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Advances in Therapy Sep 2023Desmoid tumors (DT) are rare, locally aggressive, fibroblastic soft-tissue tumors that are characterized by infiltrative growth and can affect organs and adjacent... (Review)
Review
Desmoid tumors (DT) are rare, locally aggressive, fibroblastic soft-tissue tumors that are characterized by infiltrative growth and can affect organs and adjacent structures, resulting in substantial clinical burden impacting patients' health-related quality of life. Searches of PubMed, Embase, Cochrane, and key conferences were conducted in November 2021 and updated periodically through March 2023 to identify articles describing the burden of DT. Of 651 publications identified, 96 relevant ones were retained. Diagnosis of DT is challenging because of its morphologic heterogeneity and variable clinical presentation. Patients visit multiple healthcare providers, often facing delays in correct diagnosis. The low incidence of DT (estimated 3-5 cases per million person-years) limits disease awareness. Patients with DT experience a high symptom burden: up to 63% of patients experience chronic pain, which leads to sleep disturbance (73% of cases), irritability (46% of cases), and anxiety/depression (15% of cases). Frequently mentioned symptoms are pain, limited function and mobility, fatigue, muscle weakness, and swelling around the tumor. Overall, quality of life in patients with DT is lower than in healthy controls. There is no treatment approved by the US Food and Drug Administration for DT; however, treatment guidelines reference available options, such as active surveillance, surgery, systemic therapy, and locoregional therapy. Choice of active treatment may depend on tumor location, symptoms, and risk of morbidity. The substantial burden of illness of DT is related to difficulties in timely and accurate diagnosis, high symptom burden (pain and functional limitations), and decreased quality of life. There is a high unmet need for treatments that specifically target DT and improve quality of life.
Topics: Humans; Fibromatosis, Aggressive; Quality of Life; Pain
PubMed: 37436594
DOI: 10.1007/s12325-023-02592-0 -
Current Oncology (Toronto, Ont.) Jul 2023Pain is frequently reported during cancer disease, and it still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better... (Review)
Review
Pain is frequently reported during cancer disease, and it still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better control pain. Targeted treatments may cure cancer disease and significantly increase survival. Therefore, a novel population of patients (cancer survivors) has emerged, also enduring chronic pain (27.6% moderate to severe pain). The present review discusses the different options currently available to manage pain in (former) cancer patients in light of progress made in the last decade. Major progress in the field includes the recent development of a chronic cancer pain taxonomy now included in the International Classification of Diseases (ICD-11) and the update of the WHO analgesic ladder. Until recently, cancer pain management has mostly relied on pharmacotherapy, with opioids being considered as the mainstay. The opioids crisis has prompted the reassessment of opioids use in cancer patients and survivors. This review focuses on the current utilization of opioids, the neuropathic pain component often neglected, and the techniques and non-pharmacological strategies available which help to personalize patient treatment. Cancer pain management is now closer to the management of chronic non-cancer pain, i.e., "an integrative and supportive pain care" aiming to improve patient's quality of life.
Topics: Humans; Analgesics, Opioid; Chronic Pain; Quality of Life; Cancer Pain; Pain Management; Neoplasms
PubMed: 37504360
DOI: 10.3390/curroncol30070500 -
Neuro-oncology Oct 2023Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our...
BACKGROUND
Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies.
METHODS
This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index).
RESULTS
For the 74 children (median age 10.3 years; range 3-18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1-100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment.
CONCLUSIONS
With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues.
Topics: Child; Humans; Neurofibromatosis 1; Neurofibroma, Plexiform; Benzimidazoles; Pain
PubMed: 37115514
DOI: 10.1093/neuonc/noad086 -
Redox Biology Jun 2023Bone cancer pain (BCP) impairs patients' quality of life. However, the underlying mechanisms are still unclear. This study investigated the role of spinal interneuron...
Bone cancer pain (BCP) impairs patients' quality of life. However, the underlying mechanisms are still unclear. This study investigated the role of spinal interneuron death using a pharmacological inhibitor of ferroptosis in a mouse model of BCP. Lewis lung carcinoma cells were inoculated into the femur, resulting in hyperalgesia and spontaneous pain. Biochemical analysis revealed that spinal levels of reactive oxygen species and malondialdehyde were increased, while those of superoxide dismutase were decreased. Histological analysis showed the loss of spinal GAD65+ interneurons and provided ultrastructural evidence of mitochondrial shrinkage. Pharmacologic inhibition of ferroptosis using ferrostatin-1 (FER-1, 10 mg/kg, intraperitoneal for 20 consecutive days) attenuated ferroptosis-associated iron accumulation and lipid peroxidation and alleviated BCP. Furthermore, FER-1 inhibited the pain-associated activation of ERK1/2 and COX-2 expression and prevented the loss of GABAergic interneurons. Moreover, FER-1 improved analgesia by the COX-2 inhibitor Parecoxib. Taken together, this study shows that pharmacological inhibition of ferroptosis-like cell death of spinal interneurons alleviates BCP in mice. The results suggest that ferroptosis is a potential therapeutic target in patients suffering on BCP and possibly other types of pain.
Topics: Mice; Animals; Hyperalgesia; Cancer Pain; Ferroptosis; Quality of Life; Pain; Bone Neoplasms; Cell Death
PubMed: 37084690
DOI: 10.1016/j.redox.2023.102700 -
JAMA Network Open Nov 2023Pain is challenging for patients with advanced cancer. While recent guidelines recommend acupuncture and massage for cancer pain, their comparative effectiveness is... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Pain is challenging for patients with advanced cancer. While recent guidelines recommend acupuncture and massage for cancer pain, their comparative effectiveness is unknown.
OBJECTIVE
To compare the effects of acupuncture and massage on musculoskeletal pain among patients with advanced cancer.
DESIGN, SETTING, AND PARTICIPANTS
A multicenter pragmatic randomized clinical trial was conducted at US cancer care centers consisting of a northeastern comprehensive cancer center and a southeastern cancer institute from September 19, 2019, through February 23, 2022. The principal investigator and study statisticians were blinded to treatment assignments. The duration of follow-up was 26 weeks. Intention-to-treat analyses were performed (linear mixed models). Participants included patients with advanced cancer with moderate to severe pain and clinician-estimated life expectancy of 6 months or more. Patient recruitment strategy was multipronged (eg, patient database queries, mailings, referrals, community outreach). Eligible patients had English or Spanish as their first language, were older than 18 years, and had a Karnofsky score greater than or equal to 60 (range, 0-100; higher scores indicating less functional impairment).
INTERVENTIONS
Weekly acupuncture or massage for 10 weeks with monthly booster sessions up to 26 weeks.
MAIN OUTCOMES AND MEASURES
The primary end point was the change in worst pain intensity score from baseline to 26 weeks. The secondary outcomes included fatigue, insomnia, and quality of life. The Brief Pain Inventory (range, 0-10; higher numbers indicate worse pain intensity or interference) was used to measure the primary outcome. The secondary outcomes included fatigue, insomnia, and quality of life.
RESULTS
A total of 298 participants were enrolled (mean [SD] age, 58.7 [14.1] years, 200 [67.1%] were women, 33 [11.1%] Black, 220 [74.1%] White, 46 [15.4%] Hispanic, and 78.5% with solid tumors). The mean (SD) baseline worst pain score was 6.9 (1.5). During 26 weeks, acupuncture reduced the worst pain score, with a mean change of -2.53 (95% CI, -2.92 to -2.15) points, and massage reduced the Brief Pain Inventory worst pain score, with a mean change of -3.01 (95% CI, -3.38 to -2.63) points; the between-group difference was not significant (-0.48; 95% CI, -0.98 to 0.03; P = .07). Both treatments also improved fatigue, insomnia, and quality of life without significant between-group differences. Adverse events were mild and included bruising (6.5% of patients receiving acupuncture) and transient soreness (15.1% patients receiving massage).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial among patients with advanced cancer, both acupuncture and massage were associated with pain reduction and improved fatigue, insomnia, and quality of life over 26 weeks; however, there was no significant different between the treatments. More research is needed to evaluate how best to integrate these approaches into pain treatment to optimize symptom management for the growing population of people living with advanced cancer.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04095234.
Topics: Female; Humans; Male; Middle Aged; Acupuncture Therapy; Fatigue; Massage; Musculoskeletal Pain; Neoplasms; Quality of Life; Sleep Initiation and Maintenance Disorders; Adult; Aged
PubMed: 37962891
DOI: 10.1001/jamanetworkopen.2023.42482 -
Medicine Jul 2023To critically evaluate the effects of massage therapy on cancer pain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To critically evaluate the effects of massage therapy on cancer pain.
METHODS
Nine Chinese and English databases (PubMed, Cochrane Library, Embase, SCOPUS, Web of Science core, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang, and VIP) were systematically searched from the inception of databases to November 2022 for randomized controlled trials. According to Cochrane Collaboration, 2 reviewers independently assessed the risk of bias and extracted data from the included studies. All analyses were performed with Review Manager 5.4.
RESULTS
Thirteen randomized controlled trials were included in the meta-analysis, containing 1000 patients (498 in the massage therapy group and 502 in the control group). Massage therapy could significantly relieve cancer pain in patients (standardized mean difference = -1.16, 95% confidence interval [-1.39, -0.93], P < .00001), especially those in the perioperative period and those with hematological malignancies. Foot reflexology and hand acupressure had a moderate effect on cancer pain relief, with hand acupressure being more effective. Massage duration of 10 to 30 minutes and a program length of ≥1 week had a better effect and could significantly relieve pain. The occurrence of adverse events was reported in 4 of the 13 studies, all of which were no adverse events.
CONCLUSIONS
Massage therapy can be used as a complementary alternative therapy to relieve cancer pain in patients with hematological malignancies, breast cancer, and cancers of the digestive system. It is suggested that chemotherapy patients use foot reflexology, and perioperative period patients use hand acupressure. A massage duration of 10 to 30 minutes and a program length of ≥1 week is recommended to achieve better effects.
Topics: Humans; Female; Cancer Pain; Massage; Complementary Therapies; Breast Neoplasms; Hematologic Neoplasms
PubMed: 37417622
DOI: 10.1097/MD.0000000000033939 -
BMC Cancer Jun 2023Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS... (Review)
Review
Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with NF1 and symptomatic, inoperable PN. In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported outcomes (decreased tumor-related pain and improvements in quality of life, strength, and range of motion). Selumetinib is currently the only licensed medical therapy indicated for use in pediatric patients with symptomatic, inoperable NF1-PN, with approval based on the results of this pivotal clinical study. Several other MEK inhibitors (binimetinib, mirdametinib, trametinib) and the tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN. Careful consideration of multiple aspects of both disease and treatments is vital to reduce morbidity and improve outcomes in patients with this complex and heterogeneous disease, and clinicians should be fully aware of the risks and benefits of available treatments. There is no single treatment pathway for patients with NF1-PN; surgery, watchful waiting, and/or medical treatment are options. Treatment should be individualized based on recommendations from a multidisciplinary team, considering the size and location of PN, effects on adjacent tissues, and patient and family preferences. This review outlines the treatment strategies currently available for patients with NF1-PN and the evidence supporting the use of MEK inhibitors, and discusses key considerations in clinical decision-making.
Topics: Child; Humans; Neurofibromatosis 1; Neurofibroma, Plexiform; Quality of Life; Protein Kinase Inhibitors; Mitogen-Activated Protein Kinase Kinases
PubMed: 37328781
DOI: 10.1186/s12885-023-10996-y -
Drug Design, Development and Therapy 2023This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effect of Low-Dose Esketamine on Postoperative Neurocognitive Dysfunction in Elderly Patients Undergoing General Anesthesia for Gastrointestinal Tumors: A Randomized Controlled Trial.
PURPOSE
This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients undergoing general anesthesia for gastrointestinal tumors.
METHODS
Sixty-eight elderly patients were randomly allocated to two groups: the esketamine group (group Es) (0.25 mg/kg loading, 0.125mg/kg/h infusion) and the control group (group C) (received normal saline). The primary outcome was the incidence of delayed neurocognitive recovery (DNR). The secondary outcomes were intraoperative blood loss, the total amount of fluid given during surgery, propofol and remifentanil consumption, cardiovascular adverse events, use of vasoactive drugs, operating and anesthesia time, the number of cases of sufentanil remedial analgesia, the incidence of postoperative delirium (POD), the intraoperative hemodynamics, bispectral index (BIS) value at 0, 1, 2 h after operation and numeric rating scale (NRS) pain scores within 3 d after surgery.
RESULTS
The incidence of DNR in group Es (16.13%) was lower than in group C (38.71%) ( <0.05). The intraoperative remifentanil dosage and the number of cases of dopamine used in group Es were lower than in group C ( <0.05). Compared with group C, DBP was higher at 3 min after intubation, and MAP was lower at 30 min after extubation in group Es (0.05). The incidence of hypotension and tachycardia in group Es was lower than in group C (0.05). The NRS pain score at 3 d after surgery in group Es was lower than in group C ( 0.05).
CONCLUSION
Low-dose esketamine infusion reduced to some extent the incidence of DNR in elderly patients undergoing general anesthesia for gastrointestinal tumors, improved intraoperative hemodynamics and BIS value, decreased the incidence of cardiovascular adverse events and the intraoperative consumption of opioids, and relieved postoperative pain.
Topics: Humans; Aged; Remifentanil; Anesthesia, General; Delirium; Pain, Postoperative; Gastrointestinal Neoplasms
PubMed: 37408867
DOI: 10.2147/DDDT.S406568 -
Cell Reports Sep 2023Polycystic ovary syndrome (PCOS) is an endocrine disorder and the main cause of anovulatory infertility, in which persistent activation of androgen receptor (AR) due to...
Polycystic ovary syndrome (PCOS) is an endocrine disorder and the main cause of anovulatory infertility, in which persistent activation of androgen receptor (AR) due to aberrant acetylation modifications of transcription is a potential trigger; however, the precise mechanisms of AR activation are poorly understood. In this study, AR activation in dehydroepiandrosterone- and letrozole-induced rat PCOS ovaries coincided with a marked increase of a chromatin acetylation "reader" BRD4. Further bioinformatic analysis showed that the AR promoter contained highly conserved binding motifs of BRD4 and HIF-1α. BRD4 and HIF-1α inducibly bound to the histone 3/4 acetylation-modified AR promoter, while administration of a BRD4-selective inhibitor JQ1 reduced the binding and AR transcription and improved the adverse expression of the core fibrotic mediators in PCOS ovaries and DHT-treated granulosa cells. Our data indicate that BRD4 upregulation and the resultant AR transcriptional activation constitute an important regulatory pathway that promotes ovarian fibrosis in PCOS.
Topics: Animals; Female; Humans; Rats; Cell Cycle Proteins; Fibrosis; Nuclear Proteins; Polycystic Ovary Syndrome; Receptors, Androgen; Transcription Factors
PubMed: 37669164
DOI: 10.1016/j.celrep.2023.113090 -
Asian Pacific Journal of Cancer... Jun 2023Breast cancer is the most prevalent from of cancer among women worldwide and leading cause of death. Breast cancer can be treated surgically, systemically (with hormonal... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of Scapular Strengthening Exercises on Shoulder Dysfunction for Pain and Functional Disability after Modified Radical Mastectomy: A Controlled Clinical Trial.
BACKGROUND
Breast cancer is the most prevalent from of cancer among women worldwide and leading cause of death. Breast cancer can be treated surgically, systemically (with hormonal therapy, chemotherapy) or with radiotherapy. Through the years, breast cancers management evolved towards conservation surgery. A surgical remove of partial or complete breast tissue, surrounding tissues, and nearby lymph nodes is called mastectomy. In Modified Radical Mastectomy, there is removal of entire breast tissue and lymph nodes. Treatment of modified radical mastectomy may lead to side effects such as shoulder pain, restricted shoulder mobility and anatomical and biomechanical changes of the shoulder, and also reduce functional disability.
METHOD
Eighty six participants were included in this study. Two groups, each of 43 were made, Group A (control group) was given conventional exercises and Group B (study group) was given scapular strengthening exercises with conventional exercises. Outcome measures - Shoulder Pain And Functional Disability, Shoulder range of motion were assessed both pre and post-test.
RESULT
Group B had lower pain intensity (77.116 ± 5.798vs 82.837 ± 3.860) and functional disability (70.326 ± 5.281 vs 77.791± 5.102) and higher shoulder flexion (167.98 ± 8.230 vs 107.05 ±8.018), abduction (156.91 ± 8.230 vs 107.63 ±8.230) and external rotation (62.372 ± 7.007 vs 41.907 ±6.771) range of motion than Group A.
CONCLUSION
The current study concluded that, scapular strengthening exercises along with conventional treatment proved beneficial and effective rather than only conventional treatment on shoulder dysfunction for pain and functional disability after modified radical mastectomy.
Topics: Humans; Female; Shoulder; Shoulder Pain; Mastectomy, Modified Radical; Breast Neoplasms; Mastectomy; Exercise Therapy
PubMed: 37378941
DOI: 10.31557/APJCP.2023.24.6.2099