5-year Actuarial Survival Research Articles

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

OBJECTIVE:To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer.METHODS:A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival.RESULTS:Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01).CONCLUSIONS:Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Trasplante cardíaco pediátrico: pasado, presente y futuro

Introduction and objectiveSingle-center data on pediatric heart transplantation over long time frames remains scarce. We analyze our experience and how risk profile between early and current eras has evolved as well as the future implications. Material and methodsWe divided 163 pediatric heart transplants (158 patients) between 1990-2015 into two groups: the first 13 years (59 transplants) and the most recent 13 years (104 transplants). Congenital heart disease was present in 50.3% (n=82) (of them, 80.5% (n=66) univentricular heart); dilated cardiomyopathy 33.7% (n=55); hypertrophic cardiomyopathy 4.3% (n=7); re-transplant 3.6% (n=5) and others 7.9% (n=14). Mean age was 5.1±3.2 years (range 11 days-17 years); mean weight 17.2±3kg (range 2.8-70). Descriptive and comparative analysis along with multivariate and survival analysis were included (Software-R-Core-Team-2013). ResultsSince 2003, the overall number of transplants increased and Glenn (n=14) and Fontan (n=10) stages were the most prevalent types of congenital heart disease. Early mortality was 20.2% (n=33) and a significative decrease was detected for the second era (14.4% vs 30.5%, p<0.0011). Mean follow-up was 10.4±3.6 years (range 3.2 months-21.1 years). Actuarial 10-year survival improved significantly after 2003 (80.8% vs 60.9%, P<.034). Prior univentricular palliation (OR 2.7, range 1.9-3.6, CI 95%, P<.039) and era (OR 5.8, range 3.4-6.9, CI 95%, P<.011) were associated to a higher risk for adverse events (multivariate analysis). ConclusionThe risk profile of pediatric transplant patients has significantly increased over time. Transplantation following single-ventricle palliation has increased dramatically and remains a surgical challenge. Despite this, long-term survival has consistently improved over the years.

Reducing Prosthesis-Patient Mismatch With Edwards Magna Prosthesis for Aortic Valve Replacement.

Prosthesis-patient mismatch (PPM) is associated with increased mid-term and long-term mortality rates after aortic valve replacement (AVR). This study aimed to evaluate the efficacy of the Carpentier-Edwards Perimount Magna and Magna Ease (CEPMs) aortic bioprostheses to reduce the incidence of PPM.Methods and Results:Altogether, 282 consecutive patients (113 women, mean age 69.9±9.9 years) underwent AVR with a CEPMs between 2008 and 2015. They were divided into 3 groups based on the risk of PPM as a result of their body surface area and aortic annular diameter (BSA/AnnD ratio): low-risk (LR) group: 0.64±0.05 m2/cm (n=94); medium-risk (MR) group: 0.73±0.02 m2/cm (n=94); high-risk (HR) group: 0.83±0.05 m2/cm (n=94). The 30-day mortality rate was 0.4%. The 5-year actuarial survival rates were 93.2%, 92.3%, and 94.8% for groups LR, MR, and HR, respectively. No explants as a result of structural valve deterioration occurred. No patients showed severe PPM, defined as a measured effective orifice area index (EOAI) <0.65 cm2/m2. Although there were significant (P<0.05) differences in EOAI (0.98±0.2, 0.90±0.21, and 0.88±0.1 cm2/m2among the LR, MR, and HR groups, respectively), the corresponding transvalvular mean pressure gradients (13.0±5.5, 12.3±4.0, 12.7±5.3 mmHg) and regression rates of the left ventricular mass (29.8%, 28.7%, 28.9%) were similar among groups. CEPMs provide low surgical risk and reduce the risks of PPM, even in HR patients, with excellent hemodynamics.

Risk Factors and Outcome of Children with Relapsed/Refractory Acute Leukemia after T-Cell-Rich Haploidentical Hematopoietic Cell Transplantation

Background: T-cell rich (TCR) HLA-haploidentical SCT (haplo-SCT) is a form of T-cell therapy that has a high degree of efficacy in hematologic malignancies. Previously we reported the safety profile assessing GVHD prophylaxis that was conducted with anti-human thymocyte immunoglobulin (ATG), tacrolimus, methotrexate (MTX) and prednisolone (PSL) in unmanipulated haplo-SCT (Clin Transplant 2010, Transfus Med 2014). We evaluated efficacy and toxicity of TCR haplo-SCT in children with very high risk refractory/relapsed acute leukemia (VHR-R/R AL).Methods: VHR-R/R AL were defined as: relapse after SCT, very early or early relapse, induction failure(2 or more) and relapse of risk factor with MLL rearrangement, Ph+, Mo7 and 5q-. From Aug 2000 to April 2014, consecutive 38 patients (pts) with VHR-R/R AL who underwent TCR-haplo-SCT were included. The median age of pts was 8.2(0.3-19.1) years old. The diagnosis included ALL (n=27), AML (n=8), M/NKL (n=3). The disease status at TCR-haplo-SCT were 18 in CR (positive MRD: 8 pts), 20 in non-CR. HLA disparities were 2/8 in 1pt, 3/8 in 9 pts, 4/8 in 28 pts. Donors included fathers (n=21), mothers (n=14), and siblings (n=3). Thirty one pts received myeloablative conditioning (TBI based: 20 pts, Bu based: 11 pts) and 34 pts of them received ATG (rabbit, thymoglobulin 2.5mg/kg) containing regimen. The GVHD prophylaxis was conducted with tacrolimus, MTX and PSL. Thirty four pts received peripheral blood stem cells and 4 pts received BM.Results: Neutrophil engraftment (defined as >0.5x109/L) was 95% with a median day of 13 (range, 10-15). With a median 1640 days follow-up (range, 320-5510 days) in pts without events, the actuarial 3-year overall survival (OS) and disease-free survival (DFS) were 57% and 39%, respectively. On competing-risk analysis, 1-year cumulative incidences of grade II-IV acute GVHD and chronic GVHD were 71% and 63%, respectively; 3-year cumulative incidences of relapse and non-relapse mortality (NRM) were 40% and 20%. On univariate analysis, 3-year OS in pts with acute GVHD vs. without acute GVHD were 70% vs. 22% (p=.0006), in pts CR vs. non-CR at TCR-SCT were 83% vs. 32% (p=.007), in pts infused CD3 cell doses >=5 x 108/kg vs. <5 x 108/kg were 83% vs. 25% (p=.005), according to age at TCR-SCT <9 vs. >=9 were 79% vs. 34% (.008), respectively. In contrast, the occurrence of acute GVHD had no significant difference in infused CD3 cell doses.Conclusions: These data suggest that TCR haplo-SCT following low-dose ATG containing conditioning combined with our GVHD prophylaxis is well tolerated, facilitates engraftment, and has significant anti-leukemic activity, particularly in pediatric patients with refractory/ relapsed population. DisclosuresNo relevant conflicts of interest to declare.

From scratch: developing a hepatic resection service for metastatic colorectal cancer.

Waitemata District Health Board has New Zealand's largest catchment and busiest colorectal unit. The upper gastrointestinal unit was established in 2005, in part to provide a hepatic resection service for patients with colorectal carcinoma metastatic to the liver. The aim of this investigation was to report on quality indicators for the hepatic resection of colorectal carcinoma in the development of a regional resection service. Prospectively collected data on patients undergoing hepatic resection for colorectal carcinoma between 2005 and 2014 was reviewed and correlated with costing data and national hepatic resection rates. A total of 123 patients underwent 138 hepatic resections for metastatic colorectal cancer with a median hospital stay of 8 days (range 4-37 days), a zero 30-day mortality and a median cost of NZ$21 374 for minor hepatectomy and NZ$43 133 for major hepatectomy. Actuarial 5-year disease-free survival was 44%, with 28 patients alive and disease free at 5 years post-resection. Median overall survival was not reached. Review of national hepatic resection rates indicate that Waitemata District Health Board performs one sixth of all hepatic resections in New Zealand and that this treatment modality may be underutilized in the management of patients with metastatic colorectal cancer. A regional hepatic resection centre for colorectal metastases can be established in areas of population need and can provide a high-quality, cost-effective service.

NORMOTHERMIC EXTRACORPOREAL PERFUSION IN SITU IN DECEASED ORGAN DONORS WITH IRREVERSIBLE CARDIAC ARREST AND ONE HOUR OF ASYSTOLE. 5-YEAR OUTCOMES OF KIDNEY TRANSPLANTATION

Aim.The global shortage of deceased organ donors caused increasing interest to the transplant program based on the use of organs from the donors with sudden irreversible cardiac arrest, or asystolic donors (DCD). Ischemia-reperfusion injury as a result of cardiac arrest remains a key problem that limits the use of organs from DCD. Our clinical study was intended to determine the acceptability of renal transplants derived from the DCD using extracorporeal perfusion in situ after 60 minutes of asystole.Materials and methods.In 2009–2014, St. Petersburg Organ Procurement Organization (OPO) obtained kidneys from 29 DCD with critically expanded warm ischemic time (WIT). The design of this study was approved by the Scientifi c Board and Ethics Committee of the State Research Institute for Emergency Medicine (Decision 7/0615/09). Initially, no one of died patients was considered as potential organ donors. In case of failed advanced CPR the death of a patient was declared initiating the protocol of subnormothermic extracorporeal abdominal perfusion with ECMO, thrombolytics (strepokinase 1.5 mln U), and LD. The procedures were established by the authorized OPO team which arrived with perfusion equipment in 30–40 minutes after declaration of donors’ death. Mean WIT was 58.1 (19.39) minutes (Mean (SD). Resuscitated grafts were transplanted into 58 recipients. The outcomes of transplantation of resuscitated kidneys were compared to those of 112 KTx from 115 brain death donors (BDDs).Results.Immediate functioning of kidney grafts was observed in 28 (48.3%) of 58 recipients. There were 4 cases of primary graft non-function. By the end of the fi rst post-transplant year there was an acute rejection rate of 12.1% (9 episodes of rejection) in the DCD group vs. 23.2% (26 episodes of rejection) in the BDD group (p &lt; 0.05). The actuarial 5-year graft survival rate was 82.8% (n = 48) in DCD group, and 87.5% (n = 98) in BDD group (p &gt; 0.05). Creatinine levels at the end of the fi fth year were 0.094 (0.06) and 0.103 (0.07) mmol/l in DCD and BDD groups, respectively (p &gt; 0.05).Conclusions.Kidneys from DCDs with critically expanded WIT could be successfully used for transplantation if in situ organ “resuscitation” perfusion procedures are included into procurement protocol. The 5-year outcomes meet the generally accepted criteria for grafts’ and recipients’ rates of survival and functioning. This approach could substantially expand the organ donors’ pool.

Can we eliminate neoadjuvant chemoradiotherapy in favor of neoadjuvant multiagent chemotherapy for select stage II/III rectal adenocarcinomas: Analysis of the National Cancer Data base.

Stage II and III rectal cancers have been effectively treated with neoadjuvant chemoradiotherapy (NCRT) followed by definitive resection. Advancements in surgical technique and systemic therapy have prompted investigation of neoadjuvant multiagent chemotherapy (NMAC) regimens with the elimination of radiation (RT). The objective of the current study was to investigate factors that predict for the use of NCRT versus NMAC and compare outcomes using the National Cancer Data Base (NCDB) for select stage II and III rectal cancers. In the NCDB, 21,707 patients from 2004 through 2012 with clinical T2N1 (cT2N1), cT3N0, or cT3N1 rectal cancers were identified who had received NCRT or NMAC followed by low anterior resection. Kaplan-Meier analyses, log-rank tests, and Cox-proportional hazards regression analyses were conducted along with propensity score matching analysis to reduce treatment selection bias. The 5-year actuarial overall survival (OS) rate was 75% for patients who received NCRT versus 67.2% for those who received NMAC (P < .01). On MVA, those who received NCRT had improved OS (hazard ratio, 0.77. P < .01), and this effect was confirmed on propensity score matching analysis (hazard ratio, 0.72; P = .01). In the same model, the following variables improved OS: age < 65 years, having private insurance, treatment at an academic center, living in an affluent zip code, a low comorbidity score, receipt of adjuvant chemotherapy, and a shorter interval before surgery (all P < .05). African Americans, men, patients with high-grade tumors, those with cT3N1 tumors, and those who underwent incomplete (R1) resection had worse OS (all P < .05). In this series, the elimination of neoadjuvant RT for select patients with stage II and III rectal adenocarcinoma was associated with worse OS and should not be recommended outside of a clinical trial. Cancer 2017;123:783-93. © 2016 American Cancer Society.

Outcomes of patients with inflammatory breast cancer treated by breast-conserving surgery.

Inflammatory breast cancer (IBC) is rare and associated with a poor prognosis. Following neoadjuvant chemotherapy or endocrine therapy, the multidisciplinary team selected a small number of patients for breast-conservation therapy (BCT). The aim of this study was to determine the outcome of IBC patients treated with BCT in Edinburgh. Between January 1999 and December 2013, thirty-five women with IBC were treated by BCT. The median follow-up was 80months. The 5-year actuarial survival for the 35 patients was 70.3%. Median survival for 20 neoadjuvant chemotherapy patients was 12.9years (95% CI 7.6, 18.1), and for 14 patient neoadjuvant endocrine therapy patients, it was 11.8years (95% CI 1.1, 22.6) (p=0.34). Five patients developed locoregional recurrence (LRR) between 11 and 72months after BCT (median 37months). Three had breast only recurrence, one patient had both breast and axillary recurrence, and one developed axillary recurrence. The 5-year LR-free survival was 87.5% (95% CI 76.0, 99.0). In 4 of the 5 patients with LRR, systemic metastases were diagnosed within 6months and survival post-LRR in these 4 patients was short. IBC is not an absolute contraindication to BCT. LRR in patients after BCT appears part of widespread recurrent disease rather than inadequate local treatment. Multicentre data should be collected to confirm that women with IBC who have a good response to systemic therapy may be offered BCT in the knowledge that in a larger series our observations are confirmed.

Therapeutic experience of vincristine/cyclophosphamide/melphalan or mitoxantrone/prednisone combination therapy plus thalidomide as first-line induction therapy for newly diagnosed multiple myeloma in a single institution of China.

To investigate the safety and efficacy of the combination regimen vincristine, cyclophosphamide, melphalan or mitoxantrone and prednisone (VCMP) plus thalidomide as first-line induction therapy for newly diagnosed multiple myeloma (MM). Three hundred and ninety-six symptomatic, newly diagnosed MM patients were treated with VCMP plus thalidomide in our hospital for the past 11 years, and clinical data of these patients were retrospectively analyzed. Of the 396 patients enrolled, the total response rate was 77.3%. Forty-three patients relapsed after sCR and CR. Mean cycles to first response were six cycles (range 1-16 cycles). A total of 53% of patients achieved at least a PR within the first cycle of therapy. The actuarial 1-year, 3-year and 5-year overall survival of all patients were 89.4%, 29.5% and 10.6%, respectively. The probabilities of 1-year, 3-year and 5-year progression-free survival of all patients were 84.0%, 23.1% and 8.4%, respectively. The major adverse events were gastrointestinal symptoms, electrolytes and glucose metabolism disorders, hypertension, infection, peripheral nerve disease and hematological adverse events, which were mostly below grade 3 and could be alleviated by symptomatic treatment. We concluded that VCMP plus thalidomide is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed MM including elderly patients and patients with renal failure.

Long-term outcomes of high-dose-rate brachytherapy for intermediate- and high-risk prostate cancer with a median follow-up of 10 years.

To evaluate the long-term outcomes of high-dose-rate (HDR) brachytherapy for patients with intermediate- and high-risk prostate cancer. We retrospectively analysed a prospective longitudinal cohort database including a single-surgeon series of 507 consecutive men treated with external beam radiotherapy and an HDR prostate brachytherapy boost between August 2000 and December 2009. The risk factors used were based on the D'Amico classification. We measured the incidence of no biochemical evidence of disease (bNED) based on the Phoenix definition of failure (nadir PSA + 2 ng/mL). We also reviewed the incidence of urethral stricture in this cohort. With minimum and median follow-ups of 6 and 10.3 years, respectively, the bNED rates for men with intermediate- and high risk disease were 93.3% and 74.2%, respectively, at 5 years and 86.9% and 56.1%, respectively, at 10 years. The 10-year bNED rate for men with only one intermediate-risk factor was 94%, whereas for patients with all three high-risk factors it was 39.5%. The overall urethral stricture rate was 13.6%. Before 2005, the urethral stricture rate was 28.9% and after January 2005 it was 4.2%. For the 271 men with a minimum follow-up of 10 years the actuarial 10-year prostate cancer-specific survival rate was 90.8% and the actuarial overall survival rate was 86.7%. For men with intermediate- or high-risk prostate cancer features, who are considered not suitable for, or wish to avoid a radical prostatectomy, HDR prostate brachytherapy remains an appropriate treatment option. From December 2004, prevention strategies decreased the risk of post-brachytherapy urethral strictures.

Modern Demographics, Oncologic Outcomes, and Prognostic Factors in Women With Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer. The current treatment paradigm is trimodality approach with neoadjuvant chemotherapy, modified radical mastectomy (MRM), and post-mastectomy radiation therapy (PMRT). Advancements in systemic therapy have improved survival increasing the importance of locoregional control. Even with improving outcomes, survival rates remain unsatisfactory prompting the need to identify individuals that may benefit from treatment intensification. We report tumor characteristics, patient demographics, and oncologic outcomes of IBC in the modern era in order to identify subgroups with poor outcomes. We searched the Surveillance, Epidemiology, and End Results (SEER) database for women with breast cancer. This cohort was narrowed to women with non-metastatic [Adjusted AJCC 6th M (1988+) M0] IBC [Adjusted AJCC 6thT (1988+) T4d] with MRM [(1998+) Breast] with or without external beam PMRT. To be included, patients were treated with either ipsilateral MRM with or without reconstruction with the specified race, age, hormone receptor [ER/PR Status], grade, nodal stage [(1988+)], marital, and radiation data. A minimum of 5 years of follow-up was required. We report the actuarial 5-year cause-specific survival. We identified a cohort of 4841 women treated between 1998 and 2007. The median age of diagnosis was 55. The actuarial 5-year CSS for the whole cohort was 56% (95% CI; 54.0-57.2). Black women made up 13% while white women, other races, and unknown represented 81%, 6%, and <1% respectively. Blacks, whites, and other had 5-year CSS of 42% (37.3-46.0), 58% (55.8-59.3), and 59% (51.8-64.9) respectively. Blacks had a statistically significant (SS) lower CSS than the other groups. PMRT (n = 2903) had a SS benefit compared to no RT (n = 1439) with 5-year CSS of 59% (57.3-61.3) and 49% (46.7-52.4) respectively. Women over 70 years of age had a SS lower CSS compared to women between 50-69, but not when compared to ages 20-49. Patients with high-grade histology had a SS lower CSS than intermediate and low-risk patients with CSS of 49% (47-51.8), 68% (64.6-70.8), and 82% (71.6-89.1) respectively. Negative hormone receptor status or being divorced/widowed was also associated with SS worse survival compared to receptor positive disease and being married respectively. Our study confirms that IBC has several tumor factors are associated with worse survival and suggests some patient factors are associated with health disparity. As such, select patients (e.g. black women) may benefit from individualized treatment intensification including additional adjuvant systemic therapy and/or dose escalated PMRT. Select patients may also benefit from more intense post-treatment surveillance and support. Long-term follow-up and prospective data, if feasible, is needed to confirm our findings and conclusions.

The Largest Known Survival Analysis of Patients With Brain Metastasis From Thyroid Cancer Based on Prognostic Groups

Purpose To analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM) from differentiated thyroid cancer (DTC). Methods and Materials A total of 37 patients with DTC who were diagnosed with BM between 1995 and 2014 were included. We reviewed the clinical characteristics, treatment modalities, and image findings of BM. Factors associated with survival were evaluated, and the patients were divided into three prognostic groups (Groups A, B, and C) for comparative analysis. Results The median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs) were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A) had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B) had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C) had the least favorable prognosis with a median survival of 1.5 months. Conclusions The survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors.

Preoperative short-course radiation therapy for rectal cancer provides excellent disease control and toxicity: Results from a single US institution

PurposePreoperative short-course radiation therapy (SCRT) has rarely been used for rectal cancer in the United States, although 2 randomized phase 3 trials demonstrate equivalence to conventional chemoradiation (CRT), and recent updates to national guidelines include this regimen as a treatment option. We sought to evaluate the efficacy and safety of preoperative SCRT followed by immediate surgery within 1 week to treat rectal cancer in the US setting. Methods and materialsAll patients treated with preoperative SCRT (4 Gy × 5 fractions for total 20 Gy) followed by planned surgery within 1 week at our institution were retrospectively evaluated. Censored cases with ≥2 years of follow-up were included along with any disease failure or death. Patients with cM1 disease were excluded. Patients with yp stage II/III disease typically received adjuvant chemotherapy from the 1990s onwards. The primary outcomes were actuarial (Kaplan-Meier) 5-year locoregional control (LC), disease-free survival (DFS), and overall survival (OS) as well as late severe (greater than or equal to grade 3) toxicity. ResultsOur analysis included 202 consecutive patients with clinical stage I-III disease treated from 1977 through 2011. Median follow-up was 6.5 years (range, 2-29.2). Five-year disease outcomes were 95.9% ± 1.5% for LC, 76.4% ± 3.1% for DFS, and 84.6% ± 2.6% for OS. For patients with locally advanced rectal cancer (cT3-4 and/or cN+), 5-year LC, DFS, and OS were 95.1% ± 2.1%, 73.3% ± 4.3%, and 80.6% ± 3.7%, respectively. The late severe toxicity rate was 11.4%. ConclusionsSCRT followed by immediate surgery is a safe and effective treatment for patients with rectal cancer in the United States. Though SCRT has not been widely adopted, recent updates to the national guidelines for rectal cancer as well as financial pressures to reduce healthcare costs may lead to increased utilization of this treatment regimen in the future.

Hypofractionation with no boost after breast conservation in early-stage breast cancer patients

The aim of this study was to evaluate local control, survival and toxicity profile of a consecutive cohort of early-stage breast cancer (EBC) patients treated with adjuvant hypofractionated radiotherapy (HF) with no boost delivered to the lumpectomy cavity, after breast-conserving surgery (BCS). Between 2005 and 2015, a total of 493 women affected with EBC were treated with HF (46Gy/20 fractions or 40.05Gy/15 fractions) to the whole breast without boost to tumor bed, because of age and/or favorable tumor characteristics. The primary endpoint was 5-year actuarial local control (LC); secondary endpoints included survival, toxicity profile and cosmesis. Median follow-up was 57months (range 6-124). Actuarial 5-year overall, cancer-specific, disease-free survival and LC were 96.3, 98.9, 97.8 and 98.6%, respectively. On multivariate analysis, tumor stage (T1 vs. T2) and hormonal status (positive vs. negative estrogen receptors) were significantly correlated with LC. Only 2% of patients experienced ≥G3 acute skin toxicity. Late toxicity was mild with only 1 case of G3 fibrosis. Most of the patients (95%) had good-excellent cosmetic results. HF to the whole breast with no boost delivered to the tumor bed is a safe and effective option for a population of low-risk breast cancer patients after BCS, with excellent 5-year LC, mild toxicity profile and promising cosmetic outcome. A subgroup of patients with larger tumors and/or with no estrogen receptor expression may potentially benefit from treatment intensification with a boost dose to the lumpectomy cavity.

Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).

Axillary Versus Femoral Arterial Cannulation During Repair of Type A Aortic Dissection?: An Old Problem Seeking New Solutions.

The goal of this study was to compare early postoperative outcomes and actuarial-free survival between patients who underwent repair of acute Type A aortic dissection with axillary or femoral artery cannulation. A total of 305 patients from five academic medical centers underwent acute Type A aortic dissection repair via axillary (n = 107) or femoral (n = 198) artery cannulation between January 2000 and December 2010. Major morbidity, operative mortality, and 5-year actuarial survival were compared between groups. Multivariate logistic regression was used to determine predictors of operative mortality, and Cox regression hazard ratios were calculated to determine predictors of long-term mortality. Operative mortality was not influenced by cannulation site (16% for axillary cannulation vs. 19% for femoral cannulation, p = 0.64). In multivariate logistic regression analysis, hemodynamic instability (p < 0.001) and prolonged cardiopulmonary bypass time (>200 min; p = 0.05) emerged as independent predictors of operative mortality. Stroke rates were comparable between the two techniques (14% for axillary and 17% for femoral cannulation, p = 0.52). Five-year actuarial survival was comparable between the groups (55.1% for axillary and 65.7% for femoral cannulation, p = 0.36). In Cox regression analysis, predictors of long-term mortality were: age (p < 0.001), stroke (p < 0.001), prolonged cardiopulmonary bypass time (p = 0.001), hemodynamic instability (p = 0.002), and renal failure (p = 0.001). The outcomes of femoral versus axillary arterial cannulation in patients with acute Type A aortic dissection are comparable. The choice of arterial cannulation site should be individualized based on different patient risk profiles.

The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients.

We sought to determine whether the mode of sensitization in highly sensitized patients contributed to kidney allograft survival. An analysis of the United Network for Organ Sharing dataset involving all kidney transplants between 1997 and 2014 was undertaken. Highly sensitized adult kidney transplant recipients [panel reactive antibody (PRA) ≥98%] were compared with adult, primary non-sensitized and re-transplant recipients. Kaplan-Meier survival analyses were used to determine allograft survival rates. Cox proportional hazards regression analyses were conducted to determine the association of graft loss with key predictors. Fifty-three percent of highly sensitized patients transplanted were re-transplants. Pregnancy and transfusion were the only sensitizing event in 20 and 5%, respectively. The 10-year actuarial graft survival for highly sensitized recipients was 43.9% compared with 52.4% for non-sensitized patients, P < 0.001. The combination of being highly sensitized by either pregnancy or blood transfusion increased the risk of graft loss by 23% [hazard ratio (HR) 1.230, confidence interval (CI) 1.150-1.315, P < 0.001], and the combination of being highly sensitized from a prior transplant increased the risk of graft loss by 58.1% (HR 1.581, CI 1.473-1.698, P < 0.001). The mode of sensitization predicts graft survival in highly sensitized kidney transplant recipients (PRA ≥98%). Patients who are highly sensitized from re-transplants have inferior graft survival compared with patients who are highly sensitized from other modes of sensitization.

Comparison between antegrade and retrograde cerebral perfusion or profound hypothermia as brain protection strategies during repair of type A aortic dissection.

The goal of this study was to compare early postoperative outcomes and actuarial-free survival between patients who underwent repair of acute type A aortic dissection by the method of cerebral perfusion used. A total of 324 patients from five academic medical centers underwent repair of acute type A aortic dissection between January 2000 and December 2010. Of those, antegrade cerebral perfusion (ACP) was used for 84 patients, retrograde cerebral perfusion (RCP) was used for 55 patients, and deep hypothermic circulatory arrest (DHCA) was used for 184 patients during repair. Major morbidity, operative mortality, and 5-year actuarial survival were compared between groups. Multivariate logistic regression was used to determine predictors of operative mortality and Cox Regression hazard ratios were calculated to determine the predictors of long term mortality. Operative mortality was not influenced by the type of cerebral protection (19% for ACP, 14.5% for RCP and 19.1% for DHCA, P=0.729). In multivariable logistic regression analysis, hemodynamic instability [odds ratio (OR) =19.6, 95% confidence intervals (CI), 0.102-0.414, P<0.001] and CPB time >200 min(OR =4.7, 95% CI, 1.962-1.072, P=0.029) emerged as independent predictors of operative mortality. Actuarial 5-year survival was unchanged by cerebral protection modality (48.8% for ACP, 61.8% for RCP and 66.8% for no cerebral protection, log-rank P=0.844). During surgical repair of type A aortic dissection, ACP, RCP or DHCA are safe strategies for cerebral protection in selected patients with type A aortic dissection.

Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma.

Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis. To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification. This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015. Progression-free survival (PFS). The secondary outcome was overall survival. The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30-24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02-1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04-1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at least 12 mm, 90% (9%) for class 2 UMs with LBD of less than 12 mm, and 30% (7%) for class 2 UMs with LBDs of at least 12 mm. The independent prognostic value of LBD and the 12-mm LBD cutoff were corroborated in the independent validation 241-patient cohort. Class 2 UMs had better prognosis when the LBD was less than 12 mm at the time of treatment. These findings could have important implications for patient counseling, primary tumor treatment, clinical trial enrollment, metastatic surveillance, and adjuvant therapy.

The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study.

Tumor differentiation and cancer-related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha-fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077-2088).