Relapse and resistance in acute myeloid leukemia post venetoclax: improving second lines therapy and combinations.

INTRODUCTION: The combined use of the BCL-2 inhibitor venetoclax with azacitidine now is the standard of care for patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy with outcomes exceeding those achieved with hypomethylating agents alone. Venetoclax in combination with intensive chemotherapy is also increasingly used both as frontline as well as salvage therapy. However, resistance to and relapse after venetoclax-based therapies are of major concern and outcomes after treatment failure remain poor. AREAS COVERED: A comprehensive search was performed using PubMed database (up to April 2024). Studies evaluating venetoclax-based combination treatments in AML and studies assessing markers of response and resistance to venetoclax were investigated. We summarize the status of venetoclax-based therapies in the frontline and relapsed/refractory setting with focus on the main mechanisms of resistance to BCL-2 inhibition. Further, strategies to overcome resistance including combinatorial regimens of hypomethylating agent (HMA) + venetoclax + inhibitors targeting actionable mutations like IDH1/2 or FLT3-ITD and the introduction of novel agents like menin-inhibitors are addressed. EXPERT OPINION: Although venetoclax is reshaping the treatment of unfit and fit AML patients, prognosis of patients after HMA/VEN failure remains dismal, and strategies to abrogate primary and secondary resistance are an unmet clinical need.

Immunotherapy for advanced and recurrent malignant pleural mesothelioma.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of immune checkpoint inhibitors (single-agent or combination therapy) in people with advanced malignant pleural mesothelioma in a first-line or salvage setting.

Sintilimab plus GemOx is an effective salvage therapy in patients with refractory/relapsing nodal peripheral T cell lymphomas.

PURPOSE: The retrospective study was to explore the effectiveness and safety of GemOx (gemcitabine, oxaliplatin) plus sintilimab (belongs to the class of drugs known as immune checkpoint inhibitors, particularly targeting the PD-1 receptor) in relapse or refractory nodal PTCLs. METHODS: Patients with nodal PTCL who initiated salvage therapy with sintilimab and GemOx between January 2020 to September 2021 were identified from the database of the hematology department of the Second Affiliated Hospital of Zhejiang University School of Medicine. All patients received 2-4 cycles (3 weeks/cycle) of treatment of sintilimab (200 mg, I.V, D1) in combination with GemOx. Treatment response was assessed every six weeks during the salvage treatment phase. Eligible patients received maintenance therapy according to the investigator's decision. Follow-ups were routinely conducted every three months. RESULTS: 31 patients with r/r nodal PTCLs were enrolled, including 23 PTCL-NOS, 4 AITL, and 4 ALCL. 21 (67.7%) patients received at least two lines of therapy. 71.0% (95% CI, 53.4%-83.9%) of patients documented objective response of 2-4 cycles of sintilimab plus GemOx therapy, including 9 complete response and 13 partial response. 21 (67.7%) patients received consolidation therapy, including 5 autologous stem-cell transplantation and 12 histone deacetylase inhibitors. After a median 25.6 months follow-up, the median PFS was 22.0 (95% CI,11.8-24.7) months, and the median OS was 26.2 (95% CI, 24.4 -NA) months. 29 (93.5%) patients experienced at least one adverse event, and 26 (83.9% patients only had mild (grade 1-2) AEs.Univariable Cox regression showed the progression risk of AITL is 22.7 (3.9- 131.0, p < 0.01) times of PTCL-NOS, while the HR of ALCL was 1.14 (0.33-3.96,p = 0.833). CONCLUSION: Sintilimab plus GemOx showed encouraging activity and manageable toxicity for patients with r/r PTCL.

Does the initial treatment of primary tumor impact prognosis after recurrence in locally advanced rectal cancer? Results from a retrospective cohort analysis.

INTRODUCTION: The role of neoadjuvant therapy (NAT) in the treatment of locally advanced rectal cancer (LARC) has been well proven, but its impact on patients who relapse remains unknown. This study aims to elucidate the influence of initial treatment and MRI-defined risk factors on postrecurrent survival in patients with LARC recurrence. PATIENTS AND METHODS: LARC patients who underwent radical surgery and subsequently developed recurrence were retrospectively identified. Patients were stratified on the basis of MRI-defined local risk assessment and the initial treatment modality for the primary tumor (NAT or primary surgery). The patients were classified into four groups: high-risk LARC with NAT (HiN), high-risk LARC with primary surgery (HiS), low-risk LARC with NAT (LoN), and low-risk LARC with primary surgery (LoS). The primary endpoint was survival after recurrence. RESULTS: A total of 381 patients who experienced relapse were identified from among 2329 LARC patients. Salvage surgery was performed on 33.1% of these patients. Patients who experienced single-site recurrence or who underwent salvage surgery exhibited significantly prolonged survival times after recurrence (P < 0.001). Patients in the HiS group had poorer survival after recurrence than those in the other three groups (P = 0.034). This subset of patients, characterized by receiving less adjuvant treatment after primary surgery, had a shorter recurrence interval than those in the other groups (P = 0.001). CONCLUSIONS: Our findings reaffirm the prognostic significance of salvage surgery in patients from a LARC cohort who experienced relapse. Moreover, MRI-defined high-risk LARC patients who received upfront surgery without NAT had shorter intervals of recurrence and poorer survival outcomes after recurrence. Our results highlight the critical role of NAT in improving patient survival after recurrence. TRIAL REGISTRATION: Supplementary registration was carried out at clinicaltrials.gov (Registration number: NCT06314737) on March 14, 2024. The study was retrospectively registered.

[Selected donor CD34(+) cell boosts for salvage treatment of poor graft function following allogeneic hematopoietic stem cell transplantation in primary myelofibrosis: 3 cases report].

A retrospective analysis was conducted on three patients with primary myelofibrosis who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from 2020 to 2023. They subsequently developed poor graft function. The patients received selected donor CD34(+) cell boosts as salvage therapy. There were two male patients and one female patient, with a median age of 68 (39-69) years. The median time from allo-HSCT to the selected donor CD34(+) cell boost was 83 (56-154) days. The median infusion of selected donor CD34(+) cells was 7.67 (7.61-9.06) ×10(6)/kg, with a CD34(+) cell purity of 97.76% (96.50%-97.91%) and a recovery rate of 70% (42%-75%) . Hematological recovery was achieved in two cases. No acute GVHD was observed in any of the three patients. One case of moderate oral chronic GVHD was noted. Selected donor CD34(+) cell boosts for the treatment of poor graft function after allo-HSCT in primary myelofibrosis was effective and no severe acute or chronic GVHD was observed.

Surgical Ablative Therapies in Patients With Radiorecurrent Prostate Cancer.

Management of recurrent prostate cancer following radiotherapy and subsequent radical prostatectomy poses considerable challenges due to potential complications for patients. Focal therapies have emerged as a burgeoning approach in prostate cancer treatment. Research indicates that ablative therapies exhibit encouraging oncological efficacy while maintaining acceptable functional outcomes in salvage interventions. Here, we present a contemporary review of focal therapy treatment modalities as well as oncologic and functional outcomes.

Cryotherapy versus radical prostatectomy as a salvage treatment for radio-recurrent prostate cancer.

INTRODUCTION: The aim of this study is to compare outcomes of SRP (salvage radical prostatectomy) with SCAP (salvage cryoablation of the prostate) in local radio-recurrent PCa (prostate cancer) patients. MATERIALS AND METHODS: A retrospective analysis of a multicentric European Society of Uro-technology (ESUT) database was performed. Data on patients with local recurrent PCa after radiotherapy who underwent salvage treatment were collected. Patients and their respective disease characteristics, perioperative complications as well as oncological outcomes were then described. The treatment success rate was defined as PSA nadir < 0,4 ng/ml. Any complications were graded according to the modified Clavien system. A descriptive and comparative analysis was performed using SPSS software. RESULTS: 25 patients underwent SRP and 71 patients received SCAP. The mean follow-up was 24 months. The median PSA level before initial treatment was 8.3 (range 7-127) ng/ml. The success rates of SRP and SCAP were largely comparable (88% (22 patients) vs. 67.7% (48 patients), respectively, p = 0.216). The mean serum PSA levels at 12 months after salvage treatment were 1.2 ± 0.2 ng/mL vs. 0.25 ± 0.5 ng/mL, p > 0.05). During the follow-up period, only 3 (12%) patients in the SRP group had PSA recurrence compared with 21 patients (29.6%) in the SCAP group. The 5-year BRFS was similar (51,6% and 48,2%, p = 0,08) for SRP and SCAP respectively. The 5-year overall survival rate was 91.7%, and 89,7% (p = 0.669) and the 5-year cancer-specific survival was 91.7%, and 97,1% (p = 0.077), after SRP and SCAP respectively. No difference was found regarding the complications. CONCLUSIONS: Both SRP and SCAP should be considered as valid treatment options for patients with local recurrence of PCa after radiotherapy. SCAP has a potentially lower risk of morbidity and acceptable intermediate-term oncological efficacy, but a longer follow up and a higher number of patients is ideally needed to draw any long-term conclusions regarding the oncological data.

Salvage Endovascular Thrombectomy for Splenic Vein Thrombosis After Pancreas Transplantation: A Single-Center Experience and Systematic Literature Review.

OBJECTIVES: Technical graft loss, usually thrombotic in nature, accounts for most of the pancreas grafts that are removed early after transplant. Although arterial and venous thrombosis can occur, the vein is predominantly affected, with estimated overall rate of thrombosis of 6% to 33%. In late diagnosis, the graft will need to be removed because thrombectomy will not restore its functionality. However, in early diagnosis, a salvage procedure should be attempted. MATERIALS AND METHODS: We conducted a retrospective, descriptive analysis of a prospective database of patients who underwent pancreas transplant from April 2008 to June 2020 at a single center. We evaluated post-transplant clinical glucose levels, imaging, treatment, and outcomes. We also performed a systematic review of publications for endovascular treatment of vascular graft thrombosis in pancreas transplant. RESULTS: In 67 pancreas transplants analyzed, 13 (19%) were diagnosed with venous thrombus. In 7 of 13 patients (54%), systemic anticoagulation was prescribed because of a non-occlusive thromboses, resulting in complete resolution for all 7 patients. Six patients (46%) required endovascular thrombectomy because of the presence of complete occlusive thrombosis; 4 of these patients (67%) needed a second procedure because of recurrence of the thrombosis. One of the 6 patients (17%) required a surgical approach, resulting in successful removal of the recurrent clot. Twelve of the 13 grafts (92%) were rescued. Graft survival at 1 year was 84%; graft survival at 3, 5, and 10 years remained at 70%. CONCLUSIONS: Pancreas vein thrombosis represents a frequent surgical complication and remains as a challenging problem. In our experience, early diagnoses and an endovascular approach combined with aggressive medical treatment and follow-up can be used for successful treatment and reduce graft loss.

[Clinical efficacy and safety of liposomal amphotericin B in the salvage treatment of invasive fungal disease in patients with hematological diseases].

Objective: To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases. Methods: Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated. Results: Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg(-1)·d(-1) and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status (OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication (OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion: L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

Systematic review and recommendations for re-irradiation for intraprostatic radiorecurrent prostate cancer after definitive radiation therapy.

PURPOSE: Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy. METHODS: We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation. RESULTS: Work up of biochemically recurrent prostate cancer includes PSMA PET/CT and multiparametric MRI, followed by biopsy to confirm IRR. Management options include continued surveillance, palliative hormonal therapy, and salvage local therapy. Salvage local therapy can be delivered using re-irradiation with low dose rate brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiotherapy (SBRT), as well as non-radiation modalities, such as cryotherapy, high-intensity focused ultrasound, irreversible electroporation and radical prostatectomy. Data demonstrate that HDR brachytherapy and SBRT have similar efficacy compared to the other salvage local therapy modalities, while having more favorable side effect profiles. Recommendations for radiation therapy planning and delivery using HDR and SBRT based on the available literature are discussed. CONCLUSION: Salvage re-irradiation is safe and effective and should be considered in patients with IRR.

Salvage chemotherapy regimens with arsenic trioxide for relapsed or refractory neuroblastoma: a promising approach.

In patients with relapsed or refractory neuroblastoma (NB), the limited efficacy of conventional chemotherapies necessitates the exploration of new treatment options. Previous studies have highlighted the anti-tumor properties of arsenic trioxide (ATO) in high-risk NB (HR-NB). This study aims to assess the effectiveness and safety of ATO combined with salvage chemotherapy regimens, featuring cyclophosphamide and topotecan, as a foundational treatment for children with relapsed or refractory NB. Eleven patients (four relapsed, seven refractory NB) were retrospectively analyzed for efficacy and treatment relevance. Salvage treatments, incorporating ATO (0.18 mg/kg daily for 8 h intravenously on days 1 to 10), were administered upon disease progression or relapse, with assessments conducted every two cycles. Treatments had 63.6% efficacy, with six cases of partial response, one case of stable disease, and four cases of disease progression. The overall response rate was 54.5%, and the disease control rate was 63.6%. Importantly, the systemic toxicity experienced by patients following salvage chemotherapy with ATO was mild. Salvage chemotherapy regimens featuring ATO demonstrated potential for prolonging disease stabilization for relapsed or refractory HR-NB patients, exhibiting both favorable efficacy and safety profiles. This suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.

Point 1. The inadequate effectiveness of traditional chemotherapy in individuals with recurrent or resistant neuroblastoma (NB) necessitates the investigation of novel therapeutic approaches. Point 2. Arsenic trioxide (ATO)-based salvage treatments are both effective and less toxic in relapsed or refractory NB. Point 3. Salvage chemotherapy regimens incorporating ATO have shown promise in extending disease stabilization in relapsed or refractory high-risk NB patients, with favorable efficacy and safety profiles, which suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.

Additional injection laryngoplasty as a salvage treatment for unilateral vocal fold paralysis.

OBJECTIVES: Injection laryngoplasty (IL) has been widely used as an initial treatment option for unilateral vocal fold paralysis (UVFP). An additional (second) IL is considered a salvage treatment for unsatisfactory outcomes of initial IL resulting from inadequate injection or early resorption of the injection material. This study aims to evaluate the efficacy of additional IL, distinguishing between "salvage" (within 4 months) and "repeated" injections (beyond 4 months), and to analyze prognostic factors for successful outcomes. METHODS: This retrospective study involved patients who received IL at Asan Medical Center from January 2014 to December 2020. Voice parameters were collected after each procedure, and those who conducted the statistical analysis were blinded to the study subjects. Among the 65 patients who underwent additional IL, 51 patients were enrolled in this study. Postinjection grade, roughness, breathiness, asthenia, strain (GRBAS) scales were used to determine satisfactory treatment outcomes. Success of the additional IL was defined as a postinjection grade of dysphonia score of 0 or 1, with a reduction in grade compared with the preinjection grade. RESULTS: The mean age of the patients was 61.6 years. Out of a total of 51 patients, 37 were men participating in the study. The odds ratio represents the likelihood of success in the second IL. Improved voice outcome after the additional IL was maintained in 23 (45%) patients. Compared with the failure group, the success group had a longer injection time interval between the initial and additional injection (9.1 vs. 7.4 months, respectively, p = 0.010). The success group had a higher proportion of patients with injection intervals >6 months (73.9% vs. 42.9%, p = 0.026). Logistic regression analysis revealed an injection interval >6 months had an odds ratio of 0.265 (confidence interval: 0.080-0.874, p = 0.029). CONCLUSIONS: Additional injections would benefit the patients whose voice outcomes are maintained for a longer period (>6 months) after the first injection.

Step-by-step demonstration of "sciatic-nerve-preserved beyond-LEER" in a Thiel-embalmed cadaver: a novel salvage surgery for recurrent gynecologic malignancies.

OBJECTIVE: Complete resection is the curative treatment choice for recurrent gynecological malignancies. Laterally extended endopelvic resection (LEER) is an effective surgical salvage therapy for lateral recurrence. However, when a recurrent tumor occupies the ischial spine and sacrum, LEER is not indicated, and surgical salvage therapy is abandoned. Theoretically, complete resection of such a tumor is possible by additional pelvic bone resection along with the standard LEER. Nevertheless, owing to the anatomical complexities of the beyond-LEER procedure, 2 major issues should be solved: sciatic nerve injury and tumor disruption during pelvic bone amputation. To overcome these technical challenges, we applied a multidirectional beyond-LEER approach, a novel salvage surgical procedure, with an aim of demonstrating its technical feasibility. METHODS: We created a simulation model of a laterally recurrent tumor that occupied the right ischial spine and sacrum in a Thiel-embalmed cadaver. RESULTS: Multidirectional approaches, including laparoscopic, perineal, and dorsal phases, were safely applied. We laparoscopically marked the L4-L5-S1 complex and S2 nerve with different colored tapes, and by pulling them out into a dorsal surgical field, the sciatic nerve was safely preserved. The dissection lines of the multidirectional approaches were aligned using tapes as landmarks, and complete tumor clearance without tumor disruption was accomplished. By following the cadaveric training, the first laparoscopic-assisted beyond-LEER procedure was successfully performed in a patient with recurrent ovarian cancer. CONCLUSION: Using a Thiel-embalmed cadaver, we demonstrated the technical feasibility of a sciatic nerve-preserved beyond-LEER procedure, which was successfully performed in a patient with recurrent ovarian cancer.

A Machine Learning Approach for Predicting Biochemical Outcome After PSMA-PET-Guided Salvage Radiotherapy in Recurrent Prostate Cancer After Radical Prostatectomy: Retrospective Study.

BACKGROUND: Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. OBJECTIVE: This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer. METHODS: This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. RESULTS: Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (<66 Gy in 57/979, 5.8% vs 46/50, 92% of patients; P<.001). The RSF model, validated internally and externally, demonstrated robust predictive performance (Harrell C-index range: 0.54-0.91) across training and validation datasets, outperforming a previously published nomogram. CONCLUSIONS: The developed RSF model demonstrates enhanced predictive accuracy, potentially improving patient outcomes and assisting clinicians in making treatment decisions.

Undetectable PSA predicts outcome after salvage radiotherapy for biochemical recurrence following radical prostatectomy.

BACKGROUND AND PURPOSE: Salvage radiotherapy (SRT) is a curative treatment option in patients with biochemical recurrence after radical prostatectomy (RP). Undetectable prostate-specific antigen (PSA) < 0.1 ng/mL following SRT predicts biochemical progression-free survival (BPFS). The aim of this large retrospective study was to evaluate whether this effect persists in an extended follow-up of >5 years. MATERIALS AND METHODS: A total of 678 patients treated with SRT for biochemical recurrence after RP were included. Exclusion criteria were lymph node or distant metastases, pre-SRT PSA > 3 ng/mL, and receipt of androgen deprivation therapy (ADT) between RP and SRT. All patients received a median dose of 70.2 (range 59.4-72.0) Gy to the prostatic fossa. The log-rank test (Kaplan-Meier) and Cox regression analysis were used to evaluate the impact of disease- and treatment-related parameters on BPFS, metastasis-free survival (MFS), and overall survival (OS). RESULTS: Median follow-up after SRT was 5.6 (range 0.1-14.5) years. The 5-year BPFS was 77.8 % in patients with a PSA nadir < 0.1 ng/mL (undetectable) and 16.3 % in the remaining cohort (p < 0.001). Five-year MFS was 95.3 % with undetectable PSA versus 84.0 % with detectable PSA (p < 0.001), and 5-year OS values were 97.5 % and 92.7 % with undetectable versus detectable PSA, respectively (p = 0.04). In multivariate analysis, undetectable PSA was the strongest predictor of BPFS (HR = 0.122; 95 %CI: 0.080-0.187; p < 0.001) and MFS (HR = 0.262; 95 %CI: 0.136-0.594; p < 0.001), but was not significant for OS (HR = 0.615; 95 %CI: 0.298-1.269; p = 0.189). CONCLUSION: PSA < 0.1 ng/mL following SRT without ADT is a significant predictor of BPFS and MFS. The results suggest that it might be feasible to withhold ADT in selected patients if they have undetectable PSA after SRT. Prospective studies are warranted to confirm these findings.

Evaluation of chronic perilunate dislocations: A comparative study of single-stage, two-stage ORIF, and salvage procedures.

OBJECTIVE: This study aims to evaluate the outcomes of open reduction and internal fixation (ORIF) for chronic perilunate dislocations using single-stage, two-stage, and salvage procedures. The study also compares these approaches with each other and with results from existing literature. METHODS: A total of 15 patients with chronic perilunate injuries from 2013 to 2019 were included in the study. Pre-operative and post-operative assessments were conducted using plain radiographs, with CT scans performed selectively for detailed morphology and fracture pattern analysis. Among the patients, 13 underwent ORIF, while 2 underwent salvage procedures. Among the ORIF cases, single-stage procedures were performed in 4 patients, and two-stage procedures in 9 patients. External fixators, including unilateral uniplanar external fixators (UUEF) and bilateral uniplanar external fixators (BUEF), were applied in 5 and 4 patients, respectively. Our methodology of treating chronic perilunate injuries has evolved over the years. We started with single stage ORIF then graduated to a two staged procedure initially using a external fixator as a carpal distractor applied only on the radial side and finally settling down with bilateral carpal distraction using external fixators both on the radial and ulnar sides. RESULTS: Among the 15 patients, 3 were lost to follow-up. Of these, one underwent four-corner fusion, while the remaining two had UUEF. The mean time interval between injury and surgery was 3.60 months. The post-operative mean scapholunate angle measured 52.46°, with a negative radio-lunate angle (indicating flexion) observed in two patients, while others showed a positive angle (indicating extension). Two cases exhibited nonunion and avascular necrosis (AVN) of the scaphoid, while one case presented with lunate AVN. Mid-carpal and radio-carpal arthritis was observed in 4 and 2 patients, respectively. Functional outcomes were evaluated using Mayo's wrist score categorized as good for two-stage BUEF cases and satisfactory for UUEF and single-stage procedures. CONCLUSION: Staged reduction utilizing the BUEF followed by open reduction has demonstrated superior outcomes when compared to UUEF, single-stage open reduction and salvage procedures. LEVEL OF EVIDENCE: 4.

Effects of brain radiotherapy strategies on survival in the era of MRI for patients with limited stage small cell lung cancer.

BACKGROUND AND PURPOSE: In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC). METHODS: This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI. RESULTS: 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group. CONCLUSION: The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.