Salvage Treatment Research Articles

912P Selection of personalized salvage treatments in advanced refractory head and neck squamous cell carcinomas via multi-omics tumor profiling

912P Selection of personalized salvage treatments in advanced refractory head and neck squamous cell carcinomas via multi-omics tumor profiling

Effective utilization of polypectomy in endoscopic salvage treatment of rectal neuroendocrine tumors: a retrospective cohort study.

Current guidelines recommend endoscopic resection for rectal neuroendocrine tumors (RNETs) under 10 mm. Incomplete resections necessitate salvage procedures, highlighting the need for complete R0 resection. This study evaluates the efficacy and safety of wide hot snare polypectomy (WHSP) compared to endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for the salvage treatment of small RNETs. This retrospective study was conducted at Korea University Guro Hospital from January 2018 to December 2022. It compared the outcomes of salvage resections for RNETs ≤10 mm using 2 approaches: ESD and EMR vs. WHSP. Demographics, tumor characteristics, and clinical outcomes were compared. Efficacy was evaluated by the histological complete resection rate and procedure time, while safety was assessed by the incidence of complications. Out of 135 patients undergoing salvage resection for RNET, 14 who underwent transanal excision were excluded. Of the remaining 121, 99 underwent EMR or ESD, and 22 underwent WHSP. Baseline characteristics were similar between the 2 groups. The WHSP group demonstrated a significantly higher R0 resection rate (72.7% vs. 49.5%, P = 0.010) and a shorter median procedure time (3.5 minutes vs. 8.3 minutes). No complications were reported in the WHSP group. WHSP is a rapid, straightforward, safe, and effective approach for the salvage treatment of RNETs less than 10 mm in diameter, particularly in patients without additional risk factors.

219: Outcome of intraoperative radiotherapy as a salvage treatment for locally recurrent rectal cancer

219: Outcome of intraoperative radiotherapy as a salvage treatment for locally recurrent rectal cancer

2324: Is the biopsy still necessary for salvage treatment of recurrent prostate cancer after radiotherapy?

2324: Is the biopsy still necessary for salvage treatment of recurrent prostate cancer after radiotherapy?

ABCL-006 Azacytidine plus rituximab–gemcitabine–oxaliplatin as salvage treatment in patients with relapsed/refractory diffuse large B-cell lymphoma

ABCL-006 Azacytidine plus rituximab–gemcitabine–oxaliplatin as salvage treatment in patients with relapsed/refractory diffuse large B-cell lymphoma

The Impact of Pembrolizumab as a Salvage Therapy Based on HER2 Expression in Advanced Gastric Cancer.

Immune checkpoint inhibitors (ICIs) are used as salvage treatments for advanced gastric cancer (AGC) regardless of HER2 status. This study assessed the efficacy of ICIs based on HER2 expression in AGC patients who received pembrolizumab as salvage monotherapy at Samsung Medical Center from November 2017 to March 2023. HER2 status was determined via immunohistochemistry, and tumor response and survival outcomes were compared accordingly. Among the 113 patients analyzed, with a median age of 61 years and 64.6% being male, 12 patients (10.6%) were HER2-positive, and 101 patients (89.4%) were HER2-negative. Of 92 evaluable patients, none had a complete response. However, 50% of HER2-positive patients had a partial response, compared to 4.9% of HER2-negative patients (p < 0.001). The disease control rate was 70% in HER2-positive and 37.8% in HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). Pembrolizumab as a salvage chemotherapy for the treatment of AGC demonstrated superior effectiveness in HER2-positive patients compared with HER2-negative patients.

Incidence, risk factors and therapy response of acute graft-versus-host disease after myeloablative hematopoietic stem cell transplantation with posttransplant cyclophosphamide.

Posttransplant cyclophosphamide, sirolimus and mycophenolate mofetil (PTCy/siro/MMF) constitutes an innovative and well-tolerated acute graft-versus-host disease (aGVHD) prophylaxis after allogeneic stem cell transplantation (allo-HSCT), but risk factors for aGVHD incidence and therapy failure in this setting are scarce. This study prospectively registered all consecutive adult patients with hematologic malignancies who received a myeloablative allo-HSCT using PTCy/siro/MMF prophylaxis at our institution between 2017 and 2023. A total of 385 patients were included, of whom 44%, 34% and 22% were transplanted from matched sibiling, matched unrelated and haploidentical donors, respectively. The 180-day cumulative incidence of aGVHD was 21% (95% confidence interval [CI] 17-25%) for grade II-IV and 11% (95% CI 8-14%) grade III-IV aGVHD. The use of haploidentical donors was associated with an increased risk of severe aGVHD. Among 75 patients receiving first-line systemic corticosteroids, 49% achieved a sustained complete response, while 23% and 24% developed steroid-dependent (SD-aGVHD) and steroid-refractory aGVHD (SR-aGVHD), respectively. SR-aGVHD was associated with worse salvage treatment response and overall survival compared to SD-aGVHD. The 1-year cumulative incidence of aGVHD-related mortality was 5.4% (95% CI, 3.3-8.1). Risk factors for aGVHD-related mortality included haploidentical donors, older donors, diagnosis of myeldysplastic neoplasms, and grade IV aGVHD. This study confirms a low incidence aGVHD with PTCy/siro/MMF prophylaxis. SR-aGVHD showed poorer response to salvage therapies and worse survival, while haploidentical donors and older donor age were negative predictors for aGVHD-related deaths.

Outcome of patients with large B-cell lymphoma treated with tafasitamab plus lenalidomide either before or after CAR T-cell therapy

AbstractTafasitamab plus lenalidomide (TAFA-LEN) treatment relevance pre- or post-anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is debated. We analyzed patients with large B-cell lymphoma in the DESCAR-T registry treated with axi[1]cel or tisa-cel in ≥3rd line and TAFA-LEN before (n = 15, “TL-pre-CAR-T” set) or directly after (n = 52, “TL-post-CAR-T” set) CAR T-cell therapy. We compared TAFA-LEN v. other treatments using inverse probability weighting in the TL-post-CAR[1]T set. In the TL-post-CAR-T set, the median progression-free survival (mPFS), overall survival (mOS), and duration of response (mDOR) since the first treatment for progression (mPFS2/mOS2/mDOR2) were 3, 4.7, and 8.1 months, respectively. The best overall response rate (bORR) and best complete response rate (bCRR) after TAFA-LEN were 13.5% and 7.7%, respectively. Outcomes were better for patients who relapsed >6 months after CAR T-cell therapy (mPFS2: 5.6 vs 2 months, P = .0138; mOS2: not reached vs 3.8 months, P = .0034). The bORR and bCRR between TAFA-LEN and other treatments were 20.6% vs 24.9% and 11.6% vs 15.6%, respectively. Outcomes were similar between TAFA-LEN and other treatments (mPFS2: 2.9 vs 2.4 months, P = .91; mOS2: 3.3 vs 5.5 months, P = .06). In an exploratory analysis of the TL-pre-CAR-T set, the median TAFA-LEN treatment duration before CAR-T was 3.7 months with no patient becoming CD19 negative. The bORR, bCRR, 6- month PFS, and OS rates after CAR T-cell infusion were 45.5%, 36.4%, 20.1%, and 58.2%, respectively. Neither TAFA-LEN nor comparative salvage treatment improved outcomes for patients relapsing after CAR T-cell therapy.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with fruquintinib and tislelizumab for patients with microsatellite stable colorectal cancer liver metastasis following failure of multiple-line therapy.

The prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy. From February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%). HAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

A Population Pharmacokinetic Model of Tocilizumab in Kidney Transplant Patients Treated for Chronic Active Antibody-Mediated Rejection: Comparison of Plasma Exposure Between Intravenous and Subcutaneous Administration Schemes.

Tocilizumab prevents the clinical worsening of chronic active antibody-mediated rejection (CAAMR) in kidney transplant recipients. Following a global shortage of the intravenous pharmaceutical form in 2022, patients were switched from monthly intravenous administration of 8 mg/kg to weekly subcutaneous injection of 162 mg, raising the question of bioequivalence between these schemes of administration. We aimed to compare the areas under the curve (AUC) of tocilizumab in virtual simulations of populations treated with the two administration schemes and to identify the covariates that could contribute to pharmacokinetic variability of tocilizumab in kidney transplant patients with CAAMR who received tocilizumab as salvage treatment. This retrospective monocentric study included 43 kidney transplant patients (202 tocilizumab concentrations) with CAAMR treated with intravenous or subcutaneous tocilizumab between December 2020 and January 2023. We developed a population pharmacokinetic model using nonlinear mixed effects modeling and identified the covariates that could contribute to tocilizumab AUC variability. Monte Carlo simulations were then performed to assess the subcutaneous and intravenous tocilizumab AUC for 0-28 days (M1), 56-84 days (M3), 140-168 days (M6), and 308-336 days (M12). Bioequivalence was defined by SC/IV AUC geometric mean ratios (GMRs) between 0.80 and 1.25. A two-compartment model with parallel linear and nonlinear elimination best described the concentration-time data. Significant covariates for tocilizumab clearance were body weight, urinary albumin-to-creatinine ratio (ACR), and inflammation status [C-reactive protein (CRP) ≥5 mg/L]. The GMR values and their 90% confidence intervals at M3, M6, and M12 were within the 0.8-1.25 margin for equivalence. Conversely, the 90% prediction intervals of the GMR were much wider than the 90% confidence intervals and did not fall within 0.8 and 1.25. From month 3 of treatment, the subcutaneous and intravenous tocilizumab administration schemes provided average bioequivalent pharmacokinetic exposure at the population level but not at the individual level. Body weight, inflammation, ACR, and administration scheme should be considered to personalize the dose of tocilizumab for patients with CAAMR. Further studies are required to determine the target of tocilizumab exposure in kidney transplant patients with CAAMR.

Tongue squamous cell carcinoma treated by 5-aminolevulinic acid administrated through Microdrop method

BackgroundPostoperative recurrence of tongue squamous cell carcinoma (TSCC) has always been a clinical problem for patients and doctors. Surgery and radiotherapy are the main treatment methods for TSCC, but reoperation often leads to functional impairment. Side effects of radiotherapy include mucosal gland damage, dry mouth, weakened or lost taste. Improved treatment is needed. ObjectiveTo evaluate the clinical outcome of a patient with TSCC treated with Microdrop aminolevulinic acid (ALA) photodynamic treatment (PDT) twice. MethodsALA was dissolved in 5 % lidocaine and the concentration of ALA was 20 % by Microdrop method. Then, the tumor tissue was expanded 1 cm outward, and the injection points were evenly distributed with an upper and lower left and right interval of 2–3 mm. The 1 ml syringe was used to perform the injection in the skin of the tumor area, and there was a small cuticle at each injection point. A pathologically confirmed patient with TSCC received twice Microdrop ALA-PDT treatments, which were evaluated at 1 month and 4 months later. ResultsAfter 3 h of Microdrop ALA injection, the wavelength of semiconductor laser was set to 630 nm, and the energy of 300 mW /cm2 was irradiated for 30 min. After two treatments, the lesions were not visible, and no recurrence occurred after 4 months of follow-up. The patient's tongue function was well preserved and the cosmetic effect was good. ConclusionMicrodrop ALA-PDT may be effective in the salvage treatment of select tongue squamous cell carcinoma.

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.

Conventional versus high-dose salvage chemotherapy for relapsed testicular germ cell tumours

Since the introduction of cisplatin-based combination chemotherapy, patients with metastatic germ cell tumours achieve very high cure rates of >80%. Nevertheless, about 30% of patients relapse despite guideline-endorsed first-line treatment. Of these, again about 50% of patients can still achieve cure with platinum-based salvage chemotherapy and eventually post-chemotherapy residual mass resection.Salvage chemotherapy generally involves platinum-based combination chemotherapy, either as conventional dose cisplatin-based combinations again or as high-dose chemotherapy with subsequent autologous stem cell transplantation.To date, high level evidence from randomised trials supporting the use of salvage high-dose chemotherapy for all patients relapsing after first-line treatment remains lacking, but a large international retrospective registry study had shown a 15% overall survival benefit for patients undergoing salvage high-dose chemotherapy.In this article, we summarise the available literature on the different salvage treatment approaches and discuss these in the light of current treatment guideline recommendations for the management of testicular cancer.

Salvage treatments after focal therapy for prostate cancer - a comprehensive review.

To review the literature on salvage treatments after focal therapy (FT) for prostate cancer (PCa). A non-systematic literature review was conducted on PubMed, Scopus, and Web of Science up to March 15, 2024, for studies that assessed salvage treatment outcomes in patients with recurrent PCa after primary FT. Original prospective and retrospective studies with more than 10 patients were included. Reviews, editorial comments, conference abstracts, and studies focusing solely on whole-gland treatments were excluded. Twenty-one studies with a total of 1012 patients were included. The most reported salvage treatments were salvage radical prostatectomy followed by re-do ablation therapy. Only one study evaluated salvage radiation therapy. Except for one prospective study, all studies were retrospective. Oncological outcomes showed acceptable biochemical recurrence rates. Functional outcomes varied, with significant impacts observed on erectile function across modalities, though continence rates were less impacted. Complications were generally low across all treatment options. Salvage treatment post-primary FT is feasible, safe, and has reasonable oncologic outcomes. However, significant declines in sexual function are common, while continence is comparatively less affected. The literature primarily consists of retrospective studies; hence, future research should focus on large-scale prospective evaluations to better define treatment protocols and improve patient outcomes.

Radiotherapy and chemoradiotherapy for postoperative recurrence in patients with esophageal squamous cell carcinoma.

The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients. Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post-recurrence survival (PRS) and prognostic factors were evaluated by Kaplan-Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction. A total of 170 patients were enrolled, with a median age of 60 years (range 43-77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p < 0.05) for PRS. Salvage treatment was not associated with PRS (p = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (p = 0.043) and had no significant differences in toxic reactions compared to RT (p = 0.924). In addition, RT showed better prognoses (p = 0.020) and lower toxic reactions (p = 0.030) than CRT in patients with positive LNs. Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs.

Arthroscopic-Assisted Lower Trapezius Tendon Transfer for Irreparable Posterosuperior Rotator Cuff Tears Using a Quadricipital Tendon Allograft and a Double-Row Construct

Lower trapezius transfer is a joint salvage treatment option for irreparable posterosuperior rotator cuff tears in relatively young patients. It requires the use of a tendinous graft to bridge the gap between the lower trapezius and the greater tuberosity. Inlay fixation of hamstring autografts and onlay single-row fixation of Achilles allografts have been described in the literature. This technical note describes an arthroscopic-assisted lower trapezius transfer using a quadricipital tendon allograft fixed with an onlay knotless double-row construct.

CAR-T Therapy in Relapsed Refractory Multiple Myeloma.

Multiple myeloma is a plasma cell neoplasm. The emergence of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has improved the prognosis of multiple myeloma patients. However, some patients are still insensitive to conventional therapy or frequently relapse after remission. Chemotherapy based on proteasome inhibitors or immunomodulatory drugs is ineffective in controlling the progression of relapsed refractory multiple myeloma. No consensus has been reached on treating relapsed refractory multiple myeloma to date. Recently chimeric antigen receptor T cells therapy has shown promising results that could achieve rapid remissions of patients and improve their prognoses. Additionally, most patients in chimeric antigen receptor T cell clinical trials were triple-refractory multiple myeloma patients, indicating that chimeric antigen receptor T cell immunotherapy could overcome drug resistance to new drugs. Since single immunotherapies are prone to acquired resistance, combination immunotherapies based on emerging immunotherapies may solve this issue. Achieving complete remission and minimal residual disease negative status as soon as possible is beneficial to patients. This paper reviewed the main chimeric antigen receptor T cell products in relapsed refractory multiple myeloma, and it explained the drug resistance mechanism and improvement methods of chimeric antigen receptor T cells therapy. This review summarized the best beneficiaries of chimeric antigen receptor T cell therapy and the salvage treatment of disease recurrence after chimeric antigen receptor T cell therapy, providing some ideas for the clinical application of chimeric antigen receptor T cells.

Comparison of the Long-term Survival Outcome of Surgery versus Stereotactic Body Radiation Therapy as Initial Local Treatment for Pulmonary Oligometastases from Colorectal Cancer: A Propensity Score Analysis

PurposeOptimal local treatment for pulmonary oligometastases from colorectal cancer (CRC) remains unclear. We aimed to compare the long-term survival outcomes between surgery and stereotactic body radiotherapy (SBRT) as the initial local treatment for CRC pulmonary oligometastases. Materials and MethodsWe retrospectively reviewed 335 consecutive patients who initially underwent surgery or SBRT for CRC pulmonary metastases from 2011 to 2022, and 251 patients (173 surgery and 78 SBRT) were ultimately included. Freedom from intrathoracic progression (FFIP), progression-free survival (PFS), and overall survival (OS) were compared using stabilized inverse probability of treatment weighting (sIPTW) analysis. In addition, patterns of intrathoracic progression and subsequent treatment were analyzed. ResultsMedian follow-up was 61.6 months for surgery and 54.4 months for SBRT. After sIPTW adjustment, significant differences emerged in both FFIP and PFS between surgery and SBRT (FFIP: hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.31–0.79; PFS: HR = 0.56, 95% CI, 0.36–0.87). The 3- and 5-year FFIP rates were 58.6% and 54.8%, respectively, after surgery, and 34.6% and 31.3%, respectively, after SBRT (P = 0.006). The 3- and 5-year PFS rates were 49.4% and 45.2%, respectively, after surgery, and 28.8% and 26.1%, respectively, after SBRT (P = 0.010). However, OS was not significantly affected by treatment approach (HR = 0.93, 95% CI, 0.49–1.76). The 3- and 5-year OS rates were 85.9% and 73.1%, respectively, after surgery, and 78.9% and 68.7%, respectively, after SBRT (P = 0.849). Recurrence at the treated site was more prevalent after SBRT than after surgery (33.3% vs. 16.9%), whereas new intrathoracic tumors occurred more frequently after surgery than after SBRT (71.8% vs. 43.1%). Both groups chose radiotherapy as the primary local salvage treatment. ConclusionsNotwithstanding the significant differences in FFIP and PFS between surgery and SBRT, the long-term survival of patients with CRC pulmonary oligometastases did not depend on the initial choice of the local treatment approach.

SCOPING: A Pilot Study Exploring the Role of A Series of Clinical Observational Parameters as Indicators of Nerve Regeneration.

Following the repair of a mixed peripheral nerve, functional recovery requires successful nerve regeneration across the repair site and, eventually, reinnervation of distal targets. Reliably determining a failing nerve repair so that revision may be performed before irreversible muscle atrophy remains a challenge in peripheral nerve surgery. This study aimed to ascertain whether any commonly used clinical examination tests during surveillance after nerve repair can detect a failing repair and prompt earlier salvage intervention. A prospective observational cohort study was performed to evaluate commonly used clinical determinants of neuron regeneration that may provide early surrogate recovery measures. Sequential cutaneous thermography was used to identify temperature differences between denervated and normal skin in the hand operated on, with the contralateral hand as a control. Six out of nine patients completed between 6 and 18 months of follow-up. Tinel sign progression was observed in all subjects. Tinel progression rate was associated with motor and sensory Medical Research Council grade. The delta temperature was calculated to document the size and direction of any temperature differentials in the hand detected by thermography, but we did not have sufficient data to calculate any correlations with motor and sensory Medical Research Council grade. Specifically, the progression of Tinel sign is associated with recovery measured by progression of the British Medical Research Council motor and sensory grades. The use of thermographic imaging demonstrates that there is a difference in temperature between an injured and noninjured nerve. Future studies could investigate to what extent thermographic imaging predicts final nerve repair outcomes.

Salvage Cryoablation for Recurrent Prostate Cancer Following Radiation-A Comprehensive Review.

The treatment options for prostate cancer typically entail active surveillance, surgery, radiation, or a combination of the above. Disease recurrence remains a concern, with a wide range of recurrence rates having been reported in the literature. In the setting of recurrence, the salvage treatment options include salvage prostatectomy, salvage high-intensity focused ultrasound (HIFU), stereotactic body radiotherapy (SBRT), salvage brachytherapy, and salvage cryoablation. In this review, we analyze the currently available data related to salvage cryoablation for recurrent prostate cancer following radiation.