Association of Contrast and Acute Kidney Injury in the Critically Ill: A Propensity-Matched Study.

BACKGROUND: Despite evidence that low osmolar radiocontrast media is not associated with acute kidney injury, it is important to evaluate this association in critically ill patients with normal kidney function. METHODS: This retrospective observational study included 7,333 adults with an ICU stay at a six-hospital health system in south Florida. Patients who received contrast were compared with unexposed control subjects prior to and following propensity score (PS) matching derived from baseline characteristics, admission diagnoses, comorbidities, and severity of illness. Acute kidney injury (AKI), defined as initial onset (stage I) or increased severity, was determined from serum creatinine levels according to Kidney Disease: Improving Global Outcomes guidelines. RESULTS: Based on 2,306 PS-matched pairs obtained from 2,557 patients who received IV contrast and 4,776 unexposed control subjects, the increase in AKI attributable to contrast was 1.3% (19.3% vs 18.0%; P = .273), and no association was found between contrast and the pattern of onset and recovery. Hospital mortality increased by 14.3% subsequent to AKI (18.0 vs 3.6; P < .001), but the risk ratio in relation to patients with stable AKI did not vary when stratified according to contrast. Multivariable regression identified sepsis, metabolic disorders, diabetes, history of renal disease, and severity of illness as factors that were more strongly associated with AKI. CONCLUSIONS: In critically ill adults with normal kidney function, low osmolar radiocontrast media did not substantively increase AKI. Rather than limiting the use of contrast in ICU patients, efforts to prevent AKI should focus on the susceptibility of patients with sepsis, diabetes complications, high Acute Physiology and Chronic Health Evaluation scores, and history of renal disease.

Cross-sectional survey to inform the development of a telehealth support model: a feasibility study for women undergoing breast cancer surgery.

BACKGROUND: For patients undergoing breast cancer surgery, the pre- and post-operative periods can be characterised by feelings of fear, anxiety, and uncertainty. Telehealth offers an opportunity to provide perioperative support to surgical patients and overcome some of the barriers to accessing care. AIMS: In order to inform the development of a telehealth support model for women undergoing breast cancer surgery, this feasibility study explored: (a) access and preferences for telehealth; and (b) the proportion of participants who reported problems with unmet information and preparation needs related to surgery, post-operative pain, anxiety, and quality of life. METHODS: Women aged 18-85 years attending for a follow-up appointment within 2 months of undergoing surgery for breast cancer were asked to complete a baseline (T1) and 1-month follow-up (T2) survey. Surveys assessed telehealth access and preferences, preparatory information receipt and preparedness for surgery, and anxiety, pain, and quality of life. RESULTS: Fifty-three T1 (45% consent rate) and 50 T2 surveys were returned. One fifth of the sample (20%) travelled 50 km or more to access surgery. Most participants had access to a device suitable for telehealth (75%); however, only 15% indicated that they would have accepted a teleconsultation with their surgeon post-operatively if this had been offered. The most frequently reported unmet preparatory information needs were information about: how long it would take to recover from the surgery; how other patients had experienced similar surgery; and practical needs such as parking or transport. Approximately one third of the sample reported potentially clinically significant symptoms of anxiety, and less than one in ten women reported moderate levels of pain. CONCLUSIONS: While the majority of women had access to a suitable device and internet connection for telehealth, less than one fifth would have accepted a home-based video-link teleconsultation with their surgeon post-operatively. A small proportion of the sample would have liked more information about aspects of surgery including about managing side effects and anxiety. The key findings in terms of teleconsultation preferences and information and preparation needs from this study will be incorporated into the telehealth support model being developed.

Prospective Validation of Diagnostic Tumor Biomarkers in Men Treated With Radiotherapy for Prostate Cancer.

Background: In prior retrospective studies, we assessed a number of prostate tumor tissue biomarkers that were associated independently with the clinical outcome of men treated with radiotherapy (RT) ± androgen deprivation therapy (ADT). In this report, the associations of selected biomarkers with biochemical or clinical disease failure (BCDF) were prospectively evaluated in men with T1-T3 prostate cancer on a randomized hypofractionation trial. Methods: Biomarkers were analyzed in 263 of 303 men randomly assigned to standard vs moderate hypofractionation. Median follow-up was 65.9 months. Archival tissue was analyzed for Ki-67 (n = 231), MDM2 (n = 209), p16 (n = 195), Cox-2 (n = 126), p53 (n = 206), bcl2 (n = 223), bax (n = 210), and PKA (n = 160). The base model for multivariable Fine-Gray regression analysis included treatment assignment and risk groups. All statistical tests were two-sided. Results: Each biomarker was tested one at a time relative to the base model and selected for inclusion in multivariable analysis. Ki-67 (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.19 to 4.48, P = .01) and bcl2&bax (HR = 2.19, 95% CI = 1.08 to 4.46, P = .03) were statistically significantly related to higher BCDF and were independently statistically significant when considered jointly (Ki-67: HR = 2.26, 95% CI = 1.12 to 4.58, P = .02; bcl2&bax: HR = 2.14, 95% CI = 1.03 to 4.41, P = .04). At 2.5 years postradiotherapy, the C-index of Ki-67 was 73.2%, while for the base model was only 46.2%; Ki-67 was the most statistically significant when tested without bcl2&bax. Conclusions: In this prospective multiple biomarker analysis in men with prostate cancer treated with RT±ADT, both Ki-67 and bcl2&bax were independently related to early BCDF; however, Ki-67 alone is indicated to be the most clinically meaningful by C-index analysis and is universally available.

Robotic-assisted ventral hernia repair: a multicenter evaluation of clinical outcomes.

BACKGROUND: The open approach continues to be widely performed for ventral hernia repair, while the minimally invasive laparoscopic approach has grown adoption over the last decade. Recently, robotic operation was described as a new modality due to the ease for performing intracorporeal closure of the hernia defect. This study is one of the first multi-institutional case series evaluating robotic-assisted laparoscopic ventral hernia repairs, with the goal of describing robotic-assisted surgical techniques for ventral and incisional hernia repair and the outcomes in teaching and community hospital settings. METHODS: Medical records of consecutive patients (including surgeon's learning curve cases) who underwent ventral or incisional hernia repair utilizing the da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale CA) were retrospectively reviewed. Data collected included preoperative history and perioperative outcomes. RESULTS: Data for a total of 368 patients from four institutions involving five surgeons were analyzed. They were predominantly females (60.3 %), and the mean age was 51 years. The majority of the patients were obese or morbidly obese (47.8 and 20.9 %), and 83.2 % of the patients had a history of prior abdominal operation. Conversion rate was 0.8 %, and mean length of stay was 1 day. Total postoperative complications rate up to 30 days was 8.4 %, of which incidence of paralytic ileus was 2.4 %. CONCLUSION: This large case series of 368 patients demonstrates reproducibility of safety and performance associated with robotic-assisted ventral hernia repairs performed by five surgeons at four institutions. In addition, the results of short term perioperative outcomes for surgeons during their early experience for robotic-assisted cases are in the range of what is reported in the existing published data on laparoscopic and open ventral hernia repairs. Further comparative evidence initiatives are being pursued to determine the benefits of robotic-assisted technique and technology for long-term and patient-reported outcomes.

A multicenter study of initial experience with single-incision robotic cholecystectomies (SIRC) demonstrating a high success rate in 465 cases.

BACKGROUND: Recently, the robotic single-site platform has been used to ameliorate the difficulties seen in single-incision laparoscopic surgery (SILC) while preserving the benefits of standard laparoscopic cholecystectomy. The purpose of this study is to describe the clinical outcomes of a large series of single-incision robotic cholecystectomy (SIRC). METHODS: Medical records of consecutive patients who underwent SIRC were retrospectively reviewed. All procedures were performed by six surgeons at five different North American centers involved in the study. All patients included in the study underwent a cholecystectomy attempted through single site at the umbilicus, using the da Vinci(®) Surgical System (Intuitive Surgical Inc. Sunnyvale, CA). RESULTS: A total of 465 patients met study criteria. Median age was 48 years (range 18-89); 351 (75.5 %) were female and 304 (66.4 %) were overweight or obese. Except for gender, case characteristics differed significantly by surgeon/site. Previous abdominal surgery was reported for 226 (48.6 %) cases. SIRC was successfully completed in 455 (97.8 %) cases, and there were no conversions to open surgery. Median surgical time was 52 min with a decreasing trend after 55-85 cases. Male gender, obesity and diagnoses other than biliary dyskinesia were independent predictors of longer surgical times. The complication rate was 2.6 %. CONCLUSIONS: Our large, multicenter study demonstrates that robotic single-site cholecystectomy is safe and feasible in a wide range of patients.

Predictors of poor outcome despite recanalization: a multiple regression analysis of the NASA registry.

BACKGROUND: Mechanical thrombectomy with stent-retrievers results in higher recanalization rates compared with previous devices. Despite successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b) of 70-83%, good outcomes by 90-day modified Rankin Scale (mRS) score ≤2 are achieved in only 40-55% of patients. We evaluated predictors of poor outcomes (mRS >2) despite successful recanalization (TICI ≥2b) in the North American Solitaire Stent Retriever Acute Stroke (NASA) registry. METHODS: Logistic regression was used to evaluate baseline characteristics and recanalization outcomes for association with 90-day mRS score of 0-2 (good outcome) vs 3-6 (poor outcome). Univariate tests were carried out for all factors. A multivariable model was developed based on backwards selection from the factors with at least marginal significance (p≤0.10) on univariate analysis with the retention criterion set at p≤0.05. The model was refit to minimize the number of cases excluded because of missing covariate values; the c-statistic was a measure of predictive power. RESULTS: Of 354 patients, 256 (72.3%) were recanalized successfully. Based on 234 recanalized patients evaluated for 90-day mRS score, 116 (49.6%) had poor outcomes. Univariate analysis identified an increased risk of poor outcome for age ≥80 years, occlusion site of internal carotid artery (ICA)/basilar artery, National Institute of Health Stroke Scale (NIHSS) score ≥18, history of diabetes mellitus, TICI 2b, use of rescue therapy, not using a balloon-guided catheter or intravenous tissue plasminogen activator (IV t-PA), and >30 min to recanalization (p≤0.05). In multivariable analysis, age ≥80 years, occlusion site ICA/basilar, initial NIHSS score ≥18, diabetes, absence of IV t-PA, ≥3 passes, and use of rescue therapy were significant independent predictors of poor 90-day outcome in a model with good predictive power (c-index=0.80). CONCLUSIONS: Age, occlusion site, high NIHSS, diabetes, no IV t-PA, ≥3 passes, and use of rescue therapy are associated with poor 90-day outcome despite successful recanalization.

Predictors of Mortality in Acute Ischemic Stroke Intervention: Analysis of the North American Solitaire Acute Stroke Registry.

BACKGROUND AND PURPOSE: Failure to recanalize predicts mortality in acute ischemic stroke. In the North American Solitaire Acute Stroke registry, we investigated parameters associated with mortality in successfully recanalized patients. METHODS: Logistic regression was used to evaluate baseline characteristics and recanalization parameters for association with 90-day mortality. A multivariable model was developed based on backward selection with retention criteria of P<0.05 from factors with at least marginal significance (P≤0.10), then refit to minimize the number of excluded cases (missing data). RESULTS: Successfully recanalized patients had lower mortality (25.2% [59/234] versus 46.9% [38/81] P<0.001). There was no difference in symptomatic intracranial hemorrhage between patients with successful versus failed recanalization (9% [21/234] versus 14% [11/79]; P=0.205). However, mortality was significantly higher in patients with symptomatic intracranial hemorrhage (72% [23/32] versus 26% [73/281]; P<0.001). Proximal occlusion (internal carotid artery or vertebrobasilar), initial National Institutes of Health Stroke Scale≥18, use of rescue therapy (P<0.05), and 3+ passes (P<0.10) were associated with mortality in recanalized patients. In the multivariate model with good predictive power (c index=0.72), proximal occlusion, initial National Institutes of Health Stroke Scale≥18, and use of rescue therapy remained significant independent predictors of 90-day mortality. CONCLUSIONS: Failure to recanalize and presence of symptomatic intracranial hemorrhage resulted in increased mortality. Despite successful recanalization, proximal occlusion, high National Institutes of Health Stroke Scale, and need for rescue therapy were predictors of mortality.

Post-radiotherapy prostate biopsies reveal heightened apex positivity relative to other prostate regions sampled.

BACKGROUND AND PURPOSE: Prostate biopsy positivity after radiotherapy (RT) is a significant determinant of eventual biochemical failure. We mapped pre- and post-treatment tumor locations to determine if residual disease is location-dependent. MATERIALS AND METHODS: There were 303 patients treated on a randomized hypofractionation trial. Of these, 125 underwent prostate biopsy 2-years post-RT. Biopsy cores were mapped to a sextant template, and 86 patients with both pre-/post-treatment systematic sextant biopsies were analyzed. RESULTS: The pretreatment distribution of positive biopsy cores was not significantly related to prostate region (base, mid, apex; p=0.723). Whereas all regions post-RT had reduced positive biopsies, the base was reduced to the greatest degree and the apex the least (p=0.045). In 38 patients who had a positive post-treatment biopsy, there was change in the rate of apical positivity before and after treatment (76 vs. 71%; p=0.774), while significant reductions were seen in the mid and base. CONCLUSION: In our experience, persistence of prostate tumor cells after RT increases going from the base to apex. MRI was used in planning and image guidance was performed daily during treatment, so geographic miss of the apex is unlikely. Nonetheless, the pattern observed suggests that attention to apex dosimetry is a priority.

Reliability and accuracy of simple visual estimation in assessment of peripheral arterial stenosis.

PURPOSE: To evaluate reliability, accuracy, and agreement of simple visual estimation (SVE) in determining the degree of peripheral arterial stenosis compared with calibrated measurements. MATERIALS AND METHODS: In 2 sessions, 23 interventionists with a wide range of experience and subspecialty training reviewed 42 angiographic images of lower extremity and carotid arteries (21 iliofemoral arteries and 21 carotid arteries). An independent physician measured all lesions using manual calipers. Intrarater and interrater reliability were assessed by intraclass correlation. A ± 5% error was considered the threshold for accuracy, and weighted κ statistics were computed to assess agreement with respect to the degree of stenosis (< 50%, nonsignificant; 50%-80%, significant; > 80%, severe). RESULTS: Intrarater reliability of SVE was 0.99, and interrater reliability was 0.83. Accuracy varied from 52.8% for images of severe stenosis to 26.5% and 18.1% for significant and nonsignificant stenosis, respectively (P < .001). Agreement between SVE and caliper with regard to degree of stenosis was good (weighted κ 0.56) overall with correct classification ranging from 92.6% for severe stenosis to 53.4% and 68.2% for significant and nonsignificant stenosis, respectively (P < .001). Misclassification of nonsignificant and significant stenosis was more frequent for carotid arteries than for lower extremities. CONCLUSIONS: Despite high reliability, SVE of peripheral arterial stenosis has limited accuracy in determining the exact degree of stenosis. Although severe stenosis is readily identified by SVE, arterial stenosis of < 80% is frequently overestimated, especially for carotid arteries, and should be confirmed by caliper assessment.

Volumetric spectroscopic imaging of glioblastoma multiforme radiation treatment volumes.

PURPOSE: Magnetic resonance (MR) imaging and computed tomography (CT) are used almost exclusively in radiation therapy planning of glioblastoma multiforme (GBM), despite their well-recognized limitations. MR spectroscopic imaging (MRSI) can identify biochemical patterns associated with normal brain and tumor, predominantly by observation of choline (Cho) and N-acetylaspartate (NAA) distributions. In this study, volumetric 3-dimensional MRSI was used to map these compounds over a wide region of the brain and to evaluate metabolite-defined treatment targets (metabolic tumor volumes [MTV]). METHODS AND MATERIALS: Volumetric MRSI with effective voxel size of ∼1.0 mL and standard clinical MR images were obtained from 19 GBM patients. Gross tumor volumes and edema were manually outlined, and clinical target volumes (CTVs) receiving 46 and 60 Gy were defined (CTV46 and CTV60, respectively). MTVCho and MTVNAA were constructed based on volumes with high Cho and low NAA relative to values estimated from normal-appearing tissue. RESULTS: The MRSI coverage of the brain was between 70% and 76%. The MTVNAA were almost entirely contained within the edema, and the correlation between the 2 volumes was significant (r=0.68, P=.001). In contrast, a considerable fraction of MTVCho was outside of the edema (median, 33%) and for some patients it was also outside of the CTV46 and CTV60. These untreated volumes were greater than 10% for 7 patients (37%) in the study, and on average more than one-third (34.3%) of the MTVCho for these patients were outside of CTV60. CONCLUSIONS: This study demonstrates the potential usefulness of whole-brain MRSI for radiation therapy planning of GBM and revealed that areas of metabolically active tumor are not covered by standard RT volumes. The described integration of MTV into the RT system will pave the way to future clinical trials investigating outcomes in patients treated based on metabolic information.

A phase II study of capecitabine plus docetaxel in gemcitabine-pretreated metastatic pancreatic cancer patients: CapTere.

PURPOSE: Docetaxel and capecitabine combination is synergistic in preclinical models. We investigated the efficacy and toxicity of this combination as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma (mPC), pretreated with gemcitabine-based chemotherapy. METHODS: Eligible patients were treated with capecitabine 800 mg/m(2) orally PO bid on days 1-14 in combination with intravenous docetaxel 30 mg/m(2) on days 1 and 8 of each 21-day cycle. The primary end point was overall response rate. Using a three-stage sequential design, two interim analyses for early stopping due to lack of efficacy were planned and conducted after 13 and 26 patients were accrued. Secondary end points included time to treatment failure, progression-free survival (PFS), overall survival (OS) and 50 % drop in CA19-9 levels. RESULTS: Forty-three patients were evaluable for toxicity and 42 evaluable for response, at a median age of 64 years. The majority of patients (74 %) had ECOG PS 0-1. Six patients (14 %) achieved a partial tumor response, and stable disease for ≥2 cycles was observed in 59 % of patients (n = 25). Thirty-five percent (n = 11/31) of patients had a ≥50 % decrease in CA19-9 levels. The median PFS was 3.7 months (95 % CI 2.1-4.3 months), and the median OS was 5.3 months (95 % CI 4.3-8.6 months). Treatment was generally well tolerated. Grade 3 toxicity and grade 4 toxicity were seen in 45 and 5 % of patients, respectively. One patient had a potential treatment-related mortality. CONCLUSIONS: The combination of capecitabine and docetaxel is active and well tolerated in mPC patients pretreated with gemcitabine-based therapy.

Randomized trial of hypofractionated external-beam radiotherapy for prostate cancer.

PURPOSE: To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer. PATIENTS AND METHODS: Between June 2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed. RESULTS: There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT. CONCLUSION: The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.

FOXP3 subcellular localization predicts recurrence in oral squamous cell carcinoma.

Forkhead box protein P3 (FOXP3) expression in tumor infiltrating CD4(+)T cells is generally associated with an intrinsic capacity to suppress tumor immunity. Based on this notion, different studies have evaluated the prognostic value of this maker in cancer but contradictory results have been found. Indeed, even within the same cancer population, the presence of CD4(+)FOXP3(+)T cells has been associated,with either a poor or a good prognosis, or no correlation has beenfound. Here, we demonstrate,in patients with oral squamous cell carcinoma (OSCC), that what really represents a prognostic parameter is not the overall expression of FOXP3 but its intracellular localization.While overallFOXP3 expression in tumor infiltrating CD4(+)T cells does not correlate with tumor recurrence, its intracellular localization within the CD4 cells does: nuclear FOXP3 (nFOXP3) is associated with tumor recurrence within 3 years, while cytoplasmicFOXP3 (cFOXP3) is associated with a lower likelihood of recurrence. Thus, we propose elevated levels of the cFOXP3/nFOXP3 ratio within tumor infiltrating CD4(+) T cells as a predictor of OSCC recurrence.

Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory.

Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, prohibitive costs associated with current technology required for culture and expansion of tumor-reactive T-cells, the need for intense preconditioning regimens to induce lymphopenia, and the unpredictable anti-tumor effect of adoptively transferred T-cells remain significant impediments for its clinical implementation. Here we report a simplified combinatorial approach that involves short activation of CD8(+) T cells in the presence of IL-12 followed by adoptive transfer into tumor bearing animals after a single injection of cyclophosphamide. This approach resulted in complete eradication of B16 melanoma, and the establishment of long term immunological memory capable of fully protecting mice after a second B16 melanoma challenge. The activated donor cells were unique because they simultaneously exhibited traits for cytotoxic effector function, central memory-like, homing, and senescence. After tumor eradication and within three months after transfer, CD8+ cells exhibited a conventional memory CTL phenotype. Moreover, these memory CTLs acquired functional attributes characteristic of memory stem cells, including the ability to resist chemotherapy-induced toxicity. Our results suggest that short-term T-cell receptor signaling in the presence of IL-12 promotes promiscuous qualities in naïve CTL which - upon transfer into lymphopenic hosts- are sufficient to eradicate tumors and generate life-long tumor-specific memory.

Oncogenic IRFs provide a survival advantage for Epstein-Barr virus- or human T-cell leukemia virus type 1-transformed cells through induction of BIC expression.

miR-155, processed from the B-cell integration cluster (BIC), is one of the few well-studied microRNAs (miRNAs) and is involved in both innate immunity and tumorigenesis. BIC/miR-155 is induced by distinct signaling pathways, but little is known about the underlying mechanisms. We have identified two conserved potential interferon (IFN) regulatory factor (IRF)-binding/interferon-stimulated response element motifs in the Bic gene promoter. Two oncogenic IRFs, IRF4 and -7, in addition to some other members of the family, bind to and significantly transactivate the Bic promoter. Correspondingly, the endogenous levels of IRF4 and -7 are correlated with that of the BIC transcript in Epstein-Barr virus (EBV)-transformed cells. However, RNA interference studies have shown that depletion of IRF4, rather than of IRF7, dramatically decreases the endogenous level of BIC by up to 70% in EBV- or human T-cell leukemia virus type 1 (HTLV1)-transformed cell lines and results in apoptosis and reduction of proliferation rates that are restored by transient expression of miR-155. Moreover, the endogenous levels of the miR-155 target, SHIP1, are consistently elevated in EBV- and HTLV1-transformed cell lines stably expressing shIRF4. In contrast, transient expression of IRF4 decreases the SHIP1 level in EBV-negative B cells. Furthermore, the level of IRF4 mRNA is significantly correlated with that of BIC in adult T-cell lymphoma/leukemia (ATLL) tumors. These results show that IRF4 plays an important role in the regulation of BIC in the context of EBV and HTLV1 infection. Our findings have identified Bic as the first miRNA-encoding gene for IRFs and provide evidence for a novel molecular mechanism underlying the IRF/BIC pathway in viral oncogenesis.

A Phase I Study using low-dose fractionated whole abdominal radiotherapy as a chemopotentiator to full-dose cisplatin for optimally debulked stage III/IV carcinoma of the endometrium.

OBJECTIVE: To evaluate the feasibility of combining low-dose fractionated whole abdominal radiation (LDF-WAR) with weekly full-dose cisplatin (FD-CDDP) for patients with stage III/IV endometrial carcinoma. METHODS: Patients with optimally debulked stage III/IV carcinoma of the endometrium (without extra-abdominal disease) were eligible for the study. Postoperatively, patients received the institutional standard systemic chemotherapy and vaginal brachytherapy. Patients then underwent experimental six weekly cycles of FD-CDDP (40 mg/m², maximum 70 mg IV) followed by LDF-WAR 6-8 hours after initiation of chemotherapy. In a conservative design, 6 patients were accrued to two sequential cohorts of LDF-WAR, at 0.5 Gy/fraction [Fx] (total 3 Gy) and 0.75 Gy/Fx (total 4.5 Gy). Toxicities and laboratory studies were evaluated at each visit. RESULTS: Twelve patients were enrolled from January 2005 to June 2009 with median follow-up of 13.5 months (range: 5-27 months). Seventy-five percent of enrolled patients had uterine papillary serous histology. Eleven patients at least partially completed therapy (range: 2-6 cycles of FD-CDDP/LDF-WAR) with one additional patient opting out at the higher dose level. Combination therapy overall was well tolerated. Three patients in each cohort experienced grade 3 acute hematologic events with one recorded grade 4 toxicity in the second cohort. Of patients receiving any of the experimental treatment, five have experienced recurrences. Three of these patients were in cohort one and received 0.5 Gy/Fx LDF-WAR. CONCLUSION: Combination therapy with LDF-WAR as a novel chemopotentiator to FD-CDDP is a feasible adjuvant regimen in optimally debulked patients with stage III/IV endometrial carcinoma. Further investigation is warranted to determine treatment efficacy.

Processing sentinel nodes in breast cancer: when and how many?

OBJECTIVES: To analyze a series of sentinel nodes (SNs) from patients with node-positive breast cancer to determine their diagnostic value, to delineate a working algorithm, and to assess the clinical value of our common practice DESIGN: A prospectively collected database. SETTING: Tertiary referral center. PATIENTS: One hundred five patients with node-positive breast cancer who underwent SN biopsy. MAIN OUTCOME MEASURES: The diagnostic value of SNs by analyzing the sensitivity of processing the hottest, 2 hottest, hot and blue, or hot, blue, and suspicious SNs. RESULTS: Three hundred fifty-three axillary SNs were recorded in the database. An analysis of the 282 radioactive axillary nodes for which the 10-second count was recorded reveals that the most radioactive node was positive in 73 of 94 analyzable patients (77.7%). Consideration of the 2 most intense axillary nodes was sufficient to diagnose nodal disease in an additional 12 patients, representing a significant increase in sensitivity to 90.4% (P < .001). Examination of all other radioactive nodes did not diagnose any additional cases. On the basis of all 105 patients, consideration of nonradioactive blue axillary nodes did not add significant diagnostic value relative to testing only radioactive nodes: sensitivity of 86.7% vs 88.6% (P = .50), whereas consideration of all hot, blue, and suspicious nodes improved sensitivity to 96.2% (P = .002). CONCLUSIONS: Processing of the 2 hottest nodes, along with suspicious but nonhot and nonblue nodes, is sufficient for initial axillary staging. Additional radioactive SNs should be processed only in the presence of nodal disease.

Lack of survival improvement in patients with peripheral T-cell lymphoma: a Surveillance, Epidemiology, and End Results analysis.

In patients with aggressive non-Hodgkin lymphomas (NHLs), T-cell lymphoma (TCL) confers a poor prognosis. Since rituximab has increased survival for patients with diffuse large B-cell lymphoma (DLBCL), we hypothesized that the difference in outcome by phenotype became more pronounced recently and evaluated these changes using the Surveillance, Epidemiology, and End Results (SEER) Program. Cases diagnosed in 1992-1997 (era 1) and 1998-2003 (era 2) were evaluated for outcomes according to immunophenotype and era. A total of 22,252 patients with DLBCL and 2222 with TCL were included. In both eras, patients with TCL were more likely to die from their disease than those with DLBCL. Death from NHL decreased significantly from era 1 to era 2 for all DLBCL patients grouped by age and stage but in none of the TCL groups. Improved outcomes for DLBCL after the introduction of rituximab-based therapies in 1997 have no counterpart in patients with TCL, pointing to the need for new therapies to treat TCL.

Efficacy and toxicity of chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel for unresectable stage III non-small cell lung cancer.

INTRODUCTION: In 2003, consolidation docetaxel was a promising concept for unresectable stage IIIA/B nonsmall cell lung cancer (NSCLC). To test the hypothesis that chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel would be feasible and clinically active, we conducted a phase II study. METHODS: Thirty-two patients with unresectable stage IIIA/B NSCLC received irinotecan (30 mg/m) and carboplatin dosed to a target area under the concentration curve of 2, each administered weekly for 7 weeks. Concurrent radiotherapy was administered more than 7 weeks to a total dose of 63 Gy in 35 fractions. Consolidation docetaxel (75 mg/m) was administered every 3 weeks for 3 doses 4 weeks after chemoradiotherapy. The primary end point was objective response rate by RECIST. RESULTS: Complete responses occurred in 4 patients and partial responses occurred in 14, for an objective response rate of 56.3% (95% confidence interval [CI], 37.7-73.6%). Median progression-free survival was 6.5 months (95% CI, 4.6-13.5); median duration of survival was 14.8 months (95% CI, 6.9-27.3). The most common hematologic toxicity was leukopenia, which were grade 3 or 4 in 16 patients (50%). Radiation pneumonitis (grade >or=2) occurred in 13 of 31 treated patients (42%). CONCLUSIONS: These findings suggested that concurrent chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel is clinically active based on median survival in patients with unresectable stage III NSCLC; however, the 42% incidence of clinical radiation pneumonitis was unexpected and warrants further investigation to determine the mechanism and preventive strategies.