Reduced Risk Of Recurrence Research Articles

Advances in CNS lymphoma

Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma restricted to the brain, spinal cord, cerebrospinal fluid and eye, in the absence of systemic disease. PCNSL is a diffuse large B-cell lymphoma in greater than 95% of the cases. There has been significant progress in the treatment for this disease and therapeutic regimens have been evolving. Prompt diagnosis and early institution of therapy are essential for improved outcomes. Age and performance status are two important prognostic factors in this disease and patients should be stratified based on these factors in order to establish the best therapeutic approach. High-dose methotrexate based multi-drug chemotherapy is the standard of care induction treatment of newly diagnosed PCNSL. The role of rituximab in upfront therapy is uncertain due to conflicting results from two randomized studies. Consolidation regimens to reduce recurrence risk include thiotepa-based high-dose chemotherapy and autologous stem cell transplant, non-myeloablative chemotherapy alone or whole brain radiation. Delayed neurocognitive side effects are higher with radiation regimens particularly in older patients. Approximately 50% of the patients with PCNSL develop recurrent disease and 10% to 30% of patients have primary refractory disease that are challenging to treat. More insight into the pathophysiology of PCNSL has led to development of clinical trials with novel targeted agents and immunotherapies based on the molecular properties of the disease, that have demonstrated early evidence of activity in the recurrent and refractory setting. Current research is focused on the development of effective and less neurotoxic strategies for prolonged disease-free survival.

Tumour-infiltrating CD8+ lymphocytes and colorectal cancer recurrence by tumour and nodal stage

BackgroundIntratumoural T-cell infiltrate intensity cortes wrelaith clinical outcome in stage II/III colorectal cancer (CRC). We aimed to determine whether this association varies across this heterogeneous group.MethodsWe performed a pooled analysis of 1804 CRCs from the QUASAR2 and VICTOR trials. Intratumoural CD8+ and CD3+ densities were quantified by immunohistochemistry in tissue microarray (TMA) cores, and their association with clinical outcome analysed by Cox regression. We validated our results using publicly available gene expression data in a pooled analysis of 1375 CRCs from seven independent series.ResultsIn QUASAR2, intratumoural CD8+ was a stronger predictor of CRC recurrence than CD3+ and showed similar discriminative ability to both markers in combination. Pooled multivariable analysis of both trials showed increasing CD8+ density was associated with reduced recurrence risk independent of confounders including DNA mismatch repair deficiency, POLE mutation and chromosomal instability (multivariable hazard ratio [HR] for each two-fold increase = 0.92, 95%CI = 0.87–0.97, P = 3.6 × 10−3). This association was not uniform across risk strata defined by tumour and nodal stage: absent in low-risk (pT3,N0) cases (HR = 1.03, 95%CI = 0.87–1.21, P = 0.75), modest in intermediate-risk (pT4,N0 or pT1-3,N1-2) cases (HR = 0.92, 95%CI = 0.86–1.0, P = 0.046) and strong in high-risk (pT4,N1-2) cases (HR = 0.87, 95%CI = 0.79–0.97, P = 9.4 × 10−3); PINTERACTION = 0.090. Analysis of tumour CD8A expression in the independent validation cohort revealed similar variation in prognostic value across risk strata (PINTERACTION = 0.048).ConclusionsThe prognostic value of intratumoural CD8+ cell infiltration in stage II/III CRC varies across tumour and nodal risk strata.

A pilot study on surgical reduction of the levator hiatus-the puborectalis sling.

Female pelvic organ prolapse recurrence has been shown to be associated with levator hiatal distensibility. Reducing hiatal size surgically may reduce recurrence risk. This study aims to demonstrate a novel surgical procedure, the puborectalis sling (PR sling), designed to reduce the levator hiatal area, and to assess the medium-term safety and efficacy of this procedure. One hundred fifteen women undergoing prolapse repair with a pre-operative hiatal area on Valsalva of ≥ 35cm2 were recruited into this phase 1 prospective multicentre pilot study. All underwent a PR sling procedure after completion of standard repairs. Primary outcome was levator hiatal area measured on ultrasound. One hundred ten patients were evaluated at least 3months post-operatively. At 2.5yearsaverage follow-up, there was an average of 12cm2 (range 6-16cm2) reduction in hiatal area from a mean pre-operative hiatal area of 43.9 (35-63) cm2. Thirty per cent (28/93) were symptomatic of prolapse, 66% (61/93) had clinical prolapse recurrence whilst 49% (46/93) had sonographic recurrence. Three patients required a return to theatre; one case of infection resulted in mesh removal, one had severeobstructed defecation requiring sling loosening and another had buttock pain with faecal impaction that resolved after manual disimpaction. There were no long-term sequelae. The levator hiatal area can be reduced surgically, with almost 30% reduction in area seen in this pilot study. The reduction was significant and sustained up to 2years with no major long-term complications.

A whole slide image-based machine learning approach to predict ductal carcinoma in situ (DCIS) recurrence risk

BackgroundBreast ductal carcinoma in situ (DCIS) represent approximately 20% of screen-detected breast cancers. The overall risk for DCIS patients treated with breast-conserving surgery stems almost exclusively from local recurrence. Although a mastectomy or adjuvant radiation can reduce recurrence risk, there are significant concerns regarding patient over-/under-treatment. Current clinicopathological markers are insufficient to accurately assess the recurrence risk. To address this issue, we developed a novel machine learning (ML) pipeline to predict risk of ipsilateral recurrence using digitized whole slide images (WSI) and clinicopathologic long-term outcome data from a retrospectively collected cohort of DCIS patients (n = 344) treated with lumpectomy at Nottingham University Hospital, UK.MethodsThe cohort was split case-wise into training (n = 159, 31 with 10-year recurrence) and validation (n = 185, 26 with 10-year recurrence) sets. The sections from primary tumors were stained with H&E, then digitized and analyzed by the pipeline. In the first step, a classifier trained manually by pathologists was applied to digital slides to annotate the areas of stroma, normal/benign ducts, cancer ducts, dense lymphocyte region, and blood vessels. In the second step, a recurrence risk classifier was trained on eight select architectural and spatial organization tissue features from the annotated areas to predict recurrence risk.ResultsThe recurrence classifier significantly predicted the 10-year recurrence risk in the training [hazard ratio (HR) = 11.6; 95% confidence interval (CI) 5.3–25.3, accuracy (Acc) = 0.87, sensitivity (Sn) = 0.71, and specificity (Sp) = 0.91] and independent validation [HR = 6.39 (95% CI 3.0–13.8), p < 0.0001;Acc = 0.85, Sn = 0.5, Sp = 0.91] cohorts. Despite the limitations of our cohorts, and in some cases inferior sensitivity performance, our tool showed superior accuracy, specificity, positive predictive value, concordance, and hazard ratios relative to tested clinicopathological variables in predicting recurrences (p < 0.0001). Furthermore, it significantly identified patients that might benefit from additional therapy (validation cohort p = 0.0006).ConclusionsOur machine learning-based model fills an unmet clinical need for accurately predicting the recurrence risk for lumpectomy-treated DCIS patients.

Patient-Perceived Lack of Choice in Receipt of Radioactive Iodine for Treatment of Differentiated Thyroid Cancer.

For many patients with differentiated thyroid cancer, use of radioactive iodine (RAI) does not improve survival or reduce recurrence risk. Yet there is wide variation in RAI use, emphasizing the importance of understanding patient perspectives regarding RAI decision making. All eligible patients diagnosed with thyroid cancer from 2014 to 2015 from the Georgia and Los Angeles SEER registries were surveyed (N = 2,632; response rate, 63%). Patients in whom selective RAI use is recommended were included in this analysis (n = 1,319). Patients were asked whether they felt like they had a choice to receive RAI (yes or no), how strongly their physician recommended RAI (5-point Likert-type scale), whether they received RAI (yes or no), and how satisfied they were with their RAI decision (more [score of 4 or greater] v less). Multivariable, weighted logistic regression with multiple imputation was used to assess the associations between patient characteristics and perception of no RAI choice and between perception of no RAI choice with receipt of RAI and decision satisfaction. More than half of respondents (55.8%) perceived they did not have an RAI choice, and the majority of patients (75.9%) received RAI. The odds of perceiving no RAI choice was greater among those whose physician strongly recommended RAI (adjusted odds ratio [OR], 1.56; 95% CI, 1.13 to 2.17). Patients who perceived they did not have an RAI choice were more likely to receive RAI (adjusted OR, 2.50; 95% CI, 1.64 to 3.82) and report lower decision satisfaction (adjusted OR, 2.31; 95% CI, 1.67 to 3.20). Many patients did not feel they had a choice about whether to receive RAI. Patients who perceived they did not have a choice were more likely to receive RAI and report lower decision satisfaction, suggesting a need for more shared decision making to reduce overtreatment.

Outcomes of trimodality bladder-sparing therapy for muscle-invasive bladder cancer.

Although radical cystectomy is considered the standard of care for muscle-invasive bladder cancer (MIBC), recent data has suggested comparable survival outcomes for bladder-sparing trimodality therapy (TMT). We conducted a retrospective, single-institution analysis of MIBC patients to evaluate the efficacy of TMT as an alternative, curative approach to surgical intervention. We conducted a retrospective analysis of MIBC patients assessed by a multidisciplinary team at the Juravinski Cancer Centre from 2010-2016. Patients underwent transurethral resection of bladder tumor (TURBT) followed by radiotherapy with or without concurrent chemotherapy. Patients could receive neoadjuvant treatment. Clinical data and response rates were summarized, and overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Our analytic cohort included 115 patients, of whom 53 underwent TMT and 62 underwent radiotherapy alone following TURBT. Median age at diagnosis was 79 years and median followup was 21 months. Complete response rates in those receiving TMT and radiation without chemotherapy were 84.4% and 66.7%, respectively. For TMT patients, three-year OS and DFS were 68.5% and 49.6%, respectively. Patients who received TMT had reduction in risk of mortality (hazard ratio [HR] 0.49; p=0.026) and disease recurrence (HR 0.55; p=0.017) compared to those who had radiation without chemotherapy. Overall, four patients had grade 3 or higher late toxicity. In this single-institution analysis, TMT appears to be a safe and effective approach in the short-term management of MIBC in appropriately selected patients. Extended followup and analysis are necessary to validate these results.

Local lymph node recurrence after central neck dissection in papillary thyroid cancers: A meta analysis

BackgroundProphylactic central neck dissection (CND) at the time of total thyroidectomy (TT) remains controversial in clinically node-negative (cN0) papillary thyroid carcinoma (PTC). This systematic review and meta-analysis was performed to compare the local recurrence between patients who underwent TT plus CND and those who underwent TT alone. MethodsThe publicly available literature published from January 1990 to October 2017 concerning TT plus prophylactic CND versus TT for PTC was retrieved by searching the national and international online databases. Meta-analysis was performed after the data extraction process. ResultsTwenty-five studies with comparison between TT+CND and TT alone were eligible and included in this meta-analysis. For both PTC and papillary thyroid microcarcinoma (PTMC), the overall recurrence in TT+CND group was significantly lower than that in TT alone group. The central compartment recurrence was significantly higher in TT alone group than TT+CND group (OR=3.41, 95% Cl [2.00∼5.80], P<0.00001), while no significant difference of lateral compartment recurrence was observed between the two groups (OR=1.19, 95%Cl [0.81∼1.77], P=0.38). We compared ipsilateral CND+TT with TT alone and found that the recurrence was not significantly different between the two groups (OR=1.44, 95%Cl [0.74∼2.81], P=0.28). On the other hand, bilateral CND+TT showed significantly low recurrence (OR=2.48, 95%Cl [1.75∼3.53], P<0.00001). ConclusionsThe addition of CND to TT resulted in a greater reduction in risk of local recurrence than TT alone, especially preventing central neck recurrences. Additionally, we discovered that bilateral CND in patients with PTC>1cm was necessary.

Use of complementary/integrative methods: cancer survivors' misconceptions about recurrence prevention.

Many cancer survivors use complementary and alternative health methods (CAM). Because we are unaware of high-level evidence supporting CAM for preventing cancer recurrence, we studied post-treatment survivors who use CAM to assess (1) the percentage who included preventing recurrence as a motive for using CAM, (2) characteristics of survivors who use CAM intended to prevent recurrence, and (3) CAM domains associated with use for recurrence prevention. We studied participants in the American Cancer Society's Study of Cancer Survivors-I (nationwide study of adult survivors) who used CAM (excluding osteopathy, yoga, tai chi, or qi gong users, as well as anyone whose only reported CAM was prayer/meditation). Multivariable logistic regression was used to examine associations of independent variables with CAM use for recurrence prevention. Among 1220 survivors using CAM, 14.8% reported recurrence prevention as a reason for CAM use (although only 0.4% indicated this was their only reason). The following were independently associated with odds of CAM use to prevent recurrence: not being married/in a marriage-like relationship (OR = 1.53, 95% confidence interval [CI] 1.05-2.23), using mind-body (OR = 1.65, 95% CI 1.08-2.51) or biologically based (OR = 4.11, 95% CI 1.96-8.59) CAM and clinically relevant fear of recurrence (OR = 1.96, 95% CI 1.38-2.78). Approximately 1/7 of survivors who use CAM have unrealistic expectations about CAM reducing recurrence risk. This expectation is strongly associated with the use of biologically based CAM. Patient education should support informed decisions and realistic expectations regarding any complementary/integrative or mainstream/conventional clinical intervention.

PCN216 ADJUVANT CHEMOTHERAPY GUIDED BY A 21-GENE EXPRESSION ASSAY IN HORMONE-RECEPTOR POSITIVE EARLY-STAGE BREAST CANCER: USE OF SIMULATION MODELING TO EXTEND AND TRANSLATE CLINICAL TRIAL RESULTS INTO PRACTICE

Translation of clinical trial findings in to practice requires information on variation of trial results in real-world settings and outcomes beyond trial follow-up. We developed a simulation model to extend the "Trial Assigning IndividuaLized Options for Treatment” (TAILORx) and examine long-term outcomes and variation of trial findings for clinically-relevant subgroups of women. We conducted an empirical Bayesian analysis with a Monte Carlo sampling method for probabilistic sensitivity analysis using data independent of TAILORx. Women eligible were diagnosed with HER2-, hormone receptor positive (HR+), node–negative breast cancer and recurrence scores (RS) between 11-25. The trial was also simulated for alternative RS categories including 11-30, 18-30, and 26-30. Women were followed up to 20-years to assess long-term outcomes. Input parameters were derived from SEER, Oxford Overview and published data. Hazard ratios (HRs) of no-chemo vs chemo were estimated using Cox models. To assess predictive validity of the trial simulations, we compared estimates for each trial endpoint (invasive disease-free interval (iDFI) and distant recurrence-free interval interval (DRFI)) with TAILORx published results. The HRs for no-chemo vs. chemo for 9 and 20-year iDFI and DRFI were not statistically significant in the 11-25 and 18-30 RS groups. Majority (72%) of the simulations showed that omission of chemotherapy resulted in a statistically significant decrease in the 9-year iDFI rate among women with RS 26-30. The results varied by age. On average, simulated results were similar to the published TAILORx findings at 9-years in the RS 11-25 group. The model projections show that long-term recurrence rates remain low with omission of chemotherapy among women diagnosed with node-negative, HR+ breast cancer and RS 11-25 and 18-30. Chemotherapy may show some benefit in reducing recurrence risk in RS 26-30 category. Simulation modeling can be used to extend trial data by synthesizing information from historical trials.

Abstract 273: Acute and Long-term Efficacy of Interleukin-1 Inhibitor Anakinra in Idiopathic and Secondary Pericarditis in Patients Refractory or Intolerant to Conventional Therapy

Background: In contrast to its use in idiopathic recurrent pericarditis, efficacy and optimal treatment duration of Anakinra are unclear in patients with pericarditis secondary to known autoimmune or inflammatory conditions, who are refractory or intolerant to conventional therapy (colchicine and corticosteroid [CS]). Methods: Retrospective chart review of 12 adults hospitalised between January 2016 and October 2018 treated with Anakinra 100mg SQ daily for pericarditis refractory or intolerant to conventional therapy (CT+A group), and 22 consecutive hospitalised patients treated with conventional therapy only (CT group). Results: Diagnosed autoimmune/inflammatory condition was present in 83.3% (10/12) of CT+A and 40.9% (9/22) of CT group (p=0.07, Table 1). The most common etiologies in CT+A group were RA and Undifferentiated Connective Tissue Disease (Figure 1). All 12 CT+A patients had symptom relief at discharge, 100% vs. 72.7% (16/22) in CT group (p=0.04). There was a trend in CT+A compared to CT group towards shorter time to symptom improvement (1.75+/-1.29 vs. 3.55+/-3.06 days; p=0.06) and symptom relief (3.75+/-1.87 vs 5.63+/-3.28 days; p=0.08). CS were tapered successfully in 71.4% (5/7) in CT+A vs. 66.7% (6/9) of patients in the CT group (p=0.56). Mean length of stay was longer in CT+A (13.0+/-16.2 vs. 8.68+/-5.07 days; p=0.25). There were no recurrences during treatment in CT+A group, 0% vs. 40.9% (9/22) in CT group (p=0.009). Treatment was discontinued at discharge or followup in all CT+A and 12 of 24 CT patients. There was a trend towards reduced post-treatment relapse risk in CT+A 16.7% (2/12) vs. 41.7% (5/12) in CT group (p=0.18). Within CT+A group, extended treatment in 6 patients after symptom relief at discharge (mean: 5.58+/-6.5 months) did not reduce post-treatment relapse risk, 16.7% (1/6) vs 16.7% (1/6) (p&gt;0.9). Adverse effects were infrequent; elevated transaminases (n=1) and local injection-site reaction (n=1). Neither required permanent Anakinra discontinuation. Conclusion: In hospitalised patients with new-onset or recurrent pericarditis (secondary or idiopathic) refractory or intolerant to CT, Anakinra is associated with improved symptom relief and reduced recurrence risk. Extended continuation of Anakinra after symptom relief does not reduce post-treatment relapse risk.

Abstract P5-14-03: Patient perspectives on HER2+ breast cancer recurrence: Results from an online patient survey

Abstract Background: The objective of this study was to gather insights from patients with early-stage HER2+ breast cancer regarding fears and knowledge of breast cancer recurrence and approaches to reducing risk of recurrence. Methods: From Nov. 7-30, 2017, patients with stage I-IIIC HER2+ breast cancer were recruited via postings to Breastcancer.org discussion boards to participate in an online survey comprising 17 questions designed to quantify fears and emotions related to recurrence, identify and characterize knowledge gaps, and understand what patients are willing to tolerate to reduce recurrence risk. Results: Of 307 respondents, 87% were aged ≥40 years and over half were ≥50 (58%). The majority had completed (48%) or were undergoing (39%) postsurgical treatment. Recurrence was a concern for 93% of patients and was the highest rated concern for 78%; however, most patients (76%) perceived their personal risk of recurrence to be moderate or low. 59% of patients felt they were at least somewhat informed about risk of recurrence; 55% had discussed risk of recurrence with their health care team, with discussions most frequently initiated by the patient (56%) vs the health care team (40%). Oncologists were the primary source of information about risk of recurrence (58%), but patients also frequently sourced information from online content (29%), published research (18%), and Breastcancer.org (15%). Almost all (96%) patients were at least somewhat involved in treatment planning. While 55% of patients would inquire about a new drug if it conferred a 10%-20% reduction in risk of recurrence, 26% required a benefit of ≥50%. For treatments reducing the risk of recurrence, patients were willing to tolerate (in order from most to least willing) hot flashes, fatigue, diarrhea, joint pain, and nausea/vomiting. Conclusions: While patients with HER2+ breast cancer are highly concerned about recurrence, most feel that their personal risk is moderate. Patients are highly engaged in treatment planning, often initiate discussions about risk of recurrence, and supplement their knowledge with their own research. The threshold to motivate inquiry into a new drug to reduce recurrence risk was &amp;lt;20% for over half of patients. Patients were also frequently willing to tolerate common adverse events. Citation Format: Jenkins M. Patient perspectives on HER2+ breast cancer recurrence: Results from an online patient survey [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-14-03.

Abstract P6-16-06: Twitter chats: Utilizing an innovative technology platform to offer education and tools to people with breast cancer

Abstract Background. The use of social media for health information and peer support has grown significantly over time. According a 2015 study from the Pew Research Center, 65 percent of U.S. adults utilize social media, up from 7 percent a decade earlier. A 2014 study reported 72 percent of adult internet users search online for health information, often focused on specific diseases or treatments, with 16 percent seeking others with similar health concerns. Twitter, a popular social media platform for information- and support-seekers, grew from 54 million monthly active users in 2010 to approximately 241 million in 2013. To address the growing use of Twitter as an information and support portal, Living Beyond Breast Cancer (LBBC) decided to pilot a Twitter chat in 2014. The goals for the chat were to: (1) increase understanding of a breast cancer concern; (2) connect impacted individuals to one another in a supportive and safe online space; (3) offer practical resources for further exploration; and (4) increase LBBC's reach online among users interested in breast cancer. Methods. LBBC staff researched best practices for Twitter chats. The topic of triple-negative breast cancer (TNBC) was chosen for LBBC's pilot program to coincide with Triple Negative Breast Cancer Awareness Day. The staff developed 7 questions and 10 alternates to deliver over 60 minutes. Using publicly available data from Symplur, hashtags were considered and developed. A panel was recruited of one medical oncologist, two advocates, and two women with TNBC. Panelists were encouraged to prepare Tweets in advance and, during the chat, to use assigned hashtags, correct medical inaccuracies, and attend to emotional concerns among chat participants. LBBC staff developed resource-rich tweets. The program was promoted over social media channels. At the end of the chat, participants were offered an incentivized opportunity to evaluate the program via a URL link to LBBC's existing survey instrument. Results. Using the #TNBCchat hashtag, the March 3, 2014, program and activity the next week produced 234 tweets from 127 contributors, reaching 198,985 accounts. Participants wrote 118 tweet replies and retweeted 291 comments. Questions covered the definition of and treatments for TNBC, differences between metastatic and early-stage disease, unique emotional concerns, and methods to reduce recurrence risk. The three most popular tweets promoted the program, introduced panelists, and shared resources about PARP inhibitors. Encouraged by the pilot program's reach and results, LBBC has delivered 20 Twitter chats as of June 2018. Topics have included nutrition, parenting, caregiving, and breast reconstruction. Over time, LBBC staff has refined the program model with the goals of increasing engagement, delivering more useful content, and driving users toward the evaluation. Conclusions. Twitter chats allow nonprofit organizations to inexpensively utilize innovative technology to provide educational information to and foster a community of support among people impacted by breast cancer. By utilizing core organizational principles of appropriate program delivery, LBBC delivers practical content that may improve the quality of life of users in distant locations. Citation Format: Guglielmino JE, Ormerod CL, Grillo AB, Sood SA. Twitter chats: Utilizing an innovative technology platform to offer education and tools to people with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-16-06.

Abstract P5-16-11: Intraoperative central nipple biopsy in subcutaneous mastectomies - A retrospective analysis of 200 patients

Abstract Background: Subcutaneous nipple sparing mastectomies (NSM) are an important tool in modern oncoplastic surgery. Especially when an immediate implant-based reconstruction (IBR) is desired, clean margins are of the utmost importance. Central nipple biopsies during surgery serve two main purposes. Most importantly, it is hypothesized that a general recurrence risk reduction occurs due to elimination of glandular and ductal components within the nipple. In addition, intraoperative pathological evaluation of this biopsy may increase clean margin resection rates. This trial aimed to evaluate complication rates, local recurrence and clean margin resection rates in a head-to-head retrospective manner. Methods: Starting in 2015, intraoperative central nipple biopsy in NSM with IBR was introduced at the Municipal Breast Cancer Centre Cologne, Holweide, Germany. This trial evaluates global complication rates (necrosis, implant loss, seroma and hematoma), long term local recurrence and clean margin status for cohort 1 (n=100) SSM with nipple biopsy vs. cohort 2 (control, n = 100) without nipple biopsy. In case of an involved central nipple biopsy, the nipple areola complex was removed. This analysis is a single center, multi-surgeon, retrospective, head to head analysis. Median follow-up is three years. All IBR procedures used an epipectoral implant pocket. Results: Global complication rates did not differ significantly between both cohorts. There was no increased rate of implant loss and or revision surgery. Within the medium three-year follow-up there was no case of local recurrence within nipple areola complex for both cohorts. An Involved central nipple biopsy was however found in 2% (n=2 /100) of the performed SSM procedures leading to the immediate removal of the nipple areola complex. Surgical time did not increase with central biopsy. A significantly higher rate of re-surgery due to involved margins was shown in the control cohort. Conclusions: This analysis showed that intraoperative evaluation of the ductal components of the nipple is a safe procedure. At least 2% of the patients showed an immediate advantage of this procedure since clean margins were obtained by removing the nipple areola complex during the same surgery. The medium follow-up showed no significant difference in local recurrence. We therefore strongly, recommend a central nipple biopsy for all NSM procedures. Citation Format: Eichler C, Stephan S, Thangarajah F, Puppe J, Mathias W. Intraoperative central nipple biopsy in subcutaneous mastectomies - A retrospective analysis of 200 patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-16-11.

Abstract P6-14-06: A patient-centered approach to education: Evaluating and improving radiation treatment education in breast cancer patients

Abstract Introduction Breast cancer patients rapidly receive large amounts of information from multiple practitioners during treatment. It is therefore essential that education be presented in an appropriate manner to promote satisfaction and retention of important facts regarding treatment. Educational materials at the Memorial Radiation Oncology Department have not been evaluated by patients, and it is unclear how effectively and efficiently they express information. We hypothesized that satisfaction was already very good, but patients lacked knowledge of key aspects of their radiation treatment. This quality improvement project aimed to achieve a patient comprehension of key treatment-related concepts of 75% by March 2018 via evaluating and improving educational materials. Methods A survey was designed to evaluate patient satisfaction with and comprehension of educational materials. The survey inquired about satisfaction with several specific aspects of their education and tested understanding of concepts that impact treatment. The survey was administered to all breast cancer patients over a three-month period. Those results were used for a PDSA cycle to implement improvements. These improvements included eliminating redundant resources, reemphasizing essential concepts throughout treatment, and consolidating important concepts from the materials into a more accessible one-page summary sheet. Following those changes, the surveys was adapted and administered to every breast cancer patient over another three-month period, which were analyzed to evaluate the effectiveness of and satisfaction with the interventions. Statistical comparisons were performed using Student's t-test and Fisher's exact test. Results Following the interventions, overall satisfaction improved from 97% to 100% (p=1.0). However, 27% and 18% of patients still did not remember receiving an informational letter and physician handout, respectively. On knowledge based questions, average percent correct improved from 52% to 78% (p=&amp;lt;0.001). However, there were areas where comprehension declined following the interventions. Select results of individual survey items are shown below in Table 1: Table 1: Outcomes of Educational InterventionsCategoryInitial Result (%) (n=31)Final Result (%) (n=26)Change (%)p-valueRemembered getting pre-treatment letter7465-90.566Remembered getting post-consult physician handout9488-60.651Watched emailed informational video14N/AN/AN/ACorrectly reported recurrence risk reduction associated with radiation treatment3016-140.341Correctly identified timing of peak skin reaction4788+410.002Correctly identified contraindication of antioxidant use during radiation treatment2964+350.015 Conclusions A patient-centered approach to developing and delivering patient education can lead to better satisfaction and patient comprehension, thereby improving compliance and encouraging patient engagement, which has a positive impact on outcomes. Although some education remained unmemorable or improperly emphasized following the interventions, overall trends in comprehension validate tailoring educational materials to patient feedback. In the future, the PDSA cycles will be continued with a focus on addressing persistent educational deficits and identifying further avenues to improve patient retention. Citation Format: Ladbury CJ, Ridings JW, Yancy D. A patient-centered approach to education: Evaluating and improving radiation treatment education in breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-14-06.

Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation.

Background Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. Methods All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. Results A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). Conclusion Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied.

Adherence to adjuvant endocrine therapy in postmenopausal breast cancer patients: A 5-year prospective study

PurposeAdjuvant endocrine therapy (ET) in breast cancer reduces recurrence risk and increases overall survival. The aim of the study was to quantify non-adherence and discontinuation to ET in postmenopausal women with breast cancer, and identify possible clinical or social risk factors. MethodsWomen with hormone-receptor positive breast cancer (N = 138), mean age 58 (SD 9.3) years, filled in 4 questionnaires within 1–12, 24, 36 and 48–60 months after surgery; Subjective Health Complaints Inventory (SHC), Functional Assessment of Cancer Therapy-Social Support Subscale (FACT-ES), and Quality of Patient Information Questionnaire (QPI). Adherence to Tamoxifen (Tam) or Aromatase Inhibitors (AI) was examined using the self-reported Morisky Medication Adherence Scale (MMAS-8) and data from the Norwegian Prescription Database (NorPD). Kaplan-Meier curves and Cox proportional hazards regression models estimated adherence to ET. ResultsThe estimate of discontinued ET within 60 months was 38%. Self-reported discontinuation was 7% compared with 25% from the NorPD. Being overweight or obese were significantly time dependent factors predictive for discontinuing ET, p = 0.025. ConclusionCloser follow-ups, tailor-made information about the proven benefits of ET, and keeping a normal body mass index (BMI) may improve adherence to ET in postmenopausal women with breast cancer.

Comparison of three surgical treatment options for unicameral bone cysts in humerus.

Treatment of unicameral bone cysts (UBC) in the humerus with drainage screws is scarcely reported in the literature. The aim of this retrospective study was to compare drainage screws and alternative treatment methods with respect to the number of required surgical procedures to achieve sufficient UBC healing, postoperative fractures/recurrences/complications, and radiological outcome. Medical archives of two tertiary orthopedic referral centers were screened for all patients who were treated surgically for humeral UBC in the period 1991-2015 with a histologically/cytologically confirmed diagnosis. Sex, age, all surgical procedures, fractures, complications, recurrences, and the final radiological outcome were compared between patients treated with drainage screws, elastic intramedullary nails, or curettage with optional grafting. The study included 106 operated patients with a mean age of 10.3 years, with a mean follow-up of 5.7 years. The average number of UBC-related surgical procedures in sex-matched and age-matched treatment groups was 2.7 with drainage screws, 2.8 with intramedullary nails, and 3.5 with curettage/grafting (P=0.54). Intramedullary nails (odds ratio 0.20) and older age (odds ratio for each year 0.83) predicted a lower risk of postoperative UBC recurrence. Patients with drainage screws had the highest UBC recurrence rates and the lowest rates of changed initial treatment method. There was no difference between the treatment groups in the postoperative fracture rate, complications, or the final radiological outcome. UBC treatment in the humerus therefore requires approximately three surgical procedures, irrespective of the treatment modality chosen. Adding an elastic intramedullary nail to a humeral UBC cyst may reduce recurrence risk and prevent further fractures. Level of Evidence: Level III - therapeutic retrospective comparative study.

Feasibility and outcome of total laparoscopic radical hysterectomy with no-look no-touch technique for FIGO IB1 cervical cancer.

ObjectivesIntraoperative tumor manipulation and dissemination may possibly compromise survival of women with early-stage cervical cancer who undergo minimally-invasive radical hysterectomy (RH). The objective of the study was to examine survival related to minimally-invasive RH with a “no-look no-touch” technique for clinical stage IB1 cervical cancer.MethodsThis retrospective study compared patients who underwent total laparoscopic radical hysterectomy (TLRH) with no-look no-touch technique (n=80) to those who underwent an abdominal radical hysterectomy (ARH; n=83) for stage IB1 (≤4 cm) cervical cancer. TLRH with no-look no-touch technique incorporates 4 specific measures to prevent tumor spillage: 1) creation of a vaginal cuff, 2) avoidance of a uterine manipulator, 3) minimal handling of the uterine cervix, and 4) bagging of the specimen.ResultsSurgical outcomes of TLRH were significantly superior to ARH for operative time (294 vs. 376 minutes), estimated blood loss (185 vs. 500 mL), and length of hospital stay (14 vs. 18 days) (all, p<0.001). Oncologic outcomes were similar between the 2 groups, including disease-free survival (DFS) (p=0.591) and overall survival (p=0.188). When stratified by tumor size (<2 vs. ≥2 cm), DFS was similar between the 2 groups (p=0.897 and p=0.602, respectively). The loco-regional recurrence rate following TLRH was similar to the rate after ARH (6.3% vs. 9.6%, p=0.566). Multiple-pelvic recurrence was observed in only 1 patient in the TLRH group.ConclusionOur study suggests that the no-look no-touch technique may be a useful surgical procedure to reduce recurrence risk via preventing intraoperative tumor spillage during TLRH for early-stage cervical cancer.

Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial

BackgroundChronic subdural haematoma (CSDH) is a common neurosurgical condition, typically treated with surgical drainage of the haematoma. However, surgery is associated with mortality and morbidity, including up to 20% recurrence of the CSDH. Steroids, such as dexamethasone, have been identified as a potential therapy for reducing recurrence risk in surgically treated CSDHs. They have also been used as a conservative treatment option, thereby avoiding surgery altogether. The hypothesis of the Dex-CSDH trial is that a two-week course of dexamethasone in symptomatic patients with CSDH will lead to better functional outcome at six months. This is anticipated to occur through reduced number of hospital admissions and surgical interventions.MethodsDex-CSDH is a UK multi-centre, double-blind randomised controlled trial of dexamethasone versus placebo for symptomatic adult patients diagnosed with CSDH. A sample size of 750 patients has been determined, including an initial internal pilot phase of 100 patients to confirm recruitment feasibility. Patients must be recruited within 72 h of admission to a neurosurgical unit and exclusions include patients already on steroids or with steroid contraindications, patients who have a cerebrospinal fluid shunt and those with a history of psychosis. The decision regarding surgical intervention will be made by the clinical team and patients can be included in the trial regardless of whether operative treatment is planned or has been performed. The primary outcome measure is the modified Rankin Scale (mRS) at six months. Secondary outcomes include the number of CSDH-related surgical interventions during follow-up, length of hospital stay, mRS at three months, EQ-5D at three and six months, adverse events, mortality and a health-economic analysis.DiscussionThis multi-centre trial will provide high-quality evidence as to the effectiveness of dexamethasone in the treatment of CSDH. This has implications for patient morbidity and mortality as well as a potential economic impact on the overall health service burden from this condition.Trial registrationISRCTN, ISRCTN80782810. Registered on 7 November 2014. EudraCT, 2014-004948-35. Registered on 20 March 2015.Dex-CSDH trial protocol version 3, 27 Apr 2017.This protocol was developed in accordance with the SPIRIT checklist. Available as a separate document on request.

A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis: A British Society for Haematology Guideline.

The previous BSH guideline for the management of erythrocytosis was published in 2005 (McMullin et al, 2005) and amended in 2007 (McMullin et al, 2007). Here, we re‐evaluate the literature formulate guidance on the management of specific situations encountered in polycythaemia vera (PV) and the management of the other types of secondary erythrocytosis. Recommendations for the diagnostic pathway of investigation of an erythrocytosis, risk stratification and management of PV are in the accompanying guideline (McMullin et al, 2018). We review evidence and outline guidance on management of acute thrombotic events and secondary prevention of thrombosis in PV. The unusual thrombotic events, splanchnic vein and cerebral vein thromboses are discussed and haemorrhage. The specific situations of surgery and pregnancy and guidance on management of pruritus are included. The evidence for the management of other causes of erythrocytosis, including idiopathic erythrocytosis, congenital erythrocytosis, hypoxic pulmonary disease and post‐transplant erythrocytosis, is reviewed and recommendations made.