Prediction of lung malignancy progression and survival with machine learning based on pre-treatment FDG-PET/CT.

BACKGROUND: Pre-treatment FDG-PET/CT scans were analyzed with machine learning to predict progression of lung malignancies and overall survival (OS). METHODS: A retrospective review across three institutions identified patients with a pre-procedure FDG-PET/CT and an associated malignancy diagnosis. Lesions were manually and automatically segmented, and convolutional neural networks (CNNs) were trained using FDG-PET/CT inputs to predict malignancy progression. Performance was evaluated using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Image features were extracted from CNNs and by radiomics feature extraction, and random survival forests (RSF) were constructed to predict OS. Concordance index (C-index) and integrated brier score (IBS) were used to evaluate OS prediction. FINDINGS: 1168 nodules (n=965 patients) were identified. 792 nodules had progression and 376 were progression-free. The most common malignancies were adenocarcinoma (n=740) and squamous cell carcinoma (n=179). For progression risk, the PET+CT ensemble model with manual segmentation (accuracy=0.790, AUC=0.876) performed similarly to the CT only (accuracy=0.723, AUC=0.888) and better compared to the PET only (accuracy=0.664, AUC=0.669) models. For OS prediction with deep learning features, the PET+CT+clinical RSF ensemble model (C-index=0.737) performed similarly to the CT only (C-index=0.730) and better than the PET only (C-index=0.595), and clinical only (C-index=0.595) models. RSF models constructed with radiomics features had comparable performance to those with CNN features. INTERPRETATION: CNNs trained using pre-treatment FDG-PET/CT and extracted performed well in predicting lung malignancy progression and OS. OS prediction performance with CNN features was comparable to a radiomics approach. The prognostic models could inform treatment options and improve patient care. FUNDING: NIH NHLBI training grant (5T35HL094308-12, John Sollee).

Prognostic Factors in Clival Chordomas: An Integrated Analysis of 347 Patients.

OBJECTIVE: To investigate prognostic factors of clival chordoma using the largest patient set to date. METHODS: Appropriate studies were identified per search criteria, data satisfying criteria were extracted, and survival analysis was performed to investigate prognostic factors of clival chordoma. RESULTS: A total of 347 patients from the literature cohort met our inclusion criteria. Of 346 cases in which extent of resection was reported, gross total resection (GTR), subtotal resection, and biopsy were achieved in 118 (34.1%), 205 (59.2%), and 21 (6.1%) cases, respectively. Two (0.6%) subjects did not undergo surgery. Of 185 cases in which surgical approach was reported, 56 (30.3%) underwent an endoscopic transoral approach, 17 (9.2%) microscopic transsphenoidal, 45 (24.3%) endoscopic or microscopic, 45 (24.3%) craniotomy, and 22 (11.9%) other approaches. There was no significant difference in GTR rates of different surgical approaches (P = 0.101). Median follow-up was 46.6 months. The 5- and 10-year rates for progression-free survival (PFS) were 59.2% and 47.9%, respectively. The 5- and 10-year rates for overall survival (OS) were 77.3% and 63.9%, respectively. On multivariate analysis for both PFS and OS, GTR demonstrated significantly improved outcomes when compared with subtotal resection (hazard ratio 0.45, 95% confidence interval 0.22-0.90, P = 0.025 for PFS; hazard ratio 0.20, confidence interval 0.06-0.65, P = 0.008 for OS). CONCLUSIONS: GTR rates were comparable in different surgical approaches. GTR was a significant predictor of longer PFS and OS in clival chordoma.

Prognostic Factors and Treatment of Spinal Astrocytomas: A Multi-institutional Cohort Analysis.

STUDY DESIGN: Retrospective cohort analysis of patients with spinal astrocytoma from multi-institutional data and the literature. OBJECTIVE: To determine the prognostic factors, treatment, and survival of patients. SUMMARY OF BACKGROUND DATA: Our current understanding of the epidemiology, prognosis, and optimal treatment of spinal astrocytoma is limited. The literature is confined to case reports or small institutional case series. METHOD: Patient demographics, tumor characteristics, treatments, and outcomes were extracted. Univariate Kaplan-Meier survival analysis was performed to identify prognostic factors followed by multivariate Cox proportional hazard analysis. Wilcoxon signed-rank test was performed on pre- and postoperational functional status as measured by McCormick score. RESULTS: Ninety-four patients from four institutions and 339 patients from the literature were included. For the multi-institutional cohort, WHO grade IV tumors had shorter progression-free survival (PFS) than those of lower grades, whereas gross total resection (GTR) (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.14-1.27, P = 0.124) trended toward longer PFS when compared to subtotal resection (STR). Age 18 years or older, paresthesia as a presenting symptom, and higher WHO grade were associated with shorter overall survival (OS), whereas thoracic tumor location when compared to cervical tumor location, biopsy when compared to STR, and radiotherapy (HR: 0.42, 95% CI: 0.20-0.88, P = 0.022) were associated with longer OS. For the literature cohort, GTR (HR 0.43, 95% CI: 0.24-0.77, P = 0.005) was associated with longer PFS when compared to STR, whereas higher WHO grade was associated with shorter PFS. Higher WHO grade and recurrence/progression were associated with shorter OS. Postoperative McCormick score was significantly higher than preoperative score (P < 0.001), but subgroup analysis of the change in McCormick score by extent of resection revealed no differences among groups (P = 0.551). CONCLUSION: In patients with spinal astrocytomas, GTR likely resulted in longer PFS when compared to STR. Adjuvant radiotherapy appears to be effective in improving survival outcomes for high-grade tumors. LEVEL OF EVIDENCE: 4.

Recurrent lumbar disc herniation: Is there a correlation with the surgical technique? A multivariate analysis.

PURPOSE: The recurrence of a lumbar disc herniation (LDH) is a common cause of poor outcome following lumbar discectomy. The aim of this study was to assess a potential relationship between the incidence of recurrent LDH and the surgical technique used. Furthermore, we tried to define the best surgical technique for the treatment of recurrent LDH to limit subsequent recurrences. MATERIALS AND METHODS: A retrospective study was conducted on 979 consecutive patients treated for LDH. A multivariate analysis tried to identify a possible correlation between (1) the surgical technique used to treat the primary LDH and its recurrence; (2) technique used to treat the recurrence of LDH and the second recurrence; and (3) incidence of recurrence and clinical outcome. Data were analyzed with the Pearson's Chi-square test for its significance. RESULTS: In 582 cases (59.4%), a discectomy was performed, while in 381 (40.6%), a herniectomy was undertaken. In 16 cases, a procedure marked as "other" was performed. Among all patients, 110 (11.2%) had a recurrence. Recurrent LDH was observed in 55 patients following discectomy (9.45%), in 45 following herniectomy (11.8%), and in 10 (62.5%) following other surgery. Our data showed that 90.5% of discectomies and 88.2% of the herniectomies had a good clinical outcome, whereas other surgeries presented a recurrence rate of 62.5% (Pearson's χ2< 0.001). No statistical differences were observed between discectomy or herniectomy, for the treatment of the recurrence, and the incidence for the second recurrences (P > 0.05). A significant statistical correlation emerged between the use of other techniques and the incidence for the second recurrences (P < 0.05). CONCLUSIONS: The recurrence of an LDH is one of the most feared complications following surgery. Although the standard discectomy has been considered more protective toward the recurrence compared to herniectomy, our data suggest that there is no significant correlation between the surgical technique and the risk of LDH recurrence.

Comparison of chemoradiotherapy with radiotherapy alone for "biopsy only" anaplastic astrocytoma.

BACKGROUND: It has become increasingly common to incorporate adjuvant chemotherapy with radiotherapy in the treatment of resected anaplastic astrocytoma based on results from recent phase II/III randomized trials. However, whether or not combined chemoradiotherapy is associated with improved survival outcome in patients who undergo "biopsy only" is less clear. METHODS: The US National Cancer Database was used to identify patients with histologically confirmed, biopsy-only anaplastic astrocytoma who received either radiotherapy alone or combined chemoradiotherapy from 2006 through 2014. RESULTS: In total, 1896 patients with biopsy-only anaplastic astrocytoma were included, among whom 363 (19.1%) received radiotherapy alone and 1533 (80.9%) received combined chemoradiotherapy. The median age at diagnosis was 60 years. Combined chemoradiotherapy was associated with a significant survival benefit when compared with radiotherapy alone on univariable analysis (median, 13.2 versus 5.6 months; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50-0.65; p < 0.001) and on multivariable analysis (HR, 0.62; 95% CI, 0.55-0.71; p < 0.001). A significant survival benefit for combined chemoradiotherapy persisted in a propensity score-matched analysis (HR, 0.67; 95% CI, 0.56-0.78; p<0.001). CONCLUSIONS: Our results suggest that combined chemoradiotherapy may be associated with significantly improved survival over radiotherapy alone in patients with anaplastic astrocytoma who undergo biopsy only.

Generalized Indeterminate Cell Histiocytosis Presenting as Eroded Papules and Crusts.

Indeterminate cell histiocytosis (ICH) is a very rare histiocytic disease. We reported a case of generalized ICH presenting as eroded papules and crusts, accompanied with intermittent fever, pulmonary disorder, lymphadenectasis in the mediastinum, and the retroperitoneum. The histopathology indicated a neoplasm that was composed of small nests of large cells with ample pale cytoplasm. Immunohistochemistry results and the absence of Birbeck granules led us to the diagnosis of ICH. Four months later, the patient died of anemia, ascites, and swelling of the limbs.

Risk of stroke in imaging-proven subclavian steal syndrome.

To determine the risk of stroke in patients with subclavian steal syndrome (SSS). We identified 165 patients with imaging-provenSSS from two hospitals. Demographic, clinical and imaging data were retrospectively collected. Patients were followed up for stroke events. Stroke occurred in 43 patients with a median follow-up of 28months. Seven of these cases were identified prospectively and 36 cases retrospectively. On multivariate analysis, presence of symptoms at presentation (p=0.029) was a significant predictor of stroke. Presence of symptoms at presentation predicted stroke in imaging-proven SSS.

Prognostic Factors in Patients With Spinal Chordoma: An Integrative Analysis of 682 Patients.

BACKGROUND: The low incidence of spinal chordoma precludes a prospective study of prognostic factors with a large patient cohort. OBJECTIVE: To perform a comprehensive integrative analysis on the prognostic factors, treatment, and outcomes of patients with spinal chordoma using data from 2 institutions and the literature. METHODS: Appropriate studies were identified per search criteria. The local database was retrospectively searched to include a similar patient cohort. RESULTS: Overall, 108 studies from the literature and 30 patients from our local institution were identified, resulting in a total of 682 patients. The median age was 57 years old and 35.2% were female. The median follow-up was 46 months (range: 1-408). The median progression-free survival (PFS) and overall survival (OS) were 72 months and 115 months, respectively. Significant prognostic factors for PFS on multivariate analysis included age (pediatric vs adult, hazard ratio [HR]: 2.00-14.36), tumor location (mobile spine vs sacral spine, HR: 0.31-0.87), pathology (differentiated vs classic, HR: 2.48-10.90),and chemotherapy (HR:1.11-3.85). Significant prognostic factors for OS on multivariate analysis included age (geriatric vs adult, HR: 1.52-3.45 and pediatric vs adult, HR: 1.73-9.36), bladder or bowel dysfunction (HR: 1.27-5.43), pathology (dedifferentiated vs classic, HR: 2.38-11.09), recurrence or progression (HR: 1.72-4.48), and metastases (HR: 1.11-2.47). CONCLUSION: In patients with spinal chordoma, young age, location in sacral spine, dedifferentiated pathology, and chemotherapy were negative predictors of PFS, while young and old age, bladder or bowel dysfunction at presentation, dedifferentiated pathology, recurrence or progression, and metastases portended a worse OS.

Diagnostic Value and Safety of Brain Biopsy in Patients With Cryptogenic Neurological Disease: A Systematic Review and Meta-analysis of 831 Cases.

BACKGROUND: The role of brain biopsy in patients with cryptogenic neurological disease is uncertain. OBJECTIVE: To determine the risks and benefits of diagnostic brain biopsy for nonneoplastic indications in immunocompetent patients. METHODS: Appropriate studies were identified by searching electronic databases. RESULTS: We screened 3645 abstracts and included 20 studies with a total of 831 patients. Indications for biopsy were: (1a) severe neurological disease of unknown etiology in adults (n = 7) and (1b) in children (n = 2); (2) suspected primary angiitis of the central nervous system (PACNS) (n = 3); (3) chronic meningitis of unknown cause (n = 3); (4) atypical dementia (n = 4); and (5) nonneoplastic disease (n = 1). Diagnostic success rates calculated for subgroups were 51.3% (34.5-68.1) for 1a, 53.8% (42.9-64.5) for 1b, 74.7% (64.0-84.1) for 2, 30.3% (17.2-45.4) for 3, and 60.8% (41.2-78.8) for 4. Clinical impact rates were 30.5% (13.6-50.6) for 1a (n = 6), 67.1% (42.8-87.3) for 1b (n = 2), 8.3% (2.3-20.0) for 3 (n = 1), and 14.2% (6.5-24.3) for 4 (n = 2). Lymphoma (n = 32) and Creutzfeldt-Jakob disease (n = 30) were the most common diagnoses on the final histopathology reports of positive brain biopsies in 1a. In 1b, encephalitis (n = 7), PACNS (n = 6), and demyelination (n = 6) were the most common. The odds ratio for achieving a diagnostic biopsy when there was a radiological target was 3.70 (P = .014, 95% confidence interval, 1.31-10.42). CONCLUSION: Brain biopsy in cryptogenic neurological disease was associated with the highest diagnostic yield in patients with suspected PACNS. The greatest clinical impact was seen in children with cryptogenic neurological disease. The presence of a radiological target was associated with a higher diagnostic yield.