Failure-free Survival Rates Research Articles

QUALITY OF LIFE IN PATIENTS WITH SKULL BASE CHORDOMA AND CHONDROSARCOMA TREATED WITH PENCIL BEAM SCANNING PROTON THERAPY

Abstract AIMS The objective of this study is to assess the health-related quality of life (HRQoL) of skull base chor- doma/chondrosarcoma patients treated with proton therapy (PT). METHOD Seventy seven adult patients with skull base chordoma/chondrosarcoma completed the EORTC-QLQ-C30 and the BN20 Questionnaires prior to PT, Clinical outcome and therapy related acute and late toxicities have been recorded in course of the follow-up. The data was collected, categorized and analyzed, comparing the posttreatment scores to each patient’s baseline. In order to assess the impact of the clinical outcome and toxicities on HRQoL, the scores were correlated to collected clinical outcomes. RESULTS Median follow-up was 51 months. 6-year overall survival and local failure free survival rates observed were 85.1% and 80.3%. One G3 brain radiation necrosis and one G4 optic nerve disorder were documented during FU. HRQL deteriorated after the completion of proton therapy and returned to baseline values one year thereafter. After the second and third year, we observed further decrease in HRQL. This development was unrelated to tumor relapse. However, comparing the whole cohort over time, global QoL did not change substantially over the course of follow-up. GTR was correlated to better QoL at all time points. Disease progression was correlated with overall worse QoL and higher neurological symptoms already before PT, and higher symptom burden one year thereafter. Males had better QoL before and one year after PT than females. CONCLUSION PT achieves an excellent local and distant control in patients with skull base chordoma/chondrosarcoma. The HRQoL in these patients decreases immediately after the treatment completion, returns to the baseline from one year thereafter, and tends to deteriorate again with longer FU. The observed changes in global HRQoL were however not substantial in the whole cohort over the course of follow-up.

Involved-field high-dose chemoradiotherapy with respiratory motion management for esophageal squamous cell carcinoma.

We investigated the clinical outcomes of involved-field high-dose (≥66 Gy) chemoradiotherapy (CRT) combined with respiratory motion management for esophageal squamous cell carcinoma (ESCC). Patients who underwent definitive CRT for histologically confirmed ESCC in our department between 2012 and 2018 were retrospectively analyzed. Respiratory motion management strategies included breath-holding (63%) and mask immobilization (29%) based on individual measurements of respiratory tumor motion using radiographic fluoroscopy with endoscopically placed clip markers as landmarks. We evaluated patient characteristics, treatment efficacy, failure patterns, and toxicities. We enrolled 35 patients with a prescribed dose of 66-70 Gy in 33-35 fractions. The overall response rate within 6 months post-CRT was 94.3%; the median follow-up period for survivors was 43 months. The 2-year overall survival (OS), progression-free survival, and locoregional failure-free survival rates were 51.4%, 42.9%, and 42.9%, respectively. A significant difference in OS was observed between patients with and without esophageal fistulas after CRT (p = 0.002, log-rank test). Disease failure occurred in 16 patients (45.7%), including one (2.9%) with out-of-field regional nodal failure. Major grade 3 or higher toxicities included decreased white blood cell count (48.6%), neutrophil count (34.3%), and esophageal stenosis (31.4%). No grade 3 or higher cardiopulmonary toxicities were observed. Bronchial/tracheal tumor compression and a higher radiotherapy dose (70 Gy) were significantly correlated with esophageal fistulas. Involved-field high-dose CRT with respiratory motion management may be a feasible treatment option for ESCC. However, a comprehensive assessment of esophageal fistula risk is required to identify suitable candidates.

Results of the JRS-I LRA0401 and LRB0402 Japan Rhabdomyosarcoma Study Group trials for low-risk embryonal rhabdomyosarcoma.

Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4g/m2. However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6g/m2 and 17.6g/m2, respectively, without decreasing the FFS rates. Subgroup-A patients received eight cycles (24weeks) of vincristine, actinomycin D, and 1.2g/m2/cycle cyclophosphamide. Subgroup-B patients received eight cycles (24weeks) of vincristine, actinomycin D, and 2.2g/m2/cycle cyclophosphamide, followed by six cycles (24weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy. In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48-96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59-97) and 94% (95% CI, 63-99), respectively. There were no unexpected grade 4 toxicities and no deaths. Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS.

Clinical analysis on the impact of pretransplant iron overload on allogeneic hematopoietic stem cell transplantation for patients with acquired severe aplastic anemia in pediatric

This study aimed to investigate the effect of iron overload on the transplant outcomes of pediatric patients with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on the clinical data of 74 children with SAA who received allo-HSCT at the Hematology Department of Wuhan Children's Hospital between January 2018 and August 2022. Children with iron overload (serum ferritin >1 000 μg/L) before transplantation had a longer disease course, received more red blood cell transfusions, and had a higher number of CD34(+) cells infused. Moreover, iron overload significantly delayed the reconstitution of regulatory T cells after transplantation, increasing the incidence of hemorrhagic cystitis and grade Ⅲ-Ⅳ acute graft-versus-host disease after transplantation. However, iron overload did not significantly affect the overall survival and failure-free survival rates of the children.

Structure-specific rigid dose accumulation dosimetric analysis of ablative stereotactic MRI-guided adaptive radiation therapy in ultracentral lung lesions.

Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions. We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021. Patients had a median distance from the proximal bronchial tree (PBT) of 0.38 cm. Tumors were most often lung primary (64.3%) and HILUS group A (85.7%). A structure-specific rigid registration approach was used for cumulative dose analysis. Kaplan-Meier log-rank analysis was used for clinical outcome data and the Wilcoxon Signed Rank test was used for dosimetric data. Here we show that SMART dosimetric improvements in favor of delivered plans over predicted non-adapted plans for PBT, with improvements in proximal bronchial tree DMax of 5.7 Gy (p = 0.002) and gross tumor 100% prescription coverage of 7.3% (p = 0.002). The mean estimated follow-up is 17.2 months and 2-year local control and local failure free survival rates are 92.9% and 85.7%, respectively. There are no grade ≥ 3 toxicities. SMART has dosimetric advantages and excellent clinical outcomes for ultracentral lung tumors. Daily plan adaptation reliably improves target coverage while simultaneously reducing doses to the proximal airways. These results further characterize the therapeutic window improvements for SMART. Structure-specific rigid dose accumulation dosimetric analysis provides insights that elucidate the dosimetric advantages of SMART more so than per fractional analysis alone.

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study

Background and PurposeTo investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC).MethodsA total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated.ResultsThe median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively.ConclusionsPatients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

The long-term outcomes and safety of severe aplastic anemia treated with porcine antilymphocyte globulin plus cyclosporine, with or without thrombopoietin receptor agonists: a double-center retrospective study

ABSTRACT Background Porcine antilymphocyte globulin (p-ALG) combined with cyclosporine (CsA) has been commonly used for severe aplastic anemia (SAA) patients, but few studies on the combination of p-ALG and thrombopoietin receptor agonist (TPO-RA). Research design and methods We retrospectively analyzed the data of 85 people with diagnosed SAA who underwent p-ALG plus CsA, with or without TPO-RA from 2014 to 2023. Results The overall response rates were 55.3% and 65.9% at 3 and 6 months, and the TPO-RA group were 66.7% and 72.3% at 3 and 6 months, without TPO-RA group were 27.8% and 55.6%. In multivariate analysis, baseline platelet count of > 10 × 109/L was a simple predictor of favorable response at 6 months (p = 0.015). The median follow-up time for all patients was 39 months (range 0.4 ~ 104), the 5-year overall survival (OS) rate was 90.6% [95% CI = 82.1–95.2%], and the failure-free survival (FFS) rate was 68.9% [95% CI = 56.6–78.4%]. Having hematologic responses in 6 months was an independent positive predictor for FFS (p = 0.000). Twelve patients (14.1%) suffered from serum sickness, and 9.5% of patients had mild hepatic impairment. Conclusions p-ALG along with CsA is an effective choice for patients with SAA. p-ALG combined with TPO-RA may contribute to the early restoration of hematopoiesis.

The influence of Gleason score ≤ 6 histology on the outcome of high-risk localized prostate cancer after modern radiotherapy

We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2–177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

Outcome After Modern Proton Beam Therapy in Childhood Craniopharyngioma: Results of the Prospective Registry Study KiProReg

BackgroundCraniopharyngiomas (CPs) are rare tumours of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. Aim of this study was to analyse survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs. Patients and methodsWithin the prospective XXXX study (XXXX), data of 74 childhood patients with CP, receiving PBT between 08/2013-06/2022 were eligible. Late toxicities were analysed according to the grading system of CTCAE 4.0. Results: Median follow-up (FU) since first diagnosis was 4.3 years (range, 0.8-14.7). 75.7% of patients received PBT at time of disease progression or recurrence, whereas 24.3% as part of their primary therapy (definitive or adjuvant). Predominantly (85.1%), pencil beam scanning technique was used. Median total dose and initial tumour volume were 5400 cGyRBE (relative biological effectiveness) and 17.64 cm³ (range, 3.07-300.59), respectively. The estimated (±SE) 3-year overall survival, progression-free and cystic failure-free survival rate after PBT were 98.2% (±1.7), 94.7% (±3.0), and 76.8% (±5.4), respectively. All local failures (n=3) were in-field relapses necessitating intervention and occurred exclusively in patients receiving PBT at progression or recurrence. Early cystic enlargements after PBT were typically asymptomatic and self-limiting. Fatigue, headaches, vision disorders, obesity and endocrinopathies were the predominant late toxicities. No high grade (≥3) new-onset visual impairment or cognitive deterioration occurred compared to baseline. The presence of cognitive impairments at the end of FU correlated with size of the planning target volume (p=0.034), Dmean dose to the temporal lobes (p=0.032,p=0.045) and the number of surgical interventions prior to PBT (p=0.029). Conclusions: Our findings demonstrate favourable local control rates using modern PBT with acceptable late toxicities. Cyst growth within 12 month after radiotherapy is typically not associated with tumour progression. Longer FU has to be awaited to confirm results.

Revolutionizing localized prostate cancer treatment: Stereotactic radiotherapy "Moroccan experience".

Prostate cancer is the most common urological cancer, and its incidence is increasing. Radical prostatectomy and radiotherapy are theprimary treatments for localized forms. Stereotactic Body RadioTherapy (SBRT), a new and innovative therapy, has been validated for some cancer localizations but not yet for localized prostate cancer. Our study aims to report the efficacy and tolerance results of SBRT for localized prostate cancer. This is a retrospective study of 27 patients with localized prostate cancer (CaP) who were treated with SBRT in our department from 2017 to 2021 using transponders for tumor tracking. The dose was 36.25 Gy delivered in five fractions of 7.25 Gy. The delineation and doses of organs at risk were determined based on the recommendations of the SFRO and the TG101 report of medical physics. All patients were treated using a latest-generation linear accelerator (True Beam STXÒ). Acute toxicities were observed in 33.3% of cases, with 22.2% grade 1 or 2 genitourinary (GU) and no grade 3 while 11.1% gastrointestinal (GI) toxicities were reported as grade 1-2 (7.4%) and one case grade 3 (3.7%). Late grade 1 or 2 GU toxicity was observed in 14.84% of cases, with no reports of late GI toxicity. After a 26-month follow-up period, the biochemical failure-free survival rate was 92.6%. The results of our study are consistent with the existing literature and support the safety and effectiveness of SBRT as a treatment option for localized prostate cancer (CaP). In the United States, both ASTRO and the NCCN recognize SBRT as a valid treatment option for localized CaP. Ongoing phase III trials are being conducted to further substantiate these long-term results and to establish SBRT as the future standard of care for localized CaP.

A Systematic Review and Meta-Analysis of the Cancer.

Prostate cancer is the second- leading cause of cancer death among men. We aimed to evaluate high-intensity focused ultrasound (HIFU), open radical prostatectomy (ORP), robot-assisted radical prostatectomy (RARP), and external beam radiation therapy (RT) in the treatment of localized low- and intermediate-risk prostate cancer. We searched bibliographic databases for case-control, cohort, and randomized controlled studies. We used MeSH subject headings and free text terms for prostate cancer, HIFU, ORP, RARP, RT, failure-free survival (FFS), biochemical disease-free survival (BDFS), urinary incontinence (UI), and erectile dysfunction (ED). Fourteen studies were included in the review, for a total of 34 927 participants. Among the 8 studies of HIFU as the primary treatment of localized low- and intermediate- risk prostate cancer, 4 studies reported 5-year FFS rates ranging from 67.8% to 97.8%, 3 studies reported 5-year BDFS ranging from 58% to 85.4%, 5 studies reported 1-year UI rates ranging from 0% to 6%, and 4 studies reported 1-year ED rates ranging from 11.4% to 38.7%. Furthermore, our search revealed a 5-year FFS benefit favoring ORP compared to RT, a 1-year UI rate favoring ORP compared to RARP, and a 1-year ED rate favoring ORP compared to RARP. Our systematic review and meta-analysis revealed lack of studies with active comparators comparing HIFU to standard of care (ORP, RARP, or RT) in primary treatment of localized low- and intermediate-risk prostate cancer. Open radical prostatectomy has favorable efficacy outcomes compared to RT, while RARP has beneficial functional outcomes compared to ORP, respectively.

Long-term clinical outcomes and prognosis after definitive radiotherapy for patients with cervical esophageal squamous cell carcinoma: a single-institution retrospective study.

Definitive radiotherapy has become a more common treatment for cervical esophageal squamous cell carcinoma (CESCC), but data about long-term clinical outcomes is still relatively sparse. The purpose of this study was to describe long-term clinical outcomes after definitive radiotherapy for CESCC, and identify the prognostic factors influencing these outcomes. We retrospectively analyzed all patients who received definitive radiotherapy for CESCC at our institution between 2006 and 2014. The overall survival (OS) rate, locoregional failure-free survival (LRFFS) rate, and toxicities were retrospectively evaluated during long-term follow-up. Univariate and multivariate analyses were performed to identify prognostic factors. A total of 120 patients were included for analysis. The median prescribed radiation dose for the gross tumor and metastatic lymph nodes was 60 Gy. Elective nodal irradiation (ENI) was performed on 99 patients (83%); 90 patients (75%) received concurrent chemotherapy. The OS rates were 22.7% at 5 years and 14.9% at 8 years. The LRFFS rates at 3, 5, and 8 years were 27.5%, 21.7%, and 15.0%, respectively. The univariate analysis suggested that N classification and non-regional lymph node metastasis (M1Lym) status were independent risk factors for overall survival (P<0.01). A dose of more than 60 Gy didn't have a statistically significant influence in the multivariate analysis, although a total dose of more than 60 Gy was associated with improved survival in the univariate analysis. Concurrent chemotherapy was not associated with OS or LRFFS time in the univariate or multivariate analysis. A total of 74 patients (61.7%) experienced locoregional treatment failure. The most commonly documented acute toxicities were grade 1 and grade 2 toxicities in 61 patients (50.8%). There were 2 patients diagnosed with hypothyroidism as a late toxicity event. Definitive radiotherapy is a reasonable curative treatment option with laryngopharyngeal preservation for CESCC patients. Radical treatments for lymph node metastases may improve the OS and LRFFS times. Monitoring for thyroid function may be warranted during long-term follow-up.

New Aplastic Anemia Preconditioned with Fludarabine, Thiotepa, Cyclophosphamide, and Anti-Thymocyte Globulin

Aplastic anemia (AA) is one of life-threatening hematological disorder that can be cured by hematopoietic stem cell transplantation. When the absence of a matched sibling donor, haploidentical stem cell transplantation (haplo-HSCT) becomes an alternative choice for AA patients. We used a prospective study aimed to confirm the feasibility of Thiotepa-based modified post-transplantation cyclophosphamide (PTCY) strategy in haplo-HSCT for AA patients. We analyzed the outcomes of 15 patients who had undergone haplo-HSCT between October 2021-May 2023 in our clinical center. The modified condition regimen consisted of anti-thymoglobulin/antilymphocyte globulin, fludarabine, thiotepa, busulfan and modified low and high-dose cyclophosphamide, mycophenolate mofetil (MMF) and tacrolimus (FK-506)/cyclosporin (CsA) were administered as graft versus host disease (GVHD) prophylaxis after transplantation. The median follow-up time was 267 (range 97-532) days. All 15 patients were successfully implanted (100%), the median times for neutrophil and platelet engraftment were 14 (range 12-19) days and 12 (range 8-25) days, respectively. But one patient developed secondary graft failure because of infected with COVID-19、cytomegalovirus and H1N1. Fortunately, she subsequently underwent a successful secondary haplo-HSCT. The most common regimen-related toxicity was canker sore, hemorrhagic cystitis occurred in 3 patients during transplantation. The cumulative incidence of grade Ⅰ-Ⅱ aGVHD and cGVHD were 13.3% and 6.7% respectively, whereas the incidence of grade Ⅲ-Ⅳ aGVHD was not found so far. All 15 patients are alive, with a failure-free survival rate of 100% and GVHD relapse-free survival rate of 100%. The efficacy evaluation of haplo-HSCT, 14 patients achieved CR and 1 patient achieved PR. Because of 7 patients received the prevention strategy of Letermovir since August 2022, the reactivation rate of cytomegalovirus (CMV) was only 20% and 60% of Epstein-Barr virus (EBV) reactivation, but the CMV diseases and post-transplantation lymphoproliferative disorder (PTLD) were rare. Our study using Thiotepa-based modified haplo-HSCT demonstrated an encouraging result with prolonged survival and reduced complications for aplastic anemia patients.

Efficacy of Radiomics in Predicting Oncologic Outcome of Liver-Directed Combined Radiotherapy in Locally Advanced Hepatocellular Carcinoma.

We investigated whether radiomic features extracted from three-phase dynamic contrast-enhanced computed tomography (CECT) can be used to predict clinical outcomes, including objective treatment response (OR) and in-field failure-free survival rate (IFFR), in patients with hepatocellular carcinoma (HCC) who received liver-directed combined radiotherapy (LD-CRT). We included 409 patients, and they were randomly divided into training (n = 307) and validation (n = 102) cohorts. For radiomics models, we extracted 116 radiomic features from the region of interest on the CECT images. Significant clinical prognostic factors are identified to predict the OR and IFFR in the clinical models. We developed clinical models, radiomics models, and a combination of both features (CCR model). Among the radiomic models evaluated for OR, the OR-PVP-Peri-1cm model showed favorable predictive performance with an area under the curve (AUC) of 0.647. The clinical model showed an AUC of 0.729, whereas the CCR model showed better performance (AUC 0.759). For the IFFR, the IFFR-PVP-Peri-1cm model showed an AUC of 0.673, clinical model showed 0.687, and the CCR model showed 0.736. We also developed and validated a prognostic nomogram based on CCR models. In predicting the OR and IFFR in patients with HCC undergoing LD-CRT, CCR models performed better than clinical and radiomics models. Moreover, the constructed nomograms based on these models may provide valuable information on the prognosis of these patients.

Propensity Score Matching Analysis Comparing the Efficacy and Steroid Tapering Benefit of Extracorporeal Photopheresis to Best Available Therapy in Third-Line or Beyond Treatment for Chronic GvHD

Graft-versus host disease (GVHD) is one of the major limitations to allogeneic hematopoietic stem cell transplantation (HCT). Although corticosteroids with calcineurin inhibitors are established first line-therapy for chronic graft-versus-host disease (cGVHD), approximately one-half of cGVHD patients are refractory to corticosteroid therapy. The goal of the present study was to compare treatment outcomes of patients treated with extracorporeal photopheresis (ECP) and best available therapy (BAT) as third-line or beyond treatment for cGVHD. Using propensity score matching (PSM), treatment outcomes were compared between ECP-treated patients (n=74) and a historical cohort of cGVHD patients treated with BAT (n=132). By adjusting for unbalanced risk factors between the groups, including GVHD severity at the start of therapy, acute GVHD history, and baseline corticosteroid dose, 62 patients were balanced and selected for PSM. In the PSM cohort, the ECP group showed a 12-month failure-free survival (FFS) rate of 70.1% versus 32.5% in the BAT group (P < .0001; hazard rate [HR], .214), and 93.1% 12 months' overall survival (OS) rate of 93.1% versus 68.1% in the BAT group (P=.0249; HR, .3811); multivariate analysis confirmed ECP's superior FFS and OS compared with BAT. Generalized linear model analysis showed faster tapering of corticosteroids and higher rates of prednisone discontinuation in the ECP versus BAT PSM groups in the first 6 months. The ECP group also had a higher percentage of prednisone discontinuation, by 6% at month 0, by 14.9% at month 3, and by 22.5% at month 6. The current study demonstrates superior FFS, OS, and steroid tapering efficacy for ECP compared with BAT as third-line therapy or beyond in cGVHD patients.

Long-Term Outcomes Following Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy in High-Risk Prostate Cancer: Update From the FASTR/FASTR-2 Trials

There is limited data on the long-term outcomes of ultrahypofractionated radiation therapy in high-risk prostate cancer. The FASTR and FASTR-2 trials were designed to assess the tolerability of stereotactic ablative radiation therapy (SABR) in this context. Herein, the long-term results are reported. Eligible patients had localized high-risk prostate cancer and were either ≥70 years old, had a score of ≥3 on the Vulnerable Elderly Scale, or declined standard therapy. Nineteen patients from a single institution were enrolled on FASTR between 2011 and 2015. They received 40 Gy to the prostate and 25 Gy to the pelvic lymph nodes in 5 weekly fractions, with 12 months of androgen deprivation therapy (ADT). Thirty patients from the same institution were enrolled on FASTR-2 between 2015 and 2017. They received 35 Gy to the prostate alone in 5 weekly fractions, with 18 months of ADT. Updated toxicity and outcomes were assessed retrospectively. Kaplan-Meier estimates were calculated for biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival, and overall survival. Forty-four patients were eligible for analysis, 16 from FASTR and 28 from FASTR-2. Thirty-four patients (77%) were >70 years old. High-risk features included Gleason score ≥8 (n=20, 46%), T3-T4 disease (n=12, 27%), and baseline prostate-specific antigen > 20 (n=22, 50%). Median follow-up was 6.4 years. The 5-year cumulative incidence of late grade ≥3 genitourinary/gastrointestinal toxicity was 32% in FASTR and 11% in FASTR-2. At 5 years, the combined rates of biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival, and overall survival were 72%, 90%, 92%, and 83%, respectively. SABR can be safely delivered in high-risk prostate cancer by optimizing technical delivery, particularly with adherence to strict dose constraints for organs at risk. The clinical outcomes in FASTR and FASTR-2 were largely comparable to more standard fractionation schemes plus ADT, but further modifications may improve disease control. Larger randomized trials are necessary to better understand the efficacy and tolerability of this approach.

Long-Term Outcomes Following Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy in High-Risk Prostate Cancer: Update from the FASTR/FASTR-2 Trials.

There has been emerging interest in the role of ultra-hypofractionated radiotherapy for high-risk prostate cancer, especially given its low α/β ratio. However, there is limited data on the long-term outcomes of this treatment strategy. The FASTR and FASTR-2 clinical trials were designed to assess the tolerability of stereotactic ablative body radiotherapy (SABR) in high-risk prostate cancer. FASTR was discontinued early due to unacceptable acute toxicity, whereas the acute toxicities in FASTR-2 were minimal. Herein, the long-term results from these trials are reported. Eligible patients had at least 1 high-risk feature as per the National Comprehensive Cancer Network criteria for high-risk prostate cancer, no evidence of metastatic disease, and either a score of 3+ on the Vulnerable Elderly Scale or declined standard therapy. A total of 19 patients from a single institution were enrolled on FASTR between 2011 and 2015. They received 40 Gy to the prostate and 25 Gy to the pelvic lymph nodes in 5 fractions delivered once weekly for 5 weeks, along with 1 year of androgen deprivation therapy (ADT). The excessive acute toxicity in FASTR prompted several modifications in FASTR-2, including the omission of nodal irradiation. A total of 30 patients from the same institution were enrolled on FASTR-2 between 2015 and 2017. They received 35 Gy to the prostate alone in 5 fractions delivered once weekly for 5 weeks, along with 18 months of ADT. A total of 44 patients were eligible for analysis, 16 from FASTR and 28 from FASTR-2. Most patients were >70 years old (77%). High-risk features included Gleason score ≥8 (46%), T3-T4 disease (27%) and baseline PSA >20 (50%). With a median follow-up of 6.4 years, the cumulative incidence of grade ≥3 genitourinary/gastrointestinal toxicity was 50% among FASTR patients and 7% among FASTR-2 patients. At 5 years, the combined rates of biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival and overall survival were 72%, 90%, 92% and 83%, respectively. A total of 12 patients (27%) required further treatment. No significant differences in clinical outcomes were noted between the FASTR and FASTR-2 cohorts. SABR for high-risk prostate cancer is an attractive option for reducing treatment burden. Clinical outcomes and toxicity with the FASTR-2 protocol were comparable to conventionally-fractionated radiotherapy plus ADT. Larger prospective, randomized trials exploring the role of SABR with ADT in high-risk disease are necessary to better understand the efficacy and tolerability of this approach.

Comparison of Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide versus Umbilical Cord Blood Transplantation in Adult Patients with Aplastic Anemia

Aplastic anemia patients who are refractory to immunosuppressive therapy or with very low neutrophil counts require allogeneic hematopoietic stem cell transplantation (HSCT). Umbilical cord blood transplantation (UCBT) has been a treatment option when an HLA-matched donor is not available, and HSCT from a related haploidentical donor using post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis (PTCy-haplo) recently became another important approach. We aimed to compare the outcomes of PTCy-haplo and UCBT in adult patients with aplastic anemia to identify more effective and safer approaches for alternative donor transplantation. Data in a nationwide registry were analyzed retrospectively to assess the outcomes of aplastic anemia patients age ≥16 years who underwent PTCy-haplo or UCBT as their first HSCT between 2016 and 2020. The primary endpoint was 1-year overall survival (OS) after HSCT. Secondary endpoints included 1-year failure-free survival (FFS), neutrophil and platelet engraftment, and acute and chronic GVHD. Eighty-three patients who underwent PTCy-haplo (n=24) or UCBT (n=59) were eligible. The 1-year OS rate was 78.5% (95% confidence interval [CI], 55.7% to 90.5%) in the PTCy-haplo group and 77.5% (95% CI, 64.5% to 86.3%; P=.895) in the UCBT group. The 1-year FFS rate was 78.7% (95% CI, 56.1% to 90.6%) in the PTCy-haplo group and 62.2% (95% CI, 48.5% to 73.3%; P=.212) in the UCBT group. Among patients age <40 years, the PTCy-haplo group had a significantly higher FFS rate (92.9% [95% CI, 59.1% to 99.0%]) vs 63.9% [95% CI, 43.2% to 78.7%]; P=.047). Neutrophil engraftment and platelet engraftment rates were significantly higher in the PTCy-haplo group compared with the UCBT group: 95.8% (95% CI, 73.9% to 99.4%) vs 78.0% (95% CI, 65.1% to 86.6%, P < .001) and 83.3% (95% CI, 61.5% to 93.4%) vs 72.9% (95% CI, 59.6% to 82.4%; P=.025). No significant difference was observed in the cumulative incidence of grade II-IV acute GVHD and chronic GVHD between the 2 groups. Aplastic anemia patients achieved significantly higher neutrophil and platelet engraftment rates with PTCy-haplo than with UCBT. OS and the incidences of acute and chronic GVHD were similar between the 2 groups. In patients age <40 years, the FFS rate was higher in the PTCy-haplo group. PTCy-haplo is promising for alternative donor transplantation in adult patients with aplastic anemia.

Single centre retrospective analysis of extracorporeal photopheresis (ECP) therapy in patients heavily pre-treated for chronic graft-versus-host disease (cGvHD) with steroid failure

BackgroundExtracorporeal photopheresis (ECP) is recommended as a second- or later-line therapy for chronic GvHD (cGvHD). Benefits include reasonable response with avoidance of intense systemic immunosuppression, which can translate into lowering the risk of systemic toxicity and opportunistic infection. MethodsWe evaluated 75 patients treated with ECP for cGvHD from 2007 to 2021 at Princess Margaret Cancer Centre, and analyzed overall response rate (ORR) and clinical benefit (CB) at 3, 6 and 12 months plus other long-term treatment outcomes. ResultsWith a median follow-up of 72 months, a gradual increase in ORR was noted over time: 21% (16 out of 75 patients), 57% (36/63) and 70% (32/46) at month 3, 6 and 12, respectively. Gradual increase in CB was also observed over time with CB rate of 23% (17/75), 62% (39/63), and 76% (35/46) at months 3, 6 and 12, respectively. A total of 27 failures (36%) were noted, due to: 1) ECP resistance requiring switch to other therapy (n = 14, 19%), 2) non-relapse mortality (n = 10, 13%), 3) relapse of primary disease (n = 1, 1%) or 4) ECP procedure-related complication (n = 1, 1%, line infection), with 20 deaths (27%) observed. Failure-free survival (FFS) and overall survival (OS) rates were 68.3% and 85.9% at 12 months, respectively. After starting ECP, the proportions of patients who completely discontinued steroids were 17%, 32%, and 64% at months 3, 6 and 12, respectively. ConclusionECP is an effective treatment option for heavily pre-treated cGvHD patients.

Long-term outcomes of whole-pelvis radiation therapy using volumetric modulated arc therapy for high-risk prostate cancer†.

This study investigated the outcomes of whole-pelvis radiation therapy (WPRT) using volumetric modulated arc therapy (VMAT) for high-risk prostate cancer. We retrospectively analysed 112 patients with high-risk prostate cancer who started WPRT at our hospital between August 2011 and August 2015. The prescribed dose was 78Gy in 39 fractions to the prostate and 46.8Gy in 26 fractions to the pelvic lymph node (LN) area. All patients received long-term androgen deprivation therapy. We evaluated late gastrointestinal (GI) and genitourinary (GU) toxicities using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period for censored cases was 97 (interquartile range [IQR] = 85-108) months. The median age was 72 (IQR = 67-75) years. The high-risk and very-high-risk groups included 41 (36.6%) and 71 patients (63.4%), respectively. The median risk of LN invasion calculated by the Roach formula was 36.9 (IQR = 26.6-56.3) %. The 8-year overall survival, biochemical failure-free survival, disease-free survival and distant metastasis-free survival rates were 88.4, 91.9, 83.8 and 98.0%, respectively. Only one patient experienced common iliac LN recurrence, which was outside the pelvic irradiation area. All patients with recurrent disease were categorized into the very-high-risk group. The 8-year cumulative rates of ≥Grade 2 late GI and GU toxicities were 12.8 and 11.8%, respectively. No patients experienced Grade 4 or higher toxicities. WPRT using VMAT for high-risk prostate cancer was well tolerated and effective.