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Background: The purpose of this study was to compare safety and efficacy outcomes between immediate breast reconstruction (IBR) and mastectomy alone in locally advanced breast cancer patients., Methods: We conducted a comprehensive literature search of PUBMED, EMBASE, and Cochrane databases. The primary outcomes evaluated were overall survival, disease-free survival, and local recurrence. The secondary outcome was the incidence of surgical complications. All data were analyzed using Review Manager 5.3., Results: Sixteen studies, involving 15,364 participants were included in this meta-analysis. Pooled data demonstrated that patients underwent IBR were more likely to experience surgical complications than those underwent mastectomy alone (HR: 3.96, 95%CI [1.07,14.67], p = 0.04). No significant difference was found in overall survival (HR: 0.94, 95%CI [0.73,1.20], p = 0.62), disease-free survival (HR: 1.03, 95%CI [0.83,1.27], p = 0.81), or breast cancer specific survival (HR: 0.93, 95%CI [0.71,1.21], p = 0.57) between IBR group and Non-IBR group., Conclusions: Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of locally advanced breast cancer patients. However, IBR brings with it a nonnegligible higher risk of complications and needs to be fully evaluated and carefully decided., (© 2024. The Author(s).)

Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy based on genetically engineered T cells derived from patients. The introduction of CAR T-cell therapy has changed the treatment paradigm of patients with B-cell lymphoid malignancies. However, challenging issues including managing life-threatening toxicities related to CAR T-cell infusion and resistance to CAR T-cell therapy, leading to progression or relapse, remain. This review summarizes the issues with currently approved CAR T-cell therapies for patients with relapsed or refractory B-cell lymphoid malignancies, including lymphoma and myeloma. We focus on unique toxicities after CAR T-cell therapy, such as cytokine-related events and hematological toxicities, and the mechanisms underlying post-CAR T-cell failure.

Effective cellular therapy using CD19 chimeric antigen receptor T-cells for the treatment of advanced B-cell malignancies raises the question of whether the administration of adoptive cellular therapy (ACT) posttransplant could reduce relapse and improve survival. Moreover, several early phase clinical studies have shown the potential beneficial effects of administration of tumor-associated antigen-specific T-cells and natural killer cells posttransplant for high-risk patients, aiming to decrease relapse and possibly improve survival. In this article, we present an in-depth review of ACT after transplantation, which has the potential to significantly improve the efficacy of this procedure and revolutionize this field., (© 2024 Wiley Periodicals LLC.)

Background: Allogeneic hemopoietic stem cell transplantation (HSCT) currently remains the only curative treatment for patients with myelofibrosis (MF). Transplant related mortality (TRM) and relapse, remain two significant complications which need to be addressed., Aims: The aim of this manuscript is to review current available reports on changes which have recently occurred, to improve the outcome of MF patients undergoing an allogeneic HSCT., Methods: Published papers were used to analyze different aspects of allogeneic HSCT., Results: Changes and updates are provided on selection of patients, prognostic systems, managing splenomegaly, conditioning regimens, predicting transplant outcome, stem cell sources, stem cell donors, graft versus host disease (GvHD) prophylaxis, patients with blast phase, hematopoietic reconstitution, disease markers, donor chimerism, and treatment of relapse., Conclusions: The review outlines new transplant platforms which are now available for patients with myelofibrosis, together with persisting problems, among which, older age combined with marrow fibrosis and an inflammatory disease. Relapse also requires aggressive monitoring of drivers mutations, and early cellular therapy., (© 2024 Wiley Periodicals LLC.)

Objective: To evaluate real-world treatment patterns and clinical outcomes in recurrent/advanced endometrial cancer patients who progressed following prior systemic therapy in clinical practice in Europe., Design: Endometrial Cancer Health Outcomes-Europe (ECHO-EU) is a retrospective patient chart review study., Setting: ECHO-EU is a multicentre study conducted in the UK, Germany, Italy, France and Spain., Participants: Patients with recurrent/advanced endometrial cancer who progressed between 1 July 2016 and 30 June 2019 following prior first-line systemic therapy were eligible and data were collected until last available follow-up through November 2021., Primary and Secondary Outcome Measures: Data collected included patient demographics, clinical and treatment characteristics, and clinical outcomes. Kaplan-Meier analyses were performed since initiation of second-line therapy to estimate time to treatment discontinuation, real-world progression-free survival (rwPFS) and overall survival (OS)., Results: A total of 475 patients were included from EU5 countries. Median age was 69 years at advanced endometrial cancer diagnosis, 78.7% had stage IIIB-IV disease, 45.9% had Eastern Cooperative Oncology Group status ≥2 at second-line therapy initiation. In second line, a majority of patients initiated either non-platinum-based chemotherapy (55.6%) or endocrine therapy (16.2%). Physician-reported real-world overall response rate (classified as complete or partial response) to second-line therapy was 34.5%, median rwPFS was 7.4 months (95% CI 6.2 to 8.0) and median OS was 11.0 months (95% CI 9.9 to 12.3)., Conclusions: Patients had poor clinical outcomes with a median OS of <1 year and rwPFS of approximately 7 months, highlighting the significant unmet medical need in pretreated recurrent/advanced endometrial cancer patients. Novel therapies with potential to improve PFS and OS over conventional therapies could provide significant clinical benefit., Competing Interests: Competing interests: Authors report the following conflicts of interest: SSK, employment with OPEN Health which received consulting fees from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA (MSD); YQ, former employment with OPEN Health which received consulting fees from MSD, and stock with AstraZeneca; JZ, employment with Eisai; VSP, employment with MSD and stock with Merck & Co., Inc., Rahway, NJ, USA; VG and NM, employment with M3 EU; CM, honoraria from AstraZeneca, GlaxoSmithKline, MSD, consulting fees from GlaxoSmithKline, MSD, Novartis, PharmaMar, Roche, and Seagen, and advisory board participation with GlaxoSmithKline and Karypharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a)., Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study., Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0)., Conclusion: GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis., Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis., Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1-43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49-1.10) and 0.64 (0.44-0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45-1.02) and 0.61 (0.41-0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3-5, 74% and 72%), respectively., Conclusion: Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC., Trial Registration: ClinicalTrials.gov Identifier: NCT03517449., Competing Interests: Kan Yonemori has received lecture fees from Eisai, Pfizer, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR pharma, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Boeringer Ingelheim, Ono, Daiichi-Sankyo, Bayer, Jansen, Sanofi, and AstraZeneca; is a member of the advisory board for Eisai, AstraZeneca, Sanofi, Genmab, Gilead, OncXerna, Takeda, Novartis, and MSD; research funding from MSD, Daiichi-Sankyo, Merck Biopharma, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, and Haihe; and is principle investigator for MSD, Daiichi-Sankyo, AstraZeneca, Taiho, Merk Biopharma, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boeringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, and Haihe., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a key treatment option for hematologic malignancies (HMs), although it carries significant risks. Up to 30% of patients relapse after allo-HSCT, of which up to 2% to 5% are donor-derived malignancies (DDMs). DDMs can arise from a germline genetic predisposition allele or clonal hematopoiesis (CH) in the donor. Increasingly, genetic testing reveals that patient and donor genetic factors contribute to the development of DDM and other allo-HSCT complications. Deleterious germline variants in CEBPA, DDX41, GATA2, and RUNX1 predispose to inferior allo-HSCT outcomes. DDM has been linked to donor-acquired somatic CH variants in DNMT3A, ASXL1, JAK2, and IDH2, often with additional new variants. We do not yet have evidence to standardize donor genetic sequencing prior to allo-HSCT. The presence of hereditary HM disorders should be considered in patients with myeloid malignancies and their related donors, and screening of unrelated donors should include family and personal history of cytopenia and HMs. Excellent multidisciplinary care is critical to ensure efficient timelines for screening and necessary discussions among medical oncologists, genetic counselors, recipients, and potential donors. After allo-HSCT, HM relapse monitoring with genetic testing effectively results in genetic sequencing of the donor, as the transplanted hematopoietic system is donor-derived, which presents ethical challenges for disclosure to patients and donors. We encourage consideration of the recent National Marrow Donor Program policy that allows donors to opt-in for notification about detection of their genetic variants after allo-HSCT, with appropriate genetic counseling when feasible. We look forward to prospective investigation of the impact of germline and acquired somatic genetic variants on hematopoietic stem cell mobilization/engraftment, graft-versus-host disease, and DDM to facilitate improved outcomes through knowledge of genetic risk., (Copyright © 2023. Published by Elsevier Inc.)

Background: Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic and transcriptomic profiling of tumor samples with a molecular tumor board (MTB) approach to make real‑time treatment decisions for children with relapsed/refractory solid tumors., Methods: Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; stratum 2-relapsed/refractory CNS tumors; and stratum 3-relapsed/refractory rare solid tumors. Tumor samples were sent for tumor/normal whole-exome (WES) and tumor whole-transcriptome (WTS) sequencing, and the genomic data were used in a multi-institutional MTB to make real‑time treatment decisions. The MTB recommended plan allowed for a combination of up to 4 agents. Feasibility was measured by time to completion of genomic sequencing, MTB review and initiation of treatment. Response was assessed after every two cycles using Response Evaluation Criteria in Solid Tumors (RECIST). Patient clinical benefit was calculated by the sum of the CR, PR, SD, and NED subjects divided by the sum of complete response (CR), partial response (PR), stable disease (SD), no evidence of disease (NED), and progressive disease (PD) subjects. Grade 3 and higher related and unexpected adverse events (AEs) were tabulated for safety evaluation., Results: A total of 186 eligible patients were enrolled with 144 evaluable for safety and 124 evaluable for response. The average number of days from biopsy to initiation of the MTB-recommended combination therapy was 38 days. Patient benefit was exhibited in 65% of all subjects, 67% of neuroblastoma subjects, 73% of CNS tumor subjects, and 60% of rare tumor subjects. There was little associated toxicity above that expected for the MGT drugs used during this trial, suggestive of the safety of utilizing this method of selecting combination targeted therapy., Conclusions: This trial demonstrated the feasibility, safety, and efficacy of a comprehensive sequencing model to guide personalized therapy for patients with any relapsed/refractory solid malignancy. Personalized therapy was well tolerated, and the clinical benefit rate of 65% in these heavily pretreated populations suggests that this treatment strategy could be an effective option for relapsed and refractory pediatric cancers., Trial Registration: ClinicalTrials.gov, NCT02162732. Prospectively registered on June 11, 2014., (© 2024. The Author(s).)

Despite recent advances in frontline therapy for diffuse large B-cell lymphoma (DLBCL), at least a third of those diagnosed still will require second or further lines for relapsed or refractory (rel/ref) disease. A small minority of these can be cured with standard chemoimmunotherapy/stem-cell transplant salvage approaches. CD19-directed chimeric antigen receptor T-cell (CAR-19) therapies are increasingly altering the prognostic landscape for rel/ref patients with DLBCL and related aggressive B-cell non-Hodgkin lymphomas. Long-term follow up data show ongoing disease-free outcomes consistent with cure in 30-40% after CAR-19, including high-risk patients primary refractory to or relapsing within 1 year of frontline treatment. This has made CAR-19 a preferred option for these difficult-to-treat populations. Widespread adoption, however, remains challenged by logistical and patient-related hurdles, including a requirement for certified tertiary care centers concentrated in urban centers, production times of at least 3-4 weeks, and high per-patients costs similar to allogeneic bone-marrow transplantation. Bispecific antibodies (BsAbs) are molecular biotherapies designed to bind and activate effector T-cells and drive them to B-cell antigens, leading to a similar cellular-dependent cytotoxicity as CAR-19. May and June of 2023 saw initial approvals of next-generation BsAbs glofitamab and epcoritamab in DLBCL as third or higher-line therapy, or for patients ineligible for CAR-19. BsAbs have similar spectrum but generally reduced severity of immune related side effects as CAR-19 and can be administered in community settings without need to manufacture patient-specific cellular products. To date and in contrast to CAR-19, however, there is no convincing evidence of cure after BsAbs monotherapy, though follow up is limited. The role of BsAbs in DLBCL treatment is rapidly evolving with trials investigating use in both relapsed and frontline curative-intent combinations. The future of DLBCL treatment is bound increasingly to include effector cell mediated immunotherapies, but further optimization of both cellular and BsAb approaches is needed., (© 2024. The Author(s).)

Radiation therapy (RT) after breast conserving surgery decreases the risks of local recurrence and breast cancer mortality in the multidisciplinary management of patients with breast cancer. However, breast cancer is a heterogeneous disease, and the absolute benefit of post-operative RT in individual patients varies substantially. Clinical trials aiming to identify patients with low-risk early breast cancer in whom post-operative RT may be safely omitted, based on conventional clinical-pathologic variables alone, have not provided sufficiently tailored information on local recurrence risk assessment to guide treatment decisions. The majority of patients with early breast cancer continue to be routinely treated with RT after breast conserving surgery. This approach may represent over-treatment for a substantial proportion of the patients. The clinical impact of genomic signatures on local therapy decisions for early breast cancer has been remarkably modest due to the lack of high-level evidence supporting their clinical validity for assessment of the risk of local recurrence. Efforts to personalise breast cancer care must be supported by high level evidence to enable balanced, informed treatment decisions. These considerations underpin the importance of ongoing biomarker-directed clinical trials to generate the high-level evidence necessary for setting the future standard of care in personalised local therapy for patients with early breast cancer., Competing Interests: Declaration of competing interest BHC reports in-kind support from Veracyte and NanoString for biomarker testing in clinical trial conduct., (Copyright © 2024 The Author. Published by Elsevier Ltd.. All rights reserved.)

Background Aims: This study aimed to comprehensively assess the impact of stem cell selection between bone marrow (BM) and peripheral blood (PB) in unrelated hematopoietic stem cell transplantation (HSCT) for hematological malignancies. Our objective was to identify specific factors associated with better transplant outcomes., Methods: A retrospective analysis was conducted using data from the Japanese HSCT registry. Inclusion criteria were patients aged 0-70 years who underwent their first unrelated HSCT with BM or PB, with an 8/8 or 7/8 allele HLA match for hematological malignancies between 2010 and 2020., Results: Among 10 295 patients, no significant difference was observed in overall survival, relapse, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) or non-relapse mortality between the groups. Patients who received PB showed no clear difference in acute GVHD but had a greater rate of chronic GVHD, resulting in poor chronic GVHD-free, relapse-free survival (CRFS). Subgroup analyses highlighted the importance of patient-specific factors in source selection. Patients with non-Hodgkin lymphoma and a greater hematopoietic cell transplantation-comorbidity index showed better CRFS and GRFS when BM was the preferred source. Similar trends were observed among patients with standard-risk disease for CRFS. However, no such trends were evident among patients aged 0-24 years, indicating that both sources are viable choices for young patients., Conclusions: This real-world retrospective analysis showed similar basic outcomes for BM and PB in an unrelated setting. The results support that BM may still be preferred over PB, especially when the long-term quality of life is a major concern. A consideration of individual factors can further optimize transplant success. Further research is warranted to explore the long-term implications of stem cell source selection., 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: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China., Patients and Methods: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed., Results: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%., Conclusion: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation., (© 2024. The Author(s).)

Background: There is no evidence supporting the feasibility of laparoscopic pancreaticoduodenectomy (LPD) compared to open pancreatoduodenectomy (OPD) following neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC)., Methods: The clinical data of consecutive patients with borderline resectable PDAC who received NACT and underwent either LPD or OPD between January 2020 and December 2022 at Fudan University Shanghai Cancer Center was prospectively collected and retrospectively analyzed., Results: The analysis included 57 patients in the OPD group and 20 in the LPD group. Following NACT, the LPD group exhibited a higher median CA19-9 decrease rate compared to the OPD group (85.3% vs. 66.9%, P = 0.042). Furthermore, 3 anatomically borderline PDACs in the LPD group and 5 in the OPD group were downstaged into resectable status (30.0% vs. 12.3%, P = 0.069). According to RECIST criteria, 51 (66.2%) patients in the entire cohort were evaluated as having stable disease. The median operation time for the LPD group was longer than the OPD group (419 vs. 325 min, P < 0.001), while the venous resection rate was 35.0% vs. 43.9%, respectively (P = 0.489). There was no difference in the number of retrieved lymph nodes, with a median number of 18.5 in the LPD group and 22 in the OPD group, and the R1 margin rate (15.0% vs. 12.3%) was also comparable. The incidence of Clavien-Dindo complications (35.0% vs. 66.7%, P = 0.018) was lower in the LPD group compared to the OPD group. Multivariable regression analysis revealed that a tumor diameter > 3 cm before NACT (HR 2.185) and poor tumor differentiation (HR 1.805) were independent risk factors for recurrence-free survival, and a decrease rate of CA19-9 > 70% (OR 0.309) was a protective factor for early tumor recurrence and overall survival., Conclusions: LPD for PDAC following NACT is feasible and oncologically equivalent to OPD. Effective control of CA19-9 levels is beneficial in reducing early tumor recurrence and improving overall survival., (© 2023. The Author(s).)

Objective: To evaluate pre-operative predictors of early (<30 days) severe complications (grade Dindo 3+) in patients with gynecological malignancy submitted to pelvic exenteration (PE)., Methods: We retrospectively analyzed 129 patients submitted to surgery at Fondazione Policlinico Gemelli between 2010 and 2019. We included patients affected by primary or recurrent/persistent cervical, endometrial, or vulvar/vaginal cancers. Post-operative complications were graded according to the Dindo classification. Logistic regression was used to analyze potential predictors of complications., Results: We performed 63 anterior PE, 10 posterior PE, and 56 total PE. The incidence of early severe post-operative complications was 27.9% (n=36), and the early mortality rate was 2.3% (n=3). More frequent complications were related to the urinary diversion and intestinal surgery. In univariable analysis, hemoglobin ≤10 g/dL (odds ratio [OR]=4.2; 95% confidence interval [CI]=1.65-10.7; p=0.003), low albumin levels (OR=3.9; 95% CI=1.27-12.11; p=0.025), diabetes (OR=4.15; 95% CI=1.22-14.1; p=0.022), 2+ comorbidities at presentation (OR=5.18; 95% CI=1.49-17.93; p=0.012) were predictors of early severe complications. In multivariable analysis, only low hemoglobin and comorbidities at presentation were independent predictors of complications., Conclusion: Pelvic exenteration is an aggressive surgery characterized by a high rate of post-operative complications. Pre-operative assessment of comorbidities and patient health status are crucial to better select the right candidate for this type of surgery., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART., (© 2023 Wiley Periodicals LLC.)

Objectives: We investigated the outcomes of liver transplant in patients with hepatocellular carcinoma., Materials and Methods: Prospectively, recipients of deceased donor liver transplants from 2007 to 2021 at Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, were enrolled into the study. The Milan criteria were applied for selection of liver transplant candidates diagnosed with hepatocellular carcinoma. Patients with diagnosis of acute liver failure and who underwent secondary liver transplant were excluded. All patients diagnosed with hepatocellular carcinoma were given mechanistic target of rapamycin inhibitor with calcineurin inhibitor minimization 4 weeks after liver transplant. Patients were assigned to the experimental group (with hepatocellular carcinoma; n = 82) or the control group (without hepatocellular carcinoma; n = 1076). We recorded the etiologies of liver cirrhosis in the experimental group, demographic data from all patients, and postoperative complications., Results: Of 1158 total patients, mean age was 44.15 ± 14.71 years (range, 1-73 years) and 712 were male patients (61.5%). In the experimental group (n = 82), there were 76 patients (92.68%) who were within the Milan criteria; others were excluded intraoperatively. All patients were followed for a median of 65.3 ± 40.8 months (range 10-197 months). Patient survival rates in the experimental group and control group at 3 months, 1 year, and 3 years were 89%, 80%, and 78% versus 84%, 81%, and 70%, respectively (P = .742). Hepatocellular carcinoma reoccurred in 6 patients (7.31%) at mean of 16.83 months postoperatively., Conclusions: Liver transplant for patients with hepatocellular carcinoma in the post-Milan criteria era is associated with acceptable outcomes.

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: 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.)

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.)

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 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: 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.)

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.)

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.)

Context: Craniopharyngioma is a benign brain tumor with frequent local recurrence or progression after treatment. GH replacement therapy (GHRT) is prescribed in children with GH deficiency resulting from childhood-onset craniopharyngioma., Objective: To evaluate whether a shorter delay of GHRT initiation after childhood-onset craniopharyngioma completion therapy increased the risk of a new event (progression or recurrence)., Methods: Retrospective, observational, monocenter study. We compared a cohort of 71 childhood-onset patients with craniopharyngiomas treated with recombinant human GH (rhGH). Twenty-seven patients were treated with rhGH at least 12 months after craniopharyngioma treatment (>12-month group) and 44 patients before 12 months (<12-month group), among which 29 patients were treated between 6 and 12 months (6-12 month group). The main outcome was the risk of tumor new event (progression of residual tumor or tumor recurrence after complete resection) after primary treatment in the >12-month group and in the <12 month or in the 6- to 12-month group patients., Results: In the >12-month group, the 2- and 5-year event-free survivals were respectively 81.5% (95% CI, 61.1-91.9) and 69.4% (95% CI, 47.9-83.4) compared with 72.2% (95% CI, 56.3-83.1) and 69.8% (95% CI, 53.8-81.2) in the <12-month group. The 2- and 5-year event-free survivals were the same in the 6- to 12-month group (72.4%; 95% CI, 52.4-85.1). By log-rank test, the event-free survival was not different between groups (P = .98 and P = .91).The median time for event was not statistically different.In univariate and multivariate analysis, the risk of craniopharyngioma new event was not associated with the GHRT time delay after craniopharyngioma treatment., Conclusions: No association was found between GHRT time delay after childhood-onset craniopharyngioma treatment and an increased risk of recurrence or tumor progression, suggesting GH replacement therapy can be initiated 6 months after last treatment for craniopharyngiomas., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Programmed cell death-1 (PD-1) inhibitor was proven to be useful for the recurrent/metastatic head and neck squamous carcinoma (R/M HNSCC) patients. Though both PD-1 inhibitor alone and combination with chemotherapy showed some benefit for PFS and OS, the survival outcome was still not satisfactory. Some studies showed the possible benefit for PD-1 inhibitors combination with radiation for head and neck squamous carcinoma, however there was few studies concerned about synergy of concurrent PD-1 inhibitor combination with chemoradiotherapy for R/M HNSCC. So, we aimed to explore the potential effect and toxicity of the concurrent PD-1 inhibitor and chemoradiotherapy for R/M HNSCC., Methods: We consecutively enrolled the R/M HNSCC patients treated with concurrent PD-1 inhibitor and chemoradiotherapy from August 2018 to April 2022 in Sichuan Cancer hospital. All the patients received the combination of PD-1 inhibitor and chemotherapy, and followed with synergy of concurrent PD-1 inhibitor and chemoradiotherapy, then maintenance PD-1 inhibitor. ORR and DCR was calculated by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST-1.1), and Common terminology criteria for adverse events (CTCAE-4.0) was used to evaluate the toxicity.The Kaplan-Meier method was used to analyze OS and PFS., Results: 40 R/M HNSCC patients were enrolled in our stuty. The median follow up time was 14 months. 22 patients had recurrent disease only, 16 patients had metastatic disease only, and 2 patients had both recurrence and metastasis disease. For the recurrent lesions, 23 patients received a median radiation dose of 64 Gy (range 50-70 Gy). 18 patients received a median dose of 45 Gy (range 30-66 Gy) for metastatic lesions. The median courses of PD-1 inhibitors and chemotherapy were 8 and 5 respectively. After the treatment, the ORR and DCR were 70.0% and 100%. The median OS was 19 months (range 6.3-31.7 months), with 1 and 2-years OS rates of 72.8% and 33.3%. The median PFS was 9 months (range 3.1-14.9 months), with 6 and 12 months PFS rates of 75.5% and 41.4% respectively. The PFS had no statistical significance in PD-L1 negative and positive group (7 vs 12 months, p = 0.059). The most common grade 3 or 4 adverse events(AE) were leucopenia (25.0%), neutropenia (17.5%), anemia (10.0%), thrombocytopenia (5.0%), hyponatremia (2.5%), and pneumonia(2.5%). No grade 5 AE was observed., Conclusions: The synergy of concurrent PD-1 inhibitor treatment with chemoradiotherapy shows promise as a treatment strategy and an acceptable toxicity for the R/M HNSCC patients., (© 2023. The Author(s).)

Background: Rechallenge with platinum-combination chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) after disease progression on platinum-combination chemotherapy occasionally leads to a favorable response. The efficacy and safety of platinum-combination chemotherapy with or without immune-checkpoint inhibitor (ICI) for patients with recurrent NSCLC after surgery followed by adjuvant platinum-doublet chemotherapy remains uncertain., Methods: Patients who relapsed after surgery plus adjuvant platinum-doublet chemotherapy and received platinum-combination chemotherapy with or without ICI between April 2011 and March 2021 at four Nippon Medical School hospitals were retrospectively analyzed., Results: Among 177 patients who received adjuvant platinum-doublet chemotherapy after surgery, a total of 30 patients who received platinum-combination rechemotherapy with or without ICI after relapse were included in this study. Seven patients received ICI-combined chemotherapy. The median disease-free survival (DFS) after surgery was 13.6 months. The objective response rate and disease-control rate were 46.7% and 80.0%, respectively. The median progression-free survival and overall survival were 10.2 and 37.5 months, respectively. Patients with longer DFS (≥12 months) had a better prognosis than others. The most common grade ≥3 toxicity associated with this treatment was neutropenia (33%). Grade ≥3 immune-related adverse events were pneumonitis (14%) and colitis (14%). Treatment-related deaths did not occur in this study., Conclusion: Platinum-combination chemotherapy with or without ICI for patients with postoperative recurrent NSCLC who previously received adjuvant platinum-doublet chemotherapy was effective and safe. In particular, this therapy may be promising for patients with longer DFS., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Previous studies have illustrated associations between the presence of activating killer cell immunoglobulin-like receptor (KIR) genes and lower susceptibility to hematologic malignancies in humans. In addition, favorable hematopoietic stem cell transplantation (HSCT) outcomes have been reported in patients who received transplants from donors with KIR genotypes dominant for activating KIR receptors. However, the association of activating KIR genes on an allelic level with disease and their impact on HSCT outcome has been little investigated to date. To this end, we genotyped a large transplantation cohort for KIR 2 Ig domains and short cytoplasmic tail 4 (KIR2DS4) polymorphisms and investigated their association with disease. We next investigated the impact of KIR-AA genotype donor KIR2DS4 polymorphisms (AA/KIR2DS4 versus AA/ KIR 1 Ig domain [KIR1D]) on clinical outcomes of HSCT in myeloid versus lymphoid patient subgroups. Among 2810 transplantation donor-recipient pairs, 68.8% (n = 1934) were 10/10 HLA-matched and 31.2% (n = 876) were 9/10 HLA-matched. The distribution of KIR1D was equal in patients and donors (P = .205). Multivariate analysis in 10/10 HLA-matched patients with lymphoid disease showed improved HSCT outcomes when they received grafts from AA/KIR1D donors (overall survival: hazard ratio [HR], .62, P = .002; disease free survival: HR, .70, P = .011; graft-versus-host disease-free and relapse-free survival: HR, .67, P = .002; nonrelapse mortality: HR, .55, P < .001). This effect was not seen in either 9/10 HLA-matched patients with lymphoid disease or patients with myeloid disease. Our study indicates that the presence of KIR1D alleles is not associated with disease in patients, and, interestingly, using grafts from AA/KIR1D donors translated into beneficial survival outcomes in 10/10 HLA-matched patients with lymphoid disease., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Pericarditis is common after radiofrequency ablation for atrial fibrillation (AF)., Objectives: Study investigators hypothesized an empirical post-AF ablation treatment protocol with colchicine may reduce the incidence and severity of pericarditis. PAPERS (Post-Ablation PEricarditis Reduction Study) aimed to quantify the risks and benefits associated with prophylactic use of colchicine to prevent pericarditis following AF ablation., Methods: PAPERS is a multicenter, prospective, randomized controlled study. Patients were randomized on the day of the procedure to receive no postprocedure prophylaxis (group A; standard of care arm) or colchicine 0.6 mg orally twice daily for 7 days starting immediately post-procedure (group B; study arm). All participants underwent a follow-up survey at 14 days postoperatively. The primary endpoint was the development of clinical pericarditis within 2 weeks following ablation. Secondary outcomes included the incidence of pericarditis by ablation type and medical therapy., Results: Among 139 patients enrolled, 66 were randomized to standard of care (group A), and 73 patients were randomized to the colchicine arm (group B). The primary outcome of clinical pericarditis was reached in 7 of 66 (10.6%) patients in group A and in 7 of 73 (9.6%) patients in group B (P = 0.84). The rate of gastrointestinal discomfort was 10 of 66 (15%) in group A and 34 of 73 (47%) in group B (P < 0.001). There was an increased incidence of pericarditis in patients who underwent cavotricuspid isthmus ablation (17 of 50; 34%) in addition to pulmonary vein isolation (6 of 69; 8.7%; P = 0.001)., Conclusions: Prophylactic colchicine therapy initiated after the ablation procedure in patients with AF did not affect the incidence of post-ablation pericarditis and was associated with an increased incidence of gastrointestinal side effects., Competing Interests: Funding Support and Author Disclosures The 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.)

Context: Previous studies report that outcomes of growth hormone (GH) replacement therapy (GHRT) might be less beneficial in growth hormone deficient (GHD) women compared with men., Objective: This study investigated possible contributing factors regarding this previously found sex difference., Methods: This retrospective cohort study, conducted at a nationwide outpatient clinic (the Dutch National Registry of GH Treatment in Adults), included Dutch adult GHD men (n = 1335) and women (n = 1251) treated with GHRT. The patients' baseline characteristics, details of GHRT, and the tolerability and long-term safety of GHRT were measured., Results: During treatment, sensitivity analysis showed that insulin-like growth factor-1 (IGF-1) SD scores remained subnormal more often in women (P < 0.001), while scores above normal were more frequent in men (P < 0.001). Women reported more adverse events (P < 0.001), especially symptoms related to fluid retention, and more often needed a dose reduction or temporary stop of GHRT (P = 0.001). In percentages, both sexes equally discontinued GHRT, as was also true for the risk in developing type 2 diabetes mellitus, benign neoplasms, and tumor recurrence. The risk of developing malignant neoplasms was higher in men (P = 0.012)., Conclusion: Data obtained from the Dutch National Registry of GH Treatment in Adults indicate that GHD women might be treated suboptimally, reflected as lower IGF-1 status and lower GHRT tolerability, leading to more frequent changes in treatment regimen but not discontinuation of GHRT. Regarding long-term safety, we found a higher risk for development of malignancies in GHD men., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In myelodysplastic syndromes (MDS), in addition to disease-related symptoms, many adverse events are associated with anticancer agents, myeloablative conditioning (MAC), and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Isolation and bed rest in a clean room severely limit physical activity, resulting in cardiopulmonary and muscle weakness. In addition, post-transplant patients may experience general fatigue, gastrointestinal symptoms, and infections associated with a weakened immune system, as well as graft-versus-host disease, which causes further decline in physical function and activities of daily living (ADL). Most reports on the rehabilitation of patients with hematopoietic tumors involve interventions before and after chemotherapy or transplantation. However, an important issue is to establish effective and feasible exercise programs in a clean room setting, where activity is severely limited and physical function is most likely to decline., Case Report: This case report describes the treatment progress of a 60-year-old man with MDS and thrombocytopenia scheduled to receive MAC and allo-HSCT, who continued bicycle ergometer and step exercises from admission to discharge. The patient was admitted for allo-HSCT, and on day 4, he started bicycle ergometer and step exercise in a clean room and continued until discharge. As a result, exercise tolerance and lower-extremity muscle strength were maintained at the time of hospital discharge. Furthermore, the patient was able to continue rehabilitation in a restricted environment without adverse events., Conclusions: The rehabilitation and treatment course of this case may provide valuable information for patients with MDS and thrombocytopenia., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

TP53 mutations (TP53MTs) have been associated with poor outcomes in various hematologic malignancies, but no data exist regarding its role in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HSCT). Here, we took advantage of a large international multicenter cohort to evaluate the role of TP53MT in this setting. Among 349 included patients, 49 (13%) had detectable TP53MT, of whom 30 showed a multihit configuration. Median variant allele frequency was 20.3%. Cytogenetic risk was favorable (71%), unfavorable (23%), and very high (6%), with complex karyotype present in 36 patients (10%). Median survival of patients with TP53MT was 1.5 vs 13.5 years for those with wild-type TP53 (TP53WT; P < .001). Outcome was driven by multihit TP53MT constellation (P < .001), showing 6-year survival of 56% for individuals with single-hit vs 25% for those with multihit TP53MT vs 64% for those with TP53WT. Outcome was independent of current transplantation-specific risk factors and conditioning intensity. Similarly, cumulative incidence of relapse was 17% for single-hit vs 52% for multihit vs 21% for TP53WT. Ten patients with TP53MT (20%) presented as leukemic transformation vs only 7 (2%) in the TP53WT group (P < .001). Out of the 10 patients with TP53MT, 8 showed multihit constellation. Median time to leukemic transformation was shorter for multihit and single-hit TP53MT (0.7 and 0.5 years, respectively) vs 2.5 years for TP53WT. In summary, multihit TP53MT represents a very high-risk group in patients with myelofibrosis who are undergoing HSCT, whereas single-hit TP53MT alone showed similar outcome to patients with nonmutated TP53, informing prognostication for survival and relapse together with current transplantation-specific tools., (© 2023 by The American Society of Hematology.)

Background: The present study evaluated the efficacy and safety of nab-paclitaxel (nab-PTX) with a concurrent PD-1/PD-L1 inhibitor in patients with refractory relapsed small-cell lung cancer (SCLC). Patients & methods: We retrospectively analyzed 240 patients with refractory relapsed SCLC: 40 patients were treated with nab-PTX plus PD-1/PD-L1 inhibitor, and 200 received traditional chemotherapy. Results: Median progression-free survival in the nab-PTX plus PD-1/PD-L1 inhibitor and traditional chemotherapy groups was 3.6 and 2.5 months (p = 0.0021), respectively. The median overall survival was 8.0 and 5.2 months (p = 0.0002), respectively. No new safety issues were identified. Conclusion: Nab-PTX plus PD-1/PD-L1 inhibitor significantly improved survival in patients with refractory relapsed SCLC compared with traditional chemotherapy.

The past two decades have seen an unprecedented trend towards de-escalation of surgical therapy in the setting of early BC, the most prominent examples being the reduction of re-excision rates for close surgical margins after breast-conserving surgery and replacing axillary lymph node dissection by less radical procedures such as sentinel lymph node biopsy (SLNB). Numerous studies confirmed that reducing the extent of surgery in the upfront surgery setting does not impact locoregional recurrences and overall outcome. In the setting of primary systemic treatment, there is an increased use of less invasive staging strategies reaching from SLNB and targeted lymph node biopsy (TLNB) to targeted axillary dissection (TAD). Omission of any axillary surgery in the presence of pathological complete response in the breast is currently being investigated in clinical trials. On the other hand, concerns have been raised that surgical de-escalation might induce an escalation of other treatment modalities such as radiation therapy. Since most trials on surgical de-escalation did not include standardized protocols for adjuvant radiotherapy, it remains unclear, whether the effect of surgical de-escalation was valid in itself or if radiotherapy compensated for the decreased surgical extent. Uncertainties in scientific evidence may therefore lead to escalation of radiotherapy in some settings of surgical de-escalation. Further, the increasing rate of mastectomies including contralateral procedures in patients without genetic risk is alarming. Future studies of locoregional treatment strategies need to include an interdisciplinary approach to integrate de-escalation approaches combining surgery and radiotherapy in a way that promotes optimal quality of life and shared decision-making., Competing Interests: Declaration of competing interest Maggie Banys-Paluchowski received honoraria for lectures and participation in advisory boards from: Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, AstraZeneca, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, ExactSciences, and study support from: EndoMag, Mammotome, MeritMedical, Gilead, Sirius Pintuition, Hologic. Thorsten Kühn received honoraria from: Merit Medical, Endomagnetics, Hologic, Sirius Medical, Pfizer, MSD, Astra Zeneca, Daiichi Sankyo, Exact Sciences and study support from: Mammotome, Merit Medical, Sirius Medical, Endomagnetics, Hologic. David Krug has received honoraria from Merck Sharp & Dohme and Pfizer as well as research funding from Merck KGaA. Nina Ditsch received honoraria from: AstraZeneca, BLÄK, Daiichi-Sankyo, if-Kongress München, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, onkowissen, Pfizer, RG Ärztefortbildungen, Roche, Seagen, UKA, BZKF Förderung, SerMA pilot Universität Augsburg. Other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Benign choledochojejunal anastomotic stricture (CJS) is a common complication of pancreaticoduodenectomy and choledochojejunostomy. CJS is generally treated with balloon dilation, using balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP); however, its long- and short-term outcomes have not been fully evaluated. Therefore, we evaluated the treatment outcomes of balloon dilation with BE-ERCP for CJS., Methods: We retrospectively analyzed 40 patients who had undergone balloon dilation with BE-ERCP for CJS between January 2009 and December 2022. The primary outcomes were technical and clinical success, and adverse event rates of balloon dilation using BE-ERCP for CJS. The secondary outcomes were long-term treatment outcomes for CJS recurrence, and evaluation of risk factors for recurrence., Result: Technical and clinical success rates were 93% (37/40) and 100% (37/37), respectively. CJS recurrence occurred in 32% (20/37). No procedure-related adverse events were observed. The significant risk factors of CJS after balloon dilation were its early occurrence after surgery (unit hazard ratio [HR] for month, 0.87; 95% confidence interval [CI], 0.76-0.99; p-value = 0.04) and residual waist during balloon dilation (HR, 5.46; 95% CI, 1.18-25.1; p-value = 0.03). Receiver operating characteristic curve analysis of time from surgery to balloon dilation revealed an area under the curve of 0.80 (95% CI, 0.65-0.94) and the cut-off value was 13.2 months., Conclusion: Treatment of CJS with balloon dilation was effective, although CJS recurrence occurred in one-third of the patients. The risk factors for recurrence were early occurrence of CJS after surgery and remaining waist circumference during balloon dilation., (© 2023. The Author(s).)

Background: Hematologic toxicities, including coagulopathy, endothelial activation, and cytopenias, with CD19-targeted chimeric antigen receptor (CAR) T-cell therapies correlate with cytokine release syndrome (CRS) and neurotoxicity severity, but little is known about the extended toxicity profiles of CAR T-cells targeting alternative antigens. This report characterizes hematologic toxicities seen following CD22 CAR T-cells and their relationship to CRS and neurotoxicity., Methods: We retrospectively characterized hematologic toxicities associated with CRS seen on a phase 1 study of anti-CD22 CAR T-cells for children and young adults with relapsed/refractory CD22+ hematologic malignancies. Additional analyses included correlation of hematologic toxicities with neurotoxicity and exploring effects of hemophagocytic lymphohistiocytosis-like toxicities (HLH) on bone marrow recovery and cytopenias. Coagulopathy was defined as evidence of bleeding or abnormal coagulation parameters. Hematologic toxicities were graded by Common Terminology Criteria for Adverse Events V.4.0., Results: Across 53 patients receiving CD22 CAR T-cells who experienced CRS, 43 (81.1%) patients achieved complete remission. Eighteen (34.0%) patients experienced coagulopathy, of whom 16 had clinical manifestations of mild bleeding (typically mucosal bleeding) which generally subsided following CRS resolution. Three had manifestations of thrombotic microangiopathy. Patients with coagulopathy had higher peak ferritin, D-dimer, prothrombin time, international normalized ratio (INR), lactate dehydrogenase (LDH), tissue factor, prothrombin fragment F1+2 and soluble vascular cell adhesion molecule-1 (s-VCAM-1). Despite a relatively higher incidence of HLH-like toxicities and endothelial activation, overall neurotoxicity was generally less severe than reported with CD19 CAR T-cells, prompting additional analysis to explore CD22 expression in the central nervous system (CNS). Single-cell analysis revealed that in contrast to CD19 expression, CD22 is not on oligodendrocyte precursor cells or on neurovascular cells but is seen on mature oligodendrocytes. Lastly, among those attaining CR, grade 3-4 neutropenia and thrombocytopenia were seen in 65% of patients at D28., Conclusion: With rising incidence of CD19 negative relapse, CD22 CAR T-cells are increasingly important for the treatment of B-cell malignancies. In characterizing hematologic toxicities on CD22 CAR T-cells, we demonstrate that despite endothelial activation, coagulopathy, and cytopenias, neurotoxicity was relatively mild and that CD22 and CD19 expression in the CNS differed, providing one potential hypothesis for divergent neurotoxicity profiles. Systematic characterization of on-target off-tumor toxicities of novel CAR T-cell constructs will be vital as new antigens are targeted., Trial Registration Number: NCT02315612., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Consolidation with autologous hematopoietic stem cell transplantation (HSCT) has improved survival for patients with central nervous system tumors (CNSTs). The impact of the autologous graft CD34+ dose on patient outcomes is unknown. We wanted to analyze the relationship between CD34 + dose, total nucleated cell (TNC) dose, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality (NRM), endothelial-injury complications (EIC), and time to neutrophil engraftment in children undergoing autologous HSCT for CNSTs. A retrospective analysis of the CIBMTR database was performed. Children aged <10 years who underwent autologous HSCT between 2008 to 2018 for an indication of CNST were included. An optimal cut point was identified for patient age, CD34 + cell dose, and TNC, using the maximum likelihood method and PFS as an endpoint. Univariable analysis for PFS, OS, and relapse was described using the Kaplan-Meier estimator. Cox models were fitted for PFS and OS outcomes. Cause-specific hazards models were fitted for relapse and NRM. One hundred fifteen patients met the inclusion criteria. A statistically significant association was identified between autograft CD34+ content and clinical outcomes. Children receiving >3.6×10 6 /kg CD34 + cells experienced superior PFS (p = .04) and OS (p = .04) compared to children receiving ≤3.6 × 10 6 /kg. Relapse rates were lower in patients receiving >3.6 × 10 6 /kg CD34 + cells (p = .05). Higher CD34 + doses were not associated with increased NRM (p = .59). Stratification of CD34 + dose by quartile did not reveal any statistically significant differences between quartiles for 3-year PFS (p = .66), OS (p = .29), risk of relapse (p = .57), or EIC (p = .87). There were no significant differences in patient outcomes based on TNC, and those receiving a TNC >4.4 × 10 8 /kg did not experience superior PFS (p = .26), superior OS (p = .14), reduced risk of relapse (p = .37), or reduced NRM (p = .25). Children with medulloblastoma had superior PFS (p < .001), OS (p = .01), and relapse rates (p = .001) compared to those with other CNS tumor types. Median time to neutrophil engraftment was 10 days versus 12 days in the highest and lowest infused CD34+ quartiles, respectively. For children undergoing autologous HSCT for CNSTs, increasing CD34 + cell dose was associated with significantly improved OS and PFS, and lower relapse rates, without increased NRM or EICs., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Chimeric antigen receptor T cell (CAR-T) therapy in hematologic malignancies has made great progress, but there are still some problems. First, T cells from tumor patients show an exhaustion phenotype; thus, the persistence and function of the CAR-Ts are poor, and achieving a satisfactory curative effect is difficult. Second, some patients initially respond well but quickly develop antigen-negative tumor recurrence. Thirdly, CAR-T treatment is not effective in some patients and is accompanied by severe side effects, such as cytokine release syndrome (CRS) and neurotoxicity. The solution to these problems is to reduce the toxicity and enhance the efficacy of CAR-T therapy. In this paper, we describe various strategies for reducing the toxicity and enhancing the efficacy of CAR-T therapy in hematological malignancies. In the first section, strategies for modifying CAR-Ts using gene-editing technologies or combining them with other anti-tumor drugs to enhance the efficacy of CAR-T therapy are introduced. The second section describes some methods in which the design and construction of CAR-Ts differ from the conventional process. The aim of these methods is to enhance the anti-tumor activity of CAR-Ts and prevent tumor recurrence. The third section describes modifying the CAR structure or installing safety switches to radically reduce CAR-T toxicity or regulating inflammatory cytokines to control the symptoms of CAR-T-associated toxicity. Together, the knowledge summarized herein will aid in designing better-suited and safer CAR-T treatment strategies.

Background: To investigate the feasibility and safety of watershed analysis after target pulmonary vascular occlusion for the wedge resection in patients with non-palpable and non-localizable pure ground-glass nodules during uniport thoracoscopic surgery., Methods: A total of 30 patients with pure ground-glass nodules < 1 cm in diameter, localized in the lateral third of the lung parenchyma, were enrolled. Three-dimensional reconstruction of thin-section computed tomography (CT) data was performed using Mimics software before surgery to observe and identify the target pulmonary vessels supplying the lung tissue in the area where the pulmonary nodules were localized and to temporarily block the target pulmonary vessels during surgery. Next, the extent of the watershed was determined with the expansion-collapse method, and finally, wedge resection was performed. After wedge resection of the target lung tissue, the blocked pulmonary vessel was released, thus allowing operators to complete the procedure without damaging pulmonary vessels., Results: None of the patients experienced postoperative complications. The chest CT of all patients was reviewed six months after the operation, revealing no tumor recurrence., Conclusions: Our results suggest that watershed analysis following target pulmonary vascular occlusion for wedge resection in pulmonary pure ground-glass nodules is a safe and feasible approach., (© 2023. The Author(s).)

Introduction: Prostate cancer (PCa) is men's second most predominant cancer worldwide. Because the prostate-specific antigen test is used in diagnostics, PCa is more often diagnosed in the early stages, making radical treatment of the disease possible. However, it is estimated that over a million men worldwide suffer from radical treatment-related complications. Thus, focal treatment has been proposed as a solution, which aims to destroy the predominant lesson that determines the progression of the disease. The main objective of our study is to compare the quality of life and efficacy of patients diagnosed with PCa before and after the treatment with focal high-dose-rate brachytherapy and to compare results with focal low-dose-rate brachytherapy and active surveillance., Methods and Analysis: 150 patients diagnosed with low-risk or favourable intermediate-risk PCa who meet the inclusion criteria will be enrolled in the study. Patients are going to be randomly assigned to the study groups: focal high-dose-rate brachytherapy (group 1), focal low-dose-rate brachytherapy (group 2) and active surveillance (group 3). The study's primary outcomes are quality of life after the procedure and time without biochemical disease recurrence. The secondary outcomes are early and late genitourinary and gastrointestinal reactions after the focal high-dose and low-dose-rate brachytherapies and evaluation of the importance and significance of in vivo dosimetry used for high-dose-rate brachytherapy., Ethics and Dissemination: Bioethics committee approval was obtained before this study. The trial results will be published in peer-reviewed journals and at conferences., Trial Registration Number: Vilnius regional bioethics committee; approval ID 2022/6-1438-911., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with prior colorectal polyps are at high risk for metachronous colorectal neoplasia, especially in the presence of obesity. We assessed the impact of 2 common bariatric surgeries, vertical sleeve gastrectomy and roux-n-Y gastric bypass, on the risk of colorectal neoplasia recurrence. This nationally representative analysis included 1183 postbariatric adults and 3193 propensity score-matched controls, who all had prior colonoscopy with polyps and polypectomy. Colorectal polyps reoccurred in 63.8% of bariatric surgery patients and 71.7% of controls at a mean follow-up of 53.1 months from prior colonoscopy. There was a reduced odds of colorectal polyp recurrence after bariatric surgery compared with controls (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.58 to 0.83). This effect was most pronounced in men (OR = 0.58, 95% CI = 0.42 to 0.79), and post roux-n-Y gastric bypass (OR = 0.57, 95% CI = 0.41 to 0.79). However, the risk of rectal polyps or colorectal cancer remained consistent between groups. This study is the first to our knowledge to show a reduction in risk of polyp recurrence following bariatric surgery., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)