Shaping Clinical Policy for Salvage Radiotherapy After Radical Prostatectomy in Prostate Cancer: Bridging the Gap Between Clinical Trials and Daily Practice.

PURPOSE AND OBJECTIVE: Salvage radiotherapy (sRT) can have similar outcomes to adjuvant radiotherapy (aRT) if administered at the earliest evidence of biochemical recurrence. RADICALS-RT was the first trial to support this hypothesis and a policy of observation after radical prostatectomy (RP) with early sRT has become the new standard of care since then. This study assessed the impact of RADICALS-RT in the clinical practice regarding the timing of sRT for prostate cancer initially treated with RP. METHODS: Data from 297 patients who underwent sRT after radical RP were retrospectively collected. Two groups were created and analyzed on the basis of the date of RADICALS-RT presentation at ESMO. After these results were released in October 2021, our institutional postoperative radiotherapy policy was revisited, and a third group was created and analyzed separately. RESULTS: Median PSA for Groups 1, 2, and 3 were 0.33, 0.27, and 0.2, respectively. Less than one-third of patients in Groups 1 and 2 had a postoperative PSA of 0.2 ng/mL or less at the time of sRT. Group 3 showed statistically significant differences in median PSA at the time of sRT compared with Groups 1 and 2. CONCLUSIONS: RADICALS-RT demonstrated a significant impact on clinical practice only after being complemented with real local evidence.

Role of Surgery in Vestibular Schwannoma following prior Stereotactic Radiosurgery.

Stereotactic radiosurgery (SRS) is widely used for treating vestibular schwannoma (VS), offering high tumour control rates, especially in small to medium-sized tumours. However, a subset of patients experiences SRS failure, requiring subsequent salvage microsurgery (MS). The primary reason for salvage surgery is continued tumour growth, but other causes include symptom progression and cystic enlargement. Salvage surgery is more challenging due to increased tumour adhesion to critical structures, resulting in higher complication rates, particularly for facial nerve preservation. Studies suggest subtotal resection may offer better outcomes than gross total resection in terms of facial nerve function, though treatment remains complex and outcomes vary.

Usefulness of Upfront Neck Dissection Before Chemoradiation Therapy for Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Locally advanced squamous cell carcinoma of the head and neck (L/A SCCHN) is typically treated with surgery or chemoradiation therapy (CRT), whereas salvage surgery is considered for residual disease post-CRT. However, salvage surgery after radiation therapy presents challenges due to tissue fibrosis. Planned neck dissection (ND) combined with CRT, as well as positron emission tomography after CRT, have been proposed strategies, but no definitive consensus has been reached. Therefore, this study aimed to investigate the utility of "upfront ND" performed prior to CRT to enhance local control and reduce complications. PATIENTS AND METHODS: We retrospectively reviewed 121 patients who underwent primary CRT for oropharyngeal, hypopharyngeal, or laryngeal cancer at Tokyo Medical University Hospital from January 2015 to September 2021. Patients without cervical lymph node metastasis or with unresectable nodes were excluded. All patients underwent pre-treatment imaging and staging. CRT consisted of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy. Selective ND or modified radical neck dissection was performed based on lymph node involvement. RESULTS: Overall, 35 patients underwent upfront ND, whereas 54 did not. The upfront ND group exhibited significantly better 2-year locoregional recurrence-free survival than the group without upfront ND (93.7% vs. 71.0%). No significant differences were noted in adverse events between groups. CONCLUSION: The findings highlight upfront ND before CRT as a viable option for locally advanced head and neck cancer, particularly beneficial in cases with extranodal extension. This approach enhances local control and may reduce the need for salvage surgery, thus improving patient outcomes.

Is extended resection for locally advanced thoracic cancer with cardiopulmonary bypass justified?

BACKGROUND: Resection of intrathoracic tumor with cardiopulmonary bypass (CPB) remains a relatively under-reported intervention in literature, and its role in managing locally advanced mediastinal and lung cancers is a topic of ongoing debate. Our aim was to review our experience and assess the role of CPB for treating locally advanced mediastinal and lung cancers. METHODS: Between 2015 and 2020, this study initially included 10 patients with primary locally advanced thoracic malignancies with apparent adjacent cardiovascular invasion demonstrated by thoracic imaging scans. Operation was performed based on a multidisciplinary tumor board consensus. Eventually, 8 patients (3 primary lung cancers and 5 mediastinal cancers) received either salvage or elective resection with CPB; two completed surgery without requiring CPB. RESULTS: Regarding the extent of adjacent structure involvement, 4 patients presented with involvement of the superior vena cava (SVC), 1 involved the right atrium (RA), 2 involved the SVC and RA, and 1 involved the SVC, the origin of main pulmonary artery, and the ascending aorta. Thirty-day mortality occurred in two of three patients receiving salvage surgery due to respiratory insufficiency. With the long-term follow-up, one patient died of recurrence 25 months postoperatively, one survived with recurrence 30 months postoperatively, and four were alive without recurrence for 35, 36, 49, and 107 months after operations. CONCLUSION: In certain patients, particularly for elective surgical candidates rather than salvage resection, CPB allows for extended resection of locally advanced thoracic cancers with acceptable perioperative safety and survival.

Immunotherapy for advanced and recurrent malignant pleural mesothelioma.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[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.

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

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