Two-year Survival Rates Research Articles

Early diagnosis of myocardial infarction in patients presenting late after chest pain onset

Abstract Background The European Society of Cardiology (ESC) recommends the clinical use of the 0/1h-algorithms in patients with suspected acute coronary syndrome (ACS) to rule-out or rule-in non-ST elevation myocardial infarction (NSTEMI). However, the diagnostic performance of the ESC 0/1h-algorithms was only validated in patients presenting within 12 hours after chest pain onset (=early presenters) to the emergency department (ED). To this date, evidence regarding their performance in patients with chest pain onset >12h (=late presenters) is lacking. Purpose To evaluate the diagnostic performance of the ESC 0/1h-algorithms in late presenters. Methods We prospectively enrolled patients presenting to the ED with symptoms suggestive of ACS such as acute chest discomfort. Two independent cardiologists adjudicated the final diagnoses based on all available clinical information including serial hs-cTn concentrations, follow-up information and cardiac imaging. Hs-cTnT/I concentrations at 0h and 1h were measured in a blinded fashion. The primary diagnostic endpoint was the diagnostic performance of the hs-cTnT/I ESC 0/1h-algorithms in patients presenting late after chest pain onset compared to those presenting early. Diagnostic performance was quantified by safety of rule-out (sensitivity and negative predictive value), accuracy of rule-in (specificity and positive predictive value), and efficacy (proportion of patients) classified as rule-out or rule-in within 1 hour after presentation to the ED. The primary prognostic endpoint was all-cause mortality after 30-days and two-years in patients in whom NSTEMI was ruled-out by the ESC 0/1h-algorithms. Results Among 4733 patients, 308/4733 (7%) presented late to the ED. The ESC hs-cTnT 0/1h-algorithm ruled-out 185/308 (60%) of late presenters with a sensitivity of 100% (95% CI, 93.7–100) and a negative predictive value (NPV) of 100% (95% CI, 98.0–100). Sixty-one of 308 (20%) were ruled-in with a specificity of 95.2 (95% CI, 91.8–97.2) and a positive predictive value (PPV) of 80.3% (95% CI, 68.7–88.4). The remaining 62/308 (20%) were classified as observe with a NSTEMI prevalence of 13%. In comparison, 59% of early presenters were ruled-out (sensitivity 99.3% [95% CI, 98.4–99.7]; NPV 99.8 [99.5–99.9]), 17% were ruled-in (specificity 96.2 [95% CI, 95.5–96.8]; PPV 81.4 [95% CI, 78.4–84.0]), and 45% were classified as observe. Late presenters in whom NSTEMI was ruled-out had 30-day and two-year survival rates of 100% and 98.2%, respectively. Similar findings were made for the ESC hs-cTnI 0/1h-algorithm. Conclusion The ESC hs-cTnT/I algorithms also provide excellent diagnostic performance for early triage and specifically safe rule-out of NSTEMI in patients presenting late after chest pain onset to the ED. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss Heart Foundation, Swiss National Science Foundation

Phase I Trial of an IMRT-based Contralateral Esophagus Sparing Technique (CEST) in Locally Advanced NSCLC and SCLC Treated to 70 Gy

Severe acute esophagitis (AE), grade (G) ≥3 by CTCAE, occurs in ∼7-21% of locally advanced NSCLC or SCLC patients (pts) treated with concurrent chemo/radiation therapy (CRT) to ≥60 Gy once-daily. G3+ AE represents a dose-limiting toxicity and is associated with poor treatment outcomes, as shown in RTOG 0617. We hypothesized that formalized sparing of the contralateral esophagus (CE) reduces the risk of severe AE by preserving partial organ functionality. We performed a phase I clinical trial to prospectively test an empirically developed CE-sparing technique on an IRB-approved protocol (registered with clinicaltrials.gov). Pts with locally advanced NSCLC (+/- solitary brain metastasis) or limited-stage SCLC with gross tumor within 1 cm of the esophagus were eligible. Pts were treated with IMRT or VMAT and daily CBCT to 70 Gy at 2 Gy/fraction. The PTV was a uniform 5 mm expansion. The esophageal wall contralateral to gross tumor was contoured as an avoidance structure to guide a steep dose falloff gradient across the esophagus, except on slices where tumor surrounded the esophagus. Target coverage was always prioritized over CE sparing, and 99% of ITV and PTV were covered by 70 Gy and ≥63 Gy, respectively. To be analyzable for the primary endpoint of G3+ AE (CTCAE v4), pts needed to have received concurrently ≥5 cycles of weekly carboplatin/paclitaxel or ≥2 cycles of platinum + pemetrexed or etoposide and have had ≤3 days of unplanned treatment interruption unrelated to esophagitis. Survival times were calculated from date of registration. Of 27 pts accrued between 7/2015 and 1/2019, 25 completed treatment and were analyzable for secondary endpoints while 20 were analyzable for the primary endpoint (analysis was performed with complete follow-up until February 9, 2020). Median age was 67 years (range, 51-81 years). There were 15 males and 10 females. Nineteen pts had NSCLC and 6 had SCLC. AJCC stage (7th ed.) distribution was: IIIA 52%, IIIB 40%, IV 8%. Total dose was 70 Gy (n = 24) or 68 Gy (n = 1). Median esophagus V60 was 11% (1-29%). Median CE max dose, V55, and V45 were 66 Gy (44-71 Gy), 1.4cc (0-5.3cc), and 2.7cc (0-9.2cc), respectively. Median follow-up was 33.3 months (11.1-52.2 months). The rate of G3+ AE was 0%. Other radiation-related toxicities were: G2 AE 25%, G2+ pneumonitis 12% (G2 n = 2, G5 n = 1), G3+ cardiac toxicity 8% (G3 n = 1, G5 n = 1). There was no isolated local tumor failure. Two-year overall survival rate was 67% (95% CL, 45-82%), and median progression free-survival time was 25.9 months (95% CL, 11.2 to not reached). CE sparing is associated with substantially reduced AE in CRT pts treated to 70 Gy, with no G3+ AE despite gross tumor within 1 cm of the esophagus. We hypothesize that contralateral wall sparing converts the esophagus from a serial to a parallel organ, a concept that may be readily adaptable into clinical practice.

Radical nephrectomy with resection of vena cava thrombus using extracorporeal circulation and deep hypothermic circulatory arrest.

Patients with renal cell carcinoma (RCC) with level 3 or 4 caval thrombus have a poor prognosis, with reported five-year survival rates of 30-40%. The aim of this study was to assess the perioperative morbidity and long-term oncological outcomes for radical nephrectomy with resection of vena cava thrombus using a combined surgical approach, including extracorporeal circulation and deep hypothermic circulatory arrest. A retrospective review was performed of the institutional case log to identify all radical nephrectomies with caval thrombus performed from January 2006 to May 2020. Twenty-five patients were identified with level 2 thrombus in one (4%), level 3 thrombus in eight (32%), and level 4 in 16 (64%). The median followup was 20.6 months (range 0.2-133.3). The median age at surgery was 68.4 years (range 44.2-85.5). Twenty-one (84%) patients were symptomatic at presentation. Six (24%) patients had distant metastases at diagnosis. The median circulatory arrest time was 15 minutes (range 6-35). The 30-day grade ≥3 complication rate was 8%. The 30-day mortality rate was 8%. The one-year, two-year, three-year, and five-year recurrence-free survival (RFS) rates were 53%, 18%, 10%, and 10%, respectively. The median time to systemic treatment was 7.7 months (range 1.2-25.7). The one-year, two-year, three-year, and five-year overall survival (OS) rates were 70%, 43%, 36%, and 31%, respectively. Radical nephrectomy with resection of vena cava thrombus using extracorporeal circulation and deep hypothermic circulatory arrest is associated with some morbidity and mortality but remains a safe and effective strategy for advanced RCC patients who would otherwise be managed palliatively.

Value of interim 18F-FDG PET/CT for predicting progression-free survival in stage ⅢB/IV EGFR-mutant non–small-cell lung cancer patients with EGFR-TKI therapy

ObjectivesWe retrospectively investigated the prognostic value of FDG-PET performed for patients with Stage ⅢB/IV EGFR-mutant non–small-cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitor (TKI) therapy. MethodsA total of 78 patients newly diagnosed with Stage ⅢB/IV EGFR-mutant NSCLC who received baseline and interim PET/CT examination and were treated with EGFR-TKI therapy were included. Interim PET was performed after 4–6 weeks of treatment. Cox proportional hazards regression analysis was used to assess the association between quantitative 18F-FDG PET/CT parameters, other clinicopathological factors and progression-free survival (PFS), non-durable clinical benefit (non-DCB). Five interim PET variables were analyzed in this study in the prediction of non-DCB. ResultsThe one-year and two-year progression-free survival rates of the patients were 33.9% (28.6–39.2%) and 20.7% (16.1–25.3%), respectively. Multivariable analysis indicated that interim PET relevant factors ΔSUVmax (p = 0.002, p = 0.014) and ΔSUVmean (p = 0.000, p = 0.030) were independent risk factors for predicting the PFS or non-DCB of patients receiving EGFR-TKI treatment. The optimal cutoff values of the parameters in the tumor survival analyses were 56.74% for ΔSUVmax (p = 0.002) and 36.48% for ΔSUVmean (p = 0.001). ΔSUVmax had the highest diagnostic value in the prediction of non-DCB. The one-year progression-free survival rates (95% confidence intervals) of patients with ΔSUVmax ≥ 56.74% and ΔSUVmax <56.74% were 59.5% (44.2–74.8%) and 5.7% (0.0–13.3%), respectively (p = 0.000). ConclusionAn early PET scan after 4–6 weeks can effectively predict the PFS and non-DCB of patients with Stage ⅢB/IV EGFR-mutant NSCLC receiving EGFR-TKI therapy.

Wilm's Tumor 1-guided preemptive treatment with hypomethylating agents for molecular relapse of AML and MDS after allogeneic transplantation.

Hypomethylating agents (HMA) for relapsed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic transplantation (allo-SCT) are most effective when used at the stage of molecular relapse. As Wilm's Tumor 1 (WT1)- expression has proven to serve as broadly applicable, sensitive and specific minimal residual disease (MRD) marker, we measured WT1-expression in 35 AML and MDS patients using a standardized assay for the guidance of therapy with HMA and donor lymphocyte infusions (DLI). Molecular relapse was detected in median 168 days post-transplant prompting therapy with a median of six HMA cycles and at least one DLI (n = 22, 63%). Hereby, 13 patients (37%) achieved major response (=MRD- complete remission [CR]), and 7 patients (20%) achieved minor response (=MRD+ CR), whereas 15 patients (43%) progressed into hematologic relapse. Two-year overall survival (OS) rate was 35% including 11 patients (31%) with ongoing MRD- remission for a median of 21 months. Patients with the major response after six cycles had significantly better OS suggesting that those not achieving MRD negativity after six cycles are candidates for alternative therapies. Combining MRD-monitoring of WT1-expression and preemptive therapy with HMA and DLI appears as a practicable and efficient approach for imminent relapse after allo-SCT.

A non-surgical option in large bronchopleural fistulas: Bronchoscopic conical stent application.

This study aims to compare the results of the open surgical approach versus endobronchial conical stent application in the treatment of extensive fistulas. Between December 2004 and April 2016, a total of 36 patients (34 males, 2 females; mean age 59.6±8.1 years; range, 40 to 72 years) with a bronchopleural fistula of ≥8 mm in diameter and underwent either conventional open surgery with stump-supported intercostal muscle flap or endobronchial ultra-flex expandable stenting were retrospectively analyzed. The demographic and clinical characteristics of the patients, operative data including the length of hospital stay, thoracic drainage time, and early mortality, and survival data were recorded. The mean hospitalization time was 17.4±4.5 days for the bronchoscopic group and 22.5±6.7 days for the invasive surgery group (p=0.026). The median time to removal of thoracic drains was 15 (range, 10 to 30) days for the bronchoscopic group and 26 (range, 14 to 55) days for the surgical group (p=0.027). Early mortality rates of both approaches were in favor of the bronchoscopic approach (χ2=7.058; p=0.008). Two-year survival rate was 76.47% (n=13) in the bronchoscopic group and 70% (n=7) in the surgical group. There was no statistically significant difference in the survival rates between the two groups (χ2=0.132; p=0.716). Our study results suggest that bronchoscopic approach can be the first choice in the treatment algorithm of fistulas with a diameter of ≥8 mm presenting with empyema in selected cases.

Treatment strategy and outcomes in locally advanced head and neck squamous cell carcinoma: a nationwide retrospective cohort study (KCSG HN13\u201301)

BackgroundBy investigating treatment patterns and outcomes in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), we aimed at providing valuable insights into the optimal therapeutic strategy for physicians in real-world practice.MethodsThis is a multi-institutional study enrolled the patients with stage III to IVB LA-HNSCC, except for nasopharyngeal carcinoma, from 2004 to 2015 in thirteen referral hospitals capable of multidisciplinary care.ResultsA total of 445 LA-HNSCC patients were analyzed. The median age was 61 years (range, 24–89). The primary tumor location was the oropharynx in 191 (43%), oral cavity in 106 (24%), hypopharynx in 64 (14%), larynx in 57 (13%) and other sites in 27 (6%). The most common stage was T2 in 172 (39%), and N2 in 245 (55%). Based on treatment intents, 229 (52%) of the patients received definitive concurrent chemoradiotherapy (CCRT) and 187 (42%) underwent surgery. Approximately 158 (36%) of the study population received induction chemotherapy (IC). Taken together, 385 (87%) of the patients underwent combined therapeutic modalities. The regimen for definitive CCRT was weekly cisplatin in 58%, 3-weekly cisplatin in 28% and cetuximab in 3%. The preferred regimen for IC was docetaxel with cisplatin in 49%, and docetaxel, cisplatin plus fluorouracil in 27%. With a median follow-up of 39 months, one-year and two-year survival rates were 89 and 80%, respectively. Overall survival was not significantly different between CCRT and surgery group (p = 0.620).ConclusionsIn patients with LA-HNSCC, the majority of patients received combined therapeutic modalities. Definitive CCRT, IC then definitive CCRT, and surgery followed by adjuvant CCRT or radiotherapy are the preferred multidisciplinary strategies in real-world practice.

Spatially Fractionated Radiation Therapy Using Lattice Radiation in Far-advanced Bulky Cervical Cancer: A Clinical and Molecular Imaging and Outcome Study.

Spatially fractionated radiation therapy (SFRT) has shown promise in generating high tumor response and local control in the treatment of various palliative and locally advanced bulky tumors. SFRT has not yet been studied systematically in cancer of the cervix. Here we report the first series of patients receiving SFRT for advanced/bulky cervical cancer. Ten patients with far-advanced bulky cervical cancer, stage IIIB-IVA (seven squamous cell and three adeno/adenosquamous carcinomas) received lattice radiation therapy (LRT), a variant of SFRT. The LRT regimen consisted of a dose of 24 Gy in three fractions, given to an average of five high-dose spheres within the gross tumor volume (GTV). The dose in the peripheral GTV was limited to 9 Gy in three fractions, using the volumetric modulated arc therapy (VMAT) technique. LRT was followed subsequently by conventionally fractionated external beam irradiation to 44.28 Gy (range: 39.60-45.00 Gy in 1.8 Gy fractions). All patients received concurrent cisplatin chemotherapy. Tumor response was assessed clinically, by morphological imaging (CT, MRI) and 18FDG PET/CT. Tumor control and survival rates were estimated using Kaplan-Meier analysis. All patients had local control at a median follow-up of 16 months (1-77). The two-year disease-specific survival rate was 53.3%. All cancer deaths were due to metastatic failure with local control maintained. Among the three patients who died of disease, all had adeno- or adenosquamous carcinoma histology, and no deaths from disease occurred among the patients with squamous cell carcinoma (P = 0.010). There were no grade ≥3 short-term or long-term treatment-related complications. Intra-treatment morphological tumor regression was highly variable (mean: 54%, range: 6-91%). After therapy, the complete metabolic response was 88.9% (8/9), and one patient out of the nine patients with post-treatment PET-CT had partial response (11.1%). Our preliminary data suggest that LRT-based SFRT is well tolerated in patients with far-advanced bulky cervical cancer and results in favorable tumor responses and high local control. These observations confirm prior reports of favorable tumor control and toxicity outcomes with SFRT in other advanced/bulky malignancies. Our findings are corroborated by high molecular-imaging-based tumor response. These encouraging hypothesis-generating results require cautious interpretation and confirmation with larger patient cohorts, preferably through a multi-institutional controlled randomized clinical trial.

The Role of Primary Tumor Resection in Colorectal Cancer Patients with Asymptomatic, Synchronous, Unresectable Metastasis: A Multicenter Randomized Controlled Trial.

We aimed to assess the survival benefits of primary tumor resection (PTR) followed by chemotherapy in patients with asymptomatic stage IV colorectal cancer with asymptomatic, synchronous, unresectable metastases compared to those of upfront chemotherapy alone. This was an open-label, prospective, randomized controlled trial (ClnicalTrials.gov Identifier: NCT01978249). From May 2013 to April 2016, 48 patients (PTR, n = 26; upfront chemotherapy, n = 22) diagnosed with asymptomatic colorectal cancer with unresectable metastases in 12 tertiary hospitals were randomized (1:1). The primary endpoint was two-year overall survival. The secondary endpoints were primary tumor-related complications, PTR-related complications, and rate of conversion to resectable status. The two-year cancer-specific survival was significantly higher in the PTR group than in the upfront chemotherapy group (72.3% vs. 47.1%; p = 0.049). However, the two-year overall survival rate was not significantly different between the PTR and upfront chemotherapy groups (69.5% vs. 44.8%, p = 0.058). The primary tumor-related complication rate was 22.7%. The PTR-related complication rate was 19.2%, with a major complication rate of 3.8%. The rates of conversion to resectable status were 15.3% and 18.2% in the PTR and upfront chemotherapy groups. While PTR followed by chemotherapy resulted in better two-year cancer-specific survival than upfront chemotherapy, the improvement in the two-year overall survival was not significant.

Two-year follow-up of patients with heart failure with reduced ejection fraction receiving cardiac contractility modulation

Aim. To assess the 2-year prognosis of patients with heart failure with reduced ejection fraction (HFrEF) receiving cardiac contractility modulation (CCM).Material and methods. This single-center observational study included 55 patients (46 men, mean age 53±11 years) with NYHA class II-III HFrEF receiving optimal medical therapy, with sinus rhythm, QRS &lt;130 ms or QRS&lt;150 ms with nonspecific intraventricular conduction delay. NYHA class II and III were established in 76% and 24% of patients, respectively. All patients were implanted with CCM devices between October 2016 and September 2017. Follow-up visits were carried out every 3 months during the 1styear and every 6 months during the 2ndyear of observation. The primary composite endpoint was mortality and heart transplantation. Secondary composite endpoints included death, heart transplantation, paroxysmal ventricular tachycardia/ ventricular fibrillation, hospitalizations due decompensated HFResults.The one-year and two-year survival rate was 95% and 80%, respectively. Primary endpoint was observed in 20% of patients. NYHA class III and higher levels of N-terminal pro-brain natriuretic peptide (NTproBNP) were associated with unfavorable prognosis (p=0,014 and p=0,026, respectively). NTproBNP was an independent predictor of survival (p=0,018). CCM contributed to a significant decrease in hospitalizations due to decompensated HF (p&lt;0,0001). The secondary endpoint was observed in 18 (33%) of patients during the 1styear. The predictor for the secondary composite endpoint was NTproBNP (p=0,047).Conclusion. CCM is associated with a significant decrease in hospitalization rate due to decompensated HF. The 2-year survival rate of patients with NYHA class II-III HF receiving CCM was 80%. The NTproBNP level was an independent predictor of survival in patients receiving CMM for 2 years. Further longer-term studies of the CCM efficacy are required.

Abstract 4727: Molecular heterogeneity in glioblastoma multiforme influences variant clonality and neoantigen prediction accuracy

Abstract Gliomas originate from neuroglial progenitor cells in the brain or spinal cord and have an incidence of ~6 cases per 100,000 individuals each year in the United States. Approximately half of glioma cases present as an aggressive type of astrocytoma known as glioblastoma multiforme (GBM). Due to its location and diffuse morphology, GBM has only a 30% two-year survival rate and additional treatment strategies are needed. Clinical trials for GBM personalized neoantigen vaccines have recently reported neoantigen-specific T cell responses, but treatment efficacy remains low. We posit that this may be due to GBM's high molecular heterogeneity, which could complicate the identification of clonal neoantigens for vaccine design. To address this topic, we performed whole-exome sequencing (WES) and RNA-seq on 30 human brain tumors. This cohort contains 21 primary/recurrent GBMs and 19 brain metastases derived from breast cancer, non-small cell lung cancer, or melanoma. We integrated variant calls, RNA expression, and HLA typing data for input into pVACtools, a suite of tools for neoantigen prediction, to obtain candidate neoantigen sequences with IC50 &amp;lt; 500nM. Mutation and neoantigen burden varied widely between the two tumor types. The range of variant counts for GBM samples is 7-169 (median 81), while the brain metastases have a range of 158-1317 (median 274.5). In addition, the former's class I and II neoantigen counts range from 1-312 (median 14), while the latter's range from 3-1159 (median 23.5). The percentage of variants that created neoantigens per sample ranged from 0.0-54.0% (median 7.1%). These counts exclude a recurrent GBM with two distinct hypermutated subclones that contain missense mutations in MSH6, a canonical DNA damage repair gene. By comparing intratumoral heterogeneity levels, we found that GBM patients had a lower proportion of clonal variants and neoantigens than tumors that had metastasized to the brain. In addition, the proportion of variants and neoantigens missed by single sector sequencing was significantly higher in GBM compared to brain metastases, indicating substantial heterogeneity in this tumor type. Variation in immune cell infiltrate was assessed using transcriptome data, and while many tumors demonstrated cellular heterogeneity, there was no clear correlation between this metric and tumor type. We are performing TCR sequencing to further investigate the immune landscape heterogeneity by determining TCR clonality diversity per region. Overall, this analysis demonstrates that GBM contains cellular and molecular heterogeneity, which can complicate clonal neoantigen selection. Multi-sample sequencing as a standard for GBM genomic analysis could alleviate these inconsistencies to improve neoantigen vaccine design and increase treatment efficacy. Citation Format: Megan M. Richters, Maximilian Schaettler, Zach L. Skidmore, Cody A. Ramirez, Matthew C. Mosior, Obi L. Griffith, Malachi Griffith, Gavin P. Dunn. Molecular heterogeneity in glioblastoma multiforme influences variant clonality and neoantigen prediction accuracy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4727.

Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients.

Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.40[0.26-0.55] μg/ml. Low muscle mass as defined by a lean tissue index (LTI) < 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes.

Analysis of treatment outcomes in patients with progressive locally advanced non-resectable and disseminated medullary thyroid cancer receiving vandetanib outside of clinical trials (Russian experience)

The study objective is to perform retrospective analysis of the efficacy and safety of vandetanib for metastatic and non-resectable medullary thyroid cancer in routine clinical practice. Materials and methods. We analyzed treatment outcomes in 46 patients treated with vandetanib. We also evaluated progression-free survival, overall survival, time to progression, and frequency of adverse events. Results. At a median follow-up time of 27.4 months (range: 2.5–106.5 months) and median duration of vandetanib therapy of 21 months, disease progression was registered in 32.6 % of cases, whereas stable disease was observed in 28.3 % of cases and 8.7 % of study participants demonstrated partial response. One patient had complete response to treatment. Almost one-third of patients (28.2 %) died, including 2 individuals whose death was not associated with cancer. The one-year and three-year progression-free survival rates were 67.3 % and 33.3 %, respectively; the two-year and five-year overall survival rates were 82.4 % and 29.4 %, respectively. The efficacy of therapy was confirmed by a 79.4 % decrease in the serum level of calcitonin after treatment initiation. Side effects were observed in 33.9 % of patients (primarily skin and gastrointestinal toxic reactions) and were easily managed in most of the cases. Eight individuals (17.4 %) required cessation of vandetanib due to adverse events. Conclusion. Our findings suggest high efficacy and acceptable safety profile of vandetanib in the treatment of progressive locally advanced non-resectable and disseminated medullary thyroid cancer

Characteristics of MR Imaging for Staging and Survival Analysis of Neuroendocrine Carcinoma of the Endometrium: A Multicenter Study in Japan.

Purpose:This study aimed to examine MRI features and staging of neuroendocrine carcinoma (NEC) of the endometrium and evaluate survival.Methods:Clinical data, pathological, and preoperative pelvic MRI findings in 22 patients with histologically surgery-proven endometrial NEC were retrospectively reviewed. Tumors were pure NEC (n = 10) or mixed histotype (n = 12), with 13 large and nine small cell type.Results:International Federation of Gynecology and Obstetrics (FIGO) staging was I, II, III, and IV in 6, 2, 12, and 2 patients, respectively. In 13 (76.4%) of 17 patients with pathological deep myometrial invasion, MRI showed abnormal diffusely infiltrative high T2 signal intensity throughout the myometrium with loss of normal uterine architecture. All tumors had restricted diffusion (apparent diffusion coefficient map low signal intensity, diffusion weighted imaging high signal intensity). Accuracy of T staging by MRI for all cases was 81.8%, with reference to pathology staging, while patient-based sensitivity, specificity, and accuracy for detecting metastatic pelvic lymph nodes was 60.0%, 100%, and 77.8%, respectively. Two intrapelvic peritoneal dissemination cases were detected by MRI. During follow-up (mean 30.4, range 3.3–138.4 months), 16 patients (72.7%) experienced recurrence and 12 (54.5%) died of disease. Two-year disease-free and overall survival rates for FIGO I, II, III, and IV were 66.7% and 83.3%, 50% and 100%, 10% and 33.3%, and 0% and 0%, respectively.Conclusion:Abnormal diffusely infiltrative high T2 signal intensity throughout the myometrium with normal uterine architecture loss and obvious restricted diffusion throughout the tumor are suggestive features of endometrial NEC. Pelvic MRI is reliable for intrapelvic staging of affected patients.

Comparison of minimally invasive versus open surgery in the treatment of endometrial carcinosarcoma

ObjectiveThe aim of this study was to compare perioperative and oncologic outcomes between minimally invasive and open surgery in the treatment of endometrial carcinosarcoma.MethodsWe retrospectively identified all patients with newly...

Surgical Treatment of Lung Cancer: How Has the Introduction of the 8th Edition of the TNM Classification Affected Guideline-Based Therapy?

The 8th edition of the TNM classification combined with the latest update of the S3-guideline (by AWMF/Scientific Medical Societies in Germany) on prevention, diagnosis, therapy and follow-up of lung cancer led to several changes in staging and treatment of lung cancer. The aim of this study was to identify differences in the distribution of patients due to changes from the 7th to the 8th edition that affected staging. The influence on surgical therapy will be discussed by using the recommendations of the latest S3 guideline. Prospective analysis of all primary cases at two thoracic surgical centres in the year 2016 and follow-up in March 2019. Comparison of the 7th edition of tumour classification for lung cancer with the 8th edition, focused on changes in tumour staging and its effects on the appropriate surgical therapy according to the latest S3 guideline. A total of 432 primary cases comprised the study population. According to the 8th edition, 82 patients (7th edition: n = 85) in stage I, 43 (n = 49) patients in stage II, 100 (n = 91) patients in stage III and 207 (n = 207) patients are assigned to stage IV. 81 changes (18.7%) were detected (77 upgrades vs. 4 downgrades). 63 patients (14.6%) exhibited a different graduation within the stages. 18 patients (4.1%) were classified in different tumour stages. As a result, fewer patients (n = 12; 2.8%) should have surgery according to the latest S3 guidelines. 290 patients (67.1%) were classified to new subgroups (IA1-3, IIIC and IVA/B). Two-year survival was significantly higher in IVA (25.2%) vs. IVB (13.0%) patients (p < 0.05). The 8th edition of the TNM-classification affords a higher level of differentiation. In this study, the new TNM classification led to a shift in the distribution, with a tendency to increase the tumour stage. This is mainly caused by changes in the T-descriptor and stage grouping. As a result, fewer patients in stage I - IIIA should have surgery according to the latest S3 guidelines. A significantly higher two-year survival rate was detected in stage IVA (M1a and M1b) compared to IVB and justifies the new differentiation due to the metastatic pattern.

The Clinical Value of PNI in Assessing the Prognosis of Small Cell Lung Cancer

To evaluate the clinical value of prognostic nutritional index (PNI) in assessing the prognosis of small cell lung cancer (SCLC) patients. The clinical data of SCLC patients who were initial diagnosed by pathology and conformed to the conditions of this study from January 2017 to January 2018 were retrospectively collected. The PNI values were calculated and divided into high PNI and low PNI groups according to the median value. The potential prognostic factors for SCLC patients were analyzed. One hundred and five patients were divided into high-PNI and low-PNI groups according to the PNI median (48.68). The median survival time was 25.1 months and 14.2 months respectively. The one-year survival rates were 82.5% and 65.3% respectively and the two-year survival rates were 49.7% and 28.4% respectively, the differences were all statistically significant ( P<0.05). Univariate analysis showed that gender, ECOG PS score, clinical stage and PNI were correlated with overall survival (OS) ( P<0.05). Multivariate analysis showed that PNI (odds ratio ( OR)=0.331，95% confidence interval: 0.189-0.580) and gender ( OR=1.897，95% confidence interval: 1.051-3.423) were independent prognostic factors for SCLC patients. Low PNI patients generally symbolize poor prognosis, PNI calculation is simple and easy to obtain, worthy of clinical promotion.

The significance of immune-regulatory molecule B7-H4 in small cell lung cancer.

B7-H4, a member of the B7 family, is detected in various cancers and is closely related to tumor development and prognosis. However, little is known about the clinical value of B7-H4 in small cell lung cancer (SCLC). Immunohistochemical analysis was carried out on 103 SCLC specimens. The relationship between B7-H4 staining and the major clinical parameters of SCLC was analyzed, and the two-year survival rates were investigated by chi-square test. Only 5.83% of the SCLC specimens tested positive for B7-H4. B7-H4 was detected on the membrane and in the cytoplasm of tumor cells. In contrast, B7-H4 expression was not detected in normal lung tissue samples. B7-H4 was not found to be associated with major clinical parameters, such as tumor size, gender, age, smoking status, limited/extensive stage, tumor node metastasis, Karnofsky Performance Status, lymph node metastasis status, distant metastasis, or ki-67. Moreover, no obvious differences were observed in the two-year survival rates of B7-H4 positive or B7-H4-negative SCLC patients. There is no correlation between B7-H4 expression and the proliferation or progression of SCLC. Therefore, B7-H4 is not a useful biomarker for SCLC prognosis.

The value of intravoxel incoherent motion imaging in predicting the survival of patients with astrocytoma.

The evaluation of the prognosis of gliomas may have great value in individualized treatment. To evaluate the value of intravoxel incoherent motion (IVIM) in predicting the survival of patients with astrocytoma and comparing it to apparent diffusion coefficients (ADC). Sixty patients with pathologically confirmed cerebral astrocytomas underwent IVIM scans before any treatment was performed. Patients were divided into death group and survival group according to a two-year follow-up. ADC and quantitative parameters of IVIM including D, D*, and f were measured. Independent sample t test was used to compare the two groups of parameters. The accuracy of each parameter for two-year survival rate was analyzed by receiver operating characteristic (ROC) curve and Kaplan-Meier survival curves. The correlation between quantitative parameters and survival days was analyzed by Pearson correlation analysis. The ADC, D*, and f values were statistically significant different between the death and the survival groups (P < 0.05). The AUC of the ADC, D*, and f were 0.811, 0.858, and 0.892, respectively. The ADC cut-off value of 0.668 × 10-3 mm2/s corresponded to 82.6% sensitivity and 73% specificity. The D* cut-off value of 3.913 × 10-3 mm2/s corresponded to 78.4% sensitivity and 87% specificity. The f cut-off value of 0.487 corresponded to 83.8% sensitivity and 87% specificity. Significant log rank test was performed for each parameter to predict overall survival (P < 0.05). There was a correlation between ADC (r = 0.625, P = 0.023), D* (r = -0.655, P = 0.012), f (r = -0.725, P = 0.000) and survival days. The D* and f values demonstrated great potential in predicting the two-year survival rate for patients with astrocytoma.

8th Edition Tumor, Node, and Metastasis T-Stage Prognosis Discrepancies: Solid Component Diameter Predicts Prognosis Better than Invasive Component Diameter.

The biggest change in the 8th edition of the tumor, lymph node, and metastasis (TNM) classification is the recommendation of the solid component diameter and invasive size for determining the clinical and pathological T-factor, respectively. Here, we validated new proposals for the Lung Cancer TNM classification’s revision and compared clinical and pathological T-stages. We retrospectively analyzed 177 cases of non-small cell lung cancers without lymph node metastasis, and involving complete resection, that occurred in our department between January 2017 and March 2019. We reviewed the overall tumor diameter, solid component diameter, and clinical T-factor on computed tomography (CT), and the pathological tumor diameter, pathological invasion diameter, pathological T-factor, and prognosis. The difference between the pathological invasive size and solid size on CT was within 5 mm in 99 cases (56%). At a two-year recurrence-free survival rate, the clinical T-stage demonstrated a better prognostic outcome than the pathological T-stage. Despite including the benign findings, the solid component diameter was better correlated with prognosis than the invasive size. Therefore, in cases of discrepancies of clinically and pathologically detected tumor size, the solid CT size should also be used for the pathological T classification.