Lobar versus sublobar resection for atypical lung carcinoid: An analysis from the National Cancer Database.

BACKGROUND: There is a knowledge gap regarding lobar versus sublobar resection for atypical carcinoid (AC) of the lung. As such, the authors sought to understand and analyze the outcomes of sublobar resection versus lobectomy in this patient population. METHODS: A retrospective analysis using the National Cancer Database was performed to compare overall survival (OS) between patients treated with lobectomy and patients treated with sublobar resection for AC of the lung between the years 2004 and 2016. Patient characteristics were compared with χ2 tests. The Kaplan-Meier method was used to estimate OS distributions, and the log-rank test was used to compare distributions by treatment strategy. A multivariable Cox regression model was used to assess associations between the treatment strategy and OS. A propensity score matching method was also implemented to further eliminate treatment selection bias in the study sample. RESULTS: The database identified 669 patients with T1-T4 and N0-N3 lung ACs that were surgically resected. Unadjusted Kaplan-Meier survival curves did not demonstrate an OS difference between lobectomy and sublobar resection (p = .094). After propensity score matching, curves demonstrated a numerical improvement in OS with lobectomy; however, it was not statistically significant (p = .5). In a subgroup analysis, lobectomy and node-negative disease were associated with the best OS, whereas sublobar resection and node-positive disease were associated with the worst OS (p < .0001). Nodal involvement was associated with worse survival, regardless of surgical treatment (p < .0001). CONCLUSIONS: In patients with T1-T4 and N0-N3 ACs of the lung, lobectomy was not associated with an improvement in OS in comparison with sublobar resection.

NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

Impact of a mobile application (reminder app) on acute toxicity during radiotherapy of head-and-neck cancer - results of a randomized phase III trial (RAREST-02).

BACKGROUND: Radiotherapy of head-and-neck cancer (SCCHN) is often associated with acute toxicity. In a previous trial, daily reminders by staff members to perform skin care resulted in less dermatitis. This randomized trial investigated whether a mobile application can replace these reminders. METHODS: Patients were stratified according to tumor site, treatment and center. Fifty-three patients were eligible for per-protocol-set (25 with, 28 without app). Primary endpoint was grade ≥ 2 dermatitis until 60 Gy. Secondary endpoints included dermatitis grade ≥ 2 until end of radiotherapy (EOT), dermatitis grade ≥ 3, and mucositis grade ≥ 2 and ≥ 3. RESULTS: After an interim analysis, the study was terminated (delayed and slow accrual). Until 60 Gy, grade ≥ 2 dermatitis rates were 72% with vs. 82% without app (p = 0.38), grade ≥ 3 dermatitis rates 20% vs. 11% (p = 0.45). Until EOT, grade ≥ 2 and ≥ 3 dermatitis rates were 72% vs. 86% (p = 0.22) and 24% vs. 18% (p = 0.58). Until 60 Gy, grade ≥ 2 and ≥ 3 mucositis rates were 76% vs. 82% (p = 0.58) and 20% vs. 36% (p = 0.20). Until EOT, corresponding mucositis rates were 76% vs. 82% (p = 0.58) and 28% vs. 43% (p = 0.26). CONCLUSION: Given the limitations of this trial, the reminder app led to non-significant reduction of grade ≥ 2 dermatitis, grade ≥ 2 mucositis and ≥ 3 mucositis. Additional studies are required to define the value of reminder apps during radiotherapy for SCCHN.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

A prospective interventional study evaluating seizure activity during a radiotherapy course for high-grade gliomas (SURF-ROGG).

BACKGROUND: Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may improve patient monitoring and anti-epileptic treatment. This study evaluates seizure activity during radiotherapy for high-grade gliomas. METHODS: The primary objective this prospective interventional study is the evaluation of seizure activity during a course of radiotherapy for high-grade gliomas. Progression of seizure activity is defined as increased frequency of seizures by > 50%, increased severity of seizures, or initiation/increase by ≥25% of anti-epileptic medication. Seizure frequency up to 6 weeks following radiotherapy and electroencephalography activity typical for epilepsy will also be evaluated. Patients keep a seizure diary during and up to 6 weeks following radiotherapy. Every day, they will document number (and type) of seizures and anti-epileptic medication. Once a week, the findings of the diary are checked and discussed with a neurologist to initiate or adjust anti-epileptic medication, if necessary. Patients complete a questionnaire regarding their satisfaction with the seizure diary. If the dissatisfaction rate is > 40%, the seizure diary will be considered not suitable for the investigated indication. Thirty-five patients (32 patients plus drop-outs) should be enrolled. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with progression of seizure activity is 30% (rate under the alternative hypothesis), assuming a 'natural' background progression-rate of 10% without radiotherapy (null hypothesis). DISCUSSION: If an increase in seizure activity during a course of radiotherapy for high-grade glioma occurs, the findings of this study may pave the way for a larger prospective trial and will likely lead to closer patient monitoring and better anti-epileptic treatment. TRIAL REGISTRATION: clinicaltrials.gov ( NCT04552756 ); registered on 16th of September, 2020.

Role of Prophylactic Cranial Irradiation in Extensive-Stage Small Cell Lung Cancer.

Patients with small cell lung cancer (SCLC) are at significant risk of developing brain metastases during their disease course. Prophylactic cranial irradiation (PCI) has been incorporated into SCLC treatment guidelines to diminish the risk of developing brain metastases. In 2007, a randomized trial suggested that PCI decreases the incidence of brain metastases and prolongs overall survival (OS) in patients with extensive-stage SCLC (ES-SCLC) who have responded to initial therapy. However, this study did not include modern central nervous system imaging with CT or MRI prior to randomization. A more recent Japanese trial with MRI staging and surveillance demonstrated that PCI diminished the incidence of brain metastases but did not improve survival. This review examines the largest clinical studies, controversies, and future directions of PCI in patients with ES-SCLC.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2).

PURPOSE: To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. METHODS: This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2­year overall survival (OS). Arm A was considered insufficiently active if 2­year OS was ≤40% (null hypothesis = H0), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H0 was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable. RESULTS: Two-year OS was 71% in arm A (95% CI: 55-87%) vs. 53% in arm B (95% CI: 36-71%); H0 was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30-1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25-1.04) for progression, 0.43 (0.13-1.40) for locoregional failure, and 0.43 (0.17-1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044). CONCLUSION: Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.

Beam angle comparison for distal esophageal carcinoma patients treated with intensity-modulated proton therapy.

PURPOSE: To compare the dosimetric performances of intensity-modulated proton therapy (IMPT) plans generated with two different beam angle configurations (the Right-Left oblique posterior beams and the Superior-Inferior oblique posterior beams) for the treatment of distal esophageal carcinoma in the presence of uncertainties and interplay effect. METHODS AND MATERIALS: Twenty patients' IMPT plans were retrospectively selected, with 10 patients treated with the R-L oblique posterior beams (Group R-L) and the other 10 patients treated with the S-I oblique posterior beams (Group S-I). Patients in both groups were matched by their clinical target volumes (CTVs-high and low dose levels) and respiratory motion amplitudes. Dose-volume-histogram (DVH) indices were used to assess plan quality. DVH bandwidth was calculated to evaluate plan robustness. Interplay effect was quantified using four-dimensional (4D) dynamic dose calculation with random respiratory starting phase of each fraction. Normal tissue complication probability (NTCP) for heart, liver, and lung was calculated, respectively, to estimate the clinical outcomes. Wilcoxon signed-rank test was used for statistical comparison between the two groups. RESULTS: Compared with plans in Group R-L, plans in Group S-I resulted in significantly lower liver Dmean and lung V30Gy[RBE] with slightly higher but clinically acceptable spinal cord Dmax . Similar plan robustness was observed between the two groups. When interplay effect was considered, plans in Group S-I performed statistically better for heart Dmean and V30Gy[RBE] , lung Dmean and V5Gy[RBE] , and liver Dmean , with slightly increased but clinically acceptable spinal cord Dmax . NTCP for liver was significantly better in Group S-I. CONCLUSIONS: IMPT plans in Group S-I have better sparing of liver, heart, and lungs at the slight cost of spinal cord maximum dose protection, and are more interplay-effect resilient compared to IMPT plans in Group R-L. Our study supports the routine use of the S-I oblique posterior beams for the treatments of distal esophageal carcinoma.

A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited-stage small cell lung cancer in elderly patients versus younger patients.

BACKGROUND: Platinum and etoposide with thoracic radiation followed by prophylactic cranial irradiation constitute the standard treatment for limited-stage small cell lung cancer (LS-SCLC). Many patients with LS-SCLC are elderly with comorbidities. METHODS: Individual patient data were collected from 11 phase 2 or 3 trials for LS-SCLC conducted by the National Clinical Trials Network and activated from 1990 to 2010. The primary endpoint was overall survival (OS); the secondary endpoints were progression-free survival (PFS), the rate of severe adverse events, and off-treatment reasons. The outcomes were compared for patients 70 years old or older (elderly patients) and patients younger than 70 years (younger patients). RESULTS: Individual patient data from 1049 younger patients (81%) and 254 elderly patients (19%) were analyzed. In the multivariate model, elderly patients, in comparison with younger patients, had worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.18-1.63; median OS for elderly patients, 17.8 months; OS for younger patients, 23.5 months) and worse PFS (HR, 1.19; 95% CI, 1.03-1.39; median PFS for elderly patients, 10.6 months; median PFS for younger patients, 12.3 months). Elderly patients, in comparison with younger patients, experienced more grade 5 adverse events (8% vs 3%; P < .01) and more grade 3 or higher dyspnea (11% vs 7%; P = .03) but less grade 3 or higher esophagitis/dysphagia (14% vs 19%; P = .04) and less grade 3 or higher vomiting (11% vs 17%; P = .01). Elderly patients completed treatment less often, discontinued treatment because of adverse events and patient refusal more frequently, and died during treatment more frequently. CONCLUSIONS: Elderly patients with LS-SCLC have worse PFS and OS and more difficulty in tolerating therapy. Future trials should incorporate assessments of elderly patients, novel monitoring of adverse events, and more tolerable radiation and systemic therapies.

Prognostic factors and a new scoring system for survival of patients irradiated for bone metastases.

BACKGROUND: Personalized therapy for bone metastases should consider the patients' remaining lifespan. Estimation of survival can be facilitated with scoring tools. A new tool was developed, specifically designed to estimate 12-month survival. METHODS: In 445 patients irradiated for bone metastases, radiotherapy regimen plus 13 factors (age, gender, Karnofsky performance score (KPS), primary tumor type, interval between cancer diagnosis and RT of bone metastases, visceral metastases, other (non-irradiated) bone metastases, sites of bone metastases, number of irradiated sites, pathological fracture, fractionation of RT, pre-RT surgery, pre-RT administration of bisphosphonates/denosumab, pre-RT systemic anticancer treatment) were retrospectively analyzed for survival. Factors achieving significance (p < 0.05) or borderline significance (p < 0.055) on multivariate analysis were used for the scoring system. Twelve-month survival rates were divided by 10 (factor scores); factor scores were summed for each patient (patient scores). RESULTS: On multivariate analysis, survival was significantly associated with KPS (hazard ratio (HR) 1.91, p < 0.001) and primary tumor type (HR 1.12, p < 0.001); age achieved borderline significance (HR 1.14, p = 0.054). These factors were used for the scoring tool. Patient scores ranged from 8 to 17 points. Three groups were designated: 8-9 (A), 10-14 (B) and 15-17 (C) points. Twelve-month survival rates were 9, 38 and 72% (p < 0.001); median survival times were 3, 8 and 24 months. CONCLUSIONS: This new tool developed for patients irradiated for bone metastases at any site without spinal cord compression allows one to predict the survival of these patients and can aid physicians when assigning the treatment to individual patients.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1.2020.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."

A New Diagnosis-Specific Survival Score for Patients to be Irradiated for Brain Metastases from Non-small Cell Lung Cancer.

INTRODUCTION: Personalized treatment helps one achieve optimal outcomes in patients with non-small cell lung cancer (NSCLC). Understanding patients' survival prognoses in a palliative situation like intracerebral metastases is critical. A new survival score, the WBRT-30-NSCLC, was developed for patients with intracerebral metastases from NSCLC. METHODS: Eight factors were investigated in 157 patients receiving 10 × 3 Gy of whole-brain radiotherapy (WBRT) including age, gender, Karnofsky performance score (KPS), interval from diagnosis of NSCLC to WBRT, pre-WBRT systemic treatment, primary tumor control, number of intracerebral metastases, and metastasis outside the brain. Factors significant (p < 0.05) or showing a trend (p < 0.08) on multivariate analysis were used for the WBRT-30-NSCLC. Patient scores were derived by adding factor scores (6-month survival rates divided by 10). WBRT-30-NSCLC was compared to other scores for intracerebral metastases from NSCLC. RESULTS: On multivariate analysis, age (p = 0.005), KPS (p < 0.001), systemic treatment (p = 0.018), and metastasis outside the brain (p < 0.001) were significant; number of intracerebral metastases (p = 0.075) showed a trend. Four groups were designed (912, 1317, 1820, and 22 points) with 6-month survival rates of 3, 26, 65, and 100%. Positive predictive value (PPV) to predict death ≤ 6 months after WBRT was 97% (updated DS-GPA classification 86%, Rades-NSCLC 88%), and PPV to predict survival ≥ 6 months was 100% (updated DS-GPA 78%, Rades-NSCLC 74%). CONCLUSIONS: The WBRT-30-NSCLC appeared very precise in identifying patients with intracerebral metastases from NSCLC dying ≤ 6 months or surviving ≥ 6 months. It appeared more precise than previous scores and can support physicians developing personalized treatment regimens.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

Small-spot intensity-modulated proton therapy and volumetric-modulated arc therapies for patients with locally advanced non-small-cell lung cancer: A dosimetric comparative study.

PURPOSE: To compare dosimetric performance of volumetric-modulated arc therapy (VMAT) and small-spot intensity-modulated proton therapy for stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A total of 24 NSCLC patients were retrospectively reviewed; 12 patients received intensity-modulated proton therapy (IMPT) and the remaining 12 received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTV) on averaged 4D-CTs. The dose-volume-histograms (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases of each field per fraction. DVH indices were compared using Wilcoxon rank sum test. RESULTS: Compared with VMAT, IMPT delivered significantly lower cord Dmax , heart Dmean , and lung V5 Gy[ RBE ] with comparable CTV dose homogeneity, and protection of other OARs. In terms of plan robustness, the IMPT plans were statistically better than VMAT plans in heart Dmean , but were statistically worse in CTV dose coverage, cord Dmax , lung Dmean , and V5 Gy[ RBE ] . Other DVH indices were comparable. The IMPT plans still met the standard clinical requirements with interplay effects considered. CONCLUSIONS: Small-spot IMPT improves cord, heart, and lung sparing compared to VMAT and achieves clinically acceptable plan robustness at least for the patients included in this study with motion amplitude less than 11 mm. Our study supports the usage of IMPT to treat some lung cancer patients.

A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases.

BACKGROUND: This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases. METHODS: One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS). RESULTS: On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p < 0.001), nature of tumor (p < 0.001) and period from cancer detection to irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001). CONCLUSION: In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

A New Scoring Tool to Assess Overall Survival in Patients With Intracerebral Metastases From Gynecological Cancers.

OBJECTIVE: This study aimed to facilitate individualized treatment strategies for intracerebral metastases from gynecological cancers by creating a specific overall survival (OS) score. METHODS/MATERIALS: Fifty-six patients irradiated for cerebral metastases from gynecological cancers were included. Eleven factors were retrospectively analyzed for OS: age, Eastern Cooperative Oncology Group (ECOG) performance score, cancer type, histology, histologic grading, initial stage, number of lesions, extracerebral metastases, time between cancer diagnosis and brain metastases treatment, recursive partitioning analysis class, and type of treatment. Independent predictors of OS were incorporated in the score (better OS, 1 point; worse OS, 0 points). RESULTS: On Cox proportional hazards analysis, performance score (hazards ratio, 1.98; 95% confidence interval, 1.30-3.23; P = 0.001), no extracerebral metastases (3.34; 1.46-8.96; P = 0.003), and recursive partitioning analysis class 1 (3.27; 1.97-5.65; P < 0.001) were significant. The following points were assigned: ECOG score 1 to 2 = 1 point, ECOG score 3 to 4 = 0 points, no extracerebral metastases = 1 point, extracerebral metastases = 0 points. Sum scores were 0 (n = 32), 1 (n = 15), or 2 points (n = 9). Six-month OS rates were 6%, 67%, and 100%, respectively (P < 0.001). CONCLUSIONS: A predictive tool including 3 groups with significantly different OS probabilities was designed for patients with cerebral metastases from gynecological cancers. This tool will aid in choosing individual treatments.

Neutrophil-to-Lymphocyte Ratio Predicts Outcome in Limited Disease Small-cell Lung Cancer.

INTRODUCTION: Patients with limited disease small-cell lung cancer (SCLC) receive radiochemotherapy followed by prophylactic cranial irradiation. The prognosis of these patients remains poor with a median survival of 16-24 months. Systemic inflammation was suggested as an important prognostic factor for outcomes. This study investigated the impact of systemic inflammation measured with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at first diagnosis in patients with limited disease SCLC for outcomes. METHODS: Data of 65 patients receiving radiochemotherapy for limited disease SCLC were analyzed. NLR and PLR were obtained from blood sample at first diagnosis of SCLC and 12 characteristics including gender, age, ECOG, T-category, N-category, pack years, smoking during radiotherapy, respiratory insufficiency, hemoglobin levels during radiotherapy, radiation dose (<56 vs. ≥56 Gy), concurrent radiochemotherapy, and prophylactic cranial irradiation (PCI) were evaluated for local control, metastasis-free survival, and overall survival. RESULTS: Survival rates at 1, 2, and 3 years were 71, 45, and 28%, respectively. Median survival time was 20 months. Independent factors for improved survival were NLR < 4 (p = 0.03), ECOG 0-1 (p = 0.002), and PCI (p = 0.015). Lower T-category was an independent positive factor of local control (p = 0.035). Improved metastasis-free survival was associated with NLR < 4 (p = 0.011), ECOG 0-1 (p = 0.002), N-category 0-1 (p = 0.048), non-smoking during radiotherapy (p = 0.009), and PCI (p = 0.006). CONCLUSION: NLR was found to be an independent prognostic factor for overall survival. The evaluation of NLR can help identify patients with poor prognosis and appears a useful prognostic marker in clinical practice. A prospective analysis is warranted to confirm these findings.