5-year Actuarial Survival Rate Research Articles

Renal Cancer in Recipients of Kidney Transplant.

The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48) recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66); 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17-73); 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days). Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.

Can Perhexiline Be Utilized Without Long-Term Toxicity? A Clinical Practice Audit.

Perhexiline, originally used as a first-line prophylactic antianginal agent, is now regarded primarily as a treatment for otherwise refractory myocardial ischemia. Recent studies have also demonstrated its short-term utility in heart failure, hypertrophic cardiomyopathy, and inoperable aortic stenosis. Its benefits on myocardial energetics state are potentially counter-balanced by risk of hepatotoxicity and peripheral neuropathy during long-term treatment if drug accumulation occurs. Since perhexiline exhibits complex pharmacokinetics with wide inter-individual variability, its long-term use requires regular plasma concentration monitoring. In this study, the risk of neuro- and hepato-toxicity during long-term perhexiline therapy in relation to the intensity of therapeutic drug monitoring was investigated. Furthermore, determinants of mortality during perhexiline treatment were evaluated. In 170 patients treated with perhexiline for a median of 50 months (interquartile range: 31-94 months), outcomes and relationship to plasma drug concentrations were documented. Rationale for treatment with perhexiline included myocardial ischemia in 88% and severe systolic heart failure in 38%. Plasma concentrations were within the therapeutic range of 150-600 ng/mL on 65% of assay occasions and toxic levels accounted for 8.8% of measurements. No patient developed hepatotoxicity attributable to perhexiline while 3 developed peripheral neuropathy possibly induced by treatment. Actuarial 5-year survival rate was 83% overall, and 76.3% in patients with associated systolic heart failure. This first audit of a large population treated long-term perhexiline demonstrates the following: (1) Although the frequency of monitoring is less than ideal, therapeutic drug monitoring effectively limits occurrence of toxic drug concentrations and virtually eliminates long-term hepato- and neuro-toxicity and (2) Mortality rates during long-term therapy, notably for patients with concomitant heart failure, are surprisingly low.

Efficacy of Carperitide in Hemodialysis Patients Undergoing Cardiac Surgery.

Recently, performance of cardiac surgery in hemodialysis patients has increased, but the mortality rate is high. We retrospectively examined the early and long-term outcomes in 128 dialysis patients who underwent cardiac surgery with or without carperitide infusion and were followed for 2 years. Sixty-three patients received carperitide infusion during surgery and 65 patients did not. The hospital mortality rate was 1.6% in the carperitide group and 12.3% in the non-carperitide group, being significantly lower in the carperitide group. The 2-year actuarial survival rate was 90.5% ± 3.7% in the carperitide group, and 76.9% ± 5.2% in the non-carperitide group, while the major adverse cardiovascular and cerebrovascular events (MACCE)-free rate at 2 years postoperatively was 90.5% ± 3.7% in the carperitide group and 67.7% ± 5.8% in the non-carperitide group. These findings suggest that carperitide improves the early postoperative outcome in dialysis patients undergoing cardiac surgery, as has already been demonstrated in non-dialysis patients. An early postoperative cardioprotective effect of carperitide and improvement of renal function in oliguric patients might have contributed to this outcome. However, this was a retrospective study, so a prospective investigation is required to demonstrate the mechanisms involved. In addition, further evaluation of the long-term results would be desirable.

Factors Associated With Early Mortality in Patients Treated With Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Concurrent chemoradiation therapy (con-CRT) is recommended for fit patients with locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with toxicity, and observed survival continues to be limited. Identifying factors associated with early mortality could improve patient selection and identify strategies to improve prognosis. Analysis of a multi-institutional LA-NSCLC database consisting of 1245 patients treated with con-CRT in 13 institutions was performed to identify factors predictive of 180-day survival. Recursive partitioning analysis (RPA) was performed to identify prognostic groups for 180-day survival. Multivariate logistic regression analysis was used to create a clinical nomogram predicting 180-day survival based on important predictors from RPA. Median follow-up was 43.5 months (95% confidence interval [CI]: 40.3-48.8) and 127 patients (10%) died within 180 days of treatment. Median, 180-day, and 1- to 5-year (by yearly increments) actuarial survival rates were 20.9 months, 90%, 71%, 45%, 32%, 27%, and 22% respectively. Multivariate analysis adjusted by region identified gross tumor volume (GTV) (odds ratio [OR] ≥100 cm(3): 2.61; 95% CI: 1.10-6.20; P=.029) and pulmonary function (forced expiratory volume in 1 second [FEV1], defined as the ratio of FEV1 to forced vital capacity [FVC]) (OR <80%: 2.53; 95% CI: 1.09-5.88; P=.030) as significant predictors of 180-day survival. RPA resulted in a 2-class risk stratification system: low-risk (GTV <100 cm(3) or GTV ≥100 cm(3) and FEV1 ≥80%) and high-risk (GTV ≥100 cm(3) and FEV1 <80%). The 180-day survival rates were 93% for low risk and 79% for high risk, with an OR of 4.43 (95% CI: 2.07-9.51; P<.001), adjusted by region. A clinical nomogram predictive of 180-day survival, incorporating FEV1, GTV, N stage, and maximum esophagus dose yielded favorable calibration (R(2) = 0.947). This analysis identified several risk factors associated with early mortality and suggests that future research in the optimization of pretreatment pulmonary function and/or functional lung avoidance treatment may alter the therapeutic ratio in this patient population.

The efficacy of adjuvant therapy for pancreatic invasive intraductal papillary mucinous neoplasm (IPMN).

The literature investigating pancreatic invasive intraductal papillary mucinous neoplasm (IPMN) has largely come from small institutional studies, preventing adequately powered comparisons of adjuvant therapy versus surgery alone (SA) within specific patient subgroups. Patients with resected, stage I through IV, invasive IPMN and conventional pancreatic ductal adenocarcinoma (PDAC) were identified in the National Cancer Data Base (1998-2010). Cox modeling of patients with invasive IPMN was used to compare overall survival (OS) between patients who received adjuvant therapy and those who underwent SA. A second model was used to compare OS between patients with invasive IPMN and those with PDAC. For the 1220 patients with invasive IPMN, the median OS was 28.9 months; the 1-year and 5-year actuarial survival rates were 76% and 17%, respectively; and 47% received adjuvant therapy. Cox modeling associated SA with worse OS (hazard ratio, 1.36; 95% confidence interval, 1.17-1.58; P = .00005) as well as American Joint Committee on Cancer (AJCC) TNM stage III/IV disease, positive lymph node status, positive margins, and poor tumor differentiation (all P ≤ .05). In addition, Cox modeling stratified by the following characteristics demonstrated improved OS with adjuvant therapy: AJCC TNM stage II or III/IV, positive lymph node status, positive margins, and poorly differentiated tumors. There was no survival advantage from adjuvant therapy for patients who had AJCC TNM stage I or lymph node-negative disease. Patients who had invasive IPMN had improved risk-adjusted OS compared with those who had PDAC (hazard ratio, 0.73; 95% confidence interval, 0.68-0.78; P < .00001). Invasive IPMN appears to be more indolent than conventional PDAC. Adjuvant therapy is associated with improved OS compared with SA in patients with invasive IPMN, especially for those with higher stage disease, positive lymph nodes, positive margins, or poorly differentiated tumors. Conversely, this benefit does not extend to patients with stage I or lymph node-negative disease.

Laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: results of a multicenter cohort study on 196 patients.

Laparoscopy is widely accepted as a feasible option for distal pancreatectomy. However, the experience in laparoscopic distal pancreatectomy (LDP) for pancreatic ductal adenocarcinoma (PDAC) is limited to a small number of studies, reported by expert centers. The present study aimed to evaluate perioperative and oncological outcomes after LDP for PDAC in a large, multicenter cohort of patients. A retrospective analysis of the data on 196 patients with histologically verified PDAC, operated at Oslo University Hospital-Rikshospitalet (Oslo, Norway), Asan Medical Center (Seoul, Republic of Korea), Institut Mutualiste Montsouris (Paris, France) and University Hospital Southampton (Southampton, UK) between January 2002 and April 2015 was conducted. The patients with standard (SLDP) and extended (i.e., en bloc with adjacent organ, ELDP) resections were compared in terms of perioperative and oncological outcomes. Out of 196 LDP procedures, 191 (97.4%) were completed through laparoscopy, while five (2.6%) were converted to open surgery. ELDP was performed in 30 (15.7%) cases. Sixty-one (31.9%) patients experienced postoperative complications, including 48 (25.1%) with pancreatic fistula. The rate of clinically relevant fistula (grade B/C) was 15.7%. Median postoperative hospital stay was 8 (2-63) days. Median follow-up was 16months. Median survival was 31.3months (95% CI 22.9-39.6). Three- and 5-year actuarial survival rates were 42.4 and 30%, respectively. SLDP was associated with significantly higher survival compared with ELDP (p=0.032). LDP seems to be a feasible and safe procedure, providing satisfactory oncological outcomes in patients with PDAC.

First and repeat liver resection for primary and recurrent intrahepatic cholangiocarcinoma

BackgroundRecurrence after resection of intrahepatic cholangiocarcinoma (ICC) remains common. The present study sought to evaluate risk factors for recurrence and the results of repeat liver resection (RLR) for recurrent ICC. MethodsBetween 1997 and 2012, clinical data and outcomes of 125 consecutive patients undergoing liver resection for ICC were retrospectively analyzed. ResultsThe rate of R0 resection was 89% (n = 110). Overall median survival was 35 months, and 1-, 3-, and 5-year actuarial survival rates were 80%, 48%, and 28%, respectively. Recurrence occurred in 76 patients (63.5%) and was intrahepatic only for 39 patients (51%). Tumor size greater than 5 cm was identified as an independent risk factor for recurrence (P ≤ .0001). RLR for recurrent ICC was feasible in 10 patients (25%) with a median survival after recurrence of 25 months (16 to 76). ConclusionsTumor size more than 5 cm represents an independent risk factor for recurrence after resection of ICC. RLR in case of recurrent ICC, when feasible, is associated with longer overall survival.

Close or positive resection margins are not associated with an increased risk of chest wall recurrence in women with DCIS treated by mastectomy: a population-based analysis.

Mastectomy is effective treatment for ductal carcinoma in situ (DCIS) but some women will develop chest wall recurrence. Most chest wall recurrences that develop after mastectomy are invasive cancer and are associated with poorer prognosis. Past studies have been unable to identify factors predictive of chest wall recurrence. Therefore, it remains unclear if a subset exists of women with DCIS treated by mastectomy experience a high rate of recurrence in whom more aggressive treatment may be of benefit. We report outcomes of all women in Ontario (N = 1,546) diagnosed with pure DCIS from 1994 to 2003 treated with mastectomy without radiotherapy and evaluate factors associated with the development of chest wall recurrence. Treatments and outcomes were validated by chart review. Proportional differences were compared using Chi square analyses. Survival analyses were used to study the development of chest wall recurrence in relation to patient and tumor characteristics. Median follow-up was 10.1 years. Median age was 57.1 years. 36 patients (2.3%) developed chest wall recurrence. The 10-year actuarial chest wall recurrence-free survival rates and invasive chest wall recurrence-free survival rates were 97.6 and 98.6%, respectively. There was no difference in cumulative 10 year rates of chest wall recurrence by age at diagnosis (<40 years = 5.2%, 40–44 years = 1.3%, 45–50 years = 2.9%, >50 years = 2.1%; p = 0.19), nuclear grade (high = 3.0%, intermediate = 1.4%, low = 1.0%, unreported = 2.5%; p = 0.41), or among women with close or positive resection margins (positive = 3.0%, 2 mm or less = 1.4%, >2 mm = 1.5%, unreported = 2.8%; p = 0.51). On univariate and multivariable analysis, none of the factors were significantly associated with the development of chest wall recurrence. In this population cohort, individuals treated by mastectomy experienced low rates of chest wall recurrence. We did not identify a subset of patients with a high rate of chest wall recurrence, including those with positive margins.

Carcinoma infiltrante de mama operable con axila negativa: cuadro clínico-patológico y factores pronósticos de sobrevida

OBJETIVO: identificar el cuadro clínico-patoldgico y determinar la tasa de recurrencia y los factores pronósticos que influyen en la sobrevida a 5 años del carcinoma infiltrante de mama. MATERIAL: Revisión retrospectiva de las historias clínicas de 39 pacientes con carcinoma de mama invasor operable con axila negativa, sometidas a mastectomía radical clásica (n=29) o modificada (n=10) desde 1966 a 1995. LUGAR: Hospital de Trujillo. RESULTADOS.- La edad medía fue 49 años y el tiempo medio de enfermedad 9,8 meses. Veinte pacientes fueron posmenopáusicas y diecinueve premenopáusicas. Las molestias más frecuentes fueron la presencia de tumor (100%) dolor (25,6%). La mama izquierda (66,7%) y el cuadrante superoexterno (48,79%) fueron los mayormente comprometidos. El tipo histológico más frecuente fue el carcinoma ductal infiltrante (89,8%). Las tasas de recurrencia local y a distancia a 5 años posmastectomia fueron de 1,5,4% y 20,5%, respectivamente. En la serie total, la tasa de sobrevida a 5 años, según el método actuarial de Kaplan-Meier, fue de 76%. En el análisis univariado, usando la prueba de log-rank, fueron factores pronósticos significativamente relacionados con la sobrevida el grado histológico (p &lt; 0,01)y nuclear (P &lt; 0,01), la invasión de vasos sanguíneos (p &lt; 0,05), el índice mitótico (P &lt; 0,05); la fibrosis peritumoral (p&lt;0,01), la multicentricidad del tumor (p &lt;0,05) y el tipo de mastectomía (p &lt; 0,01); y en el análisis multivariante de Cox, sólo tuvieron significancia estadística el grado histológico (p = 0,0026) y nuclear (P = O,0026), el índice mitótico (p = 0, 0191) y el tipo de mastectomía (p = 0,0388). CONCLUSIONES: El grado histológico y nuclear, el índice mitótico y el tipo de mastectomía son factores que influyen significativamente en la sobrevida de pacientes con carcinoma de mama operable y axila negativa y estos parámetros deben ser tenidos en consideración en la estratificación de pacientes para un tratamiento adyuvante postoperatorio.

Does Vaginal Cuff Length After Radical Hysterectomy Predict a Localized Recurrence of Cervical Cancer? [236

OBJECTIVE: The recurrence for cervical cancer after radical hysterectomy is 10–20%. Traditional therapy is to remove the upper one third or 2 cm of the vagina. Our aim was to determine whether the length of vaginal margin is associated with localized recurrence of cancer. METHODS: A review of patients treated by radical hysterectomy and pelvic lymphadenectomy was conducted ranging from 1987 to 2005. Vaginal length (mm) was defined as the length of vaginal tissue from a normal cervix to the distal vaginal margin. RESULTS: A total of 169 patients with stage IB1 cervical cancer were identified. The mean age was 41 years. There were 108 patients with squamous carcinoma and 46 patients with adenocarcinoma. Forty-seven patients had grade 3 tumors; 66 patients had lymph vascular space invasion. Fifteen patients had metastases to the pelvic lymph nodes at presentation. The median follow-up was 12 years with 19 recurrences: seven vaginal, eight pelvic, and four distant. Twenty-six patients died of disease. The 5-year actuarial survival rate is 89%. Mean vaginal cuff length was 13 mm and did not correlate with vaginal (P=.377) or pelvic (P=.318) recurrence. Cell type and vaginal cuff length were not associated with localized recurrence. CONCLUSION: Vaginal cuff length at time of radical hysterectomy is not associated with recurrent cancer in the vagina or pelvis. Surgeons should tailor therapy according to the individual patient; however, excessive margins are not necessary; vaginal margins are unnecessary to prevent localized recurrence.

Exercise performance in patients with impaired left ventricular function following aorto coronary bypass.

We studied 40 patients with preoperative ejection fraction (EF) of 0.35 or less who underwent aortocoronary bypass. An average of 3.1 saphenous vein grafts per patient were inserted and revascularization was considered complete in 33 (82%) of the subjects in the group. Mean follow-up period was 29 months (range 12-65 months). Early mortality was 5% (2 patients) and there were 7 late deaths (3 cardiac and 4 non-cardiac). The 5-year cardiac actuarial survival rate was 74 +/- 13% (+/- SEM). Angina has improved in 29 (94%) of the 31 long-term survivors with 23 (74%) being totally asymptomatic. Twenty-two of the long-term survivors performed an exercise test at the end of their follow-up period. These tests revealed that bypass surgery in such patients results in significantly enhanced myocardial oxygen consumption with concomitant increase in effort level and duration. The exercise ability is probably directly related to the degree of revascularization.

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.

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.

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.

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.

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.