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Summary: Aim: This study aims to investigate the predictive factors for conversion therapy in patients with unresectable hepatocellular carcinoma (uHCC) and to evaluate the prognosis of conversion cases by comparing them with partial response (PR) and complete response (CR) cases. Methods: In this retrospective multicentre study, we included a total of 946 uHCC patients treated with atezolizumab and bevacizumab (Atez/Bev) from September 2020 to September 2023. Results: Out of the patients, 43 (4.5%) received conversion therapy following Atez/Bev treatment. The overall response rate was 65.1% and 23.7% in the conversion and non‐conversion group, respectively, with a statistical significance (p < 0.001). Multivariate analyses identified that BCLC stage B or an earlier stage (p = 0.045), absence of macrovascular invasion and extrahepatic spread (p = 0.045), and a low value of neutrophil to lymphocyte ratio (p = 0.04) were significantly favourable predictive factors associated with conversion therapy. The conversion group showed significantly better survival compared to the non‐conversion group (p < 0.001). In the landmark analysis at 6, 12 and 18 months, the conversion group exhibited better survival compared to PR patients in the non‐conversion group (p = 0.04, 0.01 and 0.03, respectively) and there were no significant differences in the overall survival (OS) between the conversion group and patients who achieved a CR (p = 0.7, 1.0 and 0.3, respectively). Conclusions: Patients with low tumour burden and low value of NLR were more likely to undergo conversion therapy. The OS of patients undergoing conversion therapy showed better survival compared to those achieving PR and was comparable to those with CR patients. Conversion therapy could be considered if feasible. [ABSTRACT FROM AUTHOR]

The diagnosis and treatment of head and neck undifferentiated carcinoma (HNUC) present significant challenges. Herein, we present the case of a patient with advanced HNUC who underwent conversion surgery following treatment with a combination of pembrolizumab and nimotuzumab. During therapy, histological transformation from undifferentiated to sarcomatoid carcinoma was detected at the primary site. This case not only highlights the potential of immune combination-targeted therapy to reduce tumour burden and increase the surgical options for patients, but also reveals the complex alterations in tumour biology that may occur during treatment. It emphasizes the necessity for routine pathological assessments throughout the therapeutic regimen to guide personalised therapeutic strategies and optimise patient prognoses. [ABSTRACT FROM AUTHOR]

The conversion success rate (CSR) has crucial implication for clinical outcomes of initially unresectable colorectal liver metastases (CRLM) following conversion therapy. This study aimed to develop a simple predictive scoring model for identifying CSR according to baseline magnetic resonance imaging (MRI) features, and confirm its performance and prognostic significance in a validation cohort. A total of 155 consecutive patients with initially unresectable CRLM were retrospectively reviewed in the study. A simple MRI-based predictive scoring model for identifying CSR was developed in the development cohort (n = 104) by using multivariable logistic regression analyzes. The diagnostic performance was evaluated for the predictive score. Thereafter, patients in the validation cohort (n = 51) were stratified into groups with predicted high CSR or low CSR according to the score. The progression-free survival (PFS) and overall survival (OS) were compared between two groups using the log-rank test. The predictive score of CSR, named mrNISE, incorporated the number of CRLM ≥ 10, the largest size ≥ 50 mm, poorly defined tumor-liver interface, and peritumoral enhancement. The AUC of the mrNISE score was 0.845 for the development cohort and 0.776 for the validation cohort. According to the score, patients with predicted high CSR had better PFS and OS than those with low CSR in both development and validation cohorts. The predictive score demonstrated great performance for identifying CSR of initially unresectable CRLM. Stratifying patients by the score, personalized treatment goals can be formulated before conversion therapy to improve clinical prognosis and reduce adverse events caused by ineffective treatment. [ABSTRACT FROM AUTHOR]

Some special therapeutic responses may appear during immunotherapy, such as hyperprogression, pseudoprogression and so on. Dissociated response of immunotherapy has been clinically reported in recent years mainly in lung cancer and kidney cancer. Since there were poor prognosis and simple treatment of advanced head and neck cancer, the application of immunotherapy in head and neck cancer has risen in recent years. But the dissociated response of immunotherapy in head and neck cancer is rarely reported. We reported two series of cases of advanced head and neck cancer that showed dissociated response after immunotherapy, tumor progression was assessed by imaging methods such as PET-CT, enhanced CT and enhanced MR, and reviewed the literature related to dissociated response in immunotherapy. We propose that the dissociated response of immunotherapy may affect the treatment strategy of advanced head and neck cancer, but more clinical analyses and researches are needed to confirm it. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy. Methods: A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed. Results: A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively. Conclusions: With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery. Trial registration: This was a retrospective study and it did not interfere with treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects. [ABSTRACT FROM AUTHOR]

The weak evidence base and profound consequences of gender-affirming interventions for youth call for a particularly sensitive and complex psychoanalytic exploration. However, prohibitions on knowing at the individual and social levels significantly constrain psychoanalytic work with trans-identified youth. Barriers to exploration and thinking that patients bring to treatment are reinforced and reified by the dominant socio-political trends that saturate the contexts in which young people dwell. These trends increasingly frame any attempt to deeply explore why a young person is seeking medical or surgical gender-affirming interventions as “off-limits” and a form of conversion therapy. Furthermore, politically driven clinicians who promote medical gender-affirming interventions misrepresent and attempt to discredit clinicians who explore the meaning and function of trans identification, or who express concern that transitioning may be a drastic solution to various forms of psychic pain. In doing so, they minimise the significance of the weak evidence base for these interventions and their serious, known risks. At the same time, they obscure or deny the psychic pain that is sometimes humming beneath the experience of gender dysphoria. The author asks: If there are significant uncertainties and risks of harm associated with medical interventions for young people, do we want to know? [ABSTRACT FROM AUTHOR]

With the development of comprehensive treatment, locoregional transarterial chemotherapy has become an alternative conversion therapy, palliative therapy, and neoadjuvant therapy for many solid malignant tumors. Locoregional transarterial chemotherapy, which is most frequently used for treating liver cancer, has the characteristics of high regional efficacy and few systemic adverse reactions. In recent years, the number of relevant reports of locoregional chemotherapy for treating initially inoperable colorectal cancer (CRC), including non-metastatic and metastatic CRC, has gradually increased. However, the specific treatment options for such locoregional therapy are not the same, and its indications, medication regimens and combined treatments have not reached any consensus. In this review, the application status of locoregional transarterial chemotherapy in primary and metastatic CRC patients has been reviewed and summarized to provide a reference for future clinical work and scientific research. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice. Due to the lack of typical clinical manifestations in the early stage, most patients in China are in the advanced stage at the time of confirmed diagnosis and thus lose the opportunity for surgical resection, which leads to a poor prognosis. Therefore, it is necessary to explore related therapies for converting unresectable HCC into resectable HCC. In recent years, the improvement in local therapy such as transarterial interventional therapies and radiation therapy technology, together with the clinical application of new targeted therapies and immune checkpoint inhibitors, has brought new opportunities and challenges in the conversion therapy for advanced HCC, and local therapy combined with systemic therapy may have a good synergistic effect, improve the conversion rate of surgery. This article investigates the value of local therapy combined with systemic therapy in the conversion therapy for HCC, in order to provide a basis for the clinical treatment of unresectable HCC. [ABSTRACT FROM AUTHOR]

Due to the insidious onset and poor prognosis of primary liver cancer, most patients are found to have unresectable primary liver cancer at initial diagnosis. In recent years, with the advent of targeted therapy, immunotherapy, and local therapy, some patients with advanced liver cancer have achieved successful conversion and undergone radical surgical resection, but at the same time, such treatment has brought many issues, such as the identification of potential population for conversion, the selection of conversion regimen, the necessity and timing of surgical resection after conversion, and the necessity and duration of adjuvant therapy after conversion surgery. This article discusses the above problems in conversion therapy for liver cancer based on the author’s own experience. [ABSTRACT FROM AUTHOR]

Simple Summary: Potential curative options for hepatocellular carcinoma include liver transplant, surgical resection, and ablation. Unfortunately, only 15–30% of patients are eligible for curative options at the time of presentation. Therefore, it is crucial to explore and evaluate treatment methods than can potentially convert nonsurgical candidates into surgical candidates. One such treatment option that can be used as a conversion strategy is yttrium-90 radioembolization. This study examines the success rate of using boosted dose radiation segmentectomy to convert nonsurgical candidates into eligible candidates for transplant or surgical resection. Background/Objectives: The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). Methods: In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. Results: Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child–Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. Conclusions: This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection. [ABSTRACT FROM AUTHOR]

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients. Plain Language Summary: The 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. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery. Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts. Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229– 1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119– 1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092– 0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079– 0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373– 4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147– 372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent. Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the benefit of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC). Patients and Methods: A retrospective cohort study was conducted involving 40 patients initially deemed unresectable HCC (uHCC). They received surgery following successful conversion therapy involving lenvatinib. The patients were matched in a 1:1 ratio to with a control group who underwent direct surgery, based on pre-treatment clinical data. Results: The median recurrence-free survival (RFS) duration for the conversion therapy cohort was notably longer than that of the direct surgery cohort (25 months vs 11 months). Furthermore, the 1- and 2-year RFS rates were significantly higher in the conversion therapy group compared to the direct surgery group (1 year: 70.5% vs 40.1%; 2 years: 49.0% vs 19.1%). The survival curves indicated a statistically significantly longer RFS in the conversion therapy cohort compared to the direct surgery cohort (P = 0.007). While patients achieving good remission based on both RECIST 1.1 and mRECIST criteria showed superior median RFS, no significant disparity was observed in the survival curves. The subgroup analysis revealed significantly improved prognosis among patients in the conversion therapy group who were male, older, had a history of alcohol consumption, were non-smokers, had liver cirrhosis, possessed Child-Pugh A liver function, had a tumor diameter exceeding 5 cm, and had an AFP ≥ 400 ng/mL. Among the cohort of 40 patients, only 8 individuals encountered severe adverse reactions, which were managed through dose reduction. None of the patients experienced multiple severe adverse reactions concurrently. Conclusion: For patients with unresectable hepatocellular carcinoma, conversion therapy offers a significantly better prognosis than direct surgery for uHCC patients. [ABSTRACT FROM AUTHOR]

Xinlin Li,1 Kai Chen,1 Xu Feng,1 Xinhua Wu,1 Shiguai Qi,1 Qingmiao Wang,2 Zhengrong Shi1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Fifth People’s Hospital of Chongqing, Chongqing, Chongqing, People’s Republic of ChinaCorrespondence: Zhengrong Shi, Email shizr@hospital.cqmu.edu.cnPurpose: The purpose of This study is exploring the intraoperative and perioperative differences between patients undergoing conversion surgery and those undergoing direct surgery, so as to improve preoperative preparation.Methods: The retrospective study was approved by an ethics review committee. A total of 232 patients with hepatocellular carcinoma who underwent surgical resection at the First Affiliated Hospital of Chongqing Medical University from September 2022 to December 2023 were included, comprising 210 operating patients and 53 conversion patients. Propensity score matching was employed for comparison in order to minimize bias.Results: The conversion group had more intraoperative bleeding (each P=0.001), longer operation time (P=0.033; PSM p=0.025), and higher intraoperative blood transfusion rate (p=0.001; PSM p=0.044). The incidence of perioperative complications, including perioperative ascites formation (p=0.011; PSM p=0.005), moderate to severe anemia (p=0.001; PSM p=0.002), postoperative blood transfusion (p=0.004; PSM p=0.036), and postoperative ICU transfer (p=0.041; PSM p=0.025), was higher in the conversion group compared to the operation group. The postoperative hospital stay (p=0.001; PSM p=0.003) was prolonged in the conversion group.Conclusion: Post-conversion operations carry a higher risk of bleeding and are more likely to result in moderate to severe anemia and ascites formation in the perioperative period. However, the risk is reversible with adequate preoperative blood preparation and prompt postoperative symptomatic treatment. Conversion patients should be encouraged to undergo operating therapy when they can withstand surgical resection.Keywords: conversion therapy, hepatocellular carcinoma, perioperative complications, hepatectomy, perioperative complications

Abstract Aim The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy. Methods A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed. Results A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively. Conclusions With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery. Trial registration This was a retrospective study and it did not interfere with treatment decisions.

Abstract Background Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear. Methods A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed. Results 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35–0.60) and PFS (0.49, 95% CI, 0.35–0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%). Conclusions The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone. Trial registration International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

Abstract Background Hepatocellular carcinoma is a highly lethal tumor worldwide, and China has a correspondingly high incidence and mortality rate. For patients with unresectable hepatocellular carcinoma, the prognosis is often poor. The objective of this retrospective study was to investigate the effects of conversion therapies on these patients. Methods The study included patients between the ages of 18 and 75 who were initially diagnosed with unresectable hepatocellular carcinoma and received conversion therapy. After completing surgery, the patients underwent pathological diagnosis, which showed complete necrosis. The study was conducted retrospectively at the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2019 to December 2021. The main objectives of the study were to evaluate the overall survival and recurrence-free survival. Results A total of 60 patients who met the inclusion criteria were enrolled. The median age of the patients was 56.6 ± 9.5 years, and 85% of them were male. The one-year overall survival rate (OS) was 98.3%, and the three-year OS was 95.6%. The one-year recurrence-free survival rate (RFS) was 81.1%, and the three-year RFS was 71.4%. In subgroup analysis, there was no statistically significant difference in RFS between patients with BCLC stages 0-A and BCLC stages B-C (p = 0.296). Additionally, there was no statistically significant difference in RFS between patients who received postoperative new adjuvant therapy and those who did not (p = 0.324). Conclusions Conversion therapy followed by surgical resection could be a promising treatment for patients with initially unresectable hepatocellular carcinoma, and the prognosis is good with a pathological complete response.

Background: Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear. Methods: A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed. Results: 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35–0.60) and PFS (0.49, 95% CI, 0.35–0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%). Conclusions: The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone. Trial registration: International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289). [ABSTRACT FROM AUTHOR]

Despite empirical evidence documenting its harms and substantial legislative efforts to ban its practice, conversion therapy remains a tragically prevalent practice in the United States. Recently, a circuit split between the Ninth and Eleventh Circuits has developed, raising questions about the future of conversion therapy regulation. This Note takes a retrospective look at the last ten years of conversion therapy bans and related legal challenges, questions the effectiveness of enacted bans, and explores routes for more effective regulation. This Note ultimately argues that conversion therapy bans must shift their focus to the regulation of unlicensed practitioners in order to better protect minors from the empirically demonstrated harms of conversion therapy. [ABSTRACT FROM AUTHOR]

Aim: 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. Methods: 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. Results: 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 (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non‐SN lesions underwent sequential local therapy. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Peritoneal metastasis in gastric cancer has a poor prognosis and is increasing in prevalence. Neoadjuvant chemotherapy is used for advanced tumors; however, surgery is generally not considered for metastatic and unresectable diseases. Recently, conversion surgery, a treatment which aims for an R0 resection following chemotherapy, has become a novel therapeutic option with better survival rates. In addition to surgery, hyperthermic intraperitoneal chemotherapy (HIPEC) leads to significant tumor reduction, but it is limited by its morbidity. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) delivers high concentrations of chemotherapy, but does not remove the tumor, making it useful mostly in palliative settings. Intraperitoneal (IP) therapy, known for its minimally invasive nature and repeatability, shows promise but requires further research. Ultimately, an integrated approach involving systemic chemotherapy, radical gastrectomy, HIPEC, PIPAC and IP chemotherapy can be used to optimize treatment outcomes of gastric cancer patients with peritoneal metastasis. [ABSTRACT FROM AUTHOR]

Background This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. Methods The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. Results Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P  = .370 and.334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. Conclusions For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma is a highly lethal tumor worldwide, and China has a correspondingly high incidence and mortality rate. For patients with unresectable hepatocellular carcinoma, the prognosis is often poor. The objective of this retrospective study was to investigate the effects of conversion therapies on these patients. Methods: The study included patients between the ages of 18 and 75 who were initially diagnosed with unresectable hepatocellular carcinoma and received conversion therapy. After completing surgery, the patients underwent pathological diagnosis, which showed complete necrosis. The study was conducted retrospectively at the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2019 to December 2021. The main objectives of the study were to evaluate the overall survival and recurrence-free survival. Results: A total of 60 patients who met the inclusion criteria were enrolled. The median age of the patients was 56.6 ± 9.5 years, and 85% of them were male. The one-year overall survival rate (OS) was 98.3%, and the three-year OS was 95.6%. The one-year recurrence-free survival rate (RFS) was 81.1%, and the three-year RFS was 71.4%. In subgroup analysis, there was no statistically significant difference in RFS between patients with BCLC stages 0-A and BCLC stages B-C (p = 0.296). Additionally, there was no statistically significant difference in RFS between patients who received postoperative new adjuvant therapy and those who did not (p = 0.324). Conclusions: Conversion therapy followed by surgical resection could be a promising treatment for patients with initially unresectable hepatocellular carcinoma, and the prognosis is good with a pathological complete response. [ABSTRACT FROM AUTHOR]

Background: The clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear. Method: Retrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed. Results: The results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006). Conclusions: Compared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC. [ABSTRACT FROM AUTHOR]

Sexual orientation and gender identity/expression change efforts (SOGIECEs) are discredited practices that are associated with serious negative effects and incompatible with modern standards for clinical practice. Despite evidence linking SOGIECEs with serious iatrogenic effects, and despite support for LGBTQ+-affirmative care alternatives, SOGIECE practices persist. In the 1970s and 1980s, Behavior Therapy published articles testing and/or endorsing SOGIECEs, thereby contributing to their overall development, acceptance, and use. The Behavior Therapy Task Force on SOGIECEs was assembled to conduct a rigorous review of the SOGIECE articles published in Behavior Therapy and to decide whether, and what, formal action(s) should be taken on these articles. This report provides a detailed review of the historic SOGIECE literature published in Behavior Therapy and outlines the Task Force's deliberative and democratic processes resulting in actions to: (1) add prominent advisory information to k = 24 SOGIECE papers in the form of digital "black box" disclaimers that caution readers that the SOGIECE practices tested or described in these papers are inconsistent with modern standards, (2) offset organizational financial benefits from the publication of these papers, and (3) promote LGBTQ+-affirmative practices. SOGIECEs are not the only concerning practices across the field's history, and the pages of today's scientific journals include practices that will be at odds with tomorrow's moral standards and ethical guidelines. This report calls for precautionary measures and editorial safeguards to minimize the future likelihood and impact of problematic published scholarship, including the need to fully include those with relevant lived experiences in all aspects of clinical science and peer review. [ABSTRACT FROM AUTHOR]

The literature on reparative justice focuses for the most part on the grounds and limits of wrongdoers' duties to their victims. An interesting but relatively neglected question is that of what – if anything – victims owe to wrongdoers. In this paper, I argue that victims are under a duty to accept wrongdoers' apologies. I claim that to accept an apology is to form the belief that the wrongdoer's apologetic utterance or gesture has the requisite verdictive, commissive and expressive dimensions; to communicate as much to him; and to recognise that his apology changes one's normative status in relation to him, and to comport oneself accordingly. I then offer a Kantian argument for the duty to accept and qualify that argument in the light of some hard cases. I end the paper by addressing the objection that victims do not owe it to wrongdoers to engage in any form of reparative encounter. [ABSTRACT FROM AUTHOR]

This article addresses the U.S. Supreme Court’s embrace, in 303 Creative LLC v. Elenis, of a First Amendment objection to state public accommodations laws that the Court avoided in Masterpiece Cakeshop v. Colorado Civil Rights Commission: such laws compel governmental orthodoxy. These objections invoke West Virginia Board of Education v. Barnette’s celebrated language: “If there is any fixed star in our constitutional constellation, it is that no official, high or petty, can prescribe what shall be orthodox in politics, nationalism, religion or other matters of opinion or force citizens to confess by word or act their faith therein.” They also cite Barnette’s progeny, including Wooley v. Maynard and Hurley v. Irish-American Gay, Lesbian and Bisexual Group of Boston. Business owners, their lawyers, and judges who have invoked these cases argue that state public accommodations laws requiring that businesses not discriminate based on sexual orientation in providing goods and services compel both speech and silence. In 303 Creative, Justice Gorsuch’s majority (6- 3) opinion quotes the beginning of Barnette’s “fixed star” passage but adapts it: the fixed star becomes “the principle that the government may not interfere with ‘an uninhibited marketplace of ideas.’” Gorsuch moves from the public school room—in which a state law compelled Jehovah’s Witness children to salute the flag, despite their religious beliefs—to the commercial marketplace, but gives little guidance about how broadly the protection of creative expression in this “marketplace of ideas” will extend. While Justice Gorsuch situates the Court’s protection of website designer Lorie Smith against compelled speech— and orthodoxy—in the commercial marketplace as the latest in a series of courageous First Amendment decisions by the Court protecting individuals against an encroaching state, Justice Sotomayor’s dissent excoriates the majority for departing from the long history of the Court courageously defending citizenship-expanding antidiscrimination laws against backlash and repeated First Amendment challenges. This article argues that 303 Creative’s use of Barnette extracts it from its wartime, antitotalitarian context, ignores crucial distinctions drawn in Barnette, and (as Justice Sotomayor’s 303 Creative dissent warns) “‘trivializes the freedom protected in Barnette,’” while also undermining public accommodations laws. The article also considers the recent invocation of Barnette and its progeny to challenge other forms of governmental regulation, including state regulation of crisis pregnancy centers and state bans on conversion therapy. [ABSTRACT FROM AUTHOR]

Over the last ten years, there has been a substantial increase in the number of children and adolescents referred to gender clinics for possible gender dysphoria. The gender affirming model of care, a dominant treatment approach in Canada, is based on low quality evidence. Other countries are realizing this and making psychosocial treatments and/or exploratory psychotherapy a first line of treatment for gender related distress in young patients. Psychodynamic (exploratory) psychotherapy has established efficacy for a range of conditions, and has been used in youth and adults with gender dysphoria. In Canada, the adoption of psychodynamic psychotherapy for gender dysphoria is impeded by some academics who argue that it may violate laws against conversion therapy. Psychodynamic psychotherapy is not conversion therapy and should be made available in Canada as a treatment modality for gender dysphoria. [ABSTRACT FROM AUTHOR]

This is a mixed methods international survey of therapists (n = 89) belonging to Therapy First, an organization supporting the use of exploratory therapy, rather than gender affirmative therapy, with gender-questioning clients. The method used was an electronic questionnaire, producing a 33% response rate from members. Responses were analyzed using thematic analysis. This article reports qualitative responses relating to therapists' experiences of anxiety in working in a hostile professional environment, and their adoption of strategies to minimize risk of allegations of conversion therapy. Therapist strategies included refining existing marketing approaches to serve preferred client groups, and reliance on proven therapy models. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced‐stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post‐surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced‐stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancy globally, with the majority of patients presenting at the initial diagnosis with locally advanced or metastatic disease, precluding the opportunity for curative surgical intervention. With the exploration and advancement of locoregional treatments, novel molecular-targeted therapies, anti-angiogenic agents, and immunomodulatory drugs, the management of HCC has seen an increase in objective response rates and prolonged duration of response significantly enhancing the potential for conversion to resectable disease in intermediate and advanced-stage unresectable HCC. Herein, we present a case of Barcelona Clinic Liver Cancer stage B unresectable HCC, where after two courses of treatment with transarterial chemoembolization combined with atezolizumab plus bevacizumab significant tumor reduction was achieved. Per Response Evaluation Criteria in Solid Tumors 1.1, partial response culminated in successful curative surgical resection. No drug-related adverse reactions occurred during hospitalization, and there has been no recurrence during the 11-month postoperative follow-up. For patients with Barcelona Clinic Liver Cancer stage B (intermediate-stage) unresectable HCC, the transarterial chemoembolization combined with atezolizumab plus bevacizumab regimen may offer improved therapeutic outcomes leading to a higher success rate of conversion therapy and, thus, improved survival. [ABSTRACT FROM AUTHOR]

Background: 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). Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Rainbow research tends to prioritise gender and sexuality experiences over the racialised experiences of Asian rainbow young people. Informed by an intersectional lens, we employed a hope-based ecological framework to examine how multiple overlapping axes of oppression (e.g. cisgenderism, heterosexism and racism) shape the aspirations of these youth. We drew on the voices of Asian participants from the 2021 Aotearoa New Zealand Identify Survey, who had responded to an open-text question on their hopes for rainbow young people (n = 217; age range = 14 to 26). The content analysis identified seven prominent categories of hope across three ecological levels (macro exo and meso). These categories were societies: 1) break away from cisheterosexist expectations; 2) confront racism and intersection with cisheterosexism; 3) promote rainbow-inclusive education; 4) ban sexual orientation and gender identity change efforts; 5) improve access to culturally safe health care; 6) dismantle white-dominated rainbow spaces; and 7) provide more rainbow-inclusive family support. These hopes were constructed amidst the desire to challenge unacceptance and exclusion by the wider society for not adhering to white cisheterosexist expectations. The study provides critical insights for community organisations, education settings, and government to consider in addressing the diverse needs of Asian rainbow young people. [ABSTRACT FROM AUTHOR]

Background: Patients with peritoneal metastasis (PM) from gastric cancer (GC) exhibit poor prognosis. Chemoimmunotherapy offers promising clinical benefits; however, its efficacy and predictive biomarkers in a conversion therapy setting remain unclear. The authors aimed to retrospectively evaluate chemoimmunotherapy efficacy in a conversion therapy setting for GC patients with PM and establish a prediction model for assessing clinical benefits. Materials and methods: A retrospective evaluation of clinical outcomes encompassed 55 GC patients with PM who underwent chemoimmunotherapy in a conversion therapy setting. Baseline PM specimens were collected for genomic and transcriptomic profiling. Clinicopathological factors, gene signatures, and tumor immune microenvironment were evaluated to identify predictive markers and develop a prediction model. Results: Chemoimmunotherapy achieved a 41.8% objective response rate and 72.4% R0 resection rate in GC patients with PM. Patients with conversion surgery showed better overall survival (OS) than those without the surgery (median OS: not reached vs 7.82 m, P<0.0001). Responders to chemoimmunotherapy showed higher ERBB2 and ERBB3 mutation frequencies, CTLA4 and HLA-DQB1 expression, and CD8+ T cell infiltration, but lower CDH1 mutation and naïve CD4+ T cell infiltration, compared to nonresponders. A prediction model was established integrating CDH1 and ERBB3 mutations, HLA-DQB1 expression, and naïve CD4+ T cell infiltration (AUC= 0.918), which were further tested using an independent external cohort (AUC= 0.785). Conclusion: This exploratory study comprehensively evaluated clinicopathological, genomic, and immune features and developed a novel prediction model, providing a rational basis for the selection of GC patients with PM for chemoimmunotherapy-involved conversion therapy. [ABSTRACT FROM AUTHOR]

Conversion therapy for initially unresectable hepatocellular carcinoma (iuHCC) using lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus a PD-1 inhibitor (LTP) has achieved promising results. However, further comparative research is necessary to evaluate the effectiveness and safety of conversion surgery (CS) for iuHCC. Data for 32 consecutive patients with iuHCC receiving CS and 419 consecutive patients with resectable HCC receiving initial surgery (IS) between November 2019 and September 2022 were collected retrospectively. After propensity score matching (PSM), 65 patients were selected. Before matching, the CS group had longer EFS (not reached vs. 12.9 months, P < 0.001) and similar OS (not reached vs. not reached, P = 0.510) compared with the IS group. Similar results for EFS (P = 0.001) and OS (P = 0.190) were obtained after matching. The multivariable Cox model (HR = 0.231, 95% CI: 0.105–0.504; P < 0.001) and subgroup analyses confirmed that CS could improve EFS. The CS group had significantly lower incidence of microvascular invasion (MVI) than the IS group (3.1% vs. 50.4%, P < 0.001). Moreover, the two groups had similar safety profiles. CS is effective and safe for patients with iuHCC receiving LTP. LTP has the potential to reduce risk factors for postoperative recurrence, especially MVI, which may influence surgical decision-making. [ABSTRACT FROM AUTHOR]

A 44-year-old woman with Lynch syndrome was referred to our hospital for treatment of recurrence of microsatellite instability-high rectal cancer. [18F]Fluorodeoxyglucose (18FDG)-positron emission tomography revealed a peritoneal metastasis with invasion to the small intestine and left ureter. The peritoneal metastasis was diagnosed initially as unresectable because of extensive invasion to the left ureter requiring nephrectomy. Hence, first-line treatment with pembrolizumab was started. After the first course of pembrolizumab, she developed hydronephrosis and a resulting urinary tract infection (UTI). A percutaneous nephrostomy was performed to control the UTI. After six courses of pembrolizumab, 18FDG-positron emission tomography showed that the peritoneal metastasis was smaller with significantly reduced 18FDG uptake, and it was then diagnosed as resectable without nephrectomy. She underwent R0 resection of the peritoneal metastasis with partial resection of the small intestine. Intraoperatively, the peritoneal metastasis showed no invasion of the left ureter, allowing its preservation. The percutaneous nephrostomy was removed postoperatively, and she has not developed any subsequent UTIs. Histopathologically, the tumor showed a pathological complete response to pembrolizumab. To the best of our knowledge, this is the first case of conversion therapy with pembrolizumab for peritoneal metastasis with hydronephrosis. [ABSTRACT FROM AUTHOR]

The incidence of primary liver cancer (PLC) has experienced a significant global increase, primarily attributed to the rise in hepatocellular carcinoma (HCC). Unfortunately, HCC is often diagnosed in advanced stages, leaving patients with limited treatment options. Therefore, transformation therapy is a crucial approach for long-term survival and radical resection in patients with advanced HCC. Conversion therapy has demonstrated promise in the treatment of advanced HCC. When integrated with the FOLFOX regimen, hepatic artery infusion chemotherapy (HAIC) can significantly improve tumor response efficiency, leading to high conversion and resection rates. We reviewed landmark trials of HAIC in combination with different drugs or means for the treatment of HCC to determine the clinical value of HAIC-centric translational therapies in HCC treatment. Furthermore, we specifically emphasize the advantages associated with employing FOLFOX-HAIC in the treatment of advanced HCC. The combination of HAIC with the FOLFOX regimen can help prevent the low intratumoral accumulation and high adverse reaction rate caused by the FOLFOX alone, holding significant potential in the comprehensive treatment of future HCC patients. [ABSTRACT FROM AUTHOR]

BackgroundGastric cancer (GC) is one of the leading causes of cancer-related death in China, and with the extensive development of conversion therapy, the treatment of advanced unresectable gastric cancer (AUGC) patients has ushered in a new dawn. This study aimed to analyze the efficacy of conversion therapy in AUGC patients and explored the relevant factors affecting the efficacy.MethodWe collected information from GC patients who received conversion therapy from this center and designed a retrospective study.ResultsWe collected relevant clinical data from 160 patients with AUGC. A total of 120 patients who underwent routine R0 resection were identified as conversion cases. A total of 25 patients (15.6%) achieved pCR, 92 patients (57.5%) achieved objective response rate (ORR), 140 patients (87.5%) achieved disease control rate (DCR), and 20 cases (12.5%) observed tumor progression. There were 86 patients who achieved pathological downgrading, with a total downgrading rate of 53.8%. Among the 160 patients, 37 patients (23.1%) had postoperative complications of varying degrees. A total of 72 patients (45.0%) had tumor recurrence/progression at the end of follow-up. The last chemotherapy and surgery (CST) (OR = 1.046, 95% CI 1.013–1.081, p = 0.006), tumor invasion (OR = 32.096, 95% CI 5.091–202.349, p < 0.001), and distant metastasis (OR = 7.050, 95% CI 1.888–26.323, p = 0.004) were independent factors influencing the efficacy of conversion therapy.ConclusionConversion therapy may have a good therapeutic efficacy for AUGC, and some clinical factors affect the efficacy response.

The diagnosis and treatment of head and neck undifferentiated carcinoma (HNUC) present significant challenges. Herein, we present the case of a patient with advanced HNUC who underwent conversion surgery following treatment with a combination of pembrolizumab and nimotuzumab. During therapy, histological transformation from undifferentiated to sarcomatoid carcinoma was detected at the primary site. This case not only highlights the potential of immune combination-targeted therapy to reduce tumour burden and increase the surgical options for patients, but also reveals the complex alterations in tumour biology that may occur during treatment. It emphasizes the necessity for routine pathological assessments throughout the therapeutic regimen to guide personalised therapeutic strategies and optimise patient prognoses.

With the continuous emergence of biotherapy drugs in recent years, great progress has been made in the systemic therapy for advanced liver cancer. Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs has become the first-line regimen recommended for the treatment of advanced liver cancer and has achieved clear oncology benefits and survival benefits. The regimens for immunotherapy combined with local treatment continue to emerge and have clearly improved objective response rate, and targeted and immune therapeutic regimens combined with sequential surgical treatment are reshaping the treatment pattern of advanced liver cancer and have finally improved radical surgical resection rate and long-term survival rate. Such changes in treatment guided by immunotherapy with or without targeted therapy have brought great challenges and thus require meticulous thoughts. With exploration of immune and targeted therapies combined with sequential surgical regimen as an example, there is a series of new problems and challenges before they are widely applied in routine diagnosis and treatment, including the selection of drug combination regimens, the evaluation of therapeutic efficacy, the treatment of toxic and side effects, surgical standards and timing, postoperative adjuvant treatment regimens, the validation of long-term survival benefits, and the selection of second-line treatment regimens for primary and secondary drug resistance. This article puts forward some suggestions and thoughts for several key aspects. [ABSTRACT FROM AUTHOR]

Progress in the systemic therapies, represented by the molecular target therapies and immune checkpoint inhibitors (ICIs), have significantly improved the prognosis of unresectable hepatocellular carcinoma (uHCC), but long term survial remains limitted. As one of the major combination of systemic and surgical therapies, conversion therapy provides potentially curative opportunity to some uHCC patients. It is widely reported from different domestic centers.The first Chinese expert consensus about it was released in 2021. Yet at the same time, there are many key issues in the practice and theory remains to be resolved. Actively thinking, exploring and finally resolving these issues are essential for establishing and promoting the standardized theoretical system of uHCC conversion therapy.

Surgery is still the first choice for patients with hepatocellular carcinoma(HCC). However, about 70% of HCC patients in China are first diagnosed in the advanced stage and have lost the opportunity for surgery. Recently, the rapid development of systematic therapy has brought new hope for patients with advanced HCC. The combination of molecular targeted therapy and immunotherapy with or without local therapy significantly improves the survival of advanced HCC and alters the landscape of surgical treatment in advanced HCC. In addition, systemic therapy also brings new opportunities for perioperative treatment of HCC patients. Conversion therapy, neoadjuvant therapy, and postoperative adjuvant therapy can increase the chances of surgical treatment, reduce the risk of postoperative metastasis and recurrence, and prolong the overall survival of HCC patients. Systematic therapy based on molecular targeted therapy and immunotherapy has been applied through the whole process of HCC surgical treatment, and has completely altered the surgery paradigm of HCC. However, further research is needed to determine the optimal combination protocol, screen the sensitive populations, address drug resistance, and reduce systemic adverse events.

Gastric cancer is one of the common malignant tumors of digestive system in our country. The proportion of patients in advanced and late stage is large, and the choice of perioperative treatment program is always difficult in clinic. For most locally advanced gastric cancer, compared with standard radical surgery combined with postoperative adjuvant chemotherapy, perioperative treatment mode may further improve the survival of patients. However, the efficacy of conventional chemotherapy regimen has reached a plateau, while the progress of traditional molecular targeted therapy is relatively slow. In recent years, with the increasing role of immunotherapy in the treatment of advanced gastric cancer, more and more clinical studies have shown that immunotherapy can also achieve better efficacy in perioperative gastric cancer patients. This article reviewed the research progress of immunotherapy in perioperative gastric cancer in recent years.

Wenxuan Li,1,&ast; Zhikai Zheng,2,3,&ast; Jiongliang Wang,2,3,&ast; Tianqing Wu,2,3,&ast; Juncheng Wang,2,3 Yangxun Pan,2,3 Jinbin Chen,2,3 Dandan Hu,2,3 Li Xu,2,3 Yaojun Zhang,2,3 Minshan Chen,2,3 Zhongguo Zhou2,3 1Cancer Center, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncheng Wang; Zhongguo Zhou, Department of Liver Surgery, Sun Yat-sen University Cancer Center, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343115 ; +86-20-87343117, Email wangjch@sysucc.org.cn; zhouzhg@sysucc.org.cnPurpose: The aim of this study was to investigate the efficacy and safety of conversion surgery for advanced hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC).Patients and Methods: Data from 172 HCC patients treated at Sun Yat-sen University Cancer Center between January 2016 and June 2021 with effective assessment of HAIC treatment response were retrospectively analyzed. Clinical pathological data, treatment process, survival, and occurrence of adverse events were recorded. Patients were grouped according to whether they achieved imaging remission after HAIC, underwent conversion surgery, and met the surgical resection criteria. Efficacy and safety were analyzed.Results: The median progression-free survival (PFS) and overall survival (OS) in the imaging remission group were 8.6 months and 26.3 months, respectively, which were longer than the 4.6 months (P< 0.05) and 15.6 months (P< 0.05) in the nonremission group. Compared with 6.7 months and 18.9 months in the HAIC maintenance group, the median PFS and median OS in the conversion surgery group were 16.5 months (P< 0.05) and 45.0 months (P< 0.05), but there was a higher risk of treatment-related hemoglobin decrease, alanine aminotransferase increase, aspartate aminotransferase increase, and total bilirubin increase (P< 0.05). The risk of biliary fistula, abdominal hemorrhage and ascites in the HAIC conversion surgery group was higher than that of the single surgery group (P< 0.05). Compared with the conversion surgery group, the median PFS and median OS of patients in the HAIC maintenance group who met the resection criteria were shorter: 7.1 months (P< 0.05) and 21.7 months (P< 0.05), respectively. All adverse events during the study were less than moderate, and no toxicity-related deaths occurred during follow-up.Conclusion: HAIC-based conversion therapy had acceptable toxic effects and could effectively stabilize intrahepatic lesions in advanced HCC, improve the survival benefit of patients, and provide some patients with the opportunity for conversion surgery to further improve prognosis.Keywords: hepatic arterial infusion chemotherapy, advanced hepatocellular carcinoma, conversion therapy