[Spatially fractionated radiotherapy : introduction into clinical practice]. / Radiothérapie fractionnée dans l'espace : introduction en pratique clinique.

Spatially fractionated radiotherapy is a new concept involving partial irradiation of tumor volumes. Different techniques are described: mini-beam and micro-beam radiotherapy (pre-clinical) and LATTICE radiotherapy (L-RT) (clinical). Although L-RT is emergent in clinical practice and its evidence is still limited, it has still revealed excellent outcomes. At least three clinical situations can be discussed: definitive palliative radiotherapy, dose escalation (boost) or salvage radiotherapy. The interaction between L-RT and the immune system is still under investigation. Preclinical observations have already demonstrated a strong interaction, with tumor response dependent on immune system stimulation and the generation of an abscopal effect.

La radiothérapie fractionnée dans l'espace est un nouveau concept consistant en une irradiation partielle des volumes tumoraux. Plusieurs techniques sont ainsi décrites : les radiothérapies mini-beam et micro-beam (pré-clinique) et la radiothérapie LATTICE (L-RT) (clinique). Bien que la L-RT soit relativement nouvelle dans la pratique clinique et que les preuves quant à son utilisation soient encore limitées, elle montre des résultats prometteurs. Au moins trois situations cliniques peuvent être examinées en détail : la radiothérapie palliative définitive, l'escalade de dose (boost) ou encore la radiothérapie de sauvetage. L'interaction entre la L-RT et le système immunitaire est encore en cours d'investigation, mais des observations précliniques ont déjà démontré une interaction forte, avec notamment la dépendance de la réponse tumorale à la stimulation du système immunitaire et la génération d'un effet abscopal.

Efficacy and safety of high-dose chemotherapy as the first or subsequent salvage treatment line in patients with relapsed or refractory germ cell cancer: an international multicentric analysis.

BACKGROUND: In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen. PATIENTS AND METHODS: Data were retrospectively collected to explore the efficacy of HD-CTX administered as the first (group A) or subsequent salvage CTX (group B) after a CDR. The primary endpoint was OS from the time of HD-CTX. Associations of survival, overall response rate (ORR), and toxicity with clinical characteristics were explored using stratified Kaplan-Meier and Cox regression models. RESULTS: Overall, 283 patients with GCC were included from 11 international centers, with 159 patients (56%) in group A and 124 patients (44%) in group B. The first salvage treatment was administered between 1998 and 2022, with a median follow-up of 27.0 [standard deviation (SD) 46.2] months for group A and 17.0 (SD 48.5) months for group B. The median OS from HD-CTX treatment initiation was not reached in group A, compared with 25 months in group B (P = 0.00027), associated with 2- and 5-year OS rates of 74% and 63% (group A) versus 53% and 37% (group B), respectively. When administered as the first salvage treatment, HD-CTX was associated with a higher ORR (79% versus 60%; P = 0.013) and lower nonhematologic grade ≥3 toxicity rate (78% versus 97%; P < 0.001). Concerning risk factor analysis for the total cohort, the International Prognostic Factors Study Group score was the only independent predictor of OS in multivariable analysis (P = 0.006). CONCLUSIONS: When administered as the initial salvage treatment or after CDR, HD-CTX exhibits curative potential for patients with RR GCC. The efficacy and safety outcomes were more favorable when HD-CTX was conducted as the first salvage treatment line.

Salvage Reconstruction of a 12-cm Tendon Defect Following Chronic Achilles Rerupture-15-Year Follow-Up: A Case Report.

CASE: A 39-year-old man with a chronic Achilles rupture status post (1) failed primary repair and (2) secondary xenograft repair with graft rejection, resulting in a 12-cm Achilles tendon defect, which was reconstructed utilizing an Achilles bone block allograft and flexor hallucis longus (FHL) tendon transfer. At 15-year follow-up, the patient reported good functionality and satisfaction with the repair, with positive patient-reported outcome measures. Physical examination revealed excellent strength and range of motion. Magnetic resonance imaging confirmed the integrity and incorporation of the Achilles/FHL graft composite. CONCLUSION: This case study provides valuable insight into successful long-term management of complex chronic Achilles ruptures with large defects.

Salvage radiofrequency ablation followed by external beam radiotherapy for inoperable recurrent differentiated thyroid cancer.

PURPOSE: The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT. MATERIALS AND METHODS: Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed. RESULTS: Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred. CONCLUSIONS: Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.

Comparison of upfront haploidentical hematopoietic stem cell transplantation and salvage haploidentical hematopoietic stem cell transplantation after immunosuppressive therapy in children with acquired severe aplastic anemia - a multicenter study.

Background: For children with severe aplastic anemia, if the first immunosuppressive therapy (IST) fails, it is not recommended to choose a second IST. Therefore, for patients without matched sibling donor (MSD) and matched unrelated donor (MUD), haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) can be chosen as a salvage treatment. This article aims to explore the comparison between upfront Haplo-HSCT and salvage Haplo-HSCT after IST. Methods: 29 patients received salvage Haplo-HSCT, and 50 patients received upfront Haplo-HSCT. The two groups received Bu (Busulfan, 3.2mg/kg/d*2d on days -9 to-8), CY (Cyclophosphamide, 60mg/kg/d*2d on days -4 to-3), Flu (fludarabine, 40mg/m2/d*5d on days -9 to -5) and rabbit ATG (Anti-thymocyte globulin, total dose 10mg/kg divided into days -4 to -2). Results: The OS of the salvage Haplo-HSCT group showed no difference to the upfront Haplo-HSCT group (80.2 ± 8.0% vs. 88.7 ± 4.8%, p=0.37). The FFS of the salvage Haplo-HSCT group also showed no difference to the frontline Haplo-HSCT group (75 ± 8.2% vs. 84.9 ± 5.3%, p=0.27). There was no significant difference in the incidence of other complications after transplantation between the two groups, except for thrombotic microangiopathy (TMA). In the grouping analysis by graft source, the incidence of II-IV aGVHD in patients using PBSC ± BM+UCB was lower than that in the PBSC ± BM group (p=0.010). Conclusion: Upfront Haplo-HSCT and salvage Haplo-HSCT after IST in children with acquired severe aplastic anemia have similar survival outcomes. However, the risk of TMA increases after salvage Haplo-HSCT. This article provides some reference value for the treatment selection of patients. In addition, co-transplantation of umbilical cord blood may reduce the incidence of GVHD.

Paradigm Shifts in Hodgkin Lymphoma Treatment: From Frontline Therapies to Relapsed Disease.

Combination chemotherapy with or without radiation has served as the primary therapeutic option for classic Hodgkin lymphoma (cHL), leading to durable remission in a majority of patients with early- and advanced-stage cHL. Patients with relapsed/refractory (RR) cHL could still be cured with salvage chemotherapy and autologous stem-cell transplantation. Brentuximab vedotin (BV) and the anti-PD-1-blocking antibodies, nivolumab and pembrolizumab, are highly effective treatments for cHL and have revolutionized the management of the disease. Recent studies incorporating BV and PD-1 blockade into salvage therapy for RR cHL and into frontline treatment regimens have changed the cHL treatment paradigm. The novel agents are also useful in the treatment of older patients who have poor outcomes with traditional therapy. This manuscript will review current strategies for approaching the management of previously untreated, RR, and challenging populations with cHL, including how to incorporate the novel agents.

A Comprehensive Review of the Current State of Robot-assisted Laparoscopic Salvage Prostatectomy.

BACKGROUND AND OBJECTIVE: Salvage robot assisted radical prostatectomy (sRARP) is performed for patients with biochemical or biopsy proven, localized prostate cancer recurrences after radiation or ablative therapies. Traditionally, sRARP has been avoided by lower volume surgeons due to technical demand and high complication rates. Post-radiation sRARP outcomes studies exist but remain few in number. With increasing use of whole gland and focal ablative therapies, updates on sRARP in this setting are needed. The aim of this narrative review is to provide an overview of recently reviewed studies on the oncologic outcomes, functional outcomes, and complications after post-radiation and post-ablative sRARP. Tips and tricks are provided to guide surgeons who may perform sRARP. MATERIALS AND METHODS: We performed a non-systematic literature search of PubMed and MEDLINE for the most relevant articles pertaining to the outlined topics from 2010-2022 without limitation on study design. Only case reports, editorial comments, letters, and manuscripts in non-English languages were excluded. Key Content and Findings: Salvage robotic radical prostatectomy is performed in cases of biochemical recurrence after radiation or ablative therapies. Oncologic outcomes after sRARP are worse compared to primary surgery (pRARP) though improvements have been made with the robotic approach when compared to open salvage prostatectomy. Higher pre-sRARP PSA levels and more advanced pathologic stage portend worse oncologic outcomes. Patients meeting low-risk, EAU-biochemical recurrence criteria have improved oncologic outcomes compared to those with high-risk BCR. While complication rates in sRARP are higher compared to pRARP, Retzius sparing approaches may reduce complication rates, particularly rectal injuries. In comparison to the traditional open approach, sRARP is associated with a lower rate of bladder neck contracture. In terms of functional outcomes, potency rates after sRARP are poor and continence rates are low, though Retzius sparing approaches demonstrate acceptable recovery of urinary continence by 1 year, post-operatively. CONCLUSIONS: Advances in the robotic platform and improvement in robotic experience have resulted in acceptable complication rates after sRARP. However, oncologic and functional outcomes after sRARP in both the post-radiation and post-ablation settings are worse compared to pRARP. Thus, when engaging in shared decision making with patients regarding the initial management of localized prostate cancer, patients should be educated regarding oncologic and functional outcomes and complications in the case of biochemically recurrent prostate cancer that may require sRARP.

Efficacy and safety of salvage endoscopy in the treatment of residual or recurrent colorectal neoplasia after endoscopic resection: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of salvage endoscopy for residual or recurrence of colorectal tumors after endoscopic resection. METHODS: Multiple databases including PubMed, EMBASE and the Cochrane Library were searched to screen for eligible studies and perform data extraction and pooled analysis. RESULTS: Sixteen studies on salvage endoscopy for residual or recurrent colorectal cancer after endoscopic resection were included, covering approximately 994 patients. The results of the meta-analysis demonstrated that salvage endoscopic therapy for residual or recurrent colorectal tumors following endoscopic resection achieved an en bloc resection rate of 92% (95% CI 0.85-0.97; I2 = 91%) and an R0 resection rate of 82% (95% CI 0.75-0.87; I2 = 78%). The rates of intraoperative or postoperative bleeding and perforation were 10%/1% and 5%/2%, and the recurrence rate was 2%. CONCLUSIONS: Salvage endoscopic resection is an effective and safe treatment strategy for residual or recurrent colorectal tumors after endoscopic resection.

Salvage prostate intensity modulated radiation therapy after cryotherapy failure.

Cryotherapy is an ablative therapy that can be used to treat localized prostate cancer. In case of recurrence, treatment options are not well-defined, and their outcomes are unknown. We therefore collected all patients treated with radiotherapy after cryotherapy for prostate cancer recurrence in Nantes (France) between 2012 and 2019. We identified ten patients. After a median follow-up of 5 years, two patients presented late grade 3 toxicities; one patient presented a grade 3 rectal hemorrhage, and one had a grade 3 hematuria. Two patients relapsed at 61 and 62 months, and three patients died of other causes. Radiotherapy to treat local prostate cancer recurrence after cryotherapy seems feasible and effective in local control. These results do not allow us to recommend this technique in current practice but are encouraging for the conduct of prospective trials.

Remission induction versus immediate allogeneic haematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukaemia (ASAP): a randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: Whether high-dose cytarabine-based salvage chemotherapy, administered to induce complete remission in patients with poor responsive or relapsed acute myeloid leukaemia scheduled for allogeneic haematopoietic stem-cell transplantation (HSCT) after intensive conditioning confers a survival advantage, is unclear. METHODS: To test salvage chemotherapy before allogeneic HSCT, patients aged between 18 and 75 years with non-favourable-risk acute myeloid leukaemia not in complete remission after first induction or untreated first relapse were randomly assigned 1:1 to remission induction with high-dose cytarabine (3 g/m2 intravenously, 1 g/m2 intravenously for patients >60 years or with a substantial comorbidity) twice daily on days 1-3 plus mitoxantrone (10 mg/m2 intravenously) on days 3-5 or immediate allogeneic HSCT for the disease control group. Block randomisation with variable block lengths was used and patients were stratified by age, acute myeloid leukaemia risk, and disease status. The study was open label. The primary endpoint was treatment success, defined as complete remission on day 56 after allogeneic HSCT, with the aim to show non-inferiority for disease control compared with remission induction with a non-inferiority-margin of 5% and one-sided type 1 error of 2·5%. The primary endpoint was analysed in both the intention-to-treat (ITT) population and in the per-protocol population. The trial is completed and was registered at ClinicalTrials.gov, NCT02461537. FINDINGS: 281 patients were enrolled between Sept 17, 2015, and Jan 12, 2022. Of 140 patients randomly assigned to disease control, 135 (96%) proceeded to allogeneic HSCT, 97 (69%) after watchful waiting only. Of 141 patients randomly assigned to remission induction, 134 (95%) received salvage chemotherapy and 128 (91%) patients subsequently proceeded to allogeneic HSCT. In the ITT population, treatment success was observed in 116 (83%) of 140 patients in the disease control group versus 112 (79%) of 141 patients with remission induction (test for non-inferiority, p=0·036). Among per-protocol treated patients, treatment success was observed in 116 (84%) of 138 patients with disease control versus 109 (81%) of 134 patients in the remission induction group (test for non-inferiority, p=0·047). The difference in treatment success between disease control and remission induction was estimated as 3·4% (95% CI -5·8 to 12·6) for the ITT population and 2·7% (-6·3 to 11·8) for the per-protocol population. Fewer patients with disease control compared with remission induction had non-haematological adverse events grade 3 or worse (30 [21%] of 140 patients vs 86 [61%] of 141 patients, χ2 test p<0·0001). Between randomisation and the start of conditioning, with disease control two patients died from progressive acute myeloid leukaemia and zero from treatment-related complications, and with remission induction two patients died from progressive acute myeloid leukaemia and two from treatment-related complications. Between randomisation and allogeneic HSCT, patients with disease control spent a median of 27 days less in hospital than those with remission induction, ie, the median time in hospital was 15 days (range 7-64) versus 42 days (27-121, U test p<0·0001), respectively. INTERPRETATION: Non-inferiority of disease control could not be shown at the 2·5% significance level. The rate of treatment success was also not statistically better for patients with remission induction. Watchful waiting and immediate transplantation could be an alternative for fit patients with poor response or relapsed acute myeloid leukaemia who have a stem cell donor available. More randomised controlled intention-to-transplant trials are needed to define the optimal treatment before transplantation for patients with active acute myeloid leukaemia. FUNDING: DKMS and the Gert and Susanna Mayer Stiftung Foundation.

Predictors of salvage therapy for parasagittal meningiomas treated with primary surgery, radiosurgery, or surgery plus adjuvant radiotherapy.

OBJECTIVE: Parasagittal meningiomas (PM) are treated with primary microsurgery, radiosurgery (SRS), or surgery with adjuvant radiation. We investigated predictors of tumor progression requiring salvage surgery or radiation treatment. We sought to determine whether primary treatment modality, or radiologic, histologic, and clinical variables were associated with tumor progression requiring salvage treatment. METHODS: Retrospective study of 109 consecutive patients with PMs treated with primary surgery, radiation (RT), or surgery plus adjuvant RT (2000-2017) and minimum 5 years follow-up. Patient, radiologic, histologic, and treatment data were analyzed using standard statistical methods. RESULTS: Median follow up was 8.5 years. Primary treatment for PM was surgery in 76 patients, radiation in 16 patients, and surgery plus adjuvant radiation in 17 patients. Forty percent of parasagittal meningiomas in our cohort required some form of salvage treatment. On univariate analysis, brain invasion (OR: 6.93, p < 0.01), WHO grade 2/3 (OR: 4.54, p < 0.01), peritumoral edema (OR: 2.81, p = 0.01), sagittal sinus invasion (OR: 6.36, p < 0.01), sagittal sinus occlusion (OR: 4.86, p < 0.01), and non-spherical shape (OR: 3.89, p < 0.01) were significantly associated with receiving salvage treatment. On multivariate analysis, superior sagittal sinus invasion (OR: 8.22, p = 0.01) and WHO grade 2&3 (OR: 7.58, p < 0.01) were independently associated with receiving salvage treatment. There was no difference in time to salvage therapy (p = 0.11) or time to progression (p = 0.43) between patients receiving primary surgery alone, RT alone, or surgery plus adjuvant RT. Patients who had initial surgery were more likely to have peritumoral edema on preoperative imaging (p = 0.01). Median tumor volume was 19.0 cm3 in patients receiving primary surgery, 5.3 cm3 for RT, and 24.4 cm3 for surgery plus adjuvant RT (p < 0.01). CONCLUSION: Superior sagittal sinus invasion and WHO grade 2/3 are independently associated with PM progression requiring salvage therapy regardless of extent of resection or primary treatment modality. Parasagittal meningiomas have a high rate of recurrence with 80.0% of patients with WHO grade 2/3 tumors with sinus invasion requiring salvage treatment whereas only 13.6% of the WHO grade 1 tumors without sinus invasion required salvage treatment. This information is useful when counseling patients about disease management and setting expectations.

Network meta-analysis of CAR T-Cell therapy for the treatment of 3L+ R/R LBCL after using published comparative studies.

INTRODUCTION: Studies have compared chimeric antigen receptor (CAR) T-cell therapies and salvage chemotherapy in relapsed/refractory large B-cell lymphoma (LBCL) patients, but further evidence of their relative effectiveness is warranted. METHODS: Our systematic review identified studies comparing efficacy and safety outcomes of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel) and tisagenlecleucel (tisa-cel) trials to salvage chemotherapy cohorts in LBCL patients with ≥2 prior lines of treatment; and an extended evidence network included indirect comparisons comparing CAR T-cell therapies. We conducted network meta-analyzes using Bayesian hierarchical modeling. RESULTS: Three studies comparing ZUMA-1 (axi-cel), TRANSCEND (liso-cel) and JULIET (tisa-cel) trials to salvage chemotherapy within the SCHOLAR-1 cohort were identified. Axi-cel (odds ratio [OR]:5.63; 95% credible interval [CrI]:2.66-12.42) and liso-cel (OR:4.26; 95%CrI:2.33-7.93) showed a significant increased overall response rate compared to tisa-cel, but not to one-another. Axi-cel demonstrated significant improvements in overall survival relative to liso-cel (hazard ratio [HR]:0.54; 95%CrI:0.37-0.79) and tisa-cel (HR:0.47; 95%CrI:0.26-0.88). Higher rates of grade ≥3 neurological events were observed with axi-cel than with tisa-cel and liso-cel. CONCLUSIONS: We highlight important differences in clinical outcomes between CAR T-cell therapies. Axi-cel demonstrated improved overall survival compared to tisa-cel and liso-cel, and both axi-cel and liso-cel showed higher response rates compared to tisa-cel.

Evaluation of first-line and salvage therapies for unresectable malignant mesothelioma: A systematic review and network meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) of systemic therapies for unresectable malignant mesothelioma have reported conflicting results. It is crucial and urgent to find optimal treatment options for this malignancy, which currently has a poor prognosis. METHODS: Databases PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences were searched until February 29, 2024. The main outcomes of interest were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). RESULTS: We analyzed 16 RCTs with a total of 5018 patients. Among first-line therapies, nivolumab and ipilimumab significantly increased OS and resulted in fewer grade ≥3 TRAEs. Bevacizumab plus chemotherapy significantly increased PFS. Among salvage therapies, ramucirumab and chemotherapy was associated with the best OS and PFS, but resulted in more grade ≥3 TRAEs. Subgroup analysis by histologic types suggested that in first-line settings, bevacizumab and chemotherapy increase OS the most for epithelioid type, while the nivolumab plus ipilimumab treatment increases OS the most for non-epithelioid type. In salvage therapies, ramucirumab and chemotherapy increase OS for both epithelioid and non-epithelioid types. CONCLUSION: Nivolumab plus ipilimumab was associated with the best OS among first-line treatments. Ramucirumab and chemotherapy was associated with the best clinical outcomes in salvage settings. Treatment for malignant mesothelioma should be tailored based on different clinicopathological characteristics.

Salvage Reirradiation for Locally Recurrent Prostate Cancer: Results From a Prospective Study With 7.2 Years of Follow-Up.

PURPOSE: There are no well-established re-treatment options for local recurrence after primary curative radiation therapy for prostate cancer (PCa), as prospective studies with long-term follow-up are lacking. Here, we present results from a prospective study on focal salvage reirradiation with external-beam radiation therapy with a median follow-up of 7.2 years. MATERIALS AND METHODS: From 2013 to 2017, 38 patients with biopsy-proven locally recurrent PCa >2 years after previous treatment and absence of grade 2-3 toxicity from the first course of radiation were included. The treatment was 35 Gy in five fractions to the MRI-based target volume and 6 months of androgen-deprivation therapy starting 3 months before radiation. The Phoenix criteria defined biochemical recurrence-free survival (bRFS), and toxicity was scored according to Radiation Therapy Oncology Group criteria. RESULTS: Median age was 70 years, and median time from primary radiation to prostate-specific antigen (PSA) recurrence was 83 months. The actuarial 2-year and 5-year bRFS were 81% (95% CI, 69 to 94) and 58% (95% CI, 49 to 74), respectively. The actuarial 5-year local recurrence-free survival was 93% (95% CI, 82 to 100), metastasis-free survival was 82% (95% CI, 69 to 95), and overall survival was 87% (95% CI, 76 to 98). Two patients (5%) had durable grade 3 genitourinary toxicity, one combined with GI grade 3 toxicity. A PSA doubling time ≤6 months at salvage, a Gleason score >7, and a PSA nadir ≥0.1 ng/mL predicted a worse outcome. CONCLUSION: Reirradiation with EBRT for locally recurrent PCa after primary curative radiation therapy is clinically feasible and demonstrated a favorable outcome with acceptable toxicity in this prospective study with long-term follow-up.

Upfront multi-bipolar radiofrequency ablation for HCC in transplant-eligible cirrhotic patients with salvage transplantation in case of recurrence.

INTRODUCTION: We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure. MATERIALS AND METHODS: We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models. RESULTS: Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%. CONCLUSION: Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts.

Sequence not salvage.

Chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of multiple myeloma (MM) has fundamentally changed the relapsed and refractory therapeutic landscape, but the disease remains incurable. Two CAR-T products, idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel, Carvykti), have been FDA- and EMA-approved for the treatment of relapsed/refractory MM (RRMM); both target B-cell maturation antigen (BCMA), a surface glycoprotein highly expressed on MM cells. Despite deep and durable responses following CAR-T therapy, most patients will need subsequent treatment, and the optimal next-line therapy is presently unclear. Commentary on: Liu et al. Outcomes in patients with multiple myeloma receiving salvage treatment after BCMA-specific CAR-T therapy: A retrospective analysis of LEGEND-2. Br J Haematol 2024;204:1780-1789.

Percutaneous Ventriculoatrial Shunting as a Salvage Method in the Pediatric Hydrocephalus Patients with Peritoneal Problems.

AIM: To evaluate the efficacy of percutaneous ventriculoatrial shunting as a salvage method for pediatric patients with abdominal complications. MATERIAL AND METHODS: Data obtained from 9 patients with ventriculoperitoneal shunt dysfunctions owing to abdominal complications, who underwent ventriculoatrial shunting as salvage treatment at a single institution between January 2019 and September 2021 were retrospectively analyzed. All operations were conducted under the guidance of intraoperative fluoroscopy and ultrasound. RESULTS: The mean age of the enrolled patients was 8.1 ± 1.2 years (2-15 years). Six (67%) patients were male and 3 (33%) were female. The mean number of the patients? ventriculoperitoneal shunt revisions until atrial catheter placement was 7.5 times. The reasons for intraperitoneal catheter failure included peritoneal adhesions in 4 (44.5%) patients, pseudocyst formation in 3 (33.3%), and peritonitis in 2 (22.2%). Seven patients from the study cohort had no problem after ventriculoatrial shunt placement. Only 1 patient had shunt dysfunction related to the ventricular catheter, and ventricular catheter and shunt valve revision was performed 26 months after ventriculoatrial shunt placement. The atrial catheter of the patient was intact. One patient died from the progression of her primary disease (medulloblastoma in the 4 < sup > th < /sup > ventricle), which was unrelated to the ventriculoatrial shunt. CONCLUSION: Percutaneous ventriculoatrial shunting under the guidance of intraoperative fluoroscopy and ultrasound is a safe, effective, and easy alternative in patients with peritoneal complications and a history of multiple operations.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Salvage Therapy of Relapsed/Refractory Germ Cell Tumors: A Single-Center Experience.

INTRODUCTION: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. METHODS: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1-3 plus etoposide 750 mg/m2 on days 1-3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. RESULTS: The median age of the patients was 31 (range 18-62). The median follow-up was 31.1 months (95% CI, 28.9-33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1-43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. CONCLUSION: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.