Adjuvant Therapy In Women Research Articles

3408: Ten-year results of the PORTEC-3 trial: adjuvant therapy for women with high-risk endometrial cancer

3408: Ten-year results of the PORTEC-3 trial: adjuvant therapy for women with high-risk endometrial cancer

Anatomic Location of Tissue Expander Placement Is Not Associated With Delay in Adjuvant Therapy in Women With Breast Cancer.

Tissue expanders in breast reconstruction are traditionally placed retropectoral. Increasingly, patients are undergoing prepectoral placement. The impact of this placement on the initiation of adjuvant treatment is unknown. A retrospective review was conducted to identify women diagnosed with breast cancer who underwent mastectomy followed by radiation and/or chemotherapy. Women were divided into 3 groups: prepectoral tissue expander placement, retropectoral tissue expander placement, and no immediate reconstruction. A treatment delay was defined as greater than 8 weeks between tissue expander placement and adjuvant therapy. Of 634 women, 205 (32%) underwent tissue expander placement, and 429 (68%) did not have immediate reconstruction. Of those with tissue expanders placed, 84 (41%) had prepectoral placement, and 121 (59%) had retropectoral placement. The median time to adjuvant therapy was 49 days for the entire cohort: no reconstruction, 47 days; prepectoral, 57 days; and retropectoral, 55 days. Treatment delays were observed in 34% of women: no reconstruction, 28%; prepectoral, 51%; and retropectoral, 46% (P < 0.001). Tissue expander placement was associated with a delay to adjuvant therapy when compared with no reconstruction (P < 0.001). The location of the tissue expander did not impact the odds of having a delay. On multivariable analysis, having reconstruction, having postoperative infection, not undergoing chemotherapy treatment, and being a current smoker were associated with a delay to adjuvant therapy. A delay to treatment was not associated with worse survival. Placement of a tissue expander delayed adjuvant therapy. The location of tissue expander placement, retropectoral versus prepectoral, did not impact the time to adjuvant treatment.

Adjuvant therapy in women with early stage uterine serous carcinoma: A multi-institutional study

ObjectiveUterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma. MethodsThis multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall survival. ResultsThere were 737 patients included. Most patients had Stage IA disease (75%), 49% of which had no myometrial invasion. Only 164 (24%) tumors had lymphatic/vascular space invasion. Adjuvant treatment varied: 22% received no adjuvant therapy, 17% had chemotherapy alone, 19% had cuff brachytherapy, 35% had cuff brachytherapy with chemotherapy, and 6% underwent pelvic radiation. Adjuvant treatment was significantly associated with a decreased risk of recurrence (p = 0.04). Compared with no adjuvant therapy, patients who received brachytherapy or brachytherapy/chemotherapy had improved recurrence-free survival (HR 0.59, 95% CI 0.40–0.86; HR 0.65, 95% CI 0.49–0.88, respectively) and overall survival (HR 0.53, 95% CI 0.35–0.79; HR 0.49, 95% CI 0.35–0.69, respectively). Improved survival with brachytherapy and brachytherapy/chemotherapy persisted on multivariable analyses. Chemotherapy alone was also associated with improved overall survival compared with no adjuvant treatment (HR 0.55, 95% CI 0.37–0.81). ConclusionsAdjuvant therapy was associated with a decreased risk of recurrence relative to observation alone. Adjuvant cuff brachytherapy with and without chemotherapy was associated with improved survival outcomes in patients with early stage uterine serous carcinoma.

Predictive Role of Soluble IL-6R, TNF-R1/2, and Cell Adhesion Molecules Serum Levels in the Preoperative and Adjuvant Therapy in Women with Nonmetastatic Breast Cancer: A Preliminary Study.

Soluble cell adhesion molecules (sCAMs) are involved in the development of neoplastic diseases. sCAMs can block lymphocytes and promote angiogenesis and migration of breast cancer (BC) cells. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) enhance metastatic potential via upregulation of CAMs. We assessed soluble interleukin-6 receptor subunit alpha (IL-6Ra), TNF-R1, TNF-R2, E-selectin, P-selectin, VCAM-1, ICAM-1, and EpCAM in 89 women with stage I-III BC and 28 healthy women. Blood samples were obtained at the beginning of neoadjuvant/induction (N = 49) or adjuvant treatment (N = 40), and after 2 months. Surgery revealed complete response in 29.4% of patients, partial response in 67%, and stable disease in 5.9%. Achieving a pathological response was 4 times greater for baseline levels of sIL-6Ra >5.63 ng/mL [odds ratio (OR) = 4.1, 95% confidence interval (CI): 0.8-20.4, P = 0.08] and more than 6 times for soluble tumor necrosis factor receptor 1 (sTNF-R1) ≥ 0.97 ng/mL (OR = 6.2, 95% CI: 1.2-32.3, P < 0.05). Compared with the control group, serum sP-selectin, soluble epithelial cell adhesion molecule (sEpCAM), and sTNF-R2 concentrations were significantly higher in patients who started adjuvant therapy (P < 0.05) and preoperative therapy (P < 0.01). Baseline serum sIL-6Ra concentrations were significantly higher in patients before surgery than in patients after tumor resection (P < 0.05), independent of the follow-up time. The baseline serum soluble receptors of IL-6 (sIL-6R) and TNF-α (sTNF-R1) concentrations have a predictive value for preoperative therapy in patients with BC.

Factors Associated with Plasma Levels of Tamoxifen and its Main Metabolites in Mexican Patients with Breast Cancer

Background: Tamoxifen (TAM) is commonly prescribed as adjuvant therapy in women with estrogen receptor-positive breast cancer. Unfortunately, not all patients respond adequately to this drug. This variation in pharmacological response has been associated with different factors, including genetic polymorphisms of enzymes responsible for the metabolism of TAM. Objective: To determine the concentrations of tamoxifen (TAM) and its main metabolites in Mexican women with breast cancer and to evaluate its relationship with genetic, demographic and anthropometric characteristics. Methods: Eighty-four patients with a mean age of 49.3 (± 8.8) years were included in the study. Plasma concentrations of TAM and its metabolites N-desmethyl-tamoxifen (NDT), 4- hydroxy-tamoxifen (4HT) and endoxifen (END) were determined in predose for each patient. CYP2D6 * 4, * 10 and CYP3A5 * 3 genetic polymorphisms were characterized. Demographic, anthropometric, biochemical and clinical data were recorded for each patient. Results: Plasma concentrations of 4HT and END were higher in the extensive metabolizer (EM) phenotype than in the intermediate metabolizer (IM) phenotype (p&lt;0.05). The metabolic ratio (MR) [END+4HT]/[TAM+NDT] was lower in patients with the CYP2D6 IM phenotype than those with the EM phenotype (p= 0.014). Regarding anthropometric factors, a positive correlation was found for 4HT and the END concerning age (R = 0.256 and 0.232, respectively). The body mass index (BMI) presented a statistically significant correlation with the concentrations of NDT (R=-0.351) and 4HT (R=-0.298). Conclusion: CYP2D6 phenotype, age and BMI could help to explain part of the interindividual variability of TAM plasma levels and its metabolites in the Mexican population.

Risk-Stratified Intraoperative Radiation Therapy as a Definitive Adjuvant Radiation Therapy Modality for Women With Early Breast Cancer

Radiation therapy is an integral component of adjuvant therapy in women who undergo breast conservative surgery, decreasing the likelihood of tumor recurrence and extending survival. The likelihood of tumor recurrence is highest within a proximity of the lumpectomy cavity, which prompted the idea of partial breast irradiation in place of the usual standard-of-care treatment with external beam whole breast radiation therapy. Targeted intraoperative radiation therapy (TARGIT-A) is a multicenter trial initially developed in 1999 and designed as a randomized clinical trial comparing whole breast radiation therapy to risk-adapted intraoperative radiation therapy (IORT). TARGIT-A recruited its first patient in March 2000, with the study concluding in 2012. At a median follow-up of 8.6 years, the prepathology TARGIT-A trial noted results to be noninferior to external beam radiation therapy, with no statistically significant difference in ipsilateral breast tumor recurrence, mastectomy-free survival, distant disease-free survival, or breast cancer–specific mortality. These results are consistent with the majority of retrospective and prospective trials. Risk-adapted IORT, as performed in the prospective randomized TARGIT-A trial, gives level 1 evidence that this approach is a standard option in the treatment of breast cancer.

Feasibility and Safety of Intraoperative Radiotherapy with Low Energy X-ray Photon Therapy for Recurrent Gynecological Cancer: A Case Series.

Objectives: To evaluate the feasibility and safety of low energy X-ray photon intraoperative radiotherapy (IORT) as an adjuvant therapy for recurrent gynecological cancer.Methods: Medical records of all recurrence gynecological cancer patients who underwent IORT were reviewed. Results: Between January 2018 and December 2021, five women (including cervical cancer (n = 2), endometrial cancer (n = 2), and uterine leiomyosarcoma (n = 1)), who underwent IORT and surgical resection for recurrent gynecologic cancer were reviewed. A median dose of 15.62 Gy (range, 12 to 20 Gy) was used for IORT. Repeated IORT and surgical resection was performed in two women. Three women experienced local recurrence, and three women died during follow-up. The 1-year local control rate was 60%. The 2-year overall survival rate was 30%. There was no Clavien–Dindo classification grade III–V complication. Conclusion: IORT using low energy X-ray photon therapy seems to be feasible and safe as an adjuvant therapy in women who underwent salvage surgery for recurrent gynecologic cancer. However, large-scale prospective studies are needed to confirm our findings and evaluate its efficacy.

Assessment of Health Beliefs Among Iraqi Breast Cancer Patients in Baghdad using either Tamoxifen or Trastuzumab

Breast cancer is the most diagnosed form of malignant tumour in Iraqi women. Tamoxifen and trastuzumab are highly effective adjuvant therapy for breast cancer.&#x0D; This study's objectives were to define the patient's belief in tamoxifen or trastuzumab when used as adjuvant therapy and to determine the variation in belief between the two medications in a sample of Iraqi breast cancer patients.&#x0D; The cross-section survey was conducted using the BMQ-Specific questionnaire. Ninety-seven participants (sixty-seven tamoxifen, thirty trastuzumab) participated in this study.&#x0D; The mean of specific-necessity scale for tamoxifen was (3.7) and for trastuzumab (4). The findings showed a high necessity for both medicines, and there were no significant differences in the scale of necessity between the two treatments. Regarding the scale of concern, the trastuzumab group's values are higher (3.35) than tamoxifen (3). Most participants who use tamoxifen or trastuzumab strongly agree with or agree with all the questions on the necessity scale with higher percentages for trastuzumab. Besides, the concern scale results showed the percentage of patients who agree / strongly agree is higher in the trastuzumab group. For the correlation between the need or concern score, the result showed only one significant negative correlation (R=-0.366, P-value=0.011) between the necessity score and the age of the participants for tamoxifen users. In Conclusion, this survey clearly showed a high level of necessity and a high level of concern regarding the use of two effective adjuvant therapy for women with breast cancer, tamoxifen and trastuzumab. Furthermore, this study shows that while the level of need for tamoxifen is higher than for trastuzumab, there were no significant variations between them.

Definitive Chemoradiotherapy versus Radical Hysterectomy Followed by Tailored Adjuvant Therapy in Women with Early-Stage Cervical Cancer Presenting with Pelvic Lymph Node Metastasis on Pretreatment Evaluation: A Propensity Score Matching Analysis

Simple SummaryPelvic nodal involvement is frequently present in early-stage cervical cancer patients on pretreatment imaging studies. However, it is unclear whether radical chemoradiotherapy (CRT) or radical hysterectomy RH followed by tailored adjuvant radiotherapy is more appropriate in these patients. We compared oncological outcomes of up-front surgery followed by tailored adjuvant radiotherapy and definitive CRT in these patients. We found no differences in outcomes existed between definitive CRT and hysterectomy with tailored adjuvant radiotherapy. However, after surgery, 88.7% of patients required adjuvant radiotherapy. These findings suggest that definitive CRT can avoid unplanned tri-modality therapy without compromising oncologic outcomes.To compare the oncologic outcomes between chemoradiotherapy (CRT) and radical hysterectomy followed by tailored adjuvant therapy in patients with early cervical cancer presenting with pelvic lymph node metastasis. We retrospectively analyzed the medical records of women with early cervical cancer presenting with positive pelvic nodes identified on pretreatment imaging assessment. Propensity score matching was employed to control for the heterogeneity between two groups according to confounding factors. Overall survival, disease-free survival, and pattern of failure were compared between the two groups. A total of 262 patients were identified; among them, 67 received definitive CRT (group A), and 195 received hysterectomy (group B). Adjuvant therapy was administered to 88.7% of group B. There were no significant differences between group A and group B regarding the 5-year overall survival rates (89.2% vs. 89.0%) as well as disease-free survival rates (80.6% vs. 82.7%), and patterns of failure. Distant metastasis was the major failure pattern identified in both groups. In multivariate analysis, non-squamous histology was significantly associated with poorer overall survival. As there are no significant differences in 5-year OS, DFS, and patterns of failure, definitive CRT could avoid the combined modality therapy without compromising oncologic outcomes.

Machine learning to guide the use of adjuvant therapies for breast cancer

Accurate prediction of the individualized survival benefit of adjuvant therapy is key to making informed therapeutic decisions for patients with early invasive breast cancer. Machine learning technologies can enable accurate prognostication of patient outcomes under different treatment options by modelling complex interactions between risk factors in a data-driven fashion. Here, we use an automated and interpretable machine learning algorithm to develop a breast cancer prognostication and treatment benefit prediction model—Adjutorium—using data from large-scale cohorts of nearly one million women captured in the national cancer registries of the United Kingdom and the United States. We trained and internally validated the Adjutorium model on 395,862 patients from the UK National Cancer Registration and Analysis Service (NCRAS), and then externally validated the model among 571,635 patients from the US Surveillance, Epidemiology, and End Results (SEER) programme. Adjutorium exhibited significantly improved accuracy compared to the major prognostic tool in current clinical use (PREDICT v2.1) in both internal and external validation. Importantly, our model substantially improved accuracy in specific subgroups known to be under-served by existing models. Adjutorium is currently implemented as a web-based decision support tool ( https://vanderschaar-lab.com/adjutorium/ ) to aid decisions on adjuvant therapy in women with early breast cancer, and can be publicly accessed by patients and clinicians worldwide. Methods are available to support clinical decisions regarding adjuvant therapies in breast cancer, but they have limitations in accuracy, generalizability and interpretability. Alaa et al. present an automated machine learning model of breast cancer that predicts patient survival and adjuvant treatment benefit to guide personalized therapeutic decisions.

Does the Time to Adjuvant Radiotherapy Impact Outcomes in Women With Stage III Uterine Cancer?

Adjuvant radiotherapy (ART) combined with chemotherapy (CT) is an effective adjuvant therapy in women with stage III uterine carcinoma (UC). However, there exists a sparse evidence for the optimal time to start ART. We evaluated the impact of time interval to ART initiation on survival endpoints for surgically staged patients with stage III EC receiving adjuvant multimodality therapy. We queried our prospectively- maintained database for women with FIGO stage III UC who underwent surgical staging at our institution between 12/1990 and 12/2019. All patients in the study received ART and CT with various sequences. CT consisted of 4-6 cycles of paclitaxel-carboplatin combined with ART (external beam RT (EBRT) ± vaginal brachytherapy (VB) boost). Time to RT initiation (TRTI) elapsing between surgical staging and 1st fraction of ART was calculated in weeks for each patient. We studied the influence of TRTI on relapse- free (RFS), disease- specific (DSS) and overall (OS) survival using log-rank test (continuous) and Kaplan-Meier curves to compare outcomes at weekly increments (8-12 weeks). Clinico-pathological and treatment characteristics were dichotomized at the 8 weeks' time-point and compared. Cox regression multivariate analyses (MVA) were performed to determine independent predictors for survival endpoints. 137 patients were identified. Median age was 64 years (range, 38-85), 45% of patients had non-endometrioid histology. Median number of lymph nodes (LN) examined was 23 (range, 1-55) and median number of positive LN was 2 (range, 0-18). Stage IIIC constituted 78% of the study cohort followed by stage IIIA (20%). 51% of the patients received EBRT alone, while 49% received an additional VB boost. 72 cases (52.5%) received ART ≤8 weeks after hysterectomy, and 47.5% (n = 65) received ART > 8 weeks. After a median follow up of 58 months (CI: 42-66), longer TRTI > 8 weeks was associated with worse 5-year RFS (49% (CI:36-62) vs. 71% (CI:55-83); p = 0.01), which persisted at latter time points (9-12 weeks), p<0.05 for all; with a trend when assessed as a continuous variable (p = 0.053). TRTI was neither correlated with 5-year OS or DSS. On MVA for RFS, TRTI (> vs. ≤ 8 weeks) (HR 2.9 (CI:1.4-6.03); p = 0.004), lymphovascular space invasion (HR 4.05; p = 0.009) and advanced stage (HR 3.63; p = 0.04) were all independent prognostic factors. African American race was the only independently predictive for shorter OS (HR 2.44; p = 0.002) and DSS (HR 3.26; p = 0.006). Within the context of multimodality therapy, our study suggests that earlier start of ART within 8 weeks was independently associated with improved recurrence- free survival in women with advanced stage endometrial cancer. Multi-institutional research collaboration is needed to validate our results.

Patterns and variability in treatment patterns for high-risk endometrial cancer

Objective: Because of the poor prognosis after treatment with surgery alone, high-risk endometrial cancer patients are usually treated with adjuvant therapy. However, prospective trial results have reported conflicting data, and little is known about current practice patterns. We surveyed gynecologic oncologists in the United States to determine their practice patterns and preferences for adjuvant therapy in women with high-risk endometrial cancer.

Clinical practice to address tamoxifen nonadherence.

The primary and secondary benefits of tamoxifen as adjuvant therapy in women with hormone-receptor-positive breast cancer are substantial: a 1% decrease in the risk of death each year for 10years with each additional year of treatment during the first 5years. Considerable data, however, indicate that these benefits are lost to many patients because of treatment nonadherence. Nonadherence is examined within the framework of the Common-Sense Model of Self-Regulation to describe patients' models of disease and treatment that organize their thinking and behavior, and the crucial role of the practitioner in addressing and altering these models. Common patient education and social communications about patients' hormone-receptor-positive breast cancer and tamoxifen treatment promote an acute disease paradigm in which cancer occurs within specific locations and is either present or absent. We recommend that clinicians communicate the concepts of hormone-receptor-positive breast cancer as follows: i. a non-dichotomous systemic disorder entailing a treatment goal of homeostasis and disease quiescence and ii. a disorder undetectable by currently available tests in subclinical states. Equally important, the clinician can provide a comprehensive picture of the well-documented secondary effects of tamoxifen, noting in particular the beneficial effects. Specific action plans, grounded in individual patient understanding, can be developed and reinforced, in an ongoing process that validates and integrates patient values and goals as they change over time.

Role of Transvaginal Ultrasound in Detection of Endometrial Changes in Breast Cancer Patients under Hormonal Therapy

Abstract Background Hormonal therapy is widely utilized as adjuvant therapy in women diagnosed with breast cancer, in those patients, Despite its positive risk/benefit ratio, It may cause secondary effects on the endometrium, Including endometrial atrophy, Endometrial polyp, Endometrial hyperplasia, and up to Endometrial carcinoma. Aim of the Work We aim to determine the role of TVUS in detection of endometrial changes. Aim and Patients and Methods Cross sectional Prospective study. We analyzed the data from previous scans and current scan and correlate it with the results of histopathology. All US examinations were performed by our senior radiologists at radiology department of Helwan university hospital. Study period from March 2018 to November 2018. Results The study group comprised 50 patients with breast cancer who were treated with tamoxifen for a period ranging from 3months to 5 years, by TVUS endometrial thickness measurement was ranging from (3 to 30 mm) the mean is 10.22 mm and standard deviation ± 5.76 mm, all patients were examined by TVUS, gynecological examination and they were candidate for endometrial biopsy either by D&amp;C or hysteroscopic resection. Their histopathology results were: normal endometrium with no changes (52%), endometrial hyperplasia (14%), endometrial polyp (14%), adenomyosis (10%), endometrial atrophy (6%) and endometrial carcinoma (4) %. Conclusion We evaluated the correlation between tamoxifen therapy and endometrial benign and malignant conditions and correlate the findings seen in TVUS by the histopathological results .We concluded that TVUS is a necessary screening tool for detection of endometrial abnormalities in breast cancer patients under hormonal therapy.

Overall Survival and Adjuvant Therapy in Women with Ovarian Carcinosarcoma: A Single-Institution Experience.

Background: Carcinosarcoma of the ovary (CSO) is a rare and aggressive variant of ovarian cancer. Due to the rare nature of the disease there is insufficient evidence to make recommendations regarding standard management and overall prognosis. Methods: An Institutional Review Board-approved study identified all our patients with CSO between January 2011 and May 2018. Demographic and outcome measures were abstracted from the medical records and tumor board files. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance (p < 0.05). Results: 27 women with CSO were identified. The median age at diagnosis was 65 years (range 48–91). Five women (18%) presented with early stage disease (Stage I or II) and 22 patients (82%) presented with late stage III or IV disease. Twenty patients (74%) received intravenous platinum-based combination chemotherapy. Seven patients did not receive chemotherapy during their treatment course. The median overall survival was 23 months (range 2–68 months). Overall survival was not significantly worsened by the stage of disease at diagnosis. There was no difference in survival based on the age at diagnosis, tobacco status or ethnicity (p > 0.05). Conclusion: This is one of the largest single institution experiences with CSO. The majority of our patients presented with advanced stage disease and received adjuvant platinum-based chemotherapy after cytoreductive surgery. The median overall survival of 23 months was not affected by the stage of the disease. The optimal management of this rare disease needs further study with collaborative, prospective multi-institutional trials.

Overall survival and adjuvant therapy in women with clear cell carcinoma of the ovary

Overall survival and adjuvant therapy in women with clear cell carcinoma of the ovary

Abstract P6-03-02: Budesonide and colesevelam reduce neratinib-induced diarrhea in a rat model

Abstract Background: Neratinib (Puma Biotechnology Inc.) is an irreversible pan-HER tyrosine kinase inhibitor approved for use as extended adjuvant therapy in women with early-stage HER2+ breast cancer. Diarrhea is the main adverse event of neratinib; grade 3 events are common in the absence of antidiarrheal prophylaxis (40%) [Chan et al. Lancet Oncol 2016]. To investigate the underlying pathogenic mechanisms and to explore possible targets for its prevention, we developed a reproducible rat model of neratinib-induced diarrhea. Findings from the model indicated that neratinib-induced diarrhea is multifactorial, involving anatomical disruption and mucosal inflammation in the ileum and colon [Secombe et al. Asia Pac J Clin Oncol 2017]. We investigated the effects of budesonide, a locally-acting corticosteroid used for gastrointestinal conditions, and colesevelam, a bile acid sequestrant, on neratinib-associated diarrhea and intestinal changes in this model. Methods: Male albino Wistar rats were randomly allocated to vehicle control (5% DMSO/1% carboxymethyl cellulose), neratinib 50 mg/kg alone or combined with budesonide 1 mg/kg or colesevelam 300 mg/kg by oral gavage for 14 or 28 days. Diarrhea severity was graded daily [0, no diarrhea; 1, mild; 2, moderate; 3, severe]. A tissue injury score was assigned based on validated histological criteria (villus fusion and atrophy, disruption of brush border and enterocytes, crypt losses/architectural disruption, crypt cell disruption, infiltration of polymorphonuclear cells/lymphocytes, dilation of lymphatics/capillaries, edema). Inflammation was assessed using multiplex cytokine/chemokine ELISA.Fecal bile acids were measured in pooled fecal samples over an 8-hour period. Results: Findings at 28 days: VariableControl (n=16)Neratinib (n=16)Neratinib + budesonide (n=16)Neratinib + colesevelam (n=16)Incidence of diarrhea, %Grade 137.5000Grade 212.587.5100100Grade 3012.500Mean±SEM days with grade 2 diarrhea0.1±0.115.8±2.710.0±1.0*10.0±2.1*Median (range) tissue injury scoreDistal ileum0.5 (0–2.0)4.0 (3.0–5.0)††3.0 (2.0–4.0)3.0 (2.0–4.0)†Proximal colon2.0 (0–3.0)5.0 (4.0–6.0)††3.0 (2.0–5.0)*3.0 (2.0–5.0)Distal colon0.5 (0–2.0)2.5 (2.0–4.0)††1.0 (0–2.0)*1.5 (0–2.0)Median (range) cytokine levelsaIleumIFN-γ27 (15–48)49 (39–67)†43 (29–55)–IL-463 (15–111)223 (109–318)464 (309–559)**–IL-1021 (14–54)32 (10–84)60 (52–89)*–ColonIFN-γ22 (6–32)16 (12–22)16 (6–19)–IL-4147 (88–270)165 (15–327)345 (170–433)*–IL-1054 (18–128)55 (37–96)47 (43–60)–Mean±SEM total fecal bile acids, umol/mg3.5±0.43.9±0.2–5.5±0.4††*ang/ml (IFN-γ); pg/ml (IL-4, IL-10); *p&amp;lt;0.05, **p&amp;lt;0.005 vs neratinib; †p&amp;lt;0.05, ††p&amp;lt;0.005 vs control; IFN, interferon; IL, interleukin; SEM, standard error of the mean Conclusions: Budesonide and colesevelam reduced duration of neratinib-induced diarrhea and prevented severe diarrhea. Budesonide also reduced histopathological injury and inflammation via preservation of intestinal morphology and upregulation of anti-inflammatory cytokines in the ileum and colon. The phase II CONTROL study (Clinicaltrials.gov NCT02400476) is currently investigating the effects of adding budesonide or colestipol to loperamide prophylaxis in the prevention of neratinib-induced diarrhea and will help to determine the clinical relevance of our observations. Citation Format: Bowen JM, Secombe KR, Ball IA, Shirren J, Wignall AD, Finnie JW, Olek E, Martin D, Lalani AS, Keefe D. Budesonide and colesevelam reduce neratinib-induced diarrhea in a rat model [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 P6-03-02.

Testing a biobehavioral model of fatigue before adjuvant therapy in women with breast cancer.

Fatigue is one of the most common and disabling side effects of cancer and its treatment. Although research typically has focused on fatigue that occurs during and after treatment, patients may experience fatigue even before treatment onset. The current study was designed to identify biobehavioral risk factors associated with fatigue before adjuvant therapy in women with early-stage breast cancer. Patients with stage 0 to stage IIIA breast cancer (270 women) were recruited before the onset of adjuvant or neoadjuvant therapy with radiotherapy, chemotherapy, and/or endocrine therapy. Host factors that may influence fatigue were identified from an empirically based, biobehavioral model and assessed using self-report questionnaires, medical record review, and blood collection (for genetic data). Fatigue was assessed by questionnaire. Linear regression analyses were used to evaluate the association between host factors and dimensions of fatigue, with general fatigue as the primary dimension of interest. Fatigue was elevated at the pretreatment assessment compared with published controls. Bivariate analyses identified demographic, cancer-related, and biobehavioral correlates of fatigue. In the multivariable model, predictors of general fatigue included younger age, lower educational level, lower cancer stage, and history of childhood maltreatment (all P values <.05), with the full model accounting for approximately 18.4% of the variance in fatigue. Secondary analyses identified common and specific predictors of emotional, mental, and physical dimensions of fatigue. Among women who have not yet initiated treatment of breast cancer, demographic and psychosocial factors are associated with elevated fatigue and could be used to identify at-risk patients for early intervention.

Comparison of outcomes in early-stage uterine clear cell carcinoma and serous carcinoma

PurposeThe treatment paradigm for uterine clear cell carcinoma is often linked to serous carcinoma. This study compares oncologic outcomes between women with uterine clear cell and serous carcinoma. Methods and MaterialsWe reviewed 114 women with stage I–II uterine clear cell carcinoma (n = 17, 15%) or serous carcinoma (n = 97, 85%) who underwent hysterectomy and salpingo-oophorectomy at our institution from April 1992 to December 2011; 86 (76%) had stage IA, 14 (12%) had stage IB, and 14 (12%) had stage II disease. Median followup was 57 months. ResultsPatients with uterine clear cell and serous carcinoma did not differ significantly by age ≥60 years, stage, or rate of lymphovascular invasion. There was no difference in the number of patients with clear cell or serous histology who received adjuvant radiotherapy (71% vs. 84%, respectively; p = 0.31); however, significantly fewer patients with clear cell histology received adjuvant chemotherapy (35% vs. 67%, respectively; p = 0.02). At 5 years, there were no significant differences in disease-free survival (94% vs. 84%, respectively; p = 0.27), disease-specific survival (100% vs. 92%, respectively; p = 0.20), or overall survival (100% vs. 89%, respectively; p = 0.34). The differences in chemotherapy utilization did not impact pattern of relapse, specifically peritoneal spread (7% vs. 6%, respectively; p = 0.92) or other distant sites (0% vs. 9%, respectively; p = 0.17). ConclusionsOncologic outcomes and recurrence patterns of women with stage I–II uterine clear cell carcinoma compared favorably with those of women with serous carcinoma, despite significantly less adjuvant chemotherapy use. Potential reduction in adjuvant therapy in women with clear cell carcinoma should be studied prospectively.

Trends in performance of sentinel lymph node mapping and its association with use of adjuvant therapy for women with uterine cancer

Trends in performance of sentinel lymph node mapping and its association with use of adjuvant therapy for women with uterine cancer