Significant Factors For Overall Survival Research Articles

A Multi-Institutional Retrospective Study of Repeated Stereotactic Body Radiation Therapy for Intrahepatic Recurrent Hepatocellular Carcinoma

Through this multi-institutional study, we aimed to retrospectively evaluate the safety and efficacy of repeated stereotactic body radiation therapy (SBRT) for intrahepatic recurrent hepatocellular carcinoma (HCC). Between 2005 and 2017, 709 patients with 835 HCCs underwent SBRT; those treated with repeated SBRT were eligible. The median prescribed dose was 40 Gy in 5 fractions. Eighty-one patients with 189 tumors underwent repeated SBRT (≥ 2 courses [median 2 times; range, 2-5 times]). The median follow-up periods from the first to the second SBRT were 41.5 (range, 12-99) and 20 (range, 1-81) months, respectively. The median interval between the first and second SBRT was 18 (range, 3-74) months. The 5-year local recurrence rate was 6.3% (95% confidence interval [CI], 2.3%-13.4%). The 5-year overall survival (OS) and liver-related death rates from the first SBRT were 60.4% (95% CI, 47.0%-73.8%) and 32.9% (95% CI, 20.3%-46.0%), respectively, and the 3-year rates from the second SBRT were 61.0% (95% CI, 49.9%-75.2%) and 34.5% (95% CI, 20.6%-48.9%), respectively. The frequency of grade 3 toxicity was not significantly different between the first and second SBRT (first: 11% [95% CI, 5.2%-20%]; second: 15% [95% CI, 7.9%-24%]; P = .48). Among 39 patients with no intrahepatic recurrence for 1 year after the first and second SBRT, the deterioration in liver function after the first and second SBRT was not significantly different; the albumin-bilirubin score increased 1 year after the first versus second SBRT (first, 0.143 ± 0.23; second, 0.195 ± 0.38; P = .48). Multivariate analysis revealed that the intrahepatic recurrence-free interval was the only significant factor for OS. Repeated SBRT for intrahepatic recurrent HCC resulted in high local control with safety and a satisfactory OS comparable with that of other curative local treatments for patients with well-preserved liver function.

Impact of sarcopenia on survival of pancreatic cancer patients treated with concurrent chemoradiotherapy.

To investigate the prognostic impact of sarcopenia on the survival of patients with locally advanced pancreatic cancer (LAPC) treated with concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 299 patients diagnosed with LAPC and treated with definitive CCRT from 2000 to 2015. Skeletal muscle index (SMI) was measured using computed tomography scans and sarcopenia was defined as SMI <29.6 cm2/m2 for women and <36.2 cm2/m2 for men. The significance of sarcopenia for progression-free survival (PFS) and overall survival (OS) was evaluated. Sarcopenia was present in 29 patients (9.7%). In multivariate analysis, sarcopenia was a significant factor for PFS (p = 0.043). Although sarcopenia was not a significant factor for OS (p = 0.121) in multivariate analysis, long-term survivors were observed only in the no sarcopenia group (OS at 60 months: 9.5% vs 0%, p < 0.001). In patients undergoing CCRT for LAPC, sarcopenia is an independent factor for adverse prognosis.

Geriatric nutritional risk index as a useful prognostic factor in second allogeneic hematopoietic stem cell transplantation.

Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2years after second allo-HSCT: 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2years after second allo-HSCT decreased according to the score: 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P < 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.

Prognostic Determinants Analysis and Nomogram for Bone Malignant Vascular Tumors: A Surveillance, Epidemiology and End Results (SEER) Analysis.

BackgroundThe aim and objective of our investigations were to explore the prognostic value of various clinical and pathological factors of bone malignant vascular tumors and establish a nomogram for their outcome predictions.Material/MethodsAll data of primary bone malignant vascular tumors (MVTs) patients were randomly selected from the Surveillance, Epidemiology and End Results (SEER) database. However, selected patients were clinically diagnosed with various cancers during 1988–2015. The potential prognostic factors were analyzed using SPSS (Windows, version 22.0). All prognostic factors were combined to formulate a nomogram to predict the overall survival (OS).ResultsA total of 266 selected patients were included in our study. In the univariate model, age (P<0.001), sex (p=0.0255), primary site (P<0.001), surgery (P<0.001), histologic type (P<0.001), metastasis (p=0.000), and pathological grade (P<0.001) were statistically significant for patient survival. The results of Cox analysis revealed that age (≥64) HR: 3.636, 95% CI [1.955–6.762], p=0.000, the primary site in skull HR: 2.6, 95% CI [1.584–4.268], p<0.001], without surgery HR: 1.473 95% CI [1.239–1.751], p<0.001, metastasis HR: 3.076 95% CI [1.983–4.771] p=0.000, man HR 1.802, 95% CI [1.032–3.004], p=0.045, and high malignant grade HR: 3.029, 95% CI [2.101–4.366], p=0.003 were independent unfavorable prognostic factors. Angiosarcoma had highest mortality rate among all vascular malignancies. The nomogram predicting overall survival achieved a C-index of 0.694 (95% CI 0.631, 0.745) in the SEER cohort.ConclusionsSurgery can significantly increase OS survival time for bone MVTs, and low-grade malignancy is a significant factor for OS. However, advanced age, tumor metastasis, primary site in skull, AS, and male sex are predictors of poor prognosis.

Risk factors for survival of head and neck soft tissue sarcomas: A comparison between 7th and 8th edition AJCC staging systems.

Soft tissue sarcomas of the head and neck (HNSTS) show various histological types and clinical behaviour. Recently, the 8th edition of the American Joint Committee on Cancer (AJCC) proposed a staging system for HNSTS independent of other body soft tissue sarcomas, which requires validation. Therefore, we evaluated the prognostic factors for the survival of HNSTS patients through a comparison between previous and current AJCC staging systems. This study involved 135 consecutive HNSTS patients who underwent primary surgery, chemoradiotherapy or chemotherapy. Patients were grouped into staged (S) and not staged (NS) cancer according to the AJCC 8th edition staging. Cox proportional-hazard regression analyses were used to identify factors associated with overall survival (OS), and progression-free survival (PFS) in all, S or NS patients. Median follow-up period was 75months and the 5-year OS and PFS rates of all patients were 67.8% and 53.4%, respectively, which was similar between S and NS groups. Age, tumour size and grade, overall stage (7th edition) and resection margin were the significant prognostic factors for OS and PFS in all patients and NS group (all P<0.05), whereas positive resection margin was the only significant factor for OS and PFS in the S group (P<0.001). While OS was poorly discriminated among different 8th edition T-categories, different 7th edition showed good discrimination among overall stages in all patients and the NS group. The revised staging system may not provide an improved risk stratification for survival of HNSTS patients.

Long-term outcomes of upfront surgery in patients with resectable pathological N2 non-small-cell lung cancer.

Although the standard treatment for pathological N2 (pN2) non-small-cell lung cancer (NSCLC) patients is definitive chemoradiation, surgery can be beneficial for resectable pN2 disease. Herein, we report the long-term clinical outcomes of upfront surgery followed by adjuvant treatment for selected patients with resectable pN2 disease. We performed a retrospective analysis of clinical outcomes for patients with pN2 disease who underwent surgery as the first-line therapy. Multivariable Cox regression analysis was used to identify the significant factors for overall survival (OS) and recurrence-free survival. From 2004 to 2015, a total of 706 patients with pN2 NSCLC underwent complete anatomical resection at our institution. The patients' clinical N stages were cN0, 308 (43.6%); cN1, 123 (17.4%) and cN2, 275 (39.0%). Adjuvant chemotherapy, radiotherapy and chemoradiotherapy were administered to 169 (23.9%), 115 (17.4%) and 299 patients (42.4%), respectively. With a median follow-up of 40 months, the respective median time and 5-year rate of OS were 52 months and 44.7%. According to subdivided pN2 descriptors, the median OS time was 80, 53 and 37 months for patients with pN2a1, pN2a2 and pN2b, respectively. Adjuvant chemotherapy was a significant prognostic factor for both OS [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.28-0.52; P < 0.001] and recurrence-free survival (HR 0.42, 95% CI 0.30-0.58; P < 0.001). Upfront surgery followed by adjuvant therapy for resectable N2 disease showed favourable outcomes compared to those reported in previous studies. Adjuvant chemotherapy is essential to improve the prognosis for patients undergoing upfront surgery for N2 disease.

Paclitaxel for treatment of advanced small cell lung cancer (SCLC): a retrospective study of 185 patients.

BackgroundEtoposide-/platinum-based chemotherapy is the standard first-line treatment for extensive-disease small cell lung cancer (SCLC), but responses are short-lived and subsequent options limited. Here, we present our experience with paclitaxel in advanced treatment lines.MethodsWe retrospectively studied the clinical course of all paclitaxel-treated SCLC patients between 2005 and 2015 in our institution. Prognostic and predictive factors were analyzed by Kaplan-Meier and Cox regression analyses.ResultsA total of 185 patients [119 men, median age 65 years, median ECOG performance status (PS) 1] were identified. One hundred and sixty-eight patients had extensive disease (ED) at the time of paclitaxel therapy. Paclitaxel was mainly given as third- or fourth-line therapy (93%). The response rate (RR) was 17% and disease control rate (DCR) 28%. Patients reached a median progression-free survival (PFS) of 1.6 (95% CI: 1.4–1.8) months and median overall survival (OS) of 3.3 (95% CI: 2.8–3.9) months. Main toxicities were fatigue (25%) and polyneuropathy (17%). Dose reduction of ≥25% was associated with shorter PFS [1.9 (95% CI: 1.5–2.3) vs. 1.4 (95% CI: 1.3–1.5) months; P=0.004]. Further independent predictive factors for PFS were gender, age, and hepatic/brain metastases (P<0.05). Tumor response to paclitaxel, PS, number and location of metastases, dose reduction, and smoking history were significant factors for OS in univariable analyses (P<0.05), while PS, dose reduction, status of cerebral/hepatic metastases, tumor response, and smoking history were retained as independent prognostic factors in multivariable testing. Notably, ECOG PS 2 patients had toxicity rates similar to ECOG PS 0–1 patients (63% vs. 62%), as well as a comparable DCR (29% vs. 28%), which was associated with prolonged survival (4.5 vs. 3.2 months for refractory cases, P=0.034).ConclusionsPaclitaxel has clinically relevant activity in heavily pretreated SCLC. While patients with good PS and no cerebral/hepatic metastases derive the greatest benefit, ECOG PS 2 per se should not be used as a criterion to exclude patients.

Improved Outcomes after Allogenic Hematopoietic Stem Cell Transplantation with Fludarabine/Treosulfan for Patients with Myelodysplastic Syndromes.

While allogeneic hematopoietic stem cell transplantation (allo-HCT) currently offers the only curative option for patients with myelodysplastic syndrome (MDS), there is still a high risk of relapse or transplant-related complications. We collected data on all patients who had undergone allo-HCT at our center (Copenhagen University Hospital) between 2000 and 2018. In total, 215 patients with MDS (n=196) or chronic myelomonocytic leukemia (n=19) were included. Estimated 1-year overall survival (OS) was 70.3% (95% confidence interval [CI], 64.2% to 77.0%), and the median survival was 7.7 years (95% CI, 4.7 to indeterminable). There was a significant improvement in OS over time (P=.011, comparing 2000 to 2010, 2010 to 2014, and 2014 to 2018). Treatment was standardized throughout the study period, allowing comparison between patients receiving nonmyeloablative (NMA, n=124), standard myeloablative (SMA, n=36), and fludarabine and treosulfan (FluTreo, n=55) conditioning. FluTreo has myeloablative properties but lower toxicity and replaced standard myeloablative conditioning at our center in 2014. The FluTreo group was significantly older and had more comorbidities than the SMA group but similar disease severity. One-year OS was 84.0% (95% CI, 74.3% to 94.9%), 58.3% (95% CI, 44.3% to 76.9%), and 68.3% (95% CI, 60.2% to 77.5%) for FluTreo, SMA, and NMA, respectively (P=.04). In univariate analysis, Revised International Scoring System (IPSS-R) (high versus low), donor sex mismatch, and cytomegalovirus status mismatch were significant factors for OS. In multivariate analysis of OS including age, IPSS-R, and HCT specific comorbidity index, NMA was borderline inferior to FluTreo (P=.073) while SMA was significantly inferior to FluTreo with a hazard ratio of 6.89 (95% CI, 2.53 to 18.77, P < .001). The introduction of FluTreo allowed us to administer a myeloablative regimen to a broader patient group and shows promising results.

Clinical outcomes of stereotactic body radiation therapy for small hepatocellular carcinoma.

The purpose of this study was to investigate the long-term oncologic outcomes after stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC). A total of 290 patients with HCC were registered between March 2007 and July 2013. A dose of 10-15Gy per fraction was given over three to four consecutive days, resulting in a total dose of 30-60Gy. Overall and recurrence-free survivals were estimated from the date of the start of SBRT to the date of death, the last follow-up examination, or to the date of tumor recurrence. The median follow-up period of all patients was 38.2months, and the median tumor size was 1.7cm. Overall survival (OS) rate at 5years was 44.9%. Multivariate analyses revealed that age, Child-Pugh class, tumor size, and albumin levels were significant factors for OS. The 5-year local control rate was 91.3%. In multivariate analysis, tumor size and albumin were significantly associated with local tumor control. However, there was a negative correlation between total dose and tumor size in Pearson's correlation analysis (r=-0.111, P=0.046). Stereotactic body radiation therapy was an excellent ablative treatment option for patients with small HCC. Tumor size was a significant factor for local tumor control after SBRT, although the total dose was negatively correlated with tumor size. Considering the low OS rates and the high local tumor control rates, the combined SBRT and systemic therapies may be beneficial for improving survival outcomes.

Comorbidity assessment to determine prognosis in older adult patients with classical Hodgkin lymphoma.

The clinical management of older adult patients with Hodgkin lymphoma (HL) remains a major challenge. The aim of this study was to evaluate the impact of comorbidity assessment according to a standardized approach, the Cumulative Illness Rating Scale (CIRS), on prognosis in patients with classical HL aged 60 years and older. We studied 76 consecutive older adult patients with HL (median age 69 y, range 60-84) who had been treated in our institution between 1999 and 2018. Comorbidity was assessed at diagnosis according to CIRS. Anthracycline-containing chemotherapy with curative intent was administered in 59 (78%) patients. We identified 41 (54%) patients with at least one severe comorbidity rated on CIRS grade ≥ 3. Patients with severe comorbidity were more likely to have advanced-stage disease (P = .003), to have an International Prognostic Score (IPS) > 3 (P = .03), and to not receive anthracycline-containing chemotherapy (P = .008). The probability of overall survival (OS) at 3 years was 88% (95% CI, 71%-95%) in patients without severe comorbidities, while it was only 46% (95% CI, 29%-62%) in patients with a comorbidity CIRS grade ≥ 3 (P = .0001). The impact of comorbidity on prognosis was also evident when restricting the analysis to patients treated with anthracycline-containing therapy. The 3-year OS was 93% (95% CI, 76%-98%) (P = .004) in patients without severe comorbidity and 72% (95% CI, 47%-87%) in patients with severe comorbidity (P = .004). In a multivariate analysis, presence of comorbidity, but not age, was a significant factor for OS. Therefore, we conclude that a significant proportion of older adult patients with HL has severe comorbidity on the CIRS scale, which impacts more importantly than age on prognosis.

The prognostic value of multidetector CT features in predicting overall survival outcomes in patients with pancreatic neuroendocrine tumors

PurposeTo assess the prognostic value of multidetector CT in predicting overall survival outcomes in patients with pancreatic neuroendocrine tumors (PNETs). MethodSeventy-one patients pathologically diagnosed with PNETs were retrospectively included. The clinical and imaging information was evaluated by two radiologists. The difference between well-differentiated and poorly differentiated PNETs was analyzed. Cox proportional hazards models were created to determine the risk factors for overall survival. Kaplan-Meier survival analyses with log-rank tests were used among different subgroups of patients with PNETs. ResultsIn the whole cohort, the median survival was 36 months, and the 5-year survival rate was 84.8 %. Patients with poorly differentiated PNETs were more likely to present with symptoms, abnormal tumor markers, larger diameters, irregular shapes, ill-defined margins, invasion into nearby tissues, liver and lymph node metastases, and lower enhancement ratio than those with well-differentiated PNETs (P < 0.05). In the multivariate analysis, lymph node metastases (hazard ratio: 21.52, P = 0.009) and a portal enhancement ratio less than 1.02 (hazard ratio: 30.89, P = 0.024) were significant factors for overall survival. Overall survival decreased with an ill-defined margin, irregular shape, poor differentiation, grade 3 disease, nonfunctional status, abnormal tumor marker levels, invasion into nearby tissues, lymph node and liver metastases, and lower enhancement ratio (log-rank P < 0.05). ConclusionsPoorly differentiated PNETs were more aggressiveness than well-differentiated PNETs. Lymph node metastases and a portal enhancement ratio < 1.02 were independent prognostic factors for worse overall survival outcomes in patients with PNETs.

US-guided percutanous microwave ablation for early-stage hepatocellular carcinoma in elderly patients is as effective as in younger patients: A 10-year experience.

To compare the overall survival (OS), disease-free survival (DFS) and liver-cancer-specific survival (LCSS) of elderly (≥65 years) and younger patients (< 65 years) with early-stage hepatocellular carcinoma (HCC) using ultrasound-guided percutaneous microwave ablation (US-PMMA). From January 2002 to December 2017, 510 elderly and 1053 younger patients were diagnosed with early-stage HCC according to the Milan criteria. All of these patients were treatment-naïve to US-PMMA. Baseline characteristics were collected to identify any risk factors to determine the survival outcomes. OS, DFS, and LCSS probabilities were calculated with the Kaplan-Meier method and compared using the Log-rank test. Complete ablation was achieved in all patients. Elderly patients were more likely to be, hepatitis C virus infection, comorbidities, cirrhosis, larger tumors, poor liver functional reservation, more ablation points, longer ablation time, longer hospital stays, and higher hospitalization costs (P < 0.05). Over the follow-up period (12-156 months), no significant differences were detected in OS, DFS, and LCSS between the two groups ( P = 0.092, 0.318, and 0.183). r-GT, ALB and ablation session were significant factors for OS, r-GT and ALB for LCSS, and cirrhosis, tumor number, AFP and ablation points for RFS in the multivariate analysis, respectively. No treatment-related deaths occurred in the two groups. Any complications were treated as appropriate. Although advanced age and comorbidities are intrinsic factors in elderly HCC patients, similar survival outcomes were obtained in elderly and younger HCC patients treated by US-PMWA, despite elderly patients having more comorbidities.

Comprehensive Study of Surgical Treated Lung Adenocarcinoma with Ground Glass Nodule Component.

BackgroundMore and more patients with lung adenocarcinoma were detected with ground glass nodule (GGN) due to the popularity of low-dose spiral computed tomography (LDCT) recently. The clinicopathological characteristics and epidermal growth factor receptor (EGFR) mutation features were unclear.Material/MethodsThis retrospective study enrolled patients with surgical resected primary lung adenocarcinomas with GGN component. The clinicopathological data included age, gender, smoking history, tumor staging, lymph node staging, surgical methods, subtypes, thyroid transcription factor-1 (TTF-1) expression, EGFR gene mutation and follow-up records were investigated.ResultsThere were 338 lung adenocarcinoma patients with GGN component eligible for our analysis: 219 patients (64.8%) harbored the EGFR mutation. In addition, the EGFR mutation rate was higher in patients with TTF-1+ than in patients with TTF-1− (72 out of 108 patients, 66.7% versus 147 out of 231 patients, 63.6%). In multivariable analysis, surgical procedure, tumor size, nodal stage, and subtype were still significant factors for relapse-free survival (RFS) while only subtype acted as the significant factor for overall survival (OS). In subgroup analyses, patients with TTF-1- had better prognosis in RFS (log-rank P=0.0142) when compared with those with TTF-1+ but not in OS (log-rank P=0.1113). Furthermore, patients with high-risk subtype had worse outcomes than those with low-risk subtype (RFS: log-rank P<0.0001; OS: log-rank P<0.0001). Patients who underwent limited resection experienced high risk of relapse (log-rank P<0.0001) while there was no statistical significance in OS (log-rank P=0.1644) between patients underwent lobectomy and those underwent limited resection.ConclusionsThe prognosis of lung adenocarcinomas with GGN component depends mainly on the pathological subtype and there is no significant correlation between EGFR mutation and prognosis. Lobectomy should be performed actively in patients whose preoperative puncture biopsy or intraoperative freezing indicates an invasive or worse subtype. For postoperative patients, we should consider follow-up more frequently.

Indication for and Effect of Adjuvant Chemotherapy for Stage IIa (T3N0M0) Colon Cancer.

PurposeThe efficacy of adjuvant chemotherapy (AC) in stage IIa colon cancer is controversial. This study aimed to investigate the factors influencing survival in patients with stage IIa colon cancer, the role of AC, and the indications for AC utilization by surgical oncologists.MethodsBetween January 2004 and December 2010, 736 patients with stage IIa colon cancer underwent curative resection in 1 of 6 participating hospitals. Factors related to survival were identified and analyzed according to whether AC was administered or not. After high- and low-risk groups were identified, their respective results were analyzed.ResultsThe 5-year overall survival (OS) of stage IIa colon cancer was 90.3%. With the exception of poorly differentiated histology, indications for AC did not include typical high-risk factors. The indications for AC were significantly younger patients, higher body mass index (BMI), lower American Society of Anesthesiologists (ASA) physical status classification, and higher histologic grade. BMI, preoperative carcinoembryonic antigen, and harvested lymph node (LN) count were significant factors for disease-free survival, while BMI and ASA physical status classification were significant factors for OS in the chemotherapy group. In the high-risk group, AC was associated with increased OS in univariate analysis. BMI and harvested LN count were statistically significant in multivariate analysis.ConclusionSurgical oncologists consider the patient’s condition and postoperative course rather than high-risk factors to determine use of AC. Regardless of AC use, both the extent of surgery and the patient’s subsequent status affected the survival rate in the high-risk group. None of the factors identified influenced survival rate in the low-risk group.

Relevance of calcification and contrast enhancement pattern for molecular diagnosis and survival prediction of gliomas based on the 2016 World Health Organization Classification

ObjectivesThe significance of conventional neuroimaging features for predicting molecular diagnosis and patient survival based on the updated World Health Organization (WHO) classification remains uncertain. We assessed the relevance of neuroimaging features (ring enhancement [RE], non-ring enhancement [non-RE], overall gadolinium enhancement [GdE], and intratumoral calcification [IC]) for molecular diagnosis and survival in glioma patients. Patients and methodsWe evaluated 234 glioma patients according to the updated WHO classification. Isocitrate dehydrogenase (IDH), H3F3A, BRAF hotspot mutations, TERT promotor mutation, and chromosome 1p/19q co-deletion were examined. RE, non-RE, GdE, and IC were evaluated as significant neuroimaging findings. Kaplan-Meier analyses were performed to evaluate overall survival (OS) and the correlations of prognostic factors were evaluated by log-rank tests. Univariate and multivariate analyses were performed to detect prognostic factors for OS. ResultsA total of 207 patients were eligible. In 110 patients presenting RE, 102 (93%) were glioblastoma (GBM), IDH-wild type. In 97 patients without RE, presence of GdE or IC were not significantly different between IDH-mutant and -wild type tumors, whereas presence of GdE was a significant indicator of higher WHO grades. IC was the only significant finding for 1p/19q co-deleted tumors. TERT promoter mutation was observed in 7/17 patients with diffuse astrocytic glioma, IDH-wild type; recently-defined as “molecular GBM.” IC, RE, and GdE were observed with lower prevalence in molecular GBMs. While presence of RE, GdE, and absence of IC were significant factors of OS in overall cohort, presence of GdE was not significant in OS in cases without RE, and IDH-mutant tumors. IC was a significant predictor of favorable OS in cases without RE and IDH-wild type tumors. Multivariate analysis also validated these findings. ConclusionGdE alone is not a significant predictor of IDH mutation status, but the pattern of enhancement is a significant predictor with RE demonstrating high sensitivity and specificity for GBM, IDH-wild type. Predicting “molecular GBM” by conventional neuroimaging is difficult. Moreover, GdE is not a significant factor of survival analyzed with pattern of enhancement or molecular stratifications. IC is an important radiographic finding for predicting molecular diagnosis and survival in glioma patients.

Prognostic value of neutrophil-to-lymphocyte ratio in locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

PurposeThis study aimed to investigate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in patients with locally advanced non-small cell lung cancer (NSCLC) who received concurrent chemoradiotherapy (CCRT).Materials and MethodsWe retrospectively analyzed 66 patients with locally advanced NSCLC treated with definitive CCRT. Among these patients, 95% received paclitaxel/carboplatin or docetaxel/cisplatin. The median radiation dose was 66 Gy in 33 fractions. The NLR and PLR before/after CCRT were evaluated. The maximally selected log-rank test was used to obtain the cutoff values related to the overall survival (OS).ResultsPatients with high post-CCRT NLR (>3.12) showed worse OS, locoregional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS) than those with low NLR (2-year OS: 25.8% vs. 68.2%, p < 0.001; 2-year LRPFS: 12.9% vs. 33.8%, p = 0.010; 2-year DMFS: 22.6% vs. 38.2%, p = 0.030). Patients with high post-CCRT PLR (>141) showed worse OS and LRPFS than those with low PLR (2-year OS: 37.5% vs. 71.1%, p = 0.004; 2-year LRPFS: 16.5% vs. 40.3%, p = 0.040). Patients with high NLR change (>1.61) showed worse OS and LRPFS than those with low NLR change (2-year OS: 26.0% vs. 59.0%, p < 0.001; 2-year LRPFS: 6.8% vs. 31.8%, p = 0.004). The planning target volume (hazard ration [HR] = 2.05, p = 0.028) and NLR change (HR = 3.17, p = 0.025) were the significant factors for OS in the multivariate analysis.ConclusionNLR change after CCRT was associated with poor prognosis of survival in patients with locally advanced NSCLC. An elevated NLR after CCRT might be an indicator of an increased treatment failure risk.

Neoadjuvant Chemoradiotherapy and Surgery in Patients Older Than 75 Years Old with Locally Advanced Mid-Low Rectal Cancer

This study was designed to evaluate the tolerance and clinical outcomes of neoadjuvant chemoradiotherapy and surgery in patients older than 75 years old with LARC. We reviewed clinical records of patients older than 75 years with LARC treated with neoadjuvant chemoradiotherapy in our institute from January 2013 to May 2017. All patients were treated with intensity-modulated radiotherapy (IMRT). A dose of 45-50Gy in 25 fractions was delivered to the pelvis. The primary tumors received a dose of 55Gy with simultaneous integrated boost (SIB). The concurrent chemotherapy included capecitabine alone and capecitabine plus oxaliplatin (Xelox). Surgery was performed for suitable patients at least 6 weeks after chemoradiotherapy. Adjuvant chemotherapy was performed individualized. Overall survival (OS), disease specific survival (DSS), disease free survival (DFS) and local control (LC) were calculated with Kaplan-Meier method. Univariate and multivariate analyses were performed with log-rank test and cox proportional hazards model. A total of 71 patents were enrolled in this study, the median age was 80 years (range: 75-90 years). All patients completed the neoadjuvant treatment procedure. The median follow-up duration was 31.9 months (range: 4.7-65.1 months), the 3-year OS, DSS, DFS and LC were 75.7%, 86.0%, 72.4% and 83.9%, respectively. The incidences of grade 3 or greater acute hematologic (HM), gastrointestinal (GI) and genitourinary (GU) toxicity were 5.6%, 4.2% and 1.4%, respectively. After neoadjuvant chemoradiotherapy, downstaging was observed in 59 patients (83.1%) including 36 patients (50.7%) with T-downstaging and 48 patients (67.6%) with N-downstaging. Forty-three patients (60.6%) underwent surgery including total mesorectal excision (TME) in 35 patients (81.4%) and transanal endoscopic microsurgery (TEM) in eight patients (18.6%), only two patients (5.7%) experienced surgical complications. For patients receiving definitive surgery (TME), pathological complete response (pCR) was obtained in eight patients (22.9%). Multivariate analysis revealed that only surgery was significantly associated with OS, DSS, DFS, and LC. The 3-year OS, DSS, DFS and LC for patients who received surgery or not were 90.1% vs 48.4% (HR=27.0, 95%CI: 2.6-281.8, P=0.006), 90.1% vs 66.2% (HR=13.3, 95%CI: 1.2-148.8, P=0.036), 83.2% vs 50% (HR=3.0, 95%CI: 1.1-8.4, P=0.037) and 90.6% vs 58.3% (HR=3.8, 95%CI: 1.1-13.1, P=0.034), respectively. In patients with LARC older than 75 years old, neoadjuvant chemoradiotherapy was well tolerated with excellent clinical outcomes. Surgery was a significant factor for OS, DSS, DFS, and LC with acceptable complications, which should be strongly suggested for this group of patients.

Effective Dose to Lymphocytes Predicts Lymphopenia and May Predict Survival in Patients Treated with CROSS Regimen in Patients with Squamous Cell Carcinoma of Esophagus

We hypothesized that radiation induced lymphopenia can be predicted by the effective dose to the circulating immune cells (EDIC) which can be computed by modelling the doses of the total body, lung and heart in advanced squamous cell esophageal cancer treated with trimodality therapy according to the Dutch CROSS trial regimen. To test this hypothesis, we considered circulating immune cells as an organ at risk and examined the effect of EDIC on the degree of lymphocyte drop (lymphocyte nadir) . We further explored the relationship between EDIC, lymphocyte nadir and overall survival (OS) in this group of patients. Patients with advanced non-metastatic squamous esophageal carcinoma treated in one single tertiary cancer center from 2012-2018 were eligible for this study. All patients must have RT plan available for EDIC computation and received neoadjuvant chemoRT according to Dutch CROSS trial regimen (5 weeks of weekly carboplatin AUC=2 and paclitaxel 50mg/m2, radiation dose: 41.4 Gy in 23 fractions) before a radical esophagectomy. All had weekly blood test available during and 2 months after chemoRT. We made assumptions that circulating immune cells received uniform dose for rapidly circulating ones (in heart, lung, and blood vessels) and those slow circulating ones (in lymphatic system, veins, and capillaries) inside irradiated volume. The EDIC was calculated as a function to lung, heart and total body integral doses with a verified mathematical model. Association between EDIC and lymphocyte nadir was studied, and the relationships of OS with lymphocyte nadir and EDIC were assessed using multivariant Cox regression model. This analysis included 92 eligible consecutive patients with 77 males and 15 females. The median age was 65.5 years (range 40-82). There were 1, 84, and 7 patients with stage II, III, and IV diseases, respectively. The mean PTV was 529 cc (95% CI220.5-837.5). The baseline lymphocyte was normal in 79 (86%) patients, reduced in 13 (14%) patients. The mean EDIC was 2.8 Gy (range 0.6-4.4). EDIC was found to be highly correlated with lymphocyte nadir (Spearman coefficient -0.505 p< 0.01) which was found to significantly independently associated with shorter OS (HR =0.63 p<0.001). Lymphocyte nadir was also the most significant factor in determining OS among other clinical parameters. It remained significant after adjusting for clinically significant factors Age. Exploratory analysis showed there was significant OS difference between EDIC groups (<2Gy, 2-4Gy and >4Gy). The 2-year OS rates were 66.7%, 42.7% and 16.7% for EDIC <2Gy, 2-4Gy and >4Gy respectively. Radiation dose to circulating immune cells was significantly associated with survival and lymphocyte nadir which was also a significant factor for overall survival in patients with advanced non-metastatic squamous cell cancer of esophagus. The result may advise plan optimization and further prospective study is warranted.

The influence of adjuvant radiation therapy after endoscopic resection on survival for early stage EC: an analysis of the surveillance epidemiology and end results (SEER) database.

Endoscopic resection (ER) followed by radiation therapy (RT) is a treatment option for early stage esophageal cancer (EC). We used the surveillance epidemiology and end results (SEER) database to investigate the influence of adjuvant RT after ER on survival for early stage EC. The SEER database [1998-2013] was queried for locoregional cases of EC. Tumor staging was redefined with the 8th Edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control tumor-node-metastasis (TNM) staging system. The T1-2 stage EC cases in which ER were followed by radiation or observation were included. Kaplan-Meier methods were performed to compare overall survival (OS) and cancer-specific survival (CSS) between the patients who received radiation and those who did not. Subgroup analysis was made according to AJCC stage. A multivariate Cox proportional-hazards regression model was used to identify independent covariates which may influence survival. The median survival of the no-radiation group was significantly longer than that of the radiation group [74 vs. 31 months; hazard risk (HR), 2.39; 95% confidence interval (CI), 1.782-3.197; P<0.001]. In T1a stage subgroup, patients who did not receive RT had significantly better OS and CSS outcomes (OS: 90 vs. 31 months; HR, 2.90; 95% CI, 1.766-4.773; P<0.001; CSS: 105 vs. 48 months; HR, 5.40; 95% CI, 2.636-8.226; P<0.001). In the T1b and T2 subgroup analyses, both the OS and CSS were not significantly different between the radiation group and the no-radiation group (all P>0.05). In multivariate regression analysis, radiation was not a significant factor for OS and CSS after adjustment for confounding factors (P>0.05). Using SEER data, we revealed that RT after ER did not improve survival in early stage EC patients; specifically, RT did not benefit T1b and T2 patients and may lead to poorer survival in T1a patients. Our findings do not support the addition of RT after ER for early stage EC, especially T1a EC.

Efficacy and tolerability of adjuvant therapy in ≥70-year-old patients with T3N0M0 colorectal cancer: An observational study.

This study aimed to retrospectively investigate the efficacy and tolerability of adjuvant chemotherapy in ≥70-year-old patients with stage IIA (T3N0M0) colorectal cancer. Lymphovascular invasion, perineural invasion, margin positivity, dissected lymph node count of <12, and presence of perforation/obstruction were accepted as risk factors. Those patients with at least one risk factor were regarded as having high risk. The study included 168 patients, among which 95 (56.5%) were male and 73 (43.5%) were female. The median age of patients was 73 years (range: 70-94). One hundred one (60.1%) patients were identified to have high risk. Eighty-one (87%) patients received 5-flourouracil+leucovorin and 12 (13%) patients received capecitabine regimens as adjuvant chemotherapy. The patients receiving capecitabine regimen had significantly higher rates of dose reduction at initiation and during the treatment. Among low-risk group, there was no statistically significant difference between patients with and without adjuvant chemotherapy in terms of disease-free survival or overall survival (p = 0.528 and p = 0.217, respectively). In high-risk group, patients receiving adjuvant chemotherapy significantly differed from those not receiving adjuvant chemotherapy in terms of median disease-free survival and overall survival (p = 0.009 and p < 0.001, respectively). While the grade, lymph node status, and adjuvant chemotherapy were identified as the most significant independent factors for disease-free survival, the most significant factors for overall survival were the age, Eastern Cooperative Oncology Group performance status, adjuvant chemotherapy, and recurrence. The findings of our study showed improved disease-free survival and overall survival in high-risk ≥70-year-old patients who received adjuvant chemotherapy due to T3N0M0 colorectal cancer. We believe that 5-flourouracil+leucovorin or capecitabine regimens should be recommended for these older high-risk patients who could receive adjuvant chemotherapy regardless of age.