Use Of Modern Therapies Research Articles

Survival outcomes in patients with primary plasma cell leukemia treated with novel therapies at University of California San Diego Health: A single institution experience.

e19538 Background: Plasma Cell Leukemia (PCL) is a rare, but aggressive and devastating disease for which there is a paucity of data regarding the efficacy and safety of modern therapies to guide management. Data prior to the use of modern therapies showed abysmal overall survival (OS) of approximately 4-12 months. There is generally agreement that novel therapies have improved outcomes, but data supporting this is sparse due to the rarity of the disease. As such, there is currently no standard of care agreed upon by experts, and the specific approach for treatment currently varies by provider. Methods: In this single-center retrospective study, we review the outcomes of patients diagnosed with primary plasma cell leukemia (pPCL) from 2008 to 2023 who received at least one of the novel therapies of immunomodulatory drugs (IMiD), protease inhibitors (PI), and/or anti-CD38 antibodies at University of California San Diego Health. Baseline characteristics and efficacy outcomes were collected. Results: A total of 11 patients were identified who met the inclusion criteria. The median age at time of diagnosis was 50. The median circulating plasma cells at diagnosis was 34%. All but 2 patients had > 20% circulating plasma cells. The remaining two had circulating plasma cells of 10% and 14% meeting the newly re-worked definition of plasma cell leukemia. One patient had a single extramedullary plasmacytoma at the time of diagnosis. High risk cytogenetics, defined as having t(4;14), t(14;16), t(14;20), Del17p, Gain1q, were characterized for all patients. 4 had one high risk mutation, 3 had two mutations. Only one patient’s first line did not include any of the novel therapies. 81% of patients’ first line of therapy included a form of cytotoxic chemotherapy (of which 55% of those were cisplatin, doxorubicin, cyclophosphamide, etoposide (PACE)). The most common first line of therapy was bortezomib (V), dexamethasone (D), PACE, +/- thalidomide (T) or lenalidomide (R), and +/- stem cell transplant (SCT). The other 19% of first line therapies contained exclusively novel therapies; namely VTD and daratumamab-RVD. Seven patients underwent SCT. One patient who underwent allogeneic transplant as part of their first line therapy has not yet relapsed 5 years post-transplant. Median OS was 28.8 months (95% CI 17.3 –not reached (NR)). First progression free survival (PFS) was 5.7 months (95% CI 2.3 – NR). For patients with available data, overall response rate (ORR) to 1st line of therapy was 60%. Conclusions: Our results demonstrate that the outcomes of patients with PCL have greatly improved with the use of novel therapies. The small sample size and heterogeneity of the treatments prohibited correlative statistical analysis. Prospective studies are needed to determine the best treatment option for this high-risk population which is excluded from most myeloma trials.

Analysis of racial disparities accounting for treatment received in chronic lymphocytic leukemia: A real-world cohort analysis.

7533 Background: Recent population-based studies have shown that Black patients (pts) with CLL have worse overall survival (OS) than White pts with CLL. These studies could not account for the use of modern therapies, CLL prognostic variables, or comorbidity and thus the root cause of this disparity remains unclear. Here, we use the Flatiron Health Database (FHD) to study this disparity, while accounting for disease-specific variables and treatment (tx) received. Methods: Retrospective analysis of pts with CLL in the FHD treated between 2002 to 2022 was performed. Pt characteristics such as age at diagnosis (dx), year (yr) of dx, months (mos) from dx to first tx, race, sex, IGHV status, ECOG performance status (PS), and use of small molecule inhibitors at any time (including BTK inhibitors, venetoclax, PI3K inhibitors, and lenalidomide) were collected and analyzed. OS was measured from tx start. Multivariable cox regression (MVA) was used to determine adjusted odds of survival. Results: 13646 pts with CLL were identified. Mean age at dx was 65.3 yrs, and mean time from dx to tx was 32.3 mos. 81.2%, 8.4%, and 10.4% of pts were White, Black, or other race, respectively, and 63.2% of pts were male. 61.4% of pts were IGHV unmutated, and 89.1% of pts had a ECOG PS 0/1. 58.7% of pts were treated with a small molecule inhibitor at any point during their tx. After a median follow-up of 5.3 yrs, the median OS was 10.5 yrs (95% CI: 10.2-10.8). Black pts were younger at dx (63.1 vs 65.4), had shorter time to first tx (23.6 mo vs 34 mo), were more likely to be IGHV unmutated than White pts (83% vs 60.1%), and had more small molecule inhibitor use (69% vs 58.5%). These differences were all statistically significant (p <0.01). 90.8% and 89.1% of Black and White pts had an ECOG PS of 0/1, respectively. Median OS for Black pts was 10 yrs (95% CI: 9.1-11.1) vs 10.5 yrs (95% CI: 10.2-10.8) for White pts. On MVA, Black pts had higher risk of death than White pts of the same age despite increased use of small molecule inhibitor (Table). However, the interaction between age and race was also significant, indicating a decreasing disparity between Black and White race as pts aged. Time to first tx, IGHV unmutated status, and ECOG PS were also independently associated with worse OS. Conclusions: Black race especially at younger age was independently associated with worse OS despite the use of small molecule inhibitors, IGHV status, and ECOG PS. [Table: see text]

Survival in melanoma in the nordic countries into the era of targeted and immunological therapies

ObjectivesSurvival in melanoma has been increasing and the most recent interest is to observe the population-level impact of novel targeted therapies and immunotherapy. We analysed survival in melanoma from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) over a 50-years period (1971–2020). MethodsRelative 1–5/1- and 5-year survival data were obtained from the NORDCAN database for the years 1971–2020. We estimated annual changes in survival rates and determined significant breaking points for trends. ResultsSurvival in melanoma has reached the point where 1-year survival is approaching 100% (men 97.5–98.6%, women 98.4–99.3%, depending on the country) and 5-year survival is 93% for men (91.5–95.2%) and 96% for women (95.3–97.2%). The highest survival figures were for DK. Significant increases in both 1- and 5-year survival were observed in most countries even towards the end of the follow-up (from 2006 to 2010–2011–2015 and further to 2016–2020). ConclusionsThe main increase in melanoma survival took place up to year 1990, which was probably largely achieved through successful population campaigns for sun protection and programmes for early detection of lesions. Survival increased again after year 2000 up to the last period 2016–2020. This late development coincided with the introduction of targeted therapies using BRAF and BRAF/MEK inhibitors, and towards the end of the time period availability of checkpoint inhibitors. The success of melanoma treatment in DK was mostly likely due to the efficient use of modern therapies and to the centralised treatment for metastatic disease.

P-184: Regional differences in treatment and outcome for myeloma patients in Sweden: a population based Swedish Myeloma Register study

<h3>Background</h3> The objective of this study was to investigate if there are differences in survival for Multiple myeloma (MM) patients in Sweden depending on health care region and early use of modern therapies <h3>Method</h3> Cohorts (labelled A-F) were defined by the six healthcare regions in Sweden. Modern initial therapies were defined as bortezomib in combination with melphalan, cyclophosphamide or thalidomide or as therapy including lenalidomide, pomalidomide, carfilzomib or daratumumab. Only therapies started within a year from diagnosis were considered. Data from patients with MM in the Swedish Myeloma Register diagnosed during 2008-2017 was used. Overall, 5326 patients with MM were analyzed after 250 patients who did not receive any treatment were excluded. A one year follow up report was required to evaluate treatment. To adjust for time to treatment bias, separate analyses were performed for patients alive 6 months after diagnosis. <h3>Results</h3> In all treated MM patients, we observed a significant superior overall survival (OS) for region A compared to all other regions (p<0.01 for all respectively). After adjusting for time to treatment bias there was also a superior survival for patients with high use of modern initial therapy compared to intermediate and low use (p<0.01 for both). Initial modern therapy appeared to increase in regions over time. Age adjusted incidence for region A, B, C, D, E and F was 6.3, 6.1, 6.0, 5.9, 6.4 and 7.3 per 100 000, respectively. Coverage of one-year follow up was less frequent in region A (82.6 %) compared to other regions (95.2-99.2%). In patients treated with autologous stem cell transplantation (ASCT) a significantly superior survival was observed for region A compared to all regions besides region B. When adjusting for time to treatment bias, results were similar. In patients not treated with ASCT, 75 years or older, a superior survival was observed for region A when compared to region B, E and F (log rank p=0.02, p=0.04, p=0.02). After adjusting for time to treatment bias, a difference was noted only between region A and E (log rank p=0.04, HR 1.2, CI 1.00-1.44, p=0.06). In patients not receiving ASCT younger than 75 years of age we saw no differences in OS. When adjusting for age, ISS stage and time period of diagnosis, a difference remained in survival for patients treated with ASCT when comparing region A vs C, D, E and F (p=0.01, p<0.01, p<0.01, p=0.03). In patients not treated with ASCT, 75 years or older, no differences remained between the regions in multivariate analysis. <h3>Conclusion</h3> In conclusion we observed a superior survival in region A for patients treated with ASCT. Possible explanations may be higher usage of modern initial therapy, different number in cycles of pretreatment or regional residual confounding. In patients not receiving ASCT younger than 75 years of age no difference in survival was observed. For patients not receiving ASCT, 75 years or older the small differences in survival could be adjusted for.

Survival analysis of advanced lung cancer patients undergoing personalised treatment or chemotherapy in a real clinic

IntroductionThe importance of modern treatments for the extension of overall survival in advanced lung cancer (LC) patients is rarely reported in clinical trials (crossover effect). Recent clinical trials have compared experimental treatment methods and shown that chemotherapy is no longer a comparator. We studied the relevance of innovative treatment to the extension of overall survival in Polish lung cancer patients.Material and methodsWe described the outcome in 1463 patients diagnosed and treated for advanced LC. The study included patients receiving all available forms of treatment, i.e. chemotherapy, immunotherapy, EGFR tyrosine kinase inhibitors, ALK inhibitors, and best supportive care (BSC).ResultsMedian OS (mOS) for the whole group of patients was 6.5 months. mOS was significantly higher in patients with SCC (8.0 months) and AC (7.0 months) compared to patients with SCLC (6 months) and NSCLC NOS (3.5 months). mOS was 30 months for EGFR TKI-treated patients, 34 months for patients receiving second-line immunotherapy, 8.5 months for chemotherapy patients, and 1.0 month for patients who received BSC. mOS for patients treated with ALK inhibitors and first-line immunotherapy was not reached. The use of targeted therapies or immunotherapies significantly (p &lt; 0.0001) reduced the risk of death compared to chemotherapy (HR = 0.373, 95% CI: 0.288–0.484 and HR = 0.313, 95% CI: 0.255–0.385).ConclusionsThe use of modern therapies in one of the treatment lines compared to chemotherapy significantly increased the long-term survival of advanced LC patients (34.5 vs. 8.5 months, HR = 0.336, 95% CI: 0.284– 0.397, p &lt; 0.0001). Correct and early LC diagnosis is required, because patients with late diagnosis have a particularly poor prognosis.

Nivolumab in treatment of renal cell carcinoma during renal replacement therapy

The prolongation of overall survival of advanced RCC patients requires the use of modern therapies including tyrosine kinase inhibitors and immune checkpoint inhibitors. Although these drugs have different pharmacokinetics, preclinical studies rarely indicate significant renal clearance. To date there has been a lack of prospective studies evaluating their efficacy and safety in end-stage renal disease patients undergoing dialysis. This case study describes second-line treatment of RCC with nivolumab in a dialysed patient following bilateral nephrectomy.

Hypoglycaemia unawareness in patients with type 1 diabetes

Hypoglycaemia unawareness, defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms, is an serious problem in type 1 diabetes mellitus. It is often caused by recurrent or severe hypoglycaemia, which leads to the failure of the autonomic nervous system (hypoglycaemia-associated autonomic failure - HAAF). The hypoglycaemia awareness can be restored by avoiding episodes of hypoglycaemia. Management of hypoglycaemia unawareness is complex, and can only be achieved by amultifactorial intervention of clinical care and structured patient education. In patients in whom functional intensive insulin therapy with insulin analogue, continuous subcutaneous insulin infusion using insulin pumps are ineffective in the prevention of hypoglycaemia the implementation of continuous glucose monitoring (CGM) is advisable. CGM systems equipped with low glucose alarms and prediction alarms not only significantly reduce the risk of severe hypoglycaemia, but also significantly reduce the fear of hypoglycaemia and improve the quality of life of patients and their families. The insulin pumps integrated with CGM automatically suspending insulin infusion when glucose is predicted to soon be low (PLGS) should be preferred in patient with hypoglycaemia unawareness. Hypoglycaemia management is complex and should also include structural education. Particular attention should be paid to the management of hypoglycaemia and appropriate use of modern therapy. The hypoglycaemia unawareness is very common among children under the age of 6 years who are unable to observe the early symptoms of hypoglycemia by themselves. This induces ahigh risk of frequent and severe hypoglycaemia, which can lead to structural changes in the brain, cognitive dysfunctions, poor mental abilities and behavioral disorders later in life.

ONCOPRE: A new chemotherapy benefit prediction model to assist treatment decision making.

126 Background: Clinical decision support tools (CDSTs) can help physicians make complex treatment decisions and inform care. For colon cancer, CDSTs such as Adjuvant! Online and Numeracy were widely used to estimate the effects of adjuvant treatment and guide conversations with patients. Existing CDSTs, however, do not consider more contemporary predictive and prognostic factors, such as microsatellite instability (MSI), BRAF mutational status, or the presence of additional high risk clinical or pathological features (HRFs), in their assessment of outcomes. Current CDSTs are also not optimized for handheld devices. Methods: We developed ONCOPRE, which is an adjuvant chemotherapy benefit calculator for colon cancer that addresses the limitations of current CDSTs. Based on a comprehensive review of epidemiological data and results of landmark trials, ONCOPRE was devised to predict 5 year colon cancer recurrence and death. To validate ONCOPRE, we compared its predictions with those generated by existing CDSTs as well as real-world data from 7 tertiary cancer centers across Canada. Results: ONCOPRE is able to predict 5-year DFS and OS of patients with colon cancer based on age, sex, TNM status, and contemporary risk factors such as MSI status, BRAF mutations, and other HRFs. ONCOPRE’s predictions compare favorably with real-world data and predictions from other CDSTs. ONCOPRE’s predictions are typically more optimistic than historical outcomes, and this likely reflects the fact that current day colon cancer patients experience better prognosis with the use of modern therapy and improved supportive care. These attributes make ONCOPRE a potentially new benchmark among CDSTs that can reliably predict colon cancer outcomes. Conclusions: ONCOPRE ( http://www.oncopre.com/ ) represents a new CDST that can assist in adjuvant treatment decision-making and patient counseling. We make the case that the next generation of CDSTs in oncology must take into account more contemporary clinical, biochemical, and genetic risk factors since these elements significantly affect outcomes. The ONCOPRE platform serves as a potential model on which to develop prediction tools for other forms of cancers.

Modern multiple myeloma therapy: deep, sustained treatment response and good clinical outcomes.

In the USA at the beginning of this century, the average overall survival in patients with multiple myeloma was about 3 years. Around that time, three drugs (bortezomib, lenalidomide and thalidomide) were introduced for the treatment of multiple myeloma and, in 2012, carfilzomib received accelerated approval by the US Food and Drug Administration (FDA). Driven by access to better drugs, median overall survival in younger patients (aged <50 years) was >10 years by 2014. The FDA approved 14 new drugs for the treatment of cancer in 2015; four of these were approved for the treatment of myeloma (panobinostat, daratumumab, elotuzumab and ixazomib). In 2015 and 2016, expanded label indications were approved by the FDA for lenalidomide and carfilzomib, respectively. The recent increase in approved, highly effective combination therapies for patients with multiple myeloma has led the way to redefining the goals of therapy. Here, we review and provide a clinical perspective on the treatment goals and management of multiple myeloma in the era of modern therapy. Recent meta-analyses show that minimal residual disease (MRD) negativity is associated with longer progression-free and overall survival in patients with multiple myeloma. With the use of modern combination therapy, large proportions (>60-70%) of newly diagnosed multiple myeloma patients achieve complete responses and MRD negativity. Modern combination therapies induce rapid, deep and sustainable responses (including MRD negativity), supporting a treatment paradigm shift away from palliative two-drug combinations towards the use of modern, potent, three- or four-drug combination regimens in early lines of therapy. Data support the use of modern therapy upfront rather than reserving it for later stages of the disease. As survival time increases with modern combination therapies, development of early reliable surrogate end-points for survival, such as MRD negativity, are needed for expedited read-out of future randomized clinical trials.

Oncopre: A new chemotherapy benefit prediction algorithm to assist treatment decision making.

705 Background: Clinical decision support tools (CDSTs) can help physicians make complex treatment decisions and inform care. For colon cancer, CDSTs such as Adjuvant! Online and Numeracy were widely used to estimate the effects of adjuvant treatment and guide conversations with patients. Existing CDSTs, however, do not consider more contemporary predictive and prognostic factors, such as microsatellite instability (MSI), BRAF mutational status, or the presence of additional high risk clinical or pathological features (HRFs), in their assessment of outcomes. Current CDSTs are also not optimized for handheld devices. Methods: We developed ONCOPRE, which is an adjuvant chemotherapy benefit calculator for colon cancer that addresses the limitations of current CDSTs. Based on a comprehensive review of epidemiological data and results of landmark trials, ONCOPRE was devised to predict 5-year colon cancer recurrence and death. To validate ONCOPRE, we compared its predictions with those generated by existing CDSTs as well as real-world data from 7 tertiary cancer centers across Canada. Results: ONCOPRE is able to predict 5-year DFS and OS of patients with colon cancer based on age, sex, TNM status, and contemporary risk factors such as MSI status, BRAF mutations, and other HRFs. ONCOPRE’s predictions compare favorably with real-world data and predictions from other CDSTs. ONCOPRE’s predictions are typically more optimistic than historical outcomes, and this likely reflects the fact that current day colon cancer patients experience better prognosis with the use of modern therapy and improved supportive care. These attributes make ONCOPRE a potentially new benchmark among CDSTs that can reliably predict colon cancer outcomes. Conclusions: ONCOPRE ( http://www.oncopre.com/beta/ ) represents a new CDST that can assist in adjuvant treatment decision-making and patient counseling. We make the case that the next generation of CDSTs in oncology must take into account more contemporary clinical, biochemical, and genetic risk factors since these elements significantly affect outcomes. The ONCOPRE platform serves as a potential model on which to develop prediction tools for other forms of cancers.

Abstract A70: Akt2 gain or Akt1 loss drives invasion and aggressiveness in breast cancer

Abstract Despite the improvement in the early diagnosis and the use of modern therapies, breast cancer is the second cause of death, after lung cancer, in women around the world, and this is mainly due to metastasis development distant organs. PI3K/Akt pathway is deregulated in almost 50% of breast carcinomas, and is associated to therapy resistance. Currently, there are increasing clinical trials that combine endocrine treatments with PI3K/Akt inhibitors to delay tumor resistance and to avoid tumor progression. However, these inhibitors do not distinguish between the isoform specific function of Akt1, Akt2 and Akt3. Several evidences in different models of cancer show that Akt1 and Akt2 are expressed in different stages of cancer progression, with Akt1 involved in tumor proliferation during the first steps of the carcinogenic process, and Akt2 involved in the invasive phenotype. The aim of this work was to study Akt1 and Akt2 isoforms, focusing on their particular role in cell migration and invasion in human breast tumor samples and in two human breast cancer cell lines. Tissue microarray analysis in a small cohort of human advanced breast cancer samples showed a positive association between invasive grade, Akt2 expression and E-cadherin loss. Interestingly, E-cadherin presents a heterogeneous staining in each sample, being weaker in the more invasive areas and stronger in the non-invasive areas. To understand the specific role of each isoform of Akt on tumor phenotype, T47D and IBH-6 human breast cancer cell lines were stably transfected to specifically inhibit Akt1 (shAkt1) or Akt2 (shAkt2) and the resulting phenotype in cell culture and in xenografts were analyzed. We found that Akt1 silencing inhibited cell growth through S6 and cyclin-D1 regulation, but induced cell migration and invasion in IBH-6 2D and 3D cell cultures. Contrarily, Akt2 silencing had no effect on cell proliferation but significantly inhibited cell adhesion and invasion. These phenotypes were accompanied by an opposite regulation of β1-Integrin, FAK, MMP9, F-actin and vimentin expression. Simultaneous silencing of Akt1 and Akt2 isoforms showed that Akt1 has an anti-migratory effect per se and not by upregulating Akt2 levels. Interestingly, in IBH-6 and T47D xenograft studies we observed that shAkt1 cells grew significantly more slowly than control tumors, but displayed a ducto-lobulillar invasive phenotype, similar to the phenotype gained with Akt2 overactivation by myristoylated Akt2. Contrarily, shAkt2 tumors showed no differences in growth rate, with no infiltrating morphology when compared to control tumors. Immunohistochemical analysis showed low E-cadherin and high vimentin expression in invasive T47D shAkt1 tumors, and the opposite pattern in T47D shAkt2 tumors. We are currently assessing Akt1 status, vimentin, β1-integrin, FAK and MMP9 levels in human samples to relate them with in vitro and xenografts results. Altogether, these results indicate that Akt2 overexpression as well as Akt1 inhibition play important roles in the acquisition of an invasive and aggressive phenotype. The status of each isoform-driven pathway is relevant in the design of targeted therapies that could be more effective and selective in each tumor stage. Citation Format: Cecilia Perrone, Marina Riggio, Maria May, Maria Laura Polo, Jimena Rodriguez, Diego Lucas Kaen, Claudia Lanari, Virginia Novaro. Akt2 gain or Akt1 loss drives invasion and aggressiveness in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A70.

Do Recent Advances in Diagnostic and Therapeutic Procedures Negate the Benefit of Postmastectomy Radiotherapy in N1 Patients With a Low Risk of Locoregional Recurrence?

Recent advances in breast cancer management might make the use of postmastectomy radiotherapy (PMRT) redundant in the treatment of pT1/T2N1 patients. We investigated the impact of PMRT on disease-free survival (DFS) in these patients who have a low risk of locoregional recurrence (LRR) after contemporary multidisciplinary management.Between 1998 and 2011, 1123 patients underwent upfront surgery for pathologically diagnosed pT1/T2N1 breast cancer, at a single institution. A retrospective review was performed on 692 patients who had a mastectomy with axillary lymph node (LN) clearance. Most patients received adjuvant systemic chemotherapy and/or endocrine therapy. PMRT was administered to 17.8% of the patients. The median follow-up time was 98 months.The entire cohort was divided into 2 groups, the early-era (1998-2003) and late-era (2004-2011) cohorts. Grouping was based on the use of modern therapies since 2004 including sentinel LN (SLN) biopsy, anthracycline/taxane-based chemotherapy, and aromatase inhibitors. Late-era patients had a significantly lower 5-year LRR compared with early-era patients (3.2% vs 10.3%, respectively; P < 0.001). In late-era patients, although PMRT did not significantly reduce the 5-year LRR rate (1% vs 3.8%, respectively), it did improve the 5-year DFS rate (96.1% vs 87.5%, respectively). After controlling for all clinicopathological variables, PMRT was independently associated with improved DFS. In subgroup analysis, depending on the presence of micro- or macrometastasis in the axillary nodes, the benefit of PMRT was most apparent in patients with macrometastasis (hazard ratio, 0.19). In the late-era cohort with no PMRT, the 3-year distant metastasis risk increased according to LN tumor burden (0%, 5.2%, and 9.8% in micrometastasis, SLN macrometastasis, and non-SLN macrometastasis, respectively).Advanced surgical and systemic therapies might not negate the benefit of PMRT in recently diagnosed pN1 patients who have a very low risk for LRR. Our data indicate that the overall recurrence risk combined with the LRR should be considered for an indication of PMRT, and raises the question of whether the receipt of PMRT would improve outcome in patients with micrometastasis.

The risk of colorectal cancer in patients with ulcerative colitis.

Ulcerative colitis increases the risk of developing dysplasia and colitis-associated cancer (CAC). The purpose of this study was to determine the risk factors as well as protective measures for disease burden, need for colectomy and the development of CAC in ulcerative colitis (UC) patients. A cohort of n = 434 UC patients was evaluated. Data analysis was performed by univariate and multivariate logistic regression. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated, and significance was assessed by the likelihood ratio test. Mean patient age at UC diagnosis was 45.7 ± 15.1 years which manifested mainly as pancolitis (47 %) or left-sided colitis (45.2 %). CAC was detected in ten patients (2.3 %). UC disease duration was strongly associated with the risk of CAC (P < 0.0014); disease duration between 9 and 15 years: OR of 2.5 (95 % CI 0.2-41.1), more than 15 years: OR of 21.4 (95 % CI 2.6-173.6). The risk of developing dysplasia (low-grade intraepithelial neoplasia, LGIEN and high-grade intraepithelial neoplasia, HGIEN) or the need to undergo colectomy was also significantly related to disease duration (P = 0.006, P = 0.002, respectively). Established anti-inflammatory medication (e.g., 5-ASA, anti-TNF-α) significantly reduced the risk of both dysplasia and CAC (P = 0.02). Despite the use of modern therapies for UC, CAC rates remain high. In our study, risk factors included disease duration while anti-inflammatory therapies reduced the risk. Effective control of the intestinal inflammation also reduced the disease burden as indicated by decreased risk of requiring colectomy, underscoring the need for sufficient surveillance and anti-inflammatory therapies.

Blood pressure and other determinants of new-onset atrial fibrillation in patients at high cardiovascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease studies

Evidence on new-onset atrial fibrillation in high-risk vascular patients without heart failure is limited. New-onset atrial fibrillation was a prespecified secondary objective of the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) studies. We studied 30 424 ONTARGET/TRANSCEND patients (mean age ± SD, 66.4 ± 7.0) with vascular disease or complicated diabetes who were in sinus rhythm at entry. A copy of ECG was sent to central office every time new atrial fibrillation was detected by investigators. During a median follow-up period of 4.7 years, new atrial fibrillation occurred in 2092 patients (15.1 per 1000 patient-years). Risk of atrial fibrillation increased with age, SBP and pulse pressure, left ventricular hypertrophy, BMI, serum creatinine and history of hypertension, coronary artery disease and cerebrovascular disease (all P < 0.01). After adjustment for BMI and other variables, atrial fibrillation risk increased with hip circumference. History of hypertension was associated with a 34% higher risk of new atrial fibrillation. New atrial fibrillation portended an increased risk of congestive heart failure [hazard ratio 2.89, 95% confidence interval (CI) 2.45-3.40, P < 0.01] and cardiovascular death (hazard ratio 1.22, 95% CI 1.05-1.41, P < 0.01). Risk of stroke was unaffected (hazard ratio 1.14, 95% CI 0.93-1.40), whereas that of myocardial infarction was reduced (hazard ratio 0.64, 95% CI 0.50-0.82). Patients with new atrial fibrillation were more likely to receive vitamin K antagonists (P < 0.01), statins (P < 0.05) and β-blockers (P < 0.01) than those in sinus rhythm. New atrial fibrillation is common in high-risk vascular patients and is associated with several risk factors including history of hypertension. Hip circumference was the strongest anthropometric predictor. Despite extensive use of modern therapies, new atrial fibrillation carries a high risk of congestive heart failure and death over a relatively short term.

Hodgkin lymphoma: Use of modern combined modality therapy and its effect on the risk of second malignancies: The M. D. Anderson Experience over five decades.

e18529 Background: The treatment of Hodgkin’s Lymphoma has radically changed over the past five decades. The change involved the type and number of cycles of chemotherapy; as well as the dose, fields, and techniques of radiation therapy. We here report on the change of incidence of second malignancies with the use of modern therapy. Methods: The medical record of 1671 patients diagnosed with Hodgkin’s lymphoma between June 1956 and June 2009 was reviewed. The subjects of this study are 949 patients with available follow-up information. Using logistic regression analysis we have looked at the correlation between the following factors and the risk for second malignancy: Age at diagnosis (<30, 30-50, and >50 years), Gender, stage at diagnosis (early favorable, early unfavorable, and advanced), type of chemotherapy (MOPP containing versus none), type of field of radiation used (involved fields, mantle, or extended), The use of three dimensional radiation modality, era of diagnosis by decades (<1995 versus > 1995), and relapse. Results: In univariate analysis The incidence of developing second malignancy was significantly associated with younger age at diagnosis (<30 years) (p=0.0001), the use of MOPP containing chemotherapy (p=0.004), the use of non modern radiotherapy techniques (p=0.01), patients who relapsed (p=0.0001), patients who were treated before 1995 (p=0.0001). On multivariate analysis factors that kept their significance includes: the use of MOPP containing chemotherapy (p0.0001), the use of outdate non modern radiotherapy techniques (p=0.001), patients treated before 1995, patients younger than 30 years of age at diagnosis (p=0.0001), number of radiation courses for relapsed patients (p=0.0001), and radiation dose of > 36 Gy (0.041). Conclusions: Modern therapy (standard after 1995 at our institution) represented by the use of non-MOPP chemotherapy, and modern techniques and lower doses of radiation is associated with a significant decrease of the risk of second malignancy.

Predicting outcomes in rheumatoid arthritis

Biologic therapies have brought improved efficacy in the field of rheumatoid arthritis (RA), but their use in clinical practice may be limited by concerns over cost. Predictive models are, therefore, needed to identify those people with RA with the worst potential outcomes, who will benefit most from the use of these drugs. A variety of studies have investigated factors that will predict the onset of RA to allow preventative intervention and the identification of prognostic factors to guide the need for aggressive treatment at the time of diagnosis and prognostic factors in patients who have failed on optimal traditional therapies-all strategies to guide the cost-effective use of modern therapies. Prediction rules have been developed that are sensitive and specific, but many are limited by their complexity or the need for biomarkers that will never be routinely measured in the clinic. Most rules to date have therefore failed to have a major impact on clinical practice. Probably most interesting is the prediction of response to therapy based upon early treatment response, with outcomes at as early as 3months predicting response at 12months. Further work is needed, however, to identify the efficacy of current therapies in preventing disease onset and the long-term cost-effectiveness of appropriately targeted treatment with biologics.

Breast Conservation in Women with Multifocal-Multicentric Breast Cancer: Is It Feasible?

The incidence of preoperatively identified multifocal and multicentric breast cancer is rising with improved sensitivity of imaging modalities. Based on retrospective, historic data, breast conservation in women with multiple tumors has been discouraged because of high rates of local regional recurrence (LRR). These studies, however, do not extrapolate to contemporary practice as they do not incorporate the use of modern therapies and surgical techniques. This study is designed to evaluate the feasibility of breast conservation in women with multiple breast primaries. We retrospectively reviewed the charts of 22 women who underwent breast conservation surgery for 2 or more synchronous, ipsilateral cancers between 1998 and 2008. We extracted data including tumor size, nodal staging, receptor status, adjuvant therapies administered, and local-regional recurrence. A total of 22 patients were identified. Average follow up is 3.5years. One patient (4.5%) experienced an in-breast recurrence. Both initial tumors in this patient were invasive ductal carcinoma, ER/PR, negative and HER2 positive. Time to LRR was 2.5years. Our data are consistent with those of recent studies in which multifocal/multicentric local regional recurrence in multicentric/multifocal breast is equivalent to that seen in women with unifocal cancer. The single local recurrence in this study occurred in a premenopausal women with ER/PR- disease who were HER2+. Prior retrospective studies have identified ER/PR- and HER2 overexpression as independent risk factors for recurrence following breast conservation. Additional prospective trials are warranted to better assess the oncologic safety of breast conservation in this population.

Treatment of burns

1. 1. The severe burn case carries a responsibility not only for the attending surgeon, but for all individuals participating in the treatment. Close attention to details of therapy is essential. 2. 2. The burn must be treated as a surgical wound preliminary to the application of the therapeutic agent. 3. 3. Shock is an early complication and must be dealt with by the early administration of sedatives, heat to the body, and parenteral fluids, in addition to blood transfusions. 4. 4. The local agent used may depend upon the type of burn and the experience of the attending surgeon. 5. 5. Sulfapyridine has proved of value in a limited number of cases with sepsis and upper respiratory complications. 6. 6. The acid or alkali burn should be thoroughly washed with water before applying the neutralizing agent. 7. 7. Attention to the position of the patient is important to prevent contractures and deformities, and to obtain the best functional result. 8. 8. It should be emphasized that attention to the nutrition of the patient is important and may be supplemented by frequent small blood transfusions to combat the secondary anemia, which is associated with exhaustion. 9. 9. Early skin grafting minimizes loss of fluid from the burned area. The effects of infection are also reduced, thereby limiting scarring and contractures. 10. 10. Physiotherapy may assist in the rehabilitation of the patient and restoration of function. 11. 11. The results of treatment in the severe burn case show a favorable lowering of mortality by the use of modern therapy.