Prognostic model incorporating immune checkpoint genes to predict the immunotherapy efficacy for lung adenocarcinoma: a cohort study integrating machine learning algorithms.

This study aimed to develop and validate a nomogram based on immune checkpoint genes (ICGs) for predicting prognosis and immune checkpoint blockade (ICB) efficacy in lung adenocarcinoma (LUAD) patients. A total of 385 LUAD patients from the TCGA database and 269 LUAD patients in the combined dataset (GSE41272 + GSE50081) were divided into training and validation cohorts, respectively. Three different machine learning algorithms including random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression analysis, and support vector machine (SVM) were employed to select the predictive markers from 82 ICGs to construct the prognostic nomogram. The X-tile software was used to stratify patients into high- and low-risk subgroups based on the nomogram-derived risk scores. Differences in functional enrichment and immune infiltration between the two subgroups were assessed using gene set variation analysis (GSVA) and various algorithms. Additionally, three lung cancer cohorts receiving ICB therapy were utilized to evaluate the ability of the model to predict ICB efficacy in the real world. Five ICGs were identified as predictive markers across all three machine learning algorithms, leading to the construction of a nomogram with strong potential for prognosis prediction in both the training and validation cohorts (all AUC values close to 0.800). The patients were divided into high- (risk score ≥ 185.0) and low-risk subgroups (risk score < 185.0). Compared to the high-risk subgroup, the low-risk subgroup exhibited enrichment in immune activation pathways and increased infiltration of activated immune cells, such as CD8 + T cells and M1 macrophages (P < 0.05). Furthermore, the low-risk subgroup had a greater likelihood of benefiting from ICB therapy and longer progression-free survival (PFS) than did the high-risk subgroup (P < 0.05) in the two cohorts receiving ICB therapy. A nomogram based on ICGs was constructed and validated to aid in predicting prognosis and ICB treatment efficacy in LUAD patients.

Predictive Model to Identify the Long Time Survivor in Patients with Glioblastoma: A Cohort Study Integrating Machine Learning Algorithms.

We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS<1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (P<0.05) and greater infiltration of immune suppression cells compared to LTS (P<0.05). Four genes, namely, OSMR, FMOD, CXCL14, and TIMP1, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (C-index, 0.791; 0.772-0.817) and validation cohort (C-index, 0.770; 0.751-0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.

Clinical performance evaluation of O-Ring Halcyon Linac: A real-world study.

BACKGROUND: Radiation therapy, especially the development of linear accelerators, plays a key role in cancer management. The fast-rotating coplanar O-ring Halcyon Linac has demonstrated many advantages. The previous literature has mainly focused on the machine parameters and plan quality of Halcyon, with a lack of relevant research on its clinical application. AIM: To evaluate the clinical performance of the O-ring Halcyon treatment system in a real-world application setting. METHODS: Data from sixty-one patients who were treated with the Halcyon system throughout the entire radiotherapy process in Peking Union Medical College Hospital between August 2019 and September 2020 were retrospectively reviewed. We evaluated the target tumour response to radiotherapy and irradiation toxicity from 1 to 3 mo after treatment. Dosimetric verification of Halcyon plans was performed using a quality assurance procedure, including portal dosimetry, ArcCHECK and point dose measurements for verification of the system delivery accuracy. RESULTS: Of the 61 patients in the five groups, 16, 12, 7 and 26 patients had complete response, partial response, progressive disease and stable disease, respectively. No increase in the irradiated target tumour volume was observed when separately evaluating the local response. Regarding irradiation toxicity, no radiation-induced deaths were observed. Thirty-eight percent (23/61 patients) had no radiation toxicity after radiotherapy, 56% (34/61 patients) experienced radiation toxicity that resolved after treatment, and 6% (4/61 patients) had irreversible adverse reactions. The average gamma passing rates with a 2% dose difference and 2-mm distance to agreement for IMRT/VMAT/SRT plans were ArcCHECK at 96.4% and portal dosimetry at 96.7%, respectively. All of the validated clinical plans were within 3% for point dose measurements, and Halcyon's ArcCHECK demonstrated a high pass rate of 99.1% ± 1.1% for clinical gamma passing criteria of 3%/3 mm. CONCLUSION: The O-ring Halcyon Linac could achieve a better therapeutic effect on the target volume by providing accurate treatment delivery plans with tolerable irradiation toxicity.

Abdominopelvic Lymphatic Drainage Area Irradiation for Consolidative Radiotherapy of Advanced Ovarian Carcinoma: Analysis of Clinical Application Efficacy and Dosimetric Verification.

Background: The aim of the study was to evaluate the efficacy of abdominopelvic lymphatic drainage area irradiation (APLN), instead of whole abdominal radiotherapy (WART), in the consolidative radiotherapy of advanced ovarian carcinoma patients. Methods: We conducted a retrospective analysis collecting 99 patients with locally advanced ovarian cancer treated by APLN with 45 - 50 Gy/25- 28 fractions/5-7#, instead of WART. We evaluated the clinical outcome of APLN. Five patients were selected for dosimetric verifications verses WART (30 Gy/20 fractions). The normal tissue complication probability (NTCP) was calculated for the two treatment methods. Results: The mean follow-up time was 64.10 months (5.5 - 113.2 months), after APLN consolidative radiotherapy, 1-, 3-, and 5-year overall survival (OS) was 87.9%, 81.3%, and 61.5%, median disease-free survival (DFS) was 40.8 months, 5-year local recurrence free survival (LRFS) was 75.9%, and 5-year distant metastasis free survival (DMFS) was 49.2%. One patient died due to intestinal perforation. Local recurrence in the area between WART and APLN was rare (3/99 patients). The number of surgical procedures < 2 was an independent risk factor for LRFS (P = 0.023). Dosimetric comparison showed that comparing with WART, APLN significantly reduced the organ at risk (OAR) dose: 25.37 ± 3.63 Gy (25%) for liver, 8.77 ± 5.03 Gy (25%) for kidney, 8.14 ± 1.51 Gy (25%) for small intestine, etc. NTCP was reduced by 0.04-1.04% for liver, kidney, and small intestine. Conclusion: For consolidative radiotherapy in locally advanced ovarian cancer, APLN (intensity-modulated radiotherapy 45 - 50 Gy/25 - 28 fractions) could be an alternative to WART, resulting in excellent LRFS and DFS, with acceptable toxicities, comparing with previous literature reports. Dosimetric analysis also showed the benefits of APLN in NTCP.

Using New Vaginal Doses Evaluation System to Assess the Dose-Effect Relationship for Vaginal Stenosis After Definitive Radio(Chemo)Therapy for Cervical Cancer.

Objective: The study aims to investigate if a relationship exists between vaginal doses and vaginal stenosis (VS) using posterior-inferior border of symphysis (PIBS) points and the International Commission on Radiation Units-Rectum (ICRU-R) point evaluation system for definitive radio(chemo)therapy in locally advanced cervical cancer. Methods and Materials: From a vaginal dose study in China, 351 patients were prospectively assessed. For every reference point of the PIBS system and ICRU-R point was calculated for all BT and summed with EBRT. Pearson's chi-square test and Student's unpaired t-test compared variables with and without vaginal stenosis (VS) G ≥2. The risk factors were assessed for VS G ≥2 in multi- and univariate analyses through Cox proportional hazards model followed by a dose-effect curve construction. The VS morbidity rate was compared via the log-rank test using the median vaginal reference length (VRL). Results: The patients (38-month median follow-up) had 21.3% three-year actuarial estimate for VS G ≥2. Compared to G <2 patients, VS G ≥2 patients received higher doses to PIBS points except for PIBS - 2 and had significantly shorter VRL. VRL (HR = 1.765, P = 0.038), total EBRT and BT ICRU-R point dose (HR = 1.017, p = 0.003) were risk factors for VS. With VRL >4.6 cm, the 3-year actuarial estimate was 12.8% vs. 29.6% for VRL ≤4.6 cm. According to the model curve, the risks were 21, 30, and 39% at 75, 85, and 95 Gy, respectively (ICRU-R point dose). Conclusions: PIBS system point doses correlated with late vaginal toxicity. VRL combined with both EBRT and BT dose to the ICRU-R point contribute to VS risk.

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study.

Limited evidence supports the use of early endpoints to evaluate the success of initial treatment of extranodal NK/T-cell lymphoma (ENKTCL) in the modern era. We aim to analyze progression-free survival at 24 months (PFS24) and subsequent overall survival (OS) in a large-scale multicenter cohort of patients. 1790 patients were included from the China Lymphoma Collaborative Group (CLCG) database. Subsequent OS was defined from the time of PFS24 or progression within 24 months to death. OS was compared with age- and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Patients who did not achieve PFS24 had a median OS of 5.3 months after progression, with 5-year OS rate of 19.2% and the SMR of 71.4 (95% CI, 62.9-81.1). In contrast, 74% patients achieved PFS24, and the SMR after achieving PFS24 was 1.77 (95% CI, 1.34-2.34). The observed OS rate after PFS24 versus expected OS rate at 5 years was 92.2% versus 94.3%. Similarly, superior outcomes following PFS24 were observed in early-stage patients (5-year OS rate, 92.9%). Patients achieving PFS24 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. These marked differences suggest that PFS24 may be used for study design and risk stratification in ENKTCL.

Validation of nomogram-revised risk index and comparison with other models for extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: indication for prognostication and clinical decision-making.

Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell's C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.

First-line non-anthracycline-based chemotherapy for extranodal nasal-type NK/T-cell lymphoma: a retrospective analysis from the CLCG.

The present study investigated the survival benefit of non-anthracycline (ANT)-based vs ANT-based regimens in a large-scale, real-world cohort of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL). Within the China Lymphoma Collaborative Group (CLCG) database (2000-2015), we identified 2560 newly diagnosed patients who received chemotherapy with or without radiotherapy. Propensity score matching (PSM) and multivariable analyses were used to compare overall survival (OS) and progression-free survival (PFS) between the 2 chemotherapy regimens. We explored the survival benefit of non-ANT-based regimens in patients with different treatments in early-stage disease and in risk-stratified subgroups. Non-ANT-based regimens significantly improved survivals compared with ANT-based regimens. The 5-year OS and PFS were 68.9% and 59.5% for non-ANT-based regimens compared with 57.5% and 44.5% for ANT-based regimens in the entire cohort. The clinical advantage of non-ANT-based regimens was substantial across the subgroups examined, regardless of stage and risk-stratified subgroup, and remained significant in early-stage patients who received radiotherapy. The survival benefits of non-ANT-based regimens were consistent after adjustment using multivariable and PSM analyses. These findings provide additional evidence supporting non-ANT-based regimens as a first-line treatment of patients with ENKTCL.

Risk-based, response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study.

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.

Vaginal dose of radical radiotherapy for cervical cancer in China: a multicenter study.

BACKGROUND: The posterior-inferior border of symphysis (PIBS) point system is a novel vaginal dose-reporting method and is a simple and reliable method proposed by the Medical University of Vienna proposed for both external-beam radiotherapy (EBRT) and brachytherapy (BT). In this multicenter study, we sought to first evaluate the vaginal radiation dose in Chinese cervical cancer patients according to the PIBS point system and then to analyze the factors influencing the dose distribution. METHODS: We collected data from the medical records of 936 cervical cancer patients who underwent concurrent radiochemotherapy at 13 different institutions in China. Radiation doses at points A, PIBS+ 2 cm, PIBS and PIBS-2 cm, International Commission on Radiation Units (ICRU)-R and ICRU-B were measured. RESULTS: The median total doses in EQD2α/ß = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 82.5 (52.7-392.1) Gy, 56.2 (51.4-82.1) Gy and 2.6 (0.9-7.4) Gy, respectively. The median total doses in EQD2α/ß = 3 at ICRU-R and ICRU-B were 77.5 (54.8-132.4) Gy and 79.9 (60.7-133.7) Gy, respectively. The mean vaginal reference length (VRL) was 4.6 ± 1.0 cm (median, 4.5 cm). In patients with VRL ≤4.5 cm, the mean total doses in EQD2α/ß = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 128.5, 60.7 and 0.8 Gy, respectively. In patients with VRL > 4.5 cm, the mean total doses at these three points were 68.9, 0.5 and 54.5 Gy, respectively. Classification of patients revealed significant differences (P < 0.05) between these two groups. CONCLUSIONS: With the PIBS point system, Chinese patients with a shorter VRL of < 4.5 cm received higher radiation doses at the PIBS+ 2 cm, PIBS and PIBS-2 cm points than European and American patients. Further studies are required to establish the dose-effect relationships with these points as references. The study was registered as a clinical trial (NCT03257475) on August 22, 2017.

Effect of age as a continuous variable on survival outcomes and treatment selection in patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group (CLCG).

PURPOSE: The aim of this study was to determine the impact of analyzing age as a continuous variable on survival outcomes and treatment selection for extranodal nasal-type NK/T-cell lymphoma. RESULTS: The risk of mortality increased with increasing age, without an apparent cutoff point. Patients' age, as a continuous variable, was independently associated with overall survival after adjustment for covariates. Older early-stage patients were more likely to receive radiotherapy only whereas young-adult advanced-stage patients tended to receive non-anthracycline-based chemotherapy. A decreased risk of mortality with radiotherapy versus chemotherapy only in early-stage patients (HR, 0.347, P < 0.001) or non-anthracycline-based versus anthracycline-based chemotherapy in early-stage (HR, 0.690, P = 0.001) and advanced-stage patients (HR, 0.678, P = 0.045) was maintained in patients of all ages. CONCLUSIONS: These findings support making treatment decisions based on disease-related risk factors rather than dichotomized chronological age. PATIENTS AND METHODS: Data on 2640 patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group database were analyzed retrospectively. Age as a continuous variable was entered into the Cox regression model using penalized spline analysis to determine the association of age with overall survival (OS) and treatment benefits.

[Sexual Quality of Life in Patients with Cervical Cancer Undergoing Radiotherapy].

To investigate the sexual quality of life and its influencing factors in patients with cervical cancer undergoing radiotherapy. Methods Totally 205 patients with cervical cancer who received radiotherapy in Peking Union Medical College Hospital from December 2013 to December 2018 were enrolled in this study.The Female Sexual Function Index(FSFI)scale was used to assess the sexual quality of life of these patients.The demographic data(including age,education level,marital status,family status,and occupation)and clinical data(including tumor stage and treatment method)were collected.Mann-Whitney U test and Kruskal-Wallis test were used to analyze the influence of various factors on the sexual quality of life. Results Female sexual dysfunction was common among patients with cervical cancer undergoing radiotherapy.The total FSFI score was 5.5(3.6,16.3),and the scores of subscales were as follows:desire,1.20(0,1.80);sexual arousal,0.90(0,1.80);vaginal lubrication,0.30(0,3.30);orgasm,0(0,2.80);satisfaction,2.40(1.60,3.60);and sexual pain,0(0,2.80).Age(P=0.010),duration of radiotherapy(P=0.008),marital status(P=0.020),family status(P=0.010),and occupation(P=0.024)were influential factors of sexual quality of life in cervical cancer patients undergoing radiotherapy. Conclusions The sexual quality of life of patients with cervical cancer undergoing radiotherapy is affected by multiple factors.Instructions on treatment,mental status,and post-treatment sexual life should be offered in an individualized way to improve the sexual quality of life of these patients.

Outcomes of intermediate-risk to high-risk stage I endometrial cancer: 10-year clinical experiences of using in-house multi-channel applicators in a single center.

BACKGROUND: There are only very few reports on clinical outcomes using multi-channel applicators (MCA) for patients with endometrial cancer (EC) in China. We aimed to evaluate the clinical experience of treating intermediate-risk (IR) to high-risk (HR) stage I EC using in-house made multi-channel applicators (IH-MCA) in a single institution. METHODS: Three hundred and ninety patients with stage I IR to HR EC were treated with hysterectomy and adjuvant radiotherapy from 2003 to 2015. All patients received post-operative vaginal cuff brachytherapy (VBT) alone or as a boost after external beam radiotherapy (EBRT). The prescriptions were 500 cGy per fraction for a total of 5 to 6 fractions with brachytherapy alone or 400 to 600 cGy per fraction for 2 to 3 fractions if it was combined with EBRT. Two types of applicators including a traditional rigid IH-MCA and a recent model custom-made with 3 dimension printing technology were used for treatment. The Kaplan-Meier method was used to calculate survival rate. RESULTS: Follow-up rate was 92.8% and the median follow-up time was 48 months (range 4-172 months). The 5-year overall survival (OS), progression-free survival, local recurrence, and distant metastasis rates for all patients were 96.3%, 92.1%, 2.9%, and 4.8% respectively. Two patients had isolated relapse in vagina outside the irradiated volume. The univariate and multivariate analysis showed that age and grade were the prognostic factors correlated with OS (hazard ratio: 0.368, 95% confidence interval [CI]: 0.131-1.035, P = 0.048; hazard ratio: 0.576, 95% CI: 0.347-0.958, P = 0.026,). CONCLUSIONS: For patients with IR to HR stage I EC, adjuvant VBT alone or in combination with EBRT using IH-MCA led to excellent survival and recurrence rates. Age and grade were the prognostic factors correlated with OS.

[Information Needs and Quality among Cervical Cancer Patients].

Objective To investigate the demand for scientific information among cervical cancer patients and to evaluate the quality of the relevant information available for these patients.Methods The demand for medical science information among patients with cervical cancer was investigated via questionnaire.The Discernn scoring system was used to score the cervical cancer science articles retrieved by Baidu and Sogou.A model was established to analyse the reading difficulty of these articles.Results Nearly half(53.6%)of the respondents searched for online science information at least weekly.The main target readings were the etiology and risk factors of diseases,symptoms,treatment options,adverse reactions of treatments,and prognosis.Most respondents(96.4%)thought that the network science information was reliable.Of the 104 search results included in the sample bank,13(12.5%)met the inclusion criteria,91(87.5%)were not selected,including 32 duplicates(30.8%),6 non-text webpages(5.8%),18 short texts(less than 300 Chinese characters)(17.3%),7 advertisements(6.7%),3 news articles(2.9%),22 forum posts(21.2%),and 3 academic articles(2.9%).According to the Discern scoring system,the reliability(r=0.728, P<0.001),the quality of treatment-related information(r=0.431, P<0.001),and the overall scores(r=0.559,P<0.001)of the enrolled 13 publications were consistent,as evaluated by two professional physicians.The mean overall score was 3.A lower score(less than 3)in the reliability assessment was due to the source of the content,generation methods,sponsors,citations,and the undefined parts.During the evaluation of treatment information,the average score was below 3 for each item.Analysis of the reading difficulty showed that,among these 13 articles,4 were at postgraduate thesis level(level 5),4 at undergraduate thesis level(level 4),0 at high school textbook level(level 3),and 8 was higher than middle school level(≥level 3).Eight articles(61.5%)were suitable for readers with an education background of higher middle school and only 5 articles(38.5%)were suitable for readers with an education background of middle school or lower(≤ level 2).Conclusions The vast majority of patients with cervical cancer search for clinical information through the Internet and trust their reliability.Chinese search engines have lower detection rates for high-quality medical science articles.The currently available high-quality medical science articles are small in number and difficult to read.More physicians are urged to write easy-to-read high-quality articles for these patients.

Effect of primary tumor invasion on treatment and survival in extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: a multicenter study from the China Lymphoma Collaborative Group (CLCG).

We evaluated the effect of primary tumor invasion (PTI) on treatment selection in 1356 patients with extranodal nasal-type NK/T cell lymphoma who received non-anthracycline-based chemotherapy from the updated dataset of China Lymphoma Collaborative Group. 760 (56.0%) patients had PTI. PTI showed most prominent effect in stage I disease, with 5-year overall survival (OS) of 83.0% in PTI-absent patients and 69.5% in PTI-present patients (p < .001). Radiotherapy ± chemotherapy achieved higher OS in PTI-absent stage I patients (approximately 85%). Either radiotherapy alone or chemotherapy alone was associated with an unfavorable OS in PTI-present patients (approximately 55%). Compared to radiotherapy alone, combined modality treatment improved OS in PTI-present patients (78.3% vs. 56.6%; p = .001) but showed similar OS in PTI-absent patients (85.3% vs. 83.3%; p = .560). These findings were confirmed in multivariate analyses. PTI was a robust prognostic factor and indicator for additional chemotherapy in stage I NKTCL patients.

Risk-Dependent Conditional Survival and Failure Hazard After Radiotherapy for Early-Stage Extranodal Natural Killer/T-Cell Lymphoma.

Importance: Prognosis of early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is usually estimated and stratified at diagnosis, but how the prognosis actually evolves over time for patients who survived after curative treatment is unknown. Objective: To assess conditional survival and failure hazard over time based on risk categories, previous survival, and treatment. Design, Setting, and Participants: This retrospective cohort study reviewed the clinical data of 2015 patients with early-stage NKTCL treated with radiotherapy identified from the China Lymphoma Collaborative Group multicenter database between January 1, 2000, and December 31, 2015. Patients were stratified into low-, intermediate- and high-risk groups according to a previously established prognostic model. Median follow-up was 61 months for surviving patients. Data analysis was performed from December 1, 2017, to January 30, 2018. Exposures: All patients received radiotherapy with or without chemotherapy. Main Outcomes and Measures: Conditional survival defined as the survival probability, given patients have survived for a defined time, and annual hazard rates defined as yearly event rate. Results: A total of 2015 patients were included in the study (mean [SD] age, 43.3 [14.6] years; 1414 [70.2%] male); 1628 patients (80.8%) received radiotherapy with chemotherapy, and 387 (19.2%) received radiotherapy without chemotherapy. The 5-year survival rates increased from 69.1% (95% CI, 66.6%-71.4%) at treatment to 85.3% (95% CI, 81.7%-88.2%) at year 3 for conditional overall survival and from 60.9% (95% CI, 58.3%-63.3%) at treatment to 84.4% (95% CI, 80.6%-87.6%) at year 3 for conditional failure-free survival. The annual hazards decreased from 13.7% (95% CI, 13.0%-14.3%) for death and 22.1% (95% CI, 21.0%-23.1%) for failure at treatment to less than 5% after 3 years (death: range, 0%-3.9% [95% CI, 3.7%-4.2%]; failure: 1.2% [95% CI, 1.0%-1.4%] to 4.2% [95% CI 3.9%-4.6%]). Intermediate-risk (11.4% [95% CI, 10.5%-12.3%]) and high-risk (21.6% [95% CI, 20.0%-23.2%]) patients had initially higher but significantly decreased death hazards after 3 years (<6%, range: 0%-5.9% [95% CI, 5.2%-6.7%]), whereas low-risk patients maintained a constantly lower death hazard of less than 5% (range, 0%-4.8%; 95% CI, 4.4%-5.3%). In high-risk patients, radiotherapy combined with non-anthracycline-based regimens were associated with higher conditional overall survival before year 3 compared with anthracycline-based regimens (hazard ratio [HR] for death, 1.49; 95% CI, 1.13-1.95; P = .004 at treatment; HR, 1.60; 95% CI, 1.07-2.39; P = .02 at 1 year; and HR, 1.77; 95% CI, 0.94-3.33; P = .07 at 2 years) or radiotherapy alone (HR, 2.42; 95% CI, 1.73-3.39; P < .001 at treatment; HR, 1.82; 95% CI, 1.05-3.17; P = .03 at 1 year; and HR, 2.69; 95% CI, 1.23-5.90; P = .01 at 2 years). Conclusions and Relevance: The survival probability increased and the hazards of failure decreased in a risk-dependent manner among patients with early NKTCL after radiotherapy. These dynamic data appear to provide accurate information on disease processes and continual survival expectations and may help researchers design additional prospective clinical trials and formulate risk-adapted therapies and surveillance strategies.

Risk-dependent curability of radiotherapy for elderly patients with early-stage extranodal nasal-type NK/T-cell lymphoma: A multicenter study from the China Lymphoma Collaborative Group (CLCG).

BACKGROUND: The purpose of this study was to determine the curability of early-stage extranodal nasal-type NK/T-cell lymphoma (NKTCL) in response to radiotherapy and non-anthracycline-based chemotherapy in elderly patients. METHODS: In this multicenter study from the China Lymphoma Collaborative Group (CLCG) database, 321 elderly patients with early-stage NKTCL were retrospectively reviewed. Patients received radiotherapy alone (n = 87), chemotherapy alone (n = 59), or combined modality therapy (CMT, n = 175). Patients were classified into low- or high-risk groups using four prognostic factors. Observed survival in the study cohort vs expected survival in age- and sex-matched individuals from the general Chinese population was plotted using a conditional approach and subsequently compared using a standardized mortality ratio (SMR). RESULTS: Radiotherapy conveyed a favorable prognosis and significantly improved survival compared to chemotherapy alone. The 5-year overall survival (OS) and progression-free survival (PFS) were 61.2% and 56.4%, respectively, for radiotherapy compared with 44.7% and 38.3%, respectively, for chemotherapy alone (P < 0.001). The combination of a non-anthracycline-based chemotherapy regimen and radiotherapy significantly improved PFS compared to combination of an anthracycline-based chemotherapy regimen and radiotherapy (71.2% vs 44.2%, P = 0.017). Low-risk patients following radiotherapy (SMR, 0.703; P = 0.203) and high-risk patients who achieved PFS at 24 months (SMR, 1.490; P = 0.111) after radiotherapy showed survival equivalent to the general Chinese population. CONCLUSIONS: Our findings indicate a favorable curability for this malignancy in response to radiotherapy and non-anthracycline-based chemotherapy, providing a risk-adapted follow-up and counsel scheme in elderly patients.

Risk-adapted survival benefit of IMRT in early-stage NKTCL: a multicenter study from the China Lymphoma Collaborative Group.

This study evaluated the survival benefit of intensity-modulated radiation therapy (IMRT) compared with 3-dimension conformal radiation therapy (3D-CRT) in a large national cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). This retrospective study reviewed patients with early-stage NKTCL treated with high-dose radiation therapy (RT; ≥45 Gy) at 16 Chinese institutions. Patients were stratified into 1 of 4 risk groups based on the number of risk factors: low risk (no factors), intermediate-low risk (1 factor), intermediate-high risk (2 factors), and high-risk (3-5 factors). Of the 1691 patients, 981 (58%) received IMRT, and 710 (42%) received 3D-CRT. Unadjusted 5-year overall survival (OS) and progression-free survival (PFS) were 75.9% and 67.6%, respectively, for IMRT compared with 68.9% (P = .004) and 58.2% (P < .001), respectively, for 3D-CRT. After propensity score match and multivariable analyses to account for confounding factors, IMRT remained significantly associated with improved OS and PFS. The OS and PFS benefits of IMRT persisted in patients treated with modern chemotherapy regimens. Compared with 3D-CRT, IMRT significantly improved OS and PFS for high-risk and intermediate-high-risk patients but provided limited benefits for low-risk or intermediate-low-risk patients. A risk-adapted survival benefit profile of IMRT can be used to select patients and make treatment decisions.

MicroRNA-886-3P functions as a tumor suppressor in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive disease and miRNAs may play an important role in modulating SCLC progression. We have previously screened 924 miRNAs and found that miR-886-3P was negatively associated with SCLC survival. In the current study, we further investigated the role of miR-886-3P mimic in regulating SCLC cell phenotypic alteration in vitro and xenograft tumor formation in vivo. We found that transfection of miR-886-3P mimic significantly inhibited SCLC cell proliferation, migration, and colony formation, and induced mesenchymal-epithelial transition (MET) by suppressing TGF-ß1 synthesis in vitro. Furthermore, intra-tumor injection of miR-886-3P mimic lead to necrosis and suppression of tumor invasion to the surrounding tissue in the subcutaneous xenograft tumor, and intra-vein injection of miR-886-3P mimic suppressed xenograft lung cancer growth in vivo. These findings suggested that miR-886-3P functions as a tumor suppressor in SCLC and thus, it might be a potential therapeutic molecule in the treatment of lung cancer.