Conversion Therapy Research Articles

Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab.

To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.

Easy but Efficient: Facile Approach to Molecule with Theoretically Justified Donor-Acceptor Structure for Effective Photothermal Conversion and Intravenous Photothermal Therapy.

To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2W cm-2). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.

Possibilities of reparative therapy in the treatment of patients with xerotic changes in the cornea

In recent years, in the treatment of patients with dry eye syndrome, drugs that, along with moisturizing, also have specific metabolic properties, due to the additional medicinal ingredients contained in them, deserve more and more attention. The article presents comparative data on the preparations of “artificial tears” and so-called keratoprotectors registered in Russia. In addition, a number of experimental and clinical studies by domestic authors evaluating the pharmacological and clinical effect of the new keratoprotector SPHERO®oko were reviewed. Much attention is also paid to the consideration of the original direction of SPHERO®oko application — its introduction into the corneal stroma (together with a dye) for cosmetic and functional keratopigmentation in the presence of extensive iris defects. The authors of the literature review, taking into account the results of numerous experimental studies and some clinical observations, believe that the use of SPHERO®oko has quite great opportunities in the complex treatment of xerotic changes of the cornea and conjunctiva. At the same time, it is of interest to continue the research on the possibilities of intrastromal administration of colored SPHERO®oko for keratopigmentation in the presence of extensive iris defects.

A commentary on 'Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study'.

A commentary on 'Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study'.

Terapia de conversión en cáncer gástrico: experiencia del Instituto Nacional de Cancerología de Colombia

Background: Gastric cancer (GC) represents a public health problem in Colombia and worldwide. Since most patients are at advanced stages at the time of diagnosis, it is necessary to develop management strategies as conversion therapy (CT). Objective: The aim of this study was to estimate the results of CT for treating patients with advanced and GC at Instituto Nacional de Cancerología de Colombia (INC). Material and methods: We included patients with incurable gastric cancer who underwent induction chemotherapy and intended curative surgery between 2010 and 2021. The clinical and pathological data and survival of the patients included were retrospectively reviewed. Overall survival (OS) was calculated from the time of initiation of chemotherapy until the date of death. Survival functions were estimated using the life table and Kaplan-Meier methods, and survival curves at 3 and 5 years were constructed. Results: 23 patients were analyzed; mean age was 56 years, and 17 (74%) were men. The most common criterion indicating unresectability was a T4b tumor in 13 cases (56.5%). All the patients underwent CT. Median follow-up was 28 months. Eleven patients developed disease recurrence (52%). Median survival was 41.2 months, and 3- and 5-year OS was 57.7% and 38.5%, respectively. Conclusions: CT provided an acceptable OS rate for selected patients with incurable advanced GC. This strategy requires a

Liver-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab for advanced hepatocellular carcinoma: a retrospective observational study of 23 cases.

Programmed cell death protein 1 (PD-1) or its ligand (PD-L1) monoclonal antibody combined with bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) has been established as first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Radiotherapy is a crucial local treatment for HCC. Mutual efficacy enhancement has been reported between radiotherapy, anti-angiogenesis therapy and immunotherapy in preclinical researches, but not been validated in clinical practice. Whether radiotherapy can enhance efficacy of anti-PD-1 immunotherapy plus bevacizumab for HCC remains unclear. This retrospective observational study aimed to appraise efficacy and safety of the combination of radiotherapy with pembrolizumab (a PD-1 monoclonal antibody) and bevacizumab for advanced HCC for the first time. Patients with advanced HCC treated by intrahepatic tumor-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab were consecutively included. Clinicopathological characteristics, therapeutic outcomes and treatment-related adverse events (TRAEs) were recorded and evaluated. A total of 23 patients were eventually enrolled. Median cycles of pembrolizumab and bevacizumab were 4 (median, 1-8) and 4 (median, 1-9) cycles. The objective response rates and disease control rates of irradiated intrahepatic HCC and non-irradiated extrahepatic HCC were 34.8% [95% confidence interval (CI), 16.4-57.3%] vs. 10.0% (95% CI, 1.2-31.7%), and 91.3% (95% CI, 72.0-98.9%) vs. 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.6 (95% CI, 4.7-8.5) and 18.3 (95% CI, 8.2-33.6) months, and 12-month PFS and OS rates were 17.5% (95% CI, 7.0-28.0%) and 60.9% (95% CI, 50.7-71.1%). Two patients (8.7%) with locally advanced, unresectable HCC eventually underwent curative resection of tumors after this trimodal treatment. Eighteen patients (78.3%) had ≥ grade 3 TRAEs, with myelosuppression and transaminase increase as the most common. This study firstly reported that combining radiotherapy with pembrolizumab and bevacizumab was preliminarily a feasible and effective therapeutic choice for advanced HCC in despite of more TRAEs. This tri-modal regimen may be a potential conversion therapy for unresectable, locally advanced HCC. The limitations of this study are its retrospective nature and small sample size; therefore, big-sample prospective studies are warranted to further investigate this tri-modal regimen.

Christ and the science of gender and human sexuality: The practice of LGBTQ in critical study

The study aims to assist Christians in discovering facts related to critical thinking and the application of higher criticism in handling the practice of LGBTQ, which is of paramount concern to Christians. This work is intended to help Christians confront and navigate difficult issues raised in the age of science, emphasising the practice of LGBTQ. The intersection of Christianity and the science of gender and human sexuality, particularly the practice of LGBTQ, is a complex and often contentious issue for all humanity living around the globe. This paper examines the acronym used in describing LGBTQ and its associated symbols. The finding found that LGBTQ finds its support from science as well as legal institutions. The Evangelical Christian faith organisations and Conservative Christian tradition do reject the practice of LGBTQ as inconsistent with biblical teachings, hence sinful and contrary to God's design. The paper also cites some support from traditional values applied against the practice of LGBTQ. But Progressive Christian Views tend to interpret Christian teachings on the practice of LGBTQ more inclusively and affirm its practice as consistent with principles of love and justice, which are found in the Bible. This finding affirms the complexity of the science of LGBTQ and the complexity of scriptural interpretation from different Christian traditions. The paper proposes the avoidance of some conversion therapy, like revert celibacy, that can lead to deep hatred, suicidal tendencies and isolation, which might drive a person to an unhealthy sexual orientation as one tries to relieve loneliness. If such is impossible, we call for deliberate measures to create a deep, warm, gracious, friendly, mutually accountable, humble, and forgiving environment. This piece of work concludes by examining Christ's view regarding the practice of LGBTQ by validating a biblical position since Christ is the agent of God's created humans and who should be connected to the community of faith, all for the glory of God.

Boosting Theranostic Performance of AIEgens Using Nanocatalyzer for Robust Cancer Immunotherapy

AbstractHigh‐performance theranostic systems are of paramount importance for achieving precise image‐guided cancer immunotherapy. Here, a novel nanoplatform is presented that integrates aggregation‐induced emission luminogen (AIEgen) with prussian blue (PB) nanocatalyzer for robust cancer immunotherapy. The AIEgen with dimethylamine substitution demonstrates compelling near‐infrared (NIR) light‐induced photothermal conversion and photodynamic therapy (PDT) capabilities. By incorporating AIEgen into porous PBNPs, and further enveloped within M1 macrophage membrane, a tumor‐specific theranostic nanoagent is constructed. This strategic integration effectively constrains the molecular motion of AIEgen, leading to amplified NIR‐II fluorescence brightness and PDT attributes. Moreover, PBNPs can catalyze tumor‐overexpressed H2O2 to generate oxygen to boost PDT efficacy, and PB's NIR absorption also intensifies photoacoustic imaging and photothermal effect. The integration of NIR‐II fluorescence and photoacoustic imaging provides comprehensive information for photoimmunotherapy in orthotopic breast cancer‐bearing mice. Leveraging its potent immunogenic cell death effect, the nanoagent not only significantly inhibits cancer growth, but also generates a whole‐cell therapeutic cancer vaccine to protect mice from tumor rechallenge. In highly malignant post‐surgery breast cancer models, the nanoagent enables both accurate identification of residual tumors and efficient inhibition of postoperative tumor recurrence and pulmonary metastasis. This study will offer valuable insights for creating highly efficacious and multifaceted photoimmunotherapy protocols.

Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study.

The objective of this study is to evaluate and compare the survival benefit and safety of surgery following conversion therapy versus surgery alone in patients diagnosed with surgically resectable hepatocellular carcinoma (HCC) at China Liver Cancer Staging (CNLC) IIb/IIIa stage. A total of 95 patients diagnosed with surgically resectable CNLC IIb/IIIa HCC were retrospectively enrolled in our study from November 2018 to December 2022. Among them, 30 patients underwent conversion therapy followed by hepatectomy, while the remaining 65 received surgery alone. The primary endpoint was recurrence-free survival (RFS). Propensity score matching was employed to minimize bias in the retrospective analysis. Compared to the surgery alone group, the conversion therapy group demonstrated a significantly prolonged median RFS (17.1 vs. 7.0 months; P =0.014), a reduced incidence of microvascular invasion (MVI, 23.3 vs. 81.5%; P <0.001), and a comparable rate of achieving Textbook Outcome in Liver Surgery (TOLS, 83.3 vs. 76.9%; P =0.476). Multivariate analysis indicated that conversion therapy was independently associated with improved RFS after hepatectomy (HR=0.511, P =0.027). The same conclusions were obtained after propensity score matching. The findings of our study offer preliminary evidence that preoperative conversion therapy significantly prolongs RFS in patients with surgically resectable HCC at CNLC IIb/IIIa stage. Furthermore, combining conversion therapy and hepatectomy represents a relatively safe treatment strategy.

Association between tumor morphology and efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.

The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy. Ninety-five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non-simple nodular (non-SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes. Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non-SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non-SN group (39.3% vs. 15.4%, p=0.012). Additionally, the median time to nodular progression was longer in the non-SN group (21.0months vs. 8.1months, p=0.119) compared to the SN group. Six patients with non-SN lesions underwent sequential local therapy. Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non-SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non-SN lesions.

Watch-and-wait strategy vs. resection in patients with radiologic complete response after conversion therapy for initially unresectable hepatocellular carcinoma: a propensity score-matching comparative study.

The optimal subsequent management for patients with initially unresectable hepatocellular carcinoma (uHCC) who have achieved complete response (CR) following conversion therapy remains unclear. This study aims to evaluate the feasibility and outcomes of the watch-and-wait (W-W) strategy versus surgical resection (SR) for these patients. This retrospective study reviewed patients with initially uHCC who underwent conversion therapy employing transarterial therapies combined with or without systemic therapies. Radiologic CR (rCR), clinical CR (cCR), and pathologic CR (pCR) were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared between the W-W and SR groups. Among 1880 patients with uHCC who underwent conversion therapy, 207 (11.0%) achieved rCR. Finally, we enrolled 149 patients meeting the inclusion criteria, including 74 receiving W-W strategy and 75 undergoing SR. Among the 149 patients with rCR, the W-W group demonstrated comparable 3-year OS rates to the SR group (80.9 vs 83.1%, P =0.77), but demonstrated inferior PFS rates (14.4 vs 46.5%, P =0.002). These results remained consistent after propensity score matching. For the 57 patients who achieved cCR, the W-W group exhibited comparable 3-year OS (88.1 vs 87.9%, P =0.89) and PFS rates (27.8 vs 40.8%, P =0.34) compared to SR group. Among the 75 patients in the SR group, 31 (41.3%) achieved pCR and 44 (58.7%) reached non-pCR. When compared with patients with pCR, those who achieved rCR in the W-W group showed comparable OS but inferior PFS rates. Moreover, patients who achieved rCR in the W-W group displayed both comparable OS and PFS rates to those with non-pCR. The W-W strategy offered comparable survival outcomes to SR in patients with initially uHCC who achieved rCR or cCR after conversion therapy. For these patients, the W-W strategy could be offered as an alternative treatment option.

Oncoguía de cáncer de colon 2023

Colon cancer is the third leading cause of cancer in Mexico and the world. In Mexico, it is commonly diagnosed in early and locally advanced stages. The main risk factor is lifestyle. Specialists from Instituto Nacional de Cancerología developed Oncoguía de cáncer de colon 2023 [Colon Cancer Guidelines 2023] through consensus work, based on their experience and analysis of the most recent evidence. Herein, risk factors, screening, diagnostic elements (clinical and histological), staging, and treatment (surgery as the cornerstone) are presented in early disease, locally advanced, oligometastatic scenarios, and after conversion therapy. Discussion and multidisciplinary management in decision - making for adjuvant treatment are emphasized.

A war against the natural order: Joseph Nicolosi, Reparative Therapy, and the Christian Right.

This article situates Joseph Nicolosi's first book, Reparative Therapy of Male Homosexuality, in historical context. Nicolosi, a Catholic clinical psychologist, was one of the most vocal practitioners of sexual orientation change efforts (SOCE) from the early 1990s until his death in 2017, and in these decades, the Christian Right became a key supporter of SOCE. In this article, I argue that two features of Nicolosi's book appealed to the Christian Right. First, Nicolosi relied on psychoanalytic thought to pathologize not only same-sex sexual desires but also poor parenting. The use of psychoanalytic thought was of particular interest to conservative Christians who believed that American fathers had forfeited their role as strong patriarchs. Second, Nicolosi's approach to therapy, which included changing one's dress and mannerisms and assertiveness training, stressed that same-sex desires could be eliminated through behavioral reconditioning. Nicolosi's psychological eclecticism, a common feature for mental health practitioners at the end of the twentieth century, has not been emphasized in prior scholarship on reparative therapy. Importantly, the psychological eclecticism practiced by Nicolosi became common within the Christian Right after the publication of Reparative Therapy of Male Homosexuality. By offering a close reading of Reparative Therapy of Male Homosexuality, this article demonstrates the interrelationship between one of the core texts of the ex-gay movement and the psychological and religious thought of the Christian Right at the turn of the twenty-first century. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Real-World Efficacy and Safety of China-Made Flumatinib Mesylate in the Treatment of Chronic Myeloid Leukemia in Chronic Phase

To evaluate the efficacy and safty of China-made flumatinib mesylate in the treatment of chronic myeloid leukemia in chronic phase (CML-CP). 42 CML-CP patients treated with Chinese produced flumatinib (oral, 600 mg, 1/d) were included in the study, including 14 newly diagnosed patients and 28 patients underwent conversion therapy. The hematological, cytogenetic and molecular response and safety were observed and evaluated after 3, 6 and 12 months of treatment. 35 patients were treated for more than 3 months, among which 31 patients were treated for more than 6 months and 17 patients were treated for more than 12 months. After 3 months of treatment, 33 patients underwent hematological, cytogenetic and molecular examination. Of these, 32 patients achieved complete hematological response (CHR), 13 patients achieved complete cytogenetic response (CCyR), 20 patients showed BCR-ABLIS≤10% and 7 patients reached major molecular response (MMR). After 6 months of treatment, all 30 patients who could evaluate efficacy achieved CHR, of which 17 patients achieved CCyR, 18 patients showed BCR-ABLIS≤1% and 16 patients reached MMR. After 12 months of treatment, all 17 patients were evaluated for efficacy, all achieved CHR, 10 patients obtained CCyR, 7 patients reached MMR. Grade III or IV thrombocytopenia, leukopenia and anemia occurred in 7, 2 and 1 patients, respectively. The non-hematological adverse reactions were diarrhea in 6 cases, renal function damage in 4 cases, rash and pruritus in 3 cases, liver function damage in 3 cases, nausea in 1 case, fever in 1 case, bone/joint or muscle pain in 1 case. In the real world, China-made flumatinib mesylate has a positive short-term efficacy and reliable safety in the treatment of CML-CP patients, whether as first-line treatment or second- and third-line conversion therapy.

Prognostic Value of Pathological Response for Patients with Unresectable Hepatocellular Carcinoma Undergoing Conversion Surgery

Plain Language SummaryThe combination of transarterial chemoembolization, lenvatinib, and PD-1 inhibitor is an efficacious conversion therapy for uHCC. In this multicenter retrospective study, we discovered that PR was associated with the prognosis of patients who underwent conversion surgery. Predictors of MPR included neutrophil-to-lymphocyte ratio and alpha-fetoprotein levels.

The efficacy and safety of conversion therapy after initial systemic chemotherapy in advanced esophageal cancer with distant metastases: A multicenter retrospective observational study.

310 Background: Systemic chemotherapy, with or without radiation, has been the standard treatment for esophageal squamous cell carcinoma (ESCC) with distant metastasis. The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable ESCC after initial treatment. In the present study, we examined the safety and effectiveness of conversion therapy for ESCC. Methods: Conversion therapy was defined as surgery or chemoradiation therapy (CRT) aiming at cure after initial treatment for tumors that were initially unresectable due to distant metastasis. The patients who underwent conversion therapy for ESCC between 2011 and 2021 at participating institutions were retrospectively reviewed. Patient backgrounds, treatment outcomes, and overall survival (OS) were evaluated. Results: From 22 institutions, 149 patients were enrolled. As defined, all patients received systemic chemotherapy as an initial treatment. The distant metastatic sites in para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial treatment, 116 patients underwent surgery and 33 patients received CRT as conversion therapy. Of 116 patients who underwent conversion surgery, the incidence rate of postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%, respectively. R0 resection was obtained in 87%. Regarding the non-hematological toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hematologic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p = 0.112). Pathological responders showed a significantly longer OS than non-responders (3y-OS, 56.4% vs 36.1%, p = 0.010). The distribution or number of distant metastases were not identified as prognostic factors. Conclusions: This study showed that conversion therapy for ESCC patients with distant metastasis could be conducted safely and have a favorable prognosis. Since its survival benefit would depend on the pathological response, it is important to develop an indicator to predict pathological response before surgery and carefully select appropriate candidates of conversion therapy in ESCC.

A single-arm, multi-center phase II study of tislelizumab combined with lenvatinib and GEMOX as conversion therapy in potentially resectable locally advanced biliary tract cancer (ZSAB-TransGOLP): A primary analysis.

488 Background: We have previously reported that GEMOX combined with lenvatinib and PD-1 antibody (GOLP regimen) showed promising efficacy as first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA), indicating that GOLP regimen may be an ideal conversion therapy for patients (pts) with potentially resectable advanced biliary tract cancer (BTC). This phase II trial explored the efficacy and safety of GOLP as conversion therapy in potentially resectable and locally advanced BTC. Methods: Patients with potentially resectable locally advanced BTC were enrolled and received tislelizumab (200mg, Q3W) and lenvatinib (8mg, QD) and GEMOX chemotherapy (Q3W) including gemcitabine 1000mg/m2 on day 1, 8 and oxaliplatin 85mg/m2 on day 1. Tumor responses were evaluated every 9 weeks according to RECIST v1.1, and the resectability was simultaneously discussed by MDT. For pts who were eligible for surgery, capecitabine alone was administered as adjuvant therapy after radical surgery. Pts who was not suitable for surgery continued to the original treatment regimen until progression or intolerable toxicity. The primary endpoint was R0 resection rate, and secondary endpoints included ORR, DCR, PFS, OS, CPR, MPR, RFS. Results: From December 2021 to July 2023, 41 pts were enrolled, 21 males and 20 females with a mean age of 57 years. 87.8% pts had iCCA, 7.3% had perihilar bile duct cancer and 4.9% had gallbladder cancer. TNM stage was II, IIIA, IIIB and IIIC for 2.4%, 34.1%, 58.5% and 4.9% of pts respectively. At cut-off date (September 10, 2023), the mean follow-up was 7.7 months, 39 pts completed at least three cycles of conversion therapy and 7 pts still administered with scheduled conversion therapy. The ORR was 43.9% (18/41) and the DCR was 87.8% (36/41). The median duration of therapy before surgery was 2.9 months (95%CI 2.6-4.6), R0 resection rate was 48.8% (20/41), and 2 pts underwent R1 resection. 9.1% (2/22) pts had a pCR and 22.7% (5/22) had an MPR. The most common grade 3/4 treatment-related adverse events (TRAEs) included neutropenia (31.7%), increased GGT (19.5%), leukopenia (12.2%). No grade 5 AEs occurred. Conclusions: This study demonstrates the high effectiveness and manageable safety of GOLP regimen as conversion therapy for potentially resectable locally advanced BTC. Survival data will continue to be followed up. Clinical trial information: NCT05156788 .

Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer with peritoneal metastasis.

281 Background: Although anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy has shown promising antitumor activity in advanced gastric adenocarcinoma (GC), the evidence of conversion therapy for initially GC with peritoneal metastasis is limited. This study aimed to clarify the clinical outcomes of conversion therapy for such patients. Methods: In this retrospective single institution cohort study, we analyzed 83 GC patients with peritoneal metastasis who received first-line anti-PD-1 antibody and chemotherapy and/or target therapy (trastuzumab) between November 2019 and June 2023. In patients who respond well to treatment, when preoperative imaging studies, multidisciplinary team discussions, and staged laparoscopy indicated the absence of peritoneal metastasis and the possibility of R0 resection, patients were offered conversion surgery. In this study, palliative surgery was not included. Patients were divided into two groups: conversion therapy group and palliative therapy group. Results: All patients underwent staging laparoscopy at their initial visit and underwent at least 2 treatment cycle, with a median follow-up time of 20.3 (16-24.6) months. Of the 83 patients, 32 patients presented a clinical response and underwent re-laparoscopy. Negative peritoneal metastasis and peritoneal cytology were confirmed in 25 patients who proceeded to undergo the conversion surgery. Compared with palliative therapy group, surgery group had a significantly better median progression-free survival (PFS) (20.3 vs 5.1 months; p &lt; 0.001) and a prolonged median overall survival (OS) (33.4 vs 11.7 months; p &lt; 0.001). In the surgery group, 24 (96%) of 25 patients were performed laparoscopic gastrectomy radical laparoscopic gastrectomy with more than D2 lymph node dissection (only one patient underwent open gastrectomy), 19 (76%) patients achieved R0 resection, 2 (8%) patients achieved pathologic complete response (pCR) and 4 (16%) patients reached tumor regression grade (TRG) 0-1. It was observed that patients with PCI score ≤ 2 experienced a longer median OS in comparison to those with PCI scores &gt; 2 ( unreached vs 28.5 months, P &lt; 0.031). And multivariate analysis associated with PFS among surgery cases identified signet ring cell carcinoma as an independent adverse prognostic factor (HR 4.66; 95% CI 1.19–18.22; p = 0.027). No serious treatment-related adverse events resulted in termination of treatment or death. Conclusions: Conversion surgery following first-line anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy represented a promising treatment strategy for GC patients with peritoneal metastasis. When immunochemotherapy is effective, active second-look staging laparoscopy should be performed to clarify the possibility of conversion surgery.

Phase II clinical study evaluating the efficacy and safety of disitamab vedotin combined with sintilimab and S-1 in the conversion treatment of HER2-overexpression unresectable gastric cancer.

TPS428 Background: Gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA) is the fifth commonest cancer and the fourth leading cause of cancer deaths worldwide. In about 30% to 40% of patients with advanced gastric cancer have lost the opportunity for radical surgery at the first diagnosis, and the overall 5-year survival rate is less than 50%. In recent years, conversion therapy has shown great promise. Disitamab vedotin is an antibody-drug conjugate comprising a novel HER2-directed monoclonal antibody, In previous study C008, RC48 showed a good safety profile and promising activity towards GC, and showed equivalent efficacy for HER2 IHC 2+ or HER2 IHC 3+ tumors. Methods: This study is a single-arm, phase II trial carry out at 16 academic hospitals in China, and will evaluate DV combined with Sintilimab and S-1 in patients with HER2-expressing unresectable gastric cancer. Eligible patients are at ≥ 18 to ≤ 75 years old; histologically confirmed, unresectable stage IV GC or GEJA; Single initial unresectable factor. For example, peritoneal metastasis (P1), Intraperitoneal free cancer cells positive (CY1), Paraaortic lymph node metastasis, liver metastasis (≤ 3 lesions, and ≤ 5 cm for a single lesion), ovarian metastasis; and documented histologically confirmed HER2 IHC 3+ or 2+; ECOG 0-1; at least one unresectable, measurable tumor lesion according to the RECIST version 1.1; adaptable function of the heart, liver, and kidney. 30 patients will be enrolled in this trial and receive Disitamab Vedotin(2.5mg/kg, IV, Q3W), Sintilimab (200 mg, IV, Q3W) and S-1 (twice daily on D1-14 are given at a dose calculate according to the body surface area and repeated every 3 weeks), until patients assessed by MDT to meet the criteria for surgical resection undergo gastrectomy. And the patients with peritoneal dissemination will combine with intraperitoneal administration of paclitaxel (60mg / m2, Q3W). The primary endpoint is R0 resection rate, Secondary endpoints include cORR, OS, RFS and safety. Seven patients have been enrolled in this study. Clinical trial information: NCT05627414 .

History and Iatrogenic Effects of Conversion Therapy.

Research indicates that sexual orientation change efforts (SOCEs) are not effective and furthermore commonly lead to iatrogenic effects such as depression, anxiety, and even suicide. Negative attitudes toward homosexuality derive from most formal religions and are incarnated in medical and psychological theories that support and encourage SOCEs. Oppression of sexual minorities makes it unlikely that change requests by patients are voluntary. Recently there has been a dramatic change as the field moves from reparative to affirmative approaches. Here, we review the history of SOCEs, their consequences, current affirmative treatments, and future directions in the field as they pertain to the well-being of the queer community. From an institutional community psychology perspective, we argue that even if true conversion were possible, such efforts are unethical and should not be pursued even if requested. As is the case with all psychological/psychiatric interventions, the issue is not "can" but "ought."