Outcomes in patients with multiple myeloma receiving salvage treatment after BCMA-specific CAR-T therapy: A retrospective analysis of LEGEND-2.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has shown profound efficacy and manageable toxicity in patients with relapsed/refractory multiple myeloma (RRMM). However, determining the best course of treatment for post-CAR-T therapy relapse remains a significant challenge. We conducted a retrospective analysis of patients from the phase I LEGEND-2 study (NCT03090659) enrolled at the Xi'an site, analysing the first salvage line of therapy and outcomes in patients with RRMM who progressed after receiving LCAR-B38M CAR-T therapy. Of 45 eligible patients, 34 (76%) had progressive disease (PD). Overall response rate (ORR) to salvage treatment was 50.0%. Median progression-free survival (PFS) after starting salvage treatment was 16.3 months. Median PFS of patients receiving proteasome inhibitor (PI)-based combination therapy was longer (28.2 months) than that of patients receiving a second BCMA CAR-T (including LCAR-B38M; 3.9 months, p = 0.0022) or chemotherapy (1.67 months, p = 0.0001). All patients with extramedullary disease at baseline (n = 11) progressed after CAR-T therapy; ORR to salvage therapy was 25.0% and median PFS was 9.7 months. In conclusion, salvage therapy in patients with PD after receiving LCAR-B38M CAR-T cells produced moderate efficacy, with better outcomes for PI-based salvage regimens.

Salvage vesiculectomy for local prostate cancer recurrence: surgical technique and early post-operative outcomes.

PURPOSE: Isolated recurrence in remnants of the seminal vesicles (SV) after treatment of primary prostate cancer (PCa) has become a more frequent entity with the widespread use of more sensitive next-generation imaging modalities. Salvage vesiculectomy is hypothesized to be a worthwhile management option in these patients. The primary goal of this study is to describe the surgical technique of this new treatment option. Secondary outcomes are peri- and post-operative complications and early oncological outcomes. METHODS: Retrospective multicenter study, including 108 patients with solitary recurrence in the SV treated between January 2009 and June 2022, was performed. Patients with local recurrences outside the SVs or with metastatic disease were excluded. Both SVs were resected using a robot-assisted or an open approach. In selected cases, a concomitant lymphadenectomy was performed. RESULTS: Overall, 31 patients (29%) reported complications, all but one grade 1 to 3 on the Clavien-Dindo Scale. A median PSA decrease of 2.07 ng/ml (IQR: 0.80-4.33, p < 0.001), translating into a median PSA reduction of 92% (IQR: 59-98%) was observed. At a median follow-up of 14 months, freedom from secondary treatment was 54%. Lymphadenectomy had a significant influence on PSA reduction (p = 0.018). CONCLUSION: Salvage vesiculectomy for PCa recurrence limited to the SV is a safe procedure with excellent PSA response and is a potential curative treatment in a subset of patients. A concomitant lymphadenectomy can best be performed in all patients that did not underwent one at primary treatment.

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Hybrid endoscopic submucosal dissection as a salvage option for difficult colorectal conventional endoscopic submucosal dissection.

BACKGROUND: When total submucosal dissection is difficult to achieve during conventional colorectal endoscopic submucosal dissection (C-ESD), the lesion can be resected by final snaring through salvage hybrid ESD (SH-ESD). This study aimed to examine the outcomes of SH-ESD and identify its indications that could achieve en bloc resection. METHODS: We recruited 1039 consecutive patients with colorectal lesions that underwent ESD at Hiroshima University Hospital between January 2015 and December 2020. C-ESD was attempted thoroughly in 924 lesions (C-ESD group, including 9 lesions in which ESD was discontinued), and SH-ESD was performed owing to some difficulties in 115 lesions (SH-ESD group). Risk factors for incomplete resection by SH-ESD and ESD discontinuation were evaluated using multivariate analysis. The outcomes were compared between cases with remaining undissected submucosa of < 20 mm in diameter in the SH-ESD and C-ESD groups, using propensity score matching. RESULTS: Multivariate analysis revealed that a procedure time > 80 min and remaining undissected submucosa ≥ 20 mm in diameter were significant risk factors for incomplete resection after SH-ESD and ESD discontinuation. By propensity score matching analysis, procedure time was significantly shorter in the SH-ESD group with remaining undissected submucosa < 20 mm in diameter than in the C-ESD group (71 min vs. 90 min, p = 0.0053), although no significant difference was found in the en bloc resection rate (94% vs. 87%, p = 0.0914). CONCLUSION: SH-ESD can be an alternative surgical method when conventional ESD is difficult to continue in cases in which the remaining undissected submucosa is < 20 mm in diameter.

The use of basic fibroblast growth factor to treat intractable Bell's palsy administered via transcanal endoscopic ear surgery.

PURPOSE: Facial nerve decompression surgery is an invasive procedure which has hitherto been the main option for patients with severe intractable Bell's palsy which is resistant to drug treatment. We have developed a new salvage treatment for such patients by using minimally invasive transcanal endoscopic ear surgery (TEES) to deliver the biological regenerative agent, basic fibroblast growth factor (bFGF), to the damaged facial nerve. MATERIALS AND METHODS: An endoscopic salvage treatment group was studied prospectively and was made up of severe intractable Bell's palsy patients who did not respond to high dose steroid treatment and had an ENoG value of 5 % or less. This surgery group was retrospectively compared to a similar control group who had received high dose steroid only. RESULTS: Complete recovery to House-Brackmann (HB) Grade I was achieved by 44.8 % of the endoscopic salvage treatment group which was significantly higher than the 21.2 % of the control group at one-year follow up. Patients with an ENoG value of 1 % to 5 % exhibited a significantly higher complete recovery rate of 71.4 % in the endoscopic salvage treatment group than the 28.6 % of the control group. In addition, no complications were observed including hearing loss. CONCLUSIONS: bFGF delivered via TEES shows considerable promise as a new salvage treatment of severe intractable Bell's palsy that is resistant to high dose steroid treatment without the risks presented by facial nerve decompression surgery.

Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Median 4-year outcomes of salvage irreversible electroporation for localized radio-recurrent prostate cancer.

OBJECTIVES: To evaluate the safety, and short to mid-term oncological and quality-of-life (QoL) outcomes of focal irreversible electroporation (IRE) for radio-recurrent prostate cancer (PCa) at a median follow-up of 4 years. PATIENTS AND METHODS: This was a single-centre series of men with biopsy-proven radio-recurrent PCa treated with IRE between December 2013 and February 2022, with a minimum follow-up of 6 months. Follow-up included magnetic resonance imaging at 6 months, and standard transperineal saturation template biopsies at 12 months. Further biopsies were guided by suspicion on serial imaging or prostate-specific antigen (PSA) levels. Validated questionnaires were used to measure functional outcomes. Significant local recurrence was defined as any International Society of Urological Pathology (ISUP) score ≥ 2 on biopsies. Progression-free survival was defined as no signs of local or systemic disease on either imaging or template biopsies, or according to the Phoenix criteria for biochemical recurrence. RESULTS: Final analysis was performed on 74 men with radio-recurrent PCa (median age 69 years, median PSA level 5.4 ng/mL, 76% ISUP score 2/3). The median (range) follow-up was 48 (27-68) months. One rectal fistula occurred, and eight patients developed urethral sloughing that resolved with transurethral resection. Among patients who returned questionnaires (30/74, 41%), 93% (28/30) had preserved urinary continence and 23% (7/30) had sustained erectile function at 12-month follow-up. Local control was achieved in 57 patients (77%), who needed no further treatment. Biopsy diagnosed 41(55%) patients received follow up template biopsies, in-field recurrences occurred in 7% (3/41), and out-field recurrences occurred in 15% of patients (6/41). The metastasis-free survival rate was 91% (67/74), with a median (interquartile range) time to metastases of 8 (5-27) months. The Kaplan-Meier estimated 5-year progression-free survival rate was 60%. CONCLUSIONS: These short- to mid-term safety, oncological and QoL outcome data endorse results from smaller series and show the ability of salvage focal IRE to safely achieve oncological control in patients with radio-recurrent PCa.

Salvage irreversible electroporation for radio-recurrent prostate cancer - the prospective FIRE trial.

OBJECTIVES: To prospectively assess the safety, functional- and oncological-outcomes of irreversible electroporation (IRE) as salvage therapy for radio-recurrent focal prostate cancer in a multicenter setting. PATIENTS AND METHODS: Men with focal recurrent PCa after external beam radiation or brachytherapy without metastatic disease on staging imaging and co-registration between mpMRI and biopsies were prospectively included in this multicenter trial. Adverse events were reported following the Clavien-Dindo classification. Validated questionnaires were used for patient-reported functional outcomes. Follow-up consisted of 3 monthly prostate specific antigen (PSA) levels, a 6-month mpMRI and standardised transperineal template mapping biopsies at 12-months. Thereafter follow-up was guided by MRI and/or PSMA-PET/CT and PSA. Local recurrence was defined as any ISUP score ≥2 on biopsies. RESULTS: 37 patients were analysed with a median (interquartile range (IQR)) follow up of 29 (22-43) months. Median age was 71 (53-83), median PSA was 3.5 ng/mL (2.7-6.1). 28 (75.5%) patients harboured intermediate risk and 9 patients (24.5%) high risk PCa. Seven patients (19%) reported self-limiting urgency, frequency, or hematuria (grade 1-2). Seven patients (19%) developed a grade 3 AE; urethral sludge requiring transurethral resection. At 12 months post treatment 93% of patients remained continent and erectile function sufficient for intercourse deteriorated from 35% to 15% (4/27). Local control was achieved in 29 patients (78%) and 27 patients (73%) were clear of local and systemic disease. Four (11%) patients had local recurrence only. Six (16%) patients developed metastatic disease with a median time to metastasis of 8 months. CONCLUSION: The FIRE trial shows that salvage IRE after failed radiation therapy for localised PCa is safe with minimal toxicity, and promising functional and oncological outcomes. Salvage IRE can offer a possible solution for notoriously difficult to manage radio recurrent prostate tumours.

OTSC Proctology clip as appropriate treatment for complicated anorectal fistula.

PURPOSE: Evaluation of the effectiveness and tolerability of the application of an OTSC (Ovesco Endoscopy AG Tuebingen, Germany) Proctology clip as an innovative strategy of anorectal fistulae closure when established treatment strategies had already failed or were not feasible. METHODS: Retrospective single-center study including consecutive patients treated between March 2014 and March 2016 with the OTSC Proctology system for anorectal fistula closure, including one rectovaginal and one rectourethral fistula. The primary outcome was the healing rate with a minimum follow up of 6 months. Healing was defined as closure of the internal fistula ostium and absence of secretion or local inflammation during follow up. RESULTS: A total of 66 fistula closures by the OTSC Proctology clip were investigated, including cryptoglandular fistulas (45/66 patients, 68%), fistulas associated with CED (19/66 patients, 29%), and other non-cryptoglandular fistulas (2/66 patients, 4%). 47% (31/66 patients) had a failed previous therapy. In that selected collective, a successful fistula closure was achieved in 29/66 cases (44%) after a median follow up time of 40 months (6-61 months). Suprasphincteric and high transsphincteric fistulas showed healing in 63% and 42% in CD associated fistulas. CONCLUSION: Fistula closure by the OTSC Proctology clip is an innovative, sphincter protecting treatment strategy in anorectal fistulas that can achieve long-term cure in complex anorecta.

Defining the optimal template of salvage lymph node dissection for unilateral pelvic nodal recurrence of prostate cancer following radical prostatectomy.

OBJECTIVES: Several retrospective studies have shown that salvage bilateral pelvic lymph node dissection (sLND) is a valid treatment option in the setting of oligorecurrent nodal prostate cancer following radical prostatectomy. Little is known about the optimal template of such sLND in patients with strictly unilateral pelvic recurrence on PET-CT imaging. In this study, we investigated whether a unilateral pelvic sLND could be sufficient in such a setting. METHODS: We retrospectively collected data of patients treated with sLND between 2010 and 2019 at the University Hospitals, Leuven. Patients were included if they developed recurrence following radical prostatectomy, characterized by ≤3 unilateral pelvic lymph node metastases on Choline or PSMA PET-CT and received a super-extended bilateral pelvic sLND as first metastasis-directed therapy. As a primary endpoint, we investigated in how many cases a unilateral sLND would have been sufficient. RESULTS: In total, 44 patients with strictly unilateral pelvic recurrence were treated with super-extended bilateral pelvic sLND. In 5 out of 44 (11%) patients, histological examination showed presence of prostate cancer in the contralateral hemi-pelvis. In the group with a single positive node on imaging prior to sLND, only 1 out of 27 (3%) patients had contralateral disease at final pathology. No one (0%) in this group subsequently developed recurrence in the contralateral hemi-pelvis following sLND. CONCLUSIONS: In conclusion, this study suggests that unilateral pelvic sLND could be sufficient in patients with a single unilateral pelvic lymph node recurrence on PET/CT imaging.

Ofatumumab with iphosphamide, etoposide and cytarabine for patients with transplantation-ineligible relapsed and refractory diffuse large B-cell lymphoma.

The efficacy of salvage treatment of diffuse large B-cell lymphoma (DLBCL) patients who relapse or progress (rrDLBCL) after initial therapy is limited. Efficacy and safety of ofatumumab with iphosphamide, etoposide and cytarabine (O-IVAC) was evaluated in a single-arm study. Dosing was modified for elderly patients. Patients received up to six cycles of treatment. The primary end-point was the overall response rate (ORR). Patients were evaluated every two cycles and then six and 12 months after treatment. Other end-points included progression-free survival (PFS), event-free survival (EFS), overall survival (OS) and safety. Seventy-seven patients received salvage treatment with O-IVAC. The average age was 56.8 years; 39% had an Eastern Cooperative Oncology Group (ECOG) performance status of at least 3; 78% had disease of Ann Arbor stage 3 or 4; 58% received one or more prior salvage therapies. The ORR for O-IVAC was 54.5%. The median duration of study follow-up was 70 months. The median PFS and EFS were 16.3 months each. The median OS was 22.7 months. Age, ECOG performance status and the number of prior therapy lines were independent predictors of survival. Treatment-related mortality was 15.5%. O-IVAC showed a high response rate in a difficult-to-treat population and is an attractive treatment to bridge to potentially curative therapies.

Outcomes of salvage radical prostatectomy after initial irreversible electroporation treatment for recurrent prostate cancer.

OBJECTIVE: To evaluate: (i) safety, (ii) feasibility, and medium-term (iii) oncological and (iv) functional outcomes of salvage radical prostatectomy (sRP) for recurrent localised prostate cancer (PCa) following initial focal therapy using irreversible electroporation (IRE). PATIENTS AND METHODS: An international, multicentre and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localised PCa after initial primary IRE treatment. Data were reported on (i) surgical complications, (ii) feasibility of sRP reported by surgeons, (iii) time interval between IRE and sRP and pathology results, and (iv) urinary continence, erectile function, and quality of life. RESULTS: In four participating centres, a total of 39 patients with a median (interquartile range [IQR]) age 64 (60-67) years were identified. No serious adverse events occurred during or following sRP and surgery was deemed feasible without difficulties. The median (IQR) time to recurrence following IRE was 14.3 (9.1-38.8) months. Pathology results showed localised disease in 21 patients (53.8%) and locally-advanced disease in 18 (46.2%). Positive surgical margins (PSMs) were observed in 10 patients (25.6%), of which six (15.4%) had significant PSMs. A persistent detectable prostate-specific antigen level was found in one case after sRP, caused by metastatic disease. One patient had a biochemical recurrence 6 months after sRP. These two cases, together with a PSM case, required additional therapy after sRP. After a median (IQR) follow-up of 17.7 (11.8-26.4) months, urinary continence and erectile function were preserved in 34 (94.4%) and 18 patients (52.9%), respectively, while quality of life remained stable. CONCLUSIONS: Salvage RP is safe and feasible for patients with recurrent localised PCa following initial IRE treatment. The medium-term oncological and functional outcomes are similar to primary RP. Strict patient selection for focal therapy and standardised follow-up is needed as some patients developed high-grade disease.

First-line salvage treatment options for germ cell tumor patients failing stage-adapted primary treatment : A comprehensive review compiled by the German Testicular Cancer Study Group.

PURPOSE: In this review, we summarize and discuss contemporary treatment standards and possible selection criteria for decision making after failure of adjuvant or first-line cisplatin-based chemotherapy for primarily localized or metastatic germ cell tumors. METHODS: This work is based on a systematic literature search conducted for the elaboration of the first German clinical practice guideline to identify prospective clinical trials and retrospective comparative studies published between Jan 2010 and Feb 2021. Study end points of interest were progression-free (PFS) and overall survival (OS), relapse rate (RR), and/or safety. RESULTS: Relapses of clinical stage I (CS I) patients irrespective of prior adjuvant treatment after orchiectomy are treated stage adapted in accordance for primary metastatic patients. Surgical approaches for sole retroperitoneal relapses are investigated in ongoing clinical trials. The appropriate salvage chemotherapy for metastatic patients progressing or relapsing after first-line cisplatin-based chemotherapy is still a matter of controversy. Conventional cisplatin-based chemotherapy is the international guideline-endorsed standard of care, but based on retrospective data high-dose chemotherapy and subsequent autologous stem cell transplantation may offer a 10-15% survival benefit for all patients. Secondary complete surgical resection of all visible residual masses irrespective of size is paramount for treatment success. CONCLUSIONS: Patients relapsing after definite treatment of locoregional disease are to be treated by stage-adapted first-line standard therapy for metastatic disease. Patients with primary advanced/metastatic disease failing one line of cisplatin-based combination chemotherapy should be referred to GCT expert centers. Dose intensity is a matter of ongoing debate, but sequential high-dose chemotherapy seems to improve patients' survival.

Splenectomy Outcomes in Relapsed or Refractory Immune Thrombocytopenia according to First-Line Intravenous Immunoglobulin Response.

OBJECTIVES: Although splenectomy has long been second-line option for immune thrombocytopenia (ITP) patients, an indicator that reliably predicts the efficacy of splenectomy is still being explored. We investigated the treatment outcomes of splenectomy as a second-line therapy for relapsed/refractory ITP according to first-line intravenous immunoglobulin (IVIG) responses. METHODS: Fifty-two adult patients treated with splenectomy as second-line therapy for ITP between 2009 and 2019 were included, and they were classified according to first-line IVIG responses (no response to IVIG: nonresponders; only transient IVIG response shorter than 4 weeks: poor responders; IVIG response for a longer period; stable responders). The efficacy of splenectomy was analyzed in the three subgroups. RESULTS: Of the 52 patients, 10 were IVIG nonresponders, 34 were poor responders, and the remaining 8 were stable responders. Response to splenectomy was observed in 50.0% of IVIG nonresponders, 94.1% of poor responders, and 100% of stable responders (p = 0.0030). Among the 45 patients who responded to splenectomy, 51.1% relapsed subsequently, and a significantly lower relapse rate was noted in the stable IVIG responders (12.5%, p = 0.0220) than in nonresponders (60.0%) and poor responders (59.4%). CONCLUSIONS: First-line IVIG response is indicated as a useful predictive factor for response to splenectomy.

Indications and outcomes of colorectal hybrid endoscopic submucosal dissection: a large multicenter 10-year study.

BACKGROUND AND AIMS: Hybrid endoscopic submucosal dissection (ESD) is a colorectal lesion resection procedure that includes both planned and salvage procedures. Previous colorectal hybrid ESD studies have involved single institutions or few operators over a short timeframe, and the size for indication has not been established. In this multicentre study, we investigated the clinical outcomes of hybrid ESD for colorectal tumors that met the 30 mm lesion size criterion. METHODS: From January 2008 to December 2018, colorectal hybrid ESD was performed for 172 lesions (diameter range, ≥ 20- < 30 mm) at Hiroshima GI Endoscopy Research Group. We compared clinicopathological characteristics and outcomes between 56 and 116 lesions in planned and salvage groups, respectively. We also compared data between 2008 and 2013 (the first period) and 2014 and 2018 (the second period) to assess operator experience. RESULTS: No significant difference was found in the complete en bloc resection rate between the planned and salvage groups (92.9% vs. 83.6%, respectively). Procedure time was shorter in the planned group (44.5 min) than in the salvage group (72.0 min, p < 0.01). The perforation rate was higher in the salvage group (21.6%) than in the planned group (0%, p < 0.01); however, the perforation rate during snaring in the salvage group was 1.8%. During the second period relative to the first period, we recorded a significantly higher complete en bloc resection rate (95.7% vs. 75.6%, respectively, p < 0.01) and experienced operator rate (75.5% vs. 53.9%, respectively, p < 0.01). Furthermore, no significant difference was found in the complete en bloc resection rate between the planned and salvage groups during the second period (100% vs. 94.4%, respectively). CONCLUSION: Colorectal hybrid ESD, especially salvage hybrid ESD performed by experienced operators, is adoptable and safe for lesions with diameters ranging from ≥ 20 to < 30 mm.

Real-world treatment patterns and oncological outcomes in early relapse and refractory disease after bacillus Calmette-Guérin failure in non-muscle-invasive bladder cancer.

OBJECTIVE: To assess real-world oncological outcomes between the radical cystectomy (RC) group and non-RC group for early relapse and refractory disease. METHODS: We retrospectively analyzed 953 patients with recurrent non-muscle-invasive bladder cancer (NMIBC) who received bacillus Calmette-Guérin (BCG) at 31 affiliated hospitals from 2000 to 2019. Patients with missing data on the timing of failure were excluded and 871 patients remained eligible, of whom 447, 357, and 67 were classified as early relapse/refractory disease, intermediate/late relapse disease, and intolerant disease, respectively. For early relapse/refractory disease, patients were divided into two salvage treatment groups: RC and non-RC. The clinicopathological variables of each group were examined using Kaplan-Meier plots and proportional Cox hazard ratios with matched score analyses to compare oncological outcomes between the two groups. RESULTS: Significantly worse progression-free survival and cancer-specific survival (CSS) were confirmed in the early relapse/refractory disease group compared to the intermediate/late relapse group. Of the 88 salvage patients in the RC group with early relapse/refractory disease, ≤pT1 was observed in 47, pT2 in 11, and ≥pT3 in 28 (two patients with unknown pT category). In early relapse/refractory disease, the RC group showed significantly high-risk tumor compared to the non-RC group. However, no significant difference was observed in CSS after matched score analyses (p = 0.45) between the RC and non-RC groups. CONCLUSIONS: This study found that the RC group showed no significant superiority compared to the non-RC group in CSS for early relapse/refractory disease in terms of first salvage therapy.

Functional and oncological outcomes of salvage transoral robotic surgery: a comparative study.

PURPOSE: Transoral robotic surgery (TORS) as a first-line therapy has been well-documented but evidence is missing regarding salvage therapy. The aim of this study is to compare the oncological and functional outcomes of TORS as a primary and salvage therapy. METHODS: This retrospective monocentric study included 74 patients operated by a single surgeon and sorted out into two groups: primary treatment (PT) or Salvage treatment (ST) in case of previous history of radiation therapy. Patients were further stratified by tumour location: larynx and pharynx (lST vs lPT and pST vs pPT). RESULTS: Forty-eight patients were included in PT group (64.9%) and 26 in ST group (35.1%). ST patients had more frequent cTis/T1 tumours (57.7% vs 29.2%, p = 0.0164) and no clinical lymph disease (3.8% vs 37.5%, p = 0.0016). Tracheostomy was more often performed in the ST group (57.7% vs 16.7%, p = 0.0003) and the lST subgroup (88.9% vs 9.1%, p < 0.0001). Gastric feeding tube placement was more frequent in the ST group (76.9% vs 33.3%, p = 0.0003), the pST subgroup (64.7% vs 15.4%, p = 0.0009) and the lST subgroup (100% vs 54.5%, p = 0.0297). We observed a trend for more postoperative complications in the ST group (69.2% vs 47.9%, p = 0.0783). The overall survival was lower in the ST group (p = 0.0004), and in the pST subgroup (p < 0.0001). The disease-free survival rate was lower in the ST group (p = 0.0001), the pST subgroup (p = 0.0002) and the lST subgroup (p = 0.0328). CONCLUSION: This study confirms that survival and functional outcomes after salvage TORS are worse than in first line surgery.

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

PURPOSE: 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). METHODS: 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 2-4 days (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. RESULTS: Both ITS salvage treatment protocols resulted in a statistically significant hearing improvement (p < 0.05). The initial-protocol declined hearing thresholds by 12 ± 11.7 dB (p < 0.001, d = 1, P = 99%). Mean hearing function was improved by 13.4 ± 19.1 dB in the revised-protocol group [p < 0.001, d = 0.7, P = 98%]. A clinically significant hearing improvement (> 10 dB) 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). CONCLUSION: 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.

Intratympanic steroid injection versus hyperbaric oxygen therapy in refractory sudden sensorineural hearing loss: a meta-analysis.

OBJECTIVE: The present meta-analysis aims to compare the efficacy of intratympanic steroid (ITS) injection and hyperbaric oxygen (HBO) therapy as salvage treatments for refractory sudden sensorineural hearing loss (SSNHL). DATA SOURCES: Comprehensive searches were performed in PubMed, EMBASE and the Cochrane Library from the date of the database inception to June 2020. All studies reporting the use of salvage ITS and HBO treatments in refractory SSNHL patients were included. Subsequently, the full texts of the eligible studies were evaluated. METHODS: The quality and bias of the studies were assessed using the Newcastle-Ottawa Scale and Cochrane's risk of bias tools for nonrandomized and randomized studies, respectively. The data were analyzed using Comprehensive Meta-Analysis software (Version 3; Biostat, Englewood, NJ). RESULTS: Three hundred and fourteen subjects in 3 observational studies and 1 randomized controlled trial met our inclusion criteria. The pooled results demonstrated that there were no significant differences in the mean posttreatment hearing gain between the ITS and HBO groups. The changes in word discrimination and hearing gain at 250, 500, 1000, 2000, 4000 and 8000 Hz were also comparable between the two salvage treatment groups. CONCLUSIONS: The pooled results demonstrated that there were no significant differences in hearing improvements between salvage ITS injection and salvage HBO therapy after failed primary systemic steroid treatment in patients with SSNHL. However, spontaneous recovery could bias the treatment outcomes, and these results should be interpreted with caution. Clinicians may choose these salvage treatments according to personal experience and treatment availability. In cases in which specialized HBO facilities are difficult to access, salvage ITS injection can be provided with comparable responses.

Efficacy and safety of second photodynamic therapy for local failure after salvage photodynamic therapy for esophageal cancer.

OBJECTIVES: Photodynamic therapy (PDT) is an optional salvage treatment for local failure of esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy; however, local failure after PDT sometimes occurs. In such cases, second PDT is sometimes attempted, but its outcomes remain unclear. This study aimed to evaluate the efficacy and safety of second PDT. METHODS: We enrolled patients who underwent PDT for local failure of ESCC after chemoradiotherapy. We retrospectively evaluated local-complete response (L-CR) rate and clinical outcomes of first and second PDT. The indications for PDT were lesions within the muscle layer, <3 cm in size, and <3/4 of the esophageal circumference; not suitable for salvage surgery; and absence of metastasis. Second PDT was avoided when lesions were apparently refractory to first PDT, e.g. persistence of submucosal tumor-like protruded component or rapid regrowth of tumor at the ulceration after first PDT. L-CR was defined as endoscopic disappearance of tumor and post-PDT ulcer and absence of cancer cells histologically. RESULTS: Among 82 patients who underwent first PDT, 27 underwent second PDT. The L-CR rates with first and second PDT were 63.0% and 40.7%, respectively. The 2-year overall survival rates after second PDT in patients with L-CR and local-nonCR were 79.5% and 40.5%, respectively. Five of 11 patients with L-CR survived without any recurrence. No grade ≥3 adverse events occurred. CONCLUSIONS: Second PDT demonstrated excellent safety and acceptable efficacy; therefore, it could be a useful treatment for local failure after first PDT.