[Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy].

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

Apolipoprotein C1 promotes tumor progression in gastric cancer.

Background: Gastric cancer (GC) is a malignancy with the worst prognosis that seriously threatens human health, especially in East Asia. Apolipoprotein C1 (apoc1) belongs to the apolipoprotein family. In addition, apoc1 has been associated with various tumors. However, its role in GC remains unclear. Methods: Firstly, we quantified its expression in GC and adjacent tumor tissues, using The Cancer Genome Atlas (TCGA). Next, we assessed cell invasion and migration abilities. Finally, we revealed the role of apoc1 in the tumor microenvironment (TME), immune cell infiltration and drug sensitivity. Results: Firstly, in TCGA database, it has been shown that elevated expression of apoc1 was identified in various cancers, including GC, then we found that high expression of apoc1 was significantly correlated with poor prognosis in GC. Histologically, apoc1 expression is proportional to grade, cancer stage, and T stage. The experimental results showed that apoc1 promoted cell invasion and migration. Then GO, KEGG, and GSEA pathway analyses indicated that apoc1 may be involved in the WNT pathway and immune regulation. Furthermore, we found out the tumor-infiltrating immune cells related to apoc1 in the tumor microenvironment (TME) using TIMER. Finally, we investigated the correlation between apoc1 expression and drug sensitivity, PD-1 and CTLA-4 therapy. Conclusions: These results suggest that apoc1 participates in the evolution of GC, and may represent a potential target for detection and immunotherapy in GC.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase â ¡ trial].

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Proton pump inhibitor therapy and risk of knee replacement surgery: a general population-based cohort study.

OBJECTIVE: Proton pump inhibitors (PPIs) are among the most commonly used medications for patients with osteoarthritis (OA). Various types of PPIs have different impacts on lowering serum magnesium level that may affect knee OA progression. We aimed to compare the risk of clinically relevant endpoint of knee replacement (KR) among initiators of five different PPIs with that among histamine-2 receptor antagonist (H2RA) initiators. DESIGN: Among patients with knee OA (≥50 years) in The Health Improvement Network database in the UK we conducted five sequential propensity-score matched cohort studies to compare the risk of KR over 5-year among patients who initiated omeprazole (n = 2,672), pantoprazole (n = 664), lansoprazole (n = 3,747), rabeprazole (n = 751), or esomeprazole (n = 827) with those who initiated H2RA. RESULTS: The prevalence of PPI prescriptions among participants with knee OA increased from 12.7% in 2000-44.0% in 2017. Two-hundred-and-seventy-four KRs (30.8/1,000 person-years) occurred in omeprazole initiators and 230 KRs (25.4/1,000 person-years) in H2RA initiators. Compared with H2RA initiators, the risk of KR was 21% higher in omeprazole initiators (hazard ratio [HR] = 1.21,95% confidence interval [CI]:1.01-1.44). Similar results were observed when pantoprazole use was compared with H2RA use (HR = 1.38,95%CI:1.00-1.90). No such an increased risk of KR was observed among lansoprazole (HR = 1.06,95%CI:0.92-1.23), rabeprazole (HR = 0.97,95%CI:0.73-1.30), or esomeprazole (HR = 0.83,95%CI:0.60-1.15) initiators compared with that among H2RA initiators. CONCLUSIONS: In this population-based cohort study, initiation of omeprazole or pantoprazole use was associated with a higher risk of KR than initiation of H2RA use. This study raises concern regarding an unexpected risk of omeprazole and pantoprazole on accelerating OA progression.

[Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy].

Objective: To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment. Methods: A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained. Results: Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval (HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment (HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status (HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval (HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment (HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence (HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status (HR=1.69, 95% CI: 1.02-2.81), the recurrence interval (HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence (HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions: Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

[Comparison of preoperative chemotherapy with concurrent chemoradiotherapy combined with TME for 305 patients with locally advanced rectal cancer].

Objective: To retrospectively analyze the long-term efficacy and prognostic factors of preoperative chemotherapy (PCT) or chemoradiotherapy (PCRT) combined with total mesorectal excision in locally advanced rectal cancer. Methods: Clinical pathology data of 305 patients with localized advanced rectal cancer admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from 2006 to 2018 were collected, of whom 246 patients received PCRT (PCRT group), 59 patients received PCT (PCT group). Kaplan-Meier and Log rank test were used for the survival analysis, Cox regression model was used for multivariate analysis, and the prognosis of two groups of patients were compared by the propensity score matching (PSM). Results: In the whole group of 305 patients, 20 cases of tumors located in the upper part of the rectum and at the junction of rectum and colon, 96 cases in the middle of the rectum and 189 cases in the lower part of the rectum. PCRT group included 38 cases of cT2-3 phase, 11 cases of cT4a stage, 10 cases of cT4b stage, while the cases in PCT group were 184, 0 and 62 cases, respectively, the difference is statistically significant (P<0.05). The R0 excision rates of PCRT group and PCT group were 100% (246/246) and 96.6% (57/59), respectively, and the total pathological remission rates were 13.4% and 3.3%, respectively (P<0.05). After PSM, the 3-year survival rates of PCRT group and the PCT group were 86.6% and 89.9% (P>0.05), respectively, and the progression-free survival rates were 74.6% and 77.2% (P>0.05), local recurring free survival rates were 100% and 92.3% (P>0.05), distant metastasis free survival rate were 75.6% and 77.3% (P>0.05). Pre-treatment N-positive, N-degeneration and MRF-positive were all associated with total survival (P<0.05). Conclusion: In the PCRT group, with a higher proportion of patients with stage T4b and lower rectal cancer, the long-term efficacy of PCRT was similar to that of PCT, and higher R0 excision rate and pathological complete response rate could be obtained.

[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Does smoking cessation increase risk of knee replacement? a general population-based cohort study.

OBJECTIVE: Smoking represents a major issue for global public health. Owing to methodologic challenges, findings of an association between smoking and risk of knee osteoarthritis (OA) are inconsistent. We sought to assess the relation of onset of smoking cessation to the risk of OA sequelae, i.e., knee replacement, and to perform sub-cohort analysis according to weight change after smoking cessation. DESIGN: Using The Health Improvement Network, we conducted a cohort study to examine the association between smoking cessation and risk of knee replacement among patients with knee OA. Participants who stopped smoking were further grouped into three sub-cohorts: weight gain (body mass index [BMI] increased>1.14 kg/m2), no substantial weight change (absolute value of BMI change<1.14 kg/m2), and weight loss (BMI loss>1.14 kg/m2) after smoking cessation. RESULTS: We identified 108 cases of knee replacement among 1,054 recent quitters (26.7/1,000 person-years) and 1,108 cases among 15,765 current smokers (17.4/1,000 person-years). The rate difference of knee replacement in recent quitter cohort vs current smoker cohort was 10.4 (95% confidence interval [CI]:5.3-15.6)/1,000 person-years and the adjusted hazard ratio (HR) was 1.30 (95%CI:1.05-1.59). Compared with current smokers, risk of knee replacement was higher among quitters with weight gain (HR = 1.42,95%CI:1.01-1.98), but not among those with no substantial weight change (HR = 1.29,95%CI:0.90-1.83) or those with weight loss (HR = 1.11,95%CI:0.71-1.75). CONCLUSIONS: Our large population-based cohort study provides the first evidence that smoking cessation was associated with a higher risk of knee replacement among individuals with knee OA, and such an association was due to weight gain after smoking cessation.

[A nomogram to predict non-sentinel lymph node metastasis for breast cancer patients with positive axillary sentinel lymph node].

Objective: To identify the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1~2 positive axillary sentinel lymph node (SLN) and construct an accurate prediction model. Methods: Retrospective chart review was performed in 917 breast cancer patients who underwent surgery treatment between 2002 and 2017 and pathologically confirmed 1-2 positive SLNs. According to the date of surgery, patients were divided into training group (497 cases) and validation group (420 cases). A nomogram was built to predict nSLN metastasis and the accuracy of the model was validated. Results: Among the 917 patients, 251 (27.4%) had nSLN metastasis. Univariate analysis showed tumor grade, lymphovascular invasion (LVI), extra-capsular extension (ECE), the number of positive and negative SLN and macro-metastasis of SLN were associated with nSLN metastasis (all P<0.05). Multivariate Logistic regression analysis showed the numbers of positive SLN, negative SLN and macro-metastasis of SLN were independent predictors of nSLN metastasis (all P<0.05). A nomogram was constructed based on the 6 factors. The area under the receiver operating characteristic curve was 0.718 for the training group and 0.742 for the validation group. Conclusion: We have developed a nomogram that uses 6 risk factors commonly available to accurately estimate the likelihood of nSLN metastasis for individual patient, which might be helpful for radiation oncologists to make a decision on regional nodal irradiation.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

The relation of oral bisphosphonates to bone marrow lesion volume among women with osteoarthritis.

OBJECTIVE: Bone marrow lesions (BMLs) contribute to pain and progression of knee OA. Bisphosphonates may be a potential disease-modifier through amelioration of BMLs. We sought to determine the effect of oral bisphosphonates on BML volume over 12 months. DESIGN: Women in the Osteoarthritis Initiative who newly initiated an oral bisphosphonate were propensity-score matched to non-initiators. BML volume was assessed using sagittal turbo spin echo fat-suppressed intermediate-weighted MR images at the index date and 12 months later. A validated semi-automated process was used to segment subchondral OA-related BMLs to determine total volume of BMLs based on number of voxels within the outlined area of interest. Mean change in BML volume over 12 months among bisphosphonate initiators was compared with non-initiators using multiple linear regression. RESULTS: 145 bisphosphonate initiators were identified, who were well-matched to their comparators. The difference in mean change in total BML volume between the two groups, regardless of presence of baseline BMLs, was not significant (P = 0.4, 95% CI -156.6 to +354.2). The proportion of participants with decreased, increased, or unchanged BML volumes over the 12 months were similar in both groups. Among those with baseline BMLs, bisphosphonate initiators had a greater proportion with a decrease in BML volume compared with stable or increased BML volume than non-initiators (P = 0.03). CONCLUSIONS: In this 'real-world' setting of women starting bisphosphonates, we found no clear evidence of benefit on BML volume over a 12-month period, though a trend towards a decrease in BML volume was noted.

[Subclinical heart injury in patients receiving hypofractionated radiotherapy after breast conserving surgery: a preliminary analysis of prospective study].

Objective: To evaluate the incidence of early cardiac injury in patients with left-sided breast cancer receiving hypofractionated radiotherapy after breast conserving surgery, and to investigate the correlation between cardiac injury and hypofractionated radiotherapy dose. Methods: We prospectively enrolled 103 breast cancer patients who received whole breast with or without regional nodal irradiation after breast conserving surgery using either deep inspiration breath-hold (DIBH) or free breathing (FB) radiotherapy technique. Cardiac examinations that included N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and myocardial perfusion imaging were performed routinely before and after radiotherapy. The effects of heart dose, systemic therapy and individual factors (Framingham score) on the incidence of cardiac events were analyzed. Results: The median age was 48 years. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) were 4.0, 16.9, 6.3, and 4.4 Gy, respectively. With a median follow-up of 13.4 months, no patient had clinical cardiac abnormalities. The incidence rates of subclinical cardiac events at 1- 6- and 12-month were 23.5%, 31.6%, and 41.3%, respectively. The DIBH group had a lower mean dose, maximum dose, and V5-V40 in the heart, LAD, LV, and RV than the FB group (P<0.001). Univariate analysis showed an increased incidence of subclinical cardiac events with heart Dmean >4 Gy, LAD V40 > 20%, LV Dmean >6 Gy, RV Dmean >7 Gy, or cumulative doses of anthracycline or taxane > 300 mg/m(2) (All P<0.05). Anti-HER2 targeted therapy, endocrine therapy and Framingham score were not associated with the incidence of subclinical cardiac events (all P>0.05). Multivariate analysis demonstrated that Dmean of LV and RV were independently associated with the increased incidence of subclinical cardiac events. Conclusions: Early subclinical heart injury are found in patients with left-sided breast cancer after hypofractionated radiotherapy. The increased incidence of subclinical cardiac events after radiotherapy is positively associated with the cardiac radiation doses.

[Outcomes of 33 patients with anaplastic large cell lymphoma treated after hematopoietic stem cell transplantation].

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK(+) and 9 ones (27.3%) ALK(-). Of them, 25 patients (19 ALK(+) and 6 ALK(-)) underwent auto-HSCT and 8 cases (5 ALK(+) and 3ALK(-)) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion: ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

[Prognostic analysis of definitive radiotherapy for early esophageal carcinoma(T1-2N0M0): a multi-center retrospective study of Jing-Jin-ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group].

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.

Association of tramadol with risk of myocardial infarction among patients with osteoarthritis.

OBJECTIVE: Tramadol has been widely used among patients with osteoarthritis (OA); however, there is paucity of information on its cardiovascular risk. We aimed to examine the association of tramadol with risk of myocardial infarction (MI) among patients with OA. DESIGN: Among OA patients aged 50-90 years without history of MI, cancer, or opioid use disorder in The Health Improvement Network database in the United Kingdom (2000-2016), three sequential propensity-score matched cohort studies were assembled, i.e., (1) patients who initiated tramadol or naproxen (negative comparator); (2) patients who initiated tramadol or diclofenac (positive comparator); and (3) patients who initiated tramadol or codeine (a commonly used weak opioid). The outcome was incident MI over six-months. RESULTS: Among tramadol and naproxen initiators (n = 33,024 in each cohort), 77 (4.8/1000 person-years) and 46 (2.8/1000 person-years) incident MI occurred, respectively. The rate difference (RD) and hazard ratios (HR) for incident MI with tramadol initiation were 1.9 (95% confidence interval [CI] 0.6 to 2.3)/1000 person-years and 1.68 (95% CI 1.16 to 2.41) relative to naproxen initiation, respectively. Among tramadol and diclofenac initiators (n = 18,662 in each cohort), 58 (6.4/1000 person-years) and 47 (5.1/1000 person-years) incident MIs occurred, respectively. The corresponding RD and HR for incident MI were 1.2 (95%CI -2.1 to 14.1)/1000 person-years and 1.24 (95%CI 0.84 to 1.82), respectively. Among tramadol and codeine initiators (n = 42,722 in each cohort), 127 (6.1/1000 person-years) and 103 (5.0/1000 person-years) incident MI occurred, respectively, and the corresponding RD and HR were 1.1 (95%CI:-0.3 to 2.5)/1000 person-years and 1.23 (95%CI:0.95 to 1.60), respectively. CONCLUSIONS: In this population-based cohort of patients with OA, the six-month risk of MI among initiators of tramadol was higher than that of naproxen, but comparable to, if not lower than, those of diclofenac or codeine.

Whole solid tumour volume histogram analysis of the apparent diffusion coefficient for differentiating high-grade from low-grade serous ovarian carcinoma: correlation with Ki-67 proliferation status.

AIM: To investigate whether apparent diffusion coefficient (ADC) histogram parameters based on whole solid tumour volume could differentiate high-grade (HGSOC) from low-grade serous ovarian carcinoma (LGSOC) and to correlate those parameters with the Ki-67 proliferation index. MATERIALS AND METHODS: One hundred and seven patients with HGSOCs and 19 patients with LGSOCs confirmed at surgery and histology who underwent conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) were analysed retrospectively. ADC histogram parameters (including the mean, standard deviation [SD], 10th, 25th, 50th, 75th, and 90th percentiles, kurtosis, and skewness) were obtained using the whole solid tumour volume region of interest (ROI). The Mann-Whitney U test, Pearson's chi-square test, Fisher's exact test, kappa test, Spearman's correlation, and receiver operating characteristic (ROC) curves were used for statistical analyses. RESULTS: For ADC histogram parameters, the mean (p<0.001), SD (p=0.003), and all percentiles (10th, 25th, 50th, 75th, and 90th percentile; all p<0.001) were significantly lower in HGSOC than in LGSOC, and the area under the ROC curve (AUC) was 0.717-0.807. Skewness was significantly higher in HGSOC than in LGSOC (p<0.001, AUC = 0.773); however, kurtosis was not significantly different between HGSOC and LGSOC (p=0.140). The 25th and 75th percentiles, SD and 10th percentile, and 75th percentile showed the highest sensitivity of 91.6%, specificity of 79.0%, and accuracy of 88.1%, respectively. All histogram parameters (except for kurtosis) were poorly correlated with the Ki-67 index (|r| = 0.191-0.274, p<0.05). CONCLUSION: ADC histogram parameters based on whole solid tumour volume can be helpful for differentiating between HGSOC and LGSOC.

[The 8th edition of the American Joint Committee on Cancer staging system provide improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients].

Objective: To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods: a total of 1 823 female patients with T1-2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log-rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic (ROC) analyses and the concordance index (C-index). Results: 5-year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5-year distant metastasis (DM) rate was 11.5%, 5-year disease-free survival (DFS) was 85.0%, and 5-year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS (P<0.05). Compared with stage by 7th edition, 1 278(70.1%) were assigned to a different prognostic stage group: 1 088 (85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stage ⅠA, ⅠB, ⅡA, ⅡB and ⅢA according to 8th edition of the AJCC staging system(P<0.001). Prognostic stage had significantly higher C-indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system (P<0.001). Conclusion: The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1-2N1M0 breast cancer, and has better clinical therapeutic guidance value.