5-year Actuarial Survival Research Articles

Fractionated Stereotactic Radiosurgery for Large Brain Metastases

Large brain metastases (>3 cm) present a therapeutic dilemma, as the dose delivered by stereotactic radiosurgery (SRS) in a single fraction is limited by toxicity to adjacent tissues, resulting in suboptimal local control. This study assessed the efficacy and safety of fractionated SRS for the treatment of large brain metastases. We identified 36 patients with 37 brain metastases treated with fractionated SRS. The median SRS dose was 24 Gy (range, 12 to 27 Gy) in 2 to 5 fractions and the median treatment volume was 15.6 mL (range, 10 to 82.7 mL). Kaplan-Meier analysis was used to estimate local control and overall survival rates. Of the 21 lesions with available radiographic follow-up, 6 lesions (29%) had a documented local failure, yielding an actuarial progression-free survival at 6 and 12 months of 73% and 63%, respectively. The actuarial 6-month and 1-year overall survival rates were 22% and 13%, respectively. No patients in this cohort experienced acute or late complications secondary to SRS. Fractionated SRS is feasible and safe in patients with large brain metastases. Local control rates appear to be improved when compared with that of single fraction SRS with a relative paucity of treatment-related toxicity.

Trasplante hepático en mayores de 65 años de edad: experiencia en el Hospital Pablo Tobón Uribe, Medellín, Colombia 2004-2010

El trasplante hepático se ha extendido a personas mayores de 65 años de edad, quienes anteriormente eran excluidas de los protocolos debido a la mayor morbilidad y mortalidad asociadas con la edad. Este estudio tuvo como objetivo identificar la supervivencia y las complicaciones en pacientes mayores de 65 años de edad sometidos a trasplante de hígado. Se analizaron historias clínicas de pacientes mayores de 65 años de edad trasplantados en el período comprendido entre septiembre de 2004 y noviembre de 2010, en el Hospital Pablo Tobón Uribe de Medellín, Colombia. Se estudiaron 27 pacientes con una edad promedio de 67 años. La supervivencia postrasplante en ellos fue del 85,2%, 70,4% y 63% a los 30 días, al año y a los 5 años, respecti- vamente. Se evaluaron las complicaciones postrasplante, siendo las más frecuentes el sangrado masivo y las infecciones nosocomiales. La principal causa de muerte fueron los eventos cardiovasculares. En conclusión, la selección adecuada de los pacientes permite a aquellas personas mayores de 65 años convertirse en candidatos a trasplante hepático, con una buena supervivencia actuarial a 5 años y una mejor calidad de vida.

Kidney biopsy findings in primary Sjögren syndrome.

Renal involvement is rare in primary Sjögren syndrome (PSS). In this study, we examined renal biopsy findings in patients with PSS and correlated them with their clinical and renal findings. Twenty-five patients with PSS who underwent renal biopsies from two renal units in Scotland between 1978 and 2013 were identified from renal biopsy database. We examined the renal morphologic, clinical and renal findings at the time of renal biopsy, renal and patient outcomes. The diagnosis of PSS preceded renal biopsy in 18/25 patients. In this group, the median duration of the disease was 5.5 years. Significant proteinuria, combined microscopic haematuria and proteinuria and reduced renal excretory function were found in 76, 56 and 84% of patients, respectively. The 3-year actuarial patient survival was significantly lower in patients with glomerulonephritis as compared with tubulointerstitial nephritis (66 versus 100%, P = 0.02). There was no difference in 3-year actuarial renal survival between these two groups (92 versus 92%, P = 1.0). Renal biopsy is rare in PSS and often reveals diverse pathological findings. Glomerulonephritis, as compared with tubulointerstitial nephritis, is associated with higher early mortality. Further studies are needed to evaluate the utility of renal biopsy and its impact on disease management.

Laparoscopic Parenchymal-Sparing Resections for Nonperipheral Liver Lesions, the Diamond Technique: Technical Aspects, Clinical Outcomes, and Oncologic Efficiency

Surgical management of liver lesions has moved toward "parenchymal-sparing" strategies. Although open parenchymal-sparing liver resections are supported by encouraging results, the applicability of the laparoscopic approach for nonperipheral tumors is still questionable. Our aim was to assess the feasibility, safety, and oncologic adequacy of laparoscopic parenchymal-sparing liver resection for nonperipheral lesions with a description of the technique adopted in this setting. A prospectively collected single-center database of 517 laparoscopic liver resections was reviewed. Laparoscopic nonperipheral parenchymal-sparing liver resections (LapPSLRs), that is, entirely intraparenchymal limited resections performed on nonperipheral lesions, were selected. Intra- and perioperative outcomes were analyzed along with 3-year actuarial survival for patients with colorectal liver metastases. The group comprised 49 LapPSLRs. Colorectal liver metastases were the most frequent diagnosis (n = 24 patients). Lesions were located in segments 8, 7, 4a, and 3 in 51%, 8.2%, 36.7%, and 4.1% of cases, respectively. Conversion occurred in 4 patients (8%). Intra- and postoperative short-term outcomes were calculated for the 24 isolated LapPSLR (not associated with any concurrent liver resection). Median operative time and blood loss were 215 minutes and 225 mL, respectively. Pringle maneuver was used in 75% of cases. Postoperative 90-day mortality was nil and morbidity rate was 12.5%. Median postoperative stay was 3 days. Median tumor-free margin was 4 mm and 100% R0 rate was achieved for all LapPSLRs with curative intent. Three-year overall, recurrence-free, and disease-free survival rates were 100%, 65.2%, and 69.6%, respectively. Laparoscopic parenchymal-sparing liver resections for nonperipheral liver lesions are feasible and can be performed safely without compromising perioperative and oncological outcomes.

MiR-29a/b enhances cell migration and invasion in nasopharyngeal carcinoma progression by regulating SPARC and COL3A1 gene expression.

Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with a genetic predisposition, Epstein-Barr virus infection and chromosomal abnormalities. Recently, several miRNAs have been shown to target specific mRNAs to regulate NPC development and progression. However, the involvement of miRNAs in processes leading to NPC migration and invasion remains to be elucidated. We predicted that miR-29a/b are associated with dysregulated genes controlling NPC through an integrated interaction network of miRNAs and genes. miR-29a/b over-expression in NPC cell lines had no significant effect on proliferation, whereas miR-29b mildly increased the percentage of cells in the G1 phase with a concomitant decrease in the percentage of cells in S phase. Furthermore, we demonstrated that miR-29a/b might be responsible for increasing S18 cell migration and invasion, and only COL3A1 was identified as a direct target of miR-29b despite the fact that both SPARC and COL3A1 were inhibited by miR-29a/b over-expression. Meanwhile, SPARC proteins were increased in metastatic NPC tissue and are involved in NPC progression. Unexpectedly, we identified that miRNA-29b expression was elevated in the serum of NPC patients with a high risk of metastasis. The 5-year actuarial overall survival rates in NPC patients with high serum miR-29b expression was significantly shorter than those with low serum miR-29b expression; therefore, serum miR-29b expression could be a promising prognostic marker.

High-dose-rate brachytherapy as a monotherapy for prostate cancer--Single-institution results of the extreme fractionation regimen.

We report a single-institution retrospective analysis of the outcomes, disease control, and toxicity of high-dose-rate (HDR) brachytherapy used as the only treatment modality (monotherapy) for localized prostate cancer. Between 2006 and 2012, 77 patients with diagnosed prostate cancer were treated with HDR brachytherapy as a monotherapy. The prescribed dose was 45Gy in three separate implants 21days apart, with single fraction per implant. Of the 77 patients, 67 (87%) received hormonal therapy. Prostate-specific antigen failure was defined according to Phoenix consensus, as nadir+ 2ng/mL. Toxicity was scored according to Common Terminology Criteria for Adverse Events, version 4.03. The median followup time was 57 months (4.75 years). The 5-year actuarial overall survival was 98.7%, biochemical control 96.7%, local control 96.9%, and metastasis-free survival 98.4%. Younger age at the beginning of brachytherapy predicted the onset of bounce phenomenon. There were no Grade 3 or higher acute toxicities detected, and Grade 2 genitourinary acute toxicity developed in 19 patients (24.6%). There were no Grade 2 gastrointestinal complications. No Grade 4 or 5 late toxicity was detected. There were also no Grade 3 gastrointestinal toxicities detected. One patient (1.3%) underwent transurethral resection of the prostate because of Grade 3 urethral stenosis and urinary retention. A total of 26 patients (33.8%) developed Grade 2 late toxicity. HDR brachytherapy as monotherapy for localized prostate cancer was feasible, effective, and had acceptable toxicity profile.

Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer.

PurposeTo assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife.MethodsWe extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over time, PSA velocity, and PSA nadir were evaluated from the completion of SBRT using CyberKnife. Biochemical recurrence (BCR)-free survival after primary SBRT using CyberKnife was determined using Kaplan–Meier analysis.ResultsThe rate of PSA decrease was maximal in the first month (median −3.34 ng/mL/mo), which then fell gradually with median values of −1.51, −0.32, −0.28, −0.20, and −0.03 ng/mL/mo for durations of 3, 6, 9, 12, and 24 months after SBRT using CyberKnife, respectively. The median PSA nadir was 0.31 ng/mL after a median 23 months. Kaplan–Meier analysis calculates an actuarial 5-year BCR-free survival after SBRT using CyberKnife as 80.8%.ConclusionsPSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer.

18F-fluorodeoxyglucose positron emission tomography to assess response after radiation therapy in anaplastic thyroid cancer

To assess the interest of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET/CT) to evaluate the tumor response after radiotherapy (RT) in anaplastic thyroid cancer (ATC) patients. 92 patients were treated for ATC at our institution from 1987 to 2012, out of which 64 (70%) received an aggressive multimodal treatment and 28 (30%) a palliative treatment. In the multimodal treatment group, curative-intended surgery, chemotherapy, and RT were delivered in 35 (55%), 59 (92%), and 56 (88%) patients. The maximum standardized uptake value (SUVmax) was determined in tumor (T), nodes (N) and metastases (M) in each available (18)F-FDG PET/CT. The median follow-up was 3.2years. The 1-year actuarial overall survival (OS) was 18% (median: 5.2months) in the entire population and 27% (median: 7months) in the multimodal treatment group. In the multivariate analysis, RT, surgery, and pre-RT chemotherapy independently predicted for OS, with HRs respectively of 0.1, 0.3, and 0.5. Quantification of FDG uptake with SUVmax was assessable in 26 (40%), 19 (30%), and 25 (39%) of (18)F-FDG PET/CT performed initially (prior to any treatment), prior to RT, and after RT, respectively. Mean SUVmax significantly decreased in T (p<0.001), but not in N (p=0.1) and M (p=0.3) during the assessment period, which might be related to the local effect of RT. Comparing pre- and post-RT (18)F-FDG PET/CT, the T mean relative SUVmax decrease was lower (23±54%) in the 4 patients that had a local relapse (LR) as compared with others in the 12 others patients (62±33%; p=0.3). A relative SUVmax decrease inferior to 20% significantly predicted for LR (p=0.02). The prognosis of ATC patients remains dismal despite an aggressive multimodal treatment. Although our results were not significant, (18)F-FDG PET/CT could potentially serve as a surrogate marker of treatment response in ATC.

Melanoma characteristics in Brazil: demographics, treatment, and survival analysis.

BackgroundThe incidence of melanoma, one of the most aggressive of the skin cancers, has been increasing worldwide in the last few decades. Data from Latin America and Brazil remain scarce. We aimed to describe the demographic, clinical, and histopathological data; therapy characteristics; and survival rates of the Brazilian melanoma patient population.ResultsWe collected and analysed retrospective data from 15 years at a tertiary cancer centre. We describe patient characteristics and treatment. We calculated survival, and identified the main prognostic factors through univariate and multivariate analysis. We analysed a total of 1073 patients, with a mean age of 56.7 years. Men and women experienced similar prevalence, and 91.2% of patients had white skin. The most prevalent subtype was superficial spreading, and the most prevalent anatomic location was the trunk (32.2%), followed by the lower extremities (28%). Of all cases, 567 (52.9%) were assigned to clinical stages I and II, while 382 (32.6%) were stages III and IV. Surgery was the main treatment. Sentinel node biopsy was performed in 373 patients, with 23.8% positivity. Overall actuarial 5-year survival was 67.6%. Multivariate analysis showed that gender, serum lactate dehydrogenase (LDH) levels at diagnosis; anatomic location, TNM stage, and local recurrence were significant prognostic factors.ConclusionsOverall survival was lower than worldwide rates. The main factors influencing survival were similar to those in other populations. Local recurrence was independently associated with lower survival rates. The high prevalence of advanced cases reinforces the importance of strategies to diagnose melanomas in the early stages. There is a need for future multi-institutional prospective studies to attain a better understanding of possible socioeconomic and other influences on survival among melanoma populations in Brazil and Latin America.

Hemodynamic Performance and Durability of Mosaic Bioprostheses for Aortic Valve Replacement, up to 13 Years.

This study evaluated the mid to long-term durability and hemodynamics of the small-size Mosaic bioprosthesis, a third-generation stented porcine bioprosthesis, for aortic valve replacement (AVR). From 2000 to 2012, 207 patients (117 women; age, 74±8 years; body surface area, 1.48±0.25 m(2)) underwent AVR with a Mosaic bioprosthesis. The mean follow-up period was 3.5±2.7 years (maximum, 12.4 years) and the follow-up rate was 93.7%. A 19-, 21-, 23-, 25-, and 27-mm prosthesis was used in 103, 53, 35, 13, and 3 patients, respectively. The measured effective orifice area was 1.17±0.25, 1.29±0.19, 1.39±0.24, and 1.69 cm(2)for the 19-25 mm prostheses, and the mean transvalvular pressure gradient was 19.4±6.0, 18.5±5.8, 16.5±7.3, and 13.2±2.9 mmHg, respectively. The left ventricular mass regression was significant (P<0.05) with rates of 74.6±18.8%, 75.5±30.2%, 68.1±30.5%, 55.9±12.9%, and 49.2%, respectively. The 30-day mortality rate was 1.9% and the 5- and 10-year actuarial survival rates were 86.0% and 73.7%, respectively. Valve-related comorbidities occurred in 3 patients (structural valve deterioration [SVD] in 1 after 7.2 years, and prosthetic valve endocarditis in 2). Freedom from SVD at 10-year was 96.7%. The mid to long-term performance of the small Mosaic bioprosthesis was satisfactory, with excellent hemodynamics and few valve-related adverse events.

Long-term survival after resection of pancreatic cancer: A single-center retrospective analysis

To retrospectively analyze factors affecting the long-term survival of patients with pancreatic cancer who underwent pancreatic resection. From January 2000 to December 2011, 195 patients underwent pancreatic resection in our hospital. The prognostic factors after pancreatic resection were analyzed in all 195 patients. After excluding the censored cases within an observational period, the clinicopathological characteristics of 20 patients who survived ≥ 5 (n = 20) and < 5 (n = 76) years were compared. For this comparison, we analyzed the patients who underwent surgery before June 2008 and were observed for more than 5 years. For statistical analyses, the log-rank test was used to compare the cumulative survival rates, and the χ (2) and Mann-Whitney tests were used to compare the two groups. The Cox-Hazard model was used for a multivariate analysis, and P values less than 0.05 were considered significant. A multivariate analysis was conducted on the factors that were significant in the univariate analysis. The median survival for all patients was 27.1 months, and the 5-year actuarial survival rate was 34.5%. The median observational period was 595 d. With the univariate analysis, the UICC stage was significantly associated with survival time, and the CA19-9 ≤ 200 U/mL, DUPAN-2 ≤ 180 U/mL, tumor size ≤ 20 mm, R0 resection, absence of lymph node metastasis, absence of extrapancreatic neural invasion, and absence of portal invasion were favorable prognostic factors. The multivariate analysis showed that tumor size ≤ 20 mm (HR = 0.40; 95%CI: 0.17-0.83, P = 0.012) and negative surgical margins (R0 resection) (HR = 0.48; 95%CI: 0.30-0.77, P = 0.003) were independent favorable prognostic factors. Among the 96 patients, 20 patients survived for 5 years or more, and 76 patients died within 5 years after operation. Comparison of the 20 5-year survivors with the 76 non-survivors showed that lower concentrations of DUPAN-2 (79.5 vs 312.5 U/mL, P = 0.032), tumor size ≤ 20 mm (35% vs 8%, P = 0.008), R0 resection (95% vs 61%, P = 0.004), and absence of lymph node metastases (60% vs 18%, P = 0.036) were significantly associated with the 5-year survival. Negative surgical margins and a tumor size ≤ 20 mm were independent favorable prognostic factors. Histologically curative resection and early tumor detection are important factors in achieving long-term survival.

Androgen deprivation therapy prevents bladder cancer recurrence

Although accumulating preclinical evidence indicates the involvement of androgen receptor signals in bladder cancer (BC) development, its clinical relevance remains unclear. We aimed to evaluate the predictive role of androgen deprivation therapy (ADT) in BC recurrence in prostate cancer (PC) patients. We retrospectively reviewed 20,328 patients with PC diagnosed during 1991-2013 and identified 239 (1.2%) men having primary BC. After excluding ineligible patients, 162 patients made up a final cohort. With a median follow-up of 62 months, 38 (50%) of 76 control patients without ADT experienced BC recurrence, while 19 (22%) of 86 did in ADT group. Thus, patients having received ADT for their PC showed a significantly lower risk of BC recurrence (5-year actuarial recurrence-free survival: 76% v 40%; P < 0.001) and also had a significantly smaller number of recurrence episodes (5-year cumulative recurrence: 0.44 v 1.54; P < 0.001), compared to the control patients. A multivariable analysis revealed ADT as an independent prognosticator (hazard ratio, 0.29; 95% confidence interval, 0.17-0.49) for BC recurrence. This is the first clinical study showing that ADT significantly reduces the risk of BC recurrence.

Oncologic Outcomes of Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: A Single-institution Experience

This study reports the outcomes of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by surgery in a local population of Singapore. The records of 85 patients who underwent neoadjuvant chemoradiation for locally advanced rectal cancer followed by surgery at the Tan Tock Seng Hospital (TTSH) between November 2002 and January 2012 were reviewed. The treatment protocol comprised radiotherapy to a total dose of 50.4 Gy concurrent with 5-fluorouracil-based chemotherapy. Patients underwent total mesorectal excision surgery following the completion of neoadjuvant chemoradiation. Local control, disease-free survival and overall survival were analysed using Kaplan-Meier methods. Median age of the patients was 61 years. All of them completed radiotherapy. One patient did not complete neoadjuvant chemotherapy. The median time to surgery was 52 days. Fifty-five percent (47 of 85) of patients achieved pathological downstaging and 13% (11 of 85) of patients had a pathologic complete response to preoperative treatment. The neoadjuvant chemoradiation was well tolerated. Four percent of patients had grade 3 diarrhoea and 4% of them had grade 3 dermatitis. There were no grade 4 toxicities. With a median follow-up of 41 months, the 5-year actuarial local recurrence, disease-free survival and overall survival rates were 7%, 71.9%, and 83.2% respectively. Univariate analysis showed that patients with positive surgical margins had significantly worse disease-free survival and overall survival (P=0.012 and P<0.001 respectively) and a trend towards a higher rate of local recurrence (P=0.08). Our study provides evidence that neoadjuvant chemoradiation is an effective treatment for locally advanced rectal cancer. Our outcomes are comparable with internationally published data and demonstrate the reproducibility of the neoadjuvant approach in an Asian population.

Effects of Gender on Outcomes and Survival Following Repair of Acute Type A Aortic Dissection.

Previous studies have demonstrated gender-related differences in early and late outcomes following type A dissection diagnosis. However, it is widely unknown whether gender affects early clinical outcomes and survival after repair of type A aortic dissection. The goal of this study was to compare the early and late clinical outcomes in women versus men after repair of acute type A aortic dissections. Between January 2000 and October 2010 a total of 251 patients from four academic medical centers underwent repair of acute type A aortic dissection. Of those, 79 were women and 172 were men with median ages of 67 (range, 20-87 years) and 58 years (range, 19-83 years), respectively (p < 0.001). Major morbidity, operative mortality, and 10-year actuarial survival were compared between the groups. Operative mortality was not significantly influenced by gender (19% for women vs. 17% for men, p = 0.695). There were similar rates of hemodynamic instability (12% for women vs. 13% men, p = 0.783) between the two groups. Actuarial 10-year survival rates were 58% for women versus 73% for men (p = 0.284). Gender does not significantly impact early clinical outcomes and actuarial survival following repair of acute type A aortic dissection.

Stereotactic body radiotherapy for re-irradiation of lung cancer recurrence with lower biological effective doses.

ObjectiveFew studies have evaluated re-irradiation of lung cancer recurrences with stereotactic body radiotherapy (SBRT). This study evaluates outcomes with SBRT re-irradiation for recurrent lung cancer.MethodsTwo hundred and seventy-eight patients treated with SBRT for lung cancer were retrospectively reviewed. Of those, 26 patients with 29 tumors were re-irradiated with SBRT. Ninety percent of tumors received prior external beam irradiation and 10 % received prior SBRT. Previous median radiation dose was 61.2 Gy with a median 8-month interval from previous radiation. The median re-irradiation SBRT dose was 30 Gy (48 Gy10 biological effective dose (BED)). Endpoints evaluated included local control, overall survival, and progression-free survival.ResultsTwenty-five of 29 tumors were evaluable for local control, with 27 tumors (93 %) considered in-field recurrences. In-field crude local control rate was 80 % (20/25) with 1 and 2-year actuarial rates of 78.6 and 65.5 %, respectively. One and 2-year actuarial survival rates were 52.3 and 37.0 %, respectively. One and 2-year actuarial progression-free survival rates were 56.7 and 37.0 %, respectively. Fifty-five percent of patients reported acute/chronic grades 1 and 2 toxicities. No grade 3 or higher toxicities were reported.ConclusionPatients with recurrent lung cancer have limited options. SBRT re-irradiation is tolerable even after a median 61.2 Gy to the re-irradiation site. The lower BED used provided acceptable progression-free survival with low toxicity. Given the poor prognosis with current treatment options, new paradigms for re-treatment should include SBRT-re-irradiation as an adjunct to systemic therapy for in-field lung cancer recurrence.

Bleomycin Pulmonary Toxicity in Adult Saudi Patients with Hodgkin’s Lymphoma

Background: Bleomycin pulmonary toxicity (BPT) has been well described in Hodgkin’s lymphoma (HL) patients treated with bleomycin-containing chemotherapy regimens. As the effects of genetic susceptibility or race on the development of BPT are largely unknown, we intended to examine BPT incidence, risk factors, and its effects on survival in a series of newly diagnosed Saudi Arabian adult HL patients receiving first-line bleomycin-containing chemotherapy.Methods: We carried out a retrospective review of the relevant records of 164 consecutive eligible adult HL patients treated at two centers.Results: BPT was observed in 24 of 164 patients (15%) at a median duration of 4.3 months (range, 1 to 58 months). Older age and history of concomitant lung disease were significantly associated with approximately three- (odds ratio [OR] = 3.38; 95% confidence interval [CI], 1.25-9.13; P = 0.02) and seven-fold (OR = 7.19; 95% CI, 2.64-19.54; P <0.0001) increase in BPT risk, respectively. While more patients in non-BPT group achieved CR as compared with BPT patients (93% vs. 79%; P = 0.048), the actuarial 5-year progression-free (82% vs. 63%; P = 0.29) and overall survival (OS) (94% vs. 76%; P = 0.059) for BPT and non-BPT groups, respectively were not significantly different. Nevertheless, in a multivariate analysis, the earlier incidence time of BPT considered as a time-dependent covariate was the only factor that independently influenced OS (hazard ratio = 0.99; 95% CI, 0.99-1.00; P = 0.002).Conclusion: In Saudi Arabian adult HL patients, the risk of BPT and its effect on survival outcome were comparable to that reported from developed countries. Earlier incidence time of BPT aversely influenced OS. Future studies should consider testing the efficacy and safety of non-bleomycin-containing regimens in HL. DisclosuresNo relevant conflicts of interest to declare.

Azacitidine Maintenance after Allogeneic Stem Cell Transplantation Is Feasible in Patients with Acute Myeloid Leukemia and Myelodysplasia

Background: 5-Azacidine (5-AZA) is a DNA hypomethylating agent with proven clinical activity in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A recent non-randomized study reported promising results with the use of lower doses of 5-AZA as maintenance therapy after hematopoietic stem cell transplantation (HSCT). It is important to note that 5-AZA has an immunomodulatory effect and might enhance the graft-versus-leukemia (GVL) effect. Here, we report the successful use of 5-AZA maintenance following allogeneic HSCT in patients with high risk AML and MDS.Patients and methods: Nine patients (M=6, F=3; median age=49 (36-65) years ) with high-risk AML (n=6 including 2 abnormal karyotypes) or MDS (n=3 including 1 abnormal karyotype) received 5-AZA as post-transplant maintenance at a dose of 32mg/m2 daily for 5 days every 4 weeks starting at a median time of 100 (30-210) days post-transplant. All patients were in complete remission at initiation of 5-AZA. A median of 12 cycles (1-18) were delivered. Patients’ characteristics, treatment details, response and side effects are summarized in Table I.Results: After a median follow-up of 19 months post HSCT and 15 months after starting 5-AZA treatment, five patients with normal karyotype are still in CR. Conversely, all three patients with abnormal karyotype rapidly developed disease recurrence while they were receiving 5-AZA after a median of 3 months. Overall, the actuarial 1-year progression free and overall survival rates were 65% and 90%, respectively. 5-AZA was generally well tolerated with only mild thrombocytopenia observed in 2 patients. No clinically evident graft-versus-host disease exacerbation was observed.Conclusion: These results suggest that Low-dose 5-AZA is an effective maintenance therapy post- allogeneic SCT in high-risk AML and MDS particularly when a normal diploid karyotype is present. The relative lack of efficacy in the presence of an abnormal karyotype is intriguing and questions whether these subjects might benefit from higher doses of 5-AZA or other novel therapies within the context of a well-designed clinical trial. Prospective clinical trials and longer follow-up are needed to confirm these observations. Abstract 5884 TABLE IPatients characteristics and Outcomes After Azacitidine maintenanceSubject #123456789Age at transplant655848433649495851genderMMFMFMFMMDiseaseAMLAMLAMLAMLSecondary AMLSecondary AMLMPD/MDSMDS (RAEB-2)MDS (RAEB-2)cytogeneticnormalnormalT(6,9)normalDel 5normalnormalnormalHypoploidy(43-45)Molecular abnormalityNoneNoneNoneFLT3 ITDNoneNoneNoneNoneNoneDisease status at HSCTCR2CR3CR1CR1RefractoryCR1PRPRCR1Donor typeMRDMRDMRDMRDMUDMRDMRDMRDMRDConditioningFB2+ATGFB3+ATGFB3+ATGFB4+ATGFB3+ATG+ TBI (4Gy)FB4+ATGFB4+ATGFB3+ATGFB2+ATGGVHD prophylaxisCSACSACSACSACSACSACSACSACSA, mycophenolate mofetilTime from HSCT to 5-AZA (days)37701001503021010055104Disease status at 5-AZACRCRCRCRCRCRCRCRCRnb of cycles12131241218129ToxicityNoneNoneNoneNoneGrade II thrombocytopeniaGrade II thrombocytopeniaNoneNoneNoneGVHD after 5-AZANoNoYesYesYesNoYesNoNoDisease recurrencenonoyesnoyesnononoyesSalvage therapy if recurrenceN/AN/AChemotherapy followed by DLIN/ANoneN/AN/AN/AChemotherapy followed by DLIProgression free survival, months13+24+124+319+21+18+10Status at last follow upCRCRCRCRdiedCRCRCRCRSurvival, months13+24+18+24+519+21+18+34+Stem cell source for all patients: peripheral blood; CR: complete remission; PR: partial remission; CSA: cyclosporine A; MRD: matched related donor; MUD: matched unrelated donor; PBSC: peripheral blood stem cell; CCR: continuous complete remission; FB4: 5 days fludarabine plus 4 days busulfan (130 mg/m2/day); FB3: 5 days fludarabine plus 3 days busulfan (130 mg/m2/day); FB2: 5 days fludarabine plus 2 days busulfan (130 mg/m2/day) ATG: anti-thymoglobuline; DLI: donor lymphocyte infusion. DisclosuresOff Label Use: Azacitidine maitenance post HSCT.

Cerebral Venous Thrombosis As a Complication of Treatment for Acute Lymphoblastic Leukaemia in Children and Young Adults

▪Cerebral venous thrombosis (CVT) is a significant complication of therapy in children and young adults with acute lymphoblastic leukaemia (ALL). Previous reports indicate a considerable risk of mortality and morbidity in relation to CVT. In addition, there is potential for suboptimal treatment of ALL due to avoidance of Asparaginase and the need for reversal of anticoagulant therapy for invasive procedures such as intrathecal chemotherapy. Anticoagulation may be complicated by haemorrhage.This retrospective study aimed to identify the clinical features, therapy and outcome of CVT occurring during treatment of ALL in individuals, aged 1 to 24 years, who participated in the Medical Research Council UK ALL 2003 (MRC UKALL 2003) randomised controlled trial.Cases of CVT were identified from adverse event reporting. All reports were screened for central nervous system thrombosis and grade 4 serious adverse events in the category of coagulation/thrombosis. Reporting centres were asked for additional clinical information.3126 children and young adults were enrolled in the study between 2003 and 2011, with median age 5 years, including 1776 males (56.8%). The 3 initial treatment regimens: A, B and C: corresponded to standard-risk, intermediate-risk and high-risk, respectively. 55% were treated with regimen A, 32% regimen B and 13% regimen C. 48 individuals (1.5%) developed CVT and data were returned for 42. Median age was 10 (range: 1 to 18) years and 25 cases were male (59.5%). 71.4% of cases (30/42) occurred during induction therapy. 18 cases were in individuals treated with regimen A, 22 regimen B and 2 regimen C. Median time between the most recent Asparaginase dose and CVT was 12.5 days (range: 1-111 days). 29 cases (68.4%) had received 2 doses of Asparaginase prior to thrombosis, 5 cases >2 doses and 8 cases 1 dose.Presenting symptoms were: seizures, 22 cases (52.3%); neurological impairment, 20 (47.6%); headache, 19 (45.2%); reduced conscious level, 8 (19.0%); nausea/vomiting, 8 (19.0%). Identified thrombotic risk factors included: hospitalisation, 22 (52.3%); active infection, 5; recent immobility, 5; dehydration, 6; combined oral contraceptive pill, 2. None were obese, had a high white cell count at time of CVT diagnosis or a history of recent major surgery. 13 (31.0%) had >1 thrombotic risk factor and 16 (38.1%) had no additional clinical risk factor identified. 10 had a thrombophilia screen performed, one with a repeatedly low protein S level (male, 1 year of age). 7 cases (16.7%) had cerebral infarction on imaging and 11 (26.2%) were complicated by intracranial haemorrhage (ICH).38 cases (90.5%) received anticoagulant therapy, 37 of which received low molecular weight heparin (LMWH) and one unfractionated heparin. One case had catheter-directed thrombolysis. 4 were not anticoagulated, 3 due to ICH. 2 received Antithrombin replacement therapy. Anticoagulation therapy was continued for a median of 3 months. 65.0% of cases due more Asparaginase were re-exposed (26/40), 19 of which received thromboprophylaxis during re-exposure. 2 remain on long-term therapeutic anticoagulation. In 23 cases (54.8%) CVT resulted in a delay or change to planned treatment.Neurological morbidity was reported in 4 cases (9.5%): seizure disorder, 2; hemiplegia, 1; residual hemiplegia and hemianopia with severe developmental delay, 1. 36 cases (85.7%) remain in first remission. Survival in those with CVT was 90.1%, comparable to actuarial 5-year survival of the entire cohort (91.5%). There were 4 deaths, three due to leukaemia (two in first relapse) and one due to pneumonia as a complication of stem cell transplant. There were no deaths due to CVT or bleeding on anticoagulant therapy.This study highlights the clinical features of CVT in children and young adults treated for ALL in the MRC UKALL 2003 trial, in particular the timing in relation to Asparaginase treatment, presenting features and neurological outcome. These data support LMWH as safe treatment for CVT in this clinical setting. We have demonstrated the tendency of clinicians to adjust treatment regimen and/or avoid further Asparaginase exposure in response to CVT. However, overall survival at 5 years did not differ for the cohort with CVT. Future studies should aim to further evaluate clinical predictors, alongside potential coagulation and genetic markers, in order to identify a high-risk group that may benefit from measures to reduce CVT during ALL therapy. DisclosuresNo relevant conflicts of interest to declare.

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Anti-Thymocyte Gamma-Globulin May Prevent Antibody Production After Heart Transplantation

BackgroundRabbit anti-thymocyte globulin (RATG) has been used as induction therapy in heart transplantation. RATG is polyclonal and has been postulated to have anti-humoral properties by preventing the production of circulating antibodies after heart transplant. Thus, we reviewed our patients who received RATG induction therapy and compared them with those who did not receive therapy for post-transplant de novo antibody production. MethodsBetween January 1, 2006, and January 1, 2013, we assessed 196 non-sensitized heart transplant recipients and divided them into those who received 3 to 5 days of RATG induction therapy mostly due to renal insufficiency (n = 35) versus patients who did not receive therapy (n = 161). All patients were given tacrolimus, mycophenolate mofetil, and corticosteroids. Post-transplant circulating antibodies were routinely monitored at 1, 3, 6, and 12 months after heart transplantation; 1-year and 3-year end points were assessed. ResultsThe RATG-treated group had a significantly higher 12-month freedom from de novo antibody production compared with the patients who did not receive RATG induction (89% vs 71%, log-rank P = .043); however there was no significant difference for 12-month freedom from de novo donor-specific antibody production (91% vs 88%, log-rank P = .541). Treated rejection rates in the first-year were comparable in both groups; 3-year actuarial survival, freedom from cardiac allograft vasculopathy, and freedom from non-fatal major adverse cardiac events were also similar between both groups. ConclusionsRATG induction therapy appears to reduce the production of de novo circulating antibodies in non-sensitized patients during the first year after heart transplantation. Although there were no short-term clinical differences between groups, there were imbalances in group characteristics and relatively short follow-up, which are limitations to this study. A randomized, clinical trial with longer follow-up in a larger cohort of patients is warranted.