Salvage Treatment For Patients Research Articles

Interstitial 125I Brachytherapy as a Salvage Treatment for Refractory Cervical Lymph Node Metastasis of Thoracic Esophageal Squamous Cell Carcinoma After External Irradiation With a CT-Guided Coplanar Template-Assisted Technique: A Retrospective Study.

Purpose: To analyze the outcome and prognosis of patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation, who underwent interstitial 125I brachytherapy as a salvage treatment with a CT-guided coplanar template-assisted technique. We also want to compare the dosimetry of 3D printed coplanar template-assisted interstitial 125I brachytherapy preoperative and postoperative, and to explore the accuracy of this technology. Material and methods: We retrospectively collected and analyzed the results of 32 patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation, who underwent interstitial 125I brachytherapy as a salvage treatment with a CT-guided coplanar template-assisted technique from January 2012 to December 2017. Results: The actual D90 were 114 to 240 Gy, and the median postoperative dosimetry assessment was 177.5 Gy. The local control rates at 3, 6, 9, and 12 months were 87.5%, 59.38%, 40.63%, and 31.25%, respectively. The median local control time was 7.5 months. The median overall survival time was 10.5 months (95% CI, 8.9-13.4), and the survival rates of 1- and 2-year, respectively, were 43.75% and 9.38%. There were 36 lesions in 32 patients. By performing a paired t-test analysis, there was no significant difference in D90, D100, V100, V150, V200, GTV volume, CI, EI, and HI between preoperative and postoperative (P > .05). Conclusions: Interstitial 125I brachytherapy can be used as a salvage treatment for patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation. With the auxiliary function of 3D printed coplanar template, the main dosimetry parameters verified after the operation can meet the requirements of the preoperative plan with good treatment accuracy.

Chidamide Maintenance Therapy after Induction or Salvage Treatment in Patients with Peripheral T-Cell Lymphoma Ineligible for Autologous Stem Cell Transplantation

BackgroundPeripheral T-cell lymphoma (PTCL) is a set of rare and heterogeneous clinically aggressive mature T- and natural killer cell neoplasms, all of which are associated with poor prognosis. PTCL treatments are usually associated with a high failure rate and frequent relapses. To improve the poor clinical outcomes of PTCL, novel agents that target various pathways have been intensively studied and developed. Histone deacetylase (HDAC) inhibitors are among the most significant improvements made in recent years. Chidamide, a novel benzamide class of HDAC inhibitor, showed significant efficacy in relapsed/refractory PTCL patients in previous studies. In China, a high percentage of PTCL patients are elderly and not suitable for transplantation, and many patients cannot afford transplantation. There is an urgent medical need for maintenance therapy for PTCL patients, and chidamide single-agent maintenance therapy may benefit PTCL patients ineligible for autologous stem cell transplantation (ASCT) with its proven outstanding antitumor effects.MethodsIn this prospective, single-center, single-arm study, a total of 43 patients with PTCL, including angioimmunoblastic T-cell lymphoma (AITL) (44.2%), anaplastic large-cell lymphoma, ALK − (ALCL, ALK −) (11.6%), PTCL-not otherwise specified (PTCL-NOS) (14.0%), extranodal NK/T-cell lymphoma (NKT) (16.3%), and other PTCL subtypes (14.0%), were enrolled from January 2016 to March of 2021. All patients were ineligible for transplantation. They had a median age of 59 years (22-80). Thirty-six patients (83.7%) received chidamide maintenance after induction treatment, and 7 patients (16.3%) started chidamide maintenance treatment after salvage treatment. Endpoints included progress-free survival (PFS), overall survival (OS), and safety assessment.ResultsUntil April 2021, the median follow-up time was 10.1 months (2-64.5). The complete remission rate (CR) was 44.2% and overall response rate (ORR) was 79.1%. The median PFS was 24.3 m, and the 1-year PFS rate was 68.1%. The median OS has not yet been reached, and 1-year OS rate was 84.3%. Stratified analyses of PFS and OS showed no significant differences. Grade 3/4 adverse events were mainly hematological toxicities, including neutropenia, leukopenia, thrombocytopenia, and anemia, and they were well tolerated.When used a first-line/1.5-line treatment, i.e., for patients who had achieved CR after introduction treatment (12 cases) or who did not achieve CR but received chidamide + chemotherapy consolidation treatment (24 cases), chidamide maintenance therapy was found to maintain the effect of CR (in all 12 patients) or improve the clinical outcomes to CR/PR (partial remission) (9 out of the 24 patients). Even when used after salvage treatment, chidamide maintenance was found to achieve PR and better efficacy in 4 out the 7 patients.ConclusionsChidamide maintenance treatment achieved significantly high CR and ORR rates for PTCL patients. This therapy may improve PFS and OS with a manageable safety profile for PTCL patients. This treatment thus may benefit PTCL patients who are ineligible for or cannot afford ASCT, which is an especially severe problem in China. Further large-scale, multi-center, randomized studies are required to extensively examine the efficacy and safety of chidamide maintenance therapy in PTCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P-223: Bortezomib-Thalidomide-Dexamethasone (VTD) as salvage treatment in patients with Multiple Myeloma eligible for transplantation in the real world. Long-term follow-up

<h3>Background</h3> Peru is a middle-income country with limited options to access to novel therapies in multiple myeloma (MM). Bortezomib has been introduced as salvage treatment a few years ago. In this setting, bortezomib, thalidomide, dexamethasone (VTD) became the standard salvage treatment for transplant-eligible patients <h3>Objectives</h3> To determine the response to treatment to VTD in patients with relapsed/refractory multiple myeloma eligible to transplant. To determine progression-free survival (PFS) and overall survival (OS) to VTD. <h3>Methods</h3> We retrospectively assessed the clinical efficacy and toxicity of VTD as salvage treatment in patients with relapsed/refractory MM eligible to autologous stem cell transplantation treated at Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, between January 2014 and December 2016. The treatment consisted of bortezomib 1.3 mg/m2 subcutaneously on days 1, 4, 8 and 11; thalidomide 100mg orally on days 1 through 21; dexamethasone 40mg orally on days 1, 2, 4, 5, 8, 9, 11, 12 for three-week cycles. Antithrombotic prophylaxis was based on acetylsalicylic acid. Prophylaxis against herpes zoster infection was with acyclovir 400mg twice a day, also trimethoprim/sulfamethoxazole was given each other day. <h3>Results</h3> Sixteen patients were found to fulfill the selection criteria. The median age was 52 (39-62), fifty-six percent (n=9) were male. International Staging System III disease was present in 75%.Ig G and IgA MM were 62.5% and 12.5% respectively. For VTd regimen the median number of treatment cycles delivered was four (range 2-5), totally 62 cycles. After a median follow-up of 19 months since patients received VTd (range 6-63), the overall response rate was 81%, stringent complete response (SCR) was 18.8% (n= 3), complete response 37.5%, very good partial response 12,5%. Seven out of 16 patients (43.8%) with VTD treatment who were candidates for transplantation finally were transplanted. Median PFS was 19 months (95% CI,12-NR), for the cohort who received SCT was the median PFS was 40 m (95% CI,16-NR), and for the cohort who did not undergo SCT was 14 m (95% CI, 6 - NR), however, this difference was statistically non-significant (p = 0.10). After a median follow-up of 41 months (range 7-141) since the diagnosis of MM, the median overall survival (OS) for the entire cohort was not reach (95% CI, 41– NR). For the cohort who received ASCT the median was not reached (95% CI, 41 - NR), and for the cohort who did not received was 49 months (95% CI, 22 - NR), however this difference was statistically non-significant (p = 0.20). 3-years OS was 86.7% (95%, CI, 56.4 –96.5), the 5-year OS was 66 m (95%, CI, 31.1 – 86.2). <h3>Conclusion</h3> VTD is an effective treatment in transplant-eligible patients with multiple myeloma who have relapsed after one previous therapy including thalidomide achieving high response rates and acceptable PFS and OS.

Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network

Extensive lymphatic malformations (LMs) of the head and neck region may require tracheostomy to secure the airway. Treatment of these life-threatening LMs is usually multimodal and includes sclerotherapy and surgery, among others. Recently, systemic therapy with sirolimus has been introduced as an effective treatment for venous and lymphatic malformations; its efficacy and safety profile in patients with extensive LM requiring tracheostomy are, however, as yet not fully known. We performed a retrospective, multicenter review and identified 13 patients with an extensive LM of the head and neck region, who previously underwent placement of tracheostomy and subsequently received sirolimus treatment with the aim to improve the local respiratory situation and remove the tracheostomy. Under sirolimus therapy, tracheostomy could be reversed in 8/13 (62%) patients, a further 2/13 (15%) patients improved markedly, and removal of the tracheostomy was planned at the time of writing, while 3/13 (23%) patients showed insufficient or absent response to sirolimus, rendering tracheostomy reversal not feasible. The median duration of sirolimus treatment until removal of tracheostomy was 18 months (range, 8 months to 5.6 years). Adverse events of sirolimus therapy were common [10/13 (77%) patients], yet the majority of these were mild [9/10 (90%) patients] and only one severe adverse event was recorded, with ulceration and necrosis at a catheter insertion site. In conclusion, sirolimus can be considered an effective and safe salvage treatment in patients with extensive LM even after placement of a tracheostomy, as closure of the latter was possible in the majority of patients (62%) of our retrospective cohort. A better understanding of when to start sirolimus therapy, of the duration of treatment, and of factors allowing the prediction of treatment response will require further investigation.

Outcomes of salvage treatment in patients with recurrent oral squamous cell carcinoma.

The survival outcomes of different salvage treatments for patients with recurrent oral cancer remain unclear. A total of 556 patients with recurrent oral cancer between 2010 and 2015 were reviewed. Clinical/pathological risk factors and different salvage treatments were analyzed. The 2-year disease-free survival rates after recurrence in patients not receiving salvage operation (305 patients), receiving salvage operation with (121 patients), and without (130 patients) major pathological risk factors (margin or extranodal extension) were 5.3%, 32.4%, and 77.2%, respectively (p < 0.001). The 2-year overall survival rates were 20.3%, 58.4%, and 89.2%, respectively (p < 0.001). A late-onset recurrence, salvage radiation, and salvage operation were independent factors for good disease-free and overall survival. Salvage radiation showed survival benefits among patients not indicated for salvage operations. Salvage operation was the first choice for recurrent oral cancer. Patients who received the salvage operation without major risk factors had the best survival.

Patterns of Regional Recurrence and Salvage Treatment in Patients With Oral Cancer.

Regional failure after primary treatment for oral squamous cell carcinoma (OSCC) carries a dismal outcome. Our goal was to investigate the recurrence patterns and salvage treatment in patients with OSCC and regional failure. Retrospective chart review of all patients treated for OSCC in a university-affiliated tertiary care center during 2000-2018. Data collected from patients' medical charts included demographics, clinical and pathological features, staging, treatment modalities and outcomes. Patients with insufficient data or a follow-up of less than 2 years were excluded. Out of 266 surgically treated patients, 55 developed regional recurrence and were included in the study cohort. Forty patients received surgical salvage treatment followed by adjuvant chemo-radiotherapy (CRT). Disease specific survival and overall survival were significantly higher in surgically treated patients compared to patients who received non-surgical treatment (46.7% vs. 0%, log-rank P value < .001 and 35.3% vs. 0%, log-rank P value = .001, respectively) and in patients who recurred regionally more than 10 months following initial treatment (40.8% vs 10.7%, log-rank P value = .065). Patients with early recurrence were older (73.6 vs. 61.3 years) and had a deeper invasion of the primary tumor (10.1 vs. 7 mm). Salvage neck dissection is feasible in most cases, providing the best outcomes in patients with OSCC who fail regionally. Close follow-up during the first year after initial treatment is paramount as early recurrence carries a dismal prognosis. Specifically, elderly patients and patients with deeper primary tumor invasion should be closely monitored during the first post-operative year. 4 Laryngoscope, 132:786-792, 2022.

Bendamustine Plus Rituximab as Salvage Treatment for Patients with Relapsed or Refractory Low-grade B-cell Lymphoma and Mantle Cell Lymphoma: A Single-Center Retrospective Study.

Bendamustine plus rituximab (B-R) is an effective therapy for relapsed or refractory (r/r) low-grade B-cell lymphoma (LGBCL) and mantle cell lymphoma (MCL); however, clinical data from Japanese patients treated with B-R therapy are limited. We retrospectively evaluated the efficacy and safety of B-R therapy in 42 patients who received B-R therapy at our hospital for r/r LGBCL and MCL. All patients received intravenous (IV) ritux-imab 375 mg/m2 on day 1 and IV bendamustine 90 mg/m2 on days 2 and 3 every 28 days for up to 6 cycles. The common histologic subtypes were follicular lymphoma (n = 29, 70%), marginal zone lymphoma (n = 6, 14%), and MCL (n = 5, 12%). The overall response rate was 93%, with 62% complete response and complete response unconfirmed. The median progression-free survival (PFS) was 38 months (95% confidence interval [CI], 24.6 to not reached [NR]), and the median overall survival (OS) was 80 months (95% CI, 60.7 to NR). Patients receiving a cumulative dose of bendamustine ≥ 720 mg/m2 showed a significantly longer PFS and OS. Grade 3/4 adverse events (≥ 10%) included neutropenia (55%), lymphopenia (69%), and nausea (24%). B-R therapy was effective and well tolerated, and the cumulative dose of bendamustine was associated with a favorable outcome.

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study.

IntroductionWe aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey.Material and methodsIn this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity.ResultsNinety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B-cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2–8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% ( = 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%).ConclusionsObjective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy.

Bortezomib-Thalidomide-Dexamethasone (VTD) As Salvage Treatment in Patients with Multiple Myeloma Candidates for Transplantation in the Real World

BackgroundTreatment for Multiple Myeloma (MM) has evolved greatly, ranging from corticosteroids to monoclonal antibodies. In low-resource countries, however, the first-choice treatment is still based on cyclophosphamide-thalidomide-dexamethasone (CTD) regimen, either in patients who are candidates or non-candidates for stem cell transplantation (SCT). In Peru, a few years ago, bortezomib has been introduced as salvage treatment. Bortezomib as salvage treatment has reported 6.22 months of time to progression and combined complete and partial response rates of 38% in pivotal study. 1ObjectivesTo determine the response to treatment to VTD in patients with multiple myeloma candidates to transplant. To determine progression-free survival (PFS) to VTD. To determine the percentage of transplant patients.MethodsWe retrospectively assessed the clinical efficacy and toxicity of VTD (bortezomib 1.3mg/m2 subcutaneously on days 1, 4, 8 and 11; thalidomide 100mg orally on days 1 through 21; dexamethasone 40mg orally on days 1, 2, 4, 5, 8, 9, 11, 12 for three-week cycles), as salvage treatment in patients with relapsed/refractory MM candidate to autologous stem cell transplantation treated at Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, between January 2014 and December 2016. Patients received only one prior treatment and at least 2 cycles of VTD. SPSS program was used for data analysis. Survival outcomes were estimated by Kaplan-Meier Method.ResultsSixteen patients were found to fulfill the selection criteria. The median age was 52 (39-62), fifty-six percent (n=9) were male. International Staging System III disease was present in 75%. ECOG 1-2 was present in 94%. Ig G and IgA MM were 62.5% and 12.5% respectively; lambda light chain was present in 56.3%. 37.5% of patient had renal impairment. B2µg was >3.5mg/dL in 57% of patients. CTD was the first-line in 94%, with overall response rate (ORR) of 62.5% (complete response (CR) 6.3%, very good partial response (VGPR) 12.5%, and partial response (PR) 43.8%). For VTD regimen the median number of treatment cycles delivered was three (range 2-5), totally 59 cycles. After a median of 14 months follow-up for VTD (range 4-34), the overall response rate was 75%, stringent complete response (SCR) was 18.8% (n= 3), complete response 37.5%, very good partial response 6.3%, and partial response 12.5%. Six out of 16 patients (37.5%) with VTD treatment who were candidates for transplantation finally were transplanted. Among the causes for not undergoing transplantation, infections was 40% (20% (two) of cases were pulmonary tuberculosis, one case (10%) was herpes simplex encephalitis, one case (10%) was probable pulmonary aspergillosis), relapsed disease 40%, renal failure 10%, failure of stem cell collection 10%. Median PFS was 14 months (4-33m). 2-years PFS was 37.5%. 5-years overall survival (OS) was 55%, the median was not reached (18-110m). The most common adverse events for all patients were grade 2 peripheral neuropathy and infections (four infections described above), both in 25%, deep venous thrombosis was not reported. Three deaths was reported (18.75%) all for progression disease.ConclusionVTD is an effective treatment in transplant candidates with multiple myeloma who have relapsed after one previous therapy including thalidomide. PFS is superior to Bortezomib pivotal study in relapsed disease. Infectious diseases represent 40% of cause for not undergoing transplantation.

Hyperbaric Oxygen Therapy Versus Intratympanic Steroid for Salvage Treatment of Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

The aim of this meta-analysis is to compare the efficacy of hyperbaric oxygen therapy (HBOT) and intratympanic steroids (ITS) as salvage treatment for patients with refractory sudden sensorineural hearing loss (SSNHL). Electronic search was performed in the PubMed, Embase, Cochrane Library, CNKI, and Wan Fang databases to June 1, 2020. For each outcome measure, a forest plot was generated and a pooled relative risk (RR) or mean difference (MD) was calculated. Potential publication bias in the meta-analysis was assessed using funnel plot. The numbers of cases with hearing improvements and pure tone averages (PTA) changes after salvage treatment were entered into the R software to calculate the pooled effect of HBOT compared with ITS. When pooling the results of the studies reporting the proportion of patients with hearing improvement, a fixed-effects model was used. We calculated the RR and found no significant difference when HBOT compared with ITS (RR = 1.09, 95% confidence interval [CI]: 0.83-1.42, p = 0.55). With respect to the PTA changes, a fixed-effects model was used. The improvement in the PTA (in dB) was calculated in MD and no significant difference was found between the two groups (MD = 0.55, 95% CI: -1.76-2.86, p = 0.64). Both HBOT and ITS offer some benefits for refractory SSNHL patients, and there were no significant differences in hearing outcomes between the two modalities. Future RCTs that include large samples are needed to demonstrate superiority of one of the treatments.

Immunity to childhood vaccines following high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for germ cell tumors (GCT) with comparison to Hodgkin lymphoma (HL).

5017 Background: HDCT/ASCT represents a curative salvage treatment for patients with GCT but is rarely used for other solid tumors. Patients undergoing HDCT/ASCT for hematologic neoplasms require revaccination for their childhood immunizations. Whether this is necessary in patients with GCT is unknown. Methods: In this prospective longitudinal study, patients with GCT undergoing HDCT-ASCT from 11/2010 to 5/2018 had serologies for Measles, Mumps, Rubella, Diphtheria, Tetanus, Polio, and Varicella Zoster measured before HDCT and at 3, 6, and in a subset, 12+ months after the last HDCT with results at these timepoints compared using descriptive statistics. In addition, titer levels at ≥6 months post-transplant were matched 1:1 for age and gender with HL patients who underwent HDCT/ASCT during the same time period. Immunity was compared between cohorts using the Cochran-Mantel-Haenszel test. Results: Of 80 patients with GCT (median age 30, 84% nonseminoma), 91% received 3 sequential transplants and 68 had repeat titers at ≥6 months. Immunity at baseline was &gt;95% for Diphtheria, Tetanus and Polio and 89% for Varicella Zoster but lower for Measles (74%), Mumps (85%), and Rubella (83%) (Table). Compared to baseline, proportional immunity for all infections was similar at 3, 6, and 12 months post-transplant in the GCT population (≥6 months shown in Table). Matching resulted in 58 GCT-HL pairs. One-year immunity was numerically lower for most infections in the HL vs. GCT patients and significantly decreased for Measles and Rubella (Table). Conclusions: To our knowledge, this is the first study to assess vaccine titers following HDCT/ASCT for GCT. We demonstrate that HDCT/ASCT does not result in loss of immunity to childhood vaccines and that GCT patients retain protective titers more frequently than those with HL. However, 15-31% of GCT patients lack MMR immunity at baseline and at 1-year post-ASCT. Therefore, we recommend checking MMR titers at 1-year post-ASCT with revaccination of those lacking immunity. Titer evaluation and revaccination is not necessary for other childhood immunizations.[Table: see text]

68Ga-PSMA PET/CT for Patients with PSA Relapse after Radical Prostatectomy or External Beam Radiotherapy.

The study aimed to summarize clinical characteristics associated with Gallium-68-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA PET/CT) scans as patients were restaged for prostate-specific antigen (PSA) relapse after radical prostatectomy (RP) or external beam radiotherapy (EBRT). Our analyses included multiple cox regression analyses. The study evaluated 95 patients with rising values of PSAs after RP and after EBRT. Sixty 63% of patients had a positive 68Ga-PSMA PET/CT scan. Twelve patients (13%) had a positive site in the prostate bed, 29 patients (30%) had a positive site in the regional lymph nodes, and 19 (20%) had positive sites in distant organs. After four years follow-up, 21 patients (22%) died. Using multiple Cox regression analyses, the number of positive sites on the 68Ga-PSMA PET/CT scan significantly predicted overall survival (OS) (p = 0.0001), whereas risk score and regional locations of the positive sites were not significant in the multiple Cox regression analyses. Our study indicates that the specific findings of 68Ga-PSMA PET/CT scans are important because detailed findings of the scans predict the outcome after salvage treatment of patients with PSA relapse examined with 68Ga-PSMA PET/CT scans.

Oncological Results of Salvage Treatment in Patients With Hypopharyngeal Carcinoma

Introduction and objectiveThe aim of this study is to analyse the variables related to the feasibility of salvage surgery with radical intention in patients with a local recurrence of hypopharyngeal carcinoma, and to evaluate the oncological performance of this type of surgery. MethodsRetrospective study of 96 patients with hypopharyngeal carcinoma with local tumour recurrence. ResultOnly 27 patients (28.1%) were considered for surgical salvage treatment. The variables related to feasibility of salvage surgery were non-surgical initial treatment of the tumour and a disease-free interval greater than 6 months. All 69 patients non-candidates for salvage surgery died as a result of tumour progression in a period of less than 2.5 years. The 5-year disease-specific survival rate for the patients treated with salvage surgery was 39.5%. The only variable significantly related to disease-specific survival was the status of the resection margins. Patients with extensive tumour recurrence (rT3-T4) or with simultaneous nodal involvement had a lower survival rate, but the differences did not reach statistical significance. ConclusionOnly 28% of the patients with hypopharyngeal carcinoma with local recurrence of the tumour were eligible for salvage surgery with radical intention. The patients treated with salvage surgery had a 5-year disease-specific survival of 39.5%.

Comparison of two different intratympanic corticosteroid injection protocols as salvage treatments for idiopathic sudden sensorineural hearing loss.

We aimed to investigate the effect of interval length and total count of intratympanic steroid (ITS) injections in salvage treatment of patients with idiopathic sudden sensorineural hearing loss (ISSNHL). This retrospective case-control study included 64 patients with ISSNHL, who were treated with ITS injections as salvage therapy at a tertiary referral centre. From September 2019 to December 2020, 32 patients received up to four injections every 2-4days (revised-protocol group). These patients were 1:1 matched to patients, who received up to three injections at 1-week intervals between January 2014 and August 2019 (initial-protocol group). Hearing outcomes of the two groups were compared. Both ITS salvage treatment protocols resulted in a statistically significant hearing improvement (p < 0.05). The initial-protocol declined hearing thresholds by 12 ± 11.7dB (p < 0.001, d = 1, P = 99%). Mean hearing function was improved by 13.4 ± 19.1dB in the revised-protocol group [p < 0.001, d = 0.7, P = 98%]. A clinically significant hearing improvement (> 10dB) was seen in 18 patients (58.1%) in the initial-protocol group and in 14 patients (41.9%) in the revised-protocol group. A comparison of the hearing outcomes between protocol groups revealed no statistically significant differences (p > 0.05). These results indicate that a shorter injection interval does not lead to better hearing outcomes in ITS salvage treatment for ISSNHL. Moreover, fewer ITS injections may reduce costs, physical/mental stress of the patients and lower the risk of persistent tympanic perforations.

Effective Tacrolimus Treatment for Patients with Non-Severe Aplastic Anemia That is Refractory/Intolerant to Cyclosporine A: A Retrospective Study

BackgroundFor symptomatic non-severe aplastic anemia (NSAA) patients who cannot afford anti-thymocyte globulin (ATG) or allogeneic hematopoietic stem cell transplantation (HSCT), tacrolimus (FK) may be an option if these patients do not respond or become tolerant to cyclosporine A (CsA).MethodsWe enrolled 101 NSAA patients who were refractory or intolerant to CsA with no chance of HSCT or ATG treatment and treated these patients with tacrolimus for at least 6 months, with follow-up for at least one year.ResultsThe overall response rate (ORR) was 38.6% (complete response: 9.9%; partial response: 28.7%), and the median time to optimal response was 6 (3～10) months. Thirty-two (31.7%) cases had elevated creatinine levels. Eight (7.9%) cases had elevations in AST/ALT. A total of 25.6% (10/39) of patients relapsed at the end of follow-up. Age (P=0.0005), FK concentration (4.0~12 ng/mL, P=0.0005) and intolerance to CsA (P=0.012) were the independent risk factors for ORR. Treg cell levels pre-FK treatment were much lower than those of healthy controls (3.7±0.6% vs 6.8±0.7%, P=0.0004) but increased significantly after FK treatment (3.7±0.6% vs 7.1±0.8%, P=0.0039).ConclusionOur data suggest that tacrolimus is a salvage treatment for patients with NSAA that is refractory or intolerant to CsA.

Osteochondral Autograft Transplant as a Potential Salvage Procedure for Articular Cartilage Defects of the Lateral Compartment in Lateral Meniscus-Deficient Knees: Results From a Country With Limited Availability of Meniscal Transplant.

Background:The treatment of a meniscus-deficient knee is challenging, especially when patients are young and active and are not favorable candidates for prosthetic joint replacement.Hypothesis:We hypothesized that osteochondral autologous transplant (OAT) alone can be considered a salvage treatment for patients with cartilage damage of the lateral compartment of the knee, even with lateral meniscal deficiency, if the knee alignment is close to neutral.Study Design:Case series; Level of evidence, 4.Methods:Patients with lateral meniscal deficiency, whose femorotibial angle was 170° to 180° and who underwent OAT on the lateral compartment of the knee without concomitant realignment osteotomy, were retrospectively included in this study. The International Knee Documentation Committee (IKDC) subjective score and the Japanese Orthopaedic Association score for knee osteoarthritis (JOA knee score) were recorded. The International Cartilage Repair Society (ICRS) cartilage repair assessment was used to evaluate the repaired cartilage at second-look arthroscopy.Results:The study included 10 patients (mean ± SD age, 31.7 ± 19.7 years; 3 men and 7 women) who had ICRS grade 4 cartilage lesions (mean size, 3.5 ± 1.7 cm2); the mean follow-up was 73.8 ± 42.5 months. From preoperative assessment to final follow-up, the mean IKDC subjective score improved significantly from 53.5 ± 10.0 to 85.4 ± 10.1, and the mean JOA knee score improved significantly from 81.0 ± 8.4 to 95.6 ± 5.3 (P = .004 for both). One patient with a femorotibial angle of 170° underwent revision distal femoral osteotomy owing to prolonged symptoms and progression of the valgus deformity, and 2 other patients with femorotibial angles of 170° and 171° also exhibited progression of valgus malalignment or low clinical scores postoperatively. Patients with a favorable femorotibial angle (174°-178°) exhibited relieved symptoms and preservation of femorotibial angle alignment within 1° of change at follow-up. At second-look arthroscopy (n = 8 patients), 6 patients had an ICRS score of nearly normal or normal.Conclusion:In the study patients, for which a meniscal allograft was unavailable, the OAT procedure was able to relieve the symptoms associated with cartilage lesions, even with lateral meniscal deficiency, when the femorotibial angle alignment was close to neutral.

Stereotactic Body Radiation Therapy as A Radical or Salvage Treatment for Early-stage Hepatocellular Carcinoma: A Prospective Phase II Study

Preliminary retrospective studies have shown that stereotactic body radiation therapy (SBRT) was an alternative to the local treatment of early stage hepatocellular carcinoma (HCC) with encouraging long-term efficacy and low side effects. The aim of this study was to prospectively validate the efficacy of SBRT as radical or salvage ablative treatment for early stage HCC who were not considered for surgery or local radiofrequency ablative therapy. This single-center prospective phase 2 trial enrolled patients with HCC including 1-3 tumor lesions with total diameter less than 10 cm and Child-Pugh A and B disease, without major vascular invasion or extrahepatic metastasis. Most of patients received SBRT with 45Gy in 3 fractions (36-50Gy/2-6 fraction). The endpoints were the 1-, 4-year overall survival (OS), and progression-free survival (PFS), local control (LC), and intrahepatic control (IC) rate defined by Response Evaluation Criteria in Solid Tumors. From January 2014 to December 2016, 126 eligible patients were analyzed, including 87 patients with primary HCC underwent SBRT as radical treatment and 39 with residual/recurrent HCC after TACE as salvage treatment. 97 (77.0%) patients were Child–Pugh grade A5 and 16 (13.0%) grade A6 and 13 (10.0%) grade B7-9. The median follow-up time was 50.0 months (range, 2-70 months). The median OS and PFS were 57.0 and 18.0 months, respectively. The 1-, 4-year OS, PFS, LC and IC rate were 82.0% and 51.8%, 66.9% and 20.6%, 86.7% and 63.8%, 75.2% and 29.5%, respectively. There was no significant difference in outcome between primary and residual/recurrent groups. After SBRT, one old patient with Child-Pugh B7 died at 4 months after SBRT duo to classic radiation-induced liver disease. Treatment-related GI-bleed occurred in 1 patient who died at 9 months. 21 patients (16.6%) experienced +1 score decline in Child–Pugh, and 12 (9.5%) experienced ≥2 scores decline in Child–Pugh. SBRT as a radical or salvage treatment for patients with inoperable early stage HCC was an effective and well tolerated modality. Decline in Child–Pugh score was a most common SBRT-induced hepatic toxicity.

Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the ‘real-world’ experience?

Several molecularly targeted drugs for treating radioiodine resistant differentiated thyroid carcinomas (RAIR-DTC) have been identified. Among these, sorafenib and lenvatinib have been approved for clinical use in many countries. The present review will analyze efficacy and safety 'real-world' data (RWD) emerging after their commercialization. RWDs confirmed sorafenib and lenvatinib efficacy in terms of progression-free survival and, perhaps, overall survival improvement in patients with RAIR-DTC. Lenvatinib performance in RWDs appeared somehow lower than in randomized clinical trials (RCT), probably because the decision to start treatment in 'real life' was made when patients were in worse clinical conditions than in RCTs. Concerning safety, RWD studies corroborated RCT evidence of elevated overall and serious adverse event incidence. Notably, adverse events were manageable in most cases with appropriate treatment or dose reduction/interruption, so that the need for definitive withdrawal was limited. The suitability of multikinase inhibitors (MKI) as salvage therapy in RAIR-DTCs was also confirmed by RWD experience, at least for lenvatinib in the second-line setting. RWD analysis has corroborated RCT results in terms of MKI efficacy for both first-line and salvage treatment in patients with RAIR-DTC. The safety profiles emerging from RWDs seem to justify the caution recommended by most scientific guidelines.

HL-307: A Retrospective Analysis of Brentuximab Vedotin and Pembrolizumab Combination as Salvage Treatment for Patients with Relapsed or Refractory Hodgkin Lymphoma

Context The standard treatment for Hodgkin lymphoma (HL) patients presenting a relapsed/refractory disease is salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, with commonly used chemotherapy combinations (such as DHAP, ICE, BEGEV), 25–30% of these patients fail to achieve a complete metabolic response (CMR) and to proceed to ASCT, with consequently poor outcomes. Single agents brentuximab vedotin (BV) and pembrolizumab have shown efficacy in heavily pretreated HL patients, as reported in previous studies. Objective To describe the outcome of a series of refractory HL patients with a combination of brentuximab vedotin and pembrolizumab. Patients We retrospectively collected data of seven HL patients presenting with a high-risk multi-refractory disease (at least two prior treatments received) followed at Jules Bordet Institute between May 2019 and May 2020 and treated with a combination of BV and pembrolizumab. Patients were treated according to special insurance conditions permitting treatment reimbursement. Interventions We planned to treat patients with 3-week cycles of a combination of BV and pembrolizumab, performing an early PET-CT evaluation followed by high-dose chemotherapy and ASCT consolidation for those achieving a CMR (Deauville score ≤3). After ASCT, patients received BV as maintenance for a total of 16 administration (also including pre-ASCT cycles). Main outcome measures The rate of CMR and the percentage of patients achieving ASCT. Results We included 7 patients, 6 male and 1 female, with a mean age of 27.4 years. All patients presented with an advanced-stage disease, with a mean number of received treatments of 2.56 (range 2–3). The mean follow-up time was 7.1 months, the average received cycles of treatment were 4.2 (range 2–7). A CMR was achieved in five patients (72%), with a median time to response of two cycles. One partial response and one disease progression were also observed. Five patients proceeded to ASCT (72%) and subsequent BV maintenance, with no reported disease progressions in this group. One patient achieving a CMR after two cycles subsequently lost the response and failed to proceed to ASCT. Conclusions The BV and pembrolizumab combination seems to be effective as bridge to ASCT for high-risk multi-refractory HL patients.

HL-150: Brentuximab Vedotin and Bendamustine Combination Therapy as Salvage for Relapsed-Refractory Hodgkin Lymphoma: A Real-World Single-Center Experience

Context Despite high cure rates with standard treatment, 30% patients with Hodgkin lymphoma develop relapsed or refractory (R/R) disease. Salvage therapy followed by consolidation autologous hematopoietic cell transplantation (AHCT) is the standard of care. Brentuximab vedotin (BV) is a novel anti-CD30 monoclonal antibody-drug conjugate, and approved in R/R CD30+ lymphomas, after failure of two prior lines of treatment and in post-transplant setting. BV in combination with bendamustine (Be) has been tested in the salvage setting with promising results. [1,2,3] Objective To determine the activity and safety of combination BV-Be salvage therapy in patients with R/R classical Hodgkin lymphoma (cHL). Design Single-center, retrospective, observational study. Patients or other participants Chart review of patients diagnosed with R/R cHL who received BV-Be salvage treatment, between March 2011-December 2019. BV at 1.8 mg/kg (day 1) and Be at 90 mg/sqm (days 1, 2); q21-day cycle. Main outcome measures Response rates, toxicity, PFS, and OS calculated using the Kaplan–Meier method and log-rank test. Results 20 patients diagnosed with R/R cHL received BV+Be salvage therapy. Primary refractory disease (n=3), relapsed disease [n=17 (first relapse=2, second=10, later=05)]. 03 patients post-AHCT and 01 was post Allogeneic HCT (AlloHCT). The median number of previous treatments was 02 (01-04). The median number of BV-Be cycles was 03 (01-06). Nearly 67% doses administered as out-patient. All patients were evaluable for efficacy. The CR and OR rates were 65% and 80%, respectively. 55% of responding patients proceeded to AHCT and 27% underwent AlloHCT. Median follow-up of 16 months (5-45). Median PFS 25 months (95%CI: 23-29), and 2-year OS 70%. Significantly longer PFS and OS observed in patients attaining a major clinical response to treatment and in those who received HCT. Fourteen (70%) patients experienced severe (G > 2) toxicity which were neutropenia (70%), gastrointestinal (30%), peripheral sensory neuropathy (10%), and infection (15%). Two patients expired during treatment, one with disease progression and other with neutropenic sepsis. Conclusions BV-Be is an effective, well-tolerated salvage treatment for patients with R/R cHL as a bridge to consolidation with HCT, and can be administered as an outpatient.