Survival In High-risk Patients Research Articles

The Impact of a Postmastectomy Chest Wall Scar Boost on Local Recurrence-free Survival in High-risk Patients

IntroductionA scar boost following postmastectomy radiation to a total dose of > 50 Gy can be considered in cases of invasive breast cancer with high-risk features including advanced tumor stage, lymphovascular space invasion (LVSI), and positive margins. The purpose of this study was to determine the impact of a scar boost on 5-year local recurrence-free survival (LRFS). Materials and MethodsWe retrospectively analyzed 140 patients with invasive breast cancer treated with mastectomy and postmastectomy radiation at a single institution between 2007 and 2016. Patients received 50 to 50.4 Gy to the chest wall and the majority of scar boosts were 9 to 10 Gy. LRFS was examined using the Kaplan-Meier method and univariable Cox regression. ResultsA total of 140 patients met inclusion criteria with a median follow-up time of 48 months. Ninety-four (67.1%) patients did receive a scar boost and 46 (32.9%) patients did not. On subset analysis of patients with LVSI or positive margins, 5-year LRFS was 79.3% in patients treated with scar boost compared with 71.1% in patients without a scar boost (P = .537). In patients with T3 or T4 disease, 5-year LRFS was 80.9% in those who received scar boost and 71.6% in patients who did not (P = .967). The use of a scar boost was not associated with a significant improvement in LRFS on Cox regression (hazard ratio, 0.83; 95% confidence interval, 0.37-1.84; P = .654). ConclusionUse of a scar boost following postmastectomy radiation decreased the absolute percentages of local recurrences in patients with high-risk features; however, this did not translate into a statistically significant benefit.

Bilateral Pulmonary Artery Banding before Norwood Procedure: Survival of High-Risk Patients

This study reports midterm results of high-risk patients with hypoplastic left ventricle treated with initial bilateral pulmonary artery banding (PAB) before secondary Norwood procedure (NP). Retrospective study of 17 patients admitted between July 2012 and February 2017 who underwent this treatment strategy because diagnosis or clinical status was associated with high risk for NP. Survival was compared with that of patients who underwent primary NP. Mean Aristotle comprehensive complexity score for NP would have been 19.7 ± 2.6. Risk factors included obstructed pulmonary venous return (n = 9), body weight < 2.5 kg (n = 7), total anomalous pulmonary venous connection (n = 3), and necrotizing enterocolitis (n = 1). Ten patients had a score ≥ 19.5. Early survival after PAB was 82.4% (14/17). NP was performed in 14 patients after improvement of clinical condition at a median age of 56 days and a weight ≥2,500 g. There was no 30-day mortality, but one interstage death. One patient died later after Glenn operation. One-year survival after primary PAB followed by NP was 70.6 ± 11.1%. During the same period, 35 patients with overall lower risk factors underwent primary NP; early postoperative survival and 1-year survival were 88.6 ± 5.4% and 68.6 ± 7.8%, respectively. There was no significant difference in survival between the two groups (p = 0.83) despite higher risk in the secondary Norwood group (p <0.0001). PAB before NP in high-risk patients constituted salvage management. Primary PAB provided enough time for stabilization and control of most risk factors. It allowed midterm survival equivalent to the survival after primary NP in lower risk neonates.

Evaluation of postoperative adjuvant treatment for ampulla of vater carcinoma : Multicenter, Retrospective study

Introduction: Ampulla of vater carcinoma (AOV) is an infrequent tumor that account for about 0.2% of gastrointestinal malignancies. The incidence of AOV carcinoma is steadily increasing. But there are no guidelines from both the NCCN and the ESMO for the treatment of advanced AOV carcinoma. Only a few retrospective studies have focused on the adjuvant treatment in AOV carcinoma. So, we conducted multicenter retrospective review for evaluation of postadjuvant therapy for AOV carcinoma. Method: Patients who underwent curative resection for AOV carcinoma at the four hospital ( Yonsei Gangnam severance hospital, Seoul national university hospital, Seoul national university bundang hospital, National cancer center , n = 651; 2002-2015) were reviewed. Patients with metastatic disease at surgery, or insufficient pathologic data were excluded. Adjuvant treatment were chemotherapy or chemoradiotherapy. Overall survival and recurrence free survival was compared using Kaplan –Meier estimates. Result: In multivariate analysis, age, T stage, N stage, differentiation type remained as strong and independent risk factors for recurrence free survival and overall survival. No adjuvant group were 396 patients and adjuvant treatment group were 255 patients (Chemotherapy; 84 patients, Chemoradiotherapy; 171 patients). In the high risk patients, such as patients with node-positive, adjuvant treatment was significantly associated with increased recurrence free survival and overall survival. Conclusion: Adjuvant treatment did not improve survival in low risk patients. However adjuvant treatment maybe improved recurrence free and overall survival in high risk patients ( node-positive, advanced T stage) . Prospective evaluation of appropriate adjuvant treatment should be considered.

Noninvasive Flap Preconditioning by Foam-Mediated External Suction Improves the Survival of Fasciocutaneous Axial-Pattern Flaps in a Type 2 Diabetic Murine Model.

Advances in reconstructive surgery are leading to an increased number of flaps at risk for ischemic necrosis, because of either intrinsic (e.g., larger flap size) or extrinsic (e.g., diabetes) factors. Methods to preoperatively improve flap vascularity and limit postoperative ischemia are lacking. Noninvasive suction, using either a macrodeformational silicone cup interface (external volume expansion) or a microdeformational polyurethane foam interface (foam-mediated external volume expansion), has been shown to induce angiogenesis in tissues. The authors investigated whether the preoperative use of external volume expansion/foam-mediated external volume expansion improves flap survival in an obesity-induced diabetic animal model. Db/Db mice underwent either mechanical stimulation with suction for 5 days using either external volume expansion or foam-mediated external volume expansion, or received no stimulation (n = 8 per group). Five days after the last stimulation, a critical-size, axial-pattern, fasciocutaneous flap was raised in all animals. Postoperatively, flap survival was monitored with digital imaging for 10 days. After this period, flaps were harvested to assess tissue survival, angiogenesis, and inflammation, using histology and polymerase chain reaction. Foam-mediated external volume expansion preconditioning significantly increased the viable flap area (28 percent), viable flap volume (27 percent), and flap capillary density (36 percent) in comparison to controls; vascular endothelial growth factor was also up-regulated (>300 percent). In contrast, external volume expansion resulted in a severe inflammatory response and increased flap necrosis. Foam-mediated external volume expansion improves flap survival in obese diabetic mice. This procedure may allow for improved clinical rates of flap survival in high-risk patients.

Very Low Dose of Anti-T-Lymphocyte Globulin Protects Against Severe Forms of Graft Versus Host Disease in High Risk Patients: The Experience in Our Center

BackgroundPatients undergoing hematopoietic stem cell transplantation (HSCT) are at high risk of multiple complications being graft versus host disease (GvHD) one of the most concerning. Addition of anti-T-lymphocyte globulin (ATG-Fresenius ®) reduces the incidence of acute and chronic GvHD however, optimal dose has not yet been established. Standard dose (60 mg/kg) has shown a significantly lower moderate-severe cGvHD yet its effect in Progression Free Survival (PFS) and Overall Survival (OS) is contradictory. Our primary objective was to analyze the efficacy of low ATG dose (21 mg/kg) in the prophylaxis of acute and chronic GvHD. As secondary objective we analyzed non-relapse mortality (NRM), infectious and non-infectious complications, GvHD and relapse free survival (GRFS), overall survival and progression free survival in high risk patients undergoing HSCT.Patients and methodsWe retrospectively analyzed 57 patients who underwent HSCT in our center from 2012 to 2017, receiving a total dose of 21 mg/kg (7 mg/kg on day -3, -2 and -1) of ATG as part of the GvHD prophylaxis, associated to cyclosporine/tacrolimus and MMF/short course-MTX. The conditioning regimen were myeloablative in 42 patients (73.7%). The donor was unrelated in 46 cases (80.7%). Seventeen (29.9%) had a mismatch (16 unrelated, 1 sibling). Stem cell source was peripheral blood in 51 patients (89.4%). Forty six (80.7%) patients were positive for CMV, from these 17 (36.9%) were paired with seronegative donors. The median age was 57 years old (18-70), 38(66.7%) were males. The most frequent diagnosis were Acute Myeloblastic Leukemia (40.4%), myelofibrosis (17.5%) and myelodisplastic syndrome (14%); 28 (49%) had a HCTI score ≥ 3 and 16 (29%) a high risk DRI score. Thirty patients (52.6%) were in complete remission at the moment of HSCT. (Table 1)ResultsHematopoietic engraftment was observed in 54 patients (94.7%). The median neutrophil and platelet engraftment were 14 (10-34) and 15 (9-28) days, respectively. Primary graft failure occurred in 3 patients (2 myelofibrosis, 1 AML). Twenty (39.2%) out of 51 evaluable patients developed grade 2-4 acute GvHD. The cumulative incidence of grade 3-4 aGvHD was 8.8% (95% CI, 3.2-17.9%). Skin was the most affected organ (62%). We found a cumulative incidence of moderate to severe cGvHD of 35.2% (95% CI 22.7-47.9%), only 5 cases (10.6%) were severe, with a median onset at day 177 (57-893). The median duration of immunosuppresive systemic therapy was 488 days (207-2046) in the group of patients with moderate to severe cGvHD.Twelve patients died due to transplant related events, 7 were reported before day 100, all of infectious etiology. The NRM at two years was 21.9% (95% CI, 12-33.7%). Eleven patients (19.2%) had at least two episodes of CMV reactivation and one had cytomegalic gastrointestinal disease. One patient developed postransplantation lymphoproliferative disorder associated to Epstein Barr virus. Twenty patients (35%) developed noninfectious complications, being hemorrhagic diathesis, hepatotoxicity and severe mucositis the most frequents.With a median follow up of 28 months in alive patients (3-67), the GRFS at one year, OS and PFS at two years were 47.6% (95% CI, 42.8-52.2%), 59% (95% CI, 54.5-63.2%) and 52% (95% CI, 46.9-56.5%), respectively. The relapse incidence at two years was 26.3% (95% CI 14.7-39.4%).ConclusionsIn our center, the use of low ATG doses is protective against severe forms of acute GvHD, offering also a moderate protection against chronic GvHD in a cohort with high prevalence of mismatched unrelated donors, high median age and high risk DRI and HCTI. This approach doesn't seem to have a significant negative impact neither in GRFS, OS and PFS at two years. DisclosuresNo relevant conflicts of interest to declare.

Tandom Autologous Transplantation and Combined Infusion of CD19 and Bcma-Specific Chimeric Antigen Receptor T Cells for High Risk MM: Initial Safety and Efficacy Report from a Clinical Pilot Study

Background: Multiple myeloma (MM) is an incurable plasma cell malignancies despite the advent of numerously new drugs. Survival was poor particularly for high risk patients such as R-ISS stage III. The preliminary data from our center showed that the median PFS after auto-HSCT was 24 months for patients with R-ISS III stage, while 17 months for patients that achieved PR or less after induction. Chimeric antigen receptor (CAR)-transduced T cells is a promising strategy for cancer immunotherapy. Our previous study showed good response for RRMM patients after CD19 and BCMA-specific CART therapy without severe CRS and other deadly side effects. To improve the survival of high risk patients, this study was designed to observe the safety and efficacy of combined infusion of CD19 and BCMA-specific CART cells after autologous transplantation (SZ-MM-CART02 study, NCT 03455972).Methods:18-65y NDMM in R-ISS stage III, or who only achieved PR or less after 4 cycles of PAD triplet induction were enrolled with serum creatinine (Cr) <2.0 mg/dL, and adequate hepatic, cardiac and pulmonary function. BCMA and CD19 expression on MM cells were analyzed by flow cytometry. Lymphocytes were collected from PBSCs and cultured with an anti-CD3 monoclonal antibody to activate T-cell proliferation. The cells were transduced with recombinant lentiviral verctors which respectively contained the anti-BCMA or anti-CD19 single chain variable fragment (scFv), the cytoplasmic portion of the OX40 and CD28 costimulatory moiety, and the CD3z T-cell activation domain. This is the new third generation CAR technique applied in clinic. BUCY were used as conditioning, followed by infusion of autologous stem cells. Median time to engraftment were 10 days for nutrophils. CART-19 (1×107/kg on d0) and CART-BCMA cells as split-dose (40% on d1 and 60% on d2) were infused derectly on d14 to d20 after autologous transplantation. Levels of CAR-transduced cells are measured by qPCR. The cytokine release syndrome (CRS) was graded according to the UPen cytokine release syndrome grading system. Neurotoxic side effects and other toxicities were assessed according to the CTCAE v 4.03. Plasma levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-17A proteins were determined with a cytokine kit. Imids alone were given as maintenance therapy. Responses were assessed by IMWG criteria. 10-color flow cytometry was used to monitor MRD regularly after CART treatment. The median of follow-up was 3 (2∼11) months.Results: To date, 9 patients have completed the CART cells infusion (cohort 1). All cases expressed BCMA >50% without CD19 expression on MM cells. CRS occurred in 9 patients (100%) grade1 or 2 associated with fever(n=9), fatigue (n=9), elevated IL-6 and CRP (n=9), elevated ALT (n=1, grade 1). Two patients needed to use low-dose vascular active drugs (pts 04 and 07). Other toxicities to date included coagulopathy (n=6, grade 1 for 4 pts and grade 2 for 2 pts), elevated troponin T (n=4, grade 1), and atrial flutter (n=1). There was no serious CRS or neurologic complications occurred in this group of patients.The ORR was 100% with all patients were monitored for a period of more than 2 months, which may be eventually further improved. There were 2 CR, 1 VGPR, 4 PR, 2 SD after induction; 3 CR, 2 VGPR, 4 PR after APBSCT; 3 CR, 6 VGPR after CART therapy. MRD negativity in BM increased from 37.5% after transplantation to 66.7% after CART therapy latest. Four patients (pts 02, 03, 06 and 07) obtained partial PR after transplantation, and got VGPR after CART cells infusion. We found dramatic in vivo CART expansion that median of peak value of CART copies was 1059.54 folds (ranged from 536.90 to 10997.93 folds) which was 100 folds to that with RRMM patients in our previous study.Conclusions: Tandom autologous transplantation and combined infusion of CART-19 and CART-BCMA cells could be another choice of consolidation treatment for high risk MM patients. Toxicities to date including CRS and organ function impairment seemed to be mild and reversable. It is worthy of further study to compare DFS, OS between single autologous transplantation and tandom transplantation with CART therapy. Immune environment in high risk patients with multiple myelomaI remodelled by auto-HSCT may contribute to more rapid expansion of CART cells than that in RRMM patients, suggesting that the extent of CART expansion depends more than tumor burden. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Identifying optimal candidates for early TIPS among patients with cirrhosis and acute variceal bleeding: a multicentre observational study

ObjectivesEarly placement of transjugular intrahepatic portosystemic shunt (TIPS) has been shown to improve survival in high-risk patients (Child-Pugh B plus active bleeding at endoscopy or Child-Pugh C 10–13) with cirrhosis...

The Impact of Postmastectomy Radiation Scar Boost on Local Recurrence Free Survival in High Risk Patients

The Impact of Postmastectomy Radiation Scar Boost on Local Recurrence Free Survival in High Risk Patients

Factors Associated With Interstage Mortality Following Neonatal Single Ventricle Palliation.

Several advances have led to improved hospital survival following neonatal palliation (NP) of single ventricle (SV) anomalies. Nonetheless, a number of patients continue to suffer from interstage mortality (ISM) prior to subsequent Glenn. We aim to study patients' characteristics and anatomic, surgical, and clinical details associated with ISM. A total of 453 SV neonates survived to hospital discharge following NP. Competing risk analysis modeled events after NP (Glenn, transplantation, or death) and examined variables associated with ISM. Competing risk analysis showed that one year following NP, 10% of patients had died, 87% had progressed to Glenn, 1% had received heart transplantation, and 2% were alive without subsequent surgery. On multivariable analysis, factors associated with ISM were as follows: weight ≤2.5 kg (hazard ratio, HR = 2.4 [1.2-4.6], P = .013), premature birth ≤36 weeks (HR = 2.0 [1.0-4.0], P = .05), genetic syndromes (HR = 3.2 [1.7-6.1], P < .001), unplanned cardiac reoperation (HR = 2.1 [1.0-4.4], P = .05), and prolonged intensive care unit (ICU) stay >30 days following NP (HR = 2.5 [1.4-4.5], P < .001). Palliative surgery type (shunt, Norwood, band) was not associated with ISM, although aortopulmonary shunt circulation after Norwood was (HR = 5.4 [1.5-19.2] P = .01). Of interest, underlying SV anatomy was not associated with ISM (HR = 1.1 [0.6-2.2], P = .749). In our series, ISM following NP occurred in 10% of hospital survivors. As opposed to hospital death, underlying SV anomaly was not associated with ISM. Conversely, several patient factors (prematurity, low weight, and genetic syndromes) and clinical factors (unplanned reoperation and prolonged ICU stay following NP) were associated with ISM. Vigilant outpatient management that is individualized to specific clinical and social needs, taking into account all associated factors, is warranted to improve survival in high-risk patients.

Accelerated vs. conventionally fractionated adjuvant radiotherapy in high-risk head and neck cancer: a meta-analysis

BackgroundAdjuvant radiotherapy in advanced head and neck squamous cell cancer (HNSCC) reduces the risk of local-regional failure and most likely increases the survival rate. Patients at high risk for tumor recurrence may benefit from more aggressive altered fractionation schedules in order to reduce the overall time from surgery to completion of radiotherapy. Here, we reviewed the results of six randomized trials addressing the above hypothesis.MethodsIn the six trials of interest, a total of 988 patients with locally advanced HNSCC were randomly assigned to receive either accelerated or conventionally fractionated adjuvant radiotherapy. Hazard ratios (HR) were extracted from available publications for local-regional control, distant metastasis as well as overall-, cancer specific- and disease-free survival. Meta-analysis of the effect sizes was performed using fixed and random effect models. Acute and late side effects were categorized and summarized for comparison.ResultsAccelerated radiotherapy did not improve the loco-regional control (n = 988, HR = 0.740, CI = 0.48–1.13, p = 0.162), progression-free survival (HR = 0.89, CI = 0.76–1.04, p = 0.132) or overall survival (HR = 0.88, CI = 0.75–1.04, p = 0.148) significantly. Acute confluent mucositis occurred with significant higher frequency with accelerated radiotherapy. Late side effects did not differ significantly in either group.ConclusionAccelerated radiotherapy does not result in a significant improvement of loco-regional control or overall survival in high-risk patients. Acute but not late radiation toxicity were more frequent with the accelerated RT technique. In clinical practice accelerated postoperative radiation therapy might be a suitable option only for a subset of patients.

Early Transjugular Intrahepatic Portosystemic Shunt Creation Compared to Endoscopy With Pharmacotherapy in the Management of Variceal Rebleeding in Cirrhotic Patients: A Comprehensive Systematic Review and Meta-Analysis: Presidential Poster Award

Introduction: The use of early or rescue transjugular intrahepatic portosystemic shunt (TIPS) has been evaluated in cirrhotic patients with a history of variceal bleeding. In this study, we aimed to perform a systematic review and meta-analysis of studies investigating the efficacy and safety of early TIPS in the management of variceal bleeding as well as comparing the use of early compared to rescue TIPS. Methods: Medical electronic databases were queried for clinical studies in which TIPS creation was compared with endoscopy and pharmacotherapy treatment in cirrhotic patients with a history of variceal bleeding. Search results were screened against predefined eligibility criteria and data were extracted to a standard data extraction form. Meta-analysis was performed using Comprehensive Meta-Analysis software and the risk of bias of included studies was assessed using the Cochrane tool and modified Newcastle-Ottawa scale Results: Thirty-four studies that enrolled 2876 cirrhotic patients (n=1453 in the TIPS group and n=1423 in the endoscopy with pharmacotherapy group) were included. Overall analysis displayed significantly reduced re-bleeding, odds ratio (OR) = 0.29, 95% confidence interval (CI) [0.22-0.38], p< 0.0001) and bleeding-related death (OR= 0.28, 95% CI [0.18-0.44], p< 0.0001) in the TIPS group. There was no significant difference in all-cause mortality between all TIPS and endoscopy with pharmacotherapy (OR= 0.93, 95% CI [0.74-1.16], p= 0.52) and there was an increased incidence of hepatic encephalopathy (OR= 1.80, 95% CI [1.41-2.28], p< 0.0001) in the TIPS group (pooled analysis of both early and rescue TIPS). Early use of TIPS did not reveal any differences in hepatic encephalopathy (OR= 1.27, 95% CI [0.9-1.7], p= 0.13) and showed a decreased mortality in high risk patients (Child-Pugh class C, Child-Pugh class B with active bleeding at endoscopy, and hepatic venous pressure gradient [HVPG] ≥20 mm Hg) when compared to rescue TIPS. Conclusion: TIPS creation decreases rebleeding at the cost of increased hepatic encephalopathy with no survival benefit. Early TIPS creation may confer better clinical outcomes in terms of comparable hepatic encephalopathy and improved survival in high-risk patients when compared to rescue TIPS.

Evaluation of postadjuvant therapy for ampulla of vater carcinoma: multicenter: a retrospective study

Ampulla of vater carcinoma (AOV) is an infrequent tumor that account for about 0.2% of gastrointestinal malignancies. The incidence of AOV carcinoma is steadily increasing. But there are no guidelines from both the NCCN and the ESMO for the treatment of advanced AOV carcinoma. Only a few retrospective studies have focused on the adjuvant treatment in AOV carcinoma. So, we conducted multicenter retrospective review for evaluation of postadjuvant therapy for AOV carcinoma. Patients who underwent curative resection for AOV carcinoma at the four hospital (Yonsei Gangnam severance hospital, Seoul national university hospital, Seoul national university bundang hospital, National cancer center, n =715; 2002-2015) were reviewed. Patients with metastatic disease at surgery, or insufficient pathologic data were excluded. Adjuvant treatment were chemotherapy or chemoradiotherapy. Overall survival and recurrence free survival was compared using Kaplan-Meier estimates. In univariate analysis, locally advanced T stage (T3-4) and node positive, perineural invasion, lymphovascular invasion, moderately cell differentiation were associated with adjuvant treatment. (p = < 0.001) No adjuvant group (Group 1) were 437 patient and adjuvant treatment group were 272 patients (Chemotherapy,Group 2; 94 patients, Chemoradiotherapy, Group 3; 184 patients). In the high risk patients, such as patients with node-positive, Group 3 was significantly associated with increased recurrence free survival (p = < 0.05). Adjuvant treatment did not improve survival in low risk patients. However adjuvant chemoradiation treatment maybe improved recurrence free survival in high risk patients (node-positive, advanced stage). Prospective evaluation of appropriate adjuvant treatment should be considered.

A four-protein expression prognostic signature predicts clinical outcome of lower-grade glioma

BackgroundGlioma is a wide category of brain tumor originates from glial cells. Lower-Grade Glioma (LGG) consists of World Health Organization (WHO) grade II and grade III gliomas. Since the LGGs can infiltrate into adjacent areas, the complete removal of tumor is difficult and it results in recurrence and malignant progression to high grade glioma. Our study uncovers robust survival indicators in LGG which can be checked by immunohistochemistry to predict the outcome of lower grade. In addition, it unravelled the novel therapeutic targets in order to improve the survival of LGG patients. MethodsTo identify a prognostic signature based on protein expression in LGGs, we analysed Reverse Phase Protein Array data of LGG samples (n = 380) from The Cancer Genome Atlas cohort. We made random stratification of samples into discovery (n = 228) and validation datasets (n = 152). We performed multivariate Cox proportional hazards regression analysis of proteins (n = 219) using discovery dataset with age, WHO grade and IDH mutation status. ResultsWe identified four-protein prognostic signature that can segregate patients into high- and low-risk. The signature estimates poor overall survival for high-risk patients in both discovery (hazard ratio [HR] = 4.11; 95% confidence interval [CI] = 2.18–7.75; p < 0.0001) and validation datasets (HR = 3.49; 95% CI = 1.52–8.01; p < 0.0001). Among the four markers, CHK2_pT68 was found to be protective, while MSH6, ARID1A and PAXILLIN were associated with poor survival. Additionally, Multivariate Cox proportional hazards regression analysis of this signature with age, WHO grade and IDH mutation status revealed this prognostic signature to be an independent prognosticator in both datasets. ConclusionsOur finding discovered a set of potential protein biomarkers to predict survival and it will help in the subsequent treatment management of LGG patients.

Postoperative (chemo) radiation in patients with squamous cell cancers of the head and neck \u2013 clinical results from the cohort of the clinical cooperation group \u201cPersonalized Radiotherapy in Head and Neck Cancer\u201d

BackgroundPostoperative (chemo) radiation improves tumor control and survival in high-risk patients with head and neck squamous cell carcinoma based on established risk factors. The clinical cooperation group “Personalized Radiotherapy in Head and Neck Cancer” focuses on the identification and validation of new biomarkers, which are aimed at eventually stratifying and personalizing the therapy concept. Hence, we reviewed all patients with head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, treated with postoperative (chemo) radiation from 06/2008 until 06/2015 at the Department of Radiation Oncology in the University Hospital, LMU Munich. Here we report the clinical results of the cohort, laying the foundation for further research within the framework of a clinical cooperation group.MethodsPatient data were retrospectively (until 2013) and prospectively (from 2013) collected and analyzed for outcome and treatment failures with regard to previously described and established risk factors.ResultsWe identified 302 patients (median follow-up 45 months, average age 60.7 years), having received postoperative (chemo)radiation (median 64 Gy). Chemotherapy was added in 58% of cases, mostly Cisplatin/5- Fluorouracil in concordance with the ARO 96–3 study. The 3-year overall survival, local, locoregional and distant failure estimates were 70.5, 9.7, 12.2 and 13.5%, respectively. Human papillomavirus-associated oropharyngeal cancer was associated with a significant improved overall survival, locoregional, distant and overall tumor control rates in multivariate analysis. Additionally, in multivariate analysis, for local failure, resection status and perineural invasion, for locoregional and distant failure extracapsular extension and for overall survival the presence of nodal disease were significant adverse factors. Moreover, 138 patients have been treated in concordance with the ARO 96–3 protocol, corroborating the results of this study.ConclusionsOur cohort represents a large unselected cohort of patients with head and neck squamous cell carcinoma treated with postoperative (chemo)radiation. Tumor control rates and survival rates are consistent with the results of previously reported data.

Adjuvant Sunitinib in High-Risk Patients with Uveal Melanoma: Comparison with Institutional Controls

To compare overall survival in high-risk patients with primary uveal melanoma who received adjuvant sunitinib with institutional controls. Retrospective cohort. Selection criteria were (1) monosomy 3 and 8q amplification by cytogenetic or DecisionDx-UM Class 2 and (2) monosomy 3 and large tumor size (T3-4 by American Joint Committee on Cancer classification). Exclusion criteria were date of diagnosis before 2007 or after 2013 and age <18 years. A cohort of patients who intended to receive adjuvant sunitinib for 6 months was compared with institutional historical controls with the same risk factors. Kaplan-Meier and Cox proportional hazards models were used to analyze the outcome. Propensity score was used to adjust for nonrandom assignment to sunitinib. Overall survival. From the Wills Eye Hospital Oncology Service Uveal Melanoma Cytogenetic Database (N= 1172), 128 patients fulfilled the selection and exclusion criteria. Median follow-up was 52.7 months (range, 0.26-108 months). A total of 54 patients received sunitinib. Their median age was 56 years (range, 29-81 years), and 48% were men. A total of 74 historical controls in the same risk category were identified. Their median age was 62 years (21-80 years), and 48% were men. Patients in the sunitinib group had worse cytogenetic or molecular features (monosomy 3 and 8q amplification or class 2 87% vs. 57%; P < 0.001), had smaller tumor sizes (T3-4 56% vs. 83%; P= 0.001), and were younger. There were 51 deaths, 14 (26%) in the sunitinib group and 37 (50%) in the control group. In the univariate analysis, the sunitinib group had longer overall survival (hazard ratio, 0.53; 95% confidence interval, 0.29-0.99; P= 0.041). In multivariate Cox regression analysis, interaction between use of sunitinib and age as a dichotomous variable was highly significant (P= 0.003). The following variables were statistically associated with prediction of overall survival: cytogenetic/molecular status (P= 0.015), T-size category (P= 0.022), gender (P= 0.040), and adjuvant sunitinib in patients aged <60 years (P= 0.004). Results were confirmed by propensity score analysis. In this retrospective study, the use of sunitinib in the adjuvant setting was associated with better overall survival.

Albumin-Bilirubin and Platelet-Albumin-Bilirubin Grades Accurately Predict Overall Survival in High-Risk Patients Undergoing Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma

PurposeTo evaluate albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades in predicting overall survival in high-risk patients undergoing conventional transarterial chemoembolization for hepatocellular carcinoma (HCC). Materials and MethodsThis single-center retrospective study included 180 high-risk patients (142 men, 59 y ± 9) between April 2007 and January 2015. Patients were considered high-risk based on laboratory abnormalities before the procedure (bilirubin > 2.0 mg/dL, albumin < 3.5 mg/dL, platelet count < 60,000/mL, creatinine > 1.2 mg/dL); presence of ascites, encephalopathy, portal vein thrombus, or transjugular intrahepatic portosystemic shunt; or Model for End-Stage Liver Disease score > 15. Serum albumin, bilirubin, and platelet values were used to determine ALBI and PALBI grades. Overall survival was stratified by ALBI and PALBI grades with substratification by Child-Pugh class (CPC) and Barcelona Liver Clinic Cancer (BCLC) stage using Kaplan-Meier analysis. C-index was used to determine discriminatory ability and survival prediction accuracy. ResultsMedian survival for 79 ALBI grade 2 patients and 101 ALBI grade 3 patients was 20.3 and 10.7 months, respectively (P < .0001). Median survival for 30 PALBI grade 2 and 144 PALBI grade 3 patients was 20.3 and 12.9 months, respectively (P = .0667). Substratification yielded distinct ALBI grade survival curves for CPC B (P = .0022, C-index 0.892), BCLC A (P = .0308, C-index 0.887), and BCLC C (P = .0287, C-index 0.839). PALBI grade demonstrated distinct survival curves for BCLC A (P = 0.0229, C-index 0.869). CPC yielded distinct survival curves for the entire cohort (P = .0019) but not when substratified by BCLC stage (all P > .05). ConclusionsALBI and PALBI grades are accurate survival metrics in high-risk patients undergoing conventional transarterial chemoembolization for HCC. Use of these scores allows for more refined survival stratification within CPC and BCLC stage.

Factors impacting time to engraftment in patients with high-risk neuroblastoma following autologous stem cell transplant.

e22008 Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood, with overall survival for high-risk patients (HRNBL) near 50%. The outcomes of HRNBL have improved significantly with high dose chemotherapy followed by autologous stem cell rescue (ABMT). Data about factors influencing the rate of hematopoietic recovery following ABMT in HRNBL is lacking in the literature. Methods: This is a retrospective chart review of patients with HRNBL treated at Texas Children’s Hospital from October 2011 - November 2016. Neutrophil engraftment was considered the first of three consecutive days with post-transplant neutrophil count &gt; 500 cells/uL. Red blood cell and platelet engraftment were considered at a hemoglobin &gt; 8g/dL and platelets &gt; 20,000/uL three days after the last transfusion. Race and conditioning regimen were analyzed using one-way ANOVA; amount of infused cells was analyzed using Pearson correlation coefficients; chemotherapy delay and bone marrow (BM) involvement after cycle 2 of induction chemotherapy were analyzed using independent sample t-tests. Results: The study included 17 males and 8 females with a median age at diagnosis of 3 years. 15 patients were Caucasian, 4 African-American, 5 Hispanic, and 1 Asian. The mean dose of infused CD34+ cells was 3.44x108cells/kg. 16 patients received conditioning therapy with carboplatin/etoposide/melphalan, 7 received busulfan/melphalan, and 2 received thiotepa/cyclophosphamide. Race was found to be significant for hemoglobin engraftment (p &lt; 0.001). There were trends toward significance for conditioning regimen and neutrophil engraftment (p = 0.079), presence of delays in induction chemotherapy due to hematologic toxicity for platelet engraftment (p = 0.069) and BM involvement after cycle 2 of induction chemotherapy for hemoglobin engraftment (p = 0.12). Conclusions: Knowing the barriers for timely engraftment may help develop interventions for future patients. Race significantly impacted hemoglobin engraftment. Conditioning regimen, delays in induction chemotherapy, and BM involvement after cycle 2 of induction chemotherapy trended towards significance and need to be validated in a larger dataset.

Impact of postmastectomy radiation therapy in T1-2 breast cancer patients with 1-3 positive axillary lymph nodes.

The effect of postmastectomy radiotherapy (PMRT) on T1-2 breast cancer patients with 1-3 positive axillary lymph nodes is controversial up to now. The purpose of this study was to evaluate the impact of postmastectomy radiotherapy for these patients. The prognostic factor effecting locoregional free-survival (LRFS) was also analyzed. In the retrospective clinical data of 1674 eligible patients, survival analysis was performed using the method of Kaplan-Meier and the log-rank test. Cox regression analysis was applied to identify the significant prognostic factors. We found PMRT increased 5-year LRFS (p=0.003), but could not improve 5-year disease-free survival or overall survival statistically. For patients without PMRT, multivariate analysis revealed that age, lymph node ratio and molecule subtype were risk factors effecting LRFS. To further analyze the role of PMRT, we grouped all the patients into low risk group (0 or 1 risk factor) and high risk group (2 or 3 risk factors) depending on these risk factors. We found that in low-risk group, PMRT increased only 5-year LRFS (p=0.012). However, in high-risk group, PMRT increased both 5-year LRFS (p=0.005) and 5-year disease-free survival (p=0.033), but could not improve 5-year overall survival statistically. Thus, these data provide the evidence that PMRT could improve LRFS for T1-2 breast cancer patients with 1-3 positive axillary lymph nodes. Additionally, PMRT could improve LRFS and disease-free survival for high risk patients. Age, lymph node ratio and molecule subtype were high risk factors effecting LRFS in our study.

Application of a Risk Score to Identify Older Adults with Community-Onset Pneumonia Most Likely to Benefit From Empiric Pseudomonas Therapy.

To assess the impact of empiric Pseudomonas pharmacotherapy on 30-day mortality in hospitalized patients with community-onset pneumonia stratified according to their risk (low, medium, or high) of drug-resistant pathogens. Retrospective cohort study. Veterans Health Administration database. A total of 50,119 patients who were at least 65 years of age, hospitalized with pneumonia, and received antibiotics within 48 hours of admission between fiscal years 2002 and 2007. Patients were stratified into empiric Pseudomonas therapy (31,027 patients) and no Pseudomonas therapy (19,092 patients) groups based on antibiotics received during their first 48 hours of admission. A clinical prediction scoring system developed in 2014 that stratifies patients with community-onset pneumonia according to their risk of drug-resistant pathogens was used to identify patients who were likely to benefit from empiric Pseudomonas therapy as well as those in whom antipseudomonal therapy could be spared; patients were classified into low-risk (68%), medium-risk (21%), and high-risk (11%) groups. Of the 50,119 patients, 62% received Pseudomonas therapy. All-cause 30-day mortality was the primary outcome. Empiric Pseudomonas therapy (adjusted odds ratio 0.72, 95% confidence interval 0.62-0.84) was associated with lower 30-day mortality in the high-risk group but not the low- or medium-risk groups. Application of a risk score for patients with drug-resistant pathogens can identify patients likely to benefit from empiric Pseudomonas therapy. Widespread use of this score could reduce overuse of anti-Pseudomonas antibiotics in low- to medium-risk patients and improve survival in high-risk patients.

Improved Survival of High Risk Patients with Parainfluenza Virus Following Hematopoietic Cell Transplantation: Role of Aerosolized Ribavirin

Parainfluenza viruses (PIV) ARE associated with severe respiratory tract infections among immunocompromised patients. However, the most perplexing feature of PIV following hematopoietic cell transplantation (HCT) is the dichotomous nature of risk for life-threatening infection. Specifically, the vast majority of patients will not require treatment of any kind whereas a small subset appears to be at such high risk of death that it has been questioned if successful treatment is even possible.In 2007, we implemented a standardized approach to patients diagnosed with Parainfluenza virus (PIV) following HCT at Stanford University Medical Center (Fig 1) based on the need for supplemental oxygen and/or specific risk factors. We performed both a prospective analysis of cases of lower respiratory tract infection and a retrospective review of all 2495 patients transplanted during this period. The epidemiology, risk factors, clinical status, and outcome of the 115 PIV patients using this protocol from September 2007 through May 2015 shows that prudent, risk-stratified application of antiviral therapies in can result higher survival rates among patients with PIV post-HCT. Moreover, high risk patients who received aerosolized ribavirin had a lower mortality rate than those who were either not treated or received oral ribavirin. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.