ABSTRACT
BACKGROUND: Anti-PD-1 antibodies have revolutionized cancer immunotherapy due to their ability to induce long-lasting complete remissions in a proportion of patients. Current research efforts are attempting to identify biomarkers and suitable combination partners to predict or further improve the activity of immune checkpoint inhibitors. Antibody-cytokine fusions are a class of pharmaceuticals that showed the potential to boost the anticancer properties of other immunotherapies. Extradomain A-fibronectin (EDA-FN), which is expressed in most solid and hematological tumors but is virtually undetectable in healthy adult tissues, is an attractive target for the delivery of cytokine at the site of the disease. METHODS: In this work, we describe the generation and characterization of a novel interleukin-7-based fusion protein targeting EDA-FN termed F8(scDb)-IL7. The product consists of the F8 antibody specific to the alternatively spliced EDA of FN in the single-chain diabody (scDb) format fused to human IL-7. RESULTS: F8(scDb)-IL7 efficiently stimulates human peripheral blood mononuclear cells in vitro. Moreover, the product significantly increases the expression of T Cell Factor 1 (TCF-1) on CD8+T cells compared with an IL2-fusion protein. TCF-1 has emerged as a pivotal transcription factor that influences the durability and potency of immune responses against tumors. In preclinical cancer models, F8(scDb)-IL7 demonstrates potent single-agent activity and eradicates sarcoma lesions when combined with anti-PD-1. CONCLUSIONS: Our results provide the rationale to explore the combination of F8(scDb)-IL7 with anti-PD-1 antibodies for the treatment of patients with cancer.
Subject(s)
CD8-Positive T-Lymphocytes , Fibronectins , Interleukin-7 , Humans , Fibronectins/metabolism , Fibronectins/genetics , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Interleukin-7/metabolism , Interleukin-7/pharmacology , Animals , Mice , Recombinant Fusion Proteins/pharmacology , Recombinant Fusion Proteins/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Neoplasms/drug therapy , Neoplasms/immunology , Hepatocyte Nuclear Factor 1-alpha/metabolism , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Up-Regulation , Female , Cell Line, TumorABSTRACT
The Lung Cancer Surgical Study Group (LCSSG) of the Japan Clinical Oncology Group (JCOG) was organized in 1986 and initially included 26 collaborative institutions, which has increased to 52 institutions currently. JCOG-LCSSG includes thoracic surgeons, medical oncologists, pathologists, and radiotherapists. In the early period, the JCOG-LCSSG mainly focused on combined modality therapies for lung cancer. Since the 2000s, the JCOG-LCSSG has investigated adequate modes of surgical resection for small-sized and peripheral non-small cell lung cancer and based on the radiological findings of whole tumor size and ground-glass opacity. Trials, such as JCOG0802, JCOG0804, and JCOG1211, have shown the appropriateness of sublobar resection, which has significantly influenced routine clinical practice. With the introduction of targeted therapy and immunotherapy, treatment strategies for lung cancer have changed significantly. Additionally, with the increasing aging population and medical costs, tailored medicine is strongly recommended to address medical issues. To ensure comprehensive treatment, strategies, including surgical and nonsurgical approaches, should be developed. Currently, the JCOG-LCSSG has conducted numerous clinical trials to adjust the diversity of lung cancer treatment strategies. This review highlights recent advancements in the surgical field, current status, and future direction of the JCOG-LCSSG.
ABSTRACT
Bladder cancer (BC) is the tenth most commonly diagnosed malignancy worldwide. In approximately 25% of cases, it presents as a muscle-invasive disease, requiring a radical treatment. Traditionally, the mainstay of treatment has been radical cystectomy (RC), but in the last decade, bladder-sparing treatments have been gaining growing interest. In particular, trimodal therapy (TMT) seems to yield survival results comparable to RC with less morbidity and better quality of life (QoL) outcomes. In this scenario, we aimed at shedding light on the role of the histological subtypes (HS) of BC and their prognostic significance in muscle-invasive BC (MIBC), treated either surgically or with TMT. We performed a narrative review to provide an overview of the current literature on this topic. When compared with patients diagnosed with conventional urothelial carcinoma (UC) of the same disease stage, survival did not appear to be significantly worse across the reports. But when sub-analyzed for separate subtype, some appeared to be independently associated with adverse survival outcomes such as the micropapillary, plasmacytoid, small-cell, and sarcomatoid subtypes, whereas others did not. Moreover, the optimal management remains to be defined, also depending on the therapeutic susceptibility of each histology. From this perspective, multi-disciplinary assessment alongside the routine inclusion of such entities in randomized clinical trials appears to be essential.
ABSTRACT
INTRODUCTION: The best treatment yielding clinical benefits was still equivocal and controversial for the treatment of recalcitrant plantar fasciitis (PF). This study aimed to propose a novel combination strategy of ultrasound-guided percutaneous radiofrequency ablation (RFA) and corticosteroid injection (CI) for recalcitrant PF, and to compare its therapeutic effects with CI alone and continued conservative management. METHODS: We retrospectively reviewed consecutive patients with recalcitrant PF who underwent combined strategy (RFA + CI), CI alone, and continue conservative treatment at our institution between October 2021 and February 2023. The technical pearls were described elaborately. A comparison of demographic data and clinical outcomes, including visual analog scale (VAS), Ankle-Hindfoot Scale (AOFAS-AHS), and plantar fascia thickness, were conducted among the three groups. RESULTS: Seventy-one eligible patients were enrolled in this study, with 17 in the combined strategy group, 25 in the CI group, and 29 in the continued conservative treatment group. Both the combined strategy group and the CI group showed significant improvements in VAS scores, AOFAS-AHS scores, and significant reductions in plantar fascia thickness during the 12-month follow-up period compared to those preoperatively (P < 0.05). The combined strategy group achieved comparable immediate pain relief to the CI group after the intervention ([25.7 ± 15.7] vs. [20.6 ± 17.6], P = 0.850). However, the combined strategy group demonstrated superior improvement in symptom and function compared to the CI group at the 3-month (VAS: [21.9 ± 13.5] vs. [39.6 ± 20.4]; AOFAS-AHS: [77.9 ± 12.4] vs. [60.5 ± 17.4], P < 0.05) and 12-month follow-up (VAS: [15.7 ± 12.0] vs. [56.8 ± 17.5]; AOFAS-AHS: [84.5 ± 10.7] vs. [53.8 ± 12.4], P < 0.05). Obvious adverse effects or complications were not identified in either group, while two cases (11.8%) in the combined strategy group and five cases (20.0%) in the CI group experienced unsatisfactory symptom remission. CONCLUSIONS: We introduced and detailed a novel combination strategy involving ultrasound-guided percutaneous RFA and CI for treating recalcitrant PF. The strategy is both effective and safe in alleviating pain and enhancing function throughout the entire treatment course.
ABSTRACT
BACKGROUND: Neck pain is a prevalent global musculoskeletal issue, significantly contributing to the loss of years of healthy life due to disability. Chronic nonspecific neck pain (CNNP) involves diverse symptoms impacting mobility and quality of life. While therapeutic exercises demonstrate efficacy, the role of photobiomodulation therapy (PBMT) remains uncertain. This study aims to assess the additional effects of PBMT within a multimodal therapeutic intervention for CNNP. METHODS: A randomized, two-arm, controlled, blind clinical trial follows CONSORT and SPIRIT guidelines. Participants diagnosed with CNNP will receive a stand-alone multimodal therapeutic intervention or the same program with additional PBMT. The primary outcomes will be assessed by the functional disability identified through applying the NDI (Neck Disability Index). Secondary outcomes will be pain intensity during rest and active neck movement, catastrophizing and kinesiophobia, functionality, and disability assessed at baseline, after 8 weeks, and at a 4-week follow-up. Both groups receive pain education before personalized interventions, including resistance exercises, neuromuscular activities, mobility, and body balance. The PBMT group undergoes low-level light therapy. Intention-to-treat analysis, using linear mixed models, employs data presented as mean, standard deviation, and differences with a 95% confidence interval. Non-normally distributed variables transform. Statistical significance is set at 5%. DISCUSSION: This study addresses a critical gap in understanding the combined effects of PBMT and therapeutic exercises for CNNP. The findings aim to guide clinicians, researchers, and CNNP sufferers through rigorous methodology and diverse outcome assessments, offering valuable insights into evidence-based practices for CNNP management. Data confidentiality is maintained throughout, ensuring participant privacy during statistical analysis. TRIAL REGISTRATION: Effects of adding photobiomodulation to a specific therapeutic exercise program for the treatment of individuals with chronic nonspecific neck pain, registration number: NCT05400473, on 2022-05-27.
Subject(s)
Chronic Pain , Low-Level Light Therapy , Neck Pain , Randomized Controlled Trials as Topic , Humans , Neck Pain/therapy , Neck Pain/physiopathology , Neck Pain/diagnosis , Low-Level Light Therapy/methods , Chronic Pain/therapy , Chronic Pain/physiopathology , Chronic Pain/diagnosis , Combined Modality Therapy , Treatment Outcome , Pain Measurement , Disability Evaluation , Adult , Female , Male , Middle Aged , Exercise Therapy/methods , Time Factors , Quality of LifeABSTRACT
Background: Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity. Targeted radionuclide therapy (TRT) is a systemic radiation treatment, ideally suited for precision irradiation of metastasized cancer. Therefore, the aim of this study is to explore the potential of combined TRT, targeting carbonic anhydrase IX (CAIX) which is overexpressed in ccRCC, using [177Lu]Lu-DOTA-hG250, and ICI for the treatment of ccRCC. Methods: In this study, we evaluated the therapeutic and immunological action of [177Lu]Lu-DOTA-hG250 combined with aPD-1/a-CTLA-4 ICI. First, the biodistribution of [177Lu]Lu-DOTA-hG250 was investigated in BALB/cAnNRj mice bearing Renca-CAIX or CT26-CAIX tumors. Renca-CAIX and CT26-CAIX tumors are characterized by poor versus extensive T-cell infiltration and homogeneous versus heterogeneous PD-L1 expression, respectively. Tumor-absorbed radiation doses were estimated through dosimetry. Subsequently, [177Lu]Lu-DOTA-hG250 TRT efficacy with and without ICI was evaluated by monitoring tumor growth and survival. Therapy-induced changes in the tumor microenvironment were studied by collection of tumor tissue before and 5 or 8 days after treatment and analyzed by immunohistochemistry, flow cytometry, and RNA profiling. Results: Biodistribution studies showed high tumor uptake of [177Lu]Lu-DOTA-hG250 in both tumor models. Dose escalation therapy studies in Renca-CAIX tumor-bearing mice demonstrated dose-dependent anti-tumor efficacy of [177Lu]Lu-DOTA-hG250 and remarkable therapeutic synergy including complete remissions when a presumed subtherapeutic TRT dose (4 MBq, which had no significant efficacy as monotherapy) was combined with aPD-1+aCTLA-4. Similar results were obtained in the CT26-CAIX model for 4 MBq [177Lu]Lu-DOTA-hG250 + a-PD1. Ex vivo analyses of treated tumors revealed DNA damage, T-cell infiltration, and modulated immune signaling pathways in the TME after combination treatment. Conclusions: Subtherapeutic [177Lu]Lu-DOTA-hG250 combined with ICI showed superior therapeutic outcome and significantly altered the TME. Our results underline the importance of investigating this combination treatment for patients with advanced ccRCC in a clinical setting. Further investigations should focus on how the combination therapy should be optimally applied in the future.
Subject(s)
Carbonic Anhydrase IX , Carcinoma, Renal Cell , Immune Checkpoint Inhibitors , Kidney Neoplasms , Animals , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/therapy , Carcinoma, Renal Cell/pathology , Mice , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Kidney Neoplasms/radiotherapy , Carbonic Anhydrase IX/metabolism , Carbonic Anhydrase IX/antagonists & inhibitors , Humans , Cell Line, Tumor , Radioisotopes/therapeutic use , Radioisotopes/pharmacology , Radioisotopes/administration & dosage , Lutetium/therapeutic use , Female , Antigens, Neoplasm/metabolism , Tissue Distribution , Tumor Microenvironment/drug effects , Tumor Protein, Translationally-Controlled 1 , Xenograft Model Antitumor Assays , Combined Modality Therapy/methods , Mice, Inbred BALB C , Antibodies, MonoclonalABSTRACT
OBJECTIVE: Narrowband ultraviolet B (NB-UVB) has been recommended as first-line therapy for early-stage mycosis fungoides (MF) in international guidelines. NB-UVB can be used as monotherapy or part of a multimodality treatment regimen. There is limited evidence on the effectiveness and optimal patients of NB-UVB in combination with systemic therapies in MF. We aimed to assess the effectiveness of the combination versus NB-UVB monotherapy in early-stage MF and if plaque lesion status was related to these effects. METHODS: This observational cohort study included 247 early-stage MF patients who had received NB-UVB combined with systemic therapies vs. NB-UVB monotherapy from 2009 to 2021. The primary outcome was partial or complete response. Overall response rate and median time to response were calculated. Hazard ratios (HRs) were estimated using the Cox model. RESULTS: In 139 plaque-stage patients, the response rate for combination therapy group was higher than that of monotherapy group (79.0% vs. 54.3%, p = 0.006). The adjusted HR for combination therapy compared with NB-UVB monotherapy was 3.11 (95% CI 1.72-5.63). The combination therapy group also showed shorter time to response (4 vs. 6 months, p = 0.002). In 108 patch-stage patients, the response rate and time to response in two treatment groups showed no significant difference. There was therefore an observed interaction with patients' plaque lesion status for the effect size of NB-UVB combination therapy. No serious adverse events were observed. CONCLUSIONS: Adding systemic treatments to NB-UVB did not improve the treatment outcome of patch-stage patients, but it surpassed NB-UVB monotherapy for early-stage patients with plaques.
Subject(s)
Mycosis Fungoides , Skin Neoplasms , Ultraviolet Therapy , Humans , Mycosis Fungoides/radiotherapy , Mycosis Fungoides/therapy , Male , Female , Middle Aged , Ultraviolet Therapy/methods , Adult , Skin Neoplasms/radiotherapy , Skin Neoplasms/therapy , Skin Neoplasms/pathology , Combined Modality Therapy/methods , Aged , Treatment Outcome , Retrospective Studies , Cohort StudiesABSTRACT
Purpose: The incidence of deep vein thrombosis (DVT) following total hip arthroplasty (THA) without chemoprophylaxis could be as high as 50% in Caucasians. However, according to several subsequent studies, the incidence of venous thromboembolic events (VTE) in Asians was much lower. The routine use of chemoprophylaxis, which could potentially cause increased bleeding, infection, and wound complications, has been questioned in low-incidence populations. The objective of this study is to determine the incidence of VTE after primary THA without chemoprophylaxis in an Asian population using a fast-track rehabilitation protocol and to verify the safety profile for use of 'mechanical prophylaxis alone' in patients with standard risk of VTE. Materials and Methods: This is a retrospective cohort study of 542 Hong Kong Chinese patients who underwent primary THA without chemoprophylaxis. All patients received intermittent pneumatic compression and graduated compression stockings as mechanical prophylaxis. Multimodal pain management was applied in order to facilitate early mobilisation. Routine duplex ultrasonography was performed between the fourth and seventh postoperative day for detection of proximal DVT. Results: All patients were Chinese (mean age, 63.0±11.9 years). Six patients developed proximal DVT (incidence rate, 1.1%). None of the patients had symptomatic or fatal pulmonary embolism. Conclusion: The incidence of VTE after primary THA without chemical prophylaxis can be low in Asian populations when following a fast-track rehabilitation protocol. Mechanical prophylaxis alone can be regarded as a reasonably safe practice in terms of a balanced benefit-to-risk ratio for Asian patients with standard risk of VTE.
ABSTRACT
BACKGROUND: This study describes patient-reported outcome measures (PROMs) and associated factors in patients who underwent surgery for malignant parotid tumors (MPT). METHODS: This is a retrospective study of all surgically treated MPT patients in a multidisciplinary head and neck cancer (HNC) survivorship clinic (2017-2023). PROMs included University of Washington Quality of Life Questionnaire (UW-QOL), Eating Assessment Tool (EAT-10), Patient Health Questionnaire (PHQ-8), Generalized Anxiety Disorder (GAD-7), Neck Disability Index (NDI), and Insomnia Severity Index. Multivariable regression analysis was used to investigate clinical predictors associated with PROMs. RESULTS: In 62 MPT patients, the prevalence of clinically relevant dysphagia symptoms (EAT-10), elevated symptoms of depression (PHQ-8), moderate/severe symptoms of anxiety (GAD-7), moderate/severe neck pain with activities of daily living (NDI), and moderate/severe symptoms of insomnia at last follow-up was 32.3%, 15.5%, 7.1%, 17.7%, and 7.2%, respectively. Nonparametric one-sided test revealed that patients treated with adjuvant CRT had significantly worse physical QOL, social-emotional QOL, and swallowing scores than patients treated with surgery alone (p = 0.01, p = 0.02, p = 0.03, respectively); that patients treated with surgery and adjuvant RT had significantly worse physical QOL and social-emotional QOL than patients treated with surgery alone (p < 0.01, p = 0.01, respectively) and that patients treated with surgery and adjuvant CRT had significantly worse swallowing and neck pain than patients treated with surgery and adjuvant RT (p = 0.03, p = 0.05, respectively). CONCLUSIONS: In patients with surgically treated MPT, adjuvant CRT and RT were associated with worse PROMs. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.
ABSTRACT
INTRODUCTION: Systemic and local therapies for patients with metastatic renal cell carcinoma (mRCC) are often challenging despite the evolution of multimodal cancer therapies in the last decade. In this review, we will focus on recent multidisciplinary approaches for patients with mRCC. AREAS COVERED: Systemic therapies for patients with mRCC have been garnering attention particularly after the approval of immuno-oncology (IO) agents, including anti-programmed death 1/programmed death-ligand 1. IO combinations have significantly prolonged overall survival in patients with mRCC in the first-line setting. Regarding local therapies, cytoreductive nephrectomy (CN) has become less common in the post-Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) trial era, even though CN may still benefit selected patients with mRCC. In addition, metastasis-directed local therapies, namely metastasectomy or stereotactic radiotherapy, particularly for oligo-metastatic lesions or brain metastases, may have a prognostic impact. Several ablative techniques are also evolving while maintaining high local control rates with acceptable safety. EXPERT OPINION: Multimodal cancer therapies are essential for conquering complex cases of mRCC. Modern systemic therapies including IO-based combination therapy as well as local therapies including CN, metastasectomy, stereotactic radiotherapy, and ablative techniques appear to improve oncologic outcomes of patients with mRCC, although appropriate patient selection is indispensable.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Nephrectomy , Humans , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/therapy , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Kidney Neoplasms/drug therapy , Combined Modality Therapy , Nephrectomy/methods , Survival Rate , Prognosis , Neoplasm Metastasis , Cytoreduction Surgical Procedures/methods , Patient Selection , Radiosurgery/methods , Metastasectomy/methods , Immunotherapy/methodsABSTRACT
Multimodal treatment approaches with neoadjuvant radiotherapy and chemotherapy followed by oncological and total mesorectal excision (TME) have significantly reduced the recurrence rate even in locally advanced rectal cancer. Nevertheless, up to 10% of patients develop a local relapse. Surgical R0 resection is the only chance of a cure in the treatment of locally recurrent rectal cancer (LRRC). Due to the altered anatomy and physiology of the true pelvis as a result of the pretreatment and operations as well as the localization and extent of the recurrence, the treatment decision is individualized and remains a challenge for the interdisciplinary team. Even locally advanced tumors with involvement of adjacent structures can be treated in designated centers using multimodal treatment concepts with potentially curative intent.
Subject(s)
Neoplasm Recurrence, Local , Rectal Neoplasms , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Humans , Neoplasm Recurrence, Local/pathology , Neoadjuvant Therapy/methods , Combined Modality Therapy , Neoplasm StagingABSTRACT
Orofacial pain can significantly affect physical, psychological, and overall quality of life. This study aimed to compare the effectiveness of combining photobiomodulation (PBM) with orofacial myofunctional therapy (OMT) in managing orofacial pain disorders. An electronic search of randomized controlled trials in electronic databases was performed until March 2024. Randomized controlled trials (RCTs) focusing on PBM and OMT for the management of orofacial pain were included. Risk of bias across individual studies was performed using the Cochrane risk of bias tool for interventions. A total of 10 RCTs were included, out of which 7 RCTs revealed that the combined approach of PBM and OMT had a more pronounced impact on diminishing pain and enhancing functional activity in patients with orofacial disorders. One study reported significant increases in pressure pain threshold for TMJ, masseter, and anterior temporalis muscles at both sides in the post-treatment compared with the pre-treatment in both groups. The risk of bias was low in 7, moderate in 2, and high in 1 study. The efficacy of a combined modality treatment of PBM with OMT for orofacial pain disorder shows promising results. However, further randomized controlled trials with extended follow-up periods standardized PBM and OMT parameters are warranted to obtain firm conclusions.
Subject(s)
Facial Pain , Low-Level Light Therapy , Myofunctional Therapy , Randomized Controlled Trials as Topic , Humans , Myofunctional Therapy/methods , Facial Pain/radiotherapy , Facial Pain/therapy , Low-Level Light Therapy/methods , Treatment Outcome , Combined Modality Therapy , Quality of LifeABSTRACT
OBJECTIVE: To perform a systematic review and meta-analysis of trials comparing trimodal therapy (TMT) and radical cystectomy (RC), evaluating differences in terms of oncological outcomes, quality of life, and costs. MATERIALS AND METHODS: In July 2023, a literature search of multiple databases was conducted to identify studies analysing patients with cT2-4 N any M0 muscle-invasive bladder cancer (MIBC; Patients) receiving TMT (Intervention) compared to RC (Comparison), to evaluate survival outcomes, recurrence rates, costs, and quality of life (Outcomes). The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and metastasis-free survival (MFS). Hazard ratios (HRs) were used to analyse survival outcomes according to different treatment modalities and odds ratios were used to evaluate the likelihood of receiving each type of treatment according to T stage. RESULTS: No significant difference in terms of OS was observed between RC and TMT (HR 1.07, 95% confidence interval [CI] 0.81-1.4; P = 0.6), even when analysing radiation therapy regimens ≥60 Gy (HR 1.02, 95% CI 0.69-1.52; P = 0.9). No significant difference was observed in CSS (HR 1.12, 95% CI 0.79-1.57, P = 0.5) or MFS (HR 0.88, 95% CI 0.66-1.16; P = 0.3). The mean cost of TMT was significantly higher than that of RC ($289 142 vs $148 757; P < 0.001), with greater effectiveness in terms of cost per quality-adjusted life-year. TMT ensured significantly higher general quality-of-life scores. CONCLUSION: Trimodal therapy appeared to yield comparable oncological outcomes to RC concerning OS, CSS and MFS, while providing superior patient quality of life and cost effectiveness.
ABSTRACT
Background/Objectives: Managing postoperative pain in patients with obesity is challenging. Although using a combination of pain relief methods is recommended for these patients, the true effectiveness of various intravenous non-opioid analgesics and adjuvants in multimodal anesthesia needs to be better defined. Methods: A systematic review and network meta-analysis was performed to evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, ketamine, α-2 agonists, lidocaine, magnesium, and oral gabapentinoids in adult surgical patients with obesity. The analysis aimed to compare these treatments to a placebo/no treatment or alternative analgesics, with a primary focus on postoperative pain and secondary endpoints including rescue analgesia, postoperative nausea and vomiting (PONV), and recovery quality. English-language randomized controlled trials across PubMed, Scopus, Web of Science, CINAHL, and EMBASE were considered. Quality and evidence certainty were assessed with the RoB 2 tool and GRADE, and data was analyzed with R software. Results: NSAIDs, along with acetaminophen, lidocaine, α-2 agonists, ketamine, and oral gabapentinoids, effectively reduce early postoperative pain. NSAIDs, particularly ibuprofen, as well as acetaminophen, ketamine, and lidocaine, also show benefits in later postoperative stages. Intravenous non-opioid analgesics and adjuvants show some degree of benefit in reducing PONV and the need for rescue analgesic therapy when using α-2 agonists alone or combined with oral gabapentinoids, notably decreasing the likelihood of PONV. Ketamine, lidocaine, and α-2 agonists are shown to enhance postoperative recovery and care quality. Conclusions: Intravenous non-opioid analgesics and adjuvants are valuable in multimodal anesthesia for pain management in adult surgical patients suffering from obesity.
ABSTRACT
Locally advanced cancer of the vulva (LACV) is commonly diagnosed in older women (>65 years), and is treated using combined multimodality therapy (CMT) that includes radiation therapy (RT). Compliance to optimal RT metrics, including completion of > 20 fractions, overall treatment duration of < 8 weeks (56 days), and < 1 week intra-treatment break is associated with better disease outcomes. However, published results note that a significant number of patients with LACV do not adhere to these metrics. The aim of our study is to evaluate whether a modified sequence of RT delivery, treating the localized boost volume upfront followed by the larger elective nodal volume is associated with improved compliance to optimal RT delivery metrics.
ABSTRACT
Colorectal cancer (CRC) is a frequent gastrointestinal malignancy with high rates of morbidity and mortality; 85% of these tumours are proficient mismatch repair (pMMR)-microsatellite instability-low (MSI-L)/microsatellite stable (MSS) CRC known as 'cold' tumours that are resistant to immunosuppressive drugs. Monotherapy with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors is ineffective for treating MSS CRC, making immunotherapy for MSS CRC a bottleneck. Recent studies have found that the multi-pathway regimens combined with PD-1/PD-L1 inhibitors can enhance the efficacy of anti-PD-1/PD-L1 in MSS CRC by increasing the number of CD8+ T cells, upregulating PD-L1 expression and improving the tumour microenvironment. This paper reviews the research progress of PD-1/PD-L1 inhibitors in combination with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, oncolytic virus, intestinal flora, antiangiogenic agents, chemotherapy, radiotherapy and epigenetic drugs for the treatment of pMMR-MSI-L/MSS CRC.
ABSTRACT
BACKGROUND: Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution. METHODS: We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes. RESULTS: This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels > 100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment. CONCLUSIONS: In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.
Subject(s)
Neuroblastoma , Child , Humans , Infant , Child, Preschool , Retrospective Studies , Neuroblastoma/radiotherapy , Neuroblastoma/pathology , Disease-Free Survival , Combined Modality TherapyABSTRACT
"Chronic pain after spinal surgery" (CPSS) is a nonspecific term for cases in which the end result of surgery generally does not meet the preoperative expectations of the patient and surgeon. This term has replaced the previous term i.e., failed back surgery syndrome. CPSS is challenging for both patients and doctors. Despite advancements in surgical techniques and technologies, a subset of patients continue to experience persistent or recurrent pain postoperatively. This review provides an overview of the multimodal management for CPSS, ranging from conservative management to revision surgery. Drawing on recent research and clinical experience, we aimed to offer insights into the diverse strategies available to improve the quality of life of CPSS patients.
ABSTRACT
BACKGROUND: Although immune checkpoint inhibitor (ICI)-based therapy is advantageous for patients with advanced melanoma, resistance and relapse are frequent. Thus, it is crucial to identify effective drug combinations and develop new therapies for the treatment of melanoma. SGN1, a genetically modified Salmonella typhimurium species that causes the targeted deprivation of methionine in tumor tissues, is currently under investigation in clinical trials. However, the inhibitory effect of SGN1 on melanoma and the benefits of SGN1 in combination with ICIs remain largely unexplored. Therefore, this study aims to investigate the antitumor potential of SGN1, and its ability to enhance the efficacy of antibody-based programmed cell death-ligand 1 (PD-L1) inhibitors in the treatment of murine melanoma. METHODS: The antitumor activity of SGN1 and the effect of SGN1 on the efficacy of PD-L1 inhibitors was studied through murine melanoma models. Further, The Cancer Genome Atlas-melanoma cohort was clustered using ConsensusClusterPlus based on the methionine deprivation-related genes, and immune characterization was performed using xCell, Microenvironment Cell Populations-counter, Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data, and immunophenoscore (IPS) analyses. The messenger RNA data on programmed death-1 (PD-1) immunotherapy response were obtained from the Gene Expression Omnibus database. Gene Set Enrichment Analysis of methionine deprivation-up gene set was performed to determine the differences between pretreatment responders and non-responders. RESULTS: This study showed that both, the intratumoral and the intravenous administration of SGN1 in subcutaneous B16-F10 melanomas, suppress tumor growth, which was associated with an activated CD8+T-cell response in the tumor microenvironment. Combination therapy of SGN1 with systemic anti-PD-L1 therapy resulted in better antitumor activity than the individual monotherapies, respectively, and the high therapeutic efficacy of the combination was associated with an increase in the systemic level of tumor-specific CD8+ T cells. Two clusters consisting of methionine deprivation-related genes were identified. Patients in cluster 2 had higher expression of methionine_deprivation_up genes, better clinical outcomes, and higher immune infiltration levels compared with patients in cluster 1. Western blot, IPS analysis, and immunotherapy cohort study revealed that methionine deficiency may show a better response to ICI therapy CONCLUSIONSï¼: This study reports Salmonella-based SGN1 as a potent anticancer agent against melanoma, and lays the groundwork for the potential synergistic effect of ICIs and SGN1 brought about by improving the immune microenvironment in melanomas.
Subject(s)
Immune Checkpoint Inhibitors , Melanoma, Experimental , Humans , Mice , Animals , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , CD8-Positive T-Lymphocytes , Methionine , Cohort Studies , Neoplasm Recurrence, Local , Melanoma, Experimental/drug therapy , Salmonella , Tumor MicroenvironmentABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.