen consisting of pembrolizumab plus axitinib. Despite treatment, progression of choroidal metastasis and a further decline in VA were observed. The patient underwent stereotactic radiotherapy and experienced complete resolution of the choroidal metastasis, accompanied by a slight improvement in VA. In Case 2, a 76-year-old man presented with a renal tumor accompanied by lung metastases. He underwent nephrectomy, and the histological diagnosis was papillary RCC. We initiated combination therapy consisting of nivolumab plus cabozantinib. The patient experienced a decrease in VA during treatment. We identified extensive fine metastases scattered throughout the bilateral choroid. We administered axitinib, but the patient experienced bilateral blindness. Given the absence of established therapy for choroidal metastasis, it is crucial to maintain flexibility in treatment selection. Local or systemic approaches should be used as deemed appropriate for each individual case.
PubMed: 38868281
DOI: 10.7759/cureus.60191 -
Clinical Case Reports Jun 2024Intracranial RDD is rare medical event mimicking different diagnoses. Although the surgical resection is the best treatment option, but radiation therapy can also...
KEY CLINICAL MESSAGE
Intracranial RDD is rare medical event mimicking different diagnoses. Although the surgical resection is the best treatment option, but radiation therapy can also achieves long-term suboptimal outcomes.
ABSTRACT
An 83-year-old male with a history of tension-type headaches was evaluated. He was conscious with no focal neurological deficits. His brain MRI revealed an enhancable bifrontal tumor originating from falx cerebri and superior sagittal sinus dura. Due to the patient's preference and decline for gross total resection, she underwent a stereotactic biopsy. The pathology was positive for Rosai-Dorfman diseases. He received definitive targeted radiation with a total dose of 4500 cGy administered in 200 cGy daily fractions. His 4-year follow-up showed regional tumor control with excellent neurological outcome.
PubMed: 38868118
DOI: 10.1002/ccr3.9053 -
Neurosurgery Apr 2024Despite general acceptance that corticosteroid therapy (CST) should be withheld before biopsy for suspected primary central nervous system lymphoma (PCNSL), there...
BACKGROUND AND OBJECTIVES
Despite general acceptance that corticosteroid therapy (CST) should be withheld before biopsy for suspected primary central nervous system lymphoma (PCNSL), there remains conflicting evidence surrounding the precise impact of preoperative CST on the histopathological diagnosis. The objective of this systematic review and meta-analysis was to describe and quantify the effects of preoperative CST on the diagnostic accuracy of biopsies for PCNSL.
METHODS
Primary articles were screened from Ovid MEDLINE, Embase, Web of Science, and Scopus databases. Meta-analysis was performed for immunocompetent patients with histologically confirmed PCNSL. Subgroup and regression analyses were performed to assess the effects of biopsy type, CST duration, dose, and preoperative taper on the diagnostic accuracy. In addition, the sensitivity of cerebrospinal fluid (CSF) analyses for PCNSL was assessed.
RESULTS
Nineteen studies, comprising 1226 patients (45% female; mean age: 60.3 years), were included. Preoperative CST increased the risk of nondiagnostic biopsy with a relative risk (RR) of 2.1 (95% CI: 1.1-4.1). In the stereotactic biopsy subgroup, the RR for nondiagnostic biopsy was 3.0 (95% CI: 1.2-7.5). CST taper, duration, and dose did not significantly influence diagnostic biopsy rates. The sensitivity of CSF cytology, including flow cytometry, for PCNSL was 8.0% (95% CI: 6.0%-10.7%).
CONCLUSION
Our results suggest that preoperative CST reduces the diagnostic yield of stereotactic biopsies for PCNSL. We found no evidence that tapering CST before biopsy improves diagnostic rates. CSF analysis currently has a poor sensitivity for the diagnosis of PCNSL.
PubMed: 38865324
DOI: 10.1227/neu.0000000000002944 -
Journal of Neuro-oncology Jun 2024The efficacy and safety of laser interstitial thermal therapy followed by consolidation radiosurgery (LITT-cSRS) was previously studied in brain metastasis that recurs...
INTRODUCTION
The efficacy and safety of laser interstitial thermal therapy followed by consolidation radiosurgery (LITT-cSRS) was previously studied in brain metastasis that recurs locally after initial radiosurgery (BMRS). Here, we characterize the clinical outcome of LITT-cSRS in patients with newly diagnosed brain metastasis.
METHODS
Between 2017 and 2023, ten consecutive cancer patients with newly diagnosed brain mass of unclear etiology who underwent stereotactic needle biopsy (SNB) and LITT in the same setting followed by consolidation SRS (cSRS) with > 6 months follow-up were identified retrospectively. Clinical and imaging outcomes were collected.
RESULTS
The histology of the BM were: breast cancer (n = 3), melanoma (n = 3), non-cell cell lung cancer (n = 3), colon (n = 1). There were no wound or procedural complications. All patients were discharged home, with a median one-day hospital stay (range: 1-2 days). All patients were off corticosteroid therapy by the one-month follow-up. cSRS were carried out 12-27 days (median of 19 days) after SNB + LITT. There were no subsequent emergency room presentation, 30-day or 90-day re-admission. The Karnofsky Performance Score (KPS) remains stable or improved at the 3 months-follow-up. With a median follow-up of 416 days (13.8 mo; range: 199-1,096 days), there was one local recurrence at 384 days (12.8 mo) post-LITT-cSRS. With exception of this patient with local recurrence, all patients showed decreased FLAIR volume surrounding the LITT-cSRS treated BMRS by the six-month follow-up.
CONCLUSIONS
To our awareness, this case series represent the first to describe LITT-cSRS in the setting of newly diagnosed BM. The results presented here provide pilot data to support the safety and efficacy of LITT-cSRS and lay the foundation for future studies.
PubMed: 38865010
DOI: 10.1007/s11060-024-04712-4 -
Technology in Cancer Research &... 2024Recurrence after stage III lung cancer treatment usually appears with a poor prognosis, and salvage therapy for these patients is challenging, with limited data for...
Recurrence after stage III lung cancer treatment usually appears with a poor prognosis, and salvage therapy for these patients is challenging, with limited data for reirradiation. Fifteen patients with recurrent stage III lung cancer treated with stereotactic body radiotherapy (SABR) between October 2013 and December 2017 were retrospectively evaluated for local control as a first endpoint; overall survival, disease-free survival, and treatment-related toxicity were secondary endpoints. The median age was 68 (IQR: 50-71) years, and the median tumor size was 3.3 cm (IQR: 3.0-4.5). The radiation field was all within the previous radiation (previous 80%-90% isodose line), and the median dose was 66 Gy/(2 Gy × 33 ) For SABR, the median biologically effective dose at an α/β ratio of 10 (BED) was 60.0 Gy (IQR: 39.38-85.0) and given in 3 to 5 fractions. Three patients experienced grade 3 or 4 toxicity but none experienced grade 5. The median follow-up period was 14 (IQR: 10-23) months. The local control rate was found as 86.7% in the first year, 80% in the second year, and 80% in the third year. The median disease-free survival was 8 (IQR: 6-20) months and the median overall survival was 14 (IQR: 10-23) months. The rate of overall survival was 66.6% for the first year and 33.3% for the second and third years. The disease-free survival rate was 46.6% for the first year and 40% for the second and third years. Nine patients who received doses of BED ≥ 50 Gy developed no local recurrence ( = .044). In local local-regional recurrence of lung cancer, radiosurgery as reirradiation can be used at doses of BED ≥ 50 Gy and above to provide local control for radical or palliative purposes. SABR is an important and relatively safe treatment option in such recurrences.
Topics: Humans; Radiosurgery; Middle Aged; Lung Neoplasms; Aged; Male; Female; Neoplasm Recurrence, Local; Re-Irradiation; Retrospective Studies; Neoplasm Staging; Treatment Outcome; Radiotherapy Dosage; Dose Fractionation, Radiation
PubMed: 38860536
DOI: 10.1177/15330338231208616