Salvage Therapy and Allogeneic Hematopoietic Cell Transplantation for the Severe Cytokine Storm Syndrome of Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) can be considered as a severe cytokine storm syndrome disorder. HLH typically manifests as a life-threatening inflammatory syndrome characterized by fevers, cytopenias, hepatosplenomegaly, and various other accompanying manifestations such as coagulopathy, hepatitis or liver failure, seizures or altered mental status, and even multi-organ failure. Standard up-front treatments do not always bring HLH into remission or maintain adequate response, and salvage or alternative therapies are often needed. For patients with genetic diseases that cause HLH, curative allogeneic hematopoietic cell transplantation is usually offered to prevent future episodes of life-threatening HLH. Here, we will discuss the options and approaches for salvage therapy and hematopoietic cell transplantation for patients with HLH.

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.

Ceftazidime-Avibactam as a Salvage Treatment for Severely Infected Immunosuppressed Children.

Background: Multidrug-resistant Gram-negative bacteria (MDR-GNB) are becoming increasingly common around the world, with carbapenems frequently serving as a last resort but being threatened by the growing incidence of carbapenemase-producing bacteria. Ceftazidime-avibactam (CAZ/AVI) is a potential agent against MDR-GNB but with limited clinical experience, particularly in critically ill immunosuppressed children. Methods: This study analyzed the use of CAZ/AVI as salvage treatment in severely infected immunosuppressed children from September 2019 to July 2022. Patients with confirmed GNB infection who received CAZ/AVI were matched with patients who received other antibiotics. Results: Twenty-five critically ill immunosuppressed children treated with CAZ/AVI were included. The majority had hematologic diseases. All patients presented with sepsis in all 30 courses. Septic shock presented in 36.7% of these courses. The primary sites of infection included bloodstream infection (20.0%), skin and skin structure infection (20.0%), intra-abdominal infection (13.3%) and hospital-acquired pneumonia (10.0%). Twelve of the 25 (48.0%) patients had positive microbiological cultures, mainly Pseudomonas aeruginosa and Klebsiella pneumoniae, including 5 carbapenem-resistant GNB-infected cases. Fifteen (50.0%) courses presented clinical improvement. For the initial course of each patient, the clinical response rate of the GNB recovered group was significantly higher than that of the group without GNB recovery (66.7% vs 23.1%, P = 0.047). The 14-day and 30-day mortality rates were 24.0% and 28.0%, respectively, which were significantly correlated with the absence of GNB recovery (P = 0.004 and 0.024, respectively) and hospital-acquired pneumonia as the primary site of infection (P = 0.001 and 0.006, respectively). There was no significant difference in major outcomes between patients who received CAZ/AVI and matched patients who received other antibiotics. Conclusion: CAZ/AVI could be considered a salvage strategy for immunosuppressed children with confirmed GNB infection. Caution should be taken when CAZ/AVI is applied to these patients in the absence of GNB recovery.

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.

Prostate-specific membrane antigen-radioguided surgery salvage lymph node dissection: experience with fifty oligorecurrent prostate cancer patients.

PURPOSE: The higher detection efficacy of PSMA PET for oligometastatic recurrence of prostate cancer has promoted new loco-regional treatment options. PSMA-targeted radioguided surgery (PSMA-RGS) was introduced to facilitate salvage surgery of small tumor deposits. The objectives of this retrospective analysis are to describe an independent single-center consecutive cohort of patients undergoing PSMA-RGS and to evaluate its clinical and oncological outcomes. METHOD: Between 2018 and 2022, 53 patients were treated with PSMA-RGS and 50 patients were available for final analyses. All patients were initially treated with radical prostatectomy (RP) and presented with biochemical recurrence (BCR) with at least one positive lesion on PSMA-PET imaging. After preparation of 99mTc-PSMA-I&S and intravenous injection, surgery was performed by using a gamma-probe intraoperatively. RESULTS: Median age was 70 years (IQR 65-73) and the median PSA at salvage surgery was 1.2 ng/mL (IQR 0.6-3.0). In all patients pathologically positive lesions could be removed during PSMA-RGS. 29 (58%) patients had one pathologically positive lesion, 14 (28%) had two and 7 (14%) had three or more, respectively. The overall complication rate was 26% with 4 (8%), 1 (2%), and 8 (16%) having Clavien-Dindo (CD) type I, II, and IIIb complications, respectively. During the follow-up period 31 (62%) patients experienced BCR and 29 (58%) received further therapy. CONCLUSIONS: PSMA-RGS is a promising treatment option to enhance salvage surgery in early biochemical recurrence. However, only 42% of the patients treated with PSMA RGS remain without a biochemical recurrence. Further research is mandatory to identify patients, who profit from PSMA-RGS.

Merkel cell carcinoma refractory to anti-PD(L)1: utility of adding ipilimumab for salvage therapy.

Merkel cell carcinoma (MCC) incidence has risen to approximately 3,000 cases annually in the USA. Although anti-programmed cell death (ligand) 1 (PD-(L)1) agents are now the first-line treatment for advanced MCC, approximately 50% of such patients do not persistently benefit. In PD-(L)1-refractory cases, ipilimumab (anti-cytotoxic T lymphocyte antigen-4) is often added; however, the extent of the clinical benefit of this combination is controversial. We identified one prospective study, three retrospective studies, and three case reports regarding this combination in refractory MCC. The aggregate response rate from retrospective studies was 32% (13 of 41 patients) with 4 complete responses (CR) and 9 partial responses (PR). In the prospective study, the response rate was very similar at 31% (8 of 26 patients; 4 CR, 4 PR). Response durability was highly variable (range 2 to >43 months), with patients achieving CR having greater durability. Immune-related adverse events (irAEs) were ≥grade III in 29% (retrospective cohort, N=41) and 36% (prospective cohort, N=50). While these aggregate data indicate adding ipilimumab should be considered in this setting, many patients with refractory MCC are ineligible due to comorbidities/irAEs, and approximately 70% will not benefit from this regimen. There is thus a significant unmet need in PD-(L)1-refractory MCC and clinical trials in this setting should be encouraged.

Discordance of retroperitoneal and thoracic histologic findings in patients with metastatic germ cell tumors at postchemotherapy residual tumor resection.

INTRODUCTION AND OBJECTIVES: Postchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery. PATIENTS AND METHODS: From a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy. RESULTS: All patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%. CONCLUSION: The data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen.

What is the best salvage therapy for Hodgkin lymphoma?

PURPOSE OF REVIEW: Historically, salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDT/ASCT) was the mainstay approach for relapsed or refractory classic HL. The emergence of novel agents for HL, such as brentuximab vedotin and programmed death-1 (PD-1) blockade has revolutionized therapeutic strategies, yielding excellent results. This review aims to provide a comprehensive overview of new salvage therapies and offer insights into forthcoming therapeutic options. RECENT FINDINGS: The incorporation of brentuximab vedotin and PD-1 blockade into salvage therapy before HDT/ASCT has led to markedly improved outcomes. Notably, PD-1 based salvage studies yield posttransplant 2-year progression-free survival rates approaching 90%, marking a significant advancement in the treatment of Hodgkin lymphoma (HL). Studies are beginning to explore nontransplant treatment approaches following front-line treatment failure and may identify certain risk groups eligible for these strategies. SUMMARY: The landscape of HL treatment is rapidly evolving, leading to significant changes in the standard of care. Novel agents are now administered earlier in the disease course, resulting in higher cure rates. The focus of treatment is shifting towards achieving cure with minimal toxicity, reducing exposure to various agents, and advancing research in optimizing treatment sequencing and patient selection for less intensive therapies.

Long-term Outcomes of Salvage Surgery Versus Induction Therapy Followed by Surgical Resection for Advanced NSCLC: A Propensity Score-matched Analysis.

BACKGROUND/AIM: The outcomes of lung cancer treatment have improved over time. However, in contrast to other treatments, the clinical outcomes of salvage surgery are seldom reported because the follow-up periods after salvage surgery are short. PATIENTS AND METHODS: We conducted a comprehensive study involving consecutive patients who underwent salvage surgery at two different institutions. Our analysis encompassed the exploration of clinicopathological features, perioperative variables, and surgical outcomes. Additionally, we employed propensity score matching to compare the long-term survival of patients with non-small cell lung cancer (NSCLC) who underwent salvage surgery with those who received induction chemoradiotherapy prior to surgery. RESULTS: Twenty-five patients underwent salvage procedures, while 113 patients received induction chemotherapy followed by surgery during the same study period. When assessing the overall survival (OS) from the registration date to the initial treatment date, the five-year OS rates were 73.8% in the induction group and 70.5% in the salvage surgery group (p=0.674). No significant differences were identified between the two groups in a cohort of 48 patients with NSCLC who were matched using propensity scores. CONCLUSION: In patients who underwent salvage surgery, reasonable long-term survival was achieved with outcomes comparable to those of induction chemotherapy followed by surgical resection.

Salvage High-Intensity Focused Ultrasound for Prostate Cancer after Radiation Failure: A Narrative Review.

For patients diagnosed with localized prostate cancer, there are multiple treatment options available. The traditional treatment modalities include radical prostatectomy and radiotherapy. Nevertheless, focal therapy, including high-intensity focused ultrasound (HIFU) and cryotherapy, has emerged as a less-invasive method in this setting. Some patients undergoing primary radiation therapy experience recurrence, but there is currently no consensus on the optimal approach for salvage treatment in such cases. The lack of robust data and randomized controlled trials comparing different whole-gland and focal salvage therapies presents a challenge in determining the ideal treatment strategy. This narrative review examines the prospective and retrospective data available on salvage HIFU following radiation therapy. Based on the literature, salvage HIFU for radio-recurrent prostate cancer has promising oncological outcomes, with an overall 5-year survival rate of around 85%, as well as incontinence rates of about 30% based on the patient's risk group, follow-up times, definitions used, and other aspects of the study. Salvage HIFU for prostate cancer proves to be an effective treatment modality for select patients with biochemical recurrence following radiotherapy.

Salvage radiotherapy for locally recurrent cervical and endometrial carcinoma: clinical outcomes and toxicities.

BACKGROUND: The management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma. METHODS: The study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan-Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5. RESULTS: During a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1-2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1-2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients. CONCLUSIONS: 3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

The efficacy and safety of second salvage autologous transplantation in myeloma patients.

Despite the availability of many novel therapies for multiple myeloma, it remains an incurable disease with relapse fated in almost all patients. In the era of modern agents, second autologous stem cell transplantation still holds its role in patients relapsing after first-line autologous transplant. The authors reviewed a single-center experience with a second auto-SCT for relapsed multiple myeloma. Thirty patients had received a salvage auto-SCT at the institution. The median follow-up after diagnosis was 86 months, and the median time between transplants was 59.1 months. Response before second ASCT was the following: CR - 11 cases, VGPR - 9 cases, PR - 10 cases. Most patients received reduced dose (140 mg/m2) of melphalan as a conditioning regimen for the second auto-SCT. Treatment-related mortality was 3%. With a median follow-up time of 34 months after the second transplant, median progression-free survival was 24 months. The median PFS in the patients achieving CR or VGPR at day 100 after the second transplantation was 32 months. By 15 months, all patients achieved only partial remission progressed, with a median PFS of 8.5 months. During the follow-up period, no MDS or AML developed, and the frequency of second malignancy was also low, 3%. In conclusion, second autologous stem cell transplantation is a well-tolerated and effective treatment option for relapsed multiple myeloma in selected patients, though with a shorter PFS than in first remission.

Safety and efficacy of fruquintinib-based therapy in patients with advanced or metastatic sarcoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of fruquintinib-based therapy as a salvage therapy for patients with advanced or metastatic sarcoma, including soft tissue sarcoma (STS) and bone sarcoma. METHODS: Patients with advanced or metastatic sarcoma were divided into two groups. One group received fruquintinib monotherapy, while the other received fruquintinib combined therapy. Safety and efficacy of fruquintinib-based therapy were recorded and reviewed retrospectively, including progression-free survival (PFS), overall response rate (ORR), and adverse events (AEs). RESULTS: Between August 2021 and December 2022, 38 sarcoma patients were retrospectively included. A total of 14 patients received fruquintinib alone (including 6 STS and 8 bone sarcoma), while 24 were treated with fruquintinib combined therapy (including 2 STS and 22 bone sarcoma). The median follow-up was 10.2 months (95% CI, 6.4-11.5). For the entire population, the median PFS was 8.0 months (95% CI, 5.5-13.0). The ORR was 13.1%, while the disease control rate (DCR) was 86.8%. The univariate analysis showed that radiotherapy history (HR, 4.56; 95% CI, 1.70-12.24; p = 0.003), bone sarcoma (HR, 0.34; 95% CI, 0.14-0.87; p = 0.024), and treatment method of fruquintinib (HR, 0.36; 95% CI, 0.15-0.85; p = 0.021) were significantly associated with PFS. The multivariate analysis showed that patients without radiotherapy history were associated with a better PFS (HR, 3.71; 95% CI: 1.31-10.55; p = 0.014) than patients with radiotherapy history. Patients in combination group reported pneumothorax (8.3%), leukopenia (33.3%), thrombocytopenia (12.5%), diarrhea (4.2%), and anemia (4.2%) as the most frequent grade 3 or higher treatment-emergent AEs (TEAEs), while there was no severe TEAEs occurred in the monotherapy group. CONCLUSIONS: Fruquintinib-based therapy displayed an optimal tumor control and an acceptable safety profile in patients with advanced or metastatic sarcoma.

Outcomes of children treated for relapsed or refractory acute lymphoblastic leukemia: A single tertiary care center experience.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the most common malignancies among children. Despite success in frontline treatment, 20% of children will relapse or show resistance to treatment. AIM: The aim of this study is to evaluate the clinical characteristics of children diagnosed and treated for refractory or relapsed ALL and determine 3-year overall survival (OS) outcomes. METHOD: This study involved a retrospective chart review of patients aged 1-14 years diagnosed with ALL during January 2002 to December 2018. Data were extracted for baseline characteristics at diagnosis and at relapse. RESULTS: A total of 347 newly diagnosed children with ALL were identified, among whom there were three induction failures (IF) and 28 relapses, resulting in a cohort of 31 patients with a relapse rate of 9%. The male-to-female ratio was 4.16:1, and the mean duration of first complete remission (CR1) was 26 months. Fifteen (48%) patients relapsed ≤18 months, 7 (23%) during 18-36 months, and 9 (29%) relapsed >36 months of IF or CR1. Nineteen patients (61%) had isolated bone marrow (BM) relapse, 7 (23%) patients experienced isolated extramedullary relapse (5 isolated CNS relapse and 2 isolated testicular relapse), and 5 (16%) patients experienced BM involvement with other sites (4 BM + CNS and 1 BM + testis). The 3-year OS of the cohort was 62.3%, while in patients with CR post first-salvage therapy, a 3-year OS of 79.5% was observed (p value <.05 compared with patients who did not achieve remission post first-salvage therapy, 3-year OS: 46.4%). The same statistical difference was observed in 3-year OS when comparing the duration of remission of CR prior to relapse: ≤18 months, 33.2%; 18-36 months, 66.7%; and >36 months, 87.5%. The same trend continued when comparing 3-year OS based on risk stratification at relapse: low risk (LR), 83.3%; intermediate risk (IR), 80%; and high risk (HR), 44.8%. CONCLUSION: The incidence and outcomes reported are comparable to internationally reported data regarding the duration of CR1. Risk stratification at relapse and remission status post-salvage therapy were identified as significant prognostic factors for survival. No survival difference was observed among patients who received hematopoietic stem cell transplantation after induction compared with those who received chemotherapy, which could be attributed to the smaller sample size, warranting a multi-institutional observational study. These findings corroborate the need for novel therapies and treatment approaches.

[A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia].

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

Management of patient with Fusobacterim nucletum related pleural empyema: intrapleural antibiotic therapy can be considered for salvage therapy.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Real life clinical outcomes of relapsed/refractory diffuse large B cell lymphoma in the rituximab era: The STRIDER study.

BACKGROUND: Relapse and refractory (R/R) rates after first-line R-CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. AIMS: We conducted a retrospective real-world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. MATERIAL AND METHODS: Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. RESULTS: At a median follow up of 50 months, 5-year overall survival from diagnosis (OS-1) was 66.5%, and 2-year progression free survival (PFS-1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R-CHOP. Most employed salvage treatments included platinum salt-based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS-2 and PFS-2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS-2 or PFS-2 in patients treated with platinum-based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of <2 sites were associated with better OS-2. DISCUSSION: Our findings confirm very poor outcomes of R/R DLBCL in the rituximab era. Widespread approval by national Medicine Agencies of novel treatments such as CAR-T cells and bispecific antibodies as second-line is eagerly awaited to improve these outcomes.

The role of endoscopic ultrasonography for diagnosis of residual rectal neuroendocrine tumor.

BACKGROUND: Endoscopic ultrasonography (EUS) is useful for assessing the depth and regional lymph node involvement in rectal neuroendocrine tumors (NETs). However, evidence regarding the effectiveness of EUS in identifying residual lesions in patients with incompletely resected NET is limited. We aimed to evaluate the efficacy of EUS in identifying residual rectal NETs and the clinical outcomes of salvage endoscopic treatment. METHODS: We retrospectively reviewed the records of patients who were transferred to Chosun University Hospital and received salvage treatment for incompletely resected rectal NETs between January 2012 and October 2021. RESULTS: This study included 68 incompletely resected rectal NET, of which 59 were margin-positive and 9 were margin-indeterminate. EUS detection (odds ratio (OR), 8.44; 95% confidence interval (CI), 1.18-41.35) and visual detection (OR, 7.00; 95% CI, 1.50-47.48) were associated with residual lesion in patients with incompletely resected NET. EUS detection of residual lesions showed a sensitivity of 94%, specificity of 71%, positive predictive value of 88%, negative predictive value of 83%, and accuracy of 87%. All patients underwent salvage treatment with band-ligation endoscopic mucosal resection (58.8%) and endoscopic submucosal dissection (41.2%). Residual NETs were diagnosed in 47 of 68 patients (69.1%), and no recurrence was noted during the follow-up period of 51.8 ± 22.9 months. CONCLUSIONS: EUS is a more sensitive method than visual detection for evaluating residual rectal NETs. Salvage endoscopic treatment for incompletely resected NETs is safe and effective.