Introduction
Cancer-related pain remains a prevalent and burdensome symptom among patients with cancer. An updated meta-analysis spanning all phases of the disease estimated an overall pain prevalence of 44.5%, with moderate-to-severe pain affecting 30.6% of patients (1). Cancer-related pain can substantially compromise physical function, psychological well-being, and overall quality of life.
Within the International Classification of Diseases, 11th Revision (ICD-11) framework, chronic cancer-related pain encompasses pain attributable to primary or metastatic disease as well as pain caused by anticancer treatment (2). This inclusive clinical conceptualization highlights the diversity of etiologies and underlying mechanisms of cancer-related pain. The 2025 National Comprehensive Cancer Network (NCCN) guideline provides a more detailed clinical classification by distinguishing tumor-related pain, treatment-related pain, and pain unrelated to either, as well as acute and chronic pain.
From a pathophysiological perspective, it identifies three predominant pain mechanisms: nociceptive, neuropathic, and nociplastic pain; nociceptive pain is further categorized as somatic or visceral. Accordingly, the guideline emphasizes pain screening, comprehensive assessment, and multimodal management incorporating pharmacologic and nonpharmacologic approaches. Management should be individualized according to pain severity, etiology, pathophysiology, clinical circumstances, patient-specific goals, and safety considerations (3).
Against this background, clinical studies published in 2025 highlight two complementary directions in cancer pain management: continued refinement of established therapies and expansion toward integrated multimodal and longitudinal management (Figure 1). Pharmacologic analgesia, radiotherapy, radiopharmaceuticals, and interventional procedures continue to be refined, alongside growing attention to integrative interventions, risk identification for persistent pain, structured pain assessment, and coordinated care delivery. This review synthesizes representative clinical studies in 2025 and discusses their implications for current practice and future research.
The characteristics, study designs, principal findings, and key limitations of the original studies included in this review are summarized in Table 1.
Refining established therapies in cancer pain management
Pharmacologic treatment
Among established therapies, pharmacologic treatment remains a central component of cancer pain management. Clinical studies published in 2025 suggest that progress in this area has been characterized by more rational, individualized, and safety-conscious use of analgesic medications, with particular emphasis on optimizing opioid therapy, expanding mechanism-informed multimodal strategies, and improving opioid stewardship.
One major direction was the optimization of opioid therapy, with increasing attention to administration method, formulation, titration, combination strategies, and adverse-effect management. In hospitalized patients requiring intravenous opioids, a double-blind, double-dummy randomized crossover trial showed that slow intravenous hydromorphone administration achieved comparable analgesic efficacy to rapid injection while reducing sedation, suggesting that opioid delivery characteristics may influence tolerability without compromising pain relief (4). For patients with uncontrolled cancer pain despite ongoing opioid therapy, low-dose add-on methadone demonstrated potential short-term analgesic benefit, although interpretation remains limited by the single-arm design and small sample size (5).
Opioid formulation and adverse-effect management were further evaluated in the ENhANCE multicenter randomized trial, in which oxycodone/naloxone prolonged release maintained noninferior analgesia compared with oxycodone prolonged release while reducing opioid-induced constipation in patients with advanced cancer pain (6). For breakthrough cancer pain, prospective observational data on sublingual fentanyl showed clinically meaningful pain reduction at 30 and 60 min, supporting the role of rapid-onset transmucosal formulations in selected opioid-tolerant patients (7). Clinically, breakthrough cancer pain requires prompt rescue treatment and reassessment of both the episode and background-pain control.
New or acutely severe pain should prompt evaluation for an oncologic emergency or another reversible cause; rescue treatment should be individualized according to episode characteristics, opioid tolerance, available route, and previous response, with prompt reassessment of efficacy and adverse effects (3). Frequent or inadequately relieved episodes should prompt evaluation for disease progression, incident pain, or end-of-dose failure and may require adjustment of background analgesia, treatment of the underlying pain generator, or preemptive rescue medication for predictable episodes (3). A palliative care clinic study further suggested a potential role for buprenorphine-naloxone conversion in selected patients requiring long-term opioid therapy, although further comparative evidence is needed (8).
A second direction was the expansion of multimodal and mechanism-informed pharmacologic treatment, particularly for pain that may not be adequately controlled through opioid escalation alone. Ketamine and its enantiomers have also been explored as adjunctive options for pain and comorbid depressive symptoms in patients with cancer (36). More broadly, their development reflects interest in combining anesthetic, analgesic, and antidepressant properties across distinct ketamine stereoisomers (37).
Contemporary analgesic development has likewise emphasized non-opioid strategies and mechanism-oriented approaches as complements to conventional analgesia (38). The OPTIMAL-HN randomized clinical trial illustrates this approach in patients with radiation-induced mucositis pain after head and neck cancer treatment. A multimodal regimen consisting of pregabalin, acetaminophen, naproxen, and opioids when required achieved noninferior pain control compared with opioids alone during the last week of radiotherapy and showed improved longitudinal pain outcomes after treatment (9).
These findings support the selective incorporation of non-opioid analgesics according to pain mechanism and clinical context rather than routine escalation of opioid therapy. Mechanism-directed adjuvant strategies remain more exploratory. The LiCPain pilot randomized trial evaluated continuous subcutaneous lidocaine infusion for neuropathic cancer pain and demonstrated feasibility and acceptable short-term safety, but did not establish definitive superiority over placebo (10).
Overall, current evidence supports selective, mechanism-informed use of multimodal pharmacologic strategies rather than escalation of analgesic therapy without a clear clinical rationale.
A third area of progress involved balancing opioid safety with preservation of appropriate analgesic access. Studies published in 2025 highlight the importance of distinguishing cancer pain management from opioid prescribing approaches developed for chronic non-cancer pain. A national cohort study of older adults with cancer found that the 2016 Centers for Disease Control and Prevention (CDC) opioid guideline was associated with reduced typical opioid prescribing and increased gabapentinoid prescribing, raising concerns about unintended consequences when restrictive opioid policies are applied to oncology populations (11).
Similarly, a large health-system analysis showed that opioid prescribing trends varied according to clinical context, with reductions observed among some patient groups but relatively stable prescribing among patients with metastatic cancer reporting pain (12). Beyond prescribing patterns, cancer-specific approaches to opioid safety monitoring remain important. A multicenter validation study of the Prescription Opioid Misuse Index demonstrated that screening tools originally developed for chronic non-cancer pain show insufficient psychometric validity in patients with chronic cancer-related pain (13).
Thus, opioid stewardship in cancer pain should aim to preserve appropriate analgesic access while improving safety, rather than relying on prescribing restriction alone.
Overall, advances in pharmacologic analgesia in 2025 reflect a shift from simply escalating analgesic intensity toward more individualized selection, combination, and monitoring of analgesic therapies according to pain mechanism, clinical context, and patient risk.
Radiotherapy and radiopharmaceuticals for cancer pain
Bone metastases are an important source of cancer-related pain in patients with advanced disease and are associated with reduced quality of life and increased analgesic needs (39). Radiation-based therapies remain an important treatment modality in cancer pain management, particularly in patients with painful bone metastases and selected tumor-related pain syndromes. Clinical studies published in 2025 mainly addressed three aspects: optimization of radiotherapy in both techniques and dose, palliative radiotherapy to improve pain score and quality of life, and the emerging role of radiopharmaceuticals in patients with skeletal metastatic disease.
One major area of progress was the refinement of radiotherapy mode and dose strategies for painful bone metastases. The ROBOMET randomized clinical trial compared dose-escalated single-fraction stereotactic body radiotherapy (SBRT) with conventional single-fraction three-dimensional conformal radiotherapy in patients with painful bone metastases. SBRT did not significantly improve complete pain response at 1 month after radiotherapy, although a higher complete pain response rate was observed at 3 months after SBRT (14).
These findings suggest that SBRT should not be routinely applied to all patients with painful bone metastases. Conventional single-fraction radiotherapy remains an appropriate option when rapid and convenient palliation is the primary goal, whereas SBRT may be more suitable for selected patients with better performance status and longer expected survival.
Another important development was the broader assessment of clinical benefits after palliative radiotherapy. Pain response assessment has traditionally focused on the irradiated lesion; however, this approach may not fully reflect the patient’s overall symptom burden. A multicenter prospective observational study showed that baseline nonindex pain, defined as pain arising from sites not targeted by radiotherapy, was associated with a lower likelihood of pain response, worse posttreatment quality of life, and shorter survival among patients receiving radiotherapy for painful bone metastases (15).
A related prospective analysis further showed that classification incorporating pain response and time to progression was associated with differences in quality-of-life improvement after palliative radiotherapy (16). These findings support broader outcome assessment in future studies, including index pain, nonindex pain, analgesic use, functional interference, and patient-reported quality of life.
Radiopharmaceuticals provide another approach for symptom and skeletal-event control in patients with metastatic disease. In the phase III PSMAfore trial, [177Lu]Lu-PSMA-617 delayed deterioration in health-related quality of life and worsening of pain, prolonged time to first symptomatic skeletal event, and reduced the need for radiotherapy to relieve bone pain in taxane-naive patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer (17). These results suggest that molecularly targeted radioligand therapy may influence patient-reported pain and skeletal outcomes in selected populations.
Overall, current evidence supports a more selective and patient-centered use of radiation-based treatments in cancer pain management. Conventional palliative radiotherapy remains important for painful bone metastases, whereas advanced radiotherapy techniques and radiopharmaceutical approaches should be tailored to patients most likely to derive meaningful benefit.
Interventional pain management
Interventional pain management plays an important role in cancer pain care, particularly for patients with identifiable pain generators, inadequate response to systemic analgesics, or opioid-related adverse effects that limit further dose escalation. Current consensus recommendations support intrathecal drug delivery for carefully selected patients with refractory cancer pain, while emphasizing individualized decisions regarding prognosis, comorbidities, drug selection, dose titration, and follow-up (40).
Recent evidence emphasizes that identifying treatable pain components may improve the precision of interventional management. In hospitalized patients with incurable cancer and myofascial pain syndrome, a multicenter randomized trial showed that adding a single trigger point injection with 1% lidocaine to conventional care resulted in ≥50% pain reduction at 3 days in 70.8% of patients compared with 0% in the conventional-care group (18). This finding suggests that myofascial pain can coexist with tumor-related pain and represents a potentially reversible pain component that may be overlooked when management relies primarily on systemic analgesic escalation.
Procedural refinement has also been explored in patients with upper abdominal cancer-related pain. A randomized trial comparing transdiscal and paraspinal approaches for splanchnic nerve block in advanced pancreatic cancer demonstrated comparable analgesic outcomes, whereas the transdiscal approach reduced puncture time and fluoroscopy exposure, with similar morphine consumption, functional status, patient satisfaction, and complication rates (19). Together, these findings indicate that improved identification of pain generators and procedural refinement may facilitate more targeted and patient-centered application of interventional strategies.
For patients with severe refractory pain, targeted neuraxial drug delivery remains an important option. A multicenter retrospective study of prepontine cistern intrathecal morphine delivery for intractable craniofacial cancer pain reported reductions in pain scores, breakthrough pain episodes, and systemic morphine-equivalent doses, without severe adverse events (20). Another study evaluating patient-reported outcomes after intrathecal drug delivery showed improvements in pain interference and sleep disturbance during follow-up, although broader physical, psychological, and social domains demonstrated less consistent change (21).
Neuromodulation remains an emerging area in cancer-related pain. A small retrospective case series comparing closed-loop spinal cord stimulation with dorsal root ganglion stimulation reported short-term improvements in pain and function. However, limited sample size and retrospective design prevent definitive conclusions regarding its broader application (22).
For patients with persistent severe pain despite optimized systemic and multimodal treatment, reassessment should confirm the pain generator and mechanism, the adequacy of previous treatment, adverse effects, prognosis, and patient goals (3). Intrathecal drug delivery may be considered in carefully selected patients when systemic therapy provides inadequate analgesia or causes dose-limiting toxicity (20,21,40).
Overall, current evidence supports an important but targeted role for interventional strategies in selected cancer pain scenarios. Further studies are needed to clarify long-term clinical benefits, including durability of pain relief, opioid-sparing effects, and functional outcomes, and to identify patients most likely to benefit from these approaches.
Expanding toward integrated multimodal and longitudinal cancer pain management
Integrative interventions
Integrative interventions are increasingly considered as adjunctive components of comprehensive cancer pain management, extending care beyond analgesic escalation alone. The Society for Integrative Oncology (SIO)-American Society of Clinical Oncology (ASCO) guideline defines integrative medicine as the coordinated use of evidence-based complementary approaches alongside conventional cancer care, rather than as a replacement for standard pain management (41). The guideline supports selected interventions for specific pain settings, including acupuncture for aromatase inhibitor-related joint pain, acupuncture or reflexology/acupressure for general or musculoskeletal cancer pain, hypnosis for procedural pain, and massage for pain in palliative and hospice care.
These recommendations provide a framework for incorporating integrative interventions into cancer pain management while recognizing that evidence strength varies across interventions and clinical contexts. Studies published in 2025 further explored their potential effects on pain, physical function, symptom burden, and patient-centered outcomes.
Among cancer survivors with chronic musculoskeletal pain, acupuncture has been evaluated beyond pain intensity alone. A secondary analysis of the PEACE randomized clinical trial evaluated upper- and lower-extremity function in 360 patients with cancer-related chronic musculoskeletal pain. Both electro-acupuncture and auricular acupuncture improved physical function scores at week 12 compared with the control group, and patients achieving pain relief also demonstrated greater functional improvement (23).
These findings extend the potential role of acupuncture from pain-intensity reduction to function-oriented survivorship care.
Other integrative approaches target pain within a broader symptom context. In a randomized placebo-controlled trial among patients with breast cancer receiving chemotherapy, lavender aromatherapy massage improved sleep quality and anxiety at 4 weeks, and pain scores were lower than those in the sweet almond oil massage control group. Depression and cognitive function did not differ between groups (24).
These findings suggest that lavender aromatherapy massage may provide adjunctive benefit for patients whose pain is accompanied by sleep disturbance or psychological distress.
Emerging interventions have explored additional biological and digital pathways of symptom management. In postoperative gastrointestinal cancer patients receiving chemotherapy, a post hoc analysis of the ProDeCa trial found that a four-strain psychobiotic formulation was associated with improvements in pain intensity and qualitative pain indices, particularly among participants without depression (25). Digital supportive approaches are also being investigated.
In a single-arm, unblinded pilot dosing study, patients with moderate-to-severe cancer-related pain used a virtual reality-delivered distraction intervention over 3 weeks. Pain severity, pain interference, and satisfaction with pain management improved over time, with the strongest signal observed with twice-daily use, although breakthrough opioid use did not significantly change (26). This study suggests that virtual reality may be a feasible supportive tool for selected patients.
The clinical maturity and potential applicability of these interventions should be differentiated. Among the approaches reviewed, acupuncture has a comparatively more established clinical foundation, supported by randomized evidence and existing SIO-ASCO recommendations for selected settings, including aromatase inhibitor-related arthralgia, general or musculoskeletal cancer pain, and chronic musculoskeletal pain in cancer survivors. Nevertheless, the 2025 PEACE analysis was secondary and did not include a sham control, limiting conclusions regarding treatment-specific physiological effects.
Aromatherapy massage may be considered a supportive intervention when pain coexists with anxiety or sleep disturbance, but its independent analgesic effect and long-term benefit remain uncertain. Evidence for psychobiotics is substantially more exploratory because the reported pain findings arose from a post hoc analysis of a trial in which pain was not the primary endpoint. Similarly, virtual reality currently represents an investigational digital adjunct rather than an established analgesic treatment, as the available 2025 study was a small, uncontrolled pilot with short follow-up.
These interventions should therefore be matched to the clinical context, patient preferences, treatment burden, accessibility, and strength and directness of the supporting evidence.
Overall, integrative approaches should be incorporated selectively as adjuncts to, rather than replacements for, established cancer-pain treatments. Their potential contribution extends beyond pain-intensity reduction to include functional improvement, symptom relief, and patient-centered outcomes. Future trials should define pain phenotypes and target populations prospectively, use appropriate comparators, and evaluate durability, safety, treatment burden, accessibility, cost-effectiveness, and integration within multimodal and longitudinal care pathways.
Longitudinal cancer pain management across the cancer care continuum
Effective cancer pain management extends beyond individual treatment decisions and requires longitudinal care across the cancer care continuum. Clinical studies published in 2025 increasingly examined how patients at risk of persistent pain could be identified, how pain could be assessed and managed, and how care could be coordinated across different stages of disease. These studies support a longitudinal and patient-centered approach to cancer pain management.
Identifying patients at increased risk of persistent pain is the first and critical step in longitudinal cancer pain management. A secondary analysis of women undergoing breast cancer surgery identified five biopsychosocial phenotypes based on somatosensory and psychosocial characteristics both before surgery and at 1 week postoperatively. Phenotypes characterized by greater psychosocial distress and lower quality of life were associated with higher pain intensity 1 year after surgery, suggesting that perioperative characteristics may provide information about vulnerability to persistent pain (27).
Evidence from patients with head and neck cancer further indicates that pain burden varies according to both patient and disease characteristics. In the Head and Neck 5000 cohort, clinically important general pain was present in 40.9% of patients before treatment, increased to 47.6% at 4 months, and remained present in 35.5% at 12 months. Higher pain levels were associated with younger age, smoking, depression or comorbidities, advanced-stage disease, oral cavity cancer, and human papillomavirus (HPV)-negative status (28).
Long-term survivorship data further suggest that disease characteristics at diagnosis may remain relevant to pain many years later. Among 10-year survivors of head and neck cancer, 43.3% reported some degree of pain, and advanced-stage disease at diagnosis was associated with higher pain scores. Patients with moderate or severe pain also had poorer disease-specific quality of life across eating, speech, aesthetics, and social disruption domains (29).
Clinical and biopsychosocial characteristics may therefore help identify patients at greater risk of persistent pain, supporting a risk-informed approach to longitudinal care. However, prospective validation is needed before these characteristics can be incorporated into formal risk-stratification tools.
Beyond risk identification, structured pain assessment is essential for guiding individualized treatment decisions in longitudinal cancer pain management. The MyPath Pain Care Pathway was developed as a standardized digital assessment approach covering etiology, location, intensity, flares, and treatment (30). For breakthrough cancer pain, more targeted tools may capture features not covered by general pain assessment.
The Chinese version of the Breakthrough Pain Assessment Tool showed strong psychometric properties in the study sample and comprises two dimensions covering the severity and impact of breakthrough pain, as well as onset characteristics and medication effectiveness (31). Assessment of treatment response should also incorporate outcomes that are meaningful to individual patients. Among patients with advanced cancer receiving medication for breakthrough pain, 90.8% reported an improvement in their global impression at 30 min, whereas only 46.1% achieved their own target pain score (32).
Pain assessment may therefore be most informative when it integrates pain characteristics, treatment response, and patient-defined goals to support individualized treatment decisions.
Assessment has greater clinical value when it is linked to coordinated care delivery. At the organizational level, a Plan-Do-Check-Act cycle-based pharmaceutical management intervention improved prescription compliance for three-step analgesic treatment and was associated with better pain outcomes (33). Continuity after discharge was addressed through a pharmacist-led medication therapy management model linking hospital, community, and home-based care.
In patients discharged with moderate-to-severe cancer pain, the intervention resulted in better pain control, greater medication adherence, and lower anxiety levels after 3 months than conventional care (34). The implementation of coordinated care also depends on workforce capacity. A cross-sectional study found that more than half of oncology nurses had never heard the term breakthrough pain, despite most reporting routine pain assessment using guidelines or algorithms (35).
These findings suggest that workforce knowledge and training are important implementation conditions for coordinated pain care.
These findings can be incorporated into a context-adapted and event-triggered management cycle. Across current guidelines, routine screening at every clinical encounter or contact, comprehensive multidimensional assessment when pain is reported or when new, sudden, or otherwise unexpected pain occurs, and earlier reassessment after treatment initiation or modification, rescue treatment, clinical deterioration, or emergence of toxicity are consistent operational principles (3,42-44). The operational details vary among guidelines.
The NCCN guideline directs comprehensive assessment whenever pain is reported and reassessment at each contact and as needed to meet comfort and functional goals (3). The Australian guideline uses a current pain-intensity score of at least 2 on a 0–10 scale, or new, sudden, or otherwise unexpected pain, as triggers for comprehensive assessment (42). ASCO recommends early assessment and frequent titration when opioids are initiated (43), whereas the 2025 Chinese guideline characterizes assessment as routine, quantitative, and dynamic throughout multidisciplinary care (44).
Accordingly, reassessment frequency should reflect pain acuity, clinical and treatment changes, individual risk, and the care setting.
This operational emphasis also clarifies how recent guidance extends earlier frameworks. The 2016 ASCO survivorship guideline focused on persistent pain after cancer treatment, including screening, comprehensive assessment, functional goals, nonpharmacologic care, and cautious opioid use (45). The 2018 European Society for Medical Oncology (ESMO) guideline provided a broad treatment framework organized around pain intensity and mechanism, anticancer treatment, systemic analgesia, radiotherapy, and interventional options (46).
More recent guidance retains these foundations and adds greater specificity on opioid initiation and early titration, breakthrough pain, adverse-effect prevention, tapering when appropriate, etiologic and mechanism-based classification, repeated assessment, individualized goals, multidisciplinary coordination, and continuity across settings (3,42-44). The principal advance is a more explicit link between classification, treatment selection, reassessment, and subsequent adjustment across the care continuum.
These developments have practical implications across the cancer care continuum because intervention priorities change with the clinical context. Pretreatment and perioperative care emphasize baseline classification, prevention of procedure-related pain, and early identification of biopsychosocial risk. Recent postoperative pain guidance similarly emphasizes structured pain assessment, multimodal analgesia, opioid-sparing strategies, and adjustment of analgesic management according to treatment response and adverse effects (47).
During active anticancer treatment, clinicians should address treatment-related and tumor-related pain, recognize oncologic emergencies, and adjust mechanism-directed multimodal therapy as the clinical condition changes. The early post-treatment transition requires medication reconciliation, rehabilitation, psychosocial reassessment, and coordinated transfer between hospital, community, and home care. In survivorship, persistent postsurgical, radiation-related, musculoskeletal, or neuropathic pain should be managed with function-oriented multimodal care, and new pain should prompt evaluation for recurrence, a second malignancy, or late treatment effects (45).
In progressive disease and end-of-life care, priorities include rapid symptom relief, optimization of background and rescue medication, selected radiotherapy or intervention, caregiver support, and minimization of treatment burden. Opioid reduction may be considered gradually and individually in survivorship or stable disease; routine reduction is generally inappropriate in unstable or progressive disease and near the end of life (3).
Overall, the reviewed studies and current guidelines support a repeating whole-course process of screening and classification, multidimensional assessment, context- and mechanism-appropriate treatment, reassessment, and subsequent adjustment or referral. Table 2 summarizes pain characteristics and risk factors, intervention priorities, and assessment and follow-up strategies across five clinical care contexts. The components of this framework have largely been evaluated separately, and an integrated pathway spanning the cancer care continuum has not yet been prospectively validated.
Future research should evaluate models linking risk stratification, repeated digital or clinical assessment, individualized treatment adjustment, psychosocial support, and coordinated follow-up, with longer-term assessment of pain control, physical function, opioid exposure, and quality of life.
Strengths and limitations
A key strength of this review is its timely and clinically oriented synthesis of cancer pain research published in 2025, which could help us to update the new conception and emerging frontier. By organizing emerging evidence around the refinement of established therapies and the expansion toward integrated multimodal and longitudinal management, this review connects developments in individual treatments and treatment strategies with broader changes in assessment, integrative care, and care coordination.
Several limitations should also be acknowledged. This review provides a selective rather than exhaustive synthesis, and the inclusion of studies based on clinical relevance and thematic alignment may have omitted pertinent evidence. Its focus on research published in a single year provides a timely snapshot but may not capture longer-term developments or evidence published outside this period.
Formal systematic-review methods and standardized risk-of-bias assessment were not applied. Finally, heterogeneity in study designs, patient populations, interventions, follow-up durations, and outcome measures limits direct comparisons across studies and the generalizability of the findings.
Conclusions
Clinical studies published in 2025 highlight two complementary directions in cancer pain management: continued refinement of established therapies and expansion toward integrated multimodal and longitudinal management. Pharmacologic, radiation-based, radiopharmaceutical, and interventional treatments are increasingly individualized according to pain mechanisms, patient characteristics, safety considerations, and patient-reported outcomes. In parallel, emerging research emphasizes integrative interventions, risk identification, structured assessment, and coordinated care delivery across settings.
Future research should evaluate how established therapies and integrative interventions can be combined within sustainable, multimodal models of longitudinal cancer pain management across the cancer care continuum.
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