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Radiotherapy and Oncology : Journal of... May 2024Stereotactic body radiotherapy (SBRT) has emerged as a promising new modality for locally advanced pancreatic cancer (LAPC). The current study evaluated the efficacy and...
PURPOSE
Stereotactic body radiotherapy (SBRT) has emerged as a promising new modality for locally advanced pancreatic cancer (LAPC). The current study evaluated the efficacy and toxicity of SBRT in patients with LAPC (NCT03648632).
METHODS
This prospective single institution phase II study recruited patients with histologically or cytologically proven adenocarcinoma of the pancreas after more than two months of combination chemotherapy with no sign of progressive disease. Patients were prescribed 50-60 Gy in 5-8 fractions. Patients were initially treated on a standard linac (n = 4). Since 2019, patients were treated using online magnetic resonance (MR) image-guidance on a 1.5 T MRI-linac, where the treatment plan was adapted to the anatomy of the day. The primary endpoint was resection rate.
RESULTS
Twenty-eight patients were enrolled between August 2018 and March 2022. All patients had non-resectable disease at time of diagnosis. Median follow-up from inclusion was 28.3 months (95 % CI 24.0-NR). Median progression-free and overall survival from inclusion were 7.8 months (95 % CI 5.0-14.8) and 16.5 months (95 % CI 10.7-22.6), respectively. Six patients experienced grade III treatment-related adverse events (jaundice, nausea, vomiting and/or constipation). One of the initial four patients receiving treatment on a standard linac experienced a grade IV perforation of the duodenum. Six patients (21 %) underwent resection. A further one patient was offered resection but declined.
CONCLUSION
This study demonstrates that SBRT in patients with LAPC was associated with promising overall survival and resection rates. Furthermore, SBRT was safe and well tolerated, with limited severe toxicities.
PubMed: 38815694
DOI: 10.1016/j.radonc.2024.110347 -
Journal of Clinical Neuroscience :... Jul 2024Because of its rarity, limited data concerning brain metastasis (BM) from bladder cancer (BCa) are available, so this phenomenon remains unclear. We aimed to contribute...
AIMS AND OBJECTIVES
Because of its rarity, limited data concerning brain metastasis (BM) from bladder cancer (BCa) are available, so this phenomenon remains unclear. We aimed to contribute to understanding this unique patient population's clinical behavior and outcomes.
METHODS/MATERIALS
This retrospective cohort study included 27 BCa patients with BM treated at our Cancer Institute between April 2009 and December 2022. The time from initial diagnosis to BM and overall survival from BM diagnosis were calculated (Kaplan-Meier method). Cox regression was used to test key clinicopathologic associations.
RESULTS
A total of 27 patients were included in the study (male/female = 23/4). The median patient age at BM diagnosis was 62.0 (47-79) years. The median interval from initial diagnosis to BM was 11.0 ± 2.59 (95 % CI, 5.91-16.08) months. Twenty (74.0 %) patients were diagnosed with BM by postsymptomatic imaging. The most common symptoms were headache-dizziness (n = 9, 33.3 %), seizure (n = 3, 11.1 %), hemiparesis (n = 2, 7.4 %), and vision defects (n = 2, 7.4 %). The most common sites of extracranial metastasis were the lung (n = 10, 52.6 %), bone (n = 7, 36.8 %), and lymph nodes (n = 6, 31.5 %). More than half of the patients (55.5 %) had multiple BMs. Eight (29.6 %) patients underwent surgery for BM. All of the patients received radiotherapy (RT) for BM (whole-brain radiotherapy (WBRT)/stereotactic radiotherapy (SRT) = 24/3), and eight patients received RT for the second time. Six patients were treated with systemic chemotherapy (CT) after BM. The median survival from BM was 3.0 ± 1.2 (95 % Cl, 0.4-5.5) months in the entire cohort. A low number of BMs (HR 0.270, 95 % CI 0.083-0.885; p = 0.031), surgery for BM (HR 0.174, 95 % CI 0.043-0.712; p = 0.015), CT after BM (HR 0.207, 95 % CI 0.057-0.755; p = 0.017), and better ECOG performance score (HR 0.248, 95 % CI 0.074-0.836; p = 0.025) were associated with better OS.
CONCLUSIONS
Factors associated with improved survival in BCa patients with BM include a few brain lesions, intracranial resection, CT after BM, and better ECOG performance scores. Larger-scale prospective studies are needed to define the optimal management strategy further.
Topics: Humans; Male; Middle Aged; Brain Neoplasms; Female; Urinary Bladder Neoplasms; Aged; Retrospective Studies; Prognosis
PubMed: 38815300
DOI: 10.1016/j.jocn.2024.05.027 -
Frontiers in Neurology 2024Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with...
BACKGROUND
Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with histological biopsy essential for diagnosis. Standardized treatment protocols are lacking. This disease requires urgent attention due to the increasing number of organ transplant surgeries and the use of immunosuppressive agents.
METHODS
From 2020 to 2023, our center diagnosed five patients with PCNS-PTLD. We reviewed their clinical records and conducted a comprehensive analysis of 22 literatures on PCNS-PTLD cases following renal transplantation or allogeneic hematopoietic stem cell transplantation (HSCT).
RESULTS
Four patients had previously received a kidney transplant, one had undergone allogeneic HSCT. The median time from the last transplant surgery to the diagnosis of PCNS-PTLD differs between kidney transplant (21.5 years) and allogeneic HSCT (9 months). Common symptoms included motor weakness ( = 4), headache ( = 2), confusion ( = 2), and nausea ( = 2), with ring-enhancing ( = 5), typically solitary ( = 3) and supratentorial ( = 3) lesions on imaging. Diagnosis involved robot-assisted stereotactic brain biopsy ( = 4) or craniotomy ( = 1), all showing Epstein-Barr virus and CD20 positivity. Most cases ( = 4) were monomorphic diffuse large B-cell lymphoma. Treatment included rituximab ( = 3), surgical resection ( = 2), zanubrutinib ( = 1), whole-brain radiation ( = 1), and methotrexate ( = 1). At the last follow-up, the median duration of follow-up for all patients was 19 months. During this time, 3 patients had died and 2 patients were still alive.
CONCLUSION
In patients with a history of kidney transplantation or allogeneic HSCT who are on long-term immunosuppressive therapy, any neurological symptoms, particularly the presence of supratentorial ring-enhancing masses in the brain on imaging, whether solitary or multiple, should raise high suspicion for this disease, warranting a timely brain biopsy. Additionally, we found that besides reducing immunosuppressants, zanubrutinib may be a potential, safe, and effective treatment for this condition. Moreover, post-surgical administration of rituximab in conjunction with whole-brain radiotherapy also appears to be a potentially safe and effective approach.
PubMed: 38813246
DOI: 10.3389/fneur.2024.1392691 -
Radiation Oncology (London, England) May 2024Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence....
BACKGROUND
Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC.
METHODS
Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5.
RESULTS
Fifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8-26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50-83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5-52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2-27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3-6.7 mos). Grade 1-2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted.
CONCLUSIONS
This is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated.
TRIAL REGISTRATION
Jefferson IRB#20976, approved 2/17/21.
Topics: Humans; Male; Pancreatic Neoplasms; Female; Aged; Radiosurgery; Middle Aged; Adenocarcinoma; Neoplasm Recurrence, Local; Aged, 80 and over; Magnetic Resonance Imaging; Radiotherapy, Image-Guided; Survival Rate; Prospective Studies; Retrospective Studies
PubMed: 38812040
DOI: 10.1186/s13014-024-02457-y -
Journal of Cancer Research and Clinical... May 2024The study aims to investigate whether including the inflammation-related parameters would enhance the accuracy of a nomogram for local control (LC) prediction in lung...
Incorporating the inflammation-related parameters enhances the performance of the nomogram for predicting local control in lung cancer patients treated with stereotactic body radiation therapy.
PURPOSE
The study aims to investigate whether including the inflammation-related parameters would enhance the accuracy of a nomogram for local control (LC) prediction in lung cancer patients undergoing stereotactic body radiation therapy (SBRT).
METHODS
158 primary or metastatic lung cancer patients treated with SBRT were retrospectively analyzed. The clinical, dosimetric and inflammation-related parameters were collected for the Cox regression analysis. The ACPB model was constructed by employing the clinical and dosimetric factors. And the ACPBLN model was established by adding the inflammation-related factors to the ACPB model. The two models were compared in terms of ROC, Akaike Information Criterion (AIC), C-index, time-dependent AUC, continuous net reclassification index (NRI), integrated discrimination improvement (IDI), calibration plots and decision curve analysis (DCA).
RESULTS
Multivariate Cox regression analysis revealed that six prognostic factors were independently associated with LC, including age, clinical stage, planning target volume (PTV) volume, BED of the prescribed dose (BEDPD), the lymphocyte count and neutrocyte count. The ACPBLN model performed better in AIC, bootstrap-corrected C-index, time-dependent AUC, NRI and IDI than the ACPB model. The calibration plots showed good consistency between the probabilities and observed values in the two models. The DCA curves showed that the ACPBLN nomogram had higher overall net benefit than the ACPB model across a majority of threshold probabilities.
CONCLUSION
The inflammation-related parameters were associated with LC for lung cancer patients treated with SBRT. The inclusion of the inflammation-related parameters improved the predictive performance of the nomogram for LC prediction.
Topics: Humans; Nomograms; Radiosurgery; Lung Neoplasms; Female; Male; Aged; Retrospective Studies; Middle Aged; Inflammation; Aged, 80 and over; Prognosis; Adult
PubMed: 38811379
DOI: 10.1007/s00432-024-05811-5 -
Neurosurgical Review May 2024
Letter to editor: short-term predictors of stereotactic radiosurgery outcome for untreated single non-small cell lung cancer brain metastases: a retrospective cohort study.
Topics: Humans; Radiosurgery; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Lung Neoplasms; Retrospective Studies; Treatment Outcome; Male; Female; Middle Aged; Cohort Studies; Aged
PubMed: 38805085
DOI: 10.1007/s10143-024-02483-0 -
SAGE Open Medical Case Reports 2024Birt-Hogg-Dubé syndrome, an extremely rare genetic disorder, is characterized by the development of fibrofolliculomas, lung cysts and subsequent recurrent pneumothorax,...
Birt-Hogg-Dubé syndrome, an extremely rare genetic disorder, is characterized by the development of fibrofolliculomas, lung cysts and subsequent recurrent pneumothorax, and kidney neoplasia. This report highlights the case of a 56-year-old female with a history of right vestibular schwannoma status post stereotactic radiotherapy and vulva bartholin's gland carcinoma who was initially evaluated by primary care for a 6-month history of intermittent, red, raised, widespread rash accompanied by fever, chills, and body aches. A punch biopsy of the rash was performed, which was notable for an urticarial tissue reaction with focal changes of leukocytoclasia and negative direct immunofluorescence. Laboratory tests, which included an autoimmune genetic and periodic fever panel, were unremarkable. Whole genome sequencing returned positive for a pathogenic variant in folliculin gene, consistent with a diagnosis of Birt-Hogg-Dubé syndrome.
PubMed: 38803360
DOI: 10.1177/2050313X241251759 -
Journal of Thoracic Oncology : Official... May 2024The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of...
INTRODUCTION
The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC.
METHODS
Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT.
RESULTS
The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively.
CONCLUSIONS
The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.
PubMed: 38788924
DOI: 10.1016/j.jtho.2024.05.366 -
American Society of Clinical Oncology... Jun 2024Clinical investigation of immune checkpoint inhibitors (ICIs) has expanded from indications in metastatic non-small cell lung cancer (NSCLC) to add to the treatment of... (Review)
Review
Clinical investigation of immune checkpoint inhibitors (ICIs) has expanded from indications in metastatic non-small cell lung cancer (NSCLC) to add to the treatment of early-stage or resectable NSCLC. Although completed randomized trials supported the approvals of some ICIs as perioperative therapies (ie, adjuvant, neoadjuvant, or neoadjuvant followed by adjuvant), ongoing trials are evaluating other anti-PD-(L)1 antibodies for similar indications, or in combination with stereotactic body radiotherapy (SBRT). The incorporation of immunotherapy brings potential to improve outcomes of patients with resectable NSCLC, but these advances have also increased the complexity of the treatment landscape and created important knowledge gaps. This article reviews the current standards for local therapies in NSCLC, describes the clinical trials exploring the combination of ICIs to SBRT, and explains the recent approvals of ICIs as perioperative therapies. A discussion follows to highlight three important areas of uncertainty: (1) the contribution of ICIs given in each treatment phase (neoadjuvant and adjuvant) to the overall effect of neoadjuvant chemoimmunotherapy followed by adjuvant ICIs; (2) the selection of regimens to serve as comparators in future randomized trials of perioperative therapies; and (3) the role of pathologic complete response as an intermediate end point and aid for selection of patients for adjuvant therapy. Moving forward, stakeholders will need to engage in concerted research efforts to address the relevant clinical questions regarding the optimal management of resectable NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immunotherapy; Immune Checkpoint Inhibitors; Combined Modality Therapy; Neoadjuvant Therapy; Treatment Outcome
PubMed: 38788177
DOI: 10.1200/EDBK_432500 -
International Journal of Oncology Jul 2024The prognosis for patients with non‑small cell lung cancer (NSCLC), a cancer type which represents 85% of all lung cancers, is poor with a 5‑year survival rate of... (Review)
Review
The prognosis for patients with non‑small cell lung cancer (NSCLC), a cancer type which represents 85% of all lung cancers, is poor with a 5‑year survival rate of 19%, mainly because NSCLC is diagnosed at an advanced and metastatic stage. Despite recent therapeutic advancements, ~50% of patients with NSCLC will develop brain metastases (BMs). Either surgical BM treatment alone for symptomatic patients and patients with single cerebral metastases, or in combination with stereotactic radiotherapy (RT) for patients who are not suitable for surgery or presenting with fewer than four cerebral lesions with a diameter range of 5‑30 mm, or whole‑brain RT for numerous or large BMs can be administered. However, radioresistance (RR) invariably prevents the action of RT. Several mechanisms of RR have been described including hypoxia, cellular stress, presence of cancer stem cells, dysregulation of apoptosis and/or autophagy, dysregulation of the cell cycle, changes in cellular metabolism, epithelial‑to‑mesenchymal transition, overexpression of programmed cell death‑ligand 1 and activation several signaling pathways; however, the role of the Hippo signaling pathway in RR is unclear. Dysregulation of the Hippo pathway in NSCLC confers metastatic properties, and inhibitors targeting this pathway are currently in development. It is therefore essential to evaluate the effect of inhibiting the Hippo pathway, particularly the effector yes‑associated protein‑1, on cerebral metastases originating from lung cancer.
Topics: Humans; Brain Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Radiation Tolerance; Hippo Signaling Pathway; Protein Serine-Threonine Kinases; Signal Transduction; Radiosurgery; Epithelial-Mesenchymal Transition; Molecular Targeted Therapy
PubMed: 38785155
DOI: 10.3892/ijo.2024.5656