Dosimetric analysis of brachial plexopathy after stereotactic body radiotherapy: Significance of organ delineation.

OBJECTIVES: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy. MATERIALS AND METHODS: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression. RESULTS: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-Dmax) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-Dmax) was 11.2 Gy (median) lower than BP-Dmax. Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BEDmax LQL and BP-BED0.3cc LQL, α/ß = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively. CONCLUSION: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED0.3cc LQL and BP-BEDmax LQL as potential predictors of RIBP2.

Can low-dose intravenous bevacizumab be as effective as high-dose bevacizumab for cerebral radiation necrosis?

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.

Erratum: Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4: Erratum.

[This corrects the article DOI: 10.7150/jca.39760.].

DNA barcoding of Chinese snakes reveals hidden diversity and conservation needs.

DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbour distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species-delimitation methods (ABGD, sGMYC, and sPTP) recover 320 operational taxonomic units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty-eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most probably caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes.

First national record of Microhylahmongorum Hoang, Nguyen, Phan, Pham, Ninh, Wang, Jiang, Ziegler and Nguyen, 2022 (Anura, Microhylidae, Microhyla) in China.

Background: To date, 10 species of the genus Microhyla have been recorded in China, of which six were distributed in Yunnan Province. Microhylahmongorum Hoang, Nguyen, Phan, Pham, Ninh, Wang, Jiang, Ziegler, and Nguyen, 2022 was also speculated to be distributed in Xishuangbana, Yunnan Province, China. However, there is no evidence of documentation of M.hmongorum. New information: We report the first country record of Microhylahmongorum, based on specimens collected from Yunnan border region. Morphologically, the specimen was consistent with the original descriptions of M.hmongorum. Phylogenetically, the sequences of the specimens from China clustered with the sequence of type specimens of M.hmongorum from Vietnam, with uncorrected pairwise distances of 0.9% at the 16S gene fragment analysed. Therefore, we report M.hmongorum as a new record species in China.

Risk-adapted stereotactic body radiotherapy for patients with cervical spinal metastases.

Owing to the complex anatomical structure and biomechanics, the current standard palliative treatments for cervical spinal metastases are associated with a high risk of recurrence and complications. Stereotactic body radiotherapy (SBRT) can provide radical dose to tumors while protecting normal organs to the maximum extent. However, the efficacy and safety of SBRT for cervical spinal metastases is not well characterized. Data from 71 patients with cervical spine metastases who were treated with SBRT using CyberKnife between 2006 and 2021 were obtained from our prospectively maintained database. Primary endpoint was pain response at 12 weeks following SBRT completion; secondary endpoints included local control (LC), overall survival (OS), and adverse events. Standard-risk patients were planned to receive 30 Gy (range 21-36) with median fractions of 3 (range 1-3) and high-risk patients 35 Gy (range 24-50) with median fractions of 5 (range 4-5) according to the spinal cord and esophagus dose constraints. The median follow-up time was 17.07 months (range 3.1-118.9). After 12 weeks of SBRT completion, 54 (98.2%) of 55 patients with baseline pain achieved pain response and 46 (83.6%) achieved complete pain response. LC rates were 93.1% and 90% at 1 year and 2 year, respectively. The 1-year and 2-year OS rates were 66.2% and 37.4%, respectively. Eight patients experienced grades 1-4 adverse events (six vertebral compression fracture [VCF], five of them had VCF before SBRT; and two hemiparesis). No grade 5 adverse events were observed. Therefore, risk-adapted SBRT for cervical spine metastases achieved high pain control and LC rates with acceptable adverse events.

Comparative multi-locus assessment of modern Asian newts ( Cynops, Paramesotriton, and Pachytriton: Salamandridae) in southern China suggests a shared biogeographic history.

Evolutionary biologists are always interested in deciphering the geographic context of diversification, therefore they introduced the concept of comparative phylogeography, which helps to identify common mechanisms that contribute to shared genetic structures among organisms from the same region. Here, we used multi-locus genetic data along with environmental data to investigate shared phylogeographic patterns among three Asian-endemic newt genera, Cynops, Paramesotriton and Pachytriton, which occurred in montane/submontane streams or ponds in southern China. Our 222 samples from 78 localities covered the entire range of the three genera and represented the largest dataset of this group to date. We reconstructed matrilineal genealogies from two protein-coding, mitochondrial genes, and gene network from two nuclear genes. We also estimated divergence times of major cladogenetic events and used occurrence data to evaluate niche difference and similarity between lineages. Our results revealed a common basal split in all three genera that corresponds to the separation of two geographic terrains of southern China. Those ancient divergence occurred during middle to late Miocene and likely correlate with paleoclimatic fluctuations caused by the uplift of the Qinghai-Xizang (Tibet) Plateau (QTP). Particularly, the strengthening and weakening of Asian summer monsoons during the Miocene may have profoundly impacted southern China and led to repeatedly vicariance in those newts. However, despite differences in realized niches between lineages, there is no evidence for divergence of fundamental niches. Preservation of old newt matriline lineages in mountains of southern China suggests that the region acts as both museums and cradles of speciation. Based on those results, we advocate a multi-pronged protection strategy for newts in the three genera.

Molecular phylogeny and morphological comparisons of the genus Hebius Thompson, 1913 (Reptilia: Squamata: Colubridae) uncover a new taxon from Yunnan Province, China, and support revalidation of Hebius septemlineatus (Schmidt, 1925).

We describe a new species of the genus Hebius and provide evidence for the validity of H. septemlineatuscomb. nov. Morphological and molecular analyses of Hebius specimens collected in Yunnan Province, China, revealed three distinct lineages, namely the newly described Hebius weixiensissp. nov., as well as H. octolineatus (Boulenger, 1904), and H. septemlineatuscomb. nov. (Schmidt 1925), which is removed from synonymy with H. octolineatus. Based on mitochondrial genealogy, Hebius weixiensissp. nov. is sister to H. septemlineatuscomb. nov., while H. octolineatus is sister to H. bitaeniatus. The new species and H. septemlineatuscomb. nov. showed considerable genetic divergence from their recognized congeners (uncorrected P-distance ≥3.9%). Furthermore, the new species and H. septemlineatuscomb. nov. can be diagnosed from closely related congeners by a combination of pholidosis characters.

Multi-locus genetic analyses of Quasipaa from throughout its distribution.

Montane frogs of the genus Quasipaa Dubois, 1992 occur from southern China to Southeast Asia (Frost 2021). Analyses of mtDNA (Cytb) and nuDNA data (Rag1, Rag2, Rhod, Tyr) for samples from 93 localities throughout its distribution yield a phylogeny. Clades A and B occur in Southeast Asia, clade C in northern Yangtze River, China, clade D in southwestern China, and clades E and F in southeastern China. Results place Q. yei within monophyletic Quasipaa and identify two new species. Based on nuDNA data, the basal split of clade A and B indicates an Indochinese origin of Quasipaa. The west-east diversification of five species across South China (Q. spinosa, Q. exilispinosa, Q. jiulongensis, Q. shini, Q. boulengeri) corresponds to topographic terrains II and III of China. Divergence of species from southeastern China (Q. shini, Q. jiulongensis, Q. spinosa, Q. exilispinosa) and southwestern China (Q. boulengeri) dates to 15.30-16.56 Ma (million years ago). A principal component analysis (PCA) and t-test involving 19 bioclimatic variables identifies significantly different environmental conditions between the two regions. Species' distribution models (SDM) for Q. spinosa and Q. boulengeri identify the best areas to be eastern and western South China, respectively. Thus, environmental variation appears to have influenced the genetic divergence and distributions of Quasipaa in South China. Mito-nuclear discordance indicates that some individuals of Q. exilispinosa and Q. spinosa hybridized historically.

Two new species and a new country record of the genus emAchalinus/em (Reptilia: Squamata: Xenodermidae) from China.

Combining the results from morphological and molecular analyses, we explore the taxonomy of the genus Achalinus from Southwest China. As a result, we describe two new species, A. panzhihuaensis sp. nov. and A. yangdatongi sp. nov. from southern Sichuan and southern Yunnan provinces, respectively, and we record a new country record, A. emilyae, from Guangxi Zhuang A. R.. The mitochondrial genealogy suggests that A. panzhihuaensis sp. nov. is sister to A. meiguensis, while A. yangdatongi sp. nov. clusters with the sister species A. juliani and A. ater. Both new species show considerable genetic divergence from their recognized congeners (uncorrected p-distance 6.2 % in COI gene). Furthermore, both new species can be diagnosed from closely related congeners by a combination of pholidosis characters. With our discovery, we provide a revised key to the 13 species from China and discuss some of the remaining issues regarding the taxonomy of the genus in China.

Description of a new species of Bush frog (Anura: Rhacophoridae: Raorchestes) from northwestern Yunnan, China.

Approximately half of the species in speciose genus Raorchestes were described during the past 10 years, yet only 11 species are known from Southeast Asia and southern China (SEA-SC), adjacent Himalayas, and northeastern India. Field work in northwestern Yunnan province, China resulted in the discovery of one new species in the genus based on morphological and molecular analyses. The new species is diagnosed by small size with 15.0-19.0 mm SVL in adult males (n=3); tongue pyriform, notched posteriorly; rudimentary webbing between toes; fingers and toes with narrow lateral dermal fringes; tibiotarsal articulation reaching anterior of the eye when hindlimb is stretched along the side of the body; relative finger lengths: I < II < IV < III, relative toe lengths: I < II < V < III < IV; inner metatarsal tubercle oval, outer metatarsal tubercle absent; finger discs and toe discs greyish or orange; flank near the crotch with a distinct black region between two creamy white patches, and the thigh having a similar black patch near the groin, proximal to another creamy white patch; a distinct ") ("-shaped dark marking on the back; male with external single subgular vocal sac; nuptial pad absent. A phylogenetic tree was reconstructed based on the mitochondrial genes for 16S rRNA and ND1. The results indicated that these individuals form a monophyletic group, and show high genetic divergence to their closest relatives within the genus (uncorrected p-distances > 3.2%) by distance of 16S comparable to the divergence between recognized Raorchestes species. This study further enriches the diversity of rhacophorids, especially in northwestern Yunnan.

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.

Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4.

Lung cancer is a type of malignant tumor with high morbidity and mortality. Due to its complicated etiology and clinical manifestations, no significant therapeutic advance has been made. Lung squamous cell carcinoma (LSCC) is the most common type of lung cancer. To combat this disease, novel therapeutic targets are badly requirement. ASPM (Abnormal spindle-like microcephaly-associated protein) is involved in multiple cellular or developmental processes, such as neurogenesis and brain growth. ASPM is also reported widely expressed in multiple tumor tissues and involved in the development and progression of several cancers including lung cancer. However, the potential role on ASPM on LSCC is still unclear. In this study, we reported that ASPM was related to the poor prognosis of patients with lung squamous cell carcinoma. Our results further showed that ASPM depletion dramatically inhibited the proliferation of LSCC cells, consistent with the obviously decreased of cyclin D1(CCND1) and cyclin dependent kinases 4 (CDK4) expression. In vivo assays further confirmed ASPM ablation markedly blocked tumor growth in vivo compared with control. In addition, a co-expression was found between ASPM and CDK4 in human tumor tissues. Taken together, our data provides strong evidence that ASPM promotes lung squamous cell carcinoma proliferation in vitro and in vivo, and indicates its potential role as a LSCC therapeutic target.

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.

How little is known about "the little brown frogs": description of three new species of the genus Leptobrachella (Anura: Megophryidae) from Yunnan Province, China.

Asian leaf-litter toads of the genus Leptobrachella represent a great anuran diversification in Asia. Previous studies have suggested that the diversity of this genus is still underestimated. During herpetological surveys from 2013 to 2018, a series of Leptobrachella specimens were collected from the international border areas in the southern and western parts of Yunnan Province, China. Subsequent analyses based on morphological and molecular data revealed three distinct and previously unknown lineages, which we formally describe as three new species herein. Among them, we describe a new species that occurs at the highest known elevation for Leptobrachella in China. Four species of Leptobrachella, including two new species, are found in the same reserve. Furthermore, our results suggest that the population from Longchuan County, Yunnan, may represent an additional new species of Leptobrachella, although we tentatively assigned it to Leptobrachella cf. yingjiangensis due to the small sample size examined. Lastly, we provide the first description of females of L. yingjiangensis. Our results further highlight that both micro-endemism and sympatric distributions of species are common patterns in Leptobrachella, that contribute to taxonomic and conservation challenges in these frogs. We provide an identification key for Leptobrachella known to occur in Yunnan. Given the lack of knowledge on species diversity of Leptobrachella along international border areas, we recommend that future studies include trans-boundary collaborative surveys.

A new species of the genus Leptobrachella Smith, 1925 (Anura, Megophryidae) from Guizhou, China.

Asian leaf-litter toads of the genus Leptobrachella represent charismatic anuran diversification with 80 species, of which 25 are from China. Recent new discoveries suggest that the diversity of this genus is underestimated. Here, we describe a new species of Leptobrachella, Leptobrachella bashaensis sp. nov. from the Basha Nature Reserve, Congjiang County, Guizhou Province, China. The new species is distinguished from its congeners by the following suite of morphological traits: small body size (SVL 22.9-25.6 mm in six adult males and 27.1 mm in one adult female); head longer than wide; dorsal skin slightly shagreened with small tubercles; creamy-white chest and belly with irregular black spots; distinct ventrolateral glands forming a white line; finger webbing and fringes absent; toe webbing rudimentary and lateral fringes narrow; iris bicolored with bright orange in upper half and silver in lower half; dorsal surface of tadpole head dark brown with small, brown, irregular spot, air sac-shaped bulges on both sides of body. The new species differs from all known congeners by an uncorrected p-distance of >5.3% of the 16S rRNA gene fragment examined, and the phylogenetic analysis clusters the new species with L. maoershanensis and L. laui. At present, the new species is only known from a small range of montane evergreen secondary forests in Basha Nature Reserve approximately 900 m elevation. Its natural history and conservation status are discussed.

An integrative phylogenomic approach illuminates the evolutionary history of Old World tree frogs (Anura: Rhacophoridae).

Rhacophoridae are one of the most speciose and ecologically diverse families of amphibians. Resolution of their evolutionary relationships is key to understanding the accumulation of biodiversity, yet previous hypotheses based on Sanger sequencing exhibit much discordance amongst generic relationships. This conflict precludes the making of sound macroevolutionary conclusions. Herein, we conduct the first phylogenomic study using broad-scale sampling and sequences of 352 nuclear DNA loci obtained using anchored hybrid enrichment targeted sequencing. The robust time-calibrated phylogenetic hypothesis clarifies several long-disputed relationships and facilitates the testing of evolutionary hypotheses on spatiotemporal diversification and reproductive modes. The major extant lineages of Rhacophoridae appear to have radiated in mainland Asia, and the spatiotemporal process corresponds with several common accumulations of biodiversity in Asia. Analyses do not detect any case of "Out of Himalaya" in Rhacophoridae. All transitions of reproductive modes appear to have evolved in an ordered, gradual sequence associated with gaining independence of standing water for larval development. The different reproductive modes are phylogenetically conserved and the completion of their transitions appear to have occurred over a period of ~30 Ma, which does not fit a pattern of a rapid burst of diversification. Innovations in reproductive modes associate statistically with the uneven distribution of species-richness between clades, where higher diversification is linked to increased terrestrial modes of reproduction. These results strengthen the hypothesis that breeding innovations drive diversification by providing new opportunities for ecological release and dispersion.

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.