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Relapse is a major cause of treatment failure in haploidentical haematopoietic progenitor cell transplant (HPCT) with PTCy. Natural killer cells suppress graft versus host disease and mediate the graft versus leukaemia effect, driven by killer cell immunoglobulin-like receptors (KIRs). Emerging research suggests that donor KIR genotype may influence graft outcome in haploidentical transplants with varying impacts between patient cohorts. This study investigates whether donors with greater KIR B motifs associate with outcomes such as greater relapse-free survival (RFS), overall survival (OS), nonrelapse mortality (NRM), acute graft versus host disease (GvHD) and infection. The study cohort included 98 haploidentical donor-recipient (D/R) pairs (myeloablative n = 37, RIC n = 61) with various haematological malignancies, receiving primary T-cell replete haploidentical HSCT with PTCγ. Following KIR SSO genotyping, donors are categorised into neutral (n = 63) or better and best (n = 35), based on KIR B motif content. Kaplan-Meier and Cox regression survival functions are performed to investigate associations with outcomes. Our results show that the better and best category has significantly poorer RFS (p = 0.013; hazard ratio [HR] 3.16, 95% CI 1.21-8.24: p = 0.018). The greater risk of relapse associated with poorer OS (p = 0.011; HR 2.24, 95% CI 1.18-4.24: p = 0.01) in the better and best category. The competing KIR receptor-ligand and missing licensing proof models failed to predict transplant outcomes. Here, we show neutral donors associate with favourable outcomes in T-cell replete haplo-HPCT with PTCγ after categorisation using the KIR B content model, due to the increased risk of relapse associated with the use of better and best donors., (© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

Background: Hepatocellular carcinoma (HCC) is a significant cause of oncologic mortality worldwide. Liver transplantation represents a curative option for patients with significant liver dysfunction and absence of metastases. However, this therapeutic option is associated with significant blood loss and frequently requires various transfusions and intraoperative blood salvage for autotransfusion (IBS-AT) with or without a leukocyte reduction filter. This study aimed to analyze available evidence on long-term oncologic outcomes of patients undergoing liver transplantation for HCC with and without IBS-AT., Methods: Per PRISMA guidelines, a systematic review of keywords "Blood Salvage," "Auto-transfusion," "Hepatocellular carcinoma," and "Liver-transplant" was conducted in PubMed, EMBASE, and SCOPUS. Studies comparing operative and postoperative outcomes were screened and analyzed for review., Results: Twelve studies totaling 1704 participants were included for analysis. Length of stay, recurrence rates, and overall survival were not different between IBS-AT group and non IBS-AT group., Conclusion: IBS-AT use is not associated with increased risk of recurrence in liver transplant for HCC even without leukocyte filtration. Both operative and postoperative outcomes are similar between groups. Comparison of analyzed studies suggest that IBS-AT is safe for use during liver transplant for HCC., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Multiple myeloma (MM) bears heterogeneous cells that poses a challenge for single-target immunotherapies. Here we constructed bispecific CS1-BCMA CAR-T cells aiming to augment BCMA targeting with CS1. Sixteen patients with relapsed or refractory (RR) MM received CS1-BCMA CAR-T infusion. Six patients (38%) had cytokine release syndrome, which was of grade 1-2 in 31%. No neurological toxicities were observed. The most common severe adverse events were hematological, including leukopenia (100%), neutropenia (94%), lymphopenia (100%) and thrombocytopenia (31%). Three patients with solitary extramedullary disease (sEMD) did not respond. At a median follow-up of 246 days, 13 patients (81%) had an overall response and attained minimal residual disease-negativity, and six (38%) reached a stringent complete response (sCR). Among the 13 responders, 1-year overall survival and progression-free survival were 72.73% and 56.26%, respectively. Four patients maintained sCR with a median duration of 17 months. Four patients experienced BCMA+ and CS1+ relapse or progression. One patient responded after anti-BCMA CAR-T treatment failure. Lenalidomide maintenance after CAR-T infusion and the resistance mechanism of sEMD were preliminarily explored in three patients. CAR-T cells persisted at a median of 406 days. Soluble BCMA could serve as an ideal biomarker for efficacy monitoring. CS1-BCMA CAR-T cells were clinically active with good safety profiles in patients with RRMM. Clinical trial registration: This study was registered on ClinicalTrials.gov, number NCT04662099., (© 2023. The Author(s).)

Hematopoietic stem cell transplantation (HSCT) offers the highest curative potential for patients with hematological malignancies. Complications including infection, graft-versus-host disease (GVHD), and relapse reflect delayed or dysregulated immune reconstitution. After transplantation, NK cells rapidly reconstitute and are crucial for immune surveillance and immune tolerance. NK cell function is tightly regulated by killer immunoglobin-like receptors (KIRs). Previous studies have revealed that donor KIRs, especially some activated KIRs (aKIRs) are closely related to transplant outcomes. Here, we performed a retrospective study, including 323 patients who received haploidentical (haplo) HSCT in our center. In univariate analysis, donor KIR2DS1, KIR2DS3 and KIR3DS1 gene protected patients with lymphoid disease from Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation, while donor KIR2DS1, KIR2DS5 and KIR3DS1 gene conferred a higher risk of CMV reactivation for patients with myeloid disease. Multivariate analysis confirmed that donor telomeric (Tel) B/x and KIR2DS3 gene best protected patients with lymphoid disease from EBV (p = 0.017) and CMV reactivation (p = 0.004). In myeloid disease, grafts lacking Tel B/x and KIR2DS5 gene correlated with the lowest risk of CMV reactivation (p = 0.018). Besides, donor aKIR genes did not influence the rates of GVHD, relapse, non-relapse mortality (NRM) and overall survival (OS) in this study. The reactivation of EBV and CMV was associated with poor prognosis of haplo-HSCT. In conclusion, we found that donor aKIR genes might have a synergistic effect on CMV and EBV reactivation after haplo-HSCT. Whether the influence of donor aKIR genes varies with disease types remained to be studied., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC)., Methods: This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR)., Results: A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E)., Conclusion: TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.

We discuss different pre-infusion, post-infusion and post-CAR T-cell relapse prognostic factors influencing the outcomes of anti-CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphomas. Despite the overall positive results of anti-CD19 CAR T-cell therapy, a significant percentage of patients relapse. We summarize the efforts made to identify predictive factors for response and durable remissions and survival. In the pre-infusion setting, the patient-related factors discussed include Eastern Cooperative Oncology Group performance status, age, and comorbidities. Disease-related factors like tumor burden, histology, and biological features are also considered. In addition, inflammation-related factors and CAR T-cell product-related factors are considered. After CAR T-cell infusion, factors such as disease response assessed by 18FDG-PET/CT scan, liquid biopsy monitoring, and CAR T-cell expansion become crucial in predicting survival outcomes. Response to 18FDG-PET/CT scan is a widely used test for confirming response and predicting survival. Liquid biopsy, in combination with 18FDG-PET/CT scan, has shown potential in predicting outcomes. CAR T-cell expansion and persistence have shown mixed effects on survival, with some studies indicating their association with response. In the setting of post-CAR T-cell relapse, prognostic factors include refractory disease, time of relapse, and elevated lactate dehydrogenase levels at CAR T-cell infusion. Enrollment in clinical trials is crucial for improving outcomes in these patients. Overall, we discuss a comprehensive overview of prognostic factors that can influence the outcomes of anti-CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphomas, highlighting the need for personalized approaches in treatment decision-making., (Copyright © 2023 by The American Society of Hematology.)

Several recent advances have affected the treatment landscape of diffuse large B-cell lymphoma. Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of chemorefractory disease. Two randomized studies in early relapse disease have expanded the label to provide access to CAR T-cell therapy as early as second line for some patients. Despite the durable remissions that have been achieved, many patients will experience relapse. There is a growing population of patients previously treated with CAR T-cell therapy facing dismal outcomes. We review the prospective studies that inform treatment options in later lines and highlight the limited data examining outcomes with novel therapies after CAR T-cell failure. The treatment landscape is anticipated to continue to evolve with the emergence of bispecific antibodies that appear to be a promising approach, particularly after CAR T-cell therapy, although little is known about overlapping mechanisms of resistance. Enrichment for patients who have received prior CAR T-cell therapy on prospective trials is a critical unmet need to inform the preferred management for these high-risk patients., (Copyright © 2023 by The American Society of Hematology.)

The outcome of patients with large B cell lymphoma (LBCL) who relapse or progress after CD19-directed chimeric antigen receptor T cell therapy (CAR-T) administered as salvage therapy beyond the second treatment line is poor. However, a minority of patients become long-term survivors despite CAR-T failure. The German Lymphoma Alliance (GLA) has proposed a hierarchical management algorithm for CAR-T failure in LBCL, aimed at allogeneic hematopoietic cell transplantation (alloHCT) as definite therapy in eligible patients. The purpose of this study was to investigate characteristics, relapse patterns, and management strategies in long-term survivors after CAR-T failure, with a particular focus on the feasibility and outcome of alloHCT. This was a retrospective analysis of all evaluable patients with a relapse/progression event (REL) observed in a previously reported GLA sample between November 2018 and May 2021. REL occurred in 214 of 356 patients (60%) who underwent CAR-T for LBCL in the previous GLA study. An evaluable dataset was available for 143 of these 214 patients (67%). Twenty-six of 143 patients (18%) survived 12 months or longer from REL, 109 (76%) died within the first year after REL, and 8 (6%) were alive but had not reached the 12-month landmark. Long-term survivors had more favorable pre-CAR-T features, had a longer interval between CAR-T and REL, and had more often received a tumor biopsy after CAR-T failure, whereas the choice of the first salvage regimen had no impact. AlloHCT was feasible in 40 of 53 patients (75%) intended and resulted in a 12-month post-transplantation overall survival of 36% in those patients who underwent transplantation with sensitive or untreated REL. AlloHCT after CAR-T failure in LBCL is feasible and may be an important contributor to long-term survival, although selection bias must be taken into account. Thus, alloHCT should be considered as a reasonable treatment option for eligible patients in this setting. However, because the overall outlook after CAR-T failure remains poor, novel effective therapeutic approaches are needed, either to allow long-term disease control per se or to improve the preconditions for successful alloHCT., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Renal-cell carcinoma (RCC) is the most common solid organ cancer in kidney transplantation recipients (KTRs)., Background: Analyze the incidence, prognosis, and evolution of primitive kidney RCC in KTRs at our institution., Material and Methods: Observational descriptive retrospective study in which all KTRs from January 2000 to December 2022 were included. We performed an annual abdominal ultrasound in all KTRs. Demographic and clinical data were collected. The surgical approach, location, size, histologic type, and tumor grade were analyzed. We assessed the coexistence of risk factors. We reported the appearance of tumors in other locations, changes in immunosuppressants (IS) after the diagnosis, and survival and recurrence rates observed during follow-up., Results: Eighteen RCCs of native kidneys were diagnosed with an incidence in our population of 1.08%. The majority were men (77.8%), with a mean age of 59.9 years. The pathologic analysis revealed 11 clear cell carcinomas, 6 papillary carcinomas, and 1 chromophobe cell carcinoma. The median tumor size was 2.7 cm. TNM stage was T1aN0M0 in 15 cases. Laparoscopy was performed to remove the tumor in most cases. All our patients underwent changes in IS therapy, with conversion to mammalian target of rapamycin inhibitors when possible and reduction of IS in all of them. After a mean follow-up of 78.6 months, survival was 100% without tumor recurrence. Seven of the patients were diagnosed with a new tumor in another location., Conclusion: In our experience, annual abdominal ultrasound in KTRs may be an option for the early detection of RCC in native kidneys., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The prognostic capacity of positive surgical margins (PSM) for biochemical recurrence (BCR) is unclear, with inconsistent findings across published studies. We aimed to systematically review and perform a meta-analysis exploring the impact of Positive surgical margin length on biochemical recurrence in men after radical prostatectomy., Methods: A search was conducted using the MEDLINE, Scopus, Embase and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The quality of the studies was assessed using the Newcastle-Ottawa scale, and the protocol was registered in advance (PROSPERO: CRD42020195908). This meta-analysis included 16 studies with BCR as the primary outcome measure., Results: Studies used various dichotomised thresholds for PSM length. A subgroup meta-analysis was performed using the reported multivariable hazard ratio (Continuous, 3, and 1 mm PSM length). PSM length (continuous) was independently associated with an increased risk of BCR (7 studies, HR 1.04 (CI 1.02-1.05), I 2  = 8% p < 0.05). PSM length greater than 3 mm conferred a higher risk of BCR compared to less than 3 mm (4 studies, HR 1.99 (1.54-2.58) I 2  = 0%, p < 0.05). There was also an increased risk of BCR associated with PSM length of less than 1 mm compared to negative surgical margins (3 studies, HR 1.46 (1.05-2.04), I 2  = 0%, P = 0.02)., Conclusion: PSM length is independently prognostic for BCR after radical prostatectomy. Further long-term studies are needed to estimate the impact on systemic progression., (© 2023. Crown.)

Background: High-power short-duration (HPSD) radiofrequency ablation of atrial fibrillation (AF) increases first-pass pulmonary vein isolation (PVI) and freedom from atrial arrhythmias while decreasing procedural time. However, the optimal power setting in terms of safety and efficacy has not been determined., Objectives: This study compared the procedural characteristics and clinical outcomes of 50-W vs 40-W during HPSD ablation of paroxysmal AF., Methods: Patients from the REAL-AF prospective multicenter registry (Real-World Experience of Catheter Ablation for Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation) undergoing HPSD ablation of paroxysmal AF, either using 50-W or 40-W, were included. The primary efficacy outcome was freedom from all-atrial arrhythmias. The primary safety outcome was the occurrence of any procedural complication at 12 months. Secondary outcomes included procedural characteristics, AF-related symptoms, and the occurrence of transient ischemic attack or stroke at 12 months., Results: A total of 383 patients were included. Freedom from all-atrial arrhythmias at 12 months was 80.7% in the 50-W group and 77.3% in the 40-W group (Log-rank P = 0.387). The primary safety outcome occurred in 3.7% of patients in the 50-W group vs 2.8% in the 40-W group (P = 0.646). The 50-W group had a higher rate of first-pass PVI (82.3% vs 76.2%; P = 0.040) as well as shorter procedural (67 minutes [IQR: 54-87.5 minutes] vs 93 minutes [IQR: 80.5-111 minutes]; P < 0.001) and radiofrequency ablation times (15 minutes [IQR: 11.4-20 minutes] vs 27 minutes [IQR: 21.5-34.6 minutes]; P < 0.001) than the 40-W group., Conclusions: There was no significant difference in freedom from all-atrial arrhythmias or procedural safety outcomes between 50-W and 40-W during HPSD ablation of paroxysmal AF. The use of 50-W was associated with a higher rate of first-pass PVI as well as shorter procedural times., Competing Interests: Funding Support and Author Disclosures The REAL-AF registry is funded through an investigator-initiated research grant (PI: Dr Osorio) from Biosense Webster Inc (NCT04088071). Drs Osorio, Zei, and Romero have received consulting and research support from Biosense Webster. Dr D’Souza has received consulting support from Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background/aim: Urachal carcinoma is a rare cancer, with limited evidence regarding systemic chemotherapy for metastatic urachal carcinoma. This study aimed to evaluate the efficacy and safety of a combination therapy of 5-fluorouracil and irinotecan (FOLFIRI) in patients with metastatic urachal carcinoma., Patients and Methods: Patients with metastatic urachal carcinoma treated with FOLFIRI between March 2008 and April 2023 at the Department of Medical Oncology, Tohoku University Hospital, were retrospectively analyzed using medical records., Results: Six patients with urachal carcinoma received FOLFIRI. The histological type was adenocarcinoma in all patients. The metastatic or recurrent sites were the peritoneum, lungs, lymph nodes, and local relapse sites. Three patients received FOLFIRI as first-line chemotherapy, and the other three received FOLFIRI as second-line chemotherapy. Two patients had only non-measurable lesions as the targets of tumor response. The best response was the stable disease or non-complete response/non-progressive disease in four patients, with a disease control rate of 67%. The median progression-free survival was 7.5 months. In two patients with ascites only as the site of metastasis, the amount of ascites and serum tumor marker levels decreased after FOLFIRI was initiated. Grade 3/4 toxicities included grade 3 neutropenia in one patient and grade 3 diarrhea in one patient., Conclusion: FOLFIRI has modest efficacy and good tolerability for the treatment of metastatic urachal carcinoma., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Chimeric antigen receptor (CAR)-T cells have recently emerged as a powerful therapeutic approach for the treatment of patients with chemotherapy-refractory or relapsed blood cancers, including acute lymphoblastic leukaemia, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma and multiple myeloma. Nevertheless, resistance to CAR-T cell therapies occurs in most patients. In this Review, we summarize the resistance mechanisms to CAR-T cell immunotherapy by analysing CAR-T cell dysfunction, intrinsic tumour resistance and the immunosuppressive tumour microenvironment. We discuss current research strategies to overcome multiple resistance mechanisms, including optimization of the CAR design, improvement of in vivo T cell function and persistence, modulation of the immunosuppressive tumour microenvironment and synergistic combination strategies., (© 2023. Springer Nature Limited.)

Background: Although laparoscopic inguinal hernia repair (LIHR) is widely performed worldwide, few studies have focused on the procedure in female patients. This study investigated the characteristics and outcomes of female patients with inguinal hernias who underwent LIHR., Materials and Methods: This study retrospectively analyzed the data of 7380 patients with inguinal hernia admitted to the General Surgery Department of Ruijin Hospital and underwent LIHR from January 2001 to December 2020. The clinical characteristics, surgical outcomes, and complications were assessed., Results: In total, 572 female patients were enrolled in this study. The proportion of femoral hernias in female patients was higher in women than in male patients (17.4% vs. 0.3%, respectively). Mesothelial cysts of the round uterine ligament (MCURL) were noted in 74 patients. The mean age of patients with MCURL was lower than that of patients without MCURL (46.4 vs. 55.6, P =0.018). Seventy cases (93.3%) of MCURL were resected laparoscopically, and 5 cases were resected through an auxiliary small incision. The round ligament was cut off in 335 patients and preserved in 237. No significant differences were observed in the number of hospitalization days, recurrence rates, or complications between the transection and preservation groups. None of the cases were converted to laparotomy, and no recurrence was noted during follow-up., Conclusion: LIHR is safe and feasible in female patients. Treatment of femoral hernia, MCURL, and the round ligament of the uterus should be carefully considered during LIHR in female patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Excessive visceral obesity in recipients of living donor liver transplantation (LDLT) is associated with mortality, and a recent study reported the correlation between visceral adiposity of male LDLT recipients and hepatocellular carcinoma (HCC) recurrence. However, there is no study on the relationship between the donor's visceral adiposity and surgical outcomes in LDLT recipients. We investigated the association of the visceral-to-subcutaneous fat area ratio (VSR) in donors and recipients with HCC recurrence and mortality in LDLT., Methods: We analyzed 1386 sets of donors and recipients who underwent LDLT between January 2008 and January 2018. The maximal chi-square method was used to determine the optimal cutoff values for VSR for predicting overall HCC recurrence and mortality. Cox regression analyses were performed to evaluate the association of donor VSR and recipient VSR with overall HCC recurrence and mortality in recipients., Results: The cutoff values of VSR was determined as 0.73 in males and 0.31 in females. High donor VSR was significantly associated with overall HCC recurrence (adjusted hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.06-1.93, p = 0.019) and mortality (HR: 1.35, 95% CI: 1.03-1.76, p = 0.030). High recipient VSR was significantly associated with overall HCC recurrence (HR: 1.40, 95% CI: 1.04-1.88, p = 0.027) and mortality (HR: 1.50, 95% CI: 1.14-1.96, p = 0.003)., Conclusions: Both recipient VSR and donor VSR were significant risk factors for HCC recurrence and mortality in LDLT recipients. Preoperative donor VSR and recipient VSR may be strong predictors of the surgical outcomes of LDLT recipients with HCC., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Retesting for Human epidermal growth factor receptor-2 (HER2) in post-neoadjuvant therapy resection is variable, and data is conflicting regarding the prognostic significance of changes in HER2 expression pre and post therapy., Methods: We identified 104 patients with localized HER2 IHC 3+ breast cancer who received neoadjuvant trastuzumab(T)/pertuzumab(P) containing chemotherapy at Yale Cancer Center between 2012 and 2022. Patients were divided into 3 cohorts by response and HER2 IHC in the residual disease: Cohort 1 pathologic complete response (pCR), Cohort 2 pre-treatment IHC 3+/post treatment IHC 1+/2+, and Cohort 3 pre-treatment IHC 3+/post-treatment IHC 3+. Kaplan-Meier survival analysis was performed to assess recurrence free survival at 36 months., Results: The overall pCR rate was 62.5% (65/104), while 37.5% (39/104) of patients had residual disease (RD). Among patients with RD, 58.9% (23/39) remained IHC 3+ and 41.1% (16/39) had reduced HER2 expression IHC1+ or 2+. In patients with HER2 IHC 3+ RD, 26% (6/23) developed local recurrence or distant metastasis while none of patients with post NAT HER2 IHC 1+ or 2+ RD had relapse (p = 0.0309). In patients with pCR, 6.15% (4/65) had recurrence. Kaplan-Meier survival analysis revealed superior disease-free survival in patients with reduced HER2 IHC expression compared to those with remained IHC 3+ (log rank p = 0.004)., Conclusion: We conclude that reduced HER2 expression by IHC following neoadjuvant treatment was associated with lower recurrence rates in HER2 IHC 3+ breast cancer. If confirmed, RD HER2 IHC expression could be used as a prognostic biomarker to stratify patients in adjuvant trials and identify patients who may benefit from more intensive adjuvant therapy and post therapy surveillance., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution., Materials and Methods: Patients with spine metastases treated with SBRT (1 fraction/18 Gy or 5 fractions/7 Gy) during the last 12 years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory., Results: From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18 Gy (75%) or 5 fractions/7 Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2 months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3 years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01)., Conclusions: According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach., (© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy., Materials and Methods: A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation., Results: There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities., Conclusion: Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Aims: There are different therapeutic approaches for biliary strictures and reducing portal hypertension in patients with symptomatic portal cavernoma cholangiopathy (PCC). Endoscopic treatment includes endoscopic biliary sphincterotomy (EST), dilation of stricture with a biliary balloon, placement of plastic stent(s) and stone extraction. Fully covered self-expandable metal stent (FCSEMS) is placed as a rescuer in case of haemobilia seen after EST, dilation of stricture and removal of plastic stent rather than the stricture treatment itself. In this retrospective observational study, we sought to assess the clinical outcomes of FCSEMS as the initial treatment for PCC-related biliary strictures., Materials and Methods: Twelve symptomatic patients with PCC both clinically and radiologically between July 2009 and February 2019 were examined. Magnetic resonance cholangiopancreatography (MRCP) and cholangiography were employed as the diagnostic imaging methods. Chandra-Sarin classification was used to distinguish between biliary abnormalities in terms of localization. Llop classification was used to group biliary abnormalities associated with PCC. Endoscopic partial sphincterotomy was performed in all the patients. If patients with dominant strictures 6-8-mm balloon dilation was first performed. This was followed by removal of the stones if exist. Finally, FCSEMS placed. The stents were removed 6-12 weeks later., Results: The mean age of the patients was 40.9 ± 10.3 years, and 91.6% of the patients were male. Majority of the patients (n = 9) were noncirrhotic. Endoscopic retrograde cholangiopancreatography (ERCP) findings showed that 11 of the 12 patients were Chandra Type I and one was Chandra Type IIIa. All the 12 patients were Llop Grade 3. All patients had biliary involvement in the form of strictures. Stent placement was successful in all patients. FCSEMSs were retained for a median period of 45 days (30-60). Seven (58.3%) patients developed acute cholecystitis. There was no occurrence of bleeding or other complications associated with FCSEMS replacement or removal. All patients were asymptomatic during median 3 years (1-10) follow up period., Conclusions: FCSEMS placement is an effective method in biliary strictures in case of PCC. Acute cholecystitis is encountered frequently after FCSEMS, but majority of patients respond to the medical treatment. Patients should be followed in terms of the relapse of biliary strictures., (© 2023. The Author(s).)

The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is dismal, calling for new therapeutic strategies. Venetoclax (VEN) is a highly selective, potent, orally bioavailable, BCL-2 inhibitor small-molecule that showed a synergistic effect with cyclophosphamide and topotecan (Cy-Topo) in murine NB models. Our aim was to evaluate the feasibility of VEN plus Cy-Topo in children with R/R NB. Four patients, who had previously failed > 3 lines of treatment, were treated with VEN plus Cy-Topo based on a 28-day schedule in an outpatient setting. BCL-2 expression in immunochemistry on tumor samples at relapse and the BCL2 gene status was evaluated in all patients. The main toxicity was hematological, with grade 4 neutropenia and thrombocytopenia occurring in all courses and leading to transient VEN discontinuation. Grade 3 oral mucositis was observed in 1/8 courses. No other grade 2-4 toxicities were observed. BCL-2 was expressed in all tumors, while no molecular abnormalities in the BCL-2 genes were detected. A stable disease was observed in all patients, without any progression during the study period. VEN plus Cy-Topo is well tolerated, with encouraging results that may be improved by testing the schedule in less advanced patients., (© 2023. The Author(s).)

Fludarabine/cyclophosphamide (Flu/Cy) is established for lymphodepletion (LD) prior to standard-of-care CAR T-cell therapy for lymphoma. There is ongoing need to test alternative LD regimens to preserve efficacy, improve safety, and address challenges including the recent national fludarabine shortage. We retrospectively evaluated outcomes among patients with relapsed/refractory aggressive B-cell lymphoma who received bendamustine (n = 27) or Flu/Cy (n = 42) LD before axicabtagene ciloleucel (axi-cel) at our institution. The median change in absolute lymphocyte count from pre-LD to time of axi-cel infusion was -0.6×10 9 /L in bendamustine cohort and -0.7×10 9 /L in Flu/Cy cohort. The best overall response/complete response rates were 77.8% (95% CI: 57.7%-91.4%)/48.1% (95% CI: 28.7%-68.1%) among bendamustine cohort and 81.0% (95% CI: 65.9%-91.4%)/50.0% (95% CI: 34.2%-65.8%) among Flu/Cy cohort. Six-month progression-free survival were 43.8% (95% CI: 24.7%-61.3%) and 55.6% (95% CI: 39.0%-69.3%) in bendamustine and Flu/Cy cohorts, while 6-month overall survival were 81.5% (95% CI: 61.1%-91.8%) and 90.4% (95% CI: 76.4%-96.3%), respectively. Relative to Flu/Cy-treated patients, bendamustine-treated patients did not show an increase in hazards associated with experiencing progression/relapse/death (aHR:1.4 [95% CI: 0.7-2.8]; p = .32) or death (aHR:1.6 [95% CI: 0.5-5.6]; p = .46), after adjusting for baseline number of prior therapies and refractory disease. Any grade/grade ≥3 CRS were observed in 89%/3.7% and 86%/4.8% among bendamustine and Flu/Cy cohorts, while any grade ICANS/grade ≥3 ICANS were observed in 30%/19% and 55%/31% respectively. While more Flu/Cy-treated patients experienced grade ≥3 neutropenia compared with bendamustine-treated patients (100% vs. 68%), grade ≥3 infectious complications were comparable (24% vs. 19% respectively). More patients received bendamustine LD and axi-cel as outpatient than Flu/Cy cohort, without increased toxicities and with shorter median inpatient stays. In conclusion, we observed comparable efficacy and lower any grade ICANS among patients receiving bendamustine relative to Flu/Cy LD, followed by axi-cel., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Objective: To evaluate adverse events (AEs) of combination lenvatinib plus pembrolizumab for the treatment of recurrent endometrial cancer (EC) and to assess outcomes by lenvatinib starting dose., Methods: We retrospectively reviewed patients with recurrent EC treated with lenvatinib plus pembrolizumab at our institution between 10/1/2019-11/30/2021. Starting dose of lenvatinib was defined as standard (20 mg) or reduced (10 mg/14 mg). AEs were manually extracted through chart review and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. PFS, overall survival (OS), and duration of response (DOR) were analyzed., Results: Forty-three patients were identified; median age was 67 years (range, 54-85). The most common histologies were serous (35%), endometrioid (23%), and carcinosarcoma (21%). Starting lenvatinib doses were 10 mg (n = 10), 14 mg (n = 10), and 20 mg (n = 23). Median number of cycles received was 8 (range, 1-42). Twenty-four patients (56%) required ≥1 lenvatinib dose reduction; 3 (7%) discontinued lenvatinib, and 1 (2%) discontinued pembrolizumab for intolerance or AE. Thirty-six patients (84%) experienced grade ≥ 3 AEs; hypertension, weight loss, anemia, fatigue, and thrombocytopenia were most common. The standard dose group experienced significantly shorter observed PFS vs the reduced dose group (P = .02). There was no difference in DOR (P = .09) or OS (P = .27) between the groups., Conclusion: In clinical practice, AEs associated with combination lenvatinib plus pembrolizumab were common and comparable to Study 309/KEYNOTE-775 findings. AEs were similar regardless of starting lenvatinib dose. Further dose optimization studies of lenvatinib plus pembrolizumab may be indicated in recurrent EC. Clinical trial data remain the gold standard to guide starting lenvatinib dosing., Competing Interests: Declaration of Competing Interest Outside the current study, A. Iasonos reports consulting fees from Mylan. N.R. Abu-Rustum reports honoraria from Klinik Essen Germany and NCCN; and GRAIL grants paid to the institution. V. Makker reports meeting/travel support by Eisai and Merck; participation on Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid), and study support to the institution by Merck, Eisai, AztraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer and Takeda. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). M. Rubinstein reports research funding from Merk, Zentalis, and AstraZeneca. A.K. Green reports research funding from Eli Lilly, Mereo Biopharma, and the American Society for Clinical Oncology (ASCO), and personal fees from Merck. All other authors have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed or refractory diffuse large B cell lymphoma (DLBCL) with 3 CD19 targeting products now FDA-approved for this indication. However, up to 60% of patients ultimately progress or relapse following CAR-T cell therapy. Mechanisms of resistance to CAR-T cell therapy in patients with DLBCL are likely multifactorial and have yet to be fully elucidated. Determining patient, tumor and therapy-related factors that may predict an individual's response to CAR-T cell therapy requires ongoing analysis of data from clinical trials and real-world experience in this population. In this review we will discuss the factors identified to-date that may contribute to failure of CAR-T cell therapy in achieving durable remissions in patients with DLBCL., Competing Interests: Declaration of competing interest C.M.B. has stock or ownership in Cabaletta Bio, Catamaran Bio, and Neximmune and had an equity interest in Mana Therapeutics. She also serves on the DSMB of SOBI., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique., Methods and Materials: Seventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis., Results: Median age at recurrence was 55 years (Range: 35-73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30-50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients., Conclusion: The use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy (SBRT) for prostate cancer (PCa). Aim of the present systematic review is to report on the role of urethra-sparing SBRT (US-SBRT) techniques for prostate cancer, with a focus on outcome and urinary toxicity., Method: A systematic review of the literature was performed on the PubMed database on May 2023. Based on the urethra-sparing technique, 13 studies were selected for the analysis and classified in the two following categories: "urethra-steering" SBRT (restriction of hotspots to the urethra) and "urethra dose-reduction" SBRT (dose reduction to urethra below the prescribed dose)., Results: By limiting the urethra D max to 90GyEQD2 (α/β = 3 Gy) with urethra-steering SBRT techniques, late genitourinary (GU) grade 2 toxicity remains mild, ranging between 12.1% and 14%. With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the risk of late GU toxicity was further reduced (< 8% at 5 years), while maintaining biochemical relapse-free survival rates up to 93% at 5 years., Conclusion: US-SBRT techniques limiting maximum doses to urethra below a 90Gy EQD2 (α/β = 3 Gy) threshold result in a low rate of acute and late grade ≥ 2 GU toxicity. A better understanding of clinical factors and anatomical substructures involved in the development of GU toxicity, as well as the development and use of adapted dose constraints, is expected to further reduce the long-term GU toxicity of prostate cancer patients treated with SBRT., (© 2023. The Author(s).)

Background: Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta was evaluated in patients with relapsed/refractory neuroblastoma., Methods: In this open-label, single-arm, Phase 2 study, patients with either refractory or relapsed high-risk neuroblastoma received dinutuximab beta by continuous infusion over 10 days of each cycle, for up to five cycles. The primary endpoint was objective response rate 24 weeks after the end of cycle 5. Secondary endpoints included adverse events, intravenous morphine use, best response, duration of response, and three-year progression-free and overall survival., Results: Of the 40 patients included, 38 had evaluable response. Objective response rate was 26% and best response rate 37%. Median duration of response was 238 days (IQR 108-290). Three-year progression-free and overall survival rates were 31% (95% CI 17-47) and 66% (95% CI 47-79), respectively. Prophylactic intravenous morphine use and duration of use decreased with increasing cycles. The most common grade 3 treatment-related adverse events were pain, diarrhea, and hypokalemia., Conclusion: Long-term continuous infusion of single-agent dinutuximab beta is tolerable and associated with clinically meaningful responses in patients with relapsed/refractory high-risk neuroblastoma., Clinical Trial Registration: The study is registered with ClinicalTrials.gov (NCT02743429) and EudraCT (2014-000588-42)., (© 2023. The Author(s).)

Background: Chronic subdural hematoma (CSDH) is a relatively common disease, especially in the elderly, for which there is no clear standard of treatment available. The authors systematically evaluated the efficacy of various surgical procedures for the treatment of chronic subdural hematoma., Methods: Electronic databases of PubMed, EmBase, Web of Science, Medicine, and the Cochrane Library were searched systematically. Based on the PRISMA template, we finally selected and analyzed 13 eligible papers to evaluate the effect of different drainage methods on CSDH. The primary outcomes were recurrence and clinical outcomes. Secondary outcomes were mortality and postoperative complications and other parameters., Results: The meta-analysis included 3 randomized controlled trials and 10 retrospective studies (non-randomized controlled trials) involving 3619 patients. The pooled results showed no statistically significant difference between non-subdural drainage (NSD) and subdural drainage (SD) in mortality and complication rates (P > 0.05). Additionally, overall pooled results showed that the use of NSD (10.9%) has a lower recurrence rate than the use of SD (11.7%), but the results were not statistically significant (relative risk ratio [RR] = 0.98; 95% confidence interval [CI] = 0.70-1.45; I2 = 47%; P = .92). However, the difference between NSD and SD in postoperative bleeding rate reached statistical significance (RR = 2.39; 95% CI = 1.31-4.36; I2 = 0 %; P = .004). Subgroup analysis showed that SD was associated with similar recurrent CSDH (RR = 0.75; 95% CI = 0.52-1.09; I2 = 0%; P = .14), good recovery (RR = 0.98; 95% CI = 0.93-1.04; I2 = 0%; P = .50), and mortality (RR = 0.98; 95% CI = 0.37-2.57; I2 = 0%; P = .96), compared to NSD., Conclusions: These results suggest that NSD and SD are equally effective in the treatment of patients with CSDH, with no difference in final clinical characteristics and radiologic outcomes. However, in patients with limited subdural space after evacuation of a hematoma, NSD may be the preferred strategy to avoid iatrogenic brain injury., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Efforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision., Methods: The SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0-1; 0-3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16-45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews., Discussion: SABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients., Trial Registration: This trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The squamous cell carcinoma (SCC) of the posterior pharyngeal wall (PPW) is associated with poor oncological outcomes based on current literature data. We reported the preliminary outcomes of a potential new treatment protocol based on neoadjuvant chemotherapy (NCT) and transoral robotic surgery (TORS)., Methods: A retrospective single-center case series was performed including a total of 20 patients diagnosed with a SCC of the PPW between October 2010 and September 2021. All patients successfully completed TORS with neck dissection after NCT. Adjuvant treatment was performed in the presence of adverse pathologic features. Loco-regional control (LRC), overall survival (OS), and disease-specific survival (DSS) were defined as the time from surgery to tumor recurrence or death, as appropriate. Survival estimates were calculated by Kaplan-Meier analysis. Surgical data and post-operative functional outcomes were also reported., Results: Estimated 3-year LRC, OS, and DSS rates (95% Confidence interval) were 59.7% (39.7-89.6), 58.6% (38.7-88.8), and 69.4% (49.9-96.6). The median hospital stay was 21 days (IQR 17.0-23.5). Oral diet and decannulation were achieved after a median of 14 days (IQR 12.0-15.0). Feeding tube and tracheostomy dependence after 6 months was observed in 3 (15%) and 2 (10%) patients, respectively., Conclusions: The use of NCT followed by TORS for PPW SCC treatment appears to have good oncological and functional outcomes for both early and locally advanced cancers. Further randomized trials and site-specific guidelines are needed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To investigate the value of integrating primary gross tumor volume (GTV p ) and gross tumor volume of nodes (GTV n ) after induction chemotherapy (IC) and dynamic changes in plasma cell-free Epstein-Barr virus DNA (cfEBV DNA) during sequential chemoradiotherapy (CRT) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC)., Materials and Methods: We retrospectively reviewed 988 patients with LA-NPC undergoing IC plus concurrent chemoradiotherapy (CCRT) between 2014 and 2018. The entire cohort was divided into four subgroups according to tumor volume and the cfEBV DNA load. Using a supervised statistical clustering approach, we stratified the subgroups into three clusters. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were calculated using Kaplan-Meier analysis and inter-group differences were compared using the log-rank test., Results: We observed that GTV p & GTV n and cfEBV DNA postIC & cfEBV DNA postCRT were powerful prognostic factors for OS (p = 0.004, p < 0.001, p < 0.001, and p < 0.001, respectively). The survival curves of the three clusters were significantly different. The 5-year OS for the low-risk, intermediate-risk and high-risk clusters were 97.0%, 86.2% and 77.1% (all P values < 0.001), respectively. The risk stratification system showed better predictive performance than the current tumor-node-metastasis (TNM) classification for OS (area under curve [AUC]: 0.653 versus 0.560, p < 0.001), DFS (AUC: 0.639 versus 0.540, p < 0.001), DMFS (AUC: 0.628 versus 0.535, p < 0.001) and LRRFS (AUC: 0.616 versus 0.513, p < 0.001)., Conclusion: Both tumor volume and the cfEBV DNA level during sequential CRT are effective prognostic indicators for patients with high-risk LA-NPC. The developed risk stratification system incorporating above factors improved survival prediction and demonstrated potential value in decision-making., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon type of non-Hodgkin lymphoma, associated with breast implant capsules. Despite improvements in our understanding of BIA-ALCL, communicating the prognosis to patients remains challenging due to limited long-term follow-up data. This has important implications for decision-making, including recommendations for subsequent reconstructive procedures. The aim of this study was to assess the longer-term oncological outcomes of patients receiving multidisciplinary treatment for BIA-ALCL., Methods: This was a retrospective cohort study of BIA-ALCL patients treated at a tertiary referral unit. The data are presented using simple descriptive statistics., Results: Between 2015 and 2022, 18 BIA-ALCL patients were treated at our institution. The median age at diagnosis was 48.5 (IQR 41-55) years. Ten patients developed BIA-ALCL after cosmetic breast augmentation, and 8 after breast reconstruction following mastectomy for cancer. All patients had a history of textured implant insertion. The median time from first implant surgery to diagnosis was 8.5 (IQR 7-12) years. All patients underwent en-bloc total capsulectomy with implant removal, and 2 received systemic therapy. Fifteen patients had Stage I (IA-IC) disease, 2 had Stage IIA and 1 Stage III BIA-ALCL, based on the TNM classification system. At a median follow-up of 45 (IQR 15-71) months, there were no episodes of local or systemic relapse or death., Conclusions: Surgical management for BIA-ALCL is sufficient in early-stage disease, and associated with excellent oncological outcomes. This information is reassuring for patients when discussing recurrence risk., (© 2023. Society of Surgical Oncology.)

Background Aims: Although calcineurin inhibitors (CNIs) have a well-established role in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), their use can be limited by significant toxicities, which may result in premature treatment discontinuation. The optimal management of patients with CNI intolerance is unknown. The objective of this study was to determine the effectiveness of corticosteroids as GVHD prophylaxis for patients with CNI intolerance., Methods: This retrospective single-center study included consecutive adult patients with hematologic malignancies who underwent myeloablative peripheral blood allogeneic HCT with anti-thymocyte globulin, CNI, and methotrexate GVHD prophylaxis in Alberta, Canada. Multivariable competing-risks regression was used to compare cumulative incidences of GVHD, relapse, and non-relapse mortality between recipients of corticosteroid versus continuous CNI prophylaxis, and multivariable Cox proportional hazards regression was applied to compare overall survival, relapse-free survival (RFS) and moderate-to-severe chronic GVHD and RFS., Results: Among 509 allogeneic HCT recipients, 58 (11%) patients developed CNI intolerance and were switched to corticosteroid prophylaxis at median 28 days (range 1-53) after HCT. Compared with patients who received continuous CNI prophylaxis, recipients of corticosteroid prophylaxis had significantly greater cumulative incidences of grade 2-4 acute GVHD (subhazard ratio [SHR] 1.74, 95% confidence interval [CI] 1.08-2.80, P = 0.024), grade 3-4 acute GVHD (SHR 3.22, 95% CI 1.55-6.72, P = 0.002), and GVHD-related non-relapse mortality (SHR 3.07, 95% CI 1.54-6.12, P = 0.001). There were no significant differences in moderate-to-severe chronic GVHD (SHR 0.84, 95% CI 0.43-1.63, P = 0.60) or relapse (SHR 0.92, 95% CI 0.53-1.62, P = 0.78), but corticosteroid prophylaxis was associated with significantly inferior overall survival (hazard ratio [HR] 1.77, 95% CI 1.20-2.61, P = 0.004), RFS (HR 1.54, 95% CI 1.06-2.25, P = 0.024), and chronic GVHD and RFS (HR 1.46, 95% CI 1.04-2.05, P = 0.029)., Conclusions: Allogeneic HCT recipients with CNI intolerance are at increased risks of acute GVHD and poor outcomes despite institution of corticosteroid prophylaxis following premature CNI discontinuation. Alternative GVHD prophylaxis strategies are needed for this high-risk population., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: There is a group of hypopharyngeal squamous cell carcinoma (HPSCC) patients for whom larynx-preserving open partial pharyngectomy (PP) and radiotherapy/chemoradiotherapy (RT/CRT) are indicated. We aimed to retrospectively evaluate the survival difference as there is no evidence directly comparing the two therapies., Methods: This study evaluated HPSCC patients who were initially treated by PP or RT/CRT at our institution between January 2007 and October 2019. Overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival (LFS), and local relapse-free survival (LRFS) were evaluated. The main analyses were performed with inverse probability of treatment weighting (IPTW) adjustments. Sensitivity analyses compared hazard ratios (HRs) obtained with three models: unadjusted, multivariate Cox regression, and propensity score-adjusted., Results: Overall, 198 patients were enrolled; 63 and 135 underwent PP and RT/CRT, respectively. IPTW-adjusted 5-year OS, DSS, LFS, and LRFS rates in the PP and RT/CRT groups were 84.3% and 61.9% (p = 0.019), 84.9% and 75.8% (p = 0.168), 94.8% and 90.0% (p = 0.010), and 75.9% and 74.1% (p = 0.789), respectively. In the IPTW-adjusted regression analysis, PP was associated with a significant benefit regarding OS (HR 0.48, 95% confidence interval [CI] 0.26-0.90) and LFS (HR 0.17, 95% CI 0.04-0.77). The results obtained with the three models in the sensitivity analyses were qualitatively similar to those of the IPTW-adjusted models., Conclusion: Despite the risk of bias related to unadjusted factors, our results suggest that PP is associated with significantly better OS and LFS compared with RT/CRT for HPSCC., (© 2023. Society of Surgical Oncology.)

Background: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) on recurrent atrial fibrillation (AF) among patients undergoing catheter ablation is not well described., Objectives: This study sought to assess the impact of SGLT2-Is on the recurrence of AF among patients with type 2 diabetes mellitus (DM) after catheter ablation., Methods: Using the TriNetX research network, we identified, by means of Current Procedural Terminology codes, patients ≥18 years of age with type 2 diabetes mellitus (DM) who had undergone AF ablation from April 1, 2014, to November 30, 2021. Patients were stratified based on the baseline SGLT2-I use. Propensity-score matching resulted in 2,225 patients in each cohort. The primary outcome was a composite of cardioversion, new antiarrhythmic drug (AAD) therapy, or re-do AF ablation after a blanking period after the index ablation. Additional outcomes included heart failure exacerbations, ischemic stroke, all-cause hospitalization, and death during 12 months of follow-up., Results: SGLT2-I use in patients with type 2 DM undergoing AF ablation was associated with a significantly lower risk of cardioversion, new AAD therapy, and re-do AF ablation (adjusted OR: 0.68; 95% CI: 0.602-0.776; P < 0.0001). At 12 months, patients on SGLT2-Is had a higher probability of event-free survival (HR: 0.85, 95% CI: 0.77-0.95; log-rank test chi-square = 8.7; P = 0.003). All secondary outcomes were lower in the SGLT2I group; however, the ischemic stroke did not differ between groups., Conclusions: Use of SGLT2-Is in patients with type 2 DM is associated with a lower risk of arrhythmia recurrence after AF ablation and thence a reduced need for cardioversion, AAD therapy, or re-do AF ablation., Competing Interests: Funding Support and Author Disclosures Dr Januzzi is a trustee of the American College of Cardiology and a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer-Ingelheim, Jana Care, Janssen, Novartis, Prevencio, Roche Diagnostics; and participates in clinical endpoint committees an data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Tumor-directed therapies (TDTs) are a constitutive part of hepatocellular carcinoma (HCC) treatment in patients awaiting liver transplantation (LT). While most patients benefit from TDTs as a bridge to LT, some patients drop out from the waiting list due to tumor progression. The study aimed to determine the risk factors for poor treatment outcome following TDTs among patients with HCC awaiting LT., Methods: A total of 123 patients with HCC were evaluated with 92 patients meeting Milan Criteria enrolled in the prospective cohort study. Tumor response was evaluated using the modified Response Evaluation Criteria for Solid Tumors for HCC 1 month after the procedure. The risk factors for progressive disease (PD) and dropout were evaluated., Results: After TDT, 55 patients (59.8%) achieved complete or partial response (44.6% and 15.2% respectively), 17 patients (18.5%) had stable disease, and 20 patients (21.7%) were assessed as PD. Multivariate analysis revealed a significant and independent association between the number of HCC foci and PD ( P  = 0.03, OR = 2.68). There was no statistically significant association between treatment response and demographics, MELDNa score, pre-and post-treatment alpha-fetoprotein (AFP), cumulative tumor burden the largest tumor size, or TDT modality. PD was the major cause of dropout in our cohort. Pre-treatment AFP levels ≥200 ng/ml had a strong association with dropout after TDTs ( P  = 0.0005)., Conclusion: This study demonstrated the presence of multifocal HCC is the sole prognostic factor for PD following TDTs in HCC patients awaiting LT. We recommend prioritizing patients with multifocal HCC within Milan criteria by exception points for LT to improve the dropout rate., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Eastern data highlight the oncological benefits of the anterior approach (AA) during right hepatectomy (RH) for hepatocellular carcinoma (HCC). However, to our knowledge, previous western data on this topic are scarce. In this study, the oncological outcomes of AA and classical approach (CA) during RH for HCC were compared., Methods: A retrospective inverse propensity score-weighted fashion (IPTW) case-control study was performed in two French hepatobiliary surgery departments. Overall survival (OS), disease-free survival (DFS), and early recurrence rate (within 2 years after surgery) were analyzed., Results: Survival analysis was performed for 114 patients (CA group,60 patients; AA group, 54 patients). Before IPTW adjustment, the 3-year DFS rates were 29.4% (AA group) and 44% (CA group), respectively. No significant differences were found in DFS (HR = 1.1, 95%CI:0.62-1.9, p = 0.77) and OS (HR = 1.2, 95%CI:0.54-2.6, p = 0.66). After IPTW, DFS and OS analyses showed no differences between the two groups (p = 0.77 and p = 0.46, respectively). Early recurrence rates were similar before and after IPTW. Satellite nodules were the only significant independent risk factor for recurrence., Conclusion: AA and CA did not result in significant differences in DFS, OS, or early recurrence after right hepatectomy for HCC before and after IPTW., (© 2023. The Society for Surgery of the Alimentary Tract.)

Introduction: Combined treatment using anti-programmed death-ligand 1 antibody (anti-PD-L1) and platinum-etoposide is the current standard first-line treatment for patients with extensive-stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES-SCLC after the first-line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES-SCLC, and treatment with irinotecan is well established as both a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second- or later-line setting for patients with ES-SCLC who have been previously treated with combined treatment., Methods: Our study will enroll total 30 patients who are diagnosed with ES-SCLC and have experienced disease progression after the combined treatment. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m 2 ) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator's decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression-free survival, and safety., Discussion: Since the present first-line treatment has been changed to the combined treatment, the second- or later-line treatment should be re-evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This study demonstrates and re-evaluates the clinical benefits of irinotecan after combined treatment with anti-PD-L1 and platinum-etoposide for patients with ES-SCLC., Registration Details: This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

This pilot study aimed to explore the preliminary effects and safety of stereotactic body radiotherapy (SBRT) combined with preventive pelvic radiotherapy and primary gross tumor volumes (GTVp) boost in patients with high-risk prostate cancer based on multiparameter magnetic resonance image (mpMRI). Tumors were contoured as GTVp based on mpMRI. The prostate and proximal seminal vesicles were considered as the clinical target volume1. The pelvic lymphatic drainage area constituted clinical target volume 2. Radiation doses were 40Gy or 45Gy/5fractions to planning target volume of primary tumor, 37.5Gy/5f to prostate, seminal vesicle, and positive pelvic lymph nodes, and 25Gy/5f to pelvic synchronously. The treatment was delivered 3 times per week. Volumetric modulated arc radiotherapy and intensity-modulated radiotherapy were used to complete SBRT. The genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated. Quality of life data was also captured. A total of 15 patients were enrolled in this study with a median age of 78 (56-87) from 2017 to 2020. All patients received SBRT. At 3 months after radiotherapy, the proportion of PSA < 0.006 ng/mL was 66.7% (10/15). The 2-year biochemical relapse-free survival was 93.3%. The incidence of grade 1 acute GU side effects was 80% (12/15); the incidence of acute grade 1 GI toxicity was 66.7% (10/15); and no grade 2 or higher acute GU and GI side effects was observed. Two patients presented with temporary late grade 2 GI toxicity. International Prostatic System Score increased rapidly after a transient increase at 1 week (P = .001). There were no significant differences in EORTC quality of life scores in all domains except global health status. In this pilot study, it was revealed that SBRT combined with preventive pelvic radiotherapy and GTVp boost based on mpMRI image was effective and well tolerated for patients with high-risk prostate cancer., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This phase II trial was designed to evaluate the efficacy and safety of S-1 combined with weekly irinotecan as a second- or third-line treatment for patients with advanced or recurrent squamous cell lung cancer., Methods: Patients with a body surface area <1.25, 1.25-1.50, and >1.50 m 2 received oral S-1 on days 1-14 at 80, 100, and 120 mg/day, respectively, and irinotecan on days 1 and 8 at 70 mg/m 2 every 3 weeks. The primary endpoint was the overall response rate, and the secondary endpoints were progression-free survival, overall survival, and the incidence and severity of adverse effects., Results: Between September 2011 and December 2014, 30 patients were enrolled in this study. The overall response rate was 6.7% (95% confidence interval [CI]: 0.8%-22.1%), and the disease control rate was 73.3%. The median progression-free survival was 3.0 months (95% CI: 2.5-3.4 months), and the median overall survival was 10.5 months (95% CI: 5.6-13.7 months). Grade 3/4 treatment-related adverse events were reported in ≥10% of the patients, including leukopenia (21%), neutropenia (21%), anemia (17%), anorexia (10%), and hypokalemia (10%)., Conclusions: Although the treatment-related adverse events were manageable, the combination of weekly irinotecan and S-1 did not have the expected effect., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: Gross tumor volume (GTV) changes during stereotactic ablative radiotherapy (SABR) for adrenal tumors are not well characterized. We studied treatment-induced GTV changes during, and after, 5-fraction MR-guided SABR on a 0.35 T unit., Methods and Materials: Details of patients treated for adrenal metastases using 5-fraction adaptive MR-SABR were accessed. GTV changes between simulation and first fraction (ΔSF1) and all fractions were recorded. Wilcoxon paired tests were used for intrapatient comparisons. Logistic and linear regression models were used for features associated with dichotomous and continuous variables, respectively., Results: Once-daily fractions of 8 Gy or 10 Gy were delivered to 70 adrenal metastases. Median simulation-F1 interval was 13 days; F1-F5 interval was 13 days. Median baseline GTVs at simulation and F1 were 26.6 and 27.2 cc, respectively (p < 0.001). Mean ΔSF1 was + 9.1% (2.9 cc) relative to simulation; 47% of GTVs decreased in volume at F5 versus F1. GTV variations of ≥ 20% occurred in 59% treatments at some point between simulation to end SABR, and these did not correlate with baseline tumor characteristics. At a median follow-up of 20.3 months, a radiological complete response (CR) was seen in 23% of 64 evaluable patients. CR was associated with baseline GTV (p = 0.03) and ΔF1F5 (p = 0.03). Local relapses were seen in 6%., Conclusion: Frequent changes in adrenal GTVs during 5-fraction SABR delivery support the use of on-couch adaptive replanning. The likelihood of a radiological CR correlates with the baseline GTV and intra-treatment GTV decline., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Migration of fully covered metal stents (FCMS) remains a limitation of the endoscopic treatment of anastomotic biliary strictures (ABS) following orthotopic liver transplantation (OLT). The use of antimigration FCMS (A-FCMS) might enhance endoscopic treatment outcomes for ABS., Methods: Single center retrospective study. Consecutive patients with ABS following OLT who underwent ERCP with FCMS placement between January 2005 and December 2020 were eligible. Subjects were grouped into conventional-FCMS (C-FCMS) and A-FCMS. The primary outcome was stent migration rates. Secondary outcomes were stricture resolution, adverse event, and recurrence rates., Results: A total of 102 (40 C-FCMS; 62 A-FCMS) patients were included. Stent migration was identified at the first revision in 24 C-FCMS patients (63.2%) and in 21 A-FCMS patients (36.2%) (p = 0.01). The overall migration rate, including the first and subsequent endoscopic revisions, was 65.8% in C-FCMS and 37.3% in A-FCMS (p = 0.006). The stricture resolution rate at the first endoscopic revision was similar in both groups (60.0 vs 61.3%, p = 0.87). Final stricture resolution was achieved in 95 patients (93.1%), with no difference across groups (92.5 vs 93.5%; p = 0.84). Adverse events were identified in 13 patients (12.1%) with no difference across groups. At a median follow-up of 52 (IQR: 19-85.5) months after stricture resolution, 25 patients (24.5%) developed recurrences, with no difference across groups (C-FCMS 30% vs A-FCMS 21%; p = 0.28)., Conclusions: The use of A-FCMS during ERCP for ABS following OLT results in significantly lower stent migration rates compared to C-FCMS. However, the clinical benefit of reduced stent migration is unclear. Larger studies focusing on stricture resolution and recurrence rates are needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Management of obstetrical and gynecologic patients with hernias poses challenges to providers. Risks for hernia development include well-described factors that impair surgical wound healing and increase abdominal pressure. Among the diverse populations cared for by obstetricians and gynecologists, pregnant patients and those with gynecologic malignancies are at the highest risk for hernia formation. This article provides an overview of the existing literature, with a focus on patients cared for by obstetrician-gynecologists and commonly encountered preoperative and intraoperative scenarios. We highlight scenarios when a hernia repair is not commonly performed, including those of patients undergoing nonelective surgeries with known or suspected gynecologic cancers. Finally, we offer multidisciplinary recommendations on the timing of elective hernia repair with obstetrical and gynecologic procedures, with attention to the primary surgical procedure, the type of preexisting hernia, and patient characteristics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Trans Oral Robotic Surgery (TORS) has proved to be a safe and feasible treatment for oropharyngeal squamous cell carcinoma (OPSCC). The aim of this study is to analyse oncological outcomes of OPSCC patients treated with TORS., Materials and Methods: This study involved 139 patients with OPSCC, treated with TORS between 2008 and 2020. Clinicopathological characteristics, treatment details and oncological outcomes were evaluated retrospectively., Results: The management strategies included TORS alone in 42.5%, TORS-RT in 25.2% and TORS-CRT in 30.9%. The ENE was noted in 28.8% of neck dissections. In 19 patients clinically classified as unknown primaries, the primary was found in 73.7%. Rates of local, regional relapses and distant metastasis were 8.6%, 7.2%, and 6.5%, respectively. The 5 year- Overall Survival and Disease Free Survival were 69.6% and 71.3%, respectively., Conclusion: TORS fits well in the modern management of OPSCC. Although definitive CRT remains a milestone, TORS is proving to be a valid and safe treatment option. The choice of the therapeutic strategy requires evaluation by a multidisciplinary team., Competing Interests: Declaration of competing interest Claudio Vicini is consultant and proctor for Intuitive Surgical Inc. Giuseppe Meccariello has nothing to declare. Manlio Gessaroli has nothing to declare. Raul Pellini has nothing to declare. Andrea De Vito has nothing to declare. Rossella Sgarzani has nothing to declare. Armando De Virgilio has nothing to declare. Andrea Costantino has nothing to declare. Flaminia Campo has nothing to declare. Giovanni Cammaroto has nothing to declare. Gerardo Petruzzi has nothing to declare. Bianca Festa has nothing to declare. Claudio Moretti has nothing to declare. Giuseppe Mercante has nothing to declare. Barbara Pichi has nothing to declare. Giuseppe Spriano has nothing to declare., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To investigate the choice of immediate breast reconstructive methods and asso-ciated outcomes after modified radical mastectomy., Methods: Retrospective analysis of patients undergoing immediate breast reconstruction after modified radical mastectomy in Peking University Third Hospital from January 2009 to May 2019. The reconstructive methods were summarized, and the clinical outcomes and the safety of immediate breast reconstruction were evaluated., Results: One hundred and twenty-three patients were enrolled in this study. Different reconstructive methods were applied according to the clinical stage, the amount of skin removal, the size of contralateral breasts, the physical condition and the preference of the patients. Seventy-nine cases were performed with tissue expander/implant two-stage reconstruction, twenty-three cases received direct breast implant insertion, seven cases were applied for latissimus dorsi (LD) myocutaneous flap transfer combined with implant insertion, five cases were provided transverse rectus abdominis myocutaneous (TRAM) flap transfer, six cases underwent tissue expander/implant combined with endoscopic LD muscle flap transfer, and three cases chose tissue expander/deep inferior epigastric artery perforator (DIEP) flap transfer. The average follow-up time was (12.3±9.0) months (3.5-41.0 months). One patient with direct implant insertion had partial blood supply distur-bance of the mastectomy flap. One case had necrosis of distal end of TRAM zone Ⅳ. One patient with expander/DIEP reconstruction had partial fat liquefaction. And two cases had expander leakage at the end of the expansion period. The tumor local recurrence occurred in one patient, and the implant was finally removed. The outcomes were evaluated by Harris method, and 90.2% patients were good or above in shape evaluation. Among the patients with implant based reconstruction, there was no obvious capsular contracture, and most of the implants had good or fair mobility., Conclusion: It is safe and feasible of immediate breast reconstruction after modified radical mastectomy for appropriate cases. The reconstructive methods can be individualized according to the individual's different conditions. The appropriate reconstructive methods could achieve satisfactory results.

Autologous stem cell transplantation (ASCT) is often used as consolidation for several subtypes of peripheral T-cell lymphoma (PTCL) in first remission. However, many patients relapse after ASCT and have a very poor prognosis. There are no approved treatment options for posttransplantation maintenance or consolidation in PTCL. PD-1 blockade has demonstrated some efficacy for patients with PTCL. We, therefore, conducted a phase 2 multicenter study of the anti-PD-1 monoclonal antibody pembrolizumab after ASCT in patients with PTCL in first remission. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles within 21 days from post-ASCT discharge (and within 60 days of stem cell infusion). The primary end point was progression-free survival (PFS) at 18 months after ASCT. Twenty-one patients were treated in this study and 67% (n = 14) completed 8 cycles of treatment. Among all patients who were evaluable, 13 of 21 were alive and achieved PFS at 18 months after ASCT, meeting the study's primary end point. The estimated 18-month PFS was 83.6% (95% confidence interval [CI], 68-100), and overall survival 94.4% (95% CI, 84-100). The toxicity profile was consistent with the known toxicity profile of pembrolizumab, with no grade 5 toxicities. In conclusion, PD-1 blockade after ASCT with pembrolizumab is feasible with a favorable safety profile and promising activity, supporting further confirmatory studies. This trial was registered at www.clinicaltrials.gov as #NCT02362997., (© 2023 by The American Society of Hematology.)

Introduction: Malignant tumors, such as hilar cholangiocarcinoma, have shown improved long-term outcomes, and measures to prevent late postoperative complications are important. Postoperative cholangitis after hepatectomy with hepaticojejunostomy (HHJ) may occur and can significantly decrease the quality of life. However, there are few reports on the incidence and pathogenesis of postoperative cholangitis after HHJ., Methods: We retrospectively reviewed 71 cases post HHJ at Tokyo Medical and Dental University Hospital from January 2010 to December 2021. Cholangitis was diagnosed using the Tokyo Guideline 2018. Cases due to tumor recurrence around the hepaticojejunostomy (HJ) were excluded. Patients with three or more episodes of cholangitis were classified as the "refractory cholangitis group" (RC group). RC group patients were divided into a "stenosis group" and "non-stenosis group" according to intrahepatic bile duct dilatation at the onset of cholangitis. Their clinical characteristics and risk factors were analyzed., Results: Cholangitis occurred in 20 patients (28.1%), with 17 (23.9%) in the RC group. Most patients in the RC group developed their first episode within the first postoperative year. The stenosis group consisted of 6 patients, and their cholangitis was treated with repeated anastomotic dilatation and stent replacement. In the non-stenosis group, cholangitis was relatively mild and treated with antibiotics. Hepatobiliary scintigraphy for these cases showed bile congestion in the jejunum near the site of the hepaticojejunostomy., Conclusion: There are two types of postoperative cholangitis, each with different pathogenesis and treatment. It is essential to assess anastomotic stenosis early and provide the necessary treatment., (© 2023. The Society for Surgery of the Alimentary Tract.)

Purpose: Chimeric antigen receptor (CAR)-T cells are a viable treatment option for patients with relapsed or refractory (r/r) aggressive B-cell lymphomas. The prognosis of patients who relapse after CAR-T cell treatment is dismal and factors predicting outcomes need to be identified. Our aim was to assess the value of FDG-PET/CT in terms of predicting patient outcomes., Methods: Twenty-two patients with r/r B-cell lymphoma who received CAR-T cell treatment with tisagenlecleucel (n = 17) or axicabtagene ciloleucel (n = 5) underwent quantitative FDG-PET/CT before (PET-0) and 1 month after infusion of CAR-T cells (PET-1). PET-1 was classified as complete metabolic response (CMR, Deauville score 1-3) or non-CMR (Deauville score 4-5)., Results: At the time of PET-1, 12/22 (55%) patients showed CMR, ten (45%) patients non-CMR. 7/12 (58%) CMR patients relapsed after a median of 223 days, three of them (25%) died. 9/10 (90%) non-CMR patients developed relapse or progressive disease after a median of 91 days, eight of them (80%) died. CMR patients demonstrated a significantly lower median total metabolic tumor volume (TMTV) in PET-0 (1 ml) than non-CMR patients (225 ml)., Conclusion: Our results confirm the prognostic value of PET-1. 42% of all CMR patients are still in remission 1 year after CAR T-cell treatment. 90% of the non-CMR patients relapsed, indicating the need for early intervention. Higher TMTV before CAR-T cell infusion was associated with lower chances of CMR., (© 2023. The Author(s).)

Total plasma exchange (TPE) can play a role in cancer treatment by eliminating immune checkpoint inhibitors. This study investigated whether TPE improved oncological outcomes in patients with HCC who underwent ABO-incompatible living donor liver transplantation (LT). The study included 152 patients who underwent ABO-incompatible living donor LT for HCC between 2010 and 2021 at Samsung Medical Center. Overall survival was analyzed using the Kaplan-Meier curve, whereas HCC-specific recurrence-free survival (RFS) was analyzed using the cumulative incidence curve after propensity score matching. Cox regression and competing risks subdistribution hazard models were used to identify the risk factors associated with overall survival and HCC-specific RFS, respectively. The propensity score matching resulted in 54 matched pairs, grouped according to whether they underwent postoperative TPE [post-transplant TPE(+)] or not [post-transplant TPE(-)]. The 5-year HCC-specific RFS cumulative incidence was superior in the post-transplant TPE (+) group [12.5% (95% CI: 3.1%-21.9%)] compared with the post-transplant TPE(-) group [38.1% (95% CI: 24.4%-51.8%), p = 0.005]. In subgroup analysis for patients with microvascular invasion and those beyond the Milan criteria, the post-transplant TPE(+) group showed significantly superior HCC-specific survival. The multivariable analysis also showed that postoperative TPE had a protective effect on HCC-specific RFS (HR = 0.26, 95% CI: 0.10-0.64, p = 0.004) and that the more post-transplant TPE was performed, the better RFS was observed (HR = 0.71, 95% CI: 0.55-0.93, p = 0.012). Post-transplant TPE was found to improve RFS after ABO-incompatible living donor LT for HCC, particularly in advanced cases with microvascular invasion and beyond Milan criteria. These findings suggest that TPE may have a potential role in improving oncological outcomes in patients with HCC undergoing LT., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Purpose: Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer., Methods: Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0)., Results: The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3‑year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3‑year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3‑year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3‑year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067)., Conclusion: Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS., (© 2023. The Author(s).)

Intrahepatic cholangiocarcinoma (ICC) with lymph node metastasis has a poor clinical prognosis. Comprehensive surgical treatment based on surgery is critical for improving the prognosis. Conversion therapy provides an opportunity for radical surgery in such patients but also increases the difficulty of surgery. The technical barrier to laparoscopic lymph node dissection is determining the extent of regional lymph node dissection after conversion therapy and formulating a suitable procedure to ensure the quality of lymph node dissection and oncological safety. One patient with initially unresectable left ICC underwent successful conversion therapy at another hospital. Then, we performed laparoscopic left hemihepatectomy with middle hepatic vein resection and regional lymph node dissection. Specific surgical techniques are used to reduce injury and bleeding, ultimately reducing the incidence of complications and promoting rapid recovery of patients. No postoperative complications were noted. The patient recovered well; no tumor recurrence was observed during the follow-up. Preoperatively planned regional lymph node dissection provides a reference for exploring the standard laparoscopic surgical treatment of ICC. Procedural regional lymph node dissection and artery protection techniques ensure quality and oncological safety in lymph node dissection. When selecting appropriate cases, as long as the laparoscopic surgical technique is mastered, laparoscopic surgery is safe and feasible with faster postoperative recovery and less trauma for left ICC., (© 2023. Italian Society of Surgery (SIC).)