Treatment-related Adverse Reactions Research Articles

Preliminary clinical use of hepatic arterial infusion chemotherapy combined with lenvatinib and tislelizumab in the treatment of unresectable intrahepatic cholangiocarcinoma

Objective: To evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and tislelizumab in the treatment of unresectable intrahepatic cholangiocarcinoma (ICC). Methods: The clinical data of 12 patients with unresectable ICC who received HAIC combined with lenvatinib and tislelizumab in the First Affliated Hospital of Soochow University from October 2021 to April 2023 were retrospectively analyzed. HAIC included gemcitabine plus oxaliplatin; this regimen was combined with lenvatinib and tislelizumab within 3-7 days after its initial administration. Relevant laboratory examinations were performed before each cycle of HAIC, and enhanced computed tomography/magnetic resonance imaging examinations were performed every 6-9 weeks. Tumor response to treatment was evaluated using the modified Response Evaluation Criteria in Solid Tumors. The objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse reactions of patients with ICC were statistically analyzed. Results: The objective response rate to HAIC combined with lenvatinib and tislelizumab was 6/12; the disease control rate was 8/12; the median progression-free survival was 11.8 months; and the median overall survival was 14.2 months. Three patients had grade Ⅳ adverse reactions (increased alanine aminotransferase and aspartate aminotransferase thrombocytopenia), while three patients had grade Ⅲ adverse reactions (increased total bilirubin, alanine aminotransferase, and aspartate aminotransferase). The remaining patients had grade Ⅰ-Ⅱ adverse reactions. There were no serious complications related to interventional surgery. Conclusions: Use of HAIC (gemcitabine plus oxaliplatin) combined with lenvatinib and tislelizumab in the treatment of unresectable ICC may be safe and feasible. Preliminary clinical studies have shown that this combination can improve the survival and prognosis of patients with ICC.

The efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant recurrent ovarian cancer

Objectives: To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer. Methods: Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible. All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021. The primary endpoint was progression-free survival (PFS). The second endpoints included overall survival, objective response rate (ORR), disease control rate (DCR) and safety. Survival analysis was performed using the Kaplan-Meier method and Log-rank test, and influence factor analysis was performed using Cox proportional risk regression models. Results: The best overall response showed that partial response was observed in 14 patients, stable disease was noted within 13 patients, and progressive disease was found in 8 patients. Therefore, the ORR and DCR of these 35 patients were 40.0% (95% CI:22.9%-57.1%) and 77.1% (95% CI:62.9%-91.4%), respectively. The median follow-up duration was 18.9 months (6.9-32.2). The median PFS was 6.5 months (95% CI:5.35-7.66). Multivariate Cox regression analysis for PFS indicated that age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Federation of Gynecology and Obstetrics (FIGO) stage, and BRCA mutation status were independent factors influencing PFS (P＜0.05). Additionally, the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment (15.0 vs 6.0 month, P=0.029). The most common treatment-related adverse reactions were fatigue (85.7%), hematologic toxic (85.7%) and hypertension (74.3%). There were no treatment-related deaths. Conclusion: Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.

Intralesional acyclovir versus intralesional Hepatitis-B vaccine in treatment of resistant plantar warts: a randomized controlled trial

Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases.

Which Drugs are More Effective in Preventing Familial Adenomatous Polyposis Progression Based on Network Meta-Analysis?

Familial adenomatous polyposis (FAP) is an inherited disorder. At present, an increasing number of medications are being employed to treat FAP; however, only a few have been assessed for their efficacy and safety. Therefore, this study aimed to conduct a network meta-analysis to compare the therapeutic outcomes and adverse drug reactions of all FAP-associated medications. Six relevant databases were searched to identify pertinent randomized controlled trials (RCTs), and information on the dosage and frequency of various drugs was extracted. Additionally, data on changes in polyp counts and dimensions, as well as treatment-related adverse reactions for different medications were collected. The Bayesian method was employed to directly or indirectly compare the impact of different treatment regimens on changes in polyp numbers and diameters, and the safety of the drugs was investigated. CXB at 16 mg/kg/day significantly reduced polyp numbers. Celecoxib at 8 mg/kg/day and sulindac (150 mg twice daily) plus erlotinib (75 mg/day) were effective for tolerant FAP patients. Additionally, EPAFFA 2 g daily and sulindac (150 mg twice daily) plus erlotinib (75 mg/day) emerged as the most effective for reducing polyp size. The most effective treatment for reducing the number of colorectal polyps is celecoxib 16 mg/kg/day. On the other hand, a daily dosage of 2 g EPA-FFA demonstrates the best results in terms of decreasing colorectal polyp diameter.

Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy.

The aim of this study is to assess the effectiveness and safety of anlotinib in conjunction with concurrent radiochemotherapy for the treatment of locally advanced head and neck malignant tumors, including cases exhibiting local or neck recurrence and metastasis. Between June 2020 and June 2023, 42 patients diagnosed with locally advanced head and neck malignant tumors or presenting with local or neck recurrence and metastasis were recruited. These individuals received treatment that combined anlotinib with concurrent radiochemotherapy, followed by a minimum of two cycles of oral anlotinib upon completion of the initial treatment regimen. Among the 19 patients diagnosed with nasopharyngeal carcinoma, 14 patients attained a complete response, while four patients achieved partial response, resulting in an overall response rate of 94.74% (18/19). Conversely, among the 23 patients with non-nasopharyngeal carcinoma, two patients achieved complete response and 16 attained partial response, yielding a response rate of 78.26% (18/23). The 6-month progression-free survival rate was 95.24%. After treatment, serum vascular endothelial growth factor receptor levels exhibited a significant decrease compared with pretreatment levels. Notably, no instances of treatment-related serious adverse reactions were recorded. The combination of anlotinib with concurrent radiochemotherapy demonstrates favorable efficacy in managing locally advanced head and neck malignant tumors, including instances of local or neck recurrence and metastasis. Furthermore, the treatment regimen is characterized by an acceptable safety profile and tolerability.

Gender differences in oral appliance treatment of obstructive sleep apnea

PurposeAlthough overall success rates for treating obstructive sleep apnea (OSA) with an oral appliance (OA) are high, they are significantly higher among females. To verify published data, the study’s purpose was to evaluate a participant sample after one year of OA use. The primary outcome was treatment response, with responders defined as having an apnea-hypopnea index (AHI) < 10 at follow-up and/or reduced by ≥50% of baseline. Secondary measures were from standardized questionnaires.MethodsA sample of 314 participants, predominately with moderate-to-severe OSA, were enrolled and instructed to use an OA every night. At baseline and one-year follow-up, polygraphic recordings and questionnaires, including sleepiness (measured using the Epworth sleepiness scale) and quality-of-life (measured using the Functional Outcomes of Sleep Questionnaire), were collected.ResultsAmong the 314 participants, 192 completed the one-year evaluation: 51 females (27%) and 141 males (73%). Overall, OA treatment resulted in 78% and 77% responders among females and males, respectively. Neither the difference in improvement nor the absolute change in AHI differed significantly based on gender, at any OSA severity level. There were no significant gender differences in sleepiness or quality of life. Treatment-related adverse reactions were more common among females.ConclusionBoth females and males with OSA respond well to OA therapy, with nonsignificant gender differences in outcomes. Thus, the hypothesis that females respond better to OA treatment is rejected.

Case report: NSCLC with pulmonary embolism after treatment with almonertinib

Rationale: Almonertinib is the first independently developed third generation epidermal growth factor receptor tyrosine kinase inhibitors in China. It can be used not only for epidermal growth factor receptor (EGFR) sensitive mutation patients but also for T790M (+) resistant patients, and has better safety and survivability compared to the first and second generation EGFR-TKIs. The previous literature and case studies have reported significant treatment-related adverse reactions in non-small cell lung cancers patients treated with almonertinib, including elevated blood creatine phosphatase, prolonged cardiac QT interval, altered myocardial contractility, interstitial lung disease, eye disease, and hematological events. But there are few individual reports of pulmonary embolism events. Patient concerns: A 55-year-old female with no history of smoking visited a local hospital with mild cough and lower sacrococcygeal pain without obvious cause. Diagnosis: She was diagnosed with right lung adenocarcinoma with multiple bone metastases (T2bN1M1c, stage IVB) after image and histological examination, with EGFR 21 exon L858R sensitive mutation. Interventions: She initially underwent surgical treatment due to the discovery of a sacral tumor, and the pathology of the surgery indicated metastatic lung adenocarcinoma. Genetic testing results showed EGFR 21 exon L858R sensitive mutation. Combined with positron emission tomography/computed tomography imaging results and sacral tumor surgical pathology results, it was considered that the patient had lung adenocarcinoma with multiple bone metastases. Treatment plan: targeted treatment with almonertinib which is the third-generation EGFR-TKIs. After only 1 month of targeted treatment, chest enhanced computed tomography revealed pulmonary embolism imaging, combined with coagulation indicators, considering pulmonary embolism. As the thromboembolic site is located at the end of the pulmonary artery branch and imaging shows that tumor lesions are stable. Consider continuing targeted treatment with almonertinib and adjuvant oral anticoagulant therapy with rivaroxaban for treatment. Outcomes: Two months later, the patient’s condition was followed up and it was found that the imaging manifestations of pulmonary embolism disappeared, but the coagulation indicators remained in a hypercoagulable state. The patient’s treatment plan remained unchanged, and the patient was hospitalized for follow-up every 6 to 8 weeks to closely observe changes in the condition. Lessons: There are many reasons for the occurrence of hypercoagulable blood in tumor patients, and there are very few reports of treatment-related pulmonary embolism events in patients who are treated with almonertinib targeted therapy. It is particularly important to determine whether the hypercoagulable blood in such patients is related to targeted therapy drugs in clinical practice, as this will affect the clinical benefits of patients in epidermal growth factor receptor tyrosine kinase inhibitors treatment and the clinical indicators which need to pay more attention in follow-up observation, to avoid serious pulmonary embolism events and thus affect the patient’s survival status and quality of life.

Therapeutic use of autologous hematopoietic bone marrow transplant combined with concentrated platelet in infected surgical wounds: single-center prospective study

The healing wound is the consecutive process of maintaining tissue integrity including inflammatory, proliferative, and remodeling processes. Stem cells can self-renew, and also to differentiate into all cell types, and are involved in physiological regeneration, use of mesenchymal stem cells deriving from the bone marrow with PRP has potentiated the healing process. We conducted a single-arm pilot prospective analytical study was performed on 15 patients whose mean age was 31 years (range: 29–51 years), with refractory abdominal wounds at a private hospital in Iraq from March 30, 2022, to March 2023. Ten days after the stem cell transplant the re-enforcement with PRP subcutaneous injection around wounds. Small papules of granulation tissue appeared over the wound, and tissue granulation increased from 80% (30.26–80.00%) to 100% (81–100%). At the same time, the wound size was reduced by 60% (52.10–78.23%). The follow-up period was 7–24 months, during which no recurrence of the wound was found. In conclusion, the current study is the first to characterize the safety and efficacy of bone marrow-derived stem cells in combination with PRP in the treatment of refractory abdominal wound infection. All patients achieved a 100% healing rate in a short time, and no treatment-related adverse reactions occurred during the treatment.

Radiofrequency regulation of the sphenopalatine ganglion in managing herpes zoster ophthalmicus neuralgia: A case series.

Trigeminal herpes zoster, which comprises 10% to 20% of cases of herpes zoster, often leads to severe pain in the ophthalmic branches. Current treatments, including drug therapy and minimally invasive interventions, have limitations; accordingly, there is a need to explore alternative approaches. This study aimed to evaluate the efficacy and safety of computerized tomography (CT)-guided pulsed radiofrequency of the sphenopalatine ganglion in patients with intractable trigeminal herpetic pain. Three patients with intractable trigeminal ophthalmic zoster neuralgia were studied. All patients complained of bursts of headache, which occurred at least 10 times a day, usually in the periorbital and frontal regions. Conventional treatments, including oral medications and radiofrequency therapy targeting the trigeminal-semilunar ganglion and supraorbital nerve, could not sufficiently provide relief. Two patients were diagnosed with herpes zoster in the ocular branch of the trigeminal nerve with conjunctivitis, while one patient was diagnosed with postherpetic neuralgia in the ocular branch of the trigeminal nerve. This study employed a novel approach that involved CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion. In all three patients, pain relief was achieved within 1 to 3 days after treatment. During the follow-up, one patient had pain recurrence; however, its severity was ≈ 40% lower than the pretreatment pain severity. The second patient had sustained and effective pain relief. However, the pain of the third patient worsened again after 2 months. The average follow-up duration was 3 months. None of the enrolled patients showed treatment-related adverse reactions or complications. Our findings indicated that CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion was a safe and effective intervention for pain in patients with trigeminal ophthalmic zoster neuralgia, suggesting that it may be a therapeutic option if other treatments fail.

The efficacy of silver needle therapy for treating low back pain: a protocol for meta-analysis of randomized controlled trials.

As population aging and unhealthy living habits may exacerbate the prevalence and burden of low back pain (LBP), effective treatment and improvement of patient quality of life are particularly critical. Silver needle therapy (SNT), having evolved from traditional acupuncture, involves placing silver needles into muscles, tendons, and fascia for treatment. However, it still lacks robust clinical evidence to substantiate its effectiveness. Therefore, it is necessary to conduct more emphasis on meta-analysis to evaluate the clinical efficacy of SNT for treating LBP. We will search PubMed, Medline, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Databases up until December 2023 to identify randomized controlled trials of SNT treatment in adult patients with LBP. The primary outcome will be the intensity of pain after pain management. Secondary outcomes will include the Oswestry Disability Index, Japanese Orthopedic Association Back Pain Evaluation Questionnaire, requirement for analgesic drugs, and treatment-related adverse reactions. Two investigators conducted the literature search, selected studies that might meet the inclusion criteria based on the title and abstract, and extracted data from the eligible literature independently and will independently assess the risk of bias using the Revised Cochrane Risk-of-Bias (RoB2) tool. Multivariate analyses (including subgroup analysis, trial sequential analysis (TSA), sensitivity analysis, etc.) will be conducted to improve the quality of evidence. Registration: PROSPERO Registration Number: CRD42023466207, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023466207.

Clinical Analysis of Mitoxantrone Liposome in the Treatment of Children with High-Risk Acute Myeloid Leukemia

To investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia (AML). The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group, and the children with high-risk AML who received idarubicin regimen were enrolled as controls, and their clinical data were analyzed. Time to bone marrow recovery, the complete remission rate of bone marrow cytology, the clearance rate of minimal residual disease, and treatment-related adverse reactions were compared between the two groups. The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day), granulocytes(18 vs 24 day), platelets(17 vs 24 day), and hemoglobin(20 vs 26 day) compared with those treated with idarubicin, there were statistical differences (P <0.05). The effective rate and MRD turning negative rate in the observation group were 90.9% and 72.7%, respectively, while those in the control group were 94.1% and 76.4%, with no statistical difference (P >0.05). The overall response rate of the two groups of patients was similar. The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML, but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

Pain control and functional recovery as therapeutic goals in patients with chronic musculoskeletal pain: two experiences with tapentadol hydrochloride.

This study aimed to evaluate pain control, functioning, and quality of life (QoL) recovery in patients with chronic low back pain (cLBP) or post-traumatic osteoarthritis (OA) pain in the ankle/foot area, treated with tapentadol prolonged release and unresponsive to other treatments. Two observational retrospective studies were conducted using clinical practice datasets of patients with chronic pain in cLBP and OA foot/ankle at different time points (total follow-up=60-90 days). The studies assessed pain intensity by the Numerical Rating Scale (NRS) pain scale (patients were classified as responder in case of ≥30% pain reduction), QoL by the 5-level EQ-5D (EQ-5D-5L) questionnaire, patient satisfaction by the 7-point Patients' Global Impression of Change (PGIC) scale; cLBP health status by the Roland Morris Disability Questionnaire (RMDQ); foot and ankle functional status by European Foot and Ankle Society (EFAS) score; and treatment-related AEs. For the cLBP setting, 37 patients were enrolled, of which 86.50% were classified as responders (n=32; CI: 75.5% ÷ 97.5%). For the foot/ankle OA pain setting, 21 patients were enrolled. Pain assessment at final follow-up was available only for 11 patients, of which 72.73% (n=8; CI: 39.0% ÷ 94.0%) were classified as responders. Statistically significant improvements were seen in the RMDQ, EQ-5D-5L, and PGIC scores in cLBP. Improvements in the EFAS, EQ-5D-5L, and PGIC scores were seen in OA as well. The incidence of treatment-related adverse reactions was low in both studies. In the study population, tapentadol prolonged release was effective and well tolerated in treating cLBP and post-traumatic foot/ankle OA chronic pain when used in a multimodal manner. The reduction in pain was accompanied by clinically relevant improvements in patients' functionality and QoL.

Therapeutic prospects of nectin-4 in cancer: applications and value.

Nectin-4 is a Ca2+-independent immunoglobulin-like protein that exhibits significantly elevated expression in malignant tumors while maintaining extremely low levels in healthy adult tissues. In recent years, overexpression of Nectin-4 has been implicated in tumor occurrence and development of various cancers, including breast cancer, urothelial cancer, and lung cancer. In 2019, the Food and Drug Administration approved enfortumab vedotin, the first antibody-drug conjugate targeting Nectin-4, for the treatment of urothelial carcinoma. This has emphasized the value of Nectin-4 in tumor targeted therapy and promoted the implementation of more clinical trials of enfortumab vedotin. In addition, many new drugs targeting Nectin-4 for the treatment of malignant tumors have entered clinical trials, with the aim of exploring potential new indications. However, the exact mechanisms by which Nectin-4 affects tumorigenesis and progression are still unclear, and the emergence of drug resistance and treatment-related adverse reactions poses challenges. This article reviews the diagnostic potential, prognostic significance, and molecular role of Nectin-4 in tumors, with a focus on clinical trials in the field of Nectin-4-related tumor treatment and the development of new drugs targeting Nectin-4.

Application of a downward tract adherence method in the manual bedside placement of post-pyloric tubes in the intensive care unit.

At present, there are few studies on the technical requirements of manual bedside placement of post-pyloric tube in Intensive Care Unit patients. To investigate the application value of downward tract adherence method in the manual bedside placement of jejunal tubes. In the downward group, 160 patients underwent manual bedside placement of jejunal tubes by a downward tract adherence method. In the conventional group, 144 patients were treated with conventional gas injection during the placement. The success rate, average time, and adverse reactions of the placement in the two groups were investigated and compared. The success rate of the placement in the downward group was significantly higher (95% vs. 75%, P< 0.001) and the average time for the successful placement was shortened (23 ± 5.91 min vs. 26 ± 5.49 min, P= 0.025) than that in the conventional group. No treatment-related adverse reactions occurred in either group, and there were also no significant differences in vital sign changes. The use of the downward tract adherence method in the manual bedside placement of postpyloric tubes for the intensive care patients at the bedside has a higher success rate, effectivity and safety.

The efficacy and safety of PD-1 inhibitor combined with TACE in the first-line treatment of unresectable hepatocellular carcinoma.

The application of immune checkpoint inhibitors (ICIs) has changed the treatment of advanced hepatocellular carcinoma. Transcatheter arterial chemoembolization (TACE) is a first-line treatment for intermediate hepatocellular carcinoma. Serving as a local treatment modality that can induce immunogenic cell death, the efficacy and safety of combined use with ICI have not been evaluated. Although there have been prospective studies aimed at evaluating the efficacy and safety of ICI combined with TACE in BCLC stage B HCC patients, there are few reports on the evaluation of BCLC stage C patients with distant metastasis or portal vein cancer thrombus. Data of unresectable hepatocellular carcinoma patients received PD-1 inhibitor and TACE were collected in Xijing Hospital from June 2019 to December 2022. The tumor response was evaluated according to the Solid Tumor Modified Response Evaluation Standard (mRECIST), including complete response (CR), partial response (PR), disease stability (SD), disease progression (PD), objective response rate (ORR), and disease control rate (DCR). The progression-free survival (PFS) and overall survival (OS) were used to estimate therapy efficacy. The treatment-related adverse events were evaluated based on National Cancer Institute Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. A total of 42 patients with unresectable hepatocellular carcinoma were included in this study, including 34 males (80.5%) and 8 females (19.5%). The average age is 54.5years, ranging from 34 to 72. The median follow-up time was 12.3months, with an ORR of 42.9% and a DCR of 90.5% as of the follow-up time. The median PFS is 7.5months (95% CI: 5.76-9.23), and the median OS has not yet been reached; 6-month PFS was 62.2%. Safety analysis showed that 41 (97.6%) patients experienced treatment-related adverse reactions, mainly including elevated AST and ALT, fever, elevated bilirubin, hypothyroidism, nausea, abdominal pain, and rash. 40 patients had grade 1/2 adverse reactions, and only one patient had grade 3 adverse reactions, manifested as intolerable rash, nausea, and vomiting. Treatment is terminated when symptomatic treatment and drug suspension cannot be alleviated. In this study, thre patients with unresectable hepatocellular carcinoma were treated with PD-1 inhibitor combined with TACE to achieve good tumor reduction effect and underwent liver cancer resection surgery. For patients with unresectable hepatocellular carcinoma, whether in BCLC stage B or stage C, effective systemic therapy (PD-1 inhibitor) combined with local therapy (TACE) can achieve a high rate of tumor regression and objective response. Some patients may even pursue surgical treatment opportunities, and the treatment-related adverse reactions are controllable, which is expected to provide new options for extending the survival of unresectable hepatocellular carcinoma patients.

Chinese expert consensus on the follow-up management of patients with prostate cancer receiving medical castration therapy（2024 edition）

With the advancement of prostate cancer (PCa) diagnosis and treatment technology, the 5-year survival rate has remarkably increased, and PCa has entered the era of chronic disease management. Medical castration therapy remains the cornerstone treatment option for PCa patients, and run throughout the various stages of patient treatment. The disease progression, treatment-related adverse reactions and related complications of PCa patients after medical castration have become a major problem in the long-term management of PCa patients, affecting the survival and quality of life of patients. In addition to focus on the disease management of prostate patients during diagnosis and treatment, patients should be closely followed up after medical castration, especially for those at the critical stage of disease treatment. Testosterone or other indicators should be monitored at important nodes of the disease (the point of initiation disease phase and the point of treatment switch) to avoid missing the optimal treatment window. Follow-up management of PCa should take into account the characteristics of the treatment stage of the disease (disease stage, previous symptoms, prognostic factors and treatment strategy) and patients' own demands, and personalized follow-up strategies should be recommended to better increase patients' treatment compliance and improve patients' prognosis. Currently, there is a lack of guidelines or consensus on the management on the follow-up and quality of life of PCa patients after medical castration in China. Therefore, the Chinese Prostate Cancer Consortium has organized domestic experts to formulate this consensus, with the aim of providing a reference for the management on the follow-up and quality of life of PCa patients receiving medical castration therapy, and to further improve the prognosis and quality of life of PCa patients in China.

Abstract 922: Comparison of adverse effects of different combination therapies of immune checkpoint inhibitors and radiotherapy: A systematic review and meta-analysis

Abstract Background: Numerous ongoing trials are investigating cancer treatment combinations based on the combination of radiotherapy and immune checkpoint inhibitors. Understanding the toxicity profile of treatment-related adverse events is crucial. The purpose of this study is to comprehensively investigate the incidence and overview of treatment-related adverse events in different combination therapies involving radiotherapy and immune checkpoint inhibitors. Methods: We conducted a systematic review and meta-analysis of different combination therapies involving radiotherapy and immune checkpoint inhibitors. We searched English-language articles published between January 1, 2000, and May 31, 2023, in Pubmed, Embase, and the Cochrane database, investigating globally approved therapies based on PD-1, PD-L1 inhibitors, or CTA-4. Only prospective trials reporting overall incidence rates or lists of treatment-related adverse events data were included, and studies recruiting fewer than 10 patients were excluded. Retrospective studies were also excluded to minimize the risk of bias. The primary outcomes were the overall incidence and overview of treatment-related adverse events of all grades and grade 3 or higher. Heterogeneity among studies was assessed using the I2 statistic. The summary measure for primary outcomes was incidence rate (95% CI). This protocol is registered in PROSPERO (CRD42023390147). Results: We identified 1300 records, of which 50 studies (1655 patients) met the inclusion criteria. The incidence of treatment-related adverse reactions in the concurrent group was 76.0% (95% CI 73.5-78.4), and the incidence of grade 3 or higher adverse events was 23.5% (21.1-25.9). In the sequential group, the incidence of treatment-related adverse reactions was 75.9% (70.8-80.6), and the incidence of grade 3 or higher adverse events was 22.5% (18.0-27.5). In the induction group, the incidence of treatment-related adverse reactions was 72.8% (65.0-79.8), and the incidence of grade 3 or higher adverse events was 37.1% (29.4-45.3). The most common specific adverse event in the concurrent group was Fatigue (27.8% [25.2-30.6]); in the sequential group, it was Fatigue (43.3% [33.3-53.7]); in the induction group, it was Fatigue (71.4% [56.7-83.4]). Grade 3 or higher adverse events in the concurrent group was Lymphocyte Count Decreased (7.2% [5.4-9.4]); in the sequential group, it was Pneumonitis (11.1% [5.7-19.0]); in the induction group, it was Fatigue (10.5% [5.6-17.7]). Conclusion: Our study provides comprehensive data on treatment-related adverse events in different combination therapies involving radiotherapy and immune checkpoint inhibitors. Our results provide an essential reference of toxicity profiles of radiotherapy combined with immune checkpoint inhibitors for clinicians in routine practice of cancer care. Citation Format: Haiyu Zhou, Zefeng Guo, Ting Wang, Liyu Cai, Peimeng You. Comparison of adverse effects of different combination therapies of immune checkpoint inhibitors and radiotherapy: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 922.

Disitamab Vedotin Alone or in Combination With Immune Checkpoint Inhibitors in Bladder-Sparing Treatment of Muscle-Invasive Bladder Cancer: A Real-World Study

PurposeTo evaluate the efficacy and safety of a novel humanized anti-HER2 antibody, RC48-ADC (Disitamab vedotin, DV), the combination of RC48-ADC with PD-1 inhibitors was used to treat muscle-invasive bladder cancer (MIBC). This combination therapy has potential applications in both bladder preservation and neoadjuvant therapy for MIBC. MethodsPatients with MIBC underwent transurethral resection of bladder tumors followed by RC48-ADC alone or in combination with PD-1 inhibitors. Radiological and endoscopic evaluations were conducted 3 months later. The primary endpoint was objective response rate (ORR), with secondary endpoints including complete response rate (CR), partial response rate (PR), and bladder preservation rate. Treatment safety was assessed according to RECIST v1.1 criteria. ResultsEleven patients were enrolled, with a median follow-up of 19.0 months. Nine patients achieved objective response, including 6 CR and 3 PR cases. The pathological ORR was 81.8%. Eight patients continued combined treatment after 3 months, maintaining a 72.7% bladder preservation rate at 16 months. One elderly patient progressed from ypT2N0M0 to ypT3N0M0 and underwent radical cystectomy but had no recurrence or metastasis 12 months postoperation. All patients reported varying degrees of treatment-related adverse reactions, which were largely manageable. ConclusionThe combination of RC48-ADC and PD-1 inhibitors proves to be a viable and safe option for bladder-sparing therapy, particularly for T2-stage MIBC patients who are ineligible for surgery and chemotherapy. This approach offers a promising new direction for bladder preservation or neoadjuvant therapy in MIBC patients.

Evaluation of the efficacy of Simparica Trio® in the prevention of the transmission of Babesia canis by infected Dermacentor reticulatus to dogs

BackgroundBabesia canis is a clinically relevant vector-borne pathogen in dogs, and its presence is expanding. The efficacy of Simparica Trio® (Zoetis) in the prevention of B. canis transmission was evaluated at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight.MethodsTwenty-four (24) dogs were randomly allocated to either a placebo-treated group or one of two treatment groups with Simparica Trio. Dogs were infested with B. canis-infected Dermacentor reticulatus ticks 21 or 28 days after treatment administration. Blood samples for antibody and DNA detection were collected from each dog prior to tick infestation until 28 days after infestation. A dog was defined as being B. canis positive if it tested positive by both an indirect immunofluorescence assay (IFA) and PCR at any time during the study.ResultsNo treatment-related adverse reactions were recorded during the study. All placebo-treated animals displayed clinical signs due to babesiosis and tested positive on both IFA and PCR. None of the Simparica Trio-treated animals displayed any clinical symptoms or tested positive, resulting in a 100% efficacy in the prevention of canine babesiosis (P < 0.0001).ConclusionsA single treatment with Simparica Trio at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight prevents the transmission of B. canis by infected D. reticulatus to dogs for at least 28 days.Graphical

Effects of Reishimmune-S, a Fungal Immunomodulatory Peptide Supplement, on the Quality of Life and Circulating Natural Killer Cell Profiles of Patients With Early Breast Cancer Receiving Adjuvant Endocrine Therapy.

To evaluate the effects of Reishimmune-S, a fungal immunomodulatory peptide, on the quality of life (QoL) and natural killer (NK) cell subpopulations in patients receiving adjuvant endocrine therapy (ET) for breast cancer (BC). Patients who received adjuvant ET for stage I-III hormone receptor-positive BC without active infection were enrolled in this prospective pilot study. Reishimmune-S was administered sublingually daily for 6 months. QoL scores, circulating immune cell levels, including lymphocyte/NK cell subpopulations, and plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured at baseline and every 4 weeks. Data were analyzed using linear mixed-effect regression models. Nineteen participants were included in the analyses. One patient with underlying asthma did not complete the study owing to the occurrence of skin rashes 15 days after the initiation of Reishimmune-S. No other adverse events were reported. Reishimmune-S supplementation significantly improved the cognitive function at 3 months and significantly decreased the fatigue and insomnia levels at 3 and 6 months, respectively. There was no significant change in the global health/QoL score between baseline and week 4 of treatment. The proportion of CD19+ lymphocytes was significantly higher at 3 and 6 months, and that of NKG2A+ and NKp30+ NK cells was significantly lower at 6 months than at baseline. In addition, fatigue positively correlated with the proportion of NKp30+ NK cells (β ± standard error: 24.48 ± 8.75, P = .007 in the mixed-effect model). Short-term supplementation with Reishimmune-S affected the circulating immune cell composition and exerted positive effects on cognitive function, fatigue, and insomnia in patients with BC undergoing adjuvant ET, providing a potential approach for the management of treatment-related adverse reactions in this patient population.