ABSTRACT
BACKGROUND AND OBJECTIVES: To analyze oncological and functional results of transoral minimally invasive surgery (TMIS) for supraglottic laryngeal carcinoma (SGLC), and investigate independent prognostic factors. METHODS: Seventy SGLC patients treated with TMIS were included. The overall survival (OS), recurrence-free survival (RFS), and postoperative functions were analyzed. RESULTS: Sixty-two patients were early-stage (Tis, T1, and T2) and eight patients were T3. Eleven patients received preoperative induction chemotherapy (IC). Sixty patients received transoral laser microsurgery (TLM), and 10 patients received transoral robotic surgery (TORS). Fifty-eight patients were scored Grade-1 by water swallow test, and 49 patients were scored Grade 0 by grade, roughness, breathiness, asthenia, strain. The 1, 3, and 5 year OS of all were 95.450%, 84.877%, and 78.026%, and RFS were 89.167%, 78.052%, and 75.451% respectively. Kaplan-Meier survival analysis showed N stage and clinical stage were associated with OS, smoking, clinical stage, surgical margins, and Ki-67 index were associated with RFS. There were no significant differences in preoperative IC or direct surgery, TLM, or TORS. Cox analyses showed smoking and surgical margins were independent prognosis factors for RFS. CONCLUSIONS: The positive margin, Ki-67 index ≥40% and P53(+)&Ki-67 index ≥40% are worse factors affecting recurrence for SGLC patients. Both smoking and surgical margins are independent prognostic factors affecting recurrence.
Subject(s)
Laryngeal Neoplasms , Robotic Surgical Procedures , Humans , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/mortality , Male , Female , Middle Aged , Aged , Robotic Surgical Procedures/methods , Neoplasm Staging , Laser Therapy/methods , Adult , Minimally Invasive Surgical Procedures/methods , Microsurgery/methods , Prognosis , Retrospective Studies , Natural Orifice Endoscopic Surgery/methods , Laryngectomy/methods , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/epidemiology , Disease-Free Survival , Kaplan-Meier EstimateABSTRACT
Surgical resection for localized hepatocellular carcinoma (HCC) is typically reserved for a minority of patients with favorable tumor features and anatomy. Neoadjuvant immunotherapy can expand the number of patients who are candidates for surgical resection and potentially reduce the chance for recurrence, but its role in HCC not defined. We retrospectively examined the outcomes of patients who underwent surgical resection for HCC at the Johns Hopkins Hospital and compared the clinical outcomes of patients who received neoadjuvant immunotherapy with those who underwent upfront resection. The clinical cohort included a total of 92 patients, 36 of whom received neoadjuvant immune checkpoint inhibitor (ICI)-based treatment. A majority of patients (61.1%) who received neoadjuvant ICI-based therapy were outside of standard resectability criteria and were more likely to have features known to confer risk of disease recurrence, including α-fetoprotein ≥ 400 ng/mL (P = 0.02), tumor diameter ≥ 5 cm (P = 0.001), portal vein invasion (P < 0.001), and multifocality (P < 0.001). Patients who received neoadjuvant immunotherapy had similar rates of margin-negative resection (P = 0.47) and recurrence-free survival (RFS) as those who underwent upfront surgical resection (median RFS 44.8 months compared with 49.3 months, respectively, log-rank P = 0.66). There was a nonsignificant trend toward superior RFS in the subset of patients with a pathologic response (tumor necrosis ≥ 70%) with neoadjuvant immunotherapy. Neoadjuvant ICI-based therapy may allow high-risk patients, including those who are outside traditional resectability criteria, to achieve comparable clinical outcomes with those who undergo upfront resection. SIGNIFICANCE: Surgical resection for localized HCC is typically only reserved for those with solitary tumors without vascular invasion. In this retrospective analysis, we show that neoadjuvant immunotherapy may allow high-risk patients, including those who are outside of standard resection criteria, to undergo successful margin-negative resection and achieve comparable long-term clinical outcomes compared with upfront resection. These findings highlight need for prospective studies on neoadjuvant immunotherapy in HCC.
Subject(s)
Carcinoma, Hepatocellular , Immunotherapy , Liver Neoplasms , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/immunology , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Liver Neoplasms/immunology , Neoadjuvant Therapy/methods , Male , Female , Middle Aged , Retrospective Studies , Aged , Immunotherapy/methods , Neoplasm Recurrence, Local/prevention & control , Immune Checkpoint Inhibitors/therapeutic use , Disease-Free Survival , HepatectomyABSTRACT
OBJECTIVE: The aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables. METHODS: Patients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model. RESULTS: A total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36-4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17-3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT. CONCLUSION: Adjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC.
Subject(s)
Chemoradiotherapy , Neoplasm Recurrence, Local , Salivary Gland Neoplasms , Humans , Male , Female , Middle Aged , Retrospective Studies , Salivary Gland Neoplasms/therapy , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/mortality , Survival Rate , Chemoradiotherapy/methods , Chemoradiotherapy/mortality , Follow-Up Studies , Aged , Prognosis , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/epidemiology , Adult , Neoplasm Staging , Propensity Score , Radiotherapy, Adjuvant/methodsABSTRACT
By 2040, there will be an estimated 26 million cancer survivors in the United States. The essential components of survivorship care are (1) surveillance for cancer recurrence, (2) surveillance for new primary cancers, (3) management of physical and psychological long-term effects of treatment, (4) prevention or mitigation of late treatment effects, and (5) coordination of care between the oncology team and primary care clinicians. Recommendations for surveillance to detect recurrence vary with cancer type and stage at diagnosis. Screening for new primary cancers is the same as for the general population. Although many cancer survivors do not undergo recommended surveillance or screening, family physicians can encourage and facilitate adherence. Family physicians should also monitor and manage the physical and psychological effects of cancer diagnosis and treatment, such as depression, lymphedema, pain, and sexual dysfunction. Cardiovascular disease is a leading cause of death for cancer survivors, often as a long-term effect of cancer treatments. Clinicians should counsel patients on cessation of tobacco and alcohol use, participation in recommended levels of physical activity, and adherence to optimal nutrition recommendations. Finally, family physicians should work with the cancer care team to coordinate the care plan and assure that all recommended components are achieved. Written survivorship care plans should be provided to cancer survivors to help them transition from active treatment to posttreatment monitoring. .
Subject(s)
Cancer Survivors , Neoplasms , Primary Health Care , Humans , Cancer Survivors/psychology , Neoplasms/therapy , Neoplasms/complications , Adult , United States/epidemiology , Neoplasm Recurrence, Local/prevention & control , SurvivorshipABSTRACT
INTRODUCTION: Postoperative radiotherapy in patients with breast cancer with one to three lymph node metastases, particularly within the pT1-2N1M0 cohort with a low clinical risk of local-regional recurrence (LRR), has incited a discourse surrounding personalised treatment strategies. Multigene testing for Recurrence Index (RecurIndex) model capably differentiates patients based on their level of LRR risk. This research aims to validate whether a more aggressive treatment approach can enhance clinical outcomes in N1 patients who possess a clinically low risk of LRR, yet a high RecurIndex-determined risk of LRR. Specifically, this entails postoperative whole breast irradiation combined with regional lymph node irradiation (RNI) following breast-conserving surgery or chest wall irradiation with RNI after mastectomy. METHODS AND ANALYSIS: The RIGAIN (RecurIndex-Guided postoperative radiotherapy with or without Avoidance of Irradiation of regional Nodes in 1-3 node-positive breast cancer) Study is a multicentre, prospective, randomised, open-label, phase III clinical trial that is being conducted in China. In this study, patients with low clinical LRR risk but high RecurIndex-LRR risk are randomly assigned in a 1:1 ratio to the experimental group or the control group. In the experimental group, RNI is performed and the control group omits RNI. Efficacy and safety analyses will be conducted, enrolling a total of 540 patients (270 per group). The primary endpoint is invasive disease-free survival, and secondary endpoints include any first recurrence, LRR-free survival, distant metastasis-free survival, recurrence-free survival, overall survival, disease-free survival, breast cancer-specific mortality and assessment of patient quality of life. The study began in April 2023 and with a follow-up period of 60 months after the last participant completes radiation therapy. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University (SYSKY-2022-097-02, V.3.1). It adheres to the Helsinki Declaration and Good Clinical Practice. Research findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04069884.
Subject(s)
Breast Neoplasms , Neoplasm Recurrence, Local , Humans , Breast Neoplasms/radiotherapy , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Prospective Studies , Neoplasm Recurrence, Local/prevention & control , Radiotherapy, Adjuvant/methods , Lymphatic Metastasis , Mastectomy , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Lymph Nodes/pathology , Clinical Trials, Phase III as Topic , Mastectomy, Segmental , AdultABSTRACT
Local recurrence post-surgery in early-stage triple-negative breast cancer is a major challenge. To control the regrowth of a residual tumor, we have developed an autologous therapeutic hybrid fibrin glue for intra-operative implantation. Using autologous serum proteins as stabilizers, we have optimized high drug-loaded lapatinib-NanoSera (Lap-NS; â¼66% L.C.) and imiquimod-MicroSera (IMQ-MS; â¼92% L.C). Additionally, plasmonic nanosera (PNS) with an â¼67% photothermal conversion efficiency under 980 nm laser irradiation was also developed. While localized monotherapy with either Lap-NS or PNS reduced the tumor regrowth rate, their combination with IMQ-MS amplified the effect of immunogenic cell death with a high level of tumor infiltration by immune cells at the surgical site. The localized combination immunotherapy with a Nano-MicroSera based hybrid fibrin implant showed superior tumor inhibition and survival with significant promise for clinical translation.
Subject(s)
Imiquimod , Female , Animals , Humans , Mice , Cell Line, Tumor , Imiquimod/chemistry , Imiquimod/pharmacology , Lapatinib/chemistry , Lapatinib/pharmacology , Immunotherapy , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Neoplasm Recurrence, Local/prevention & control , Fibrin/chemistry , Triple Negative Breast Neoplasms/therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Fibrin Tissue Adhesive/chemistry , Fibrin Tissue Adhesive/pharmacology , Mice, Inbred BALB C , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic useABSTRACT
Rationale: Pharmacological targeting of mitochondrial ion channels is developing as a new direction in cancer therapy. The opening or closing of these channels can impact mitochondrial function and structure by interfering with intracellular ion homeostasis, thereby regulating cell fate. Nevertheless, their abnormal expression or regulation poses challenges in eliminating cancer cells, and further contributes to metastasis, recurrence, and drug resistance. Methods: We developed an engineered mitochondrial targeted delivery system with self-reinforcing potassium ion (K+) influx via amphiphilic mitochondrial targeting polymer (TMP) as carriers to co-deliver natural K+ channel agonists (Dinitrogen oxide, DZX) and artificial K+ channel molecules (5F8). Results: Using this method, DZX specifically activated natural K+ channels, whereas 5F8 assembled artificial K+ channels on the mitochondrial membrane, leading to mitochondrial K+ influx, as well as oxidative stress and activation of the mitochondrial apoptotic pathway. Conclusion: The synergistic effect of 5F8 and DZX presents greater effectiveness in killing cancer cells than DZX alone, and effectively inhibited tumor recurrence and lung metastasis following surgical resection of breast cancer tumors in animal models. This strategy innovatively integrates antihypertensive drugs with artificial ion channel molecules for the first time to effectively inhibit tumor recurrence and metastasis by disrupting intracellular ion homeostasis, which will provide a novel perspective for postoperative tumor therapy.
Subject(s)
Homeostasis , Mitochondria , Animals , Mitochondria/metabolism , Mitochondria/drug effects , Humans , Homeostasis/drug effects , Mice , Cell Line, Tumor , Female , Neoplasm Recurrence, Local/prevention & control , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Apoptosis/drug effects , Potassium/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Mice, Inbred BALB C , Ion Channels/metabolism , Potassium Channels/metabolism , Mice, Nude , Neoplasm MetastasisSubject(s)
Lymphoma, Large B-Cell, Diffuse , Neoplasm Recurrence, Local , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Neoplasm Recurrence, Local/prevention & control , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymph Node Excision , Lymph Nodes/pathology , Doxorubicin/administration & dosageABSTRACT
BACKGROUND: The aim of this study was to evaluate whether the sequential use of Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) is superior to BCG alone in reducing the risk of disease recurrence in patients with non-muscle invasive bladder cancer (NMIBC) with high risk of progression. METHODS: Prospective randomized trial was conducted from March 2021 to March 2023 and included 72 patients with high risk NMIBC. Trial registration number: NCT03790384; EUDRACT Number: 2017-004540-37. Thirty-one patients underwent to BCG alone and forty-one to MMC plus BCG during the induction course. The BCG schedule comprised six weekly instillation of 81 mg Connaught strain BCG as the induction course, followed by a further three-monthly instillation at three, six and twelve months, as the maintenance course. Forty mg of MMC were administered the day prior to each weekly BCG instillation in BCG plus MMC arm. A planned interim analysis was carried out in June 2023, at the end of the 12mo follow-up period. RESULTS: Six out of thirteen 6/31(19.3%) and 10/41 (24.4%) patients experienced recurrence in BCG and BCG plus MMC group (P=0.611), respectively. BCG plus MMC did not improve Disease Free Interval (HR: 1.23 95% CI:0.46-3.50; P=0.640). Patients receiving sequential treatment experienced similar AEs (P>0.05) and more urinary symptoms (P<0.05). CONCLUSIONS: This interim pre-planned analysis suggested absence of clinical advantages in terms of disease recurrence rate when MMC is administered one day prior to BCG during induction course.
Subject(s)
BCG Vaccine , Mitomycin , Neoplasm Invasiveness , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Mitomycin/administration & dosage , Mitomycin/therapeutic use , Mitomycin/adverse effects , BCG Vaccine/therapeutic use , BCG Vaccine/administration & dosage , Male , Female , Prospective Studies , Aged , Middle Aged , Adjuvants, Immunologic/therapeutic use , Adjuvants, Immunologic/administration & dosage , Chemotherapy, Adjuvant , Antibiotics, Antineoplastic/therapeutic use , Antibiotics, Antineoplastic/administration & dosage , Drug Therapy, Combination , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/pathology , Treatment Outcome , Administration, IntravesicalABSTRACT
The incidence of preoperatively diagnosed multiple ipsilateral breast cancer (MIBC) is increasing due to improved sensitivity of screening and preoperative staging modalities including digital breast tomosynthesis (3D breast mammography) and magnetic resonance imaging (MRI). The surgical management of MIBC remains controversial. Many surgeons continue to recommend mastectomy due to high local recurrence rates in patients with MIBC undergoing breast conservation therapy reported in historic, retrospective studies. More recent retrospective studies report acceptable rates of local recurrence. Yet concerns persist due to a paucity of prospective data regarding recurrence as well as concerns for margin positivity, cosmetic outcomes and the feasibility of adequate and safe delivery of radiation following breast conserving surgery. Breast conservation has emerged as the preferred surgical strategy for eligible patients with unifocal disease. Benefits include improved quality of life, body image and sexual function and lower surgical complication rates. A recent prospective clinical trial has corroborated a large body of retrospective data confirming the safety of breast conserving therapy and adjuvant radiation in women with MIBC with good oncologic control, low rates of conversion to mastectomy and satisfactory patient-reported cosmetic outcomes. With the current rise in MIBC diagnoses, it is imperative that surgeons understand the existent evidence in order to guide shared decision-making conversations with patients diagnosed with MIBC. This comprehensive review synthesizes the best available data and offers current recommendations for management of both the primary sites of disease as well as management of the axilla in patients with MIBC.
Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Humans , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Radiotherapy, Adjuvant/methods , MastectomyABSTRACT
Hepatocellular carcinoma (HCC) is a prevalent malignancy characterized by an exceedingly high recurrence rate post-surgery, significantly impairing the prognosis of HCC patients. However, a standard in-care strategy for postoperative therapy is still lacking. Although encouraging results have been obtained in a newly published clinical trial for postoperative therapy by targeting the vascular endothelial growth factor (VEGF) and programmed death ligand 1 (anti-PD-L1), its efficacy remains constrained. Combining a hemostatic hydrogel with a nanoparticle-based drug delivery system presents an opportunity to optimize the antitumor effect. Herein, we developed a nanoplatform, termed HMSN@Sor/aP@Gel, comprising a hemostatic fibrin hydrogel and functionalized hollow mesoporous silica nanoparticles (HMSNs) loaded with sorafenib and anti-PD-L1 for locally administered targeted-immunotherapy to prevent the postoperative recurrence and metastasis of HCC. The antitumor mechanism is grounded in dual inhibition of Ras/Raf/MEK/ERK (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathways, synergistically complemented by PD-L1 blockade. HMSN@Sor/aP@Gel facilitates dendritic cell maturation, enhances cytotoxic T-lymphocyte infiltration, promotes the polarization of tumor-associated macrophages to M1 phenotype, induces tumor immunogenic cell death, reverses immunosuppression, and establishes immune memory to counter postoperative recurrence. Animal studies corroborate that HMSN@Sor/aP@Gel-mediated targeted immunotherapy significantly impedes primary and metastatic tumor growth and establishes immune memory to prevent recurrence post-surgery. This investigation presents a promising strategy for postoperative therapy with considerable potential for clinical translation.
Subject(s)
Carcinoma, Hepatocellular , Hydrogels , Immunotherapy , Liver Neoplasms , Nanoparticles , Neoplasm Recurrence, Local , Sorafenib , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/immunology , Hydrogels/chemistry , Hydrogels/administration & dosage , Animals , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Humans , Neoplasm Recurrence, Local/prevention & control , Immunotherapy/methods , Sorafenib/administration & dosage , Sorafenib/therapeutic use , Sorafenib/pharmacology , Mice , Hemostatics/administration & dosage , Hemostatics/chemistry , Hemostatics/therapeutic use , Silicon Dioxide/chemistry , Silicon Dioxide/administration & dosage , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Male , Mice, Inbred BALB C , Fibrin/administration & dosageABSTRACT
This meta-analysis evaluated the impact of prophylactic post-chemotherapy granulocyte colony-stimulating factor (G-CSF) in patients with acute myeloid leukemia (AML). Overall, the relapse rate, overall survival, event-free survival, and mortality rate were similar in G-CSF (+) compared to G-CSF (-) patients. However, the relative risk (RR) of relapse was higher in children and in secondary AML patients who were treated with G-CSF compared to the G-CSF (-) group [RR, 95% confidence interval: 1.26, 1.04-1.52, and 1.12 (1.02-1.24)]. Treatment with post-chemotherapy G-CSF should be prescribed with caution in pediatric patients with AML and secondary AML as possibly increasing the relapse risk.
Subject(s)
Granulocyte Colony-Stimulating Factor , Leukemia, Myeloid, Acute , Adolescent , Child , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Granulocyte Colony-Stimulating Factor/therapeutic use , Granulocyte Colony-Stimulating Factor/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Neoplasm Recurrence, Local/prevention & control , RecurrenceABSTRACT
Preventing the recurrence of melanoma after surgery and accelerating wound healing are among the most challenging aspects of melanoma management. Photothermal therapy has been widely used to treat tumors and bacterial infections and promote wound healing. Owing to its efficacy and specificity, it may be used for postoperative management of tumors. However, its use is limited by the uncontrollable distribution of photosensitizers and the likelihood of damage to the surrounding normal tissue. Hydrogels provide a moist environment with strong biocompatibility and adhesion for wound healing owing to their highly hydrophilic three-dimensional network structure. In addition, these materials serve as excellent drug carriers for tumor treatment and wound healing. It is possible to combine the advantages of both of these agents through different loading modalities to provide a powerful platform for the prevention of tumor recurrence and wound healing. This review summarizes the design strategies, research progress and mechanism of action of hydrogels used in photothermal therapy and discusses their role in preventing tumor recurrence and accelerating wound healing. These findings provide valuable insights into the postoperative management of melanoma and may guide the development of promising multifunctional hydrogels for photothermal therapy.
Subject(s)
Hydrogels , Melanoma , Photothermal Therapy , Wound Healing , Hydrogels/chemistry , Hydrogels/administration & dosage , Humans , Melanoma/therapy , Photothermal Therapy/methods , Animals , Wound Healing/drug effects , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/therapeutic use , Drug Carriers/chemistry , Neoplasm Recurrence, Local/prevention & controlABSTRACT
Chitosan has been widely used in biomedical fields due to its good antibacterial properties, excellent biocompatibility, and biodegradability. In this study, a pH-responsive and self-healing hydrogel was synthesized from 3-carboxyphenylboronic acid grafted with chitosan (CS-BA) and polyvinyl alcohol (PVA). The dynamic boronic ester bonds and intermolecular hydrogen bonds are responsible for the hydrogel formation. By changing the mass ratio of CS-BA and PVA, the tensile stress and compressive stress of hydrogel can controlled in the range of 0.61 kPa - 0.74 kPa and 295.28 kPa - 1108.1 kPa, respectively. After doping with tannic acid (TA)/iron nanocomplex (TAFe), the hydrogel successful killed tumor cells through the near infrared laser-induced photothermal conversion and the TAFe-triggered reactive oxygen species generation. Moreover, the photothermal conversion of the hydrogel and the antibacterial effect of CS and TA give the hydrogel a good antibacterial effect. The CS-BA/PVA/TAFe hydrogel exhibit good in vivo and in vitro anti-tumor recurrence and antibacterial ability, and therefore has the potential to be used as a powerful tool for the prevention of local tumor recurrence and bacterial infection after surgery.
Subject(s)
Anti-Bacterial Agents , Chitosan , Hydrogels , Neoplasm Recurrence, Local , Polyvinyl Alcohol , Tannins , Chitosan/chemistry , Chitosan/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogen-Ion Concentration , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyvinyl Alcohol/chemistry , Mice , Neoplasm Recurrence, Local/prevention & control , Tannins/chemistry , Tannins/pharmacology , Humans , Staphylococcus aureus/drug effects , Boronic Acids/chemistry , Escherichia coli/drug effects , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Iron/chemistry , Surgical Wound Infection/prevention & controlABSTRACT
While surgical resection is the predominant clinical strategy in the treatment of melanoma, postoperative recurrence and undetectable metastasis are both pernicious drawbacks to this otherwise highly successful approach. Furthermore, the deep cavities result from tumor excision can leave long lasting wounds which are slow to heal and often leave visible scars. These unmet needs are addressed in the present work through the use of a multidimensional strategy, and also promotes wound healing and scar reduction. In the first phase, cell membrane-derived nanovesicles (NVs) are engineered to show PD-1 and dibenzocyclooctyne (DBCO). These are capable of reactivating T cells by blocking the PD-1/PD-L1 pathway. In the second phase, azido (N3) labeled mesenchymal stem cells (MSCs) are cultured into cell sheets using tissue engineering, then apply directly to surgical wounds to enhance tissue repair. Owing to the complementary association between DBCO and N3 groups, PD-1 NVs were accumulated at the site of excision. This strategy can inhibit postoperative tumor recurrence and metastasis, whilst also promoting wound healing and reducing scar formation. The results of this study set a precedent for a new and innovative multidimensional therapeutic strategy in the postoperative treatment of melanoma.
Subject(s)
Cicatrix , Melanoma , Mesenchymal Stem Cells , Neoplasm Recurrence, Local , Animals , Cicatrix/prevention & control , Neoplasm Recurrence, Local/prevention & control , Melanoma/pathology , Wound Healing , Mice, Inbred C57BL , Cell Line, Tumor , Cell Membrane/metabolism , Humans , Mice , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Female , Skin Neoplasms/pathology , Melanoma, Experimental/pathology , MaleABSTRACT
PURPOSE: Nonmuscle-invasive bladder cancer (NMIBC) has high recurrence rates and is often treated with mitomycin C (MMC) and bacillus Calmette-Guérin (BCG). Their efficacy relies on phase 2 enzyme metabolism and immune response activation, respectively. Dietary isothiocyanates, phytochemicals in cruciferous vegetables, are phase 2 enzyme inducers and immunomodulators, and may impact treatment outcomes. We investigated the modifying effects of cruciferous vegetable and isothiocyanate intake on recurrence risk following MMC or BCG treatment. MATERIALS AND METHODS: Self-reported cruciferous vegetable intake, estimated isothiocyanate intake, and urinary isothiocyanate metabolites were collected from 1158 patients with incident NMIBC in the prospective Be-Well Study. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards regression models for risk of first recurrences, and random effects Cox shared frailty models for multiple recurrences. RESULTS: Over median follow-up of 23 months, 343 (30%) recurrences occurred. Receipt of MMC and BCG was associated with decreased risks of first recurrence (MMC: HR = 0.58; 95% CI: 0.46-0.73; BCG: HR = 0.66; 95% CI: 0.49-0.88) and multiple recurrences (MMC: HR = 0.55; 95% CI: 0.44-0.68; BCG: HR = 0.72; 95% CI: 0.55-0.95). Patients receiving BCG and having high intake (>2.4 servings/mo), but not low intake, of raw cruciferous vegetables had reduced risk of recurrence (HR: 0.56; 95% CI: 0.36-0.86; P for interaction = .02) and multiple recurrences (HR: 0.51; 95% CI: 0.34-0.77; P for interaction < .001). The inverse association between MMC receipt and recurrence risk was not modified. CONCLUSIONS: For NMIBC patients who receive induction BCG, increasing consumption of raw cruciferous vegetables could be a promising strategy to attenuate recurrence risk.
Subject(s)
BCG Vaccine , Isothiocyanates , Mitomycin , Neoplasm Recurrence, Local , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/drug therapy , Mitomycin/therapeutic use , BCG Vaccine/therapeutic use , BCG Vaccine/administration & dosage , Male , Female , Isothiocyanates/therapeutic use , Isothiocyanates/pharmacology , Prospective Studies , Aged , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/epidemiology , Treatment Outcome , Antibiotics, Antineoplastic/therapeutic use , Adjuvants, Immunologic/therapeutic use , Diet , Neoplasm Invasiveness , Follow-Up StudiesABSTRACT
Background: Myxofibrosarcoma (MFS) is a rare type of soft tissue sarcoma that is locally aggressive and has a high risk of recurrence. The effectiveness of perioperative radiotherapy (RT) in preventing local recurrence (LR) of MFS remains uncertain. This retrospective study aimed to evaluate the impact of perioperative radiotherapy on local recurrence in patients with MFS. Methods: A total of 75 patients diagnosed with MFS and treated at a single institution were included in the study. Patient data, including demographics, tumor characteristics, and treatment variables, were collected from electronic medical records. The primary endpoint was the occurrence of local recurrence. Results: Among the patients, 25/75 (33.3%) received radiation therapy, while 50/75 (66.7%) did not. Local recurrence in the radiated group was 28% (7/25) compared to 36% (18/50) in the non-irradiated group (p = 0.20). The LR rate trended higher in patients who received RT postoperatively (adjuvant) (6/12, 50%) than preoperatively (neoadjuvant) (1/13, 7.6%) (p = 0.124). Of the 54 patients with negative margins, the local recurrence rate was lower in the radiated group (1/12, 8.33) than the non-irradiated group (9/36, 25%) (p = 0.034). A subgroup analysis based on tumor grade did not reveal any significant differences in recurrence rates between the radiated and non-irradiated groups. Furthermore, there was no significant difference in recurrence rates between the irradiated and non-irradiated groups at the one-year (p = 0.32), two-year (p = 0.24), and five-year (p = 0.32) follow-up marks. Conclusion: Although radiotherapy demonstrated a trend toward reduction in recurrence rates in patients with MFS in this study, the observed difference did not reach statistical significance. Neoadjuvant radiation appears to be more effective than adjuvant radiation. However, there was a significant reduction in recurrence in patients with negative margins who received radiation demonstrating that effective surgical resection continues to be the most important intervention in patients with myxofibrosarcoma. Level of Evidence: III.
Subject(s)
Fibrosarcoma , Neoplasm Recurrence, Local , Humans , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/radiotherapy , Female , Male , Retrospective Studies , Middle Aged , Fibrosarcoma/radiotherapy , Fibrosarcoma/surgery , Aged , Radiotherapy, Adjuvant , Adult , Treatment Outcome , Soft Tissue Neoplasms/radiotherapy , Soft Tissue Neoplasms/surgery , Aged, 80 and overABSTRACT
Testicular cancer is a rare but curable male malignancy. Seminoma represents the majority of germ cell tumors and is considered radiation sensitive. Radiation treatment plays a role in adjuvant therapy after orchiectomy of stage I, IIA, and IIB seminomas. Radiation dose de-escalation has been effective in preventing tumor recurrences while also limiting acute and long-term toxicities. However, long-term risks, including the prevailing concern of secondary malignancy risk, between adjuvant radiation and chemotherapy play a role in recommendations. Ongoing work continues to be performed to reduce radiation field and dose in combination with chemotherapy while still maintaining excellent outcomes.
Subject(s)
Seminoma , Testicular Neoplasms , Humans , Male , Testicular Neoplasms/radiotherapy , Seminoma/radiotherapy , Radiotherapy, Adjuvant , Orchiectomy , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/radiotherapy , Radiotherapy Dosage , Neoplasm Recurrence, Local/prevention & controlABSTRACT
BACKGROUND/AIM: Endoscopic submucosal dissection (ESD) followed by chemoradiotherapy (CRT) has become a promising treatment modality in the management of early-stage superficial esophageal squamous cell carcinoma (SESCC). However, radiotherapy often leads to significant adverse events (AEs), including cardiopulmonary toxicity, limiting the delivery of this treatment modality. This study aimed to evaluate the efficacy of reduced-volume radiotherapy and dose-dense chemotherapy in mitigating AEs for high-risk SESCC following ESD. PATIENTS AND METHODS: We retrospectively analyzed patients treated with customized CRT after ESD between 2014 and 2023. RESULTS: Thirty-nine consecutive patients were identified. The median follow-up period was 63.4 months (range=8.3-99.8 months). All patients completed CRT, with a low incidence (3%) of grade ≥3 nonhematologic AEs. Thirteen patients (33%) had a recurrence: 10 local, one regional, and two distant. The 5-year overall and disease-free survival rates were 77% and 64%, respectively. A positive vertical resection margin was identified as a prognostic factor associated with survival. CONCLUSION: Our novel approach of combining ESD with customized reduced-volume radiotherapy and dose-dense chemotherapy shows promise in providing favorable oncologic outcomes and a safer nonsurgical strategy for high-risk SESCC. Specifically, this regimen minimized cardiopulmonary toxicity without compromising therapeutic efficacy. More aggressive adjuvant therapy may be required for patients with positive vertical resection margins after ESD.
Subject(s)
Esophageal Neoplasms , Humans , Male , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophageal Neoplasms/radiotherapy , Female , Aged , Middle Aged , Retrospective Studies , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Chemoradiotherapy , Radiotherapy Dosage , Endoscopic Mucosal Resection , Aged, 80 and over , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Treatment Outcome , AdultABSTRACT
BACKGROUND/AIM: Adjuvant capecitabine and oxaliplatin (CAPOX) therapy is standard strategy for colorectal cancer with risk of recurrence. Early dose reduction (EDR) of CAPOX therapy is commonly used in real-world practice. However, there is limited evidence regarding the effectiveness of CAPOX for patients who had EDR. Therefore, this study aimed to clarify the risks of EDR and its effect on long-term outcomes and body composition factors. PATIENTS AND METHODS: Patients who received CAPOX therapy after radical surgery for colorectal cancer between June 2013 and December 2021 were included. EDR was defined as dose reduction within four courses of CAPOX therapy. Body composition factors were measured for 1 year following surgery to determine the EDR effects. RESULTS: Eighty-four patients were included; 35 (42%) of them had EDR. The multivariate analysis revealed that underweight [odds ratio (OR)=4.95, 95% confidence interval (CI)=1.13-21.7, p=0.03] was a risk factor for EDR. Relapse-free survival (RFS) was significantly better in the non-EDR group (p=0.01). The 5-year RFS rates for the non-EDR and EDR groups were 88.7% and 65.4%, respectively. The multivariate analysis revealed that age >65 years [hazard ratio (HR)=3.97; 95% CI=1.16-13.62, p=0.03] and EDR (HR=7.62; 95% CI=1.71-33.91, p=0.005) were associated with poorer RFS. The 1-year body composition analysis revealed decreases in all factors in the EDR group. CONCLUSION: Preoperative underweight status was associated with EDR, which resulted in decreased RFS and body composition factors when compared with the non-EDR group. Therefore, avoiding EDR and early nutritional intervention after EDR may improve outcomes.