[The effects of sequence of radiotherapy and chemotherapy on prognosis of patients with early-stage extranodal NK/T cell lymphoma (nasal type) and its individualized application].

Objective: To analyze the effects of the sequence of radiotherapy and chemotherapy on the efficacy of early-stage extranodal NK/T-cell lymphoma (nasal type, ENKTCL) patients, and to provide a quantitative evaluation method for individualized radiotherapy and chemotherapy. Methods: The Chinese Lymphoma Collaborative Group (CLCG) collected the clinical data of 2 008 patients with early-stage Ⅰ/Ⅱ ENKTCL who received radiotherapy and chemotherapy from January 2000 to early September 2019 from 21 hospitals across the country, including 1 417 males and 591 females, aged 2 to 83 (42±14) years. According to the sequence of radiotherapy and chemotherapy, patients were divided into radiotherapy-first group (388 cases) and chemotherapy-first group (1 620 cases). Survival rate was estimated using Kaplan-Meier method, and multivariate Cox proportional risk model was used to screen and identify independent prognostic factors. The prognostic prediction models of the two therapies were constructed separately, and the models were used to predict the individualized mortality risk of all patients to determine the appropriate radiotherapy and chemotherapy regimen for each patient. Results: The 5-year overall survival rate was 74.2% (95%CI: 69.6%-79.2%) in the radiotherapy-first group and 69.7% (95%CI: 67.1%-72.4%) in the chemotherapy-first group. Although the 5-year overall survival rate of patients in the radiotherapy-first group was numerically higher than that of the chemotherapy-first group, the difference was not statistically significant (χ2= 2.26, HR=0.84 (95%CI: 0.68-1.05), P=0.133). Six variables including age, gender, ECOG score, LDH, Ann Arbor staging, and PTI (primary tumor invasion) were screened out as independent prognostic factors (the chemotherapy-first group: HR were 1.01, 1.25, 2.07, 0.77, 1.34, 1.49, respectively, all P<0.05; radiotherapy-first group: HR were 1.02, 1.31, 1.66, 0.78, 1.37, 1.29, all P>0.05). The mean 5-year predicted mortality risk for all patients receiving radiotherapy-first regimen was lower than those receiving chemotherapy-first regimen (26.8% vs 30.2%, P<0.001). There were individualized differences in the predicted mortality risk of patients with different clinical characteristics who received radiotherapy-first regimen or chemotherapy-first regimen. Conclusion: Patients with stage Ⅰ/Ⅱ ENKTCL treated with radiotherapy-first regimen had a better expected prognosis than patients treated with chemotherapy-first regimen. The quantitative assessment of the differential effects of the sequence of radiotherapy and chemotherapy on the mortality risk of individual patients based on their clinical characteristics was helpful for the clinical development of the optimal radiotherapy and chemotherapy plan for each patient.

[Ultrasound biomicroscopic differences between fellow eyes of acute angle-closure glaucoma and chronic angle-closure glaucoma].

Objective: To compare the structural differences of the anterior segment between fellow eyes of acute angle-closure glaucoma (AACG) and the eyes of chronic angle-closure glaucoma (CACG) with milder glaucomatous damage. Methods: In this case-control study, patients with AACG (41 eyes) and CACG (46 eyes) without prior treatment in the glaucoma clinic of Peking University People's Hospital from September 2016 to October 2018 were enrolled. Ultrasound biomicroscopy was performed under dark condition. Parameters were measured on images including lens vault (LV), anterior chamber depth (ACD), iris thickness (IT750 and IT2000), angle-opening distance (AOD500 and AOD750), and trabecular iris angle (TIA500 and TIA750). The independent t-test was used to compare the continuous variables of the fellow eyes of AACG patients and the eyes of CACG patients with milder glaucomatous damage. After adjusting for age and gender, univariate and multivariate logistic regression analyses were performed to explore the most important parameters that may distinguish AACG from CACG. Results: The mean age of AACG patients was (65±10) years old and the age of CACG patients was (67±12) years old (P>0.05). The ACD [(1.79±0.25) mm vs. (1.99±0.34) mm], IT750 [(0.39±0.07) mm vs. (0.43±0.05) mm], AOD500 [(0.12±0.06) mm vs. (0.15±0.07) mm], TIA500 (10.91°±5.23° vs. 13.93°±6.33°), and TIA750 (9.33°±5.02° vs. 13.93°±6.82°) were less and the LV [(0.99±0.44) mm vs. (0.72±0.30) mm] was greater in the fellow eyes of AACG as compared to the eyes of CACG with milder glaucomatous damage (all P<0.05). In the forward multivariate logistic regression analysis, every 1-degree decrease in TIA750 (odds ratio=0.872, 95%CI: 0.794 to 0.958, P<0.01) and every 1-mm increase in LV (odds ratio=14.138, 95%CI: 2.348 to 85.130, P<0.01) were significantly associated with AACG. Conclusions: Compared with the eyes of CACG with milder glaucomatous damage, fellow eyes of AACG have thinner peripheral iris thickness, narrower angle width, shallower ACD, and greater LV. LV and TIA750 may play important roles in distinguishing eyes predisposed to AACG or CACG. (Chin J Ophthalmol, 2021, 57: 672-678).

[Outcome of radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type].

Objective: To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL). Methods: A total of 557 patients from 2000-2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis. Results: The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 (P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population (P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy (P<0.001). Radiotherapy dose was an independent factor affecting LRC(P<0.05). Conclusions: Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Association of improved overall survival with decreased distant metastasis following asparaginase-based chemotherapy and radiotherapy for intermediate- and high-risk early-stage extranodal nasal-type NK/T-cell lymphoma: a CLCG study.

BACKGROUND: This study evaluated the survival benefit of asparaginase (ASP)-based versus non-ASP-based chemotherapy combined with radiotherapy in a real-world cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL). PATIENTS AND METHODS: We identified 376 patients who received combined radiotherapy with either ASP-based (ASP, platinum, and gemcitabine; n = 286) or non-ASP-based (platinum and gemcitabine; n = 90) regimens. The patients were stratified into low-, intermediate-, and high-risk groups using the early stage-adjusted nomogram-revised risk index. Overall survival (OS) and distant metastasis (DM)-free survival (DMFS) between the chemotherapy regimens were compared using inverse probability of treatment weighting (IPTW) and multivariable analyses. RESULTS: ASP-based (versus non-ASP-based) regimens significantly improved 5-year OS (84.5% versus 73.2%, P = 0.021) and DMFS (84.4% versus 74.5%, P = 0.014) for intermediate- and high-risk patients, but not for low-risk patients in the setting of radiotherapy. Moreover, ASP-based regimens decreased DM, with a 5-year cumulative DM rate of 14.9% for ASP-based regimens compared with 25.1% (P = 0.014) for non-ASP-based regimens. The survival benefit of ASP-based chemotherapy and radiotherapy remained consistent after adjusting the confounding variables using IPTW and multivariate analyses; additional sensitivity analyses confirmed these results. CONCLUSIONS: The findings provided support for ASP-based chemotherapy and radiotherapy as a first-line treatment strategy for intermediate- and high-risk early-stage ENKTCL.

[Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract].

Objective: To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL). Methods: The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis. Results: Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% (P=0.281), while the PFS rates were 24.8% and 48.3%, respectively (P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival (P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival(P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions: Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

[The relationship between HPV integration and prognosis of cervical cancer].

Objective: To investigate the relationship between human papillomavirus (HPV) integration and prognosis of cervical cancer patients. Methods: The data of 82 patients with cervical cancer treated in the Radiotherapy Department of Peking Union Medical College Hospital from October 2004 to June 2012 were retrospectively analyzed.The patients were divided into poor prognosis group (recurrence or metastasis after surgery and adjuvant radiotherapy) and good prognosis group based on a propensity score matching strategy.The HPV integration of the two groups were detected by whole exome sequencing to determine whether the integration sites were located in the common fragile sites (CFSs). HPV integration and integration into CFSs were compared between the two groups. Results: Among the enrolled 82 patients, 37 were divided in poor survival group and 45 in good survival group. A total of 90 integration breakpoints were identified, 30 of them occurred in poor prognosis group and 60 occurred in good prognosis group. In the poor prognosis group, HPV integration occurred in 20 patients, 13 of them were inserted in CFSs of 11 patients, and the numbers in good prognosis group were 26, 17, 11, respectively. There were no significantly statistical differences in the number of HPV integration events (P=0.289), HPV integration patients (P=0.735), CFSs integration events (P=0.427), and CFSs integration patients (P=0.591) between the two groups. In poor prognosis group, more CFSs integration events occurred in patients with metastasis than those in patients with only local recurrence (9 vs 2, P=0.003). Conclusions: No significant differences are observed in HPV integration and HPV integration into CFSs between cervical cancer patients with different prognoses. HPV integration into CFSs may be associated with distant metastasis.

[Characteristics and analysis of corneal astigmatism in age-related cataract patients over 50 years old].

Objective: To investigate the relationship between corneal astigmatism and age, axial length (AL) in age-related cataract patients over 50 years old. Methods: In this retrospective study, 1 906 eyes of 953 patients with age-related cataract were diagnosed from February 2016 to August 2016 atPeking University People's Hospital, and their demographics, preoperative AL, magnitude and meridian of the corneal astigmatism measured by IOL Master were collected. Restricted cubic splines and Spearman rank correlation coefficients were used to investigate the relationship of the magnitude of cornea astigmatism to age. Chi-square test was used to assess the relationship of the meridian of astigmatism to age, AL and the magnitude of cornea astigmatism. Results: The patients were 410 men and 543 women. The corneal astigmatism was with-the-rule (WTR) in 570 eyes (29.91%), against-the-rule (ATR) in 1 005 eyes (52.73%) and oblique in 331 eyes (17.37%). The mean age was (72±9) years old. The medians (min, max) of AL and corneal astigmatism magnitude were 23.49 mm (19.83 mm to 33.89 mm) and 0.97 D (0.06 D to 4.65 D) in right eyes and 23.41 mm (17.54 mm to 32.09 mm) and 0.92 D (0.11 D to 4.88 D) in left eyes, respectively. The corneal astigmatism was ≥0.75 D in 64.95% (619/953) of the right eyes and 61.59% (587/953) of the left eyes. Among the elderly patients over 65 years old, when the AL was between 22.00-25.99 mm (r=0.186-0.279), the value of corneal astigmatism was positively correlated with age (all P<0.01) in both eyes. The value of ATR corneal astigmatism was positively correlated with age (right eyes, r=0.278, P<0.01; left eyes, r=0.225, P<0.01), while the value of WTR corneal astigmatism had no statistically significant correlation with age (right eyes, P=0.335; left eyes, P=0.633). The prevalence of WTR astigmatism decreased with age from 43.81% (46/105) to 20.73% (51/246) in right eyes and from 40.00% (42/105) to 24.80% (61/246) in left eyes, while the prevalence of ATR astigmatism increased with age from 38.10% (40/105) to 61.38% (151/246) in right eyes and from 33.33% (35/105) to 58.94% (145/246) in left eyes. The prevalence of oblique astigmatism was not significantly changed with age (right eyes, χ(2)=31.986, P<0.01; left eyes, χ(2)=27.686, P<0.01). There was no statistically significant difference in the distribution of corneal astigmatism meridians between different AL groups (right eyes, P=0.497; left eyes, P=0.897). With the increase of the magnitude of corneal astigmatism, the prevalence of oblique astigmatism significantly decreased from 25.45% (85/334) to 0 in right eyes and from 29.78% (109/366) to 1.35% (1/74) in left eyes, while the prevalence of ATR astigmatism significantly increased from 39.82% (133/334) to 79.27% (65/82) in right eyes and from 41.80% (153/366) to 59.46% (44/74) in left eyes (right eyes, χ(2)=72.229, P<0.01; left eyes, χ(2)=72.166, P<0.01). Conclusions: A majority of age-related cataract patients over 50 years old have astigmatism ≥0.75 D before cataract surgery. When the AL is between 22.00 mm and 25.99 mm, the magnitude of corneal astigmatism increases with age among people over 65 years old, especially the magnitude of ATR corneal astigmatism, while the magnitude of WTR corneal astigmatism has no obvious increase with age. The percentage of ATR astigmatism increases while the percentage of WTR astigmatism decreases with age. (Chin J Ophthalmol, 2020, 56: 349-355).

[Long-term outcome of bilateral surgery in infant with congenital cataract using different approaches].

Objective: To explore the best surgical approach for infant with congenital cataract by comparing long-term follow-up results of bilateral congenital cataract surgery by different approaches conducted during infant age at last time of visit. Methods: This retrospective case control study includes 108 eyes of 54 infants with bilateral congenital cataract who received bilateral cataract triple procedure (vitrector lensectomy, posterior capsulotomy and anterior vitrectomy) performed by a single surgeon, by either anterior or posterior approach, followed by refractive correction by aphakic glasses or intraocular lens (if suitable)during the follow-up periods (at least for 3 years), between January 2002 and February 2013 in Department of Ophthalmology, Peking University People's Hospital. The unilateral and bilateral best corrected visual acuity (BCVA), intraocular pressure, anterior segment and fundus exam of each visit and post-operative complications were evaluated, and data collected at patients' last visit were compared between two approaches (Student's t test for continuous variables, chi-squeare test for constitutional variables). Results: A total of 44 cases (33 males) were included in anterior approach group, median age of primary surgery was 3.0 (0.5-10.0) months. The rest 10 cases (7 males) were included in the posterior approach group, median age of primary surgery was 4.0 (1.0-11.0) months. At last visit, longest follow up period of anterior and posterior group were 3.5 (3.0-8.5) years and 4.0 (3.0-7.0) years, respectively. Neither unilateral nor bilateral BCVA (logarithm of minimum angle of resolution) of both anterior and posterior approach groups at last visit showed any difference(both P>0.05).Long-term post-operation complications of anterior and posterior group include strabismus (8 cases and 2 cases), nystagmus(8 cases and 6 cases), optical opaque (4 cases and 2 cases), and ocular hypertension(2 cases and 1 case). Nystagmus (P<0.001) and optical opaque (P=0.041) was more prevalent in posterior approach group. Conclusion: For bilateral congenital cataract surgery during infant age, anterior approach would produce less post-operation complications as compared to posterior approach, and is recommended for infants without other abnormalities of posterior segment of the eye. (Chin J Ophthalmol, 2019, 55:46-50).

[Survival and prognostic factors analysis of primitive neuroectodermal tumor].

Objective: To investigate the clinical features and prognosis of primitive neuroectodermal tumor (PNET). Methods: The clinical data of 99 patients with PNET from February 1, 1998 to February 1, 2017 were retrospectively analyzed. Univariate analysis was performed using Kaplan-Meier and Log rank test. Multiviate Cox regression was applied to analyzed independent prognostic factor for patient survival. Results: Among the 99 patients, 81 were peripheral PNET(pPNET) and 18 were central PNET (cPNET) . Biopsy was performed exclusively in 16 cases, with R0 resection in 61 cases, with R1 resection in 4 cases, and with R2 resection in 18 cases. Twelve patients underwent surgery only, nine had chemotherapy only, and one received radiotherapy only. There were 72 patients who had combined treatment including chemotherapy, and 48 patients had combined therapy including radiotherapy. The one-year, three-year and five-year overall survival(OS) rates of the 99 PNET patients were 79.2%, 63.9% and 56.1% respectively, and median OS time was 14.0 months. The one-year, three-year and five-year progression free survival (PFS) rates of these patients were 42.7%, 25.7% and 19.8% respectively, and median PFS time was 8.0 months. The univariate analysis revealed that lymph node metastasis, surgical resection, numbers of cycles of chemotherapy and radiotherapy dose were the main factors affecting the OS (all P<0.05). Gender, age, lymph node metastasis, staging, and chemotherapy cycles were related to PFS in PNET patients (P<0.05). Multivariate analysis showed that the degree of surgical resection, chemotherapy cycle, and radiotherapy dosage were independent influencing factors of OS in PNET patients (risk ratio=1.856, 0.398, and 0.408, respectively, all P<0.05), and gender was an independent factor influencing PFS in PNET patients (risk ratio=0.494, P<0.05). Conclusions: Comprehensive therapy is the main therapy for PNET patients. The surgical resection, cycles of chemotherapy and radiotherapy dosage are independent prognostic factors for patient's OS.

[Relationship between visual field index and visual field morphological stages of glaucoma and their diagnostic value].

Objective: To investigate the rationality of visual field morphological stages of glaucoma, its relationship with visual field index and their diagnostic value. Methods: Retrospective series case study. Two hundred and seventy-four glaucoma patients and 100 normal control received visual field examination by Humphrey perimeter using standard automatic perimetry (SAP) program from March 2014 to September 2014. Glaucoma patients were graded into four stages according to characteristic morphological damage of visual field, distribution of mean defect (MD) and visual field index (VFI) of each stage were plotted and receiver operation characteristic curve (ROC) was used to explore its correlation with MD and VFI. The diagnostic value of MD and VFI was also compared. For the comparison of general data of subjects, categorical variables were compared using χ(2) test, numerical variables were compared using F test. MD and VFI were compared using ANOVA among stages according to visual field, followed by multiple comparisons using LSD method. The correlation between MD and VFI and different stages according to visual field defined their diagnostic value, and compared using area under the curve (AUC) of ROC. Results: No characteristic visual field damage was found in normal control group, and MD and VFI was (-0.06±1.24) dB and (99.15±0.76)%, respectively. Glaucomatous visual field damage was graded into early, medium, late and end stage according to morphological characteristic. MD for each stage were (-2.83±2.00) dB, (-9.70±3.68) dB, (-18.46±2.90) dB, and (-27.96±2.76) dB, respectively. VFI for each stage were (93.84±3.61)%, (75.16±10.85)%, (49.36±11.26)% and (17.65±10.59)%, respectively. MD and VFI of each stage of glaucomatous group and normal control group were all significantly different (F=1 165.53 and P<0.01 for MD; F=1 028.04 and P<0.01 for VFI). AUC of ROC was A(MD)=0.91 and Se(MD)=0.01 (95% confident interval was 0.89-0.94) for MD, and A(VFI)=0.97, Se(VFI)=0.01 (95% confident interval was 0.94-0.10) for VFI. So, AUC(VFI)>AUC(MD) (P<0.05). Conclusions: It is feasible and rational of glaucomatous visual field damage to be graded into early, medium, late and end stage using Humphrey perimeter. Distribution of MD and VFI for each stage was relatively concentrative. Both MD and VFI were useful for grading glaucomatous visual field damage with preference for VFI. (Chin J Ophthalmol, 2017, 53: 92-97).

Prognostic nomogram for overall survival in previously untreated patients with extranodal NK/T-cell lymphoma, nasal-type: a multicenter study.

The aim of this study was to develop a widely accepted prognostic nomogram for extranodal NK/T-cell lymphoma, nasal-type (NKTCL). The clinical data from 1383 patients with NKTCL treated at 10 participating institutions between 2000 and 2011 were reviewed. A nomogram was developed that predicted overall survival (OS) based on the Cox proportional hazards model. To contrast the utility of the nomogram against the widely used Ann Arbor staging system, the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI), we used the concordance index (C-index) and a calibration curve to determine its predictive and discriminatory capacity. The 5-year OS rate was 60.3% for the entire group. The nomogram included five important variables based on a multivariate analysis of the primary cohort: stage; age; Eastern Cooperative Oncology Group performance status; lactate dehydrogenase; and primary tumor invasion. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.72 for both cohorts, which was superior to the predictive power (range, 0.56-0.64) of the Ann Arbor stage, IPI and KPI in the primary and validation cohorts. The proposed nomogram provides an individualized risk estimate of OS in patients with NKTCL.