Prognostic Factor For Worse Overall Survival Research Articles

Association of Perioperative Skeletal Muscle Index Change With Outcome in Colorectal Cancer Patients.

The association between perioperative changes in the skeletal muscle index (SMI) and colorectal cancer (CRC) outcomes remains unclear. We aim to explore perioperative change patterns of SMI and evaluate their effects on long-term outcomes in CRC patients. This retrospective cohort study included Stage I-III CRC patients who underwent curative resection between 2012 and 2019. SMI at the third lumbar vertebra level was calculated using computed tomography scans. Optimal cut-off values for SMI were defined separately for males and females and classified as high or low preoperatively and at 3, 6, 9 and 12 months postoperatively. SMI status was further categorized into different perioperative SMI change patterns: highpre-highpost, highpre-lowpost, lowpre-highpost and lowpre-lowpost. The association with recurrence-free survival (RFS) and overall survival (OS) was examined using Cox proportional hazards models. A total of 2222 patients (median [interquartile range] age, 60.00 [51.00-68.00] years; 1302 (58.60%) men; 222 (9.99%) with preoperative low SMI) were evaluated. During a median follow-up of 60 months, 375 patients (16.88%) died, and 617 patients (27.77%) experienced a recurrence. Multivariate Cox model analysis showed that, compared to patients with highpre-highpost, those with highpre-lowpost (HR = 3.32, 95% CI: 1.60-6.51; HR = 2.54, 95% CI: 1.03-6.26; HR = 2.93, 95% CI: 1.19-7.19, all p < 0.05) had significantly worse RFS and OS (HR = 4.07, 95% CI: 1.55-10.69; HR = 4.78, 95% CI: 1.40-16.29; HR = 9.69, 95% CI: 2.53-37.05, all p < 0.05), at postoperative 6, 9 and 12 months, respectively. Patients with lowpre-lowpost were an independent prognostic factor for worse OS at postoperative 12 months (HR = 3.20, 95% CI: 1.06-9.71, p = 0.040). Patients with lowpre-highpost had similar risk of RFS compared to those with highpre-highpost at postoperative 3, 6 and 12 months (HR = 1.49, 95% CI: 0.75-2.98; HR = 1.05, 95% CI: 0.45-2.43; HR = 1.36, 95% CI: 0.31-6.06, all p > 0.05) and similar risk of OS at postoperative 3, 6, 9 and 12 months (all p > 0.05). Patients with a high preoperative SMI that decline postoperatively have poor RFS and OS. Consistently low SMI also correlates with worse OS. Patients with low SMI but increased after resection are not an indicator of better prognosis. Routine measurement of postoperative, rather than preoperative, SMI is warranted. Patients with low SMI are at an increased risk for recurrence and death, especially within the first year after surgery.

Radiotherapy with Targeted Therapy or Immune Checkpoint Inhibitors for Hepatocellular Carcinoma with Hepatic Vein and/or Inferior Vena Cava Tumor Thrombi.

This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies. Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30-65 Gy for planning target volume and 40-65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded. Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level >1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588-20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027-0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up. Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.

Blood transfusion might not be recommended for gastric cancer patients with pretransfusion minimum hemoglobin values higher than 90g/L: a real-world study covering 20 years of 13470 patients.

There was no consistent evidence whether perioperative blood transfusion (PBT) affects the long-term survival of gastric cancer (GC) patients after undergoing gastrectomy. This study aimed to investigate the effects of PBT on long-term survival of GC patients, as well as to determine the threshold of PBT and provide evidence for future surgical practice. We performed this real-world study of GC patients undergoing gastrectomy in China National Cancer Center from January 1, 2000 to December 30, 2019. Overall survival (OS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models were used to determine the risk factors for OS. In total, 13470 GC patients undergoing gastrectomy from 2000 to 2019 was included, of whom 3465 (34.6%) GC patients received PBT. PBT ratios declined from 29.1% (114/392) in 2000 to 11.2% in 2019 (149/1178), with the highest blood transfusion ratio in 2005 at 43.7% (220/504). For patients transfused with red blood cells, the median value of hemoglobin (Hb) before transfusion in the PBT group decreased from 110g/L in 2000 to 87g/L in 2019. Compared with patients who not receiving perioperative blood transfusion (NPBT), PBT group are more likely to be older (≥65, 39.1% vs. 30.1%, P<0.001), open operation (89.7% vs. 78.1%, P<0.001), higher ASA score (>2, 25.3% vs. 14.9%, P<0.001) and in the later pTNM stage (pTNM stage III, 68.5% vs. 51.5%, P<0.001). Results of multivariable Cox regression analysis showed that PBT was an independent prognostic factor for worse OS in GC patients undergoing gastrectomy (HR=1.106, 95% CI, 1.01-1.211, P=0.03). After stratified according to tumor stage, we found that PBT group had a worse prognosis only in pTNM stage III (HR=1.197, 95% CI, 1.119-1.281, P<0.001). OS was obviously poor in the PBT group when Hb levels were higher than 90g/L (90g/L<Hb≤120g/L:HR=1.196, 95% CI,1.090-1.313, P<0.001; Hb>120g/L:HR= 1.207, 95% CI, 1.098-1.327, P<0.001), while there was no difference between the two groups when Hb levels were lower than or equal to 90g/L (Hb≤90g/L: HR=1.162, 95% CI, 0.985-1.370, P=0.075). In conclusion, PBT was an independent prognostic factor for worse OS. Blood transfusion might not be recommended for gastric cancer patients with perioperative minimum Hb values higher than 90g/L.

Effect of Antacids on the Survival of Patients With Metastatic Urothelial Carcinoma Treated With Pembrolizumab

IntroductionConcomitant medications can affect the efficacy of immune checkpoint inhibitors. The association between histamine-2 receptor antagonists (H2RAs), major antacids similar to proton pump inhibitors (PPIs), and the efficacy of pembrolizumab for metastatic urothelial carcinoma (mUC) treatment has been poorly evaluated. We evaluated the impact of PPIs and H2RAs on oncological outcomes in mUC patients treated with pembrolizumab. Patients and MethodsThis retrospective multicenter study included patients with mUC treated with pembrolizumab. Patients prescribed PPIs or H2RAs within 30 days before and after the initial administration were extracted. The overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rates (ORR) were assessed. Kaplan–Meier survival curve analysis and multivariable Cox proportional hazard models were employed to assess the association between PPIs or H2RAs and survival outcomes. ResultsOverall, 404 patients were eligible for this study; 121 patients (29.9%) used PPIs, and 34 (8.4%) used H2RAs. Kaplan–Meier analysis showed significantly worse OS, CSS, and PFS in patients using PPIs compared to no PPIs (P = .010, .018, and .012, respectively). In multivariable analyses, the use of PPIs was a significant prognostic factor for worse OS (HR = 1.42, 95% CI 1.08-1.87, P = .011), CSS (HR = 1.45, 95% CI 1.09-1.93, P = .011), and PFS (HR = 1.35, 95% CI 1.05-1.73, P = .020). PPIs were not associated with ORRs. The use of H2RAs was not associated with survival or ORRs. ConclusionPPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, and H2RAs could be an alternative during administration. Both the oncological and gastrointestinal implications should be carefully considered when switching these antacids.

Surgery combined with adjuvant radiation and chemotherapy prolonged overall survival in stage IVC anaplastic thyroid cancer: a SEER-based analysis.

Anaplastic thyroid carcinoma (ATC) is a rare but aggressive malignancy, which accounts for only 1-2% of all thyroid cancers. The median overall survival (OS) time for all stages patients is at about 5 months. The benefit of surgery combined with adjuvant radiation and chemotherapy in stage IVC anaplastic thyroid cancer is still controversial. The aim of this study is to investigating surgery combined with adjuvant radiation and chemotherapy and survival outcomes in stage IVC ATC patients. Anaplastic thyroid carcinoma patients from the Surveillance, Epidemiology, and End Results database from 2004 to 2016 were used to conduct a cross-sectional study in the analysis. The endpoint of this study was overall survival. The median OS of the overall population was 2.0 months. Multivariate analysis showed that age (<67 vs. ≥67 years old, P = 0.017, HR = 1.355, 95% CI: 1.057-1.738), tumor size (<7 cm vs. ≥7 cm, P = 0.001, HR = 1.579, 95% CI: 1.202-2.073), Surgery (thyroidectomy vs. non-surgery, P < 0.001, HR = 0.554, 95% CI: 0.401-0.766), radiation therapy (P < 0.001, HR = 0.571, 95% CI: 0.445-0.733) and chemotherapy (P = 0.003, HR = 0.684, 95% CI: 0.531-0.881) were independent prognostic factor for worse OS in stage IVC ATC patients. Surgery combined with adjuvant radiation and chemotherapy exhibited the better overall survival time for 4 months. Surgery combined with adjuvant radiation and chemotherapy can improve overall survival in stage IVC ATC patients. We recommend surgical approach with fully evaluation combined with radiation therapy and chemotherapy for selected stage IVC ATC patients.

Urine Phthalate Metabolites are Elevated in Patients with Esophageal Squamous Cell Carcinoma and Associated with Advanced Cancer Stage and Poor Survival.

The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC). A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined. The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3-T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥3 μg/L and clinical stage IVB were independent prognostic factors for worse OS. The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.

Clinical Impact of the C-reactive Protein-albumin-lymphocyte Index in Post-gastrectomy Patients With Gastric Cancer.

Recently, preoperative inflammatory, immune, and nutritional statuses have attracted attention as prognostic factors in post-curative gastrectomy patients with gastric cancer (GC). The usefulness of the C-reactive protein-albumin-lymphocyte (CALLY) index as a prognostic factor in patients with various cancers, has been reported. However, reports on the clinical significance of the CALLY index in patients with GC after gastrectomy remain inadequate. In this prospective study, we focused on the preoperative CALLY index and investigated its usefulness as a prognostic factor in patients with GC. This study included 459 patients who underwent gastrectomy for GC between December 2013 and November 2017 at Kanagawa Cancer Center, Kanagawa, Japan. The preoperative CALLY index was calculated based on the preoperative blood test data. Patients were divided into high- and low-CALLY groups. The associations of the preoperative CALLY scores with clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS) after gastrectomy for GC were evaluated. The low-CALLY group was significantly older, had higher venous invasion, and a more progressive pStage than did the high-CALLY group. OS and RFS after gastrectomy in the low-CALLY group were significantly worse than those in the high-CALLY group (77.9% vs. 88.9%; p<0.001 and 73.8% vs. 87.1%; p<0.001, respectively). In the multivariate analysis, a low CALLY score was an independent prognostic factor of worse OS and RFS. Preoperative CALLY levels may be a useful prognostic predictor in patients with GC after curative gastrectomy.

Three-dimensional body composition parameters using automatic volumetric segmentation allow accurate prediction of colorectal cancer outcomes.

Parameters obtained from two-dimensional (2D) cross-sectional images have been used to determine body composition. However, data from three-dimensional (3D) volumetric body images reflect real body composition more accurately and may be better predictors of patient outcomes in cancer. This study aimed to assess the 3D parameters and determine the best predictive factors for patient prognosis. Patients who underwent surgery for colorectal cancer (CRC) between 2010 and 2016 were included in this study. Preoperative computed tomography images were analysed using an automatic segmentation program. Body composition parameters for muscle, muscle adiposity, subcutaneous fat (SF) and abdominal visceral fat (AVF) were assessed using 2D images at the third lumbar (L3) level and 3D images of the abdominal waist (L1-L5). The cut-off points for each parameter were determined using X-tile software. A Cox proportional hazards regression model was used to identify the association between the parameters and the treatment outcomes, and the relative influence of each parameter was compared using a gradient boosting model. Overall, 499 patients were included in the study. At a median follow-up of 59months, higher 3D parameters of the abdominal muscles and SF from the abdominal waist were found to be associated with longer overall survival (OS) and disease-free survival (all P<0.001). Although the 3D parameters of AVF were not related to survival outcomes, patients with a high AVF volume and mass experienced higher rate of postoperative complications than those with low AVF volume (27.4% vs. 18.7%, P=0.021, for mass; 27.1% vs. 19.0%, P=0.028, for volume). Low muscle mass and volume (hazard ratio [HR] 1.959, P=0.016; HR 2.093, P=0.036, respectively) and low SF mass and volume (HR 1.968, P=0.008; HR 2.561, P=0.003, respectively), both in the abdominal waist, were identified as independent prognostic factors for worse OS. Along with muscle mass and volume, SF mass and volume in the abdominal waist were negatively correlated with mortality (all P<0.001). Both AVF mass and volume in the abdominal waist were positively correlated with postoperative complications (P<0.05); 3D muscle volume and SF at the abdominal waist were the most influential factors for OS. 3D volumetric parameters generated using an automatic segmentation program showed higher correlations with the short- and long-term outcomes of patients with CRC than conventional 2D parameters.

Application of Small Cell Lung Cancer Molecular Subtyping Markers to Small Cell Neuroendocrine Carcinoma of the Cervix: NEUROD1 as a Poor Prognostic Factor.

Cervical small cell neuroendocrine carcinoma (CSCNEC) is a rare, aggressive type of cervical cancer. The treatment for CSCNEC follows the chemotherapeutic regimens used for small cell lung cancer (SCLC), with which it shares similar clinical and histologic features. For the first time, we applied neuroendocrine (NE) and SCLC molecular subtyping immunohistochemical markers [achaete-scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3), and yes-associated protein 1] in 45 patients with CSCNEC. For the combined NE score, 51.1% of NE-high and 48.9% of NE-low subtypes were identified. The NE-high subtype tended to show worse progression-free survival and overall survival (OS) than the NE-low subtype ( P =0.059 and P =0.07, respectively). Applying the SCLC molecular subtyping, 53.3% of cases were identified as NEUROD1-dominant, 17.8% as ASCL1-dominant, 13.3% as YAP-dominant, and 4.4% as POU2F3-dominant, while 11.1% of cases showed negative expression for all markers; the distribution was different from that of SCLC. The NEUROD1-dominant subtype exhibited the worst OS, while the POU2F3 subtype exhibited the best OS ( P =0.003), similar to SCLC. In addition, the ASCL1-dominant and NEUROD1-dominant subtypes showed high NE scores, while yes-associated protein 1-dominant and POU2F3-dominant subtypes showed low NE scores ( P =0.008). In multivariate analysis, the NEUROD1 expression was further identified as the independent prognostic factor for worse OS, together with the high FIGO stage. CSCNEC was revealed to be a heterogeneous disease with different biological phenotypes and to share some similarities and differences with SCLC. Regarding the ongoing development of tailored treatments based on biomarkers in SCLC, the application of biomarker-driven individualized therapy would improve clinical outcomes in patients with CSCNEC.

Radiologic Extranodal Extension of Metastatic Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Prognostic Utility and Diagnostic Performance.

BACKGROUND. Pathologic extranodal extension (ENE) in metastatic lymph nodes (LNs) has been associated with unfavorable prognosis in patients with non-small cell lung cancer (NSCLC). OBJECTIVE. The purpose of this article was to evaluate the prognostic utility of radiologic ENE and its diagnostic performance in predicting pathologic ENE in patients with NSCLC. METHODS. This retrospective study included 382 patients (mean age, 67 ± 10 [SD] years; 297 men, 85 women) diagnosed with NSCLC and clinical N1 or N2 disease between January 2010 and December 2016. Two thoracic radiologists reviewed staging chest CT examinations to record subjective overall impression for radiologic ENE (no ENE, possible/probable ENE, or unambiguous ENE), reviewing 30 examinations in consensus and the remaining examinations independently. Kaplan-Meier survival analysis and multivariable Cox proportional hazards model were used to evaluate the utility of radiologic ENE in predicting overall survival (OS). Prognostic utility of radiologic ENE was also assessed in patients with clinical N2a disease. In patients who underwent surgery, sensitivity and specificity were determined of radiologic unambiguous ENE in predicting pathologic ENE. RESULTS. The 5-year OS rates for no ENE, possible/probable ENE, and unambiguous ENE were 44.4%, 39.1%, and 20.9% for reader 1 and 45.7%, 36.6%, and 25.6% for reader 2, respectively. Unambiguous ENE was an independent prognostic factor for worse OS (reader 1: adjusted HR, 1.72, p = .008; reader 2: adjusted HR, 1.56, p = .03), whereas possible/probable ENE was not (reader 1: adjusted HR, 1.18, p = .33; reader 2: adjusted HR, 1.21, p = .25). In patients with clinical N2a disease, 5-year OS rate in patients with versus without unambiguous ENE for reader 1 was 22.2% versus 40.6% (p = .59) and for reader 2 was 27.6% versus 41.0% (p = .49). In 203 patients who underwent surgery (66 with pathologic ENE), sensitivity and specificity of radiologic unambiguous ENE for predicting pathologic ENE were 11% and 93% for reader 1 and 23% and 87% for reader 2. CONCLUSION. Radiologic unambiguous ENE was an independent predictor of worse OS in patients with NSCLC. The finding had low sensitivity but high specificity for pathologic ENE. CLINICAL IMPACT. Radiologic ENE may have a role in NSCLC staging workup and treatment selection.

Safety and efficacy of two-drug combination in elderly patients with locally advanced non-small cell lung cancer and validation of the Charlson Index as a predictor of survival.

The best platinum-based chemotherapy regimen remains to be determined in elderly patients treated with definitive chemoradiotherapy for advanced non-small cell lung cancer (NSCLC). Predictive indexes for toxicity and survival are also needed to give the safest and most effective treatment for this population. This is a retrospective cohort study. Patients with histologically confirmed stage IIIA, IIIB or IIIC NSCLC over 70 years of age, treated with radiotherapy and chemotherapy, were included. Patients from two cancer centers treated between 12/2006 and 08/2019 were included in the data analysis. Fifty-eight patients were enrolled in the study. The median age was 76.6 years [interquartile range (IQR): 71.6-83.4]. Thirty-nine patients were treated with concomitant chemoradiotherapy and 19 with a sequential strategy. The chemotherapy regimen consisted in a combination of platinum and taxanes. At a median follow-up of 52 months (IQR: 7-69), the 2-year progression-free survival (PFS) and overall survival (OS) were 35.5% and 66.9%, respectively. Male sex and a high Charlson index were identified as independent prognostic factors for worse OS. Acute grade 3-5 toxicities occurred in 34.4% of patients, including 1 grade 5 toxicity, and grade 3-4 late toxicities occurred in 17.2% of patients. In the whole cohort a high Charlson index was the only predictive factor for a higher risk of grade 3-5 acute toxicities (statistical trend in the concurrent cohort, P=0.06). The Charlson index correlated with toxicity and survival in elderly patients treated with chemoradiotherapy in locally advanced NSCLC. The addition of taxanes to platinum chemotherapy was safe in the present study and warrants further exploration.

Predictive factors and prognosis of immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer patients.

To investigate the influencing factors and prognosis of immune checkpoint inhibitor-related pneumonitis (CIP) in advanced non-small cell lung cancer (NSCLC) patients during or after receiving immune checkpoint inhibitors(ICIs). The clinical and laboratory indicator data of 222 advanced NSCLC patients treated with PD-1/PD-L1 inhibitors at the First Affiliated Hospital of Zhengzhou University between December 2017 and November 2021 were collected retrospectively. The patients were divided into a CIP group (n=41) and a non-CIP group (n=181) according to whether they developed CIP or not before the end of follow-up. Logistic regression was used to evaluate risk factors of CIP, and Kaplan‒Meier curves were used to describe the overall survival (OS) of different groups. The log-rank test was used to compare the survival of different groups. There were 41 patients who developed CIP, and the incidence rate of CIP was 18.5%. Univariate and multivariate logistic regression analyses showed that low pretreatment hemoglobin (HB) and albumin (ALB) levels were independent risk factors for CIP. Univariate analysis suggested that history of chest radiotherapy was related to the incidence of CIP. The median OS of the CIP group and non-CIP were 15.63 months and 30.50 months (HR:2.167; 95%CI: 1.355-3.463, P<0.05), respectively. Univariate and multivariate COX analyses suggested that a high neutrophil-to-lymphocyte ratio (NLR) level, a low ALB level and the development of CIP were independent prognostic factors for worse OS of advanced NSCLC patients treated with ICIs. Additionally, the early-onset and high-grade CIP were related to shorter OS in the subgroup. Lower pretreatment HB and ALB levels were independent risk factors for CIP. A high NLR level, a low ALB level and the development of CIP were independent risk factors for the prognosis of advanced NSCLC patients treated with ICIs.

Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients.

Data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population is limited. We report patient outcomes after surgery and proton radiotherapy (PRT). Pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (proton-based; for most, 80% proton/20% photon) at the Massachusetts General Hospital from 1981 to 2021. Endpoints of interest were overall survival (OS), disease-specific survival, progression-free survival (PFS), freedom from local recurrence (LC), and freedom from distant failure (DC). Of 204 patients, median age at diagnosis was 11.1 years (range, 1-21). Chordoma location included 59% upper and/or middle clivus, 36% lower clivus, 4% craniocervical junction, and 1% nasal cavity. Fifteen (7%) received pre-RT chemotherapy. Forty-seven (23%) received PRT, and 157 (77%) received comboRT. Median total dose was 76.7 Gy (RBE) (range, 59.3-83.3). At a median follow-up of 10 years (interquartile range, 5-16 years), 56 recurred. Median OS and PFS were 26 and 25 years, with 5-, 10-, and 20-year OS and PFS rates of 84% and 74%, 78% and 69%, and 64% and 64%, respectively. Multivariable actuarial analyses showed poorly differentiated subtype, radiographical progression prior to RT, larger treatment volume, and lower clivus location to be prognostic factors for worse OS, PFS, and LC. RT was well tolerated at a median follow-up of 9 years (interquartile range, 4-16 years). Side effects included 166 patients (80%) with mild/moderate acute toxicities, 24 (12%) patients with late toxicities, and 4 (2%) who developed secondary radiation-related malignancies. This is the largest cohort of BOS chordomas in the literature, pediatric and/or adult. High-dose PRT following surgical resection is effective with low rates of late toxicity.

Comparison of the Prognostic Value of Inflammatory and Nutritional Indices in Nonmetastatic Renal Cell Carcinoma.

Several markers that reflect inflammation and nutritional status have been associated with oncological outcomes in many tumors. This study aimed to describe the impact of pretreatment inflammatory and nutritional indices on the oncological outcomes in nonmetastatic renal cell carcinoma (RCC). A total of 213 Japanese patients with nonmetastatic RCC at Kanazawa University Hospital between October 2007 and December 2018 were included. The inflammatory and nutritional indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), were retrospectively analyzed. The optimal cutoffs for NLR, PLR, CAR, PNI, and GNRI were 2.18, 153.7, 0.025, 48.4, and 98, respectively. According to Kaplan-Meier curves, elevated NLR, PLR, CAR, and GNRI correlated with increased metastasis, while NLR and PNI correlated with worse overall survival (OS). In multivariate analysis, high CAR was an independent poor risk factor for metastasis (hazard ratio (HR), 3.08; 95% confidence interval (CI), 1.24-7.67; p = 0.016). Furthermore, high NLR showed an independent prognostic factor for worse OS (HR, 3.96; 95% CI, 1.01-15.59; p = 0.049). The pretreatment inflammatory and nutritional indices such as NLR and CAR might be promising prognostic factors for nonmetastatic RCC.

Malignant Solitary Fibrous Tumours of the Pleura Are Not All the Same: Analysis of Long-Term Outcomes and Evaluation of Risk Stratification Models in a Large Single-Centre Series.

Introduction: Malignant solitary fibrous tumours of the pleura (mSFTP) are extremely rare diseases (<5% of all pleural neoplasms) with unpredictable behaviour. Surgery remains the standard of care for these tumours; however, estimating patient prognosis and planning follow-up remain challenging. Several risk stratification models have been proposed, but a classification with diagnostic and prognostic potential has not been well standardised yet. The aim of this study was to analyse the clinicopathological data of mSFTP to investigate their prognostic features and to compare the performance of three risk stratification models proposed in the literature. Methods: Observational retrospective cohort study on all proven cases of mSFTP surgically resected with radical intent between 2000 and 2019 in a single centre. Demographic, surgical and pathological data were examined. All patients were risk-stratified by using three prediction models: modified Demicco, De Perrot and Tapias. Overall survival (OS) and disease-free survival (DFS) were analysed. Results: There were 21 men and 13 women (median age, 67 years, range, 23-83 years). Twenty-one patients (62%) were symptomatic. The median follow-up was 111 months (range, 6-258 months). The 5-year OS and DFS were 81.2% and 77.4%, respectively. Nine patients (26.5%) experimented recurrences. At univariate analysis, the presence of necrosis (p = 0.019), nuclear atypia (p = 0.006), dimension greater than 11.5 cm (median value of our cohort) (p = 0.037) and relapse/disease progression (p = 0.001) were independent prognostic factor of worse OS. The administration of adjuvant treatment was a protective independent factor for survival (p = 0.001). Radicality of resection (p = 0.005); tumour dimension (p = 0.013), presence of necrosis (p = 0.041) and nuclear atypia (p = 0.007) and pleural pattern (p = 0.011) were independent prognostic factors of worse DFS. Analysing the three risk stratification models, the Tapias score was revealed as the best index to predict both OS (p = 0.002) and DFS (p = 0.047) in patients with mSFTP. Conclusions: Using the risk stratification model proposed by Tapias, patients with the highest risk of recurrence could be identified at the time of surgery to establish a more frequent imaging surveillance and longer follow-up. The role of adjuvant treatment in mSFTP therapy has not been established yet, but further analysis on patients with a high risk of recurrence, stratified according to risk models, along with biomolecular panels may tailor future post-surgical therapies.

Prognostic value of Ki-67 index in primary intracranial tumors of infants.

Primary intracranial tumors are rare tumors in infants. They differ from those found in other pediatric age groups in terms of clinical presentation, histopathological diagnosis, adjuvant therapies, and outcome. Ki-67 index has also shown promising results as a prognostic factor in different types of intracranial tumors in children and adults. However, the importance and the best cutoff point of Ki-67 index in primary intracranial tumors of infants remains unclear. We aimed to analyze prognostic value of Ki-67 index in primary intracranial tumors of infants. This study retrospectively reviewed the records of 28 infants undergoing surgical resection for primary intracranial tumors between April 2016 and March 2021. We analyzed clinical characteristics, tumor location, extent of resection, histopathological diagnosis, Ki-67 index, and overall survival (OS). To define the most relevant cutoff value for Ki-67 index, "Cutoff Finder" was used. The median age at diagnosis was 188days for all patients. Fifteen of the patients were boys and 13 were girls. Tumors were located supratentorial in 13 patients and infratentorial in 15 patients. Gross total resection was performed in 7 of 13 supratentorial tumors and 9 of 15 infratentorial tumors. The mean Ki-67 index of the supratentorial tumors was 49.6%, the median was 55%; for infratentorial tumors, the mean was 49.9%, and the median was 70%. Tumor grade (p = 0.019) and Ki-67 index (p = 0.003) were found as significant predictors of OS in log-rank testing for Kaplan-Meier survival analysis. Univariate cox regression analysis identified high Ki-67 index as prognostic factor for worse OS, with hazard ratio of 8.852 (95% CI 1.95-64.80; p = 0.0108). High Ki-67 index was found as independent prognostic factor for worse OS in multivariate cox regression analysis (HR 7.036; 95% CI 1.229-65.82; p = 0.0457). High-grade and high Ki-67 index were associated with worse outcome. Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 72.5%.

Clinico-demographic characteristics and outcomes of radiation-induced sarcomas (RIS): a CanSaRCC study.

Radiation-induced sarcomas (RIS) tend to have aggressive behaviour and because of their rarity, the most appropriate management for these malignancies is uncertain. Using the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database, a national sarcoma registry, we aimed to investigate prognostic factors and outcomes for RIS. Retrospective study of RIS patients treated from 1996 to 2021 at three Canadian centres. RIS was defined as a sarcoma arising in a previously irradiated field following a 3+ year latency period, whose histology was distinct from the initially irradiated tumour. Clinicopathologic and treatment-related information was extracted from the CanSaRCC database. Overall survival (OS) was defined as the time from RIS diagnosis to death from any cause. Response rate (RR) to neoadjuvant chemotherapy (NACT) was based on physician assessment. Time-to-event analyses were estimated using the Kaplan-Meier method, with Cox regression for multivariate analysis. We considered a two-tailed p-value of <0.05 as statistically significant. One hundred seven tumours met the criteria for RIS and were divided into three subgroups: breast angiosarcoma (BAS, n = 54), osteosarcoma (OST, n = 16), and other soft-tissue sarcomas (STS, n = 37). Patients were mostly female (n = 85, 79%), treated initially for breast carcinomas (n = 54, 50.5%), and diagnosed with high-grade tumours (n = 61/71, 86%). None had evidence of synchronous metastasis. Patients with OST were younger (median age: 48 years, p < 0.001), and BAS had the shortest latency interval (8 versus 18 years for OST/STS, p < 0.001). Most patients underwent surgery, 76% (n = 76/100) R0; 24% (n = 26) received radiation therapy, mostly (n = 15, 57.7%) neoadjuvant. Among those receiving chemotherapy, 30 (75%) underwent NACT; among patients with documented response assessment, the RR was 68% (n = 17/25), being even higher in the BAS population (89.5%, n = 13/17). Median OS was 53 months (95% CI 34-101), with a 5-year OS of 47.6%; larger tumour size, high histologic grade and older age were independent prognostic factors for worse OS. Surgery is standard, and NACT might be useful to downsize large lesions, especially in BAS patients. Raising RIS awareness is fundamental to promoting appropriate management and fostering research through multi-institutional collaborations.

Mutation patterns and evolutionary action score of TP53 enable identification of a patient population with poor prognosis in advanced non-small cell lung cancer.

TP53 mutations are frequent in non-small cell lung cancer (NSCLC). Different categories of TP53 mutations may be associated with survival in advanced NSCLC, but their effect on prognosis is diverse. To date, a comprehensive comparison of the relationship between different classes of TP53 alterations and survival in advanced NSCLC has rarely been performed. Moreover, the prognostic significance of a novel approach called the evolutionary action of TP53 (EAp53) in advanced NSCLC is unclear. A total of 210 patients with NSCLC harboring TP53 mutation data were enrolled. Genomic and clinical data for the Memorial Sloan Kettering Cancer Center (MSKCC) cohort with advanced NSCLC were obtained from cBioPortal. Relationship between clinical characteristics and TP53 mutations was performed by Fisher's exact test or χ2 test. Overall survival (OS) analysis was evaluated using Kaplan-Meier method and Cox proportional hazards regression model. TP53 mutations were identified in 51.4% of NSCLC patients and were mainly located in exons 5, 7, and 8. The distribution patterns of missense and truncating mutations of TP53 were remarkably different. Among patients with advanced NSCLC who never received immune checkpoint inhibitor treatments, EAp53 high-risk mutations were significantly associated with poor OS in both our cohort and the MSKCC cohort. Moreover, marked differences were observed in the mutational landscape between patients with EAp53 high-risk mutations (HR group) and other patients (OT group). The HR group displayed higher mutation frequencies in the RTK, cell cycle, and DNA damage repair (DDR) pathways than the OT group. In addition, the tumor mutation burden in the HR group was significantly higher than that in the OT group. This study provided important insights into the molecular-clinical profile of TP53-mutated NSCLC patients. Moreover, the data revealed that EAp53 high-risk mutations were an independent prognostic factor for worse OS in advanced NSCLC.

Long-term treatment outcomes/toxicities of definite chemoradiotherapy (intensity-modulated radiation therapy) for early-stage “bulky” cervical cancer and survival impact of histological subtype

To investigate the long-term treatment outcomes of early stage bulky cervical cancer treated with definite chemoradiotherapy (CCRT) using intensity-modulated radiotherapy (IMRT) followed by intracavity brachytherapy (ICRT) and the impact of histologic subtype on survival. From 2004 to 2016, 126 patients with FIGO stage IB2-IIB bulky (≥4cm) cervical cancer treated with CCRT followed by ICRT were retrospectively reviewed. Long-term treatment-related acute/late toxicities and treatment outcomes including overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were reported. Different histologic subtype between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC)) of uterine cervix were also compared. Median follow-up time for alive patients was 117 months. The 5-year OS, LRRFS and DMFS were 75.3%, 87.8% and 75.6%, respectively. The most common≥grade 3 acute toxicity was hematologic toxicity (41.3%). The rates of ≥ grade 3 late toxicities were 4% of proctitis, 0.8% of urethral stricture and 0.8% of radiation dermatitis (peri-anal skin necrosis and gangrene). The 5-year OS/LRRFS/DMFS for SCC and AC/ASC were 81.7%/93.7%/81.5% and 51.9%/65.8%/53.5%, respectively (all log-rank p<0.05). The AC/ASC histology was an independent prognostic factor for worse OS, LRRFS, and DMFS (All p<0.05). After long-term follow up, definite CCRT using IMRT followed by ICRT is a feasible treatment with favorable acute and late treatment toxicities for patients with early stage bulky cervical cancer. This treatment outcomes were excellent for "bulky" FIGO stage IB2-IIB SCC of the uterine cervix but seemed insufficient for AC/ASC of uterine cervix.

Effect of Gross Tumor Volume (GTV) after Pelvic External Irradiation on Radiation Dose Selection and Prognosis in Vaginal Stump Cancer

<h3>Purpose/Objective(s)</h3> Radical radiotherapy is safe and effective for patients with vaginal stump cancer after hysterectomy. The tumor volume after external irradiation is important for selecting irradiation dose and local control. For patients with less residual tumor volume after external irradiation, the total irradiation dose < 70Gy does not affect survival. <h3>Materials/Methods</h3> Ninety-nine patients with vaginal stump cancer after hysterectomy between January 2011 and November 2018 were retrospectively analyzed in this study. All patients received radical radiotherapy without prior antitumor therapy. After pelvic irradiation of 45-50Gy, the residual tumor was further irradiated to 60-82Gy (EQD2, a/β=10) by external irradiation or brachytherapy. Cisplatin-based chemotherapy was performed concurrently with radiotherapy. The overall survival (OS), progress-free survival (PFS), local control (LC), and toxicity were analyzed. <h3>Results</h3> Seventy patients (70.7%) had received 70-82Gy (EQD2, a/β=10) for vaginal stump lesions, and external irradiation is responsible for 84.8% of patients. The Median follow-up was 49.9 months (7.4-114.7months). The 4-year actuarial OS, PFS, and LC were 84.4%, 79.2%, and 89.3%, respectively. In multivariable analysis, GTV > 9cc after pelvic radiotherapy an only independent prognostic factor for worse OS, LC (OS: hazard ratio [HR] = 6.87, CI, 1.90 to 24.83, p=0.003; LC: HR = 8.47, CI, 2.18 to 32.82, p = 0.002). In a subgroup analysis, among patients with GTV > 9cc after pelvic radiation, those with an irradiation dose ≥ 70Gy had better LC than those with a dose < 70Gy (86.5% VS. 44.4%, p=0.009). However, the OS or PFS did not show significant differences between the two groups. In patients with GTV ≤9cc, the irradiation dose ≥ 70Gy didn't show a benefit of LC (93.2% VS.100%, p=0.267). 6 patients (6.06%) developed acute grade 3 rectal toxicity, 4 of which occurred at irradiation dose ≥ 70Gy. None of the patients had complications of late G3-4 grade urinary, rectal toxicity, or lymphedema. <h3>Conclusion</h3> Radical radiotherapy is safe and effective for patients with vaginal stump cancer after hysterectomy. The tumor volume after external irradiation is important for selecting irradiation dose and local control. For patients with less residual tumor volume after external irradiation, the total irradiation dose < 70Gy does not affect survival.