Upfront Treatment Research Articles

Evaluation of Anti-Angiogenic Therapy Combined with Immunotherapy and Chemotherapy as a Strategy to Treat Locally Advanced and Metastatic Non-Small-Cell Lung Cancer

Immunotherapy has made recent improvements in disease-free survival (DFS) and/or overall survival (OS) in all stages of non-small-cell lung cancer (NSCLC). Here, we review the tumor microenvironment and its immunosuppressive effects and discuss how anti-angiogenic therapies may potentiate the anti-carcinogenic effects of immunotherapy. We also review all the past literature and discuss strategies of combining anti-angiogenic therapy and immunotherapy +/− chemotherapy and hypothesize how we can use this strategy for non-small-cell lung cancer in metastatic previously untreated/previously treated settings in previously treated EGFR-mutated NSCLC for the upfront treatment of brain metastases prior to radiation therapy and for the incorporation of this strategy into stage III unresectable disease. We assert the use of anti-angiogenic therapy and immunotherapy when combined appropriately with chemotherapy and radiotherapy has the potential to increase the long-term survivals in both the stage III and metastatic setting so that we can now consider more patients to experience curative treatment.

Stent thrombosis in the setting of ST-segment elevation acute myocardial infarction in the contemporary practice: results from the TOTAL randomized trial.

The aim was to know the risk and predictive factors of stent thrombosis (ST) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) in the contemporary practice. The TOTAL [ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone] randomized trial, being the largest trial performed in the setting of STEMI with a general application of the recent recommendations, represents a unique opportunity to know the current real-world incidence of ST as well as its associated factors. A total of 10 064 patients that received ≥1 coronary stent in the TOTAL trial comprise the study population. The risk, predictive factors, and clinical implications of ST was studied. During 1-year follow-up, 155 patients (1.54%) suffered definitive or probable ST (59 acute, 67 subacute, and 29 late). Previous infarction, the number of stents, the previous use of clopidogrel, and the use of diuretics at discharge were independent predictors for ST, whereas the use of upfront glycoprotein IIb/IIIa inhibitors, radial access, and treatment with statins at discharge were independent protective factors. The number of stents, stent diameter, upfront treatment with IIb/IIIa inhibitors, previous treatment with clopidogrel, and treatment with statins at discharge were independently associated with the risk of early ST. Only previous infarction was associated with the risk of late ST. In the contemporary practice, ST still constitutes a frequent complication of primary PCI for STEMI, occurring in 1.5% of patients. Independent predictors are different depending on the time of ST.

Efficacy and safety of first-line high-dose cytarabine in patients with primary CNS lymphoma ineligible for high-dose methotrexate: a case series

Abstract Introduction Despite recent significant advances, the treatment of elderly patients with primary central nervous system lymphoma (PCNSL) is still challenging due to comorbidities, poor baseline performance status (PS), and drug toxicities. There are proposals to use high-dose cytarabine (HD-araC) in these patients. Results Our retrospective study aimed to assess the efficacy and toxicity of HD-araC as an upfront treatment for patients with PCNSL who are ineligible for high-dose methotrexate (HD-MTX). Methods We identified 12 consecutive patients with newly diagnosed PCNSL (out of a total of 68) who received first-line treatment with HD-araC, with or without rituximab (R). Most of them had poor PS and relevant comorbidities. Six patients received this treatment upfront, while the other six received it after discontinuing HD-MTX-(based) therapy. Treatment with HD-araC resulted in poor outcome, limited response, and severe hematological and infectious complications. Patients who had previously received at least one cycle of HD-MTX appeared to have slightly better outcomes, highlighting the importance of HD-MTX in the treatment of PCNSL. Conclusion Our case series showed limited efficacy and substantial toxicity of (R)-HD-araC in patients with PCNSL ineligible for HD-MTX. This treatment should be omitted in elderly/frail patients to avoid further compromising their quality of life.

Institution-level Patterns of Care for Early-stage Oropharynx Cancers in the United States.

The adoption of transoral robotic surgery and shifting epidemiology in oropharyngeal squamous cell cancer have stimulated debate over upfront and adjuvant treatment. Institutional variation in practice patterns can be obscured in patient-level analyses. We aimed to characterize institutional patterns of care as well as identify potential associations between patterns of care and survival. This was a retrospective cohort study of patients identified from 2004-2015 in the National Cancer Database. We analyzed 42,803 cases of oropharyngeal squamous cell cancer Stage cT1-2N0-2bM0 (AJCC 7th edition) treated with curative intent surgery and/or radiotherapy. We defined facility-4-year periods to account for changing institutional practice patterns. The 42,803 patients were treated within 2578 facility-4-year periods. We assessed institutional practice patterns, including the ratio of upfront surgery to definitive radiotherapy, case volumes, use of adjuvant therapies (radiotherapy or chemoradiotherapy), and margin positivity rates. Survival associations with institutional practice patterns were estimated with Cox regression. The ratio of upfront surgery to definitive radiotherapy ranged from 80-to-1 to 1-to-23. The institution-level median rate of adjuvant radiotherapy was 69% (IQR 50%-100%), adjuvant chemoradiotherapy was 44% (IQR 0%-67%), and margin-positive resection was 33% (IQR 0%-50%). On patient-level MVA, worse overall survival was not significantly associated with institutional case volume, adjuvant radiotherapy, or adjuvant chemoradiotherapy utilization. High rates of multimodal therapy and positive margins underscore the importance of multidisciplinary care and highlight variable patterns of care across institutions. Further work is warranted to explore indicators of high-quality care and to optimize adjuvant therapy in the HPV era.

Up-Front Treatment of Elderly (Age ≥75 Years) and Frail Patients With Multiple Myeloma.

Older patients with multiple myeloma (MM) exhibit wide heterogeneity in their baseline physiologic and functional status, which demands an individualized treatment approach based on biological rather than chronological age. Various frailty scores have been developed for older patients with MM, but they are underutilized in clinical trials and in practice. Older patients with MM are underrepresented in therapeutic clinical trials, and treatment recommendations are currently derived from clinical trials of transplant-ineligible patients. This article provides a summary of phase II and III clinical trials in transplant-ineligible patients with newly diagnosed MM, highlighting outcomes in patients aged ≥75 years and frailty-based outcomes. The data available thus far show that triplet regimens are more efficacious than doublets in older patients but may be associated with higher toxicity. DRd (daratumumab/lenalidomide/dexamethasone) and VRd (bortezomib/lenalidomide/dexamethasone) are good options in patients who are nonfrail, whereas dose-adjusted DRd and VRd-lite should be offered to frail patients. Frailty should be assessed regularly to guide treatment intensification and/or deescalation. It is important that frailty measures are incorporated in clinical trials evaluating novel treatments to inform how older and frail patients will benefit from these treatments.

Validation of the lung immune prognostic index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the impower 130, 131 and 150 trials

IntroductionLIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics. MethodsData from patients with wild-type EGFR/ALK aNSCLC included in IMpower150, IMpower131, and IMpower130 (international phase 3 multicenter studies) treated with 1st-line CT +/- atezolizumab and/or bevacizumab were retrospectively analysed. LIPI was calculated based on the neutrophil/(leucocytes-neutrophils) (dNLR) ratio and serum LDH: good (dNLR < 3 and LDH < ULN), intermediate (dNLR ≥ 3 or LDH ≥ ULN) and poor (dNLR ≥ 3 and LDH ≥ ULN). ResultsOut of 2540 patients, 48.6 % were LIPI good, 40.8 % intermediate and 10.6 % poor. LIPI was significantly associated with treatment outcomes (PFS, OS) in the overall cohort (p < 0.001) and in each treatment cohort (all p < 0.001). After adjustment for age, smoking status, number of metastatic sites, brain or liver involvement and performance status, LIPI remained an independent prognostic factor for PFS and OS. In the LIPI good group (n = 1235), longer PFS was observed in patients treated with CT + IT + AA (median [m] PFS 11.27 vs. < 7.6 months with other regimens, p < 0.001), with a trend for OS (mOS 26.1 vs 20.7 months, p = 0.08). No regimen demonstrated significant PFS benefit in the LIPI poor group compared to chemotherapy. LIPI-good + PD-L1 ≥ 50 % (n = 105)showed long responses (mPFS of 11.1 months,mOS not reached). ConclusionsLIPI was prognostic for PFS and OS in prospective trials in aNSCLC, regardless of the treatment regimen. LIPI poor patients derived no benefit from combination treatment. LIPI combined to PD-L1 may improve the upfront treatment selection.

Chemotherapy followed by interval cytoreductive surgery: The most prevalent approach in the upfront treatment of patients with advanced-stage epithelial ovarian cancer in the United States

Chemotherapy followed by interval cytoreductive surgery: The most prevalent approach in the upfront treatment of patients with advanced-stage epithelial ovarian cancer in the United States

Exploring treatment decision-making at diagnosis for children with advanced cancer in low- and middle-income countries

PurposeGlobal childhood cancer survival outcomes correlate with regional contextual factors, yet upfront treatment decision-making for children with advanced or poor prognosis cancer in low- and middle-income countries (LMICs) is not well understood. This study aimed to (1) characterize the landscape of contextual factors that shape physician decision-making at diagnosis for these children in LMICs and (2) describe physician rationales for if/when to offer treatment with non-curative intent, including how they define “poor prognosis” during treatment decision-making.MethodsAn international panel of pediatric oncologists practicing in LMICs participated in two focus groups structured for the collaborative generation of factors influencing treatment decision-making, including consideration of non-curative treatment pathways at diagnosis. Thematic analysis of qualitative data was conducted, followed by member checking.ResultsEleven pediatric oncologists participated, representing all global regions defined by the World Health Organization. Participants identified a broad range of factors influencing decision-making across multiple levels, including the individual, hospital, health system, community, and country levels. All participants agreed that treatment with non-curative intent could be offered at diagnosis in certain contexts, and diverse definitions for poor prognosis were described.ConclusionsUpfront treatment decision-making for children with advanced or poor prognosis cancer in LMICs is variable and challenging. Difficulties with decision-making in LMICs may be amplified by inconsistent definitions of poor prognosis and underrepresentation of the factors that influence treatment decision-making within existing decision-making frameworks or childhood cancer treatment guidelines. Future research should explore decision-making approaches, preferences, and challenges in depth from the perspectives of pediatric cancer patients, families, and multidisciplinary clinicians.

Neoadjuvant chemotherapy followed by definitive local treatment in locally advanced sinonasal squamous cell carcinoma.

Sinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC. Medical records of patients diagnosed of locally advanced (cT3-4b, N0-3) sinonasal SCC treated with a definitive aim between January 2005 and March 2023 were retrospectively reviewed. Patients were categorized into the following groups based on the initial treatment: NAC followed by surgery, NAC followed by concurrent chemoradiotherapy (CCRT), definitive CCRT, or upfront surgery. Initial treatment plan was decided by a multidisciplinary team. Primary endpoint was overall survival (OS) and objective response rate, and secondary endpoints were progression free survival (PFS), cumulative incidence of local and distant failures, and treatment-related toxicity. The treatment response was assessed according to the RECIST criteria. Total 126 patients were included, and the median follow-up period was 25.6 months. The objective response rate to NAC was 48.2%. The subsequent resection rate was 70%, 42.9%, and 16.7% for patients with stage T3, T4a, and T4b disease, respectively. Two-year progression-free survival did not differ significantly between the NAC followed by surgery and upfront surgery groups (53.6% vs. 60.6%, P = 0.615) or between the NAC followed by CCRT and definitive CCRT groups (26.7% vs. 37.4%, P = 0.506). NAC may be a valuable treatment option for patients with locally advanced sinonasal SCC, as it provides an opportunity for curative surgery and exhibits non-inferior oncological outcomes compared with upfront definitive local treatments.

Panobinostat Synergizes with Chemotherapeutic Agents and Improves Efficacy of Standard-of-Care Chemotherapy Combinations in Ewing Sarcoma Cells.

Background: The survival rate of patients with Ewing sarcoma (EWS) has seen very little improvement over the past several decades and remains dismal for those with recurrent or metastatic disease. HDAC2, ALK, JAK1, and CDK4 were identified as potential targets using RNA sequencing performed on EWS patient tumors with the bioinformatic analysis of gene expression. Methods/Results: The pan-HDAC inhibitor Panobinostat was cytotoxic to all the Ewing sarcoma cell lines tested. Mechanistically, Panobinostat decreases the expression of proteins involved in the cell cycle, including Cyclin D1 and phospho-Rb, and DNA damage repair, including CHK1. Further, Panobinostat induces a G1 cell cycle arrest. The combination of Panobinostat with Doxorubicin or Etoposide, both of which are used as standard of care in upfront treatment, leads to a synergistic effect in EWS cells. The combination of Panobinostat and Doxorubicin induces an accumulation of DNA damage, a decrease in the expression of DNA damage repair proteins CHK1 and CHK2, and an increase in caspase 3 cleavage. The addition of Panobinostat to standard-of-care chemotherapy combinations significantly reduces cell viability compared to that of chemotherapy alone. Conclusions: Overall, our data indicate that HDAC2 is overexpressed in many EWS tumor samples and HDAC inhibition is effective in targeting EWS cells, alone and in combination with standard-of-care chemotherapy agents. This work suggests that the addition of an HDAC inhibitor to upfront treatment may improve response.

5-hydroxymethylcytosine sequencing in plasma cell-free DNA identifies unique epigenomic features in prostate cancer patients resistant to androgen deprivation therapies.

Currently, no biomarkers are available to identify resistance to androgen-deprivation therapies (ADT) in men with hormone-naive prostate cancer. Since 5-hydroxymethylcytosines (5hmC) in gene body are associated with gene activation, in this study, we evaluated whether 5hmC signatures in cell-free DNA (cfDNA) predicts early resistance to ADT. We collected a total of 139 serial plasma samples from 55 prostate cancer patients receiving ADT at three time points including baseline (prior to initiating ADT, N=55), 3-month (after initiating ADT, N=55), and disease progression (N=15) within 24 months or 24-month if no progression was detected (N=14). To quantify 5hmC abundance across the genome, we used selective chemical labeling sequencing and mapped sequence reads to individual genes. Differential methylation analysis in baseline samples identified significant 5hmC difference in 1,642 of 23,433 genes between patients with and without progression (false discovery rate, FDR<0.1). Patients with disease progression showed significant 5hmC enrichments in multiple hallmark gene sets with androgen responses as top enriched gene set (FDR=1.19E-13). Interestingly, this enrichment was driven by a subgroup of patients featuring a significant 5hmC hypermethylation in the gene sets involving AR , FOXA1 and GRHL2 . To quantify overall activities of these gene sets, we developed a gene set activity scoring algorithm and observed significant association of high activity scores with poor progression-free survival (P<0.05). Longitudinal analysis showed that the high activity scores were significantly reduced after 3-months of initiating ADT (P<0.0001) but returned to higher levels when the disease was progressed (P<0.05). This study demonstrates that 5hmC-based activity scores from gene sets involved in AR , FOXA1 and GRHL2 may be used as biomarkers to determine early treatment resistance, monitor disease progression, and potentially identify patients who would benefit from upfront treatment intensification.

HIPEC as Up-Front Treatment in Locally Advanced Ovarian Cancer

Purpose: The main objective of the study is to evaluate the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of naïve ovarian cancer women undergoing complete or near-complete cytoreduction by assessing the overall survival, the disease-specific survival, and the disease-free survival. The secondary objective is the identification of prognostic indicators of survival and recurrence of these patients. Patients—Methods: Retrospective study of treatment in naïve women with locally advanced ovarian cancer treated with cytoreductive surgery (CRS) and HIPEC and compared with those who were treated with cytoreduction alone. Clinicopathologic variables were correlated to overall survival, disease-specific survival, and disease-free survival using Kaplan–Meier method, and the multivariate Cox proportional hazards regression models. Results: 5- and 10-year overall survival, disease-specific survival, and disease-free survival rates were significantly higher in patients treated with CRS and HIPEC. These patients were 67% less likely to die from any cause (adjusted hazard ratio, aHR = 0.33, p = 0.001), 75% less likely to die from cancer (aHR = 0.25, p = 0.003), and 46% less likely to develop recurrence (aHR = 0.54, p = 0.041) compared to patients treated with CRS alone. Moreover, the poor performance status (aHR = 2.96, p &lt; 0.001), the serous carcinomas (aHR = 0.14, p = 0.007), and the morbidity (aHR = 6.87, p &lt; 0.001) were identified as independent indicators of poor overall survival. The degree of differentiation (aHR = 8.64, p = 0.003) was identified as the independent indicator of disease-specific survival (aHR = 4.13, p = 0.002), while the extent of peritoneal carcinomatosis (aHR = 2.32, p &lt; 0.001) as the independent indicator of disease-free survival. Conclusions: Treatment in naïve patients with locally advanced ovarian cancer undergoing CRS plus HIPEC appears to have improved overall, disease-specific, and disease-free survival.

Polymyalgia rheumatica and giant cell arteritis: diagnosis and management.

There have been advances in the diagnosis and treatment of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). Themes in PMR and GCA include classification criteria, ultrasound imaging of temporal and axillary arteries replacing biopsies for diagnosis of GCA, faster diagnosis and treatment with rapid access clinics for suspected GCA, and expanding treatment options with the goal of rapid suppression of inflammation and sparing steroids. Treatment is aimed at suppressing inflammation quickly in both GCA and PMR. Randomized trials have demonstrated success in reducing glucocorticoids when adding advanced therapies such as interleukin 6 (IL6) inhibitors. Other treatments including Janus kinase (JAK) inhibitors (especially a phase 3 trial of upadacitinib at 15 mg daily and secukinumab (an IL17 inhibitor) are being tested. Some uncontrolled GCA protocols are limiting glucocorticoids to initial IV pulse therapy only or rapid tapering of oral glucocorticoids with upfront treatment with tocilizumab. There is uncertainty of who should have an advanced therapy and how long to use it for and what order to consider advanced therapies when treatment fails. In PMR, studies are performed when patients cannot taper glucocorticoids effectively, whereas in GCA, advanced therapies are started with disease onset or with recurrent GCA.

A cost-effectiveness analysis of stereotactic ablative radiotherapy versus conventionally fractionated radiotherapy in the management of stage 1 non-small-cell lung cancer: Results from the TROG 09.02 CHISEL study.

Stereotactic ablative radiotherapy (SABR) is a standard of care treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC). The CHISEL trial was a phase 3 randomised controlled trial that compared SABR to conventional radiation therapy (CRT). Using patient-level data, we compared the cost-effectiveness of SABR and CRT for early-stage NSCLC. Data on treatment exposure, outcomes (recurrence, survival) and quality of life (QoL; EORTC QLQ-C30) were sourced from the trial. Quality-adjusted life years (QALYs) were estimated for the trial period using Australian utility weights for the EORTC QLQ-C30-derived QLU-C10D. Costs related to simulation, planning, delivery, verification and post-treatment monitoring were estimated by applying Australian Medicare Benefits Schedule fees. The costs of post-progression therapy and grade ≥3 toxicity were estimated using trial data and relevant literature sources. Cost-effectiveness was investigated as the incremental cost per QALY gained for SABR compared to CRT. Complete QoL data were available for 21 patients: 14 in the SABR arm and 7 in the CRT arm. Mean QALYs discounted at 5% per annum were similar between arms: 12.68 months for SABR and 12.12 months for CRT. The mean costs of delivering SABR and CRT were $4763 and $6817, respectively. The costs of monitoring were similar in both arms, $4856 and $4853 for SABR and CRT. The mean costs of post-progression therapy were $24,572 for SABR and $42,801 for CRT. The mean costs of grade ≥3 toxicity were $809 in the SABR arm and $132 in the CRT arm. Therefore, the total mean cost for SABR over the period of interest was lower for SABR than CRT. Given lower mean costs and numerically higher QALYs for SABR compared with CRT, an incremental cost-effectiveness ratio was not calculated. Compared to CRT, SABR is a cost-effective treatment for early-stage NSCLC as the estimated upfront treatment cost and the cost of subsequent care are lower for SABR for comparable mean QALYs. Assessment of the lifetime QALYs and projections of cost estimation will provide a better indication of the long-term cost-effectiveness of SABR.

Rates and predictors of loss to follow-up for sporadic vestibular schwannomas undergoing imaging surveillance.

Imaging surveillance with serial MRI, or a "wait-and-scan" approach, is a management option for patients with small or medium-sized vestibular schwannomas (VSs). Prior publications have indicated no distinct quality of life advantage to upfront treatment compared with initial wait-and-scan management. However, imaging surveillance is dependent on patient adherence to follow-up. In this study, the authors aimed to identify rates and predictors of patient loss to follow-up during wait-and-scan management of sporadic VS. A single-center study was conducted including all patients from 2013 to 2018 who had undergone upfront imaging surveillance of sporadic VS. Patient data were retrospectively obtained from the electronic medical record. Outcomes of interest included loss to follow-up unrelated to death and inconsistent adherence to imaging surveillance recommendations. Logistic regression analyses were conducted to evaluate factors associated with loss to follow-up. Over a 6-year study period, 270 patients underwent initial imaging surveillance of a sporadic VS. The median tumor diameter was 8.6 mm (range 1-28.9 mm). At the time of censoring, 106 patients (39.3%) had received treatment, 157 (58.1%) had been advised to continue follow-up, and 7 (2.6%) had died of non-VS-related causes. In total, 73 patients (27.0%) were completely lost to follow-up prior to the first treatment or death. Additionally, 60 patients (22.2%) missed at least 1 MRI follow-up or imaging follow-up was delayed by more than 1 year. Multivariable logistic regression identified an out-of-state residence (OR 3.05, 95% CI 1.58-5.89, p = 0.0009) and a smaller tumor size (unit OR per 1-mm increase in size, OR 0.88, 95% CI 0.83-0.95, p = 0.0006) to be associated with loss to follow-up. Patients living ≥ 350 miles from the hospital or with tumors ≤ 3 mm at the time of initial clinic evaluation were most likely to be lost to follow-up. Only a smaller tumor size was associated with an increased risk of inconsistent imaging follow-up (unit OR per 1-mm increase in size, OR 0.92, 95% CI 0.87-0.98, p = 0.007). Patients undergoing imaging surveillance of VS are at risk for loss to follow-up and inconsistent imaging surveillance. Patients with smaller tumors or those living farther away from the treating institution are at highest risk for being lost to follow-up.

Kidney disease, diabetes, and diameter stenosis predict Rotablation bailout in modified balloon application for severely calcified coronary lesions.

Modified balloon (MB) treatment in severely calcified coronary artery lesions is an established technique. However, some lesions require Rotablation (RA) as bailout strategy. This study aimed to assess predictors of switch from MB to RA and its impact on procedural and midterm outcomes. Four hundred and eighty-three consecutive patients were included undergoing MB treatment (n = 204) with a scoring or cutting balloon, or upfront RA treatment (n = 279) serving as control cohort. Strategy switch from MB to RA was performed in 19 of 204 patients. Procedural success was defined as successful stent implantation and TIMI III flow. In the MB cohort, median age was 72 [63-78] years, 75.5% were male and 42.1% had acute coronary syndrome. Procedure success was achieved in 89.4% of the switch group versus 98.4% of the MB only group (p < 0.001) and in 96.4% of the RA cohort. In the switch group, periprocedural complications (31.6% vs. 8.1% vs. 11.8%, p = 0.007), radiation dose (149 [126-252] vs. 59 [30-97] vs. 102 [59-156] Gcm2; p < 0.001) and contrast volume (250 [190-250] vs. 190 [150-250] vs. 195 [190--250] mL; p < 0.001) were significantly higher. Diabetes (OR 3.8, 95%CI 1.1-13.9, p = 0.042), chronic kidney disease stage 4 or 5 (OR 19.0, 95%CI 3.3-108.6, p < 0.001) and pronounced calcification resulting in higher angiographic diameter stenosis (OR 1.13, 95%CI 1.1-1.2, p = 0.001) independently predicted strategy switch. Midterm results were not affected by strategy switch regarding 1-year target lesion revascularization rates (86% vs. 89% vs. 89%; log-rank p = 0.95). Primary RA strategy might be considered in patients with severely calcified coronary artery lesions with high angiographic diameter stenosis, diabetes or impaired renal function due to increased periprocedural complication rates, radiation dose, and contrast volume following strategy switch.

Survival prognostic factors in nonsmall cell lung cancer patients with simultaneous brain metastases and poor performance status at initial presentation

PurposeAlthough the treatment of nonsmall cell lung cancer (NSCLC) has rapidly progressed recently, there is little evidence of treatment for patients with symptomatic brain metastases (BM) and poor performance status (PS). However, in symptomatic BM patients, appropriate upfront intracranial treatment can often lead to rapid improvement in PS and effective systemic therapy. Thus, this study investigated the prognostic factors for the survival of poor PS NSCLC patients with synchronous BM. MethodsData of patients with BM and Karnofsky PS (KPS) ≤70 at the first diagnosis of NSCLC who were treated in our hospital between January 2017 and December 2021 were reviewed. Patient survival was compared among patients stratified by type of first-line regimen of systemic treatment. Correlations between patient characteristics and survival were examined. ResultsFifty patients receiving aggressive treatment were enrolled. The median survival times for tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and chemotherapy alone groups were 19 (95 % confidence interval [CI], 2.8–68.5), 19 (3.0–62.0), and 13 (1.2–24.8) months, respectively. Survival in the TKI and ICI groups was significantly longer than in the chemotherapy alone group (p = 0.046, TKI vs. chemo; p = 0.022, ICI vs. chemo; p = 0.023). Both sex and type of systemic treatment correlated to survival time on univariate analysis. Chemotherapy alone for systemic treatment [p = 0.034; hazard ratio (HR), 0.44 (0.20–0.94)] remained significant for predicting overall survival in the multivariate analysis. ConclusionEven in patients with poor PS and BM at the initial diagnosis of NSCLC, the ICI group had a survival time comparable to that of the TKI group when combined with tailor-made intracranial treatment. There is a subgroup in the patient population that was previously considered unsuitable for ICI, whose PS improves with individualized intracranial treatment, and who may benefit from immunotherapy.

Stereotactic radio-neurosurgery for jugular foramen schwannomas

BackgroundStereotactic radiosurgery (SRS) represents a minimally invasive and valuable alternative for jugular foramen schwannomas (JFS), both as upfront and/or adjuvant treatment (in hybrid approaches).MethodsWe conducted a retrospective review of our cases treated at the Lausanne University Hospital (CHUV) from June 2010 to October 2023. Eleven patients underwent SRS, among whom three had prior surgery, two in our center in the frame of a planned combined approach and one in another center. Two patients received "volume-staged" SRS. The mean age at SRS was 60 years (median 68; range 29–83). Cranial nerve (CN) symptoms were present in six patients, while five were asymptomatic. The mean tumor volume at SRS was 2.1 cc (median 1.2; range 0.068–7.3 cc), with a 12 Gy marginal dose prescribed in all cases.ResultsThe mean follow-up period was 3.9 years (median 2, range 1–7). Cranial nerve function improved after SRS in six patients, while five remained stable. At the last follow-up, all tumors showed a decrease in volume, except for one patient, who underwent surgery at 18 months after SRS, for volumetric increase at 6 and 12 months, with further XII−th CN palsy and medulla oblongata compression. Although tumor decreased at 18 months, such patient needed microsurgical resection for symptom persistence and was further controlled. The mean tumor volume at 1 year post-SRS was 1.6 cc (median 0.55; range 0.028–7.77 cc), at 2 years was 1.31 cc (median 0.76; range 0.19–5), and at 3 years was 1.32 cc (median 0.59; range 0.23–4.8). No adverse radiation events were observed.ConclusionsStereotactic radiosurgery is considered a safe and effective treatment for jugular foramen schwannomas, ensuring high rates of tumor control in all patients over the long term. The cranial nerve function improved after SRS in the 6 patients who had deficits and the other 5 patients who had no deficits remained asymptomatic. For larger tumors, combined/hybrid approaches can be a valuable alternative, to obtain tumor control and to preserve neurological function.

Bile Duct Injuries after Cholecystectomy: An Individual Patient Data Systematic Review.

Background: Post-cholecystectomy bile duct injuries (BDIs) represent a challenging complication, with negative impacts on clinical outcomes. Several surgical and endoscopic/interventional radiologist (IR) approaches have been proposed to manage these damages, though with high failure rates. This individual patient data (IPD) systematic review analyzes the potential risk factors for failure after treatment interventions for BDIs, both surgical and endoscopic/IR. Methods: An extensive literature search was conducted on MEDLINE and Scopus for relevant articles published in English on the management of BDIs after cholecystectomy, between 1 January 2010 and 31 December 2023. Our series of BDIs was included. BDIs were always categorized according to the Strasberg's classification. The composite primary endpoints evaluated were the failure of treatment interventions, defined as patient death or the requirement of any other procedure, whatever surgical and/or endoscopic/IR, after the primary treatment. Results: A total of 342 cases were retrieved from our literature analysis, including our series of 19 patients. Among these, three groups were identified: "upfront surgery", "upfront endoscopy and/or IR" and "no upfront treatment", consisting of 224, 109 and 9 patients, respectively. After eliminating the third group, treatment intervention failure was observed overall in 34.2% (114/333) of patients, of whom 80.7% (92/114) and 19.3% (22/114) in the "upfront surgery" and in the "upfront endoscopy/IR" groups, respectively. At multivariable analysis, injury type D and E, and repair in a non-specialized center represented independent predictors of treatment failure in both groups, whereas laparoscopic cholecystectomy (LC) converted to open and immediate attempt of surgical repair exclusively in the first group. Conclusions: Significant treatment failure rates are responsible for remarkable negative effects on immediate and longer-term clinical outcomes of post-cholecystectomy BDIs. Understanding the important risk factors for this outcome may better guide the most appropriate therapeutical approach and improve clinical decisions in case this serious complication occurs.

Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole

BackgroundThe monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials. MethodsBetween 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed. ResultsAmong 2891 HRpos patients, 384 (13.3 %) met the primary monarchE inclusion criteria. The majority (n = 261) qualified due to having ≥ 4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7 %) met the eligibility criteria, with 126 patients (13.7 %) being node-negative. Patients from monarchE with ≥ 4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria. ConclusionPatient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.