[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.

[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.

[Clinical analysis of penetrating keratoplasty for infants with congenital corneal opacity].

Objective: To investigate the corneal graft survival and related risk factors of primary penetrating keratoplasty in congenital corneal opacity infants. Methods: It was a retrospective cohort study. Data were collected from forty-two infants (51 eyes) who were aged ≤12 months and diagnosed with congenital corneal opacity in Beijing Tongren Hospital and Beijing Anzhen Hospital from January 1, 2017 to January 31, 2018. The mean age at surgery was (5.7±2.2) months (3-12 months). The mean follow-up duration was (28.6±2.6) months (24-33 months). All the patients underwent penetrating keratoplasty. The status of the corneal grafts and complications were observed and recorded during the regular follow-up. The survival probabilities were estimated by using the Kaplan-Meier and Log-rank test. The graft survival between different influence factors was analyzed by using the χ2 test. Results: The Kaplan-Meier survival rates for penetrating keratoplasty were 84.3% (43/51) at 6 months, 78.4% (40/51) at 12 months and 60.8% (31/51) at the last follow-up. The presence of corneal neovascularization was significantly correlated with graft failure (χ²=5.264, P=0.022). The graft survival differed between eyes receiving combined surgery and mere penetrating keratoplasty and in eyes with varied surgical indications (P=0.039, <0.01). Increased intraocular pressure (7 eyes, 13.7%) and persistent epithelial defects (7 eyes, 13.7%) were the most common postoperative complications, followed by complicated cataract (4 eyes, 7.8%) and posterior capsule opacification (2 eyes, 3.9%). Conclusions: The graft survival rate was satisfactory following pediatric keratoplasty although it had a tendency to decrease with the follow-up time. Corneal neovascularization was a major risk factor of graft failure. Surgical indications and procedures also had a certain effect on the graft survival.

[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.

[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.

[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.

[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.

Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study.

In this population-based cohort study on comparative osteoporotic fracture risks between different biologic disease-modifying drugs among patients with rheumatoid arthritis (RA), we did not find a significant difference in the risk of osteoporotic fractures between RA patients receiving TNF inhibitors versus abatacept or tocilizumab. INTRODUCTION: We aimed to investigate the comparative risk of osteoporotic fractures between rheumatoid arthritis (RA) patients who initiated TNF inhibitors (TNFis) versus abatacept or tocilizumab. METHODS: Using the Korea National Health Insurance Service datasets from 2002 to 2016, RA patients who initiated TNFis, abatacept, or tocilizumab were identified. The primary outcome was a composite end point of non-vertebral fractures and hospitalized vertebral fractures; secondary outcomes were two components of the primary outcome and fractures occurring at the humerus/forearm. Propensity score (PS) matching with a variable ratio up to 10 TNFi initiators per 1 comparator drug initiator was used to adjust for > 50 baseline confounders. We estimated hazard ratios (HRs) and 95% confidence interval (CI) of fractures comparing TNFi initiators to abatacept and to tocilizumab by Cox proportional hazard models stratified by a matching ratio. RESULTS: After PS-matching, 2307 TNFi initiators PS-matched on 588 abatacept initiators, and 2462 TNFi initiators on 640 tocilizumab initiators were included. A total of 77 fractures occurred during a mean follow-up of 454 days among TNFi and abatacept initiators and 83 fractures during 461 days among TNFi and tocilizumab initiators. The PS-matched HR (95% CI) was 0.91 (0.48-1.71) comparing TNFi versus abatacept initiators, and 1.00 (0.55-1.83) comparing TNFi versus tocilizumab initiators. Analysis on vertebral and non-vertebral fractures showed similar results. CONCLUSIONS: In this nationally representative cohort, we did not find a significant difference in the risk of fractures between TNFi initiators versus abatacept or tocilizumab among RA patients.

[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.

Novel SLCO2A1compound heterozygous mutation causing primary hypertrophic osteoarthropathy with Bartter-like hypokalemia in a Chinese family.

PURPOSE: Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis and pachydermia with defects in the degradation of prostaglandin E2 (PGE2). Mutations in SLCO2A1 gene-encoding prostaglandin transporter (PGT) resulted in PHO, autosomal recessive 2 (PHOAR2). The spectrum of mutations and variable clinical complications of PHOAR2 has been delineated. In this study, we investigated a Chinese PHO family with a manifestation of Bartter-like hypokalemia. METHODS: Clinical manifestations were collected and genetic analyses were performed in the PHO family. RESULTS: The 33-year-old male proband had severe hypokalemia due to potassium loss from the kidney, while his brother had mild hypokalemia. After being treated with etoricoxib, the serum potassium level of the patient increased rapidly to the normal range which corresponded with the reduction in his serum PGE2 and PE2 metabolite (PGEM) levels. A novel SLCO2A1 compound heterozygous mutation of p.I284V and p.C459R was identified in two PHO patients in this family. CONCLUSIONS: The present findings supported that the Bartter-like hypokalemia is a new complication of PHOAR2 caused by the high level of PGE2. Etoricoxib was demonstrated to be effective for the renal hypokalemia in PHO patients.

[Clinical differences between primary nasopharyngeal NK/T-cell lymphoma and primary nasal cavity NK/T-cell lymphoma with nasopharynx extension].

Objective: To investigate the clinical and prognostic differences between primary nasopharyngeal natural killer (NK)/T-cell lymphoma (NP NKTCL) and extranodal NK/T-cell lymphoma of the nasal cavity with nasopharynx extension (N-NP NKTCL). Methods: A total of 89 patients with NP NKTCL and 113 patients with N-NP NKTCL from January 2000 to June 2015 were retrospectively analyzed. Clinical and pathological features, treatment responses and prognosis were compared between the two groups. Results: NP NKTCL patients showed similar clinicopathological features with those with N-NP NKTCL, except that the former had a relative low proportion of elevated lactate dehydrogenase (LDH) levels (28.1% vs. 41.6%; P=0.001). Both of two groups presented with high proportion of cervical lymph node involvement (55.1% and 42.5%; P=0.076). The 5-year overall survival (OS) rates in these two groups were 63.2% and 54.6%, respectively, whereas 5-year progress-free survival (PFS) rates were 50.7% and 45.6%, respectively. For the patients with stage Ⅰ and Ⅱ, the 5-year OS and PFS rates in these two groups were 68.8% and 55.7% as well as 55.6% and 47.2%, respectively. These were no statistically significant differences between two groups (all P>0.05). The complete response (CR) rate after initial chemotherapy in NP NKTCL group was 43.8%, which was significant higher than that of 19.6% in N-NP NKTCL group (P=0.006). Additionally, the CR rate after primary radiotherapy was 63.4% and 62.7%, respectively (P=0.629). The NP NKTCL patients with stage Ⅰ and Ⅱ who accepted radiotherapy with or without chemotherapy had similar survival times with chemotherapy alone, showing the 5-year OS rates of 70.5% and 33.3% (P=0.238), as well as the 5-year PFS rates of 56.7% and 33.3%, respectively (P=0.431). Similar results were found in N-NP NKTCL group, the 5-year OS rates for patients with radiotherapy with or without chemotherapy and chemotherapy alone were 57.4% and 33.3% (P=0.246), while the 5-year PFS rates were 49.3% and 16.7% (P=0.177), respectively. Besides, the relapse pattern of NP NKTCL and N-NP NKTCL groups was also similar, mainly involving the distant extra-nodal organs followed by lymph nodes. Conclusion: The patients with N-NP NKTCL and NP NKTCL showed similar clinical and prognostic features, however, the initial response to chemotherapy was different.

[Prognosis and risk factors of 1 791 patients with breast cancer treated with breast-conserving surgery based on real-world data].

Objective: To investigate the overall efficacy of early breast cancer after breast-conserving treatment. To analyze risk factors affecting local regional recurrence (LRR), distant metastasis (DM) and survival. Methods: 1 791 breast cancer patients treated with breast-conserving surgery were retrospectively analyzed. The inclusion criteria were pathologic diagnosis of invasive breast cancer without supraclavicular and internal mammary node metastasis, T1-2N0-3M0, and no neoadjuvant therapy. Univariate analysis of survival was performed by Kaplan-Meier method and log rank test. Cox regression model was used for multivariate analysis. Results: The median follow-up time was 4.2 years. For all patients, the 5-year LRR, DM, disease-free survival(DFS) and overall survival(OS) rates were 3.6%, 4.6%, 93.0% and 97.4%, respectively. The LRR rates of patients with Luminal A, Luminal B1, Luminal B2, HER-2 over-expressed and triple-negative breast cancer were 2.0%, 6.1%, 5.9%, 0 and 10.0%, while the DM rates were 3.2%, 6.7%, 8.3%, 4.8% and 7.3%, respectively. Among the N0 patients, axillary dissection was performed in 689 cases and sentinel lymph node biopsy in 652 cases. The 5-year LRR rates were 3.3% and 3.2% (P=0.859), and the OS rates were 98.2% and 98.3% (P=0.311) respectively, which showed no statistically significant. There were 1 576 patients that underwent postoperative radiotherapy. Postoperative radiotherapy significantly reduced the 5-year LRR compared with surgery alone (2.5% vs 12.9%). The 5-year LRR rates of patients who received conventional fractionated radiotherapy and hypo-fractionated radiotherapy were 2.7% and 3.1%, respectively. But the difference was not statistically significant (P=0.870). Multivariate analysis showed that age, lymphovascular invasion, pathological T staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors of LRR in breast cancer patients (all P<0.05). Histological grade and pathological N staging were independent factors of DM (all P<0.05). The age, lymphovascular invasion, pathological T and N staging, postoperative radiotherapy, ER/PR status and endocrine therapy were independent factors for DFS (all P<0.05). Histological grade, pathological N staging, ER/PR status and endocrine therapy were factors for OS (all P<0.05). Conclusions: With contemporary standard treatment, the recurrence rate of early breast cancer after breast conserving treatment is less than 10%. Node-negative patients after sentinel lymph node biopsy did not need axillary dissection. The overall utilization of radiotherapy after breast conserving surgery is satisfactory. Hypofractionated radiotherapy is as effective as conventional fractionated radiotherapy. Local regional recurrence and distant metastasis have different risk factors.

[Clinical characteristics and treatment strategies for early-stage primary gastric diffuse large B-cell lymphoma].

Objective: Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is the most common non-Hodgkin lymphoma (NHL) of extranodal origin. Most patients with PG-DLBCL had localized disease (stage Ⅰ or Ⅱ) at presentation, and will achieve complete response (CR) after induction chemotherapy. However, there has been little consensus regarding whether optimal treatment is provided by chemotherapy alone or chemotherapy plus radiotherapy, nor the treatment outcome from the addition of rituximab in localized-stage PG-DLBCL. Methods: Patients with Stage ⅠE and ⅡE PG-DLBCL were retrospectively analyzed. Patients have not undergone surgery, have received at least 3 cycles of R-CHOP or CHOP-like chemotherapy as initial therapy, and achieved CR or partial response (PR) were enrolled. Results: A total of 91 patients were studied. The median age was 51 years, included 47 males and 44 females. Fifty-two patients were at Stage ⅠE and 39 at Stage ⅡE, 64 (70.3%) patients received R-CHOP-like regimens, and 27 (29.7%) received CHOP-like regimens, the median chemotherapy cycle was 6 (3-8). Among the 91 patients, 80 (87.9%) patients achieved CR from induction chemotherapy, 11(12.1%) was evaluated PR. Of CR patients, 48 patients (60%) underwent consolidating radiotherapy and 32 patients (40%) did not receive radiotherapy; all PR patients received salvage radiotherapy. CR patients with and without radiation therapy had 4-year progression-free survival (PFS) rates of 96.4% and 96.7%, respectively (χ(2) = 0.546, P=0.46); 7/11 (63.6%) PR patients achieved CR after radiotherapy, with a median follow-up of 41 months, they were all disease free. For patients treated with R-CHOP or CHOP-like regimens, the 4-year PFS was 93.2% and 89.7%, respectively (χ(2)=0.096, P=0.757). Conclusions: Consolidation radiotherapy failed to improve the outcome for early-stage PG-DLBCL, while for PR patients, salvage radiotherapy increased CR rate and improved survival. The addition of rituximab to CHOP did not improve the efficacy.

[Retrospective analysis of the clinical features and prognostic factors of 370 patients with advanced-stage diffuse large B-cell lymphoma].

Objective: The clinical features and prognosis of diffuse large B-cell lymphoma (DLBCL) were analyzed to optimize the treatment. Methods: We retrospectively collected the clinical data of patients with advanced-stage DLBCL from January 2006 to December 2012 in National Cancer Center/Cancer Hospital. The demographic characteristics, clinical stage, histological diagnosis, treatment and prognostic characteristics of these patients were analyzed. Results: A total of 370 patients with median age of 55 years old were recruited in the study. The male-to-female ratio was 1.3∶1. Among the 361 patients who underwent therapy, 280 cases received chemotherapy alone, 65 cases received chemoradiotherapy, and 16 cases received chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT). The median follow-up period was 89 months, the 5-year overall survival (OS) rate of the entire cohort was 42.9%. The 5-year OS rate of chemotherapy alone, chemoradiotherapy and chemotherapy combined with AHSCT were 36.8%, 58.5%, 87.5%, respectively. The 5-year OS rate were significantly different between chemoradiotherapy and chemotherapy alone (P=0.001), and between chemotherapy combined with AHSCT and chemoradiotherapy (P=0.040). Univariate analysis showed that the age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, Ann Arbor stage, B symptom, bulky disease, number of extranodal sites, Ki-67 index, lactate dehydrogenase (LDH), ß2-microglobulin (ß2-MG), international prognostic index (IPI), therapeutic manner and chemotherapy combined with rituximab were significantly associated with the prognosis of advanced DLBCL patients (all P<0.05). Multivariate analysis demonstrated that the age >60 years, Ann Arbor stage IV, with B symptom, with bulky disease, ECOG PS≥1, Ki-67 index > 90%, CD5 expression, up-regulation of serum LDH and ß2-MG, and chemotherapy without rituximab were related with the poor prognosis of patients with advanced-stage DLBCL (all P<0.05). Conclusions: Chemotherapy combined with rituximab can improve the outcome of patients with advanced-stage DLBCL. The age, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index, CD5 expression, LDH, ß2-MG and chemotherapy combined with rituximab are associated with the prognosis of these patients.

[Clinical characteristics and prognosis of patients with ipsilateral breast tumor recurrence after breast conservation therapy].

Objective: To analyze the clinical features and prognosis of the ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery. Methods: From 1999 to 2013, 63 women with IBTR after breast conserving surgery were retrospectively reviewed. All patients had adequate information on tumor location both at first presentation and at recurrence, with or without regional recurrence or distant metastasis. The histologic changes between true local recurrence and elsewhere recurrence groups were compared. The local recurrence, the overall survival after IBTR (IBTR-OS), the disease-free survival after IBTR (IBTR-DFS) were also compared. Results: All patients had undergone lumpectomy, including 38 cases with additional axillary lymph node dissection and 13 cases with sentinel lymph node biopsy. There were 11.3% (7/63) cases received neoadjuvant systemic therapy, 68.3% (43/63) had adjuvant radiotherapy, 60.3% (38/63) underwent adjuvant chemotherapy and 47.6% (30/63) received hormonal therapy. Forty-five cases (71.4%) had recurrence in the same quadrant, and 18 cases (28.6%) had elsewhere recurrence. Compared with histology at presentation, 10.3% of the patients (6/58) had different ones at recurrence and 28.9% of patients (13/45) had different molecular subtypes. The conversion rate of estrogen receptor status (33.3% vs 9.5%, P=0.012) and progesterone receptor status (56.3% vs 19.0%, P=0.005) in patients with elsewhere recurrence was significantly higher than that in patients with same quadrant recurrence. Fifty-nine cases had undergone surgery after IBTR, with 48 cases of secondary breast-conserving surgery and 11 cases of salvage mastectomy. The median time to IBTR of same quadrant recurrence and elsewhere recurrence groups were 26 months and 62 months (P=0.012), respectively. There were 84.4% and 44.4% cases who had local recurrence within 5 years after breast conserving surgery, respectively. Of all cases, the overall 5-year IBTR-OS and 5-year IBTR-DFS rates were 79.4% and 60.4%, respectively. There were no significant differences in 5-year IBTR-OS (77.4% vs. 83.6%, P=0.303) or 5-year IBTR-DFS (60.0% vs. 62.8%, P=0.780) between same quadrant recurrence and elsewhere recurrence groups. Univariate analysis showed that pN0-1 (P<0.001), luminal subtype (P=0.026), adjuvant endocrine therapy (P=0.007) at first presentation, recurrent tumor < 3 cm (P=0.036) and having surgery after IBTR(P=0.002) were favorable factors of IBTR-OS. pN0-1 (P<0.001) at first presentation, recurrent tumor stage Ⅰ-Ⅱ (P<0.001) and having surgery after IBTR(P=0.001) were favorable factors of IBTR-DFS. There was no significant difference between second breast-conserving surgery and salvage mastectomy in IBTR-OS and IBTR-DFS (P>0.05). Conclusions: The IBTR after breast conserving surgery mainly occurred at the original quadrant. Second breast-conserving surgery did not affect patient's prognosis. There were significant differences in biological features between the same quadrant recurrence and elsewhere recurrence, requiring different therapeutic strategies in the future.

[Glucose and lipid metabolic disorders in myasthenia gravis patients and its mechanisms].

Objective: To investigate the glucose and lipid metabolic disorders in patients with myasthenia gravis (MG) without glucocorticoid therapy, and the relationships between insulin, insulin resistance, muscle strength, serum levels of osteocalcin, 25-hydroxy vitamin D (25OHD) and glucose and lipid metabolism. Methods: A total of 102 MG patients [(40±11) years old, 43 males and 59 females] without glucocorticoid treatment were enrolled in this cross-sectional study. Height, weight and the handgrip of dominant hands were measured. Serum levels of fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), 2-hour postprandial insulin (2 h PINS), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and osteocalcin, 25OHD were detected. Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Results: The proportion of impaired fasting glucose or impaired glucose tolerance, type 2 diabetes, dyslipidemia, hyperinsulinemia in male and female were 30.0%, 10.0%, 50.0%, 33.3% and 17.5%, 3.5%, 27.7%, 7.1%, respectively. Serum osteocalcin levels in male and female were 2.8 (1.7, 4.4) µg/L and 2.3 (1.3, 3.9) µg/L, respectively. And 25OHD levels in male and female were (93.5±34.9) nmol/L and (81.0±30.5) nmol/L, respectively. Handgrip of male and female was (37.0±9.4) kg and (20.5±6.3) kg. After adjusted for age, FINS (r=0.619, P<0.001), 2 h PINS (r=0.640, P<0.001), HOMA-IR (r=0.534, P<0.001) were positively correlated with 2 h PBG, and the handgrip was negatively correlated with TC (r=-0.486, P=0.026), LDL-C (r=-0.485, P=0.026) in male. FINS (r=0.352, P=0.008; r=0.300, P=0.026; r=0.646, P<0.001) and 2 h PINS (r=0.278, P=0.040; r=0.518, P<0.001; r=0.382, P=0.006) and HOMA-IR (r=0.695, P<0.001; r=0.583, P<0.001; r=0.818, P<0.001) were positively correlated with FBG, 2 h PBG, HbA1c, and the handgrip were negatively correlated with FBG (r=-0.424, P=0.016), 2 h PINS (r=-0.345, P=0.034) and positively correlated with HDL-C (r=0.389, P=0.037) in female. There was no association between osteocalcin, 25OHD and glucose and lipid metabolism. Multivariate linear regression analysis also found that there were significant relationships between handgrip, insulin, insulin resistance levels and glucose and lipid metabolic disorders. Conclusion: There was a high proportion of glucose and lipid metabolic disorders in MG patients without glucocorticoid treatment, and the mechanism may be related to insulin resistance induced by muscle weakness.

S-1 chemotherapy and intensity-modulated radiotherapy after D1/D2 lymph node dissection in patients with node-positive gastric cancer: a phase I/II study.

BACKGROUND: This phase I/II clinical trial investigated S-1 administered with intensity-modulated radiotherapy (IMRT) as adjuvant therapy for node-positive gastric cancer. Patients had undergone radical resection and D1/D2 lymph node dissection. METHODS: In phase I, patients received adjuvant chemoradiotherapy of IMRT (45 Gy in 25 fractions) with concurrent S-1 administered on a dose-escalation schedule to determine the recommended dose (RD). In phase II, the safety and efficacy of the RD of S-1 combined with IMRT were assessed. RESULTS: We consecutively enrolled 73 patients (56 men; median age, 53 years; range, 29-73 years) and the phase I portion of the study included 27 patients. The RD of S-1 administered concomitantly with IMRT was 80 mg m-2 day-1 orally, twice daily. The phase II analysis included 52 patients (46 new patients plus 6 from phase I). 8 patients (15.4%) developed grade 3 or 4 toxicities. There were 21 recurrence events and 15 deaths (1 bowel obstruction, 14 gastric cancer). Three-year disease-free survival and overall survival were 62.2% (95% confidence interval (CI), 48.5-75.9) and 70.0% (95% CI, 56.3-83.7), respectively. The median time to recurrence was 17.5 months (range, 3.8-42.0). The median time from recurrence to death was 7.0 months (range, 1.5-28.7). CONCLUSIONS: S-1 combined with IMRT adjuvant chemoradiotherapy is safe and efficacious for advanced gastric cancer.

[Risk-adapted postmastectomy radiotherapy based on local-regional recurrence for T1-2N1M0 breast Cancer].

Objective: To establish a risk-adapted postmastectomy radiotherapy strategy based on local-regional recurrence for intermediate-risk breast cancer (T1~2N1M0 stage). Methods: A total of 2413 patients with T1-2N1M0 breast cancer were retrospectively reviewed. Of them, 588 patients (24.4%) received postmastectomy radiotherapy (PMRT), while 1 825 (75.6%) patients did not. A comprehensive comparative study was performed by using multivariable and propensity score-matched (PSM) analyses. Results: The median follow-up time was 67.0 months, the 5-year local region recurrence free-survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were 93.8%, 85.7% and 93.3%, respectively. The 5-year local region recurrence (LRR) was 6.1%. For patients without PMRT, multivariable analysis indicated that age, tumor localization, molecular subtype, pathologic T stage and number of positive lymph node were independent factors for LRRFS (all of P<0.05). Patients with T1-2N1 breast cancer were classified into low-risk group (0-1 risk factor, 768 patients), intermediate-risk group (2 risk factors, 690 patients) and high-risk groups (≥3 risk factors, 544 patients) based on the five independent factors mentioned above. The 5-year LRRFS, DFS and OS were significantly different among the three groups (P<0.001). In low- and intermediate-risk groups, there were no significant differences in LRRFS, DFS and OS of patients who received PMRT or not (P>0.05). In high-risk group, the DFS of patients received PMRT or not were 79.8% and 74.4%, respectively (P=0.127), the OS of them were 86.8% and 87.1%, respectively (P=0.174), and the LRRFS were 93.3% and 84.3%, respectively (P=0.002). After PSM adjustment, no significant differences in LRRFS, DFS and OS were observed between PMRT-received subgroup and no PMRT subgroup of low-risk group (P>0.05). In intermediate-risk group, the LRRFS of patients received PMRT or not were 95.2% and 91.0%, respectively (P=0.037). However, in the high-risk group, the LRRFS, DFS and OS of patients received PMRT were 93.3%, 79.7% and 86.6%, respectively, while those of patients did not receive PMRT were 78.5% (P<0.001), 69.5% (P=0.038) and 85.7% (P=0.080), respectively. Conclusions: The local-regional recurrence risks of patients with pT1-2N1 breast cancer are viable and risk-adapted PMRT is available for them. Better prognoses can be achieved by the patients of intermediate and high-risk group. More samples on this subject are needed to validate the results.