Adjuvant therapy for advanced renal cell carcinoma.

PubMed

Meissner, Matthew A; McCormick, Barrett Z; Karam, Jose A; Wood, Christopher G

2018-07-01

Locally advanced, non-metastatic renal cell carcinoma (RCC) is conventionally managed with surgery. However, patients are at a high risk of RCC recurrence and have poor survival outcomes. An effective adjuvant systemic treatment is needed to improve on these outcomes. Targeted molecular and immune-based therapies have been investigated, or are under investigation, but their role in this setting remains unclear. Areas covered: A comprehensive search of PubMed and ClinicalTrials.gov was performed for relevant literature. The following topics pertinent to adjuvant therapy in RCC were evaluated: strategies for patient selection, cytokine-based immunotherapy, vaccine therapy, VEGF and non-VEGF targeted molecular agents, and immune checkpoint inhibitors. Expert commentary: Strong evidence for the incorporation of adjuvant therapy in high-risk RCC is lacking. Multiple targeted molecular therapies have been examined with only one approved for use. Genetic and molecular-based prognostic models are needed to determine who may benefit from adjuvant therapy. Developing adjuvant therapy strategies in the future depends on the results of important ongoing trials with immunotherapy and targeted agents.

Role of Adjuvant Therapy for Node-Negative Lung Cancer Invading the Chest Wall.

PubMed

Gao, Sarah J; Corso, Christopher D; Blasberg, Justin D; Detterbeck, Frank C; Boffa, Daniel J; Decker, Roy H; Kim, Anthony W

2017-03-01

The present study investigated the effect of adjuvant chemotherapy and radiation on survival among patients undergoing chest wall resection for T3N0 non-small cell lung cancer (NSCLC). Patients with T3N0 NSCLC who underwent chest wall resection were identified in the National Cancer Data Base in 2004 to 2012. The cohort was divided into patients who had received adjuvant chemotherapy, radiation therapy, chemoradiation therapy, or no adjuvant treatment. Kaplan-Meier and log-rank tests were used to compare overall survival, and a bootstrapped Cox proportional hazards model was used to determine the significant contributors to survival. A subset analysis was performed with stratification by margin status and tumor size. Of 759 patients identified, 42.0% underwent surgery alone, 23.3% underwent surgery followed by chemotherapy, 22.3% underwent surgery followed by chemoradiation therapy, and 12.3% underwent surgery followed by radiotherapy alone. Tumors > 4 cm benefited from adjuvant chemotherapy and radiation therapy in the multivariable analysis, and those ≤ 4 cm benefited only from adjuvant chemotherapy. The subgroup analysis by margin status identified that margin-positive patients with tumors > 4 cm benefited significantly from either adjuvant chemoradiation therapy or radiation therapy alone. T3N0 NSCLC with chest wall invasion requires unique management compared with other stage IIB tumors. An important determinant of management is tumor size, with tumors ≤ 4 cm benefiting from adjuvant chemotherapy and tumors > 4 cm benefiting from adjuvant chemotherapy if margin negative and adjuvant chemoradiation therapy or radiotherapy if margin positive. Copyright © 2016 Elsevier Inc. All rights reserved.

Utility of up-front transoral robotic surgery in tailoring adjuvant therapy.

PubMed

Gildener-Leapman, Neil; Kim, Jeehong; Abberbock, Shira; Choby, Garret W; Mandal, Rajarsi; Duvvuri, Umamaheswar; Ferris, Robert L; Kim, Seungwon

2016-08-01

The purpose of this study was to describe how the up-front transoral robotic surgery (TORS) approach could be used to individually tailor adjuvant therapy based on surgical pathology. Between January 2009 and December 2013, 76 patients received TORS for oropharyngeal squamous cell carcinoma (OPSCC). Clinical predictors of adjuvant therapy were analyzed and comparisons were made between recommended treatment guidelines for up-front surgery versus definitive nonsurgical approaches. Advanced N classification, human papillomavirus (HPV)-positive tumor, extracapsular spread (ECS; 26 of 76), perineural invasion (PNI; 14 of 76), and positive margins (7 of 76) were significant predictors of adjuvant chemoradiotherapy (CRT) (p < .05). Up-front TORS deintensified adjuvant therapy; 76% of stage I/II and 46% of stage III/IV patients avoided CRT. Conversely, pathologic staging resulted in 33% of patients who would have received radiotherapy (RT) alone based on clinical staging, to be intensified to receive adjuvant CRT. The TORS approach deintensifies adjuvant therapy and provides valuable pathologic information to intensify treatment in select patients. TORS may be less effective in deintensification of adjuvant therapy in patients with clinically advanced N classification disease. © 2016 Wiley Periodicals, Inc. Head Neck 38:1201-1207, 2016. © 2016 Wiley Periodicals, Inc.

Spinal cord gliomas: management and outcome with reference to adjuvant therapy.

PubMed

Nishio, S; Morioka, T; Fujii, K; Inamura, T; Fukui, M

2000-01-01

The authors review their experience with 19 consecutive cases with either astrocytic tumour (glioblastoma multiforme one, anaplastic astrocytoma one, astrocytoma 4, pilocytic astrocytoma 4) or ependymoma (10 tumours in 9 patients) of the spinal cord who were treated during the period from 1982 to 1996. The patients included 10 male and 9 female patients with a median age of 38 years. The main tumour locations included the cervicomedullary region 5 the cervical cord (8), the thoracic cord (5) and one each in the thoracolumbar region and conus medullaris. While a total removal of the tumour was achieved in 8 out of 10 ependymomas, the initial treatment for astrocytic tumours was a partial resection in 5, and biopsy in the remaining 5. As adjuvant treatment, 8 patients received radiation therapy and 2 received chemotherapy. Two patients with an astrocytic tumour received chemotherapy only, while the remaining 9 received neither radiation therapy nor chemotherapy initially. After these treatments, 6 out of the 8 patients with low grade astrocytoma have remained alive for 1.3-12.6 years, while 2 patients with high grade astrocytic tumours died within 15 months following surgery. Eight out of 9 patients with an ependymoma have remained alive for 3.0-12.3 years, while one committed suicide 2 years after surgery. As a result, 14 patients are still alive; half of them are accompanied by a mild neurological dysfunction, while the remaining one has a moderate deficit. The postoperative results and the rationale for surgery is discussed, and an approach for utilising adjuvant therapy for high grade tumours is also suggested.

Combined treatment for Coats’ disease: retinal laser photocoagulation combined with intravitreal bevacizumab injection was effective in two cases

PubMed Central

2014-01-01

Background The exact pathogenetic mechanisms of Coats’ disease remain unknown. In this report, we show two cases of Coats’ disease that achieved a favorable prognosis with the combined treatment of intravitreal bevacizumab (IVB) injection prior to photocoagulation, although both initially resisted photocoagulation therapy. Case presentations Case 1 was a 15-year-old boy with initial visual acuity of 0.4 OD. At the temporal retina, aneurysms and abnormal telangiectatic vessels were observed. Hard exudates and an exudative retinal detachment extended to the fovea. He was diagnosed as having Coats’ disease at stage 3A and we performed laser photocoagulation as an initial approach to treat peripheral aneurysms and telangiectatic vessels. After the treatment, the exudative retinal detachment was eased and visual acuity improved to 1.0; however, recurrence occurred after 5 months. The exudative change was resistant against laser photocoagulation therapy and we therefore added IVB as an adjuvant before photocoagulation. Fourteen days after IVB injection phased laser photocoagulation was given to cover the abnormal capillaries, aneurysms and the leakage area spotted in FA. A good prognosis was obtained with decreased exudation and improved visual acuity. Case 2 was an 11-year-old boy with decreased visual acuity of 0.15 OS at the initial visit. Hard exudates, retinal edema and serous retinal detachment were seen at the macula and peripheral retina. Fluorescein angiography revealed telangiectatic capillaries at the temporal retina. Our diagnosis was Coats’ disease at stage 3A. Extensive photocoagulation was performed as an initial treatment to the lesion. However, the exudative change was severe and resistant against the photocoagulation treatment. Therefore, we added IVB as an adjuvant before photocoagulation. Exudative change in the retina seemed to be eased 7 days after IVB injection, therefore, phased laser phototherapy was added to cover the abnormal capillaries. After the combination therapy, exudative change was remarkably ameliorated and better visual acuity was achieved. Conclusion Bevacizumab is considered an effective adjuvant for Coats’ disease with exudative change resistant to retinal photocoagulation therapy. PMID:24666524

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer.

PubMed

Keating, Gillian M

2009-08-20

Letrozole (Femara) is a third-generation, nonsteroidal aromatase inhibitor. Adjuvant therapy with letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo in this patient population; letrozole is generally well tolerated. Ongoing trials will help answer outstanding questions regarding the optimal duration of letrozole therapy in early breast cancer and its efficacy compared with other third-generation aromatase inhibitors such as anastrozole. In the meantime, letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy.

Trends and variations in the use of adjuvant therapy for patients with head and neck cancer.

PubMed

Chen, Michelle M; Roman, Sanziana A; Yarbrough, Wendell G; Burtness, Barbara A; Sosa, Julie A; Judson, Benjamin L

2014-11-01

The National Comprehensive Cancer Network guidelines recommend that patients with surgically resected head and neck cancers that have adverse pathologic features should receive adjuvant therapy in the form of radiotherapy (RT) or chemoradiation (CRT). To the authors' knowledge, the current study is the first analysis of temporal trends and use patterns of adjuvant therapy for these patients. Patients with head and neck cancer and adverse pathologic features were identified in the National Cancer Data Base (1998-2011). Data were analyzed using chi-square, Student t, and log-rank tests; multivariate logistic regression; and Cox multivariate regression. A total of 73,088 patients were identified: 41.5% had received adjuvant RT, 33.5% had received adjuvant CRT, and 25.0% did not receive any adjuvant therapy. From 1998 to 2011, the increase in the use of adjuvant CRT was greatest for patients with oral cavity (6-fold) and laryngeal (5-fold) cancers. Multivariate analysis demonstrated that Medicare/Medicaid insurance (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.01-1.11), distance ≥34 miles from the cancer center (OR, 1.66; 95% CI, 1.59-1.74), and academic (OR, 1.26; 95% CI, 1.20-1.31) and high-volume (OR, 1.10; 95% CI, 1.05-1.15) centers were independently associated with patients not receiving adjuvant therapy. Receipt of adjuvant therapy was found to be independently associated with improved overall survival (hazard ratio, 0.84; 95% CI, 0.81-0.86). Approximately 25% of patients are not receiving National Comprehensive Cancer Network guideline-directed adjuvant therapy. Patient-level and hospital-level factors are associated with variations in the receipt of adjuvant therapy. Further evaluation of these differences in practice patterns is needed to standardize practice and potentially improve the quality of care. Cancer 2014;120:3353-3360. © 2014 American Cancer Society. © 2014 American Cancer Society.

Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.

PubMed

Regan, M M; Walley, B A; Francis, P A; Fleming, G F; Láng, I; Gómez, H L; Colleoni, M; Tondini, C; Pinotti, G; Salim, M; Spazzapan, S; Parmar, V; Ruhstaller, T; Abdi, E A; Gelber, R D; Coates, A S; Goldhirsch, A; Pagani, O

2017-09-01

Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women <40 years at diagnosis (HR = 1.13, 95% CI 0.69-1.84) who are less likely to develop chemotherapy-induced amenorrhea. Based on comparative-effectiveness modeling of TEXT and SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup <40 years, neither detrimental nor beneficial effect of concurrent administration of OFS with chemotherapy on the efficacy of adjuvant therapy that includes chemotherapy was detected. NCT00066690 and NCT00066703. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Decreased contralateral breast volume after mastectomy, adjuvant chemotherapy, and anti-estrogen therapy, in particular in breasts with high density.

PubMed

Ishii, Naohiro; Ando, Jiro; Harao, Michiko; Takemae, Masaru; Kishi, Kazuo

2017-10-01

Adjuvant chemotherapy and anti-estrogenic therapy can result in decreased volume of the contralateral breast, following mastectomy for the treatment of breast cancer. However, no data on the effect of adjuvant therapy on contralateral breast volume have previously been reported. We aimed to evaluate the extent to which adjuvant therapy and differences in breast density contribute to decreased breast volume. We conducted a prospective cohort study, selecting 40 nonconsecutive patients who underwent immediate breast reconstruction with mastectomy and expander insertion followed by expander replacement. We measured the contralateral breast volume before each procedure. The extent of the change was analyzed with respect to adjuvant therapy and breast density measured by preoperative mammography. The greatest decrease in breast volume was 135.1 cm 3 . The decrease in breast volume was significantly larger in the adjuvant therapy (+) group, particularly in patients with high breast density, than in the adjuvant therapy (-) group. Significant differences between the chemotherapy (+), tamoxifen (+) group and the chemotherapy (-), tamoxifen (+) group were not found. Breast density scores had a range of 2.0-3.3 (mean: 2.8). In breast reconstruction, particularly when performed in one stage, preoperative mammography findings are valuable to plastic surgeons, and possible decreases in the contralateral breast volume due to adjuvant therapy, particularly in patients with high breast density, should be considered carefully. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

PubMed

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

NASA Astrophysics Data System (ADS)

Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

2016-10-01

A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

PubMed

Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

2018-05-22

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

[Organ-limited prostate cancer with positive resection margins. Importance of adjuvant radiation therapy].

PubMed

Porres, D; Pfister, D; Brehmer, B; Heidenreich, A

2012-09-01

For pT3 prostate cancer with positive resection margins, the importance of postoperative radiation therapy is confirmed by a high level of evidence. However, for the pT2,R1 situation prospective, randomized studies concerning this question are lacking. Despite better local tumor control in the pT2 stage the PSA recurrence rate lies between 25% and 40% and positive margins are an independent factor for recurrence. Retrospective studies suggest a positive effect of adjuvant or salvage radiation for the oncological outcome in the pT2,R1 situation. On the other hand the side effects profile, with a potentially negative influence of postoperative continence and various delayed toxicities, is not insignificant despite modern radiation techniques and in the era of ultrasensitive PSA analysis should be considered in the risk-benefit assessment. As long as the optimal initiation of postoperative radiation therapy is unclear, the assessment of indications for adjuvant or salvage radiation for organ-limited prostate cancer with positive resection margins should be made after an individual patient consultation and under consideration of the recurrence risk factors, such as the Gleason grade and the localization and extent of the resection margins.

Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer in Men.

PubMed

Venigalla, Sriram; Carmona, Ruben; Guttmann, David M; Jain, Varsha; Freedman, Gary M; Clark, Amy S; Shabason, Jacob E

2018-05-24

Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)-positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. Receipt of adjuvant endocrine therapy. Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. The primary study cohort comprised 10 173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961 676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%, P < .001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63; P < .001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25; P = .02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15; P < .001) or chemotherapy (odds ratio, 1.20; 95% CI, 1.07-1.34; P < .001) were statistically significantly associated with adjuvant endocrine therapy use in men. A propensity score-weighted analysis indicated that relative to no use, adjuvant endocrine therapy use in men was associated with improved overall survival (hazard ratio, 0.70; 95% CI, 0.63-0.77; P < .001). There is a sex disparate underuse of adjuvant endocrine therapy among men with HR-positive breast cancer despite the use of this treatment being associated with improved overall survival. Further research and interventions may be warranted to bridge gaps in care in this population.

Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christiansen, Hans; Hermann, Robert Michael; Martin, Alexios

Purpose: The aim of this study was to evaluate the efficacy of adjuvant radiotherapy after transoral laser microsurgery for advanced recurrent head-and-neck squamous cell carcinoma (HNSCC). Patients and Methods: Between 1988 and 2000, 37 patients with advanced local recurrences (23 local and 14 locoregional recurrences) of HNSCC without distant metastases were treated in curative intent with organ-preserving transoral laser microsurgery and adjuvant radiotherapy (before 1994 split-course radiotherapy with carboplatinum, after 1994 conventional radiotherapy). Initial therapy of the primary (8.1% oral cavity, 35.1% oropharynx, 13.5% hypopharynx, and 43.3% larynx) before relapse was organ-preserving transoral laser microsurgery without any adjuvant therapy. Results:more » After a median follow-up of 124 months, the 5-year overall survival rate was 21.3%, the loco-regional control rate 48.3%, respectively. In multivariate analysis, stage of original primary tumor (Stage I/II vs. Stage III/IV), and patient age (<58 years vs. {>=}58 years) showed statistically significant impact on prognosis. In laryngeal cancer, larynx preservation rate after treatment for recurrent tumor was 50% during follow-up. Conclusion: Our data show that organ-preserving transoral laser microsurgery followed by adjuvant radiotherapy is a curative option for patients who have advanced recurrence after transoral laser surgery and is an alternative to radical treatment.« less

Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinkham, Mark B., E-mail: mark.pinkham@health.qld.gov.au; University of Queensland, Brisbane; Foote, Matthew C.

Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapymore » because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.« less

Hospital variation and the impact of postoperative complications on the use of perioperative chemo(radio)therapy in resectable gastric cancer. Results from the Dutch Upper GI Cancer Audit.

PubMed

Schouwenburg, M G; Busweiler, L A D; Beck, N; Henneman, D; Amodio, S; van Berge Henegouwen, M I; Cats, A; van Hillegersberg, R; van Sandick, J W; Wijnhoven, B P L; Wouters, M W J; Nieuwenhuijzen, G A P

2018-04-01

Dutch national guidelines on the diagnosis and treatment of gastric cancer recommend the use of perioperative chemotherapy in patients with resectable gastric cancer. However, adjuvant chemotherapy is often not administered. The aim of this study was to evaluate hospital variation on the probability to receive adjuvant chemotherapy and to identify associated factors with special attention to postoperative complications. All patients who received neoadjuvant chemotherapy and underwent an elective surgical resection for stage IB-IVa (M0) gastric adenocarcinoma between 2011 and 2015 were identified from a national database (Dutch Upper GI Cancer Audit). A multivariable linear mixed model was used to evaluate case-mix adjusted hospital variation and to identify factors associated with adjuvant therapy. Of all surgically treated gastric cancer patients who received neoadjuvant chemotherapy (n = 882), 68% received adjuvant chemo(radio)therapy. After adjusting for case-mix and random variation, a large hospital variation in the administration rates for adjuvant was observed (OR range 0.31-7.1). In multivariable analysis, weight loss, a poor health status and failure of neoadjuvant chemotherapy completion were strongly associated with an increased likelihood of adjuvant therapy omission. Patients with severe postoperative complications had a threefold increased likelihood of adjuvant therapy omission (OR 3.07 95% CI 2.04-4.65). Despite national guidelines, considerable hospital variation was observed in the probability of receiving adjuvant chemo(radio)therapy. Postoperative complications were strongly associated with adjuvant chemo(radio)therapy omission, underlining the need to further reduce perioperative morbidity in gastric cancer surgery. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Update on adjuvant chemotherapy for early breast cancer.

PubMed

Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

2014-01-01

Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come.

Relevant factors for the optimal duration of extended endocrine therapy in early breast cancer.

PubMed

Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

2018-04-01

For postmenopausal patients with hormone receptor-positive early breast cancer, the optimal subgroup and duration of extended endocrine therapy is not clear yet. The aim of this study using the IDEAL patient cohort was to identify a subgroup for which longer (5 years) extended therapy is beneficial over shorter (2.5 years) extended endocrine therapy. In the IDEAL trial, 1824 patients who completed 5 years of adjuvant endocrine therapy (either 5 years of tamoxifen (12%), 5 years of an AI (29%), or a sequential strategy of both (59%)) were randomized between either 2.5 or 5 years of extended letrozole. For each prior therapy subgroup, the value of longer therapy was assessed for both node-negative and node-positive patients using Kaplan Meier and Cox regression survival analyses. In node-positive patients, there was a significant benefit of 5 years (over 2.5 years) of extended therapy (disease-free survival (DFS) HR 0.67, p = 0.03, 95% CI 0.47-0.96). This effect was only observed in patients who were treated initially with a sequential scheme (DFS HR 0.60, p = 0.03, 95% CI 0.38-0.95). In all other subgroups, there was no significant benefit of longer extended therapy. Similar results were found in patients who were randomized for their initial adjuvant therapy in the TEAM trial (DFS HR 0.37, p = 0.07, 95% CI 0.13-1.06), although this additional analysis was underpowered for definite conclusions. This study suggests that node-positive patients could benefit from longer extended endocrine therapy, although this effect appears isolated to patients treated with sequential endocrine therapy during the first 5 years and needs validation and long-term follow-up.

American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer

PubMed Central

Burstein, Harold J.; Prestrud, Ann Alexis; Seidenfeld, Jerome; Anderson, Holly; Buchholz, Thomas A.; Davidson, Nancy E.; Gelmon, Karen E.; Giordano, Sharon H.; Hudis, Clifford A.; Malin, Jennifer; Mamounas, Eleftherios P.; Rowden, Diana; Solky, Alexander J.; Sowers, MaryFran R.; Stearns, Vered; Winer, Eric P.; Somerfield, Mark R.; Griggs, Jennifer J.

2010-01-01

Purpose To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor–positive breast cancer. Methods A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations. Results An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences. Conclusion The Update Committee recommends that postmenopausal women with hormone receptor–positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy. PMID:20625130

Adjuvant chemotherapy with sequential cytokine-induced killer (CIK) cells in stage IB non-small cell lung cancer.

PubMed

Li, Da-Peng; Li, Wei; Feng, Jun; Chen, Kai; Tao, Min

2015-01-01

For non-small cell lung cancer (NSCLC) patients at stage IB, adjuvant chemotherapy does not improve survival. Evidence suggests that dendritic cell (DC)-activated cytokine-induced killer (DC-CIK) cell therapy in addition to chemotherapy improves survival for stage I-IIIA NSCLC patients after surgery, but there are not enough data to confirm this benefit specifically for those at stage IB. Herein, we retrospectively evaluated the efficacy and safety of this therapy administered to stage IB NSCLC patients. Sixty-six patients were treated with four-cycle adjuvant chemotherapy initiated 3 weeks after surgical resection. In addition, 28 of these patients underwent DC-CIK therapy on a trimonthly basis (average 3.1 times, range 1-6) beginning 1 month after chemotherapy. The disease-free survival (DFS) rates of the two groups were statistically similar, although patients who received DC-CIK therapy showed slightly higher 1- and 2-year DFS rates (100.0% and 96.4%, respectively, compared with 81.6% and 76.3%). More importantly, patients in the DC-CIK therapy group had significantly longer overall survival (p=0.018). For patients who received treatment after recurrence, the DC-CIK therapy group had longer progression-free survival compared with the chemotherapy-only group. In addition, patients given DC-CIK therapy experienced less fatigue and appetite loss. The rate of adverse side effects was similar between the two groups. In conclusion, for these stage IB NSCLC patients, DC-CIK therapy significantly improved 2-year DFS rates compared with those who received chemotherapy only. DC-CIK therapy also benefited patients' quality of life, and adverse events were acceptable.

Treatment of painful diabetic peripheral neuropathy.

PubMed

Rosenberg, Casandra J; Watson, James C

2015-02-01

Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.

Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

PubMed

Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

2018-02-01

The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy.

PubMed

Houédé, N; Locker, G; Lucas, C; Parra, H Soto; Basso, U; Spaeth, D; Tambaro, R; Basterretxea, L; Morelli, F; Theodore, C; Lusuardi, L; Lainez, N; Guillot, A; Tonini, G; Bielle, J; Del Muro, X Garcia

2016-09-23

Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia < 10 g/dL in 16 %, hepatic metastases in 13 %. 80 % of these patients received further anticancer therapy. Immediately after failure of adjuvant/neoadjuvant chemotherapy, most subsequent anticancer treatments were chemotherapy doublets (35/58), whereas after therapy failure in the advanced setting most patients receiving further anticancer drugs were treated with a single agent (80/114). After first progression to chemotherapy, treatment decisions were mainly driven by Performance Status and prior response to chemotherapy (>30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions.

Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature.

PubMed

Alam, Naveed; Shepherd, Frances A; Winton, Timothy; Graham, Barbara; Johnson, David; Livingston, Robert; Rigas, James; Whitehead, Marlo; Ding, Keyue; Seymour, Lesley

2005-03-01

Resected non-small cell lung cancer (NSCLC) has 5-years survival rates of 30-70%. The role of adjuvant chemotherapy remains unclear with poor compliance reported in most trials. The compliance with adjuvant chemotherapy (ACT) for stage IB and II NSCLC was analyzed using data from a North American multi-centre phase III study (accrual 1994-2001) that compared adjuvant chemotherapy to observation. Planned chemotherapy consisted of cisplatin (CIS) 50 mg/m2 days 1, 8 and vinorelbine (VIN) 25 mg/m2 days 1, 8, 15, 22 for four cycles; the VIN dose had been reduced from 30 mg/m2 after an initial cohort of patients experienced unacceptable toxicity. Four hundred and twenty-four patients were randomized after the amendment, 215 to the chemotherapy arm. Median age was 60 years, 64% were male and 84% had stage II disease. Thirty-seven patients completed one cycle, 14 completed two, 20 completed three and 108 patients completed all four cycles. Ten patients received no therapy. Multivariate analysis demonstrated statistically significant differences in compliance with extent of surgery, gender and age. Patients randomized in Canada were more likely to fail to complete chemotherapy due to refusal of therapy than their American counterparts. Patients who had pneumonectomies were more likely to discontinue therapy due to toxicity than those who had lesser resections. Extent of surgery may play a role in both the compliance and toxicity of ACT. Differences between nations in the perception of the risks and benefits of adjuvant chemotherapy regimens, both between physicians and patients, should be investigated further.

Geographic Variation in the Use of Adjuvant Therapy among Elderly Patients with Resected Non-Small Cell Lung Cancer

PubMed Central

Tien, Yu-Yu; Wright, Kara; Halfdanarson, Thorvardur R.; Abu-Hejleh, Taher; Brooks, John M.

2016-01-01

Objectives The purpose of this study was to assess to what extent geographic variation in adjuvant treatment for non-small cell lung cancer (NSCLC) patients would remain, after controlling for patient and area-level characteristics. Materials and Methods A retrospective cohort of 18,410 Medicare beneficiaries with resected, stage I-IIIA NSCLC was identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Adjuvant therapies were classified as adjuvant chemotherapy (ACT), postoperative radiation therapy (PORT), or no adjuvant therapy. Predicted treatment probabilities were estimated for each patient given their clinical, demographic, and area-level characteristics with multivariate logistic regression. Area Treatment Ratios were used to estimate the propensity of patients in a local area to receive an adjuvant treatment, controlling for characteristics of patients in the area. Areas were categorized as low-, mid- and high-use and mapped for two representative SEER registries. Results Overall, 10%, 12%, and 78% of patients received ACT, PORT and no adjuvant therapy, respectively. Age, sex, stage, type and year of surgery, and comorbidity were associated with adjuvant treatment use. Even after adjusting for patient characteristics, substantial geographic treatment variation remained. High- and low-use areas were tightly juxtaposed within and across SEER registries, often within the same county. In some local areas, patients were up to eight times more likely to receive adjuvant therapy than expected, given their characteristics. On the other hand, almost a quarter of patients lived in local areas in which patients were more than three times less likely to receive ACT than would be predicted. Conclusion Controlling for patient and area-level covariates did not remove geographic variation in adjuvant therapies for resected NSCLC patients. A greater proportion of patients were treated less than expected, rather than more than expected. Further research is needed to better understand its causes and potential impact on outcomes. PMID:27040848

Controversies in breast cancer: adjuvant and neoadjuvant therapy.

PubMed

Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

2005-06-01

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients

PubMed Central

Chandran, Sindhu; Vagefi, Parsia A.

2014-01-01

Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center's experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy. PMID:25349720

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

PubMed

Jin, Zhaohui; Hartgers, Mindy L; Sanhueza, Cristobal T; Shubert, Christopher R; Alberts, Steven R; Truty, Mark J; Muppa, Prasuna; Nagorney, David M; Smyrk, Thomas C; Hassan, Mohamed; Mahipal, Amit

2018-05-01

Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer: the ALCHEMIST trials.

PubMed

Alden, Ryan S; Mandrekar, Sumithra J; Oxnard, Geoffrey R

2015-09-01

Genotype-directed targeted therapies have revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC) but they have not yet been comprehensively studied in the adjuvant setting. Previous trials of adjuvant targeted therapy in unselected early stage NSCLC patients showed no benefit versus placebo, however retrospective data suggests improved disease free survival (DFS) with epidermal growth factor receptor (EGFR) inhibitors in patients with appropriate molecular alterations. A definitive prospective, randomized, placebo-controlled trial of targeted therapies for NSCLC is needed to determine the efficacy of targeted therapy following surgical resection and standard adjuvant therapy. The principal challenges facing such a trial are (I) identification of actionable alterations in early stage patients; and (II) realization of sufficient enrollment to power definitive analyses. The ALCHEMIST trial (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) was designed to overcome these challenges. Using the national clinical trials network (NCTN) of the National Cancer Institute (NCI), several thousand patients with operable NSCLC will undergo tumor genotyping for EGFR mutations or rearrangement of anaplastic lymphoma kinase (ALK). Following resection and completion of standard adjuvant therapy, patients with EGFR-mutant NSCLC will be randomized to erlotinib versus placebo (1:1), those with ALK-rearranged NSCLC will be randomized to crizotinib versus placebo (1:1), while those not enrolled onto the adjuvant trials will continue to be followed on the screening trial. ALCHEMIST also provides for the collection of tissue at baseline and at recurrence (if available) to characterize mechanisms of recurrence and of resistance to targeted therapy. Thus, ALCHEMIST is a platform for validation of targeted therapy as part of curative care in NSCLC and creates an opportunity to advance our understanding of disease biology.

Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients.

PubMed

Kool, M; Fontein, D B Y; Meershoek-Klein Kranenbarg, E; Nortier, J W R; Rutgers, E J T; Marang-van de Mheen, P J; van de Velde, C J H

2015-06-01

The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for its adverse events, which may negatively affect Quality of Life (QoL). The aim of this study is to assess the impact of extended adjuvant endocrine therapy on long-term QoL outcomes. 471 patients selected from the IDEAL trial were invited to complete a questionnaire 1-1.5 years after starting with extended therapy. The questionnaire consisted of the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Mean QoL outcomes were compared with EORTC reference values for stage I and II breast cancer patients and the general population. Furthermore, QoL outcomes were compared between different treatment regimens. A difference of eight points was considered clinically relevant. IDEAL patients receiving extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with reference values for stage I and II breast cancer patients (79.6 versus 64.6; p < 0.01) and the general population (79.6 versus 71.2; p < 0.01). Similar results were found for emotional function, pain, appetite loss, diarrhea and financial problems. Between treatment regimens prior to extended adjuvant endocrine therapy, differences were only found on specific QoL domains (e.g. arm symptoms). Breast cancer patients on extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with other stage I-II breast cancer patients and the general population, 6-8.5 years after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Garg, Madhur K.; Aparo, Santiago

2013-06-01

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated frommore » survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.« less

Adjuvant therapy for gastric cancer: what have we learned since INT0116?

PubMed

Jácome, Alexandre A; Sankarankutty, Ajith K; dos Santos, José Sebastião

2015-04-07

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

Incompletely obliterated cranial arteriovenous fistulae are safely and effectively treated with adjuvant ε-aminocaproic acid.

PubMed

Howard, Brian M; Grossberg, Jonathan A; Prater, Adam; Cawley, C Michael; Dion, Jacques E; Tong, Frank C

2018-07-01

Administration of ε-aminocaproic acid (εACA), as adjuvant therapy following incompletely embolized cranial dural arteriovenous (dAVFs) and direct carotid artery to cavernous sinus fistulae (CCFs), is a strategy to promote post-procedural thrombosis. However, the efficacy of εACA to treat incompletely obliterated dAVFs and CCFs has not been published. The purpose of this study was to determine if administration of εACA following incomplete embolization of cranial dAVFs or CCFs was associated with an increased likelihood of cure on follow-up imaging compared with patients not given adjuvant εACA. A retrospective cohort study was performed. All patients who underwent treatment of a dAVF or CCF at our institution between 1998 and 2016 were reviewed (n=262). Patients with residual shunting following the first attempted endovascular embolization were included in the analysis (n=52). The study groups were those treated with εACA following incomplete obliteration of the fistula and those who were not. The primary outcome was obliteration of the fistula on initial follow-up imaging. Complication rates between cohorts were compared. 20 (38%) patients with incompletely obliterated fistulae were treated with adjuvant εACA. A trend towards an improved rate of complete obliteration on initial follow-up imaging was observed in the group treated with εACA (55% vs 34% in the group not treated with εACA, p=0.14). No difference in clinical outcomes or thromboembolic complications was observed between the groups. In summary, these data suggest that administration of εACA is a safe adjuvant therapy in the management of cranial dAVFs and CCFs that are incompletely treated endovascularly. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shinohara, Eric T.; Mitra, Nandita; Guo Mengye

Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The medianmore » age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC.« less

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma.

PubMed

Kosugi, Kenzo; Saito, Katsuya; Takahashi, Wataru; Tokuda, Yukina; Tomita, Hideyuki

2017-05-01

Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles. Close follow-up magnetic resonance imaging of the head during TMZ chemotherapy showed no evidence of tumor progression. One year after the completion of TMZ chemotherapy, a bone-marrow aspiration was performed because the patient's white blood cell count decreased. He was diagnosed with t-AML based on the bone marrow examination, and then he was referred to the cancer center for the treatment of t-AML. In this case study, we continued adjuvant TMZ therapy beyond the recommended 6 cycles. Currently, there is no consensus as to how long the adjuvant TMZ therapy should be continued for the treatment of residual tumor showing no apparent interval change. A new decision-making tool to assess the clinical benefits against the side effects for long-term adjuvant TMZ therapy is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

PubMed Central

Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

2010-01-01

Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

Docetaxel-based adjuvant therapy for breast cancer patients in Asia-Pacific region: Results from 5 years follow-up on Asia-Pacific Breast Initiative-I.

PubMed

Kim, Sung-Bae; Sayeed, Ahmed; Villalon, Antonio H; Shen, Zhe-Zhou; Shah, Mazhar A; Hou, Meng-Feng; Nguyen Ba, Duc

2016-06-01

To acquire patient characteristics, safety, relapse and survival outcomes of early-stage breast cancer patients receiving docetaxel (Taxotere(R))-based regimen in adjuvant setting from the Asia-Pacific region. This was an open-label, international, longitudinal, multicenter, observational, prospective cohort of consecutive early breast cancer (EBC) patients with a high risk of recurrence being treated with various docetaxel-containing anthracycline and non-anthracycline adjuvant regimens during 2006-2013. In this study, 1542 patients were enrolled. Anthracycline-containing regimens were administered in 92% of patients, while 8% of patients received non-anthracycline-containing docetaxel-based regimens. The mean dose intensity of docetaxel was 25.8, 22.4 and 25.4 mg/m(2) /week among patients receiving docetaxel-based monotherapy, combination and sequential therapy, respectively. Adverse events were reported in 94.9% of patients (anthracycline vs non-anthracycline regimen; 95.1% vs 93.5%). Serious adverse events were reported in 12.6% of patients (12.4% vs 14.6%). Grade 4 neutropenia was reported in 25.2% of patients (24.7% vs 30.9%) and febrile neutropenia in 1.9% of patients (2% vs 0.8%). Only 7% of patients had a relapse or a second primary malignancy. At 5-year follow-up, there were 127 (8.3%) deaths (8.4% vs 6.5%). The Asia-Pacific Breast Initiative-I registry highlights the important patient and treatment characteristics of EBC patients treated with adjuvant docetaxel chemotherapy from the Asia-Pacific region that will help physicians to understand the impact of different docetaxel treatments on the clinical outcomes in this population. © 2016 John Wiley & Sons Australia, Ltd.

Comparative survival analysis of adjuvant therapy with iodine-131-labeled lipiodol to hepatic resection of primary hepatocellular carcinoma: a meta-analysis.

PubMed

Gong, Lin; Shi, Lu; Sun, Jing; Yuan, Wei-Sheng; Chen, Jian-Feng; Liu, Peng; Gong, Feng; Dong, Jia-Hong

2014-05-01

Adjuvant therapies play an important role in delaying the recurrence of hepatocellular carcinoma (HCC) in patients with resectable tumor. Among the available options, use of radionuclides is an effective strategy. This meta-analysis aims to examine the evidence pertaining to the effectiveness of adjuvant therapy with intra-arterial iodine-131-labeled lipiodol ((131)I-lipiodol) to hepatic resection of HCC. A literature survey was conducted of multiple electronic databases including PubMed/Medline, Embase, CINAHL, Cochrane library, and Google Scholar using various combinations of the most relevant key terms. The odds ratio-based meta-analysis of recurrence and survival rates was performed with RevMan software (version 5.2) using a random-effect model. Heterogeneity was assessed by χ(2) and I(2) statistics. When compared with the resection-only group, recurrence rates at 2 and 5 years were significantly lower in patients who received adjuvant therapy with intra-arterial I-lipiodol, with a corresponding odds ratio (95% confidence interval) of 0.45 (0.29-0.70) and 0.52 (0.32-0.85), respectively. The 3- and 5-year overall survival rates were found to be significantly higher in patients who received adjuvant therapy with (131)I-lipiodol than in patients who were not given any adjuvant therapy. Between-study statistical heterogeneity was moderate. Postoperative adjuvant therapy with intra-arterial (131)I-lipiodol to hepatic resection of HCC significantly improves overall and disease-free survival rates and reduces recurrence rates. However, well-designed randomized trials are needed to arrive at conclusive evidence.

Treatment of early-stage uterine papillary serous carcinoma at Roswell Park Cancer Institute, 1992-2006.

PubMed

Tchabo, Nana E; McCloskey, Susan; Mashtare, Terry L; Andrews, Christopher; Singh, Anurag K; Mhawech-Fauceglia, Paulette; Odunsi, Kunle; Lele, Shashikant; Jaggernauth, Wainwright

2009-11-01

Optimal management of early-stage uterine papillary serous carcinoma (UPSC) remains controversial. We reviewed our outcomes in this patient population. The Roswell Park Cancer Institute (RPCI) tumor registry identified all patients with Stages I and IIA UPSC treated between January 1992 and June 2006. The Fisher's exact test was used to compare recurrence rates by adjuvant therapy received. Overall survival (OS) estimates were made using the Kaplan-Meier method. Fifty-eight patients with Stage I or IIA UPSC underwent surgery. Thirty-four patients (59%) were surgically staged. Among 21 patients with Stage IA disease, 15 received adjuvant therapy. With a median follow-up of 44.7 months, only one recurrence was observed in a patient who received adjuvant brachytherapy. The 5-year OS was 66%. Among 37 patients with Stages IB-IIA, 30 patients received adjuvant therapy. With a median follow-up of 29 months, there were 7 recurrences. The 5-year OS was 60%. Although there were no significant differences in recurrence by adjuvant therapy received, a significant OS benefit was found in those who received radiation. There was no significant difference in OS distributions of those patients who received Carboplatin/Paclitaxel chemotherapy. Despite the limitations of our retrospective study, we have shown that even comprehensively staged early-stage UPSC patients are still at risk for recurrence despite adjuvant therapy received. Hence, all patients with this histologic diagnosis should be considered at high risk for recurrence and counseled appropriately regarding the risks and benefits of adjuvant therapy.

Preoperative neo-adjuvant therapy for curable rectal cancer--reaching a consensus 2008.

PubMed

Scott, N A; Susnerwala, S; Gollins, S; Myint, A Sun; Levine, E

2009-03-01

Our aim was to determine the range of neo-adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M(0)) rectal cancer. A senior oncologist from each of the four oncology centres in north Wales and the north-west of England (approximate target population 8 million - Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her understanding of the current evidence of neo-adjuvant therapy in rectal cancer. Then a representative from each centre was asked to identify which of three neo-adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions and long-course chemoradiotherapy) he/she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by magnetic resonance imaging as being T(2)-T(4) and/or N(0)-N(2). In all cases of locally advanced rectal cancer (T(3a) N(1)-T(4)), oncologists from the four oncology centres recommended long-course chemoradiotherapy before rectal resection. This consensus was maintained for cases of lower third T(3a) N(0) cancers. Thereafter, the majority of patients with rectal cancer are offered adjuvant short-course radiotherapy. Neo-adjuvant therapy is less likely to be offered if the tumour is early (T(2), N(0)) and/or situated in the upper third of the rectum.

Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis.

PubMed

Tang, Monica; Price, Timothy Jay; Shapiro, Jeremy; Gibbs, Peter; Haller, Daniel G; Arnold, Dirk; Peeters, Marc; Segelov, Eva; Roy, Amitesh; Tebbutt, Niall; Pavlakis, Nick; Karapetis, Chris; Burge, Matthew

2018-04-01

Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.

Anastrozole is cost-effective vs tamoxifen as initial adjuvant therapy in early breast cancer: Canadian perspectives on the ATAC completed-treatment analysis.

PubMed

Rocchi, A; Verma, S

2006-09-01

To conduct an economic analysis comparing tamoxifen and anastrozole (Arimidex) in the adjuvant treatment of hormone receptor-positive (HR+), post-menopausal early breast cancer patients. An economic model examined typical patients (64 years of age, HR+, 64% node negative) from the Arimidex, tamoxifen alone, or in combination (ATAC) trial over a lifetime horizon. Rates of events were derived from ATAC trial results. Post-trial event rates were drawn from the literature for tamoxifen; event rates for anastrozole were modified by the relative risks observed in the ATAC trial. Resource utilization was drawn from Statistics Canada's Population Health Model for breast cancer, supplemented by an expert panel. A public health care system perspective, 2004 Canadian prices and a 5% discount rate were employed. Anastrozole-taking patients incurred additional hormonal treatment costs compared to tamoxifen-taking patients (incremental lifetime cost, 6,974 Canadian dollars per patient), partially offset by reduced downstream recurrences of breast cancer (1,143 Canadian dollars lifetime savings per patient) for a net incremental cost of 5,796 Canadian dollars per patient on anastrozole. The anastrozole-treated patients were projected to experience a 5.6% absolute risk reduction of first breast cancer recurrence and a 2.8% absolute risk reduction in breast cancer death. This corresponded to 30,000 Canadian dollars per life year gained and 28,000 Canadian dollars per quality-adjusted life year gained (95% confidence interval, 17,428 to 54,605 Canadian dollars). The results were affected by the duration and extent of anastrozole benefit under sensitivity analysis but remained cost-effective. Compared to tamoxifen, anastrozole therapy is effective and cost-effective as initial adjuvant therapy in post-menopausal, HR+ early breast cancer patients.

Initial Treatment for Newly Diagnosed Elderly Colorectal Cancer Patients: Patterns of Care in Italy and the United States

PubMed Central

2013-01-01

Cancer is a major component of health-care expenditures in most developed countries. The costs of cancer care are expected to increase due to rising incidence (as the population ages) and increasing use of targeted anticancer therapies. However, epidemiological analysis of patterns of care may be required prior to empirically well-grounded cost analyses. Additionally, comparisons of care between health-care delivery systems and countries can identify opportunities to improve practice. They can also increase understanding of patient outcomes and economic consequences of differences in policies related to cancer screening, treatment, and programs of care. In this study, we compared patterns of colorectal cancer treatment during the first year following diagnosis in two cohorts of elderly patients from some areas of Italy and the United States using cancer registry linked to administrative data. We evaluated hospital use, initial treatments (surgery, chemotherapy, and radiation), and timeliness of surgery and adjuvant therapy, taking into account patient characteristics and clinical features, such as stage at diagnosis and the cancer subsite. We observed greater use of adjuvant chemotherapy in stage III and IV colon cancer patients and adjuvant therapy in all stages of rectal cancer patients in the US cohort. We found a higher rate of open surgeries in the Italian cohort, a similar rate of hospitalization, but a higher number of hospital days in the Italian cohort. However, in spite of structural differences between the United States and Italy in health-care organization and delivery as well as in data collection, patterns of care and the timing of care in the year after diagnosis are generally similar among patients within stage of disease at diagnosis. Comparative studies of the costs associated with patterns of cancer care will be important for future research. PMID:23962512

Improvement of chronic corneal opacity in ocular surface disease with prosthetic replacement of the ocular surface ecosystem (PROSE) treatment.

PubMed

Cressey, Anna; Jacobs, Deborah S; Remington, Crystal; Carrasquillo, Karen G

2018-06-01

To demonstrate clearing of chronic corneal opacities and improvement of visual acuity with the use of BostonSight prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in ocular surface disease. We undertook retrospective analysis of the medical records of a series of patients who underwent PROSE treatment from August 2006 to December 2014. Patients were referred for ocular surface disease of various etiologies. Primary inclusion criterion was corneal opacity that improved with PROSE treatment. Patients were excluded if topical steroids or adjuvant therapy used once PROSE treatment was initiated. Underlying disease, prior treatment, clinical presentation, and clinical course were extracted from the medical record. Four patients are included in this series. There were three females and one male; median age at time of treatment initiation was 30 years (range = 0.5-58 years). Median duration of PROSE treatment at time of retrospective analysis was 3.5 years (range = 1-8 years). Two cases had corneal opacification in the context of neurotrophic keratopathy: a unilateral case due to presumed herpes simplex keratitis and a bilateral case due to congenital corneal anesthesia associated with familial dysautonomia. One case had corneal opacity from exposure related to seventh nerve palsy, and one had corneal opacification associated with recurrent surface breakdown, neurotrophic keratopathy, and limbal stem deficiency of uncertain etiology. After consistent wear of prosthetic devices used in PROSE treatment for support of the ocular surface, visual acuity improved and clearing of the opacities was observed, without use of topical steroids or adjuvant therapy. These cases demonstrate clearing of chronic corneal opacity with PROSE treatment for ocular surface disease. This clearing can occur with no adjuvant therapy, suggesting that restoration of ocular surface function and integrity allows for corneal remodeling.

Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

PubMed Central

Al-Tonbary, Youssef; Al-Haggar, Mohammad; EL-Ashry, Rasha; EL-Dakroory, Sahar; Azzam, Hanan; Fouda, Ashraf

2009-01-01

Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC) in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL) during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I) have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II) have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX) antioxidant enzyme, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), liver enzymes, and bone marrow picture). Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment. PMID:19960046

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study

PubMed Central

Fasching, P. A.; Fehm, T.; Kellner, S.; de Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H.-C.; Guggenberger, M.; Warm, M.; Harbeck, N.; Würstlein, R.; Deuker, J.-U.; Dall, P.; Richter, B.; Wachsmann, G.; Brucker, C.; Siebers, J. W.; Fersis, N.; Kuhn, T.; Wolf, C.; Vollert, H.-W.; Breitbach, G.-P.; Janni, W.; Landthaler, R.; Kohls, A.; Rezek, D.; Noesslet, T.; Fischer, G.; Henschen, S.; Praetz, T.; Heyl, V.; Kühn, T.; Krauß, T.; Thomssen, C.; Kümmel, S.; Hohn, A.; Tesch, H.; Mundhenke, C.; Hein, A.; Rauh, C.; Bayer, C. M.; Jacob, A.; Schmidt, K.; Belleville, E.; Hadji, P.; Wallwiener, D.; Grischke, E.-M.; Beckmann, M. W.; Brucker, S. Y.

2014-01-01

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information. PMID:25568468

Computational prediction of multidisciplinary team decision-making for adjuvant breast cancer drug therapies: a machine learning approach.

PubMed

Lin, Frank P Y; Pokorny, Adrian; Teng, Christina; Dear, Rachel; Epstein, Richard J

2016-12-01

Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines. Machine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p < 0.01, representing 43% and 53% variations from ESMO/NCCN guidelines, respectively). Using ten-fold cross-validation, the best classifiers achieved areas under the receiver operating characteristic curve (AUC) of 0.940 for chemotherapy (95% C.I., 0.922-0.958), 0.899 for the endocrine therapy (95% C.I., 0.880-0.918), and 0.977 for trastuzumab therapy (95% C.I., 0.955-0.999) respectively. Overall, bootstrap aggregated classifiers performed better among all evaluated machine learning models. A machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions regarding adjuvant chemotherapy implies that certain non-clincopathologic criteria, such as patient preference and resource availability, are factored into clinical decision-making by local experts but not captured by guidelines.

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

PubMed

Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol.

PubMed

Bennett, Marsha; Bonanno, Laura; Kuhn, William

2016-10-01

The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?

The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma.

PubMed

Trinh, Van Anh; Zobniw, Chrystia; Hwu, Wen-Jen

2017-08-01

Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy. Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.

PubMed

Papadakis, Georgios Z; Mavroudis, Dimitrios; Georgoulias, Vasilios; Souglakos, John; Alegakis, Athanasios K; Samonis, George; Bagci, Ulas; Makrigiannakis, Antonis; Zoras, Odysseas

2017-04-01

Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy. 171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real time reverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CTCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS). Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho=0.361, p<0.001) with each other, while presenting significant differences across age groups (all p values<0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p=0.558) or after completion (p=0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p=0.487) or after (p=0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p=0.499; OS: p=0.220) or IGFBP-3 (DFI: p=0.900; OS: p=0.406) serum levels. IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not indicative of CTCs' presence in the blood and do not correlate with clinical outcome of women with early-stage breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adjuvant bisphosphonate treatment for breast cancer: why did something so elegant become so complicated?

PubMed

Clemons, Mark; Russell, Kent; Costa, Luis; Addison, Christina L

2012-07-01

Bisphosphonate therapy has revolutionized the care of patients with metastatic bone disease. With its demonstrated activity and anti-tumour effects in preclinical studies it was natural to transition these agents to testing in the adjuvant setting. Surprisingly, the results of adjuvant breast cancer trials have shown either modest or no benefit or even harm. We sought to explore whether there were specific patient cohorts or treatment strategies that were most likely to benefit from adjuvant bisphosphonate therapy. We compared trial designs, patient characteristics and outcomes from the six published and two presented randomized adjuvant bisphosphonate trials. Differences in trial design and patient populations make direct comparisons complicated. The most efficacious use of adjuvant bisphosphonates appears to be in patients with either biopsy evidence of osseous micrometastases, were post-menopausal or had estrogen receptor-positive tumours. Despite tremendous optimism regarding adjuvant bisphosphonate therapy, results from large trials are conflicting. Further investigation into factors influencing response to bisphosphonate treatment or selection of appropriate sub-groups of patients with desirable response characteristics is warranted.

[Long-term experience with multidisciplinary therapy of twenty-six patients with dermatofibrosarcoma protuberans].

PubMed

Mátrai, Zoltán; Liszkay, Gabriella; Plotár, Vanda; Orosz, Zsolt; Székely, Judit; Hitre, Erika; Bartal, Alexandra; Langmár, Zoltán; Bocs, Katalin; Rényi Vámos, Ferenc; Sávolt, Akos; Tóth, László

2009-10-11

Dermatofibrosarcoma protuberans is a low or moderate grade malignant, uncommon soft tissue tumor. The tumor is characterized by slow, but locally aggressive growth, low metastatic potential and high recurrence rate. Initial treatment is the radical surgical excision, using traditional wide excision or Mohs surgery. In case of positive surgical margin or local recurrence, radio-chemotherapy and recently imatinib mesylate is used as adjuvant therapy. Twenty-six patients treated multidisciplinary for dermatofibrosarcoma protuberans were followed up. Mean age of the patients was 44.7 years; mean follow-up time was 60.57 months. In fifteen cases (57.7%) R0 resection was performed, while eleven patients (42,3%) received only R1 resection. An average of 1.87 resections was necessary in order to achieve R0 resection. Six patients (23%) received adjuvant radiotherapy and two patients (7.6%) adjuvant chemotherapy following the removal of the primary tumor. Sixteen patients had no local recurrence. Ongoing treatments were needed in the case of ten patients (38.4%) who developed local recurrence. One patient has deceased due to distant metastases. Using statistical methods we examined the effects indicated as prognostic factors in the literature on local recurrence, precisely, the effect of age above 50 years and surgical radicalism. Dermatofibrosarcoma protuberans can be successfully treated with multidisciplinary therapy. A larger number of cases and randomized multicenter investigations are needed in order to reach more accurate conclusion.

Addition of adjuvant progesterone to physical-exam-indicated cervical cerclage to prevent preterm birth.

PubMed

Jung, Eun Young; Oh, Kyung Joon; Hong, Joon-Seok; Han, Bo Ryoung; Joo, Jung Kyung

2016-12-01

The aim of this study was to assess the effect of vaginal progesterone as an adjuvant therapy to physical-exam-indicated cervical cerclage (PEICC). This retrospective cohort study included 53 consecutive singleton women who underwent PEICC because of acute cervical insufficiency at 17-24 gestational weeks. The study population was divided into two groups: the adjuvant progesterone group (n = 18) and the non-adjuvant group (n = 35). A 200-mg dose of vaginal micronized natural progesterone was administered after cerclage in the adjuvant progesterone group. Primary outcome measure was spontaneous preterm birth (SPTB) at <36 weeks. The SPTB rate at <36 weeks in the adjuvant group was significantly lower than in the non-adjuvant group (17% vs 51%, P < 0.05). Adjuvant progesterone therapy was significantly associated with a reduction in SPTB at <36 weeks (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.69, P < 0.05) even after adjusting for known covariates, including a visible membrane size of ≥4 cm, gestational age, prior SPTB, and use of amnioreduction. The frequency of SPTB at <32 weeks, birthweight < 2500 g, and neonatal intensive care unit admission was significantly lower in the adjuvant progesterone group than in the non-adjuvant group (P < 0.05 for all). Adjuvant vaginal progesterone therapy with PEICC was associated with reductions in SPTB, low birthweight, and neonatal intensive care unit admission. © 2016 Japan Society of Obstetrics and Gynecology.

Activity of glycated chitosan and other adjuvants to PDT vaccines

NASA Astrophysics Data System (ADS)

Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

2015-03-01

Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

Extended Adjuvant Therapy for Breast Cancer

Cancer.gov

An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

Time-to-administration in postoperative chemotherapy for colorectal cancer: does minimally-invasive surgery help?

PubMed

Amore Bonapasta, Stefano; Checcacci, Paolo; Guerra, Francesco; Mirasolo, Vita M; Moraldi, Luca; Ferrara, Angelo; Annecchiarico, Mario; Coratti, Andrea

2016-06-01

The optimal delay in the start of chemotherapy following rectal cancer surgery has not yet been identified. However, postponed adjuvant therapy has been proven to be connected with a significant survival detriment. We aimed to investigate whether the time to initiation of adjuvant treatment can be influenced by the application of minimally invasive surgery rather than traditional open surgery. By comprehensively evaluating the available inherent literature, several factors appear to be associated with delayed postoperative chemotherapy. Some of them are strictly related to surgical short-term outcomes. Laparoscopy results in shortened length of hospital stay, reduced surgical morbidity and lower rate of wound infection compared to conventional surgery. Probably due to such advantages, the application of minimally-invasive surgery to treat rectal malignancies seems to impact favorably the possibility to start adjuvant chemotherapy within an adequate timeframe following surgical resection, with potential improvement in patient survival.

Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

PubMed

Chung, Ki-Young Y; Kelsen, David

2006-06-01

The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horowitz, David P.; Hsu, Charles C.; Wang Jingya

2011-08-01

Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients {>=}75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age {>=}75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were {>=}75 years of age and 489 of 655 patients (74.7%) were <75 years of age.more » Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.« less

Impact of partial versus whole breast radiation therapy on fatigue, perceived stress, quality of life and natural killer cell activity in women with breast cancer.

PubMed

Albuquerque, Kevin; Tell, Dina; Lobo, Philip; Millbrandt, Linda; Mathews, Herbert L; Janusek, Linda Witek

2012-06-18

This pilot study used a prospective longitudinal design to compare the effect of adjuvant whole breast radiation therapy (WBRT) versus partial breast radiation therapy (PBRT) on fatigue, perceived stress, quality of life and natural killer cell activity (NKCA) in women receiving radiation after breast cancer surgery. Women (N = 30) with early-stage breast cancer received either PBRT, Mammosite brachytherapy at dose of 34 Gy 10 fractions/5 days, (N = 15) or WBRT, 3-D conformal techniques at dose of 50 Gy +10 Gy Boost/30 fractions, (N = 15). Treatment was determined by the attending oncologist after discussion with the patient and the choice was based on tumor stage and clinical need. Women were assessed prior to initiation of radiation therapy and twice after completion of radiation therapy. At each assessment, blood was obtained for determination of NKCA and the following instruments were administered: Perceived Stress Scale (PSS), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and Functional Assessment of Cancer Therapy-General (FACT-G). Hierarchical linear modeling (HLM) was used to evaluate group differences in initial outcomes and change in outcomes over time. Fatigue (FACT-F) levels, which were similar prior to radiation therapy, demonstrated a significant difference in trajectory. Women who received PBRT reported progressively lower fatigue; conversely fatigue worsened over time for women who received WBRT. No difference in perceived stress was observed between women who received PBRT or WBRT. Both groups of women reported similar levels of quality of life (FACT-G) prior to initiation of radiation therapy. However, HLM analysis revealed significant group differences in the trajectory of quality of life, such that women receiving PBRT exhibited a linear increase in quality of life over time after completion of radiation therapy; whereas women receiving WBRT showed a decreasing trajectory. NKCA was also similar between therapy groups but additional post hoc analysis revealed that better quality of life significantly predicted higher NKCA regardless of therapy. Compared to WBRT, PBRT results in more rapid recovery from cancer-related fatigue with improved restoration of quality of life after radiation therapy. Additionally, better quality of life predicts higher NKCA against tumor targets, emphasizing the importance of fostering quality of life for women undergoing adjuvant radiation therapy.

Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients.

PubMed

Tang, Yu; Qu, Jintao; Wu, Juan; Li, Song; Zhou, Yue; Xiao, Jianru

2015-09-02

Metastatic spinal cord compression is a disastrous consequence of non-small-cell lung cancer (NSCLC). There have been few studies of the outcomes or prognostic factors in patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies. From 2002 to 2013, 116 patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies were enrolled in this retrospective analysis. Kaplan-Meier methods and Cox regression analysis were used to estimate overall survival and identify prognostic factors for survival. Multivariate analysis suggested that the Eastern Cooperative Oncology Group performance status (ECOG-PS), preoperative and postoperative Frankel scores, postoperative adjuvant radiation therapy, and target therapy were independent prognostic factors. Ninety patients died at a median of twelve months (range, three to forty-seven months) postoperatively, and twenty-six patients were still alive at the time of final follow-up (at a median of fifteen months [range, five to fifty-four months]). The complete disappearance of deficits in spinal cord function after surgery was the most robust predictor of survival. Adjuvant radiation therapy and target therapy were also associated with a better prognosis. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Lymphadenectomy and Adjuvant Therapy Improve Survival with Uterine Carcinosarcoma: A Large Retrospective Cohort Study.

PubMed

Versluis, Marco A C; Pielsticker, Cindy; van der Aa, Maaike A; de Bruyn, Marco; Hollema, Harry; Nijman, Hans W

2018-05-23

Uterine carcinosarcoma is a rare, aggressive subtype of endometrial cancer. Treatment consists of hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy (LND). The survival benefit of LND in relation to adjuvant radio- and/or chemotherapy is unclear. We evaluated the impact of LND on survival in relation to adjuvant therapy in uterine carcinosarcoma. Retrospective data on 1,140 cases were combined from the Netherlands Cancer Registry (NCR) and the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). LND was defined as the removal of any nodes. Additionally, cases where 10 nodes or less (LND ≤10) or more than 10 nodes (LND > 10) were removed were analyzed separately. Adjuvant therapy was evaluated as radiotherapy, chemotherapy, or radiochemotherapy. Associations were analyzed by χ2 test, log-rank test, and Cox regression analysis. Overall survival (OS) had improved after total abdominal hysterectomy with bilateral salpingo-oophorectomy with LND > 10 (HR 0.62, 95% CI 0.47-0.83). Adjuvant therapy was related to OS with an HR of 0.64 (95% CI 0.54-0.75) for radiotherapy, an HR of 0.65 (95% CI 0.48-0.88) for chemotherapy, and an HR of 0.25 (95% CI 0.13-0.46) for radiochemotherapy. Additionally, adjuvant treatment was related to OS when lymph nodes were positive (HR 0.22, 95% CI 0.11-0.42), but not when they were negative. LND is related to improved survival when more than 10 nodes are removed. Adjuvant therapy improves survival when LND is omitted, or when nodes are positive. © 2018 S. Karger AG, Basel.

Transoral Resection of Human Papillomavirus (HPV)-Positive Squamous Cell Carcinoma of the Oropharynx: Outcomes with and Without Adjuvant Therapy.

PubMed

Jackson, Ryan S; Sinha, Parul; Zenga, Joseph; Kallogjeri, Dorina; Suko, Jasmina; Martin, Eliot; Moore, Eric J; Haughey, Bruce H

2017-11-01

With the rise of oropharyngeal squamous cell carcinoma associated with human papillomavirus (HPV), appropriate treatment strategies continue to be tailored toward minimizing treatment while preserving oncologic outcomes. This study aimed to compare the outcomes for those undergoing transoral resection with or without adjuvant therapy for HPV-related oropharyngeal carcinoma. A case-match cohort analysis was performed at two institutions on patients with HPV-related oropharyngeal squamous cell carcinoma. All the subjects underwent transoral surgery and neck dissection. The patients treated with surgery alone were matched 1:1 to those treated with surgery and adjuvant therapy using two groups identified as confounders: T-stage (T1/2 or T3/4) and number of pathologically positive lymph nodes (≤4 or >4). The study identified 105 matched pairs, with a median follow-up period of 42 months (range 3.1-102.3 months). The patients were staged as T1/T2 (86%) or T3/4 (14%). Each group had five patients with more than four positive lymph nodes. Adjuvant therapy significantly improved disease-free survival (hazard ratio [HR] 0.067; 95% confidence interval [CI] 0.01-0.62) and was associated with a lower risk of local and regional recurrence (risk ratio [RR] 0.096; 95% CI 0.02-0.47). No difference in disease-specific survival (HR 0.22; 95% CI 0.02-2.57) or overall survival (HR 0.18; 95% CI 0.01-2.4) was observed with the addition of adjuvant therapy. The risk of the gastrostomy tube was higher for those receiving adjuvant therapy (RR 7.3; 95% CI 2.6-20.6). Transoral surgery is an effective approach for the treatment of HPV-related oropharyngeal carcinoma. The addition of adjuvant therapy appears to decrease the risk of recurrence and improve disease-free survival but may not significantly improve overall survival.

Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

PubMed

El Hage Chehade, Hiba; Wazir, Umar; Mokbel, Kinan; Kasem, Abdul; Mokbel, Kefah

2018-01-01

Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Effectiveness Research in Gynecologic Oncology

PubMed Central

Patankar, Sonali; Tergas, Ana I.

2015-01-01

The field of gynecologic oncology is faced with a number of challenges including how to incorporate new drugs and procedures into practice, how to balance therapeutic efficacy and toxicity of treatment, how to individualize therapy to particular patients or groups of patients, and how to contain the rapidly rising costs associated with oncologic care. In this chapter we examine three common and highly debated clinical scenarios in gynecologic oncology: the initial management of ovarian cancer, the role of lymphadenectomy in the treatment of endometrial cancer, and the choice of adjuvant therapy for ovarian cancer. PMID:25677027

Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

NASA Astrophysics Data System (ADS)

Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

2017-08-01

To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p < 0.2). In the definitive radiation group, overall survival at years one, two, and three were 96%, 92%, and 92%, respectively. A hemoglobin (Hb) level >12 g/dl was a factor with an average association with the overall survival (p < 0.2). The differences between both groups of therapy were not statistically significant (92% vs. 93.3%; p = 0.138). This study did not show any statistically significant overall survival for cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

Adjuvant Vascular Endothelial Growth Factor-targeted Therapy in Renal Cell Carcinoma: A Systematic Review and Pooled Analysis.

PubMed

Sun, Maxine; Marconi, Lorenzo; Eisen, Tim; Escudier, Bernard; Giles, Rachel H; Haas, Naomi B; Harshman, Lauren C; Quinn, David I; Larkin, James; Pal, Sumanta K; Powles, Thomas; Ryan, Christopher W; Sternberg, Cora N; Uzzo, Robert; Choueiri, Toni K; Bex, Axel

2018-05-18

Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal cell carcinoma (RCC). To systematically evaluate the current evidence regarding the therapeutic benefit (disease-free survival [DFS] and overall survival [OS]) and grade 3-4 adverse events (AEs) for adjuvant VEGFR-targeted therapy for resected localized RCC. A critical review of PubMed/Medline, Embase, and the Cochrane Library in January 2018 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was performed. We identified reports and reviewed them according to the Consolidated Standards of Reporting Trials and Standards for the Reporting of Diagnostic Accuracy Studies criteria. Of eight full-text articles that were eligible for inclusion, five studies (two of five were updated analyses) were retained in the final synthesis. Study characteristics were abstracted and the number needed to treat (NNT) per trial was estimated. The three randomized controlled phase III trials included the following comparisons: sunitinib versus placebo or sorafenib versus placebo (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma [ASSURE] study, n=1943), sunitinib versus placebo (S-TRAC, n=615), and pazopanib versus placebo (Pazopanib As Adjuvant Therapy in Localized/Locally Advanced RCC After Nephrectomy study, n=1135). The NNT ranged from 10 (S-TRAC) to 137 (ASSURE study). The pooled analysis showed that VEGFR-targeted therapy was not statistically significantly associated with improved DFS (hazard ratio [HR random ]: 0.92, 95% confidence interval [CI]: 0.82-1.03, p=0.16) or OS (HR random : 0.98, 95% CI: 0.84-1.15, p=0.84) compared with the control group. The adjuvant therapy group experienced significantly higher odds of grade 3-4 AEs (OR random : 5.89, 95% CI: 4.85-7.15, p<0.001). In exploratory analyses focusing on patients who started on the full-dose regimen, DFS was improved in patients who received adjuvant therapy (HR random : 0.83, 95% CI: 0.73-0.95, p=0.005). This pooled analysis of reported randomized trials did not reveal a statistically significant effect between adjuvant VEGFR-targeted therapy and improved DFS or OS in patients with intermediate/high-risk local or regional fully resected RCC. Improvement in DFS may be more likely with the use of full-dose regimens, pending further results. However, adjuvant treatment was associated with high-grade AEs. Vascular endothelial growth factor receptor-targeted therapy after nephrectomy for localized kidney cancer is not associated with consistent improvements in delaying cancer recurrence or prolonging life and comes at the expense of potentially significant side effects. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

PubMed

Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

2010-12-01

A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

A decade of letrozole: FACE

PubMed Central

2007-01-01

Third-generation nonsteroidal aromatase inhibitors (AIs), letrozole and anastrozole, are superior to tamoxifen as initial therapy for early breast cancer but have not been directly compared in a head-to-head adjuvant trial. Cumulative evidence suggests that AIs are not equivalent in terms of potency of estrogen suppression and that there may be differences in clinical efficacy. Thus, with no data from head-to-head comparisons of the AIs as adjuvant therapy yet available, the question of whether there are efficacy differences between the AIs remains. To help answer this question, the Femara versus Anastrozole Clinical Evaluation (FACE) is a phase IIIb open-label, randomized, multicenter trial designed to test whether letrozole or anastrozole has superior efficacy as adjuvant treatment of postmenopausal women with hormone receptor (HR)- and lymph node-positive breast cancer. Eligible patients (target accrual, N = 4,000) are randomized to receive either letrozole 2.5 mg or anastrozole 1 mg daily for up to 5 years. The primary objective is to compare disease-free survival at 5 years. Secondary end points include safety, overall survival, time to distant metastases, and time to contralateral breast cancer. The FACE trial will determine whether or not letrozole offers a greater clinical benefit to postmenopausal women with HR+ early breast cancer at increased risk of early recurrence compared with anastrozole. PMID:17912637

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarkaria, Jann N., E-mail: sarkaria.jann@mayo.edu; Galanis, Evanthia; Wu Wenting

Background: The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt signaling pathway as a critical modulator of cell survival. On the basis of promising preclinical data, the safety and tolerability of therapy with the mTOR inhibitor RAD001 in combination with radiation (RT) and temozolomide (TMZ) was evaluated in this Phase I study. Methods and Materials: All patients received weekly oral RAD001 in combination with standard chemoradiotherapy, followed by RAD001 in combination with standard adjuvant temozolomide. RAD001 was dose escalated in cohorts of 6 patients. Dose-limiting toxicities were defined during RAD001 combination therapy with TMZ/RT. Results: Eighteen patients were enrolled,more » with a median follow-up of 8.4 months. Combined therapy was well tolerated at all dose levels, with 1 patient on each dose level experiencing a dose-limiting toxicity: Grade 3 fatigue, Grade 4 hematologic toxicity, and Grade 4 liver dysfunction. Throughout therapy, there were no Grade 5 events, 3 patients experienced Grade 4 toxicities, and 6 patients had Grade 3 toxicities attributable to treatment. On the basis of these results, the recommended Phase II dosage currently being tested is RAD001 70 mg/week in combination with standard chemoradiotherapy. Fluorodeoxyglucose (FDG) positron emission tomography scans also were obtained at baseline and after the second RAD001 dose before the initiation of TMZ/RT; the change in FDG uptake between scans was calculated for each patient. Fourteen patients had stable metabolic disease, and 4 patients had a partial metabolic response. Conclusions: RAD001 in combination with RT/TMZ and adjuvant TMZ was reasonably well tolerated. Changes in tumor metabolism can be detected by FDG positron emission tomography in a subset of patients within days of initiating RAD001 therapy.« less

Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.

2006-10-01

Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis includedmore » lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.« less

Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

PubMed

Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

2016-09-01

We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

Treatment of Ductal Carcinoma In Situ Among Patients Cared for in Large Integrated Health Plans

PubMed Central

Haque, Reina; Achacoso, Ninah S.; Fletcher, Suzanne W.; Nekhlyudov, Larissa; Collins, Laura C.; Schnitt, Stuart J.; Quesenberry, Charles P.; Habel, Laurel A.

2013-01-01

Objective To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts. Study Design Cross-sectional study nested within a cohort of women diagnosed as having DCIS between 1990 and 2001. Methods We reviewed medical records of 3000 non-Hispanic white (69%), black (10%), Hispanic (9%), and Asian or Pacific Islander (12%) women diagnosed as having DCIS between 1990 and 2001 and treated with breast-conserving therapy. χ2 Test and multinomial logistic regression analysis were used to examine the association between race/ethnicity and use of adjuvant treatments after controlling for patient and clinical variables, including certain pathologic factors. Results We found no significant differences in DCIS adjuvant treatment among racial/ethnic groups in bivariate or multinomial analyses after adjusting for demographic characteristics, comorbidity, and clinical factors. Minority women were as likely to undergo adjuvant radiation therapy as non-Hispanic white women. However, women 70 years or older (odds ratio, 0.40; 95% confidence interval, 0.31–0.51) and women who lived in areas with low geocoded median family income (odds ratio, 0.65; 95% confidence interval, 0.48–0.89) were less likely to receive adjuvant radiation therapy. Tumor size and comedo histologic growth pattern were associated with increased likelihood of receiving radiation therapy. Conclusion Use of adjuvant therapy by minority women in these managed care plans is similar to that by non-Hispanic white women, although use was less among older women and among women who lived in poorer neighborhoods. PMID:20469955

Adherence to adjuvant endocrine therapy: is it a factor for ethnic differences in breast cancer outcomes in New Zealand?

PubMed

Seneviratne, Sanjeewa; Campbell, Ian; Scott, Nina; Kuper-Hommel, Marion; Kim, Boa; Pillai, Avinesh; Lawrenson, Ross

2015-02-01

Despite the benefits of adjuvant endocrine therapy for hormone receptor positive breast cancer, many women are non-adherent or discontinue endocrine treatment early. We studied differences in adherence to adjuvant endocrine therapy by ethnicity in a cohort of New Zealand women with breast cancer and its impact on breast cancer outcomes. We analysed data on women (n = 1149) with newly diagnosed hormone receptor positive, non-metastatic, invasive breast cancer who were treated with adjuvant endocrine therapy in the Waikato during 2005-2011. Linked data from the Waikato Breast Cancer Registry and National Pharmaceutical Database were examined to identify differences by ethnicity in adherence to adjuvant endocrine therapy and the effect of sub-optimal adherence on cancer recurrence and mortality. Overall, a high level of adherence of ≥80% was observed among 70.4% of women, which declined from 76.8% to 59.3% from the first to fifth year of treatment. Māori women were significantly more likely to be sub-optimally adherent (<80%) compared with European women (crude rate 37% vs. 28%, p = 0.005, adjusted OR = 1.51, 95% CI 1.04-2.17). Sub-optimal adherence was associated with a significantly higher risk of breast cancer mortality (HR = 1.77, 95% CI 1.05-2.99) and recurrence (HR = 2.14, 95% CI 1.46-3.14). Sub-optimal adherence to adjuvant endocrine therapy was a likely contributor for breast cancer mortality inequity between Māori and European women, and highlights the need for future research to identify effective ways to increase adherence in Māori women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Combined influence of adjuvant therapy and interval after surgery on peripheral CD4+ T lymphocytes in patients with esophageal squamous cell carcinoma

PubMed Central

LING, YANG; FAN, LIEYING; DONG, CHUNLEI; ZHU, JING; LIU, YONGPING; NI, YAN; ZHU, CHANGTAI; ZHANG, CHANGSONG

2010-01-01

The aim of this study was to investigate possible differences in cellular immunity between chemo- and/or radiotherapy groups during a long interval after surgery in esophageal squamous cell carcinoma (ESCC) patients. Cellular immunity was assessed as peripheral lymphocyte subsets in response to chemotherapy (CT), radiotherapy (RT) and CT+RT by flow cytometric analysis. There were 139 blood samples obtained at different time points relative to surgery from 73 patients with ESCC. The changes in the absolute and relative proportions of lymphocyte phenotypes were significant among the adjuvant therapy groups. There were significant differences in the absolute counts of CD4+ and CD8+ T cells among the interval groups, and a lower CD4/CD8 ratio was found in patients following a prolonged interval. RT alone had a profound effect on the absolute counts of CD3+, CD4+ and CD8+ T cells compared with the other groups. CD4+ T cells exhibited a decreasing trend during a long interval, leading to a prolonged T-cell imbalance after surgery. Univariate analysis revealed that the interaction of the type of adjuvant therapy and the interval after surgery was correlated only with the percentage of CD4+ T cells. The percentage of CD4+ T cells can be used as an indicator of the cellular immunity after surgery in ESCC patients. However, natural killer cells consistently remained suppressed in ESCC patients following adjuvant therapy after surgery. These findings confirm an interaction between adjuvant therapy and the interval after surgery on peripheral CD4+ T cells, and implies that adjuvant therapy may have selective influence on the cellular immunity of ESCC patients after surgery. PMID:23136603

Effects of a brief psychosocial intervention in patients with cancer receiving adjuvant therapy.

PubMed

Oh, Pok Ja; Kim, Soo Hyun

2010-03-01

To test the effects of a brief psychosocial intervention using CD-ROM (BPIC) on psychosocial (fighting spirit, helplessness or hopelessness, anxiety, and depression) and behavioral (self-care behaviors) outcomes in patients with cancer receiving adjuvant therapy. Quasi-experimental. A comprehensive cancer center in Seoul, South Korea. 71 patients undergoing adjuvant therapy. The study participants were assigned to either BPIC or a control group. The experimental group underwent a two-week psychosocial intervention via CD-ROM, booklet, and telephone counseling. Fighting spirit, helplessness or hopelessness, anxiety, depression, and self-care behaviors. After BPIC, the experimental group showed significantly higher scores than the control group for fighting spirit (p = 0.005) and self-care behaviors (p < 0.001). However, the groups showed no significant differences in helplessness or hopelessness (p = 0.42), anxiety (p = 0.279), and depression (p = 0.068). BPIC use improved fighting spirit and self-care behaviors in study participants. The results partially support the effectiveness of BPIC for adaptation among patients with cancer receiving adjuvant therapy. A brief psychosocial intervention using multimedia can be used effectively in clinical oncology settings to accelerate adaptation among patients with cancer in the adjuvant phase.

Trial Watch: Immunotherapy plus radiation therapy for oncological indications.

PubMed

Vacchelli, Erika; Bloy, Norma; Aranda, Fernando; Buqué, Aitziber; Cremer, Isabelle; Demaria, Sandra; Eggermont, Alexander; Formenti, Silvia Chiara; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2016-01-01

Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects. Here, we summarize recent preclinical and clinical advances in this field of investigation.

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

PubMed

McGunigal, Mary; Pollock, Ariel; Doucette, John T; Liu, Jerry; Chadha, Manjeet; Kalir, Tamara; Gupta, Vishal

2018-06-01

Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.

Treatment modalities in sinonasal undifferentiated carcinoma: an analysis from the national cancer database.

PubMed

Khan, Mohemmed N; Konuthula, Neeraja; Parasher, Arjun; Genden, Eric M; Miles, Brett A; Govindaraj, Satish; Iloreta, Alfred M

2017-02-01

Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of unknown etiology with a poor overall prognosis. Its relative rarity has made it difficult to determine the impact of different treatment modalities on survival. Retrospective study of cases in the National Cancer Data Base (NCDB). NCDB cases that were diagnosed as having SNUC between January 1, 2004, and December 31, 2013 were included in the analysis. Outcomes of patients treated with surgery followed adjuvant chemoradiotherapy were compared with definitive chemoradiotherapy. A 5-year survival rate of 42.2% was observed in the 460 patients in the analysis. American Joint Committee on Cancer (AJCC) clinical staging data were available for 304 patients. Of these patients, 60.2% had advanced tumors (AJCC stage 3 or 4). Surgery followed by adjuvant chemoradiotherapy was associated with better survival than definitive chemoradiotherapy (55.8% vs 42.6%, p = 0.007) in the study population. However, in late-stage tumors, there was no difference in survival between the 2 treatment groups (p = 0.22). For late-stage tumors, the time to initiation of adjuvant therapy was 49.2 ± 5.1 days for the surgery plus adjuvant therapy group as compared with 25.9 ± 2.6 days in the definitive chemoradiotherapy group (p < 0.0001), yet this did not appear to affect outcomes. No differences in age, gender, race, Charlson-Deyo score, facility type (academic vs nonacademic), or radiation dose were found between the 2 treatment groups (p > 0.05). Margin status played a critical role in the success of surgical resection, as no patients with positive margin status receiving adjuvant therapy survived to 5 years. Surgery may play a role in a multimodality approach to treatment of late-stage SNUC if the tumor is amenable to surgical resection and negative margins can be reliably obtained. However, in cases where there may be difficulty obtaining negative margins, or this is considered unlikely preoperatively, surgical resection does not appear to provide any additional survival benefit. © 2016 ARS-AAOA, LLC.

Treatment of Canine Oral Melanoma with Nanotechnology-Based Immunotherapy and Radiation.

PubMed

Hoopes, P Jack; Wagner, Robert J; Duval, Kayla; Kang, Kevin; Gladstone, David J; Moodie, Karen L; Crary-Burney, Margaret; Ariaspulido, Hugo; Veliz, Frank A; Steinmetz, Nicole F; Fiering, Steven N

2018-04-12

The presence and benefit of a radiation therapy-associated immune reaction is of great interest as the overall interest in cancer immunotherapy expands. The pathological assessment of irradiated tumors rarely demonstrates consistent immune or inflammatory response. More recent information, primarily associated with the "abscopal effect", suggests a subtle radiation-based systemic immune response may be more common and have more therapeutic potential than previously believed. However, to be of consistent value, the immune stimulatory potential of radiation therapy (RT) will clearly need to be supported by combination with other immunotherapy efforts. In this study, using a spontaneous canine oral melanoma model, we have assessed the efficacy and tumor immunopathology of two nanotechnology-based immune adjuvants combined with RT. The immune adjuvants were administered intratumorally, in an approach termed "in situ vaccination", that puts immunostimulatory reagents into a recognized tumor and utilizes the endogenous antigens in the tumor as the antigens in the antigen/adjuvant combination that constitutes a vaccine. The radiation treatment consisted of a local 6 × 6 Gy tumor regimen given over a 12 day period. The immune adjuvants were a plant-based virus-like nanoparticle (VLP) and a 110 nm diameter magnetic iron oxide nanoparticle (mNPH) that was activated with an alternating magnetic field (AMF) to produce moderate heat (43 °C/60 min). The RT was used alone or combined with one or both adjuvants. The VLP (4 × 200 μg) and mNPH (2 × 7.5 mg/gram tumor) were delivered intratumorally respectively during the RT regimen. All patients received a diagnostic biopsy and CT-based 3-D radiation treatment plan prior to initiating therapy. Patients were assessed clinically 14-21 days post-treatment, monthly for 3 months following treatment, and bimonthly, thereafter. Immunohistopathologic assessment of the tumors was performed before and 14-21 days following treatment. Results suggest that addition of VLPs and/or mNPH to a hypofractionated radiation regimen increases the immune cell infiltration in the tumor, extends the tumor control interval, and has important systemic therapeutic potential.

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Gadgeel, Shirish M

2017-01-01

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

Postoperative PET/CT and target delineation before adjuvant radiotherapy in patients with oral cavity squamous cell carcinoma.

PubMed

Dutta, Pinaki R; Riaz, Nadeem; McBride, Sean; Morris, Luc G; Patel, Snehal; Ganly, Ian; Wong, Richard J; Palmer, Frank; Schöder, Heiko; Lee, Nancy

2016-04-01

The purpose of this study was for us to present our evaluation of the effectiveness of positron emission tomography (PET)/CT imaging in postoperative patients with oral cavity squamous cell carcinoma (SCC) before initiating adjuvant radiation therapy. Treatment planning PET/CT scans were obtained in 44 patients with oral cavity SCC receiving adjuvant radiation. We identified target areas harboring macroscopic disease requiring higher radiation doses or additional surgery. Fourteen PET/CT scans were abnormal. Thirteen patients underwent surgery and/or biopsy, increased radiation dose, and/or addition of chemotherapy. Eleven patients received higher radiation doses. Patients undergoing imaging >8 weeks were more likely to have abnormal results (p = .01). One-year distant metastases-free survival was significantly worse in patients with positive PET/CT scans (61.5% vs 92.7%; p = .01). The estimated positive predictive value (PPV) was 38% for postoperative PET/CT scanning. We demonstrated that 32% of patients have abnormal PET/CT scans resulting in management changes. Patients may benefit from postoperative PET/CT imaging to optimize adjuvant radiation treatment planning. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1285-E1293, 2016. © 2015 Wiley Periodicals, Inc.

Adjuvant bisphosphonate treatment for breast cancer: Where are we heading and can the pre-clinical literature help us get there?

PubMed

Russell, Kent; Clemons, Mark; Costa, Luis; Addison, Christina L

2012-06-01

Bisphosphonates have demonstrated anti-tumour activity in preclinical studies of bone metastatic disease, thus it was natural to transition these agents into the adjuvant cancer therapy setting. Surprisingly, the results of adjuvant breast cancer trials have shown either modest to no benefit or even harm. We sought to explore whether the preclinical results supporting bisphosphonate use provided clues to help explain the current clinical data. Interestingly, the majority of preclinical data suggested that bisphosphonate treatment was more efficacious when administered after the establishment of osseous metastases. This is similar to the findings of one clinical study whereby patients with biopsy evidence of osseous micrometastases derive greater survival benefit from bisphosphonate treatment. Another clinical study found bisphosphonates were associated with increased incidence of visceral metastases, similar to what has been previously published in preclinical models using "preventative" dosing strategies. While the current clinical data suggest bisphosphonates may be more efficacious in post-menopausal or oestrogen depleted patients, or those with hormone receptor positive tumours, to date no appropriately designed preclinical studies have evaluated these effects. Furthermore, putative mechanisms that regulate response to bisphosphonates in other tumour types remain to be evaluated in breast cancer. Despite the initial optimism regarding adjuvant bisphosphonate therapy, the conflicting clinical results from large trials suggest that we should return to the bench to further investigate factors that may influence response to bisphosphonate treatment or identify appropriate characteristics that would indicate the sub-groups of patients most likely to benefit from bisphosphonate treatment.

In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium.

PubMed

Lobbezoo, D J A; van Kampen, R J W; Voogd, A C; Dercksen, M W; van den Berkmortel, F; Smilde, T J; van de Wouw, A J; Peters, F P J; van Riel, J M G H; Peters, N A J B; de Boer, M; Peer, P G M; Tjan-Heijnen, V C G

2016-02-01

The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan-Meier method and compared using the log-rank test. From the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2-6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3-15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors. A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Altered Blood Flow Response to Small Muscle Mass Exercise in Cancer Survivors Treated With Adjuvant Therapy.

PubMed

Didier, Kaylin D; Ederer, Austin K; Reiter, Landon K; Brown, Michael; Hardy, Rachel; Caldwell, Jacob; Black, Christopher; Bemben, Michael G; Ade, Carl J

2017-02-07

Adjuvant cancer treatments have been shown to decrease cardiac function. In addition to changes in cardiovascular risk, there are several additional functional consequences including decreases in exercise capacity and increased incidence of cancer-related fatigue. However, the effects of adjuvant cancer treatment on peripheral vascular function during exercise in cancer survivors have not been well documented. We investigated the vascular responses to exercise in cancer survivors previously treated with adjuvant cancer therapies. Peripheral vascular responses were investigated in 11 cancer survivors previously treated with adjuvant cancer therapies (age 58±6 years, 34±30 months from diagnosis) and 9 healthy controls group matched for age, sex, and maximal voluntary contraction. A dynamic handgrip exercise test at 20% maximal voluntary contraction was performed with simultaneous measurements of forearm blood flow and mean arterial pressure. Forearm vascular conductance was calculated from forearm blood flow and mean arterial pressure. Left ventricular ejection time index (LVETi) was derived from the arterial pressure wave form. Forearm blood flow was attenuated in cancer therapies compared to control at 20% maximal voluntary contraction (189.8±53.8 vs 247.9±80.3 mL·min -1 , respectively). Forearm vascular conductance was not different between groups at rest or during exercise. Mean arterial pressure response to exercise was attenuated in cancer therapies compared to controls (107.8±10.8 vs 119.2±16.2 mm Hg). LEVTi was lower in cancer therapies compared to controls. These data suggest an attenuated exercise blood flow response in cancer survivors ≈34 months following adjuvant cancer therapy that may be attributed to an attenuated increase in mean arterial pressure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Conjunctival papilloma: features and outcomes based on age at initial examination.

PubMed

Kaliki, Swathi; Arepalli, Sruthi; Shields, Carol L; Klein, Kendra; Sun, Hong; Hysenj, Eralda; Lally, Sara E; Shields, Jerry A

2013-05-01

Conjunctival papilloma is a benign epithelial tumor occurring in both children and adults with varying clinical features and outcomes. In this article, we describe our experience regarding the difference in the clinical features and outcomes of conjunctival papilloma based on age at initial examination. To evaluate the clinical features, treatment, and outcomes in patients with conjunctival papilloma based on age at initial examination. Retrospective study. Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania. Ten children and adolescents (aged ≤20 years) and 63 adults (aged >20 years) with conjunctival papilloma. Excisional biopsy, cryotherapy, oral cimetidine, topical or injection interferon alfa-2b, and photodynamic therapy. Tumor response. A comparison of conjunctival papillomas between age groups revealed significant differences in the mean number of tumors per eye (children and adolescents vs adults, 2 vs 1; P = .05), tumor basal dimension (8 vs 6 mm; P = .05), and associated feeder vessels (20% vs 47%; P = .05). Primary treatment included sole treatment with oral cimetidine (15% vs 5%), topical interferon alfa-2b (0% vs 1%), cryotherapy (0% vs 3%), photodynamic therapy (0% vs 1%), excisional biopsy and cryotherapy (38% vs 65%), excisional biopsy and cryotherapy with adjuvant oral cimetidine (8% vs 9%), and excisional biopsy and cryotherapy with adjuvant topical or injection interferon alfa-2b (38% vs 15%). Significant differences in age groups in treatment outcome during the follow-up period (mean, 24 vs 38 months) included complete regression with single treatment (38% vs 95%; P < .01) and tumor recurrence (15% vs 1%; P = .05). Conjunctival papillomas are larger and more likely to be multiple in children and adolescents than in adults. Excisional biopsy and cryotherapy with or without adjuvant oral cimetidine and/or topical interferon alfa-2b provide satisfactory tumor control. Papilloma recurrence is more common in children and adolescents than in adults.

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

Psychosocial influences on suboptimal adjuvant breast cancer treatment adherence among African American women: implications for education and intervention.

PubMed

Magai, Carol; Consedine, Nathan S; Adjei, Brenda A; Hershman, Dawn; Neugut, Alfred

2008-12-01

Despite lower incidence, African American women are at increased risk of dying from breast cancer relative to their European American counterparts. Although there are key differences in both screening behavior and tumor characteristics, an additional part of this mortality difference may lie in the fact that African American women receive suboptimal adjuvant chemotherapy and may receive suboptimal hormonal therapy, therapies that are known to increase survival. The authors consider ethnic differences in the psychosocial factors that have been shown to relate to poor screening adherence and consider how they may influence adherence to breast cancer adjuvant treatment, thus the receipt of suboptimal adjuvant chemo or hormonal therapy. To this end, they review ethnic differences in cognitive, emotional, and social network variables. Psychosocial variables should be included in research designed to understand cancer disparities as well interventions that can be tailored to culturally diverse populations to improve treatment adherence.

Evaluation of Trastuzumab-induced early cardiac dysfunction using two-dimensional Strain Echocardiography.

PubMed

Emren, Sadik Volkan; Tuluce, Selcen Yakar; Levent, Fatih; Tuluce, Kamil; Kalkan, Toygar; Yildiz, Yasar; Alacacioğlu, Ahmet; Kucukzeybek, Yüksel; Akyol, Murat; Salman, Tarık

2015-12-01

Trastuzumab, a chemotherapeutic agent used in the treatment of breast cancer. has been shown to induce subclinical left ventricular (LV) dysfunction during a three to six month period as evidenced by strain echocardiographic examination without any change occurring in the ejection fraction of LV. The present study evaluated the presence of subclinical LV dysfunction using strain echocardiography 1 day and 7 days after the initiation of trastuzumab therapy. The patients with breast cancer receiving adjuvant trastuzumab therapy underwent 2-dimensional, tissue Doppler, and strain echocardiographic examination at baseline and 1 day and 7 days after therapy. LV global longitudinal strain (GLS), global circumferential strain (GCS) values, and other echocardiographic parameters were calculated. A total of 40 females, mean age 50+/-10 years, were evaluated. Of these patients, 97% received anthracycline and 73% received radiotherapy before the initiation of trastuzumab therapy. No change was observed in any of the echocardiographic parameters 1 day after the initiation of trastuzumab therapy (p>0.05). The LV ejection fraction, tissue Doppler parameters, and GCS values did not show any changes 7 days after the initiation of therapy, whereas significant decreases were observed in GLS value (19.2+/-4.0% vs. 17.2+/-3.4, p=0.001) and systolic annular velocity of the lateral LV wall (S' velocity) (10.5+/-3.2 vs. 8.6+/-2.2, p=0.002). Trastuzumab therapy is associated with subclinical LV dysfunction as early as 7 days after initiation of the therapy as evidenced by the decreases in GLS value of LV and systolic annular velocity of the lateral LV wall.

Systemic therapy for HER2-positive early-stage breast cancer.

PubMed

Mathew, Aju; Romond, Edward H

The advent of the targeted monoclonal antbody trastuzumab for treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer marked a revolution in the understanding and management of mammary carcinoma and, in practice, separated this subtype from other kinds of primary breast malignancy. Long term follow-up from the initial large adjuvant trials continue to show remarkably positive results. Currently, at least four additional agents targeting this receptor, using different and complementary mechanisms of action compared with trastuzumab, have been incorporated into clinical trials. The small molecule tyrosine kinase inhibitors lapatinib and neratinib, in addition to the antibody pertuzumab and the antibody-drug conjugate trastuzumab-ematansine, have shown efficacy in metastatic breast cancer and are being evaluated both in neoadjuvant and adjuvant trials for early stage disease. The cytotoxic chemotherapy regimens used in combination with these agents also are evolving and different therapeutic approaches are emerging for patients depending on their relative level of risk from their cancers, thus moving clinical management toward individualized therapy. Much has been learned about managing the toxicities of treatment and pre-operative approaches have provided a means of assessing the sensitivity of individual patients' cancers to specific treatment regimens. This review traces the development of these studies and focuses on improvements in adjuvant and neoadjuvant therapy for patients with HER2-positive disease whose prognosis has changed in the last decade from dire to favorable. A path forward has been set by which the goal of cure is attainable for almost all patients faced with this aggressive form of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

A Randomized controlled trial to evaluate the impact of a Nurse Navigator Programme on outcomes of people with breast cancer: study protocol.

PubMed

Chillakunnel Hussain Rawther, Shejila; Pai, Mamatha Shivananda; Fernandes, Donald J; Mathew, Stanley; Binu, V S; Chakrabarty, Jyothi; Devi, Elsa Sanatombi; George, Anice; Nayak, Baby S

2017-04-01

To evaluate the effectiveness of a Nurse Navigator Programme on anxiety, psychological distress and quality of life in people with breast cancer. Breast cancer is the most frequently detected malignancy and a major cause of cancer death among women around the world. The lengthy course of illness from initial diagnosis to treatment and subsequent follow-up causes deterioration in physical, psychological and social status among patients. Nurses have a major role in cancer care. As women with breast cancer have to undergo various treatment modalities, continued care by a pivot nurse is thought to enhance treatment adherence. Limited studies have been reported from developing countries on Nurse Navigation Programmes. A Stratified Randomized controlled trial with repeated measures. One hundred and twenty newly diagnosed women with breast cancer admitted to surgery wards of a tertiary care hospital in South India will be recruited. (Project funded in Octo"ber 2014). Women are randomly allocated to a control and intervention group. The outcome variables are anxiety, psychological distress and quality of life. Data on outcome measures will be collected at five different time points: before surgery, at discharge, beginning of adjuvant therapy, middle of adjuvant therapy and at the end of adjuvant therapy. This study may give evidence on the effectiveness of a Nurse Navigator Programme for women with breast cancer. If significant effects were detected, the programme could be integrated into hospital services to improve the patient care. © 2016 John Wiley & Sons Ltd.

Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.

PubMed

Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

2014-05-01

To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twu, Chih-Wen; Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan; Wang, Wen-Yi

Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin.more » The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.« less

Systemic and Adjuvant Therapies for Intrahepatic Cholangiocarcinoma.

PubMed

Chun, Yun Shin; Javle, Milind

2017-01-01

Intrahepatic cholangiocarcinoma represents the second most common primary liver cancer and is increasing in incidence. Most patients are diagnosed at an advanced, nonsurgical stage and only about 1 in 5 cases are surgically resectable. Despite surgery, the 5-year survival is low at only 30%. Multifocal, node- or margin-positive disease is at a higher risk of recurrence after resection. There is no level 1 evidence in support of postoperative adjuvant therapy. A recent adjuvant therapy phase III trial from the Partenariat de Recherche en Oncologie Digestive-Actions Concertées dans les Cancers Colo-Rectaux et Digestifs (PRODIGE) group reported no survival advantage with adjuvant gemcitabine and oxaliplatin therapy. Locally advanced or metastatic cholangiocarcinoma is treated with gemcitabine-based systemic chemotherapy with suboptimal response and survival. Integration of local therapy such as focal radiation along with induction chemotherapy is now being investigated in multicenter clinical trials. Recent molecular profiling studies have indicated that about 30% to 40% of intrahepatic cholangiocarcinoma cases have actionable mutations. These include fibroblast growth factor receptor (FGFR), isocitrate dehyrogenase 1 (IDH1), epidermal growth factor receptor (EGFR), and BRAF genetic aberrations. Clinical trials targeting these mutations as well as immune therapy using programmed cell death 1 (PD1) inhibitors indicated a promising early signal showing clinical efficacy.

Multiple cardiac complications after adjuvant therapy for breast cancer: the importance of echocardiography. A case report and review of the literature.

PubMed

Gurghean, Adriana Luminita; Savulescu-Fiedler, Ilinca; Mihailescu, Anca

2017-01-31

Cardiovascular complications induced by adjuvant cancer therapies may become symptomatic after many years, being responsible for increased morbidity and mortality in long-term survivors. We report a case of a 54-year old female admitted for severe heart failure induced by myocardial and valvular damage after postoperative adjuvant therapy for left breast cancer 6 years ago. Her recent history revealed nonST elevation myocardial infarction in the absence of significant cardiovascular risk factors. Transthoracic echocardiography, tissue Doppler imaging and speckle-tracking imaging revealed severe biventricular systolic dysfunction, severe mitral and tricuspid regurgitation and severe pulmonary hypertension.

Survival After Neoadjuvant and Adjuvant Treatments Compared to Surgery Alone for Resectable Esophageal Carcinoma: A Network Meta-analysis.

PubMed

Pasquali, Sandro; Yim, Guang; Vohra, Ravinder S; Mocellin, Simone; Nyanhongo, Donald; Marriott, Paul; Geh, Ju Ian; Griffiths, Ewen A

2017-03-01

This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach. The optimal treatment for resectable esophageal cancer is unknown. A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival. In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87). This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.

[Phase II clinical trial of autologous dendritic cell vaccine with immunologic adjuvant in cutaneous melanoma patients].

PubMed

Baldueva, I A; Novik, A V; Moiseenko, V M; Nekhaeva, T L; Danilova, A B; Danilov, A O; Protsenko, S A; Petrova, T Iu; Uleĭskaia, G I; Shchekina, L A; Semenova, A I; Mikhaĭlichenko, T D; Teletaeva, G M; Zhabina, A S; Volkov, N V; Komarov, Iu I

2012-01-01

This paper describes the clinical results and immunologic changes in cutaneous melanoma patients receiving active specific immunotherapy with autologous dendritic cell vaccine (DCV) in combination with cyclophosphamide used as immunologic adjuvant. Twenty eight patients with morphologically verified stage III-IV cutaneous melanoma receiving therapy in N. N. Petrov Research Institute of Oncology between 2008 and 2011 were included in the study. All patients signed an informed consent form. Nineteen patients (67,9%) received DCV in therapeutic setting, 9 (32,1%) received it in adjuvant setting. DCV therapy was well tolerated. No serious adverse events were registered. Frequent adverse events included Grade 1-2 unspecific symptoms (fever, fatigue, flu-like symptoms) observed in 22% patients after 3,5% of vaccinations. In therapeutic settings the use DCV lead to clinical effect (PR+SD) in 36,6% of patients. PR was observed in 5% of (95% CI 0-15%) patients, SD in 31,6% (95% CI 13-56%). Duration of the objective responses was 168-965+days. Addition of immunologic adjuvant (cyclophosphamide 300 mg/m2 IV 2 hours) 3 days before vaccination increased its efficacy. In this patients group (n=12) the therapy lead to clinical benefit in 42% (95% CI 17-69%) of cases, median time to progression was 91 (95% CI 55-126) days. This regimen was selected for adjuvant therapy. In the adjuvant therapy group (n=9) the median time to progression was 112 (95% CI 58-166) days. Immunologic monitoring showed correlation ofT- and B-cell immune response with DCV clinical efficacy (p<0,05), no correlation with delayed hypersensivity reaction was observed (p>0,1). DCV is well tolerated and shows immunological and clinical response in stage III-IV skin melanoma patients.

Use of trastuzumab as an adjuvant/neoadjuvant therapy in patients with HER2-positive breast cancer in China: The Nvwa study.

PubMed

Li, Junjie; Shao, Zhimin; Xu, Binghe; Jiang, Zefei; Cui, Shude; Zhang, Jin; Liao, Ning; Jiang, Jun; Wang, Yongsheng; Ouyang, Quchang; Ying, Ziwei

2018-05-01

The aim of this study was to understand current trends in trastuzumab use in China as a neoadjuvant/adjuvant therapy for human epidermal growth factor receptor-2 positive (HER2+) breast cancer and identify factors influencing trastuzumab use.This was a retrospective, multicenter, cross-sectional study of patients diagnosed with HER2+ breast cancer (stage I-III), between July 2013 and June 2014, at 155 hospitals in 29 provinces/cities in China. Demographic and clinical data, including tumor characteristics and details of adjuvant/neoadjuvant therapies used, were collected. Data analysis included univariate analysis, multivariate logistic regression, and subgroup analyses.Of 4994 HER2+ patients (mean age 51.1 ± 9.9 years) included, only 29.8% received trastuzumab, with 30.5% in adjuvant therapy and 18.3% in neoadjuvant therapy. The highest rates of adjuvant trastuzumab were in Beijing (59.3%), Jiangsu (57.1%), and Ningxia (50.0%), while those of neoadjuvant trastuzumab were in Guangdong (24.8%), Beijing (14.1%), and Zhejiang (10.7%). Multivariate regression results revealed that factors associated with trastuzumab use were medical insurance cover for trastuzumab, residing locally to the hospital, more lymph node involvement, and more advanced tumor stage. Subgroup analysis revealed that patients receiving neoadjuvant therapy were likely to be younger, premenopausal and non-local, and had lymph node metastases, more advanced tumor, and progesterone receptor positive tumor.Trastuzumab use in patients with HER2+ breast cancer is relatively low in China, especially for neoadjuvant therapy. Insurance coverage seems to be the most correlated factor that influences the use of trastuzumab in Chinese patients with HER2+ breast cancer.

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

PubMed

Boyle, John; Czito, Brian; Willett, Christopher; Palta, Manisha

2015-08-01

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new

PubMed Central

Boyle, John; Czito, Brian; Willett, Christopher

2015-01-01

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates. PMID:26261730

Editorial--Avoiding Unethical Helicobacter pylori Clinical Trials: Susceptibility-Based Studies and Probiotics as Adjuvants.

PubMed

Graham, David Y

2015-10-01

As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g., in a population with known clarithromycin resistance) is unethical. As susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance >0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies, and studies of adjuvants and probiotics. However, the journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors, we provide examples and suggestions regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. © 2015 John Wiley & Sons Ltd.

Editorial - Avoiding unethical Helicobacter pylori clinical trials: Susceptibility-based studies and probiotics as adjuvants

PubMed Central

Graham, David Y.

2016-01-01

As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g. in a population with known clarithromycin resistance) is unethical. Since susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance greater than 0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies and of adjuvants and probiotics. However, the Journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors we provide examples and suggestion regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. PMID:26123529

Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valicenti, Richard K., E-mail: Richard.valicenti@ucdmc.ucdavis.edu; Thompson, Ian; Albertsen, Peter

Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemicalmore » recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.« less

Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agbahiwe, Harold C.; Wharam, Moody; Batra, Sachin

2013-02-01

Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves andmore » descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.« less

Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer.

PubMed

Norton, Nadine; Fox, Nicholas; McCarl, Christie-Ann; Tenner, Kathleen S; Ballman, Karla; Erskine, Courtney L; Necela, Brian M; Northfelt, Donald; Tan, Winston W; Calfa, Carmen; Pegram, Mark; Colon-Otero, Gerardo; Perez, Edith A; Clynes, Raphael; Knutson, Keith L

2018-06-14

Resected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. Pre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival. Prior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p = 0.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR = 0.23; p = 0.04). These results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting. ClinicalTrials.gov, NCT00005970 . Registered on July 5, 2000.

Association Between Adjuvant Chemotherapy and Overall Survival in Patients With Rectal Cancer and Pathological Complete Response After Neoadjuvant Chemotherapy and Resection.

PubMed

Dossa, Fahima; Acuna, Sergio A; Rickles, Aaron S; Berho, Mariana; Wexner, Steven D; Quereshy, Fayez A; Baxter, Nancy N; Chadi, Sami A

2018-04-19

Although American guidelines recommend use of adjuvant chemotherapy in patients with locally advanced rectal cancer, individuals who achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy are less likely to receive adjuvant treatment than incomplete responders. The association and resection of adjuvant chemotherapy with survival in patients with pCR is unclear. To determine whether patients with locally advanced rectal cancer who achieve pCR after neoadjuvant chemoradiation therapy and resection benefit from the administration of adjuvant chemotherapy. This retrospective propensity score-matched cohort study identified patients with locally advanced rectal cancer from the National Cancer Database from 2006 through 2012. We selected patients with nonmetastatic invasive rectal cancer who achieved pCR after neoadjuvant chemoradiation therapy and resection. We matched patients who received adjuvant chemotherapy to patients who did not receive adjuvant treatment in a 1:1 ratio. We separately matched subgroups of patients with node-positive disease before treatment and node-negative disease before treatment to investigate for effect modification by pretreatment nodal status. We compared overall survival between groups using Kaplan-Meier survival methods and Cox proportional hazards models. We identified 2455 patients (mean age, 59.5 years; 59.8% men) with rectal cancer with pCR after neoadjuvant chemoradiation therapy and resection. We matched 667 patients with pCR who received adjuvant chemotherapy and at least 8 weeks of follow-up after surgery to patients with pCR who did not receive adjuvant treatment. Over a median follow-up of 3.1 years (interquartile range, 1.94-4.40 years), patients treated with adjuvant chemotherapy demonstrated better overall survival than those who did not receive adjuvant treatment (hazard ratio, 0.44; 95% CI, 0.28-0.70). When stratified by pretreatment nodal status, only those patients with pretreatment node-positive disease exhibited improved overall survival with administration of adjuvant chemotherapy (hazard ratio, 0.24; 95% CI, 0.10-0.58). The administration of adjuvant chemotherapy in patients with rectal cancer with pCR is associated with improved overall survival, particularly in patients with pretreatment node-positive disease. Although this study suggests a beneficial effect of adjuvant treatment on survival in patients with pCR, these results are limited by the presence of potential unmeasured confounding in this nonrandomized study.

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Adjuvant Intravesical Bacillus Calmette-Guérin Therapy and Survival Among Elderly Patients With Non–Muscle-Invasive Bladder Cancer

PubMed Central

Spencer, Benjamin A.; McBride, Russell B.; Hershman, Dawn L.; Buono, Donna; Herr, Harry W.; Benson, Mitchell C.; Gupta-Mohile, Supriya; Neugut, Alfred I.

2013-01-01

Purpose: National guidelines recommend adjuvant intravesical Bacillus Calmette-Guérin (BCG) therapy for higher-risk non–muscle-invasive bladder cancer (NMIBC). Although a survival benefit has not been demonstrated, randomized trials have shown reduced recurrence and delayed progression after its use. We investigated predictors of BCG receipt and its association with survival for older patients with NMIBC. Patients and Methods: We identified individuals with NMIBC registered in the Surveillance, Epidemiology, and End Results–Medicare database from 1991 to 2003. We used logistic regression to compare those treated with BCG within 6 months of initial diagnosis with those not treated, adjusting for demographic and clinical factors. Cox proportional hazards modeling was used to analyze the association between BCG and overall survival (OS) and bladder cancer–specific survival (BCSS) for the entire cohort and within tumor grades. Results: Of 23,932 patients with NMIBC identified, 22% received adjuvant intravesical BCG. Predictors of receipt were stages Tis and T1, higher grade, and urban residence. Age > 80 years, fewer than two comorbidities, and not being married were associated with decreased use. In the survival analysis, BCG use was associated with better OS (hazard ratio [HR], 0.87; 95% CI, 0.83 to 0.92) in the entire cohort and BCSS among higher-grade cancers (poorly differentiated: HR, 0.78; 95% CI, 0.72 to 0.85; undifferentiated: HR, 0.66; 95% CI, 0.56 to 0.77). Conclusion: Despite guidelines recommending its use, BCG is administered to less than one quarter of eligible patients. This large population-based study found improved OS and BCSS were associated with use of adjuvant intravesical BCG among older patients with NMIBC. Better-designed clinical trials focusing on higher-grade cancers are needed to confirm these findings. PMID:23814517

Prognostic impact of Beclin 1, p62/sequestosome 1 and LC3 protein expression in colon carcinomas from patients receiving 5-fluorouracil as adjuvant chemotherapy.

PubMed

Park, Jae Myung; Huang, Shengbing; Wu, Tsung-Teh; Foster, Nathan R; Sinicrope, Frank A

2013-02-01

Autophagy is a cellular degradation process that can be activated in tumor cells to confer stress tolerance. During autophagy initiation and autophagosome formation, Beclin 1 binds microtubule-associated protein-1 light chain 3 (LC3I) that is converted to its membrane-bound form (LC3II) and interacts with the ubiquitin-binding protein p62/sequestosome 1 (SQSTM1). We determined the association of Beclin 1, LC3 and p62 protein expression with clinical outcome in resected stage II and III colon carcinomas (n = 178) from participants in 5-fluororuacil (5-FU)-based adjuvant therapy trials. The immunopercentage for each marker was determined and dichotomized for analysis with overall survival (OS) using Cox models. We found that autophagy markers localized to the tumor cell cytoplasm and showed increased expression relative to normal epithelial cells. Overexpression of Beclin 1, LC3 and p62 proteins were detected in 69%, 79% and 85% of tumors, respectively. Expression levels were not significantly associated with clinicopathological variables. In a multivariable analysis adjusting for tumor grade, stage and patient age, Beclin 1 overexpression was independently associated with worse OS [hazard ratio (HR), 1.82; 95% confidence interval (CI), 1.0-3.3; p = 0.042] in patients who received 5-FU-based adjuvant therapy. Neither LC3 nor p62 overexpression was prognostic. In conclusion, Beclin 1 overexpression was associated with reduced survival in colon cancer patients treated with adjuvant 5-FU. These data are consistent with preclinical evidence indicating that autophagy can protect colon cancer cells from 5-FU and support the targeting of autophagy for therapeutic advantage in this malignancy.

Comparison of Outcomes After Fluorouracil-Based Adjuvant Therapy for Stages II and III Colon Cancer Between 1978 to 1995 and 1996 to 2007: Evidence of Stage Migration From the ACCENT Database

PubMed Central

Shi, Qian; Andre, Thierry; Grothey, Axel; Yothers, Greg; Hamilton, Stanley R.; Bot, Brian M.; Haller, Daniel G.; Van Cutsem, Eric; Twelves, Chris; Benedetti, Jacqueline K.; O'Connell, Michael J.; Sargent, Daniel J.

2013-01-01

Purpose With improved patient care, better diagnosis, and more treatment options after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are expected to have improved over time in early-stage colon cancer. Data from 18,449 patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were evaluated for potential differences in time to recurrence (TTR), time from recurrence to death (TRD), and overall survival (OS) with regard to FU-based adjuvant regimens. Methods Trials were predefined as old versus newer era using initial accrual before or after 1995. Outcomes were compared between patients enrolled onto old- or newer-era trials, stratified by stage. Results Within the first 3 years, recurrence rates were lower in newer- versus old-era trials for patients with stage II disease, with no differences among those with stage III disease. Both TRD and OS were significantly longer in newer-era trials overall and within each stage. The lymph node (LN) ratio (ie, number of positive nodes divided by total nodes harvested) in those with stage III disease declined over time. TTR improved slightly, with larger number of LNs examined in both stages. Conclusion Improved TRD in newer trials supports the premise that more aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or surgery for recurrent disease) improves OS for patients previously treated in the adjuvant setting. Lower recurrence rates with identical treatments in those with stage II disease enrolled onto newer-era trials reflect stage migration over time, calling into question historical data related to the benefit of FU-based adjuvant therapy in such patients. PMID:23980089

Identifying Clinical Factors Which Predict for Early Failure Patterns Following Resection for Pancreatic Adenocarcinoma in Patients Who Received Adjuvant Chemotherapy Without Chemoradiation.

PubMed

Walston, Steve; Salloum, Joseph; Grieco, Carmine; Wuthrick, Evan; Diaz, Dayssy A; Barney, Christian; Manilchuk, Andrei; Schmidt, Carl; Dillhoff, Mary; Pawlik, Timothy M; Williams, Terence M

2018-05-04

The role of radiation therapy (RT) in resected pancreatic cancer (PC) remains incompletely defined. We sought to determine clinical variables which predict for local-regional recurrence (LRR) to help select patients for adjuvant RT. We identified 73 patients with PC who underwent resection and adjuvant gemcitabine-based chemotherapy alone. We performed detailed radiologic analysis of first patterns of failure. LRR was defined as recurrence of PC within standard postoperative radiation volumes. Univariate analyses (UVA) were conducted using the Kaplan-Meier method and multivariate analyses (MVA) utilized the Cox proportional hazard ratio model. Factors significant on UVA were used for MVA. At median follow-up of 20 months, rates of local-regional recurrence only (LRRO) were 24.7%, LRR as a component of any failure 68.5%, metastatic recurrence (MR) as a component of any failure 65.8%, and overall disease recurrence (OR) 90.5%. On UVA, elevated postoperative CA 19-9 (>90 U/mL), pathologic lymph node positive (pLN+) disease, and higher tumor grade were associated with increased LRR, MR, and OR. On MVA, elevated postoperative CA 19-9 and pLN+ were associated with increased MR and OR. In addition, positive resection margin was associated with increased LRRO on both UVA and MVA. About 25% of patients with PC treated without adjuvant RT develop LRRO as initial failure. The only independent predictor of LRRO was positive margin, while elevated postoperative CA 19-9 and pLN+ were associated with predicting MR and overall survival. These data may help determine which patients benefit from intensification of local therapy with radiation.

Active music therapy in the rehabilitation of severe brain injured patients during coma recovery.

PubMed

Formisano, R; Vinicola, V; Penta, F; Matteis, M; Brunelli, S; Weckel, J W

2001-01-01

Active improvised music therapy may offer an adjuvant from of treatment in the early rehabilitation of severe brain-injured patients. Active music therapy consists of musical improvisation between patient and therapist by singing or by playing different musical instruments, according to the vital functions, the neurological conditions and the motor abilities of the patients. We studied 34 severe brain-injured patients with a mean coma duration of 52 days +/- 37.21 and a mean interval from coma onset to the beginning of rehabilitation of 154 days on average. Our preliminary results show a significant improvement of the collaboration of the severe brain-injured patients and a reduction of undesired behaviours such as inertia (reduced psychomotor initiative) or psychomotor agitation.

Predicted Rate of Secondary Malignancies Following Adjuvant Proton Versus Photon Radiation Therapy for Thymoma.

PubMed

Vogel, J; Lin, L; Litzky, L A; Berman, A T; Simone, C B

2017-10-01

Thymic malignancies are the most common tumors of the anterior mediastinum. The benefit of adjuvant radiation therapy for stage II disease remains controversial, and patients treated with adjuvant radiation therapy are at risk of late complications, including radiation-induced secondary malignant neoplasms (SMNs), that may reduce the overall benefit of treatment. We assess the risk of predicted SMNs following adjuvant proton radiation therapy compared with photon radiation therapy after resection of stage II thymic malignancies to determine whether proton therapy improves the risk-benefit ratio. Ten consecutive patients treated with double-scattered proton beam radiation therapy (DS-PBT) were prospectively enrolled in an institutional review board-approved proton registry study. All patients were treated with DS-PBT. Intensity modulated radiation therapy (IMRT) plans for comparison were generated. SMN risk was calculated based on organ equivalent dose. Patients had a median age of 65 years (range, 25-77 years), and 60% were men. All patients had stage II disease, and many had close or positive margins (60%). The median dose was 50.4 Gy (range, 50.4-54.0 Gy) in 1.8-Gy relative biological effectiveness daily fractions. No differences in target coverage were seen with DS-PBT compared with IMRT plans. Significant reductions were seen in mean and volumetric lung, heart, and esophageal doses with DS-PBT compared with IMRT plans (all P≤.01). Significant reductions in SMNs in the lung, breast, esophagus, skin, and stomach were seen with DS-PBT compared with IMRT. For patients with thymoma diagnosed at the median national age, 5 excess secondary malignancies per 100 patients would be avoided by treating them with protons instead of photons. Treatment with proton therapy can achieve comparable target coverage but significantly reduced doses to critical normal structures, which can lead to fewer predicted SMNs compared with IMRT. By decreasing expected late complications, proton therapy may improve the therapeutic ratio of adjuvant radiation therapy for patients with stage II thymic malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

TERT promoter mutations contribute to IDH mutations in predicting differential responses to adjuvant therapies in WHO grade II and III diffuse gliomas

PubMed Central

Ding, Xiao-Jie; Qin, Zhi-Yong; Hong, Christopher S.; Chen, Ling-Chao; Zhang, Xin; Zhao, Fang-Ping; Wang, Yin; Wang, Yang; Zhou, Liang-Fu; Zhuang, Zhengping; Ng, Ho-Keung; Yan, Hai; Yao, Yu; Mao, Ying

2015-01-01

IDH mutations frequently occur in WHO grade II and III diffuse gliomas and have favorable prognosis compared to wild-type tumors. However, whether IDH mutations in WHO grade II and II diffuse gliomas predict enhanced sensitivity to adjuvant radiation (RT) or chemotherapy (CHT) is still being debated. Recent studies have identified recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) in gliomas. We previously demonstrated that TERT promoter mutations may be promising biomarkers in glioma survival prognostication when combined with IDH mutations. This study analyzed IDH and TERT promoter mutations in 295 WHO grade II and III diffuse gliomas treated with or without adjuvant therapies to explore their impact on the sensitivity of tumors to genotoxic therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter mutations were found in 112 (38%) patients. In multivariate analysis, IDH mutations (p < 0.001) were independent prognostic factors for PFS and OS in patients receiving genotoxic therapies while TERT promoter mutations were not. In univariate analysis, IDH and TERT promoter mutations were not significant prognostic factors in patients who did not receive genotoxic therapies. Adjuvant RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026) in IDH mutated WHO grade II and III diffuse gliomas but not in IDH wild-type group. Univariate and multivariate analyses demonstrated TERT promoter mutations further stratified IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to genotoxic therapies. Adjuvant RT and CHT were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data demonstrated that IDH mutated WHO grade II and III diffuse gliomas had better PFS and OS than their IDH wild-type counterparts when genotoxic therapies were administered after surgery. Importantly, we also found that TERT promoter mutations further stratify IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to adjuvant therapies. Taken together, TERT promoter mutations may predict enhanced sensitivity to genotoxic therapies in IDH wild-type WHO grade II and III diffuse gliomas and may justify intensified treatment in this subgroup. PMID:26314843

Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, Aaron M.; Czerminska, Maria; Jaenne, Pasi A.

2006-07-01

Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m{sup 2}). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patientsmore » received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range, 66-98.3%) (p = 0.20), respectively, for the patients who did not develop pneumonitis. Conclusions: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.« less

Extracorporeal blood purification therapy for sepsis and systemic inflammation: its biological rationale.

PubMed

Bellomo, R; Baldwin, I; Ronco, C

2001-01-01

EBPTs represent a promising new approach to the adjuvant treatment of severe sepsis, septic shock and MODS. Their technology is rapidly evolving and pilot animal and human studies are now taking place to prepare the territory for the first large randomized controlled trial. The rationale for EBPT is reasonable and the initial data are encouraging. The correct technology and molecular targeting, however, are still being explored. Once the best technology has been determined, it is likely that phase II and phase III trials will be performed to test the hypothesis that these therapies can indeed alter mortality in severe inflammatory multiorgan dysfunction.

Cost-effectiveness of the Decipher Genomic Classifier to Guide Individualized Decisions for Early Radiation Therapy After Prostatectomy for Prostate Cancer.

PubMed

Lobo, Jennifer M; Trifiletti, Daniel M; Sturz, Vanessa N; Dicker, Adam P; Buerki, Christine; Davicioni, Elai; Cooperberg, Matthew R; Karnes, R Jeffrey; Jenkins, Robert B; Den, Robert B; Showalter, Timothy N

2017-06-01

Controversy exists regarding the effectiveness of early adjuvant versus salvage radiation therapy after prostatectomy for prostate cancer. Estimates of prostate cancer progression from the Decipher genomic classifier (GC) could guide informed decision-making and improve the outcomes for patients. We developed a Markov model to compare the costs and quality-adjusted life years (QALYs) associated with GC-based treatment decisions regarding adjuvant therapy after prostatectomy with those of 2 control strategies: usual care (determined from patterns of care studies) and the alternative of 100% adjuvant radiation therapy. Using the bootstrapping method of sampling with replacement, the cases of 10,000 patients were simulated during a 10-year time horizon, with each subject having individual estimates for cancer progression (according to GC findings) and noncancer mortality (according to age). GC-based care was more effective and less costly than 100% adjuvant radiation therapy and resulted in cost savings up to an assay cost of $11,402. Compared with usual care, GC-based care resulted in more QALYs. Assuming a $4000 assay cost, the incremental cost-effectiveness ratio was $90,833 per QALY, assuming a 7% usage rate of adjuvant radiation therapy. GC-based care was also associated with a 16% reduction in the percentage of patients with distant metastasis at 5 years compared with usual care. The Decipher GC could be a cost-effective approach for genomics-driven cancer treatment decisions after prostatectomy, with improvements in estimated clinical outcomes compared with usual care. The individualized decision analytic framework applied in the present study offers a flexible approach to estimate the potential utility of genomic assays for personalized cancer medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Sunil; Rana, Vishal; Evans, Douglas B.

2008-03-01

Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies weremore » used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.« less

Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival Over Five Decades

PubMed Central

KIRCHOFF, DANIEL D.; DEUTSCH, GARY B.; FOSHAG, LELAND J.; LEE, JI HEY; SIM, MYUNG-SHIN; FARIES, MARK B.

2016-01-01

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized. PMID:26802836

Evolving Therapeutic Strategies in Mucosal Melanoma Have Not Improved Survival Over Five Decades.

PubMed

Kirchoff, Daniel D; Deutsch, Gary B; Foshag, Leland J; Lee, Ji Hey; Sim, Myung-Shin; Faries, Mark B

2016-01-01

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized.

Same gain, less pain: potential patient preferences for adjuvant treatment in premenopausal women with early breast cancer.

PubMed

Fallowfield, Lesley; McGurk, Rhona; Dixon, Michael

2004-11-01

The aim of this study was to determine the treatment preferences (adjuvant goserelin or cyclophosphamide, methotrexate and fluorouracil (CMF) chemotherapy) of healthy premenopausal women should they hypothetically develop oestrogen-receptor (ER) positive early breast cancer. Two hundred pre or peri-menopausal women read two scenarios describing goserelin or chemotherapy. Information included: How and where treatments were administered, side-effects, their likely persistence and impact on fertility. Women stated their unprompted initial and final preferences with reasons for the choices made. Respondents showed an overwhelming preference for goserelin. 156 (78%) women favoured goserelin, 22 (11%) chemotherapy and 22 (11%) remained undecided (P<0.0001). Primary reasons for preferring goserelin for were 105 (71%) avoidance of chemotherapy side-effects, especially hair loss, perceived convenience and less disruption to normal life 54 (36%). The minority who preferred chemotherapy, valued the treatment finishing more quickly. These results together with clinical trial data showing equivalence of goserelin with CMF regimens suggest that premenopausal women with ER-positive tumours should at least be offered the choice of either adjuvant hormone therapy or chemotherapy.

The effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder: A randomized clinical trial.

PubMed

Sepehrmanesh, Zahra; Fahimi, Hosein; Akasheh, Goudarz; Davoudi, Mohamadreza; Gilasi, Hamidreza; Ghaderi, Amir

2017-11-01

Different studies have been conducted to find the best adjuvant therapies for depression management. There are controversies over the effects of aspirin as an adjuvant therapy for depression. To determine the effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder. This randomized clinical trial was conducted at Kargarnejad Psychiatric Hospital in Kashan, Isfahan, Iran, from September 1, 2016 to November 1, 2016. The study participants included 100 patients with major depressive disorder who were assigned to aspirin and placebo groups by the use of computer-generated random numbers. Patients in these groups respectively received sertraline-aspirin and sertraline-placebo for eight consecutive weeks. Patients were prescribed 80 milligrams of aspirin twice a day. Also, sertraline was administered at a dose of 50-200 milligrams daily. Beck Depression Inventory was employed for depression severity assessment at four time points, namely before, two, four, and eight weeks after the beginning of the intervention. Medication side effects were also assessed eight weeks after the beginning of the intervention. Data were analyzed by SPSS version 12.0, using Chi-square and the Independent-samples t-test (α=0.05). Both groups were matched in terms of age (p=0.46), gender (p=0.539), and depression severity (p=0.509, with mean score 33.5±4.1 vs. 32.8±5.9) at baseline. However, depression scores were reduced significantly four and eight weeks after initiation of therapy just in the sertraline-aspirin group (p<0.05). As an adjuvant therapy, aspirin can reduce depression severity among patients with major depressive disorder. Yet, further studies are needed to prove the effectiveness of aspirin and other anti-inflammatory agents in reducing depression severity. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2016082829556N1. The authors received financial support from Research Deputy of Kashan University of Medical Sciences, Kashan, Isfahan, Iran.

Atypical onset of bicalutamide-induced liver injury.

PubMed

Yun, Gee Young; Kim, Seok Hyun; Kim, Seok Won; Joo, Jong Seok; Kim, Ju Seok; Lee, Eaum Seok; Lee, Byung Seok; Kang, Sun Hyoung; Moon, Hee Seok; Sung, Jae Kyu; Lee, Heon Young; Kim, Kyung Hee

2016-04-21

Anti-androgen therapy is the leading treatment for advanced prostate cancer and is commonly used for neoadjuvant or adjuvant treatment. Bicalutamide is a non-steroidal anti-androgen, used during the initiation of androgen deprivation therapy along with a luteinizing hormone-releasing hormone agonist to reduce the symptoms of tumor-related flares in patients with advanced prostate cancer. As side effects, bicalutamide can cause fatigue, gynecomastia, and decreased libido through competitive androgen receptor blockade. Additionally, although not as common, drug-induced liver injury has also been reported. Herein, we report a case of hepatotoxicity secondary to bicalutamide use. Typically, bicalutamide-induced hepatotoxicity develops after a few days; however, in this case, hepatic injury occurred 5 mo after treatment initiation. Based on this rare case of delayed liver injury, we recommend careful monitoring of liver function throughout bicalutamide treatment for prostate cancer.

Radiotherapy before and after radical prostatectomy for high-risk and locally advanced prostate cancer.

PubMed

Perez, Bradford A; Koontz, Bridget F

2015-05-01

Men with localized high-risk prostate cancer carry significant risk of prostate cancer-specific mortality. The best treatment approach to minimize this risk is unclear. In this review, we evaluate the role of radiation before and after radical prostatectomy. A critical review of the literature was performed regarding the application of external radiation therapy (RT) in combination with prostatectomy for high-risk localized prostate cancer. Up to 70% of men with high-risk localized disease may require adjuvant therapy because of adverse pathologic features or biochemical recurrence in the absence of systemic disease. The utility of adjuvant RT among men with adverse pathologic features are well established at least regarding minimizing biochemical recurrence risk. The optimal timing of salvage radiation is the subject of ongoing studies. Neoadjuvant RT requires further study but is a potentially attractive method because of decreased radiation field sizes and potential radiobiologic benefits of delivering RT before surgery. Salvage prostatectomy is effective at treating local recurrence after radiation but is associated with significant surgical morbidity. Combining local therapies including radical prostatectomy and RT can be a reasonable approach. Care should be taken at the initial presentation of high-risk localized prostate cancer to consider and plan for the likelihood of multimodality care. Copyright © 2015 Elsevier Inc. All rights reserved.

Successful management of Churg-Strauss syndrome using omalizumab as adjuvant immunomodulatory therapy: first documented pediatric case.

PubMed

Iglesias, E; Camacho Lovillo, M; Delgado Pecellín, I; Lirola Cruz, M J; Falcón Neyra, M D; Salazar Quero, J C; Bernabeu-Wittel, J; González Valencia, J P; Neth, O

2014-03-01

Churg-Strauss syndrome (CSS) is an anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis; it is extremely rare in childhood and defined according to the Chapel-Hill Consensus as an eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels. Children commonly have a history of asthma and sinusitis whilst clinical presentation typically involves pulmonary tract and less frequently skin, heart, gastrointestinal tract, and peripheral nerves. Cardiopulmonary disease is higher in children and prognosis is worse. It is associated with significant eosinophilia and raised serum IgE-levels. ANCA are only found in 25% of childhood cases. Here we report the case of a 10-year-old girl who presented to us with vomiting, abdominal pain, and weight loss, paresthesias of lower extremities and breathlessness as well as a history of asthma, sinusitis and allergic rhinitis. She was treated with corticosteroids, cyclophosphamide, intravenous immunoglobulin, mycophenolate mofetil (MMF), and rituximab. However, remission was only achieved after initiation of omalizumab therapy, a recombinant humanized anti-IgE antibody. To the best of our knowledge this is the first pediatric patient suffering from CSS successfully managed with adjuvant anti-IgE therapy resulting in the control of respiratory as well as gastrointestinal symptoms. © 2013 Wiley Periodicals, Inc.

Clinical outcomes in children with herpes simplex encephalitis receiving steroid therapy.

PubMed

Maraş Genç, Hülya; Uyur Yalçın, Emek; Sayan, Murat; Bayhan, Asuman; Öncel, Selim; Arısoy, Emin Sami; Kara, Bülent

2016-07-01

Herpes simplex virus encephalitis (HSE) is a significant cause of morbidity and mortality. Neurologic sequelae are common even after early initiation of acyclovir treatment. The host immune response during HSE can also lead to brain damage. There are an increasing number of reports favoring steroid use in HSE. We aimed to compare the prognosis of children with HSE with and without steroid therapy. We retrospectively screened our hospital archive from 2009 to 2014 for patients diagnosed with HSE with a positive result for herpes simplex virus polymerase chain reaction in cerebrospinal fluid. Patients ≥1 month and ≤18 years at diagnosis were included in the study. Clinical outcomes in terms of cognitive function, motor function, electroencephalographic findings, seizure frequency, and radiologic findings were compared in patients who received adjuvant steroid therapy with those who did not. Six patients (1 boy, 5 girls; aged 4 months to 10 years) were included. Overall symptom duration before hospital admission was ≤5days. Patients received acyclovir treatment for 21-28days. Three received steroid therapy early during the disease and three patients did not. No adverse effects related to steroids were observed. Follow-up duration was 6 months to 5 years. All patients had radiologic sequelae of encephalitis. Cognition, motor function, and seizure control were better in patients who received steroid therapy. Adjuvant steroid therapy seems to be effective in decreasing morbidity in children with HSE but the radiologic sequelae were the same in both groups. Copyright © 2016 Elsevier B.V. All rights reserved.

Adjuvant androgen-deprivation therapy following prostate total cryoablation in high-risk localized prostate cancer patients - Open-labeled randomized clinical trial.

PubMed

Chen, Chung-Hsin; Pu, Yeong-Shiau

2018-06-01

To investigate the efficacy and safety profile of 12-month adjuvant androgen-deprivation therapy (ADT) following total-gland cryoablation (TGC) in patients with high-risk localized prostate cancer (HRLPC). This open-label randomized trial included 38 HRLPC patients who received TGC between July 2011 and March 2013. Within 4 weeks after TGC, subjects were randomly assigned (1:1) to either the 12-month adjuvant ADT or non-adjuvant ADT group. The primary outcome was biochemical failure measured by the Phoenix definition. Adverse events were measured at month 1, 2, 3, 6, 9 and 12. In addition, a cohort of 145 HRLPC patients was selected retrospectively for outcome validation. The adjuvant ADT and non-adjuvant ADT groups did't differ in peri-operative characters, such as age, preoperative PSA, tumor stages, Gleason score, prostate size and cryoprobe number. Four patients with adjuvant ADT withdrew from this trial for personal reasons (N = 2), elevated liver function (N = 1) and poorly controlled hyperglycemia (N = 1). In contrast, none in non-adjuvant ADT group experienced adverse events. Biochemical failures were identified in 5 (26%) patients in each group during a median follow-up duration of 45 months. The median times to biochemical failure were 25 and 5.5 months for adjuvant ADT and non-adjuvant ADT groups, respectively. Biochemical-failure survival curves converged 24 months after TGC. Univariable and multivariable analyses revealed adjuvant ADT was not associated with biochemical recurrences in the validation cohort. Adjuvant ADT does not reduce biochemical failure for HRPLC patients undergoing TGC. It should be further confirmed by a larger cohort. Copyright © 2018. Published by Elsevier Inc.

Treatment Patterns and Health Resource Utilization Among Patients Diagnosed With Early Stage Resected Non-Small Cell Lung Cancer at US Community Oncology Practices.

PubMed

Buck, Philip O; Saverno, Kimberly R; Miller, Paul J E; Arondekar, Bhakti; Walker, Mark S

2015-11-01

Data on adjuvant therapy in resected non-small cell lung cancer (NSCLC) in routine practice are lacking in the United States. This retrospective observational database study included 609 community oncology patients with resected stage IB to IIIA NSCLC. Use of adjuvant therapy was 39.1% at disease stage IB and 64.9% to 68.2% at stage II to IIIA. The most common regimen at all stages was carboplatin and paclitaxel. Platin-based adjuvant chemotherapy has extended survival in clinical trials in patients with completely resected non-small cell lung cancer (NSCLC). There are few data on the use of adjuvant therapy in community-based clinical practice in the United States. This was a retrospective observational study using electronic medical record and billing data collected during routine care at US community oncology sites in the Vector Oncology Data Warehouse between January 2007 and January 2014. Patients aged ≥ 18 years with a primary diagnosis of stage IB to IIIA NSCLC were eligible if they had undergone surgical resection. Treatment patterns, health care resource use, and cost were recorded, stratified by stage at diagnosis. The study included 609 patients (mean age, 64.8 years, 52.9% male), of whom 215 had stage IB disease, 130 stage IIA/II, 110 stage IIB, and 154 stage IIIA. Adjuvant systemic therapy after resection was provided to 345 (56.7%) of 609 patients, with lower use in patients with stage IB disease (39.1%) than stage II to IIIA disease (64.9-68.2%) (P < .0001). The most common adjuvant regimen at all stages was the combination of carboplatin and paclitaxel. There were no statistically significant differences in office visits or incidence of hospitalization by disease stage. During adjuvant treatment, the total monthly median cost per patient was $17,389.75 (interquartile range, $8,815.61 to $23,360.85). Adjuvant systemic therapy was used in some patients with stage IB NSCLC and in the majority of patients with stage IIA to IIIA disease. There were few differences in regimen or health care resource use by disease stage. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment in resectable esophageal cancer?

PubMed

Altorki, Nasser; Harrison, Sebron

2017-03-01

The majority of patients with operable esophageal cancers present with locally advanced disease, for which surgical resection as a sole treatment modality has been historically associated with poor survival. Even following radical resection, most of these patients will eventually succumb to their disease due to distant metastasis. For this reason, there has been intense interest in the role of neoadjuvant therapy. Neoadjuvant therapy primarily consists of either chemotherapy, radiation therapy, or a combination of the two. Multiple studies of variable scope, design, and patient characteristics have been conducted to determine whether neoadjuvant therapy is warranted, and-if so-what is the best modality of treatment. Despite nearly three decades of study, decisions regarding neoadjuvant therapy for esophageal cancer remain controversial. Regardless, the available evidence provided by large, prospective studies supports preoperative chemotherapy as opposed to surgery alone. Therefore, in our opinion, there is no longer any question as to whether induction therapy is appropriate for locally advanced esophageal cancer. Less clear, however, is the evidence that the addition of radiation to chemotherapy in the preoperative setting is superior to neoadjuvant chemotherapy alone. Our group generally advocates for neoadjuvant chemotherapy alone followed by radical esophageal resection. The data for adjuvant therapy are soft, and particularly troubling is the high rate of treatment drop out in trials studying adjuvant therapy. Therefore, we strongly prefer neoadjuvant chemotherapy and reserve adjuvant chemotherapy for those rare, highly selected patients-patients with T1 tumors, for example-who do not receive neoadjuvant treatment and are found to have occult nodal disease at the time of surgery.

Are we ready to use biomarkers for staging, prognosis and treatment selection in early-stage non-small-cell lung cancer?

PubMed

Massuti, Bartomeu; Sanchez, Jose Miguel; Hernando-Trancho, Florentino; Karachaliou, Niki; Rosell, Rafael

2013-06-01

Lung cancer accounts for the majority of cancer-related deaths worldwide. At present, platinum-based therapy represents the standard of care in fit stage II and IIIA non-small cell lung cancer (NSCLC) patients following surgical resection. In advanced disease, personalized chemotherapy and targeted biologic therapy based on histological and molecular tumor profiling have already shown promise in terms of optimizing treatment efficacy. While disease stage is associated with outcome and is commonly used to determine adjuvant treatment eligibility, it is known that a subset of patients with early stage disease experience shorter survival than others with the same clinicopathological characteristics. Improved methods for identifying these individuals, at or near the time of initial diagnosis, may inform the decision to pursue adjuvant therapy options. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information, while real-time quantitative polymerase-chain reaction (RT-qPCR) strategy involving relatively small numbers of genes offers a practical alternative with high cross-platform performance. mRNA and/or protein expression levels of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M subunit 1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) are among the most promising potential biomarkers for early disease and their clinical utility is currently being evaluated in randomized phase II and III clinical trials. This review describes the most promising clinicopathological and molecular biomarkers with predictive and prognostic significance in lung cancer that have been identified through advanced research and which could influence adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine clinical practice.

Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ.

PubMed

Shiyanbola, Oyewale O; Sprague, Brian L; Hampton, John M; Dittus, Kim; James, Ted A; Herschorn, Sally; Gangnon, Ronald E; Weaver, Donald L; Trentham-Dietz, Amy

2016-09-15

The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society. © 2016 American Cancer Society.

Emerging Trends in Surgical and Adjuvant Radiation Therapies among Women Diagnosed with Ductal Carcinoma in Situ

PubMed Central

Shiyanbola, Oyewale O.; Sprague, Brian L.; Hampton, John M.; Dittus, Kim; James, Ted A.; Herschorn, Sally; Gangnon, Ronald E.; Weaver, Donald L.; Trentham-Dietz, Amy

2016-01-01

BACKGROUND The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. We sought to investigate recent patterns in DCIS treatment by demographic factors. METHODS Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group and geographic region. The likelihood of receiving specific treatment modalities was analyzed using multivariable logistic regression. RESULTS DCIS cases were most frequently treated with breast conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation following BCS plateaued at around 70% after 2007, with increasing utilization of mastectomy beyond 2005. Additionally, there was an increasing trend in post-mastectomy reconstruction over time, and women of African ancestry (odds ratio, 0.69; 95% confidence interval,0.66–0.72) and Hispanic women were less likely to undergo reconstruction (odds ratio, 0.83; 95% confidence interval, 0.78–0.89) compared to women of European ancestry. A similar trend was observed in contralateral risk reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk reducing mastectomy among all ancestral/ethnic groups. CONCLUSION Recent trends demonstrate a plateau in radiation therapy administration following BCS, with increasing utilization of mastectomy, reconstruction and contralateral risk reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. PMID:27244699

Targeted therapy for localized non-small-cell lung cancer: a review

PubMed Central

Paleiron, Nicolas; Bylicki, Olivier; André, Michel; Rivière, Emilie; Grassin, Frederic; Robinet, Gilles; Chouaïd, Christos

2016-01-01

Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations) is a major challenge. PMID:27462164

The effect of health insurance status on the treatment and outcomes of patients with colorectal cancer.

PubMed

Parikh, Alexander A; Robinson, Jamie; Zaydfudim, Victor M; Penson, David; Whiteside, Martin A

2014-09-01

Uninsured and underinsured cancer patients often have delayed diagnosis and inferior outcomes. As healthcare reform proceeds in the US, this disparity may gain increasing importance. Our objective was to investigate the impact of health insurance status on the presentation, treatment, and survival among colorectal cancer (CRC) patients. A total of 10,692 patients diagnosed with CRC between 2004 and 2008 identified from the Tennessee Cancer Registry were stratified into five groups: Private, Medicare, Military, Medicaid, and uninsured. Multivariable regression models were constructed to test the association of insurance with receipt of recommended adjuvant therapy and overall survival (OS). Uninsured and Medicaid patients were more often African American (AA) and presented with higher stage tumors (P < 0.001). Medicare patients were less likely to receive recommended adjuvant therapy (OR 0.54). Lack of insurance, Medicaid, and failure to receive recommended adjuvant therapy were independently associated with worse OS. Although uninsured and Medicaid patients receive recommended adjuvant therapy comparable to other patients, they present with later stage disease and have a worse OS. Future studies are needed to better explain these disparities especially in the light of changing healthcare climate in the US. © 2014 Wiley Periodicals, Inc.

Alternative Therapy and Abnormal Liver Function During Adjuvant Chemotherapy in Breast Cancer Patients

PubMed Central

Ahn, Jin-Hee; Kim, Sung-Bae; Yun, Mi Ra; Lee, Jung-Shin; Kang, Yoon-Koo

2004-01-01

Although hepatotoxicity has been rarely reported during adjuvant chemotherapy in breast cancer patients, we observed a high frequency in our patients who were also taking alternative agents. We therefore sought to determine the association between hepatotoxicity and alternative agents during adjuvant chemotherapy in breast cancer patients. All breast cancer patients were treated with the same chemotherapeutic regimen and had normal baseline liver function test (LFT). LFT was checked repeatedly during each cycle of chemotherapy. Patients showing LFT abnormalities were asked about use of alternative agents, and, after the end of chemotherapy, a questionnaire was administered to each patient on their use of alternative agents. Of 178 patients, 65 (36.5%) admitted using alternative therapy, and significantly more patients in this group developed LFT abnormalities (37/65, 56.9%) than those who denied taking alternative therapy (25/113, 22.1%, p=0.001). Although LFT abnormalities were mild to moderate and normalized in most patients after cessation of alternative agents, it remained a serious problem in one patient. In conclusion, alternative therapy may be one of the etiologies for abnormal LFT in breast cancer patients receiving adjuvant chemotherapy. PMID:15201506

The role of adjuvant therapy in the management of head and neck merkel cell carcinoma: an analysis of 4815 patients.

PubMed

Chen, Michelle M; Roman, Sanziana A; Sosa, Julie A; Judson, Benjamin L

2015-02-01

Merkel cell carcinoma (MCC) is a rare neuroendocrine malignant neoplasm that most commonly occurs in the head and neck and is rapidly increasing in incidence. The role of adjuvant chemoradiotherapy (CRT) in the management of head and neck MCC remains controversial. To evaluate the association between different adjuvant therapies and survival in head and neck MCC. Retrospective review of adult patients with head and neck MCC who had surgery recorded in the National Cancer Data Base from 1998 to 2011. Surgical excision, adjuvant radiation therapy (RT), or adjuvant CRT. Our main outcome was overall survival (OS). Statistical analysis included χ2, t tests, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. We identified 4815 patients; 92.0% underwent standard surgical excision, and 8.0% underwent Mohs surgery. On multivariate analysis, age at least 75 years (hazard ratio [HR], 2.83 [95% CI, 1.82-4.41]), larger tumor size, positive margins (HR, 1.52 [95% CI, 1.25-1.85]), and metastatic lymph nodes (HR, 2.29 [95% CI, 1.84-2.85]) were independently associated with decreased OS. Postoperative CRT (HR, 0.62 [95% CI, 0.47-0.81]) and RT (HR, 0.80 [95% CI, 0.70-0.92]) provided a survival benefit over surgery alone. Adjuvant CRT was associated with improved OS over adjuvant RT in patients with positive margins (HR, 0.48 [95% CI, 0.25-0.93]), tumor size at least 3 cm (HR, 0.52 [95% CI, 0.30-0.90]), and male sex (HR, 0.69 [95% CI, 0.50-0.94]). To our knowledge, this the first study examining the role of adjuvant CRT in head and neck MCC. Results suggest that adjuvant CRT may help improve survival in high-risk patients, such as males and those with positive margins and larger tumors.

National evaluation of multidisciplinary quality metrics for head and neck cancer.

PubMed

Cramer, John D; Speedy, Sedona E; Ferris, Robert L; Rademaker, Alfred W; Patel, Urjeet A; Samant, Sandeep

2017-11-15

The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer. The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality. In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83). Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017;123:4372-81. © 2017 American Cancer Society. © 2017 American Cancer Society.

Initial Experience With Low-Dose Methotrexate as an Adjuvant Treatment for Rapidly Recurrent Nonvasculitic Laryngotracheal Stenosis.

PubMed

Rosow, David E; Ahmed, Jamal

2017-02-01

Adult laryngotracheal stenosis (LTS) is typically managed surgically, but some patients fail treatment because of rapid restenosis or granulation tissue formation. The need for frequent surgery or tracheostomy reduces the quality of life in these patients and poses a significant challenge for the treating physician. New adjuvant treatments are required to reduce the surgical burden of this condition. To examine whether patients with rapidly recurrent nonvasculitic LTS who fail surgical management of their stenosis (ie, requiring dilation more frequently than every 6 months) experience longer intervals between surgical procedures when receiving adjuvant treatment with low-dose methotrexate. This study was a retrospective case series study of patients treated with methotrexate from January 2014 to January 2016 at a tertiary academic medical center. Participants were 10 patients with LTS without any diagnosis of vasculitis or granulomatous disease who underwent low-dose methotrexate therapy. Once-weekly treatment with oral methotrexate, 15 or 20 mg. The mean number of days between operations before and after starting methotrexate therapy was compared. Clinical courses and adverse effects of each patient were also reviewed. Among 10 patients, the mean (SD) age at the outset of study inclusion was 52 (19) years; 8 were female and 2 were male. All 10 patients experienced some clinical improvement. Three patients who were previously tracheostomy dependent were able to be decannulated. Two other patients who were tracheostomy dependent and had failed endoscopic management of their granulation tissue had complete resolution. In 6 patients who underwent at least 1 surgical procedure before and after the initiation of methotrexate treatment, the mean (SD) interval between operations increased from 61 (35) days (95% CI, 26-96 days) before starting methotrexate therapy to 312 (137) days (95% CI, 175-449 days) after starting methotrexate therapy, for an absolute difference of 251 (58) days (95% CI, 193-309 days). The median number of days between surgical procedures was 44 days before starting methotrexate therapy and 289 days after starting methotrexate therapy. Adverse effects observed included mild hair thinning and onychomycosis in 2 patients and herpes zoster infection in 1 patient. Low-dose methotrexate appears to be an effective adjunct to surgery in select patients with LTS that is resistant to surgical management and leads to a substantial increase in the number of days between surgical procedures. The patient and clinician must be aware of the adverse effects of methotrexate therapy and balance these factors against the risk of poorly controlled airway stenosis. Randomized, placebo-controlled, double-blind trials are needed to examine whether the clinical efficacy in this series of patients translates to a larger population.

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

PubMed

Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme

PubMed Central

Rosenfeld, Myrna R; Ye, Xiaobu; Supko, Jeffrey G; Desideri, Serena; Grossman, Stuart A; Brem, Steven; Mikkelson, Tom; Wang, Daniel; Chang, Yunyoung C; Hu, Janice; McAfee, Quentin; Fisher, Joy; Troxel, Andrea B; Piao, Shengfu; Heitjan, Daniel F; Tan, Kay-See; Pontiggia, Laura; O’Dwyer, Peter J; Davis, Lisa E; Amaravadi, Ravi K

2014-01-01

Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ. PMID:24991840

A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.

PubMed

Rosenfeld, Myrna R; Ye, Xiaobu; Supko, Jeffrey G; Desideri, Serena; Grossman, Stuart A; Brem, Steven; Mikkelson, Tom; Wang, Daniel; Chang, Yunyoung C; Hu, Janice; McAfee, Quentin; Fisher, Joy; Troxel, Andrea B; Piao, Shengfu; Heitjan, Daniel F; Tan, Kay-See; Pontiggia, Laura; O'Dwyer, Peter J; Davis, Lisa E; Amaravadi, Ravi K

2014-08-01

Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ.

The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

PubMed

Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

2011-10-01

The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cost-utility analysis of adjuvant chemotherapy in patients with stage III colon cancer in Thailand.

PubMed

Lerdkiattikorn, Panattharin; Chaikledkaew, Usa; Lausoontornsiri, Wirote; Chindavijak, Somjin; Khuhaprema, Thirawud; Tantai, Narisa; Teerawattananon, Yot

2015-01-01

In Thailand, there has been no economic evaluation study of adjuvant chemotherapy for stage III colon cancer patients after resection. This study aims to evaluate the cost-utility of all chemotherapy regimens currently used in Thailand compared with the adjuvant 5-fluorouracil/leucovorin (5-FU/LV) plus capecitabine as the first-line therapy for metastatic disease in patients with stage III colon cancer after resection. A cost-utility analysis was performed to estimate the relevant lifetime costs and health outcomes of chemotherapy regimens based on a societal perspective using a Markov model. The results suggested that the adjuvant 5-FU/LV plus capecitabine as the first-line therapy for metastatic disease would be the most cost-effective chemotherapy. The adjuvant FOLFOX and FOLFIRI as the first-line treatment for metastatic disease would be cost-effective with an incremental cost-effectiveness ratio of 299,365 Thai baht per QALY gained based on a societal perspective if both prices of FOLFOX and FOLFIRI were decreased by 40%.

Type of Resection (Whipple vs. Distal) Does Not Affect the National Failure to Provide Post-resection Adjuvant Chemotherapy in Localized Pancreatic Cancer.

PubMed

Bergquist, John R; Ivanics, Tommy; Shubert, Christopher R; Habermann, Elizabeth B; Smoot, Rory L; Kendrick, Michael L; Nagorney, David M; Farnell, Michael B; Truty, Mark J

2017-06-01

Adjuvant chemotherapy improves survival after curative intent resection for localized pancreatic adenocarcinoma (PDAC). Given the differences in perioperative morbidity, we hypothesized that patients undergoing distal partial pancreatectomy (DPP) would receive adjuvant therapy more often those undergoing pancreatoduodenectomy (PD). The National Cancer Data Base (2004-2012) identified patients with localized PDAC undergoing DPP and PD, excluding neoadjuvant cases, and factors associated with receipt of adjuvant therapy were identified. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression. Overall, 13,501 patients were included (DPP, n = 1933; PD, n = 11,568). Prognostic characteristics were similar, except DPP patients had fewer N1 lesions, less often positive margins, more minimally invasive resections, and shorter hospital stay. The proportion of patients not receiving adjuvant chemotherapy was equivalent (DPP 33.7%, PD 32.0%; p = 0.148). The type of procedure was not independently associated with adjuvant chemotherapy (hazard ratio 0.96, 95% confidence interval 0.90-1.02; p = 0.150), and patients receiving adjuvant chemotherapy had improved unadjusted and adjusted OS compared with surgery alone. The type of resection did not predict adjusted mortality (p = 0.870). Receipt of adjuvant chemotherapy did not vary by type of resection but improved survival independent of procedure performed. Factors other than type of resection appear to be driving the nationwide rates of post-resection adjuvant chemotherapy in localized PDAC.

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

PubMed

Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

2017-07-01

Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise <10% of PDAC. Using the NCDB 2006-2012, resected PDAC patients with stage I disease who received adjuvant therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with overall survival (OS) were identified. 3909 patients with resected stage IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Adjuvant Bisphosphonates for Postmenopausal Breast Cancer

Cancer.gov

A summary of a meta-analysis of randomized trials of bisphosphonates as adjuvant therapy for women with early-stage breast cancer that shows the drugs can reduce the rate of disease recurrence in bone.

Current Status of Adjuvant Therapy for Colon Cancer

PubMed Central

André, Thierry; Afchain, Pauline; Barrier, Alain; Blanchard, Pierre; Larsen, Annette K.; Tournigand, Christophe; Louvet, Christophe; de Gramont, Aimery

2007-01-01

Due to its frequency and persistently high mortality, colorectal cancer represents a major public health problem. The use of adjuvant chemotherapy has improved prognosis in stage III disease, but much work remains to be done in optimizing adjuvant treatment, including refinement of ability to predict disease course and response to chemotherapy. The FOLFOX4 regimen is now considered standard treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5-FU) have not proven to be more effective than 5-FU/folinic acid (FA). Oral fluoropyrimidines (eg, capecitabine, UFT + FA) now offer an alternative to intravenous 5-FU. Adjuvant chemotherapy for stage II colorectal cancer is more controversial. Use of adjuvant chemotherapy does not appear to be justified in patients with no particular risk factors (T3N0 with no poor prognosis factor). In contrast, the risk:benefit ratio in patients with one or more poor prognostic factors (T4 tumor, occlusion or perforation, poorly differentiated tumor, vascular invasion, or < 10 lymph nodes examined) appears to favor adjuvant treatment with FOLFOX4. Ongoing adjuvant trials are evaluating bevacizumab and cetuximab combined with 5-FU and oxaliplatin, and are examining the utility of such potential predictive markers as tumor microsatellite instability and loss of heterozygosity. Duration of therapy and prevention of oxaliplatin neurotoxicity are other critical areas for future research. PMID:19262714

Phenotypic characterization of circulating tumor cells in triple negative breast cancer patients.

PubMed

Agelaki, Sofia; Dragolia, Melina; Markonanolaki, Harris; Alkahtani, Saad; Stournaras, Christos; Georgoulias, Vassilis; Kallergi, Galatea

2017-01-17

Patients with triple negative breast cancer (TNBC), are considered as a poor prognosis group for whom no targeted therapies are currently available. The aim of the present study was to phenotypically characterize their CTCs in order to explore potential therapeutic targets. PBMC's cytospins were prepared from 45 early (before and after adjuvant chemotherapy), 10 metastatic TNBC and 21 hormone receptor (HR) -positive patients. The expression of Cytokeratins (CK), ER, PR, EGFR and HER2 on CTCs was assessed using immunofluoresence staining and ARIOL analysis. In early stage TNBC, ER, PR, HER2 and EGFR expressing-CTCs were detected in 24.4%, 24.4%, 20% and 40% of patients before the initiation of adjuvant chemotherapy, and in 17.8%, 13.3% 6.7% and 51.1% respectively after the completion of adjuvant treatment. Triple staining experiments revealed distinct subpopulations of CTC expressed HR, and ErbB family receptors. In patients with metastatic disease, the frequency of HER2+ CTCs was significantly increased compared to adjuvant setting (60% vs 20%, p=0.014). The presence of CK+PR- CTCs, before adjuvant treatment was associated with reduced OS (p=0.032) and DFI (p=0.04). Furthermore, the frequency of ER-, PR- and HER2+ CTCs was higher in HR(+) than in TNBC tumors (57.1%, p=0.006; 52.4%, p=0.021 and 52.38%, p=0.009, respectively). The CTCs in patients with early TNBC are phenotypically heterogeneous based on the expression of HR, EGFR and HER2 both before and after the completion of adjuvant chemotherapy whereas the presence of HER2+ CTCs prevails during disease evolution. These findings could be of clinical relevance in terms of CTC targeting.

Effect of Antioxidant Vitamins as Adjuvant Therapy for Sudden Sensorineural Hearing Loss: Systematic Review Study.

PubMed

Ibrahim, Iman; Zeitouni, Anthony; da Silva, Sabrina Daniela

2018-06-22

Sudden sensorineural hearing loss (SSNHL) is an otological emergency of unknown etiology. Recent reports showed that antioxidant drugs can benefit patients with SSNHL. This study attempted to evaluate the effect of adding antioxidant vitamins as an adjuvant therapy alongside with corticosteroids. To evaluate the effects of the 3 major antioxidant vitamins (A, C, and E) as an adjuvant therapy, administered with corticosteroids, for the treatment of SSNHL in adult patients (≥18 years). MEDLINE, EMBASE, PubMed, Web of Science and Cochrane electronic databases from January 1, 1995, through September 25, 2017. Published studies of adult patients who received antioxidant vitamins (A, C, E, or any combination of these vitamins) as an adjuvant therapy in addition to the regular treatment (corticosteroids) for SSNHL. Quality assessment was performed using the Cochrane Collaboration Tool for Assessing Risk of Bias. Each study had a control group (conventional treatment + placebo) and a trial group (antioxidant vitamin(s) + conventional treatment). From 446 manuscripts identified in the literature, 3 studies were included in the review with 279 patients. The most common vitamins used to treat SSNHL were the 3 major antioxidant vitamins A, C, and E, combined sometimes with other antioxidants such as selenium. The success of the treatment is increased in patients who received antioxidant vitamins in combination with conventional therapy. © 2018 S. Karger AG, Basel.

Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database.

PubMed

Garlipp, Benjamin; Ptok, Henry; Benedix, Frank; Otto, Ronny; Popp, Felix; Ridwelski, Karsten; Gastinger, Ingo; Benckert, Christoph; Lippert, Hans; Bruns, Christiane

2016-12-01

Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p < 0.001). One hundred forty-eight matched pairs were available for analysis of adjuvant therapy with or without oxaliplatin, showing no improvement in DFS in patients receiving oxaliplatin (76.9 ± 4.12 vs. 79.3 ± 4.44 months, p = 0.254). Local recurrence rate was not significantly different between groups in either analysis. In this cohort of rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?

PubMed Central

2011-01-01

Background Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Materials and methods Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: "Endometrial cancer", "Endometrial Neoplasms", "Endometrial Neoplasms/radiotherapy", "External beam radiation therapy", "Brachytherapy" and adequate combinations. Conclusion Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer. PMID:22118369

Effects of Adjuvant Androgen on Anemia and Nutritional Parameters in Chronic Hemodialysis Patients Using Low-dose Recombinant Human Erythropoietin

PubMed Central

Lee, Myeung Su; Ahn, Seon Ho; Song, Ju Hung

2002-01-01

Background: Recombinant human erythropoietin (epoetin) has greatly contributed to improvement of the anemia of chronic renal failure patients on hemodialysis. However, the reduced erythropoietic effect to epoetin and its high cost have induced lots of supplementary treatments. Therefore, we performed a prospective study to evaluate the effects of adjuvant low-dose androgen therapy in patients using a lower-dose of epoetin than the commonly recommended dose on anemia and the nutritional parameters. Methods : 17 patients of hemoglobin (Hgb) less than 9 g/dL even after being treated with 1,000 U epoetin subcutaneously (s.c.) 3 times per week on a stable status for more than 6 months, who were on hemodialysis at our institution were examined. They were injected with the same dose of epoetin s.c. and nandrolone decanoate 100 mg intramuscularly (i.m) weekly for another 6 months. Blood test was performed every month before therapy for 6 months and after therapy for 6 months and the mean values were reviewed for comparison. Results: Hgb (7.75±0.9 vs 8.99±1.39 g/dL, p <0.01) and hematocrit (Hct) (23.68±2.85 vs 26.66±3.91%, p <0.01) were apparently changed before and after adjuvant therapy. Hgb and Hct, weekly dose of epoetin were not statistically different in 9 male patients before and after adjuvant therapy. The weekly dose of epoetin was not statistically different in 8 female patients, but Hgb and Hct (8.02±0.6 vs 9.72±1.31 g/dL, 24.54±1.7 vs 28.74±3.06%, p <0.01) were statistically different before and after adjuvant therapy. In comparison between male and female groups, weekly doses of epoetin and nandrolone decanoate were significantly greater in the female group than the male group (epoetin: 50.66±6.23 vs 61.18±8.76 U/kg/week, nandrolone decanoate: 1.69±0.2 vs 2.04±0.29 mg/kg/week, p <0.05). Conclusion : Our data show that the adjuvant androgen therapy is effective for the anemia of hemodialysis patients who did not recover from anemia even after being continuously treated with low-dose epoetin. PMID:12298427

Carrier-Mediated Antiviral Therapy

DTIC Science & Technology

1988-01-01

methyimethacrylate). (x) Adsorption onto 0.2% aluminium hydroxide. (L) Fluid vaccine. The vaccines with nanoparticles as adjuvants were tested by...such treatment regimens, the doses of the interferons needed to obtain efficacy can result in toxic side effects. For all these reasons, methods of...adjuvants can be used in human vaccines. Besides the classic aluminum adjuvants. particulate polymeric carriers, the so-called nanoparticles , hold promise for

A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers

PubMed Central

Abderrahman, Balkees; Curpan, Ramona F; Hawsawi, Yousef M; Fan, Ping; Jordan, V Craig

2018-01-01

Prostate and breast cancer are the two cancers with the highest incidence in men and women, respectively. Here, we focus on the known biology of acquired resistance to antihormone therapy of prostate and breast cancer and compare laboratory and clinical similarities in the evolution of the disease. Laboratory studies and clinical observations in prostate and breast cancer demonstrate that cell selection pathways occur during acquired resistance to antihormonal therapy. Following sex steroid deprivation, both prostate and breast cancer models show an initial increased acquired sensitivity to the growth potential of sex steroids. Subsequently, prostate and breast cancer cells either become dependent upon the antihormone treatment or grow spontaneously in the absence of hormones. Paradoxically, the physiologic sex steroids now kill a proportion of selected, but vulnerable, resistant tumor cells. The sex steroid receptor complex triggers apoptosis. We draw parallels between acquired resistance in prostate and breast cancer to sex steroid deprivation. Clinical observations and patient trials confirm the veracity of the laboratory studies. We consider therapeutic strategies to increase response rates in clinical trials of metastatic disease that can subsequently be applied as a preemptive salvage adjuvant therapy. The goal of future advances is to enhance response rates and deploy a safe strategy earlier in the treatment plan to save lives. The introduction of a simple evidence-based enhanced adjuvant therapy as a global healthcare strategy has the potential to control recurrence, reduce hospitalization, reduce healthcare costs and maintain a healthier population that contributes to society. PMID:29162647

Socioeconomic Disparities in Breast Cancer Treatment Among Older Women

PubMed Central

Richardson, Lisa C.; Krontiras, Helen; Pisu, Maria

2014-01-01

Abstract Background: Racial disparities in breast cancer treatment among Medicare beneficiaries have been documented. This study aimed to determine whether racial disparities exist among white and black female Medicare beneficiaries in Alabama, an economically disadvantaged U.S. state. Methods: From a linked dataset of breast cancer cases from the Alabama Statewide Cancer Registry and fee-for-service claims from Medicare, we identified 2,097 white and black females, aged 66 years and older, who were diagnosed with stages 1–3 breast cancer from January 1, 2000, to December 31, 2002. Generalized estimating equation (GEE) models were used to determine whether there were racial differences in initiating and completing National Comprehensive Cancer Network Clinical Practice guideline-specific treatment. Results: Sixty-two percent of whites and 64.7% of blacks had mastectomy (p=0.27); 34.6% of whites and 30.2% of blacks had breast conserving surgery (BCS) (p=0.12). Among those who had BCS, 76.8% of whites and 83.3% of blacks started adjuvant radiation therapy (p=0.33) and they equally completed adjuvant radiation therapy (p=0.29). For women with tumors over 1 centimeter, whites and blacks were equally likely to start (16.1% of whites and 18.3% of black; p=0.34) and complete (50.6% of whites and 46.3% of black; p=0.87) adjuvant chemotherapy. There were still no differences after adjusting for confounders using GEE. However, differences were observed by area-level socioeconomic status (SES), with lower SES residents more likely to receive a mastectomy (odds ratio [OR]=1.26; 95% confidence interval [CI]: 1.01–1.57) and initiate radiation after BCS (OR=2.24; 95% CI: 1.28–3.93). Conclusions: No racial differences were found in guideline-specific breast cancer treatment or treatment completion, but there were differences by SES. Future studies should explore reasons for SES differences and whether similar results hold in other economically disadvantaged U.S. states. PMID:24350590

An economic analysis of conservative management versus active treatment for men with localized prostate cancer.

PubMed

Perlroth, Daniella J; Bhattacharya, Jay; Goldman, Dana P; Garber, Alan M

2012-12-01

Comparative effectiveness research suggests that conservative management (CM) strategies are no less effective than active initial treatment for many men with localized prostate cancer. We estimate longer-term costs of initial management strategies and potential US health expenditure savings by increased use of conservative management for men with localized prostate cancer. Five-year total health expenditures attributed to initial management strategies for localized prostate cancer were calculated using commercial claims data from 1998 to 2006, and savings were estimated from a US population health-care expenditure model. Our analysis finds that patients receiving combinations of active treatments have the highest additional costs over conservative management at $63 500, followed by $48 550 for intensity-modulated radiation therapy, $37 500 for primary androgen deprivation therapy, and $28 600 for brachytherapy. Radical prostatectomy ($15 200) and external beam radiation therapy ($18 900) were associated with the lowest costs. The population model estimated that US health expenditures could be lowered by 1) use of initial CM over all active treatment ($2.9-3.25 billion annual savings), 2) shifting patients receiving intensity-modulated radiation therapy to CM ($680-930 million), 3) foregoing primary androgen deprivation therapy($555 million), 4) reducing the use of adjuvant androgen deprivation in addition to local therapies ($630 million), and 5) using single treatments rather than combination local treatment ($620-655 million). In conclusion, we find that all active treatments are associated with higher longer-term costs than CM. Substantial savings, representing up to 30% of total costs, could be realized by adopting CM strategies, including active surveillance, for initial management of men with localized prostate cancer.

Recent Advances in Targeted Therapy for Glioma.

PubMed

Lin, Lin; Cai, Jinquan; Jiang, Chuanlu

2017-01-01

Gliomas are the most common primary malignant brain tumors, which have a universally fatal outcome. Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway. Furthermore, recent advances in targeting immunotherapy and stem cell therapy also brought numerous strategies to glioma treatment. This article reviewed the researches focused on the advanced strategies of various target therapies for improving the glioma treatment efficacy, and discussed the challenges and future directions for glioma therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Use of Adjuvant 5-Fluorouracil and Radiation Therapy After Gastric Cancer Resection Among the Elderly and Impact on Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strauss, Joshua; Hershman, Dawn L.; Department of Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY

2010-04-15

Purpose: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. Methods and Materials: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. Results: Among 1,993 patients who received combinedmore » chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. Conclusions: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.« less

Underuse of Breast Cancer Adjuvant Treatment: Patient Knowledge, Beliefs, and Medical Mistrust

PubMed Central

Bickell, Nina A.; Weidmann, Jessica; Fei, Kezhen; Lin, Jenny J.; Leventhal, Howard

2009-01-01

Purpose Little is known about why women with breast cancer who have surgery do not receive proven effective postsurgical adjuvant treatments. Methods We surveyed 258 women who recently underwent surgical treatment at six New York City hospitals for early-stage breast cancer about their care, knowledge, and beliefs about breast cancer and its treatment. As per national guidelines, all women should have received adjuvant treatment. Adjuvant treatment data were obtained from inpatient and outpatient charts. Factor analysis was used to create scales scored to 100 of treatment beliefs and knowledge, medical mistrust, and physician communication about treatment. Bivariate and multivariate analyses assessed differences between treated and untreated women. Results Compared with treated women, untreated women were less likely to know that adjuvant therapies increase survival (on a 100-point scale; 66 v 75; P < .0001), had greater mistrust (64 v 53; P = .001), and had less self-efficacy (92 v 97; P < .05); physician communication about treatment did not affect patient knowledge of treatment benefits (r = 0.8; P = .21). Multivariate analysis found that untreated women were more likely to be 70 years or older (adjusted relative risk [aRR], 1.11; 95% CI, 1.00 to 1.13), to have comorbidities (aRR, 1.10; 95% CI, 1.04 to 1.12), and to express mistrust in the medical delivery system (aRR, 1.003; 95% CI, 1.00 to 1.007), even though they were more likely to believe adjuvant treatments were beneficial (aRR, 0.99; 95% CI, 0.98 to 0.99; model c, 0.84; P ≤ .0001). Conclusion Patient knowledge and beliefs about treatment and medical mistrust are mutable factors associated with underuse of effective adjuvant therapies. Physicians may improve cancer care by ensuring that discussions about adjuvant therapy include a clear presentation of the benefits, not just the risks of treatment, and by addressing patient trust in and concerns about the medical system. PMID:19770368

[A Distal Bile Duct Carcinoma Patient Who Underwent Surgical Resection for Liver Metastasis].

PubMed

Komiyama, Sosuke; Izumiya, Yasuhito; Kimura, Yu; Nakashima, Shingo; Kin, Syuichi; Kawakami, Sadao

2018-03-01

A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach-preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of the liver. The patient received 2 courses of gemcitabine-cisplatin combination chemotherapy. No new lesions were detected after chemotherapy and the patient underwent a partial liver resection of segment 8. The pathological examination revealed a metachronous distant metastasis originating from the bile duct carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6 months. Following completion of all therapies, the patient survived without tumor recurrence for 3 years and 10 months after the initial operation. Thus, surgical interventions might be effective in improving prognosis among selected patients with postoperative liver metastasis of bile duct carcinoma.

Significant anti-tumor effect of bevacizumab in treatment of pineal gland glioblastoma multiforme.

PubMed

Mansour, Joshua; Fields, Braxton; Macomson, Samuel; Rixe, Olivier

2014-12-01

Glioblastoma multiforme (GBM) is the most aggressive subtype of malignant gliomas. Current standard treatment for GBM involves a combination of cytoreduction through surgical resection, followed by radiation with concomitant and adjuvant chemotherapy (temozolomide). The role of bevacizumab in the treatment of GBM continues to be a topic of ongoing research and debate. Despite aggressive treatment, these tumors remain undoubtedly fatal, especially in the elderly. Furthermore, tumors present in the pineal gland are extremely rare, accounting for only 0.1-0.4 % of all adult brain tumors, with this location adding to the complexity of treatment. We present a case of GBM, at the rare location of pineal gland, in an elderly patient who was refractory to initial standard of care treatment with radiation and concomitant and adjuvant temozolomide, but who developed a significant response to anti-angiogenic therapy using bevacizumab.

The ALTTO Breast Cancer Trial

Cancer.gov

A collection of material about the Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation, or ALTTO, study that will compare the targeted agents lapatinib and trastuzumab alone, in sequence, or in combination as adjuvant therapy for HER2-positive br

Role of radiation therapy in patients with resectable pancreatic cancer.

PubMed

Palta, Manisha; Willett, Christopher; Czito, Brian

2011-07-01

The 5-year overall survival of patients with pancreatic cancer is approximately 5%, with potentially resectable disease representing the curable minority. Although surgical resection remains the cornerstone of treatment, local and distant failure rates are high after complete resection, and debate continues as to the appropriate adjuvant therapy. Many oncologists advocate for adjuvant chemotherapy alone, given that high rates of systemic metastases are the primary cause of patient mortality. Others, however, view locoregional failure as a significant contributor to morbidity and mortality, thereby justifying the use of adjuvant chemoradiation. As in other gastrointestinal malignancies, neoadjuvant chemoradiotherapy offers potential advantages in resectable patients, and clinical investigation of this approach has shown promising results; however, phase III data are lacking. Further therapeutic advances and prospective trials are needed to better define the optimal role of adjuvant and neoadjuvant treatment in patients with resectable pancreatic cancer.

Gold glyconanoparticles coupled to listeriolysin O 91-99 peptide serve as adjuvant therapy against melanoma.

PubMed

Calderon-Gonzalez, R; Terán-Navarro, H; García, I; Marradi, M; Salcines-Cuevas, D; Yañez-Diaz, S; Solis-Angulo, A; Frande-Cabanes, E; Fariñas, M C; Garcia-Castaño, A; Gomez-Roman, J; Penades, S; Rivera, F; Freire, J; Álvarez-Domínguez, C

2017-08-03

Dendritic cell-based (DC-based) vaccines are promising immunotherapies for cancer. However, several factors, such as the lack of efficient targeted delivery and the sources and types of DCs, have limited the efficacy of DCs and their clinical potential. We propose an alternative nanotechnology-based vaccine platform with antibacterial prophylactic abilities that uses gold glyconanoparticles coupled to listeriolysin O 91-99 peptide (GNP-LLO 91-99 ), which acts as a novel adjuvant for cancer therapy. GNP-LLO 91-99 , when used to vaccinate mice, exhibited dual antitumour activities, namely, the inhibition of tumour migration and growth and adjuvant activity for recruiting and activating DCs, including those from melanoma patients. GNP-LLO 91-99 nanoparticles caused tumour apoptosis and induced antigen- and melanoma-specific cytotoxic Th1 responses (P ≤ 0.5). We propose this adjuvant nanotherapy for preventing the progression of the first stages of melanoma.

Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sher, David J., E-mail: dsher@lroc.harvard.edu; Thotakura, Vijaya; Balboni, Tracy A.

2011-11-15

Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distributionmore » of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC, OS, and lower late toxicity rates, and chemoradiotherapy was a successful treatment for patients with high-risk disease. In contrast, outcomes of radiation-based treatment for patients with inoperable locally advanced disease were markedly less successful.« less

The International (Ludwig) Breast Cancer Study Group Trials I-IV: 15 years follow-up.

PubMed

Castiglione-Gertsch, M; Johnsen, C; Goldhirsch, A; Gelber, R D; Rudenstam, C M; Collins, J; Lindtner, J; Hacking, A; Cortes-Funes, H; Forbes, J

1994-10-01

Adjuvant systemic therapy prolongs disease-free and overall survival in both pre- and postmenopausal patients. Available data shown benefit from multi-agent chemotherapy, prolonged tamoxifen treatment, and ovarian ablation, and that the combination of chemo- and endocrine therapy might be advantageous. In 1978 the International (Ludwig) Breast Cancer Study Group (IBCSG) initiated four complementary randomized controlled clinical trials to evaluate the roles of chemo-endocrine combinations or endocrine therapy alone in specific populations defined by risk (for pre- and perimenopausal patients) or by age (for postmenopausal patients). The results at 10 and 13 years' median follow-up for these trials are summarized in this report and are compared to those of the Overview meta-analysis with regard to chemo-endocrine or endocrine therapy combinations. Furthermore, types of first relapses by sites and second malignant diseases are reported. 1601 evaluable patients with node positive disease were included into the studies I-IV. In Trial I (491 premenopausal patients with 1-3 positive axillary nodes) we studied the addition of low-dose continuous prednisone (p) to a cyclophosphamide-methotrexate-fluorouracil (CMF) combination. In Trial II 327 premenopausal patients with four or more positive axillary nodes were randomized to one year CMFp or to a surgical oophorectomy followed by CMFp. In Trial III (463 postmenopausal patients 65 years old or younger), combined chemoendocrine therapy (one year of CMFp plus tamoxifen (T)) was compared to endocrine therapy (1 year of p + T) or to surgery alone. In Trial IV 320 postmenopausal patients 66 to 80 years old were treated either by surgery alone or by surgery followed by 1 year prednisone and tamoxifen. In Trial I the addition of prednisone allowed a higher dose of cytotoxics to be administered compared with CMF alone. Despite this increased dose intensity, 13-year disease-free survival (DFS) and overall survival (OS) were similar for the two treatment groups (49% vs. 52% DFS, 59% vs. 65% OS for CMFp vs. CMF). In Trial II the addition of surgical oophorectomy to CMFp yielded an improved outcome which approached statistical significance for the subset of 107 patients known to have estrogen receptor-positive tumors (DFS, 23% vs. 15%, p = 0.13; OS, 41% vs. 30%, p = 0.12). In Trial III combined chemoendocrine therapy improved DFS and OS compared with endocrine therapy alone (p + T) given for the same duration, or no adjuvant treatment (DFS, 35% vs. 25% vs. 14%, p < 0.0001; OS, 48% vs. 36% vs. 32%, p = 0.01). In Trial IV p + T improved DFS compared with no adjuvant therapy (27% vs. 15%, p = 0.004). Despite competing risks for this elderly population, OS was also improved but the result was not statistically significant (34% vs. 22%, p = 0.08). The overall results of these four trials indicate that the continuation of investigations on combined chemo-endocrine therapies is warranted. The prognosis of the patients, all node-positive, treated with the most effective adjuvant treatment is such that there is a large potential for improvement.

Adjuvant chemotherapy for breast cancer patients: patients' expectations and physicians' attitudes.

PubMed

Barak, Frida; Ostrowsky, Lev A; Kreitler, Shulamith

2012-06-01

Findings show that there is a certain degree of refusal on the part of breast cancer patients to undergo adjuvant therapy. Accordingly, the major goals of the study were, first, to learn more about the beliefs of breast cancer patients in regard to adjuvant therapy; second, to find out about the sources of the patients' beliefs; and third, to learn about the attitudes of oncologists concerning the same aspects of adjuvant therapy to which the patients' beliefs referred. The participants were 92 breast cancer patients (mean age 61.2) and 57 doctors of both genders specialized in oncology or affiliated domains. Both groups were administered questionnaires referring to goals of adjuvant treatment, the chances of attaining these goals, side effects, and difficulty of the treatment. Doctors were specifically asked about the views they thought proper to communicate to patients in regard to the mentioned issues. Patients were also asked about whether they had doubts about the treatment and sources of information. The findings showed disparities between the views of patients and doctors in regard to goals, chances of attainment, side effects, and difficulty of treatment. Patients endorsed more goals than doctors and tended to assign to them lower chances of attainment. Doctors were divided in their views about whether to communicate the side effects and difficulties. The results reveal the importance of outlining goals for patients undergoing adjuvant treatment and the disagreements between doctors about what should be communicated to patients, and highlight the complexity of providing to patients information that is both scientifically correct and emotionally helpful.

Safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin and 5-fluorouracil after mesorectal excision with lateral pelvic lymph node dissection for stage iii lower rectal cancer.

PubMed

Iwasa, Satoru; Souda, Hiroaki; Yamazaki, Kentaro; Takahari, Daisuke; Miyamoto, Yuji; Takii, Yasumasa; Ikeda, Satoshi; Hamaguchi, Tetsuya; Kanemitsu, Yukihide; Shimada, Yasuhiro

2015-03-01

Preoperative chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for stage III lower rectal cancer worldwide. However, in Japan, the standard treatment is TME with lateral pelvic lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5-fluorouracil (modified FOLFOX6) after TME with LPLD. This retrospective study included 33 patients who received modified FOLFOX6 after TME with LPLD for stage III lower rectal cancer. The overall completion rate of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was observed in eight patients (24%). Sensory neuropathy was observed in 32 patients (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate was 45% at 3 years. Adjuvant modified FOLFOX6 was feasible in patients with stage III lower rectal cancer after TME with LPLD. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The presentation and outcomes of mucosal melanoma in 695 patients.

PubMed

Konuthula, Neeraja; Khan, Mohemmed N; Parasher, Arjun; Del Signore, Anthony; Genden, Eric M; Govindaraj, Satish; Iloreta, Alfred M

2017-01-01

Most data on sinonasal mucosal melanoma come from small institutional studies, and therefore optimal treatment methods are not well understood. The purpose of this study was to analyze the association between treatment and survival in sinonasal mucosal melanoma. Six hundred ninety-five patients diagnosed with sinonasal mucosal melanoma between 2004 and 2010 were identified from the National Cancer Data Base. Treatment modalities and overall survival rates were determined. The 5-year overall survival was 21.7%, with a mean survival of 38.4 ± 1.7 months. The majority of patients were treated with surgery alone (31.5%) or surgery with adjuvant radiotherapy (41.4%). There was no statistical difference between survival with surgery alone and surgery with adjuvant radiation therapy (25.1% vs 25.1%, p = 0.93). Between the surgery and surgery-with-adjuvant-therapy groups, there was no difference in the number of patients with positive margins (p = 0.54), regional lymph node metastases at diagnosis (p = 0.55), morbidity scores (p = 0.58), insurance status (p = 0.13), age > 60 years (p = 0.24), or treatment at academic centers (p = 0.12). Based on this large review of patients with sinonasal mucosal melanoma, adjuvant radiation therapy may not provide a survival benefit as patients tended to do poorly regardless of adjuvant radiation status. © 2016 ARS-AAOA, LLC.

[Primary safety analysis of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients].

PubMed

Zhou, Ning-Ning; Teng, Xiao-Yu; Liu, Dong-Geng; Xu, Ran; Guan, Zhong-Zhen

2008-12-01

It has been proved that trastuzumab has clinical activity in early and advanced breast cancer with Her2-overexpression. This study was to analyze the safety of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients. Trastuzumab was administrated after adjuvant chemotherapy every 21 days. The initial dose was 8 mg/kg, and the subsequent dose was 6 mg/kg, for four to 35 cycles (medium 18 cycles). The side effects of these patients, especially cardiotoxicity, were analyzed. Thirty patients with Her2-positive early breast cancer were entered into the study. The average treatment period was one year (range nine weeks to two years). Two patients had shivering and fever during the first infusion with trastuzumab. Left ventricular ejection fraction (LVEF) level dropped in 18 cases after treatment with trastuzumab, half of which decreased more then 10%û however, no cardiac failure was observed. The post-surgical treatment of trastuzumab in Chinese patients with Her2-positive early breast cancer shows a satisfactory safety profile. However, the potential cardiotoxicity of trastuzumab should be carefully monitored during therapy.

Incidence and management of arthralgias in breast cancer patients treated with aromatase inhibitors in an outpatient oncology clinic.

PubMed

Menas, Pamela; Merkel, Douglas; Hui, Wendy; Lawton, Jessica; Harper, Abigail; Carro, George

2012-12-01

Aromatase inhibitors (AIs) are routinely used as first-line adjuvant treatment of breast cancer in postmenopausal women with hormone receptor positive tumors. The current recommended length of treatment with an AI is 5 years. Arthralgias have been frequently cited as the primary reason for discontinuation of AI therapy. Various treatment strategies are proposed in literature, but a standardized treatment algorithm has not been established. The initial purpose of this study was to describe the incidence and management of AI-induced arthralgias in patients treated at Kellogg Cancer Center (KCC). Further evaluation led to the development and the implementation of a treatment algorithm and electronic medical record (EMR) documentation tools. The retrospective chart review included 206 adult patients with hormone receptor positive breast cancer who were receiving adjuvant therapy with an AI. A multidisciplinary treatment team consisting of pharmacists, collaborative practice nurses, and physicians met to develop a standardized treatment algorithm and corresponding EMR documentation tool. The treatment algorithm and documentation tool were developed after the study to better monitor and proactively treat patients with AI-induced arthralgias. RESULTS/ CONCLUSIONS: The overall incidence of arthralgias at KCC was 48% (n = 98/206). Of these patients, 32% were documented as having arthralgias within the first 6 months of therapy initiation. Patients who reported AI-induced arthralgias were younger than patients who did not report AI-induced arthralgias (61 vs. 65 years, p = 0.002). There was no statistical difference in the incidence of arthralgias in patients with a history of chemotherapy (including taxane therapy) compared to those who did not receive chemotherapy (p = 0.352). Of patients presenting with AI-induced arthralgias, 41% did not have physician-managed treatment documented in the EMR. A standardized treatment algorithm and electronic chart documentation tools were then developed by the multidisciplinary team.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; Bosch, Walter R.; Bahl, Amit

Purpose: To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials. Methods and Materials: We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, themore » group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ statistic. Results: The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral), whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. Conclusions: Consensus descriptions of CTVs and OARs were successfully developed and can be used in clinical trials of adjuvant radiation therapy for bladder cancer.« less

Management of stage II colon cancer - the use of molecular biomarkers for adjuvant therapy decision

PubMed Central

2013-01-01

Background There is uncertainty on the benefit of adjuvant chemotherapy in patients with stage II colorectal cancers. The aim of this study is to investigate the combined role of clinical, pathological and molecular parameters to identify those stage II patients who better benefit from adjuvant therapy. Methods We examined 120 stage II colon cancer patients. Of these, 60 patients received adjuvant 5-FU chemotherapy after surgery and the other 60 did not receive therapy. Immunohistochemical (IHC) analyses were performed to evaluate the expressions of Thymidylate synthetase (TYMS), TP53 (p53), β-catenin (CTNNB1) and CD8. For TYMS, its mRNA expression levels were also investigated by real time qRT-PCR. The entire case study was characterized by the presence of a defect in the MMR (mismatch repair) system, the presence of the CpG island methylator phenotype (CIMP or CIMP-High) and for the V600E mutation in the BRAF gene. At the histo-pathological level, the depth of tumour invasion, lymphovascular invasion, invasion of large veins, host lymphocytic response and tumour border configuration were recorded. Results The presence of the V600E mutation in the BRAF gene was a poor prognostic factor for disease free and overall survival (DFS; hazard ratio [HR], 2.57; 95% CI: 1.03 -6.37; p = 0.04 and OS; HR, 3.68; 95% CI: 1.43-9.47; p < 0.01 respectively), independently of 5-FU treatment. Adjuvant therapy significantly improved survival in patients with high TYMS levels (p = 0.04), while patients with low TYMS had a better outcome if treated by surgery alone (DFS; HR, 6.07; 95% CI, 0.82 to 44.89; p = 0.04). In patients with a defect in the MMR system (dMMR), 5-FU therapy was associated to reduced survival (DFS; HR, 37.98; 95% CI, 1.04 to 1381.31; p = 0.04), while it was beneficial for CIMP-High associated tumours (DFS; HR, 0.17; 95% CI, 0.02 to 1.13; p = 0.05). Conclusions Patients’ characterization according to MMR status, CIMP phenotype and TYMS mRNA expression may provide a more tailored approach for adjuvant therapy in stage II colon cancer. PMID:23446022

Reiki therapy for postoperative oral pain in pediatric patients: pilot data from a double-blind, randomized clinical trial.

PubMed

Kundu, Anjana; Lin, Yuting; Oron, Assaf P; Doorenbos, Ardith Z

2014-02-01

To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reiki therapy for postoperative oral pain in pediatric patients: Pilot data from a double-blind, randomized clinical trial

PubMed Central

Kundu, Anjana; Lin, Yuting; Oron, Assaf P.; Doorenbos, Ardith Z.

2014-01-01

Purpose To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Methods This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Results Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Implications Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. PMID:24439640

Treatment of uveal melanoma: where are we now?

PubMed Central

Yang, Jessica; Manson, Daniel K.; Marr, Brian P.; Carvajal, Richard D.

2018-01-01

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease. PMID:29497459

Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.

2009-09-01

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. Onmore » univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.« less

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

PubMed

Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

2015-07-01

To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

Trajectories of self-reported cognitive function in postmenopausal women during adjuvant systemic therapy for breast cancer.

PubMed

Merriman, John D; Sereika, Susan M; Brufsky, Adam M; McAuliffe, Priscilla F; McGuire, Kandace P; Myers, Jamie S; Phillips, Mary L; Ryan, Christopher M; Gentry, Amanda L; Jones, Lindsay D; Bender, Catherine M

2017-01-01

In a sample of 368 postmenopausal women, we (1) determined within-cohort and between-cohort relationships between adjuvant systemic therapy for breast cancer and self-reported cognitive function during the first 18 months of therapy and (2) evaluated the influence of co-occurring symptoms, neuropsychological function, and other covariates on relationships. We evaluated self-reported cognitive function, using the Patient Assessment of Own Functioning Inventory (PAOFI), and potential covariates (e.g., co-occurring symptom scores and neuropsychological function z-scores) in 158 women receiving aromatase inhibitor (AI) therapy alone, 104 women receiving chemotherapy followed by AI therapy, and 106 non-cancer controls. Patients were assessed before systemic therapy and then every 6 months, for a total of four assessments over 18 months. Controls were assessed at matched time points. Mixed-effects modeling was used to determine longitudinal relationships. Controlling for covariates, patients enrolled before chemotherapy reported poorer global cognitive function (p < 0.001), memory (p < 0.001), language and communication (p < 0.001), and sensorimotor function (p = 0.002) after chemotherapy. These patients reported poorer higher-level cognitive and intellectual functions from before chemotherapy to 12 months after initiation of AI therapy (p < 0.001). Higher levels of depressive symptoms (p < 0.001), anxiety (p < 0.001), and fatigue (p = 0.040) at enrollment were predictors of poorer cognitive function over time. PAOFI total score was a predictor of executive function (p = 0.048) and visual working memory (p = 0.005) z-scores, controlling for covariates. Findings provide further evidence of poorer self-reported cognitive function after chemotherapy and of relationships between co-occurring symptoms and cognitive changes. AI therapy alone does not have an impact on self-reported cognitive function. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Adjuvant treatment for endometrial cancer: literature review and recommendations by the Comité de l'évolution des pratiques en oncologie (CEPO).

PubMed

Morneau, Mélanie; Foster, William; Lalancette, Marc; Van Nguyen-Huynh, Thu; Renaud, Marie-Claude; Samouëlian, Vanessa; Letarte, Nathalie; Almanric, Karine; Boily, Gino; Bouchard, Philippe; Boulanger, Jim; Cournoyer, Ghislain; Couture, Félix; Gervais, Normand; Goulet, Stéphanie; Guay, Marie-Pascale; Kavanagh, Mélanie; Lemieux, Julie; Lespérance, Bernard; Letarte, Nathalie; Morneau, Mélanie; Ouellet, Jean-François; Pineau, Gilles; Rajan, Raghu; Roy, Isabelle; Samson, Benoît; Sidéris, Lucas; Vincent, François

2013-10-01

Despite the very good prognosis of endometrial cancer, a number of patients with localized disease relapse following surgery. Therefore, various adjuvant therapeutic approaches have been studied. The objective of this review is to evaluate the efficacy and safety of neoadjuvant and adjuvant therapies in patients with resectable endometrial cancer and to develop evidence-based recommendations. A review of the scientific literature published between January 1990 and June 2012 was performed. The search was limited to published phase III clinical trials and meta-analyses evaluating the efficacy of neoadjuvant or adjuvant therapies in patients with endometrial carcinoma or carcinosarcoma. A total of 23 studies and five meta-analyses were identified. The selected literature showed that in patients with a low risk of recurrence, post-surgical observation is safe and recommended in most cases. There are several therapeutic modalities available for treatment of endometrial cancers with higher risk of recurrence, including vaginal brachytherapy, external beam radiotherapy, chemotherapy, or a combination of these. Considering the evidence available to date, the CEPO recommends the following: (1)post-surgical observation for most patients with a low recurrence risk; (2)adjuvant vaginal brachytherapy for patients with an intermediate recurrence risk; (3)adjuvant pelvic radiotherapy with or without vaginal brachytherapy for patients with a high recurrence risk; addition of adjuvant chemotherapy may be considered as an option for selected patients (excellent functional status, no significant co-morbidities, poor prognostic factors); (4)adjuvant chemotherapy and pelvic radiotherapy with or without brachytherapy and para-aortic irradiation for patients with advanced disease; © 2013.

Adjuvant radiation therapy and survival for adenoid cystic carcinoma of the breast.

PubMed

Sun, Jia-Yuan; Wu, San-Gang; Chen, Shan-Yu; Li, Feng-Yan; Lin, Huan-Xin; Chen, Yong-Xiong; He, Zhen-Yu

2017-02-01

The assess the clinical value of different types of surgical procedures and further analyze the effect of adjuvant radiation therapy (RT) for adenoid cystic carcinoma (ACC) of the breast. Patients with ACC of the breast were identified using a population-based national registration database (Surveillance, Epidemiology, and End Results, SEER). The Kaplan-Meier method and Cox regression models were performed to determine the impact of the surgical procedures and adjuvant RT associated with cause-specific survival (CSS) and overall survival (OS). A total of 478 patients with ACC of the breast were identified. The median follow-up was 59 months. The 10-year CSS and OS were 87.5% and 75.3%, respectively. For the Kaplan-Meier analysis, the 5-year CSS were 96.1%, 91.8%, 90.2%, and 94.1% in patients that received lumpectomy + adjuvant RT, lumpectomy alone, mastectomy alone, and mastectomy + adjuvant RT, respectively (p = 0.026). In the multivariate Cox analyses, lumpectomy + adjuvant RT was an independent prognostic factor for CSS and OS. Patients that received lumpectomy + adjuvant RT had better survival rates than patients that underwent lumpectomy only (CSS, p = 0.018; OS, p = 0.031) and mastectomy only (CSS, p = 0.010; OS, p = 0.004). ACC of the breast has an excellent prognosis. Breast-conserving surgery is a reasonable alternative for patients with ACC of the breast, and adjuvant RT after lumpectomy improved survival rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

ALCHEMIST: Bringing Genomic Discovery and Targeted Therapies to Early-Stage Lung Cancer

PubMed Central

Gerber, DE; Oxnard, GR; Govindan, R

2016-01-01

The identification of druggable molecular alterations represents one of the greatest advances in cancer treatment. Such progress is particularly evident for lung cancer, which now has numerous molecularly defined subsets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. However, understanding of the significance of these genomic alterations is largely limited to incurable, metastatic lung cancer. ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) is a National Cancer Institute–sponsored initiative to address these questions in earlier-stage disease. PMID:25677079

Canadian Adjuvant Initiative Workshop, March 26–27, 2013—Ottawa, Canada

PubMed Central

Krishnan, Lakshmi; Twine, Susan; Gerdts, Volker; Barreto, Luis; Richards, James C

2014-01-01

Novel adjuvants hold the promise for developing effective modern subunit vaccines capable of appropriately modulating the immune response against challenging diseases such as those caused by chronic and/or intracellular pathogens and cancer. Over the past decade there has been intensive research into discovering new adjuvants, however, their translation into routine clinical use is lagging. To stimulate discussion and identify opportunities for networking and collaboration among various stakeholders, a Canadian Adjuvant Initiative Workshop was held in Ottawa. Sponsored by the National Research Council Canada, Canadian Institutes of Health Research and the Vaccine Industry Committee, a two day workshop was held that brought together key Canadian and international stakeholders in adjuvant research from industry, academia and government. To discover innovation gaps and unmet needs, the presentations covered a board range of topics in adjuvant development; criteria for selection of lead adjuvant candidates from an industry perspective, discovery research across Canada, bioprocessing needs and challenges, veterinary vaccines, Canadian vaccine trial capabilities, the Canadian regulatory framework and WHO formulation laboratory experience. The workshop concluded with a discussion on the opportunity to create a Canadian Adjuvant Development Network. This report details the key discussion points and steps forward identified for facilitating adjuvant development research in Canada. PMID:24192752

Mixed pineal mature teratoma and germinoma in two brothers of the fraternal triplets.

PubMed

Grahovac, Gordan; Alden, Tord; Nitin, Wadhwani

2017-05-01

Intracranial teratomas are rare germ cell neoplasms that contain tissues derived from all three germ cell layers and most commonly occurring during childhood. This is the first report of pineal region mixed mature teratoma and germinoma in two fraternal brothers of fraternal triplets. We report the case of a mixed mature teratoma and germinoma of the pineal region in two brothers of fraternal triplets. Older brother was initially diagnosed at the age of 11 years with the pure teratoma of the pineal region but the review of the pathology 3 years after initial surgery revealed the mixed mature teratoma with 5% germinomatous component. The younger brother was diagnosed at the age of 13 years with the mixed mature teratoma with 10% germinomatous component tumor of the pineal region. Younger brother has been treated with adjuvant chemo-radiotherapy and older brother was treated without adjuvant therapy. Both brothers had no recurrence. Pineal mature teratomas have a good prognosis, in contrast to their immature or mixed counterparts. A rigorous histological examination of the tumor samples is mandatory, in order to not omit a mixed contingent within the tumor.

Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

PubMed

Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

2017-08-01

Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

Using tablet-based technology in patient education about systemic therapy options for early-stage breast cancer: a pilot study.

PubMed

Morgan, E R; Laing, K; McCarthy, J; McCrate, F; Seal, M D

2015-10-01

Patient education in early-stage breast cancer has been shown to improve patient well-being and quality of life, but it poses a challenge given the increasingly complex regimens and time constraints in clinical practice. Technology-aided teaching in the clinic could help to improve the understanding of adjuvant systemic therapy for patients. In this prospective pilot study, we used a clinician-administered, tablet-based teaching aid to teach patients with early-stage breast cancer about adjuvant systemic therapy. Participation was offered to newly diagnosed patients with early-stage breast cancer presenting for their first medical oncology visit at a provincial cancer centre. Participants were shown a tablet-based presentation describing procedures, rationales, risks, and benefits of adjuvant systemic therapy as an adjunct to a discussion with the medical oncologist. After the clinic visit, participants completed a questionnaire measuring satisfaction with the visit and knowledge of the treatment plan discussed. The 25 patients recruited for the study had a mean age of 57 years. An offer of upfront chemotherapy alone was made to 12 participants (48%), chemotherapy with trastuzumab to 4 (16%), and hormonal therapy to 9 (36%). Correct answers to all questions related to treatment knowledge were given by 22 patients (88%). Satisfaction with the clinic visit was high (mean satisfaction score: 4.53 ± 0.1 of a possible 5). We found that a tablet-based presentation about adjuvant systemic therapy was satisfactory to patients with early-stage breast cancer and that knowledge retention after the clinic visit was high. Tablet-based teaching could be a feasible and effective way of educating patients in the breast oncology clinic and warrants further investigation in randomized studies.

Intrahepatic Cholangiocarcinoma: expert consensus statement

PubMed Central

Weber, Sharon M; Ribero, Dario; O=Reilly, Eileen M; Kokudo, Norihiro; Miyazaki, Masaru; Pawlik, Timothy M

2015-01-01

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)], but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC–CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions. PMID:26172134

Bone health and adherence to vitamin D and calcium therapy in early breast cancer patients on endocrine therapy with aromatase inhibitors.

PubMed

Bošković, Lidija; Gašparić, Maja; Petković, Marija; Gugić, Damir; Lovasić, Ingrid Belac; Soldić, Željko; Miše, Branka Petrić; Dabelić, Nina; Vazdar, Ljubica; Vrdoljak, Eduard

2017-02-01

Randomized trials involving aromatase inhibitors (AIs) in the adjuvant treatment of breast cancer patients have reported increased osteoporosis risk. Bone loss can be reduced with appropriate life style, vitamin D and calcium supplements, and with bisphosphonate therapy. The aim of this analysis was to investigate adherence to vitamin D and calcium in postmenopausal breast cancer patients receiving adjuvant non-steroidal AIs, and oncologists' adherence to the bone health guidelines. This prospective study included 438 newly diagnosed patients and those who have already been receiving non-steroidal AIs for up to 3.5 years. Median endocrine therapy duration before recruitment in the study was 10.5 months (interquartile 4.8-26.6). Densitometry was performed on 142 patients (32.4%) before initiation of endocrine therapy, and on additional 38 (8.6%) patients at second study visit. Densitometry was not performed on 258 (59%) patients. Vitamin D and calcium were prescribed to 329/438 (75.1%) patients at some point during the study. Patients who took more than 80% of the prescribed dose were considered adherent. Self-reported adherence was 88.4%. Osteoporosis was diagnosed in 24 patients (5.5%) of the total study population, bearing in mind that 258/438 (59%) patients did not have densitometry. Bisphosphonates were prescribed to 54/438 (12.3%) patients, whilst only 19 (35.2%) of those had osteoporosis. In this analysis, lack of oncologists' adherence to the bone health guidelines was observed. In addition, a significant proportion of the patients did not adhere to the vitamin D and calcium. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

PubMed

Marmor, Schelomo; Hui, Jane Yuet Ching; Huang, Jing Li; Kizy, Scott; Beckwith, Heather; Blaes, Anne H; Rueth, Natasha M; Tuttle, Todd M

2017-08-15

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P < .01) among those who received endocrine therapy plus chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P < .01) among those who received endocrine therapy plus chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017 American Cancer Society.

Trends in the Utilization of Adjuvant Vaginal Cuff Brachytherapy and/or External Beam Radiation Treatment in Stage I and II Endometrial Cancer: A Surveillance, Epidemiology, and End-Results Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Mehul K.; Cote, Michele L.; Ali-Fehmi, Rouba

2012-05-01

Purpose: The optimal adjuvant radiation treatment for endometrial carcinoma (EC) remains controversial. Adjuvant vaginal cuff brachytherapy (VB) has emerged as an increasingly common treatment modality. However, the time trends for using VB, external beam radiation therapy (EBRT), or combined therapy (VB+EBRT) have not been well characterized. We therefore examined the utilization trends of VB, EBRT, and VB+EBRT for adjuvant RT in International Federation of Gynecologic Oncology (FIGO) stage I and II EC over time. Methods and Materials: We evaluated treatment patterns for 48,122 patients with EC diagnosed between January 1995 and December 2005, using the National Cancer Institute's Surveillance, Epidemiology,more » and End Results (SEER) public use database. Chi-squared tests were used to assess differences by radiation type (VB, EBRT, and VB+EBRT) and various demographic and clinical variables. Results: Analyses were limited to 9,815 patients (20.4%) with EC who met the inclusion criteria. Among women who received adjuvant RT, the proportion receiving VB increased yearly (12.9% in 1995 compared to 32.8% in 2005 (p < 0.0001). The increasing use of VB was proportional to the decreasing use of EBRT (56.1% in 1995 to 45.8% in 2005; p < 0.0001) and VB+EBRT (31.0% in 1995 to 21.4% in 2005; p < 0.001). Conclusions: This population-based report demonstrates an increasing trend in the use of VB in the adjuvant setting after hysterectomy for treatment of women with FIGO stage I-II EC. VB alone appears to be replacing pelvic EBRT and VB+EBRT therapy in the management of stage I-II EC.« less

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

PubMed

Fujisawa, Yasuhiro; Otsuka, Fujio

2012-10-01

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in Early Stage Non–Small Cell Lung Cancer

PubMed Central

Govindan, Ramaswamy; Mandrekar, Sumithra J.; Gerber, David E.; Oxnard, Geoffrey R.; Dahlberg, Suzanne E.; Malik, Shakun; Mooney, Margaret; Abrams, Jeffrey S.; Jänne, Pasi A.; Gandara, David R.; Ramalingam, Suresh S.; Vokes, Everett E.

2015-01-01

The treatment of patients with metastatic non-small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas (TCGA) project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is a National Cancer Institute (NCI) sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine if their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)] making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo vs. erlotinib or crizotinib respectively after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture and clonal evolution and mechanisms of resistance to therapy. In this review, we describe the concept, rationale and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. PMID:26672084

Personal and clinical social support and adherence to adjuvant endocrine therapy among hormone receptor-positive breast cancer patients in an integrated health care system.

PubMed

Kroenke, Candyce H; Hershman, Dawn L; Gomez, Scarlett L; Adams, Sara R; Eldridge, Elizabeth H; Kwan, Marilyn L; Ergas, Isaac J; Kubo, Ai; Kushi, Lawrence H

2018-04-18

We evaluated associations between personal and clinical social support and non-adherence to adjuvant endocrine therapy (AET) in a large, Northern California breast cancer (BC) cohort from an integrated healthcare network. This study included 3382 women from the Pathways Study diagnosed from 2005 to 2013 with stages I-III hormone receptor-positive BC and who responded to the Medical Outcomes Study Social Support and Interpersonal Processes of Care surveys, approximately 2 months post-diagnosis. We used logistic regression to evaluate associations between tertiles of social support and non-initiation (< 2 consecutive prescription fills within a year after diagnosis). Among those who initiated treatment, we used proportional hazards regression to evaluate associations with discontinuation (≥ 90 day gap) and non-adherence (< 80% medical possession ratio). Of those who initiated AET (79%), approximately one-fourth either discontinued AET or were non-adherent. AET non-initiation was more likely in women with moderate (adjusted OR 1.18, 95% CI 0.96-1.46) or low (OR 1.30, 95% CI 1.05-1.62) versus high personal social support (P trend = 0.02). Women with moderate (HR 1.20, 95% CI 0.99-1.45) or low (HR 1.32, 95% CI 1.09-1.60) personal social support were also more likely to discontinue treatment (P trend = 0.01). Furthermore, women with moderate (HR 1.25, 95% CI 1.02-1.53) or low (HR 1.38, 95% CI 1.12-1.70) personal social support had higher non-adherence (P trend = 0.007). Associations with clinical social support and outcomes were similar. Notably, high clinical social support mitigated the risk of discontinuation when patients' personal support was moderate or low (P value = 0.04). Women with low personal or clinical social support had higher AET non-adherence. Clinician teams may need to fill support gaps that compromise treatment adherence.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

PubMed Central

García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

2014-01-01

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

Cell and molecular mechanisms of pathogenesis and treatment of cancer.

PubMed Central

Rew, D. A.

1998-01-01

Surgery remains the mainstay of treatment for most classes of human solid tumours, with the principal exception of lymphomas, but it is insufficient in many cases to guarantee cure. With few exceptions, recurrent and metastatic solid tumours continue to defy attempts to develop effective adjuvant therapies. Recent insights into tumour biology reveal an increasingly complex picture of cell and molecular processes which confer heterogeneity and resistance to treatment upon tumours. These insights may also yield new targets for more effective adjuvant therapies. PMID:9616488

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.

PubMed

Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida

2012-12-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.

Adjuvant Treatment for Older Women with Invasive Breast Cancer

PubMed Central

Jolly, Trevor A; Williams, Grant R; Bushan, Sita; Pergolotti, Mackenzi; Nyrop, Kirsten A; Jones, Ellen L; Muss, Hyman B

2016-01-01

Older women experience a large share of breast cancer incidence and death. With the projected rise in the number of older cancer patients, adjuvant chemo-, radiation and endocrine therapy management will become a key component of breast cancer treatment in older women. Many factors influence adjuvant treatment decisions including patient preferences, life expectancy and tumor biology. Geriatric assessment predicts important outcomes, identifies key deficits, and can aid in the decision making process. This review utilizes clinical vignettes to illustrate core principles in adjuvant management of breast cancer in older women and suggests an approach incorporating life expectancy and geriatric assessment. PMID:26767315

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate.

PubMed

Feng, Yan-Ru; Jin, Jing; Ren, Hua; Wang, Xin; Wang, Shu-Lian; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Tang, Yuan; Li, Ning; Liu, Xin-Fan; Fang, Hui; Yu, Zi-Hao; Li, Ye-Xiong

2017-03-09

In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence. In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m 2 ) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included. Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036). In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Adjuvant effects of saponins on animal immune responses*

PubMed Central

Rajput, Zahid Iqbal; Hu, Song-hua; Xiao, Chen-wen; Arijo, Abdullah G.

2007-01-01

Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed. PMID:17323426

Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey.

PubMed

Basaran, Gul; Turhal, Nazım Serdar; Cabuk, Devrim; Yurt, Nevin; Yurtseven, Gul; Gumus, Mahmut; Teomete, Mehmet; Dane, Faysal; Yumuk, Perran Fulden

2011-06-01

Weight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/- taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases had statistically significant impact on weight gain following adjuvant therapy in breast cancer patients (P = 0.000, P = 0.008, P = 0.015 and P = 0.017 respectively). This study shows that Turkish women with early breast cancer gain weight after adjuvant systemic therapy, in line with European and American counterparts. This increase in weight is maintained at least one year after adjuvant therapy. Given the adverse consequences of weight gain in terms of both breast cancer prognosis and general health, it is necessary to inform patients about this change and to develop strategies for weight maintenance during and after systemic therapy.

Expression of NF-κB p50 in Tumor Stroma Limits the Control of Tumors by Radiation Therapy

PubMed Central

Crittenden, Marka R.; Cottam, Benjamin; Savage, Talicia; Nguyen, Cynthia; Newell, Pippa; Gough, Michael J.

2012-01-01

Radiation therapy aims to kill cancer cells with a minimum of normal tissue toxicity. Dying cancer cells have been proposed to be a source of tumor antigens and may release endogenous immune adjuvants into the tumor environment. For these reasons, radiation therapy may be an effective modality to initiate new anti-tumor adaptive immune responses that can target residual disease and distant metastases. However, tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice, there is an influx of tumor macrophages that ultimately polarize towards immune suppression. We demonstrate using in vitro models that this polarization is mediated by transcriptional regulation by NFκB p50, and that in mice lacking NFκB p50, radiation therapy is more effective. We propose that despite the opportunity for increased antigen-specific adaptive immune responses, the intrinsic processes of repair following radiation therapy may limit the ability to control residual disease. PMID:22761754

Maintenance treatment of recurrent ovarian cancer: Is it ready for prime time?

PubMed

DiSilvestro, Paul; Alvarez Secord, Angeles

2018-06-05

Approximately 1% of women in the United States will be diagnosed with epithelial ovarian cancer (EOC) during their lifetime. It is most likely to present at a more advanced stage, requiring aggressive therapeutic measures, and most women will succumb to this illness. Due to advancements in therapy, the oncology community has begun to shift its focus to molecular targeted agents, alternative dosing schedules, and maintenance therapy. Women who achieve a response to initial adjuvant chemotherapy may be candidates for maintenance therapy, with the goal of inducing a lasting remission or prolonging the disease-free interval before recurrence. The rationale for maintenance therapy is to delay disease progression by eliminating residual, slowly-dying cancerous cells, or impeding cell turnover. This review discusses the goals of maintenance therapy for EOC with antiangiogenic agents or poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and reviews clinical studies that have demonstrated improvements in survival outcomes. The side-effect profiles for PARP inhibitors and the implications for preserving quality of life during maintenance therapy will also be discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

An Observational Study to Examine Changes in Metabolic Syndrome Components in Breast Cancer Patients Receiving Neoadjuvant or Adjuvant Chemotherapy

PubMed Central

Dieli-Conwright, Christina M.; Wong, Louise; Waliany, Sarah; Bernstein, Leslie; Salehian, Behrouz; Mortimer, Joanne E.

2016-01-01

BACKGROUND We sought to determine the effect of chemotherapy on the development of metabolic syndrome (MetS) in premenopausal and postmenopausal women undergoing (neo) adjuvant therapy for early stage breast cancer. METHODS Eighty-six women with early stage (I-III) breast cancer who were free from clinically diagnosed MetS (defined as three out of five components of MetS) were prospectively tested for presence of the five components of MetS within one week before initiating and after completing (neo) adjuvant chemotherapy. The five components of MetS measured were waist circumference, blood pressure, and fasting levels of blood glucose, triglycerides, and high-density lipoprotein cholesterol. Anthropometrics (body weight, percent body fat, fat mass), lipid profile (total cholesterol, low-density lipoprotein cholesterol), glucose metabolism (insulin, homeostatic model assessment-insulin resistance, glycated hemoglobin), and inflammation (C-reactive protein) were also examined before initiating and after completing treatment. RESULTS The study included 46 premenopausal and 40 postmenopausal women. All individual MetS components and overall MetS score were statistically significantly increased (p<0.01) after chemotherapy. Body weight, percent body fat, fat mass, lipids, glucose metabolism, and inflammation were also statistically significantly increased (p<0.01). CONCLUSION A 12–18 week course of chemotherapy statistically significantly increases MetS and related anthropometrics, biomarkers of glucose metabolism, and inflammation in early stage breast cancer patients with no pre-existing MetS. Lifestyle interventions such as diet and exercise may be preventive approaches to employ during chemotherapy to reduce the onset of MetS in breast cancer patients. PMID:27219902

Phase II Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: 5-Year Clinical Outcomes ECOG-ACRIN Cancer Research Group E3204.

PubMed

Landry, Jerome C; Feng, Yang; Prabhu, Roshan S; Cohen, Steven J; Staley, Charles A; Whittington, Richard; Sigurdson, Elin Ruth; Nimeiri, Halla; Verma, Udit; Benson, Al Bowen

2015-06-01

The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m(2) b.i.d. Monday-Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80%. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive. The 5-year relapse-free survival rate was 81%. Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

PubMed Central

Romond, Edward H.; Jeong, Jong-Hyeon; Rastogi, Priya; Swain, Sandra M.; Geyer, Charles E.; Ewer, Michael S.; Rathi, Vikas; Fehrenbacher, Louis; Brufsky, Adam; Azar, Catherine A.; Flynn, Patrick J.; Zapas, John L.; Polikoff, Jonathan; Gross, Howard M.; Biggs, David D.; Atkins, James N.; Tan-Chiu, Elizabeth; Zheng, Ping; Yothers, Greg; Mamounas, Eleftherios P.; Wolmark, Norman

2012-01-01

Purpose Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2–positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab. PMID:22987084

Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia.

PubMed

Dhanesha, Nirav; Vázquez-Rosa, Edwin; Cintrón-Pérez, Coral J; Thedens, Daniel; Kort, Alexa J; Chuong, Vicky; Rivera-Dompenciel, Adriana M; Chauhan, Anil K; Leira, Enrique C; Pieper, Andrew A

2018-05-01

Exogenous administration of uric acid, a naturally occurring antioxidant that scavenges reactive oxygen species in vasculature, has shown protective efficacy in both rodent models of stroke and human stroke patients in Spain as an adjuvant treatment to mechanical thrombectomy. Before clinical trials can be initiated in the United States, however, confirmation of efficacy in alternative preclinical models is required in accordance with stroke therapy academic industry roundtable-RIGOR criteria. To date, preclinical efficacy has only been established in the acute setting in male rodents. To address this need, we subjected 7- to 9-week old ovariectomized female mice to filament-induced right middle cerebral artery ischemia and reperfusion, an established preclinical model of mechanical thrombectomy. Fidelity of the procedure was monitored by laser Doppler flowmetry. A separate lab randomly assigned animals to vehicle versus uric acid infusion, which was initiated immediately after 45 minutes of reperfusion. Poststroke analysis of infarction size and neurologic function were conducted by investigators blind to treatment group, with a 7-day primary endpoint and a 3-day intermediary analysis at 1and. Infarct size and neurologic function at 7 days poststroke were significantly improved in uric acid-treated animals, relative to vehicle. Efficacy of uric acid in preclinical models of stroke is now expanded to include female mice analyzed at a later time point than has been investigated previously. These results support stroke therapy academic industry roundtable-RIGOR driven determination of the suitability of acute administration of uric acid as an adjuvant to mechanical thrombectomy in clinical trials for patients with stroke. Published by Elsevier Inc.

Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG) Study

PubMed Central

Figer, Arie; Nissan, Aviram; Shani, Adi; Borovick, Riva; Stiener, Mariana; Baras, Mario; Freund, Herbert R.; Sulkes, Aaron; Stojadinovic, Alexander; Peretz, Tamar

2011-01-01

Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC). This study evaluates long-term (10-year) outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV) or 5-FU/Levamisole (5FU+LEV). Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months. Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02) and gastrointestinal toxicity with 5FU+LV (p=0.03). Female patients treated with 5FU+LEV had improved overall survival. Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset. PMID:21475636

Application of “Systems Vaccinology” to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines

PubMed Central

Lewis, David J. M.; Lythgoe, Mark P.

2015-01-01

Advances in “omics” technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing. PMID:26380327

Combination antiretroviral therapy and cancer risk.

PubMed

Borges, Álvaro H

2017-01-01

To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer risk. The relationship between cART exposure and cancer risk is complex and nuanced. It is an intriguing fact that, whether initiated during severe immunosuppression or not, cART reduces risk of Kaposi sarcoma and NHL. Further research should identify mediators of the benefit of immediate cART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.

Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer.

PubMed

Ribi, K; Aldridge, J; Phillips, K-A; Thompson, A; Harvey, V; Thürlimann, B; Cardoso, F; Pagani, O; Coates, A S; Goldhirsch, A; Price, K N; Gelber, R D; Bernhard, J

2012-05-08

In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low. Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute.

Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy.

PubMed

Frank, Jennifer Sandson; Vance, David E; Triebel, Kristen L; Meneses, Karen M

2015-12-01

Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.

Adjuvant Therapy in Early-Stage Endometrial Cancer: A Systematic Review of the Evidence, Guidelines, and Clinical Practice in the U.S.

PubMed Central

Latif, Nawar A.; Haggerty, Ashley; Jean, Stephanie; Lin, Lilie

2014-01-01

Endometrial cancer is the most common gynecologic malignancy in the U.S., with an increasing incidence likely secondary to the obesity epidemic. Surgery is usually the primary treatment for early stage endometrial cancer, followed by adjuvant therapy in selected cases. This includes radiation therapy [RT] with or without chemotherapy, based on stratification of patients into categories dependent on their future recurrence risk. Several prospective trials (PORTEC-1, GOG#99, and PORTEC-2) have shown that the use of adjuvant RT in the intermediate risk (IR) and the high-intermediate risk (HIR) groups decreases locoregional recurrence (LRR) but has no effect on overall survival. The ad hoc analyses from these studies have shown that an even larger LRR risk reduction was seen within the HIR group compared with the IR group. Vaginal brachytherapy is as good as external beam radiotherapy in controlling vaginal relapse where the majority of recurrence occur, and with less toxicity. In the high-risk group, multimodality therapy (chemotherapy and RT) may play a significant role. Although adjuvant RT has been evaluated in many cost-effectiveness studies, high-quality data in this area are still lacking. The uptake of the above prospective trial results in the U.S. has not been promising. Factors that are driving current practices and defining quality-of-care measures for patients with early-stage disease are what future studies need to address. PMID:24821823

Primary Spinal Cord Melanoma: A Case Report and a Systemic Review of Overall Survival.

PubMed

Zhang, Mingzhe; Liu, Raynald; Xiang, Yi; Mao, Jianhui; Li, Guangjie; Ma, Ronghua; Sun, Zhaosheng

2018-06-01

The incidence of primary spinal cord melanoma (PSCM) is rare. Several case series and case reports have been published in the literature. However, the predictive factors of PSCM survival and management options are not discussed in detail. We present a case of PSCM; total resection was achieved and chemotherapy was given postoperatively. A comprehensive search was performed on PubMed's electronic database using the words "primary spinal cord melanoma." Survival rates with various gender, location, treatment, and metastasis condition were collected from the published articles and analyzed. Fifty nine cases were eligible for the survival analysis; 54% were male and 46% were female. Patient sex did not influence overall survival. The most common location was the thorax. Patient sex and tumor location did not influence overall survival. The major presenting symptoms were weakness and paresthesia of the extremities. Metastasis or dissemination was noted in 45.16% of 31 patients. In the Kaplan-Meier survival analysis, patients who had metastasis had the worst prognosis. Extent of resection was not related to mortality. Patients who received surgery and surgery with adjuvant therapy had a better median survival than did those who had adjuvant therapy alone. Prognosis was worst in those patients who underwent only adjuvant therapy without surgery (5 months). Surgery is the first treatment of choice in treating PSCM. The goal of tumor resection is to reduce symptoms. Adjuvant therapy after surgery had a beneficial effect on limiting the metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Does thalidomide prolong survival in dogs with splenic haemangiosarcoma?

PubMed

Bray, J P; Orbell, G; Cave, N; Munday, J S

2018-02-01

To investigate thalidomide as an adjuvant treatment for canine haemangiosarcoma. Fifteen dogs with splenic haemangiosarcoma, initially treated by splenectomy, were included. Following recovery from surgery, all dogs received thalidomide continuously until their death. Tumour stage was established using CT scans of the chest and abdomen immediately before starting thalidomide treatment and again three months later. Cause of death was confirmed by post mortem examination. The median survival time of dogs receiving thalidomide was 172 days (95% confidence interval: 93 to 250 days). Five dogs (33% of the population receiving thalidomide) survived more than 1 year (range 458 to 660 days) after surgery. Dogs with stage 2 disease that received thalidomide also had a longer survival time than dogs with stage 3 disease (median survival time 303 versus 40 days). Of 15 dogs, 13 died from metastatic haemangiosarcoma. Treatment using thalidomide may improve survival of dogs with splenic haemangiosarcoma and should be considered a possible adjuvant therapy. © 2017 British Small Animal Veterinary Association.

Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole.

PubMed

Viale, Giuseppe; Giobbie-Hurder, Anita; Regan, Meredith M; Coates, Alan S; Mastropasqua, Mauro G; Dell'Orto, Patrizia; Maiorano, Eugenio; MacGrogan, Gaëtan; Braye, Stephen G; Ohlschlegel, Christian; Neven, Patrick; Orosz, Zsolt; Olszewski, Wojciech P; Knox, Fiona; Thürlimann, Beat; Price, Karen N; Castiglione-Gertsch, Monica; Gelber, Richard D; Gusterson, Barry A; Goldhirsch, Aron

2008-12-01

To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.

H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy.

PubMed

Rahier, Jean-François; Papay, Pavol; Salleron, Julia; Sebastian, Shaji; Marzo, Manuela; Peyrin-Biroulet, Laurent; Garcia-Sanchez, Valle; Fries, Walter; van Asseldonk, Dirk P; Farkas, Klaudia; de Boer, Nanne K; Sipponen, Taina; Ellul, Pierre; Louis, Edouard; Peake, Simon T C; Kopylov, Uri; Maul, Jochen; Makhoul, Badira; Fiorino, Gionata; Yazdanpanah, Yazdan; Chaparro, Maria

2011-04-01

Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy. The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey-Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded. Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p < 0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p = 0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p < 0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%). Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.

Towards an understanding of the adjuvant action of aluminium

PubMed Central

Marrack, Philippa; McKee, Amy S.; Munks, Michael W.

2011-01-01

The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. PMID:19247370

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer

PubMed Central

Wojcieszek, Piotr; Białas, Brygida

2012-01-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years. PMID:23378855

Evaluation of the effect of losartan and methotrexate combined therapy in adjuvant-induced arthritis in rats.

PubMed

Refaat, Rowaida; Salama, Mona; Abdel Meguid, Elham; El Sarha, Ashgan; Gowayed, Mennatallah

2013-01-05

There is increasing body of evidence documenting the involvement of angiotensin II in inflammatory diseases. Moreover the up-regulation of angiotensin II AT(1) receptors in the synovium of rheumatoid arthritis patients has been previously described. This study aimed at investigating the anti-inflammatory effect of losartan, the selective angiotensin II AT(1) receptor blocker, and comparing the efficacy of methotrexate alone and in combination with losartan in adjuvant arthritis in rats. Twelve days post adjuvant injection, Sprague-Dawley rats were treated with methotrexate (1mg/kg/week), losartan (20mg/kg/day) and their combination for 15 days. Severity of arthritis was assessed by hind paw swelling, arthrogram scores. Serum was analyzed for measurement of albumin, C-reactive protein (CRP), nitrite/nitrate concentrations, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), aspartate transaminase (AST) and alanine transaminase (ALT). Histopathological examination was done for hind paws and livers. Methotrexate and losartan monotherapies significantly reduced all parameters of inflammation and arthritis with better results in the methotrexate group except for the transaminases where losartan caused more significant reduction in their serum levels. The combined therapy showed better results than methotrexate and losartan alone. Hind paws showed better improvement of inflammatory cell infiltration and bone resorption in the combined therapy group. Disturbances in liver architecture and fibrosis caused by adjuvant arthritis were reverted to normal status in the combined therapy group in contrast to losartan and methotrexate monotherapies. In conclusion, methotrexate and losartan combined therapy provided more effective anti-inflammatory and hepatoprotective effects than either drug alone. Copyright © 2012 Elsevier B.V. All rights reserved.

Distinctive features of gastrointestinal stromal tumors arising from the colon and rectum

PubMed Central

Zhu, Rebecca; Liu, Fangfang; Grisotti, Gabriella; Pérez-Irizarry, Javier; Cha, Charles H.; Johnson, Caroline H.; Boffa, Daniel J.; Han, Dale; Johung, Kimberly L.; Zhang, Yawei

2018-01-01

Background Colon and rectal gastrointestinal stromal tumors (GISTs) are rare and poorly characterized. Because the majority of treatment guidelines for GISTs are extrapolated from tumors of gastric and small bowel origin, our aim was to better characterize the unique clinicopathologic features and prognostic factors of colon and rectal GISTs to guide clinical care. Methods The National Cancer Data Base (NCDB) was queried from 2006 to 2013 for cases of GISTs in the stomach, colon, and rectum. Patient demographics, clinical characteristics, and survival were compared. Results A total of 11,302 gastric GISTs were compared to 398 colon and 393 rectal GISTs. After propensity matching, compared to gastric GISTs, rectal GISTs had improved overall survival (HR =0.695, P=0.0264), while colon GISTs had worse overall survival (HR =1.6, P=0.0005). Surgical treatment for rectal GISTs was more likely to be local excision compared to colonic GISTs (51.1% vs. 8.4%, P<0.0001). Colon and gastric GISTs were less likely to receive systemic therapy compared to rectal GISTs (34.2% vs. 34.0% vs. 55.2%, P<0.0001). Adjuvant systemic therapy conveyed a survival advantage to rectal GISTs (HR =0.47, P=0.042) but not colon GISTs. There was a negative impact of adjuvant therapy on survival for colon GISTs <5 cm (HR =3.41, P=0.032). Conclusions Patients with rectal GISTs live longer than those with colon and gastric GISTs, and adjuvant therapy prolongs their survival. Many patients with colon GISTs are treated with adjuvant therapy despite a detrimental effect on survival. Tumor biology of colon and rectal GISTs needs to be better studied to tailor treatment.

Pilot study of acupuncture for the treatment of joint symptoms related to adjuvant aromatase inhibitor therapy in postmenopausal breast cancer patients.

PubMed

Crew, Katherine D; Capodice, Jillian L; Greenlee, Heather; Apollo, Arlyn; Jacobson, Judith S; Raptis, George; Blozie, Kimberly; Sierra, Alex; Hershman, Dawn L

2007-12-01

Aromatase inhibitors (AIs) have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. However, patients receiving AIs may experience joint symptoms, which may lead to early discontinuation of this effective therapy. We hypothesize that acupuncture is a safe and effective treatment for AI-induced arthralgias. Postmenopausal women with early-stage breast cancer who had self-reported musculoskeletal pain related to adjuvant AI therapy were randomized in a crossover study to receive acupuncture twice weekly for 6 weeks followed by observation or vice-versa. The intervention included full body and auricular acupuncture, and a joint-specific point prescription. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life measure, and serum levels of inflammatory markers, IL-1 beta and TNF-alpha. Twenty-one women were enrolled and two discontinued early. From baseline to the end of treatment, patients reported improvement in the mean BPI-SF worst pain scores (5.3 to 3.3, p = 0.01), pain severity (3.7 to 2.5, p = 0.02), and pain-related functional interference (3.1 to 1.7, p = 0.02), as well as the WOMAC function subscale and FACT-G physical well-being (p = 0.02 and 0.04, respectively). No adverse events were reported. In this pilot study, acupuncture reduced AI-related joint symptoms and improved functional ability and was well-tolerated. Musculoskeletal side effects are common among breast cancer survivors on adjuvant AI therapy, therefore, effective treatments are needed for symptom relief and to improve adherence to these life-saving medications.

Prognostic stratification model for patients with stage I non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors.

PubMed

Kang, Yeon-Koo; Song, Yoo Sung; Cho, Sukki; Jheon, Sanghoon; Lee, Won Woo; Kim, Kwhanmien; Kim, Sang Eun

2018-05-01

In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SUL max ) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SUL max on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SUL max  ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SUL max> 1.9 and observed STAS. This model exhibited significant predictive power for RFS. We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed

Korbelik, M; Naraparaju, V R; Yamamoto, N

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed Central

Korbelik, M.; Naraparaju, V. R.; Yamamoto, N.

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours. PMID:9010027

[Music as an adjuvant treatment for anxiety in pediatric oncologic patients].

PubMed

Sepúlveda-Vildósola, Ana Carolina; Herrera-Zaragoza, Octavio René; Jaramillo-Villanueva, Leonel; Anaya-Segura, Armando

2014-01-01

Music has been used as adjuvant therapy for anxiety and it is based on scientific principles. Tone, rhythm, harmony and time are crucial for its efficacy. Chemotherapy treatment frequently produces important stress in pediatric patients. This may delay treatment occasionally. Our objective was to determine if adjuvant therapy with music reduces anxiety in pediatric oncologic patients under ambulatory chemotherapy. Time series design. We included patients from 8 to 16 years of age who received ambulatory intravenous chemotherapy at the Hospital de Pediatría, Centro Médico Nacional Siglo XXI. They received treatment as usual on the first day, and music therapy during the second day of chemotherapy. A visual scale was used to categorize the level of anxiety prior and after treatment on both days. We included 22 patients. All patients experienced both moderate and high levels of anxiety prior to chemotherapy treatment on both days. There was a statistically significant reduction of anxiety on both groups after chemotherapy, but with lower levels of anxiety in the intervention group. There is an additional benefit with the use of music therapy in the reduction of anxiety in pediatric patients who receive ambulatory chemotherapy.

Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

PubMed Central

Gulati, Geeta; Heck, Siri Lagethon; Ree, Anne Hansen; Hoffmann, Pavel; Schulz-Menger, Jeanette; Fagerland, Morten W.; Gravdehaug, Berit; von Knobelsdorff-Brenkenhoff, Florian; Bratland, Åse; Storås, Tryggve H.; Hagve, Tor-Arne; Røsjø, Helge; Steine, Kjetil; Geisler, Jürgen; Omland, Torbjørn

2016-01-01

Abstract Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function. PMID:26903532

Development of Decision Support Intervention for Black Women with Breast Cancer

PubMed Central

Williams, Karen Patricia; Harrison, Toni Michelle; Jennings, Yvonne; Lucas, Wanda; Stephen, Juleen; Robinson, Dana; Mandelblatt, Jeanne S.; Taylor, Kathryn L.

2011-01-01

Adjuvant therapy improves breast cancer survival but is underutilized by Black women. Few interventions have addressed this problem. This preliminary report describes the process we used to develop a decision support intervention for Black women eligible for adjuvant therapy. Aims were to use qualitative methods to describe factors that influence Black women’s adjuvant therapy decisions, use these formative data to develop messages for a treatment decision-support intervention, and pilot test the acceptability and utility of the intervention with community members and newly diagnosed women. Thirty-four in-depth interviews were conducted with breast cancer patients in active treatment, survivors and cancer providers to gather qualitative data. Participant ages ranged from 38 to 69 years. A cultural framework was used to analyze the data and to inform intervention messages. Most women relied on their providers for treatment recommendations. Several women reported problems communicating with providers and felt unprepared to ask questions and discuss adjuvant treatment options. Other factors related to treatment experiences were: spiritual coping, collectivism, and sharing breast cancer experiences with other Black survivors. Using these formative data, we developed an intervention that is survivor-based and includes an in-person session which incorporates sharing personal stories, communication skills training and decision support. Intervention materials were reviewed by community members, researchers/clinicians and patients newly diagnosed with breast cancer. Patients reported satisfaction with the intervention and felt better prepared to talk with providers. The intervention will be tested in a randomized trial to enhance decision support and increase use of indicated adjuvant treatment. PMID:19267384

Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.

PubMed

Lonardi, S; Sobrero, A; Rosati, G; Di Bartolomeo, M; Ronzoni, M; Aprile, G; Massida, B; Scartozzi, M; Banzi, M; Zampino, M G; Pasini, F; Marchetti, P; Cantore, M; Zaniboni, A; Rimassa, L; Ciuffreda, L; Ferrari, D; Barni, S; Zagonel, V; Maiello, E; Rulli, E; Labianca, R

2016-11-01

Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations. NCT00646607. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol

2015-07-01

Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A totalmore » of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.« less

Health related quality of life of women in TEACH, a randomised placebo controlled adjuvant trial of lapatinib in early stage Human Epidermal Growth Factor Receptor (HER2) overexpressing breast cancer.

PubMed

Boyle, Frances M; Smith, Ian E; O'Shaughnessy, Joyce; Ejlertsen, Bent; Buzdar, Aman U; Fumoleau, Pierre; Gradishar, William; Martin, Miguel; Moy, Beverly; Piccart-Gebhart, Martine; Pritchard, Kathleen I; Lindquist, Deborah; Amonkar, Mayur; Huang, Yingjie; Rappold, Erica; Williams, Lisa S; Wang-Silvanto, Jing; Kaneko, Tomomi; Finkelstein, Dianne M; Goss, Paul E

2015-04-01

To evaluate health related quality of life (HRQOL) in TEACH, a phase III randomized placebo controlled trial of 12 months of adjuvant lapatinib in HER2 positive (HER2+) early breast cancer which demonstrated marginal benefit in disease-free survival. Women on TEACH completed the Short Form 36-item health survey (version2; SF-36v2) at the baseline, six and 12 months after therapy initiation and six monthly thereafter. Mean changes were compared between treatment groups for two summary measures (Physical and Mental Component Summary scores; PCS and MCS) and eight domain measures (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health), and in patients discontinuing therapy. A five-point change was deemed a Minimally Clinically Important Difference (MCID). Response analysis compared the proportion of patients demonstrating a MCID in HRQOL, and a regression analysis identified predictors of worsening HRQOL. 3074 (97%) subjects completed baseline SF-36v2. During the initial 12 months, summary SF-36v2 scores decreased in both arms but did not reach Minimally Clinically Important Difference (MCID) despite significant incidences of diarrhoea and rash in lapatinib treated patients. At six months, women receiving lapatinib had more significant reductions (p < 0.01 versus placebo) in social functioning. Early treatment discontinuations were more frequent on lapatinib (32% versus 18%), and were associated with more substantial decrements of HRQOL in both arms. For those discontinuing primarily due to adverse events, decrements in HRQOL reached MCID in Mental Summary scores (MCS) only. Lower baseline HRQOL was a significant predictor of worsening HRQOL (p < 0.05). Despite frequent but usually mild toxicities, adjuvant lapatinib is not associated with clinically significant decreases in overall HRQOL. These placebo-controlled results may also help to inform physicians and patients using lapatinib in metastatic HER2 positive breast cancer. GlaxoSmithKline. The AVON Foundation NY supported PEG, DF and BM and The Friends of the Mater Foundation supported FB. Copyright © 2015 Elsevier Ltd. All rights reserved.

Retrospective study of management of uterine sarcomas at Oxford 1990-1998: role of adjuvant treatment.

PubMed

Riddle, P J; Echeta, C B; Manek, S; Lavery, B A; Charnock, F M L; Mackenzie, I; Ganesan, T S

2002-02-01

We report a retrospective study of 47 consecutive patients with uterine sarcoma treated at the Churchill Hospital in Oxford between 1990-1998. The mainstay of treatment was surgery with adjuvant chemotherapy and radiotherapy reserved for selected patients with early stage disease. Overall 1 and 2 year survival was 49% and 30% respectively compared with 73% and 55% in the group who received adjuvant chemotherapy/radiotherapy. Median survival was 11 months for the group as a whole compared to 32.9 months in the adjuvant therapy group. This is a retrospective review with small numbers and considerable selection bias, however, given the poor survival of patients with this disease, adjuvant treatment should be considered in future trials of patients with uterine sarcoma.

ALCHEMIST: Bringing genomic discovery and targeted therapies to early-stage lung cancer.

PubMed

Gerber, D E; Oxnard, G R; Govindan, R

2015-05-01

The identification of druggable molecular alterations represents one of the greatest advances in cancer treatment. Such progress is particularly evident for lung cancer, which now has numerous molecularly defined subsets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. However, understanding of the significance of these genomic alterations is largely limited to incurable, metastatic lung cancer. ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) is a National Cancer Institute-sponsored initiative to address these questions in earlier-stage disease. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Clinical utility of gene expression profiling data for clinical decision-making regarding adjuvant therapy in early stage, node-negative breast cancer: a case report.

PubMed

Schuster, Steven R; Pockaj, Barbara A; Bothe, Mary R; David, Paru S; Northfelt, Donald W

2012-09-10

Breast cancer is the most common malignancy among women in the United States with the second highest incidence of cancer-related death following lung cancer. The decision-making process regarding adjuvant therapy is a time intensive dialogue between the patient and her oncologist. There are multiple tools that help individualize the treatment options for a patient. Population-based analysis with Adjuvant! Online and genomic profiling with Oncotype DX are two commonly used tools in patients with early stage, node-negative breast cancer. This case report illustrates a situation in which the population-based prognostic and predictive information differed dramatically from that obtained from genomic profiling and affected the patient's decision. In light of this case, we discuss the benefits and limitations of these tools.

Cognitive function after the initiation of adjuvant endocrine therapy in early-stage breast cancer: an observational cohort study.

PubMed

Ganz, Patricia A; Petersen, Laura; Castellon, Steven A; Bower, Julienne E; Silverman, Daniel H S; Cole, Steven W; Irwin, Michael R; Belin, Thomas R

2014-11-01

This report examines cognitive complaints and neuropsychological (NP) testing outcomes in patients with early-stage breast cancer after the initiation of endocrine therapy (ET) to determine whether this therapy plays any role in post-treatment cognitive complaints. One hundred seventy-three participants from the Mind Body Study (MBS) observational cohort provided data from self-report questionnaires and NP testing obtained at enrollment (T1, before initiation of ET), and 6 months later (T2). Bivariate analyses compared demographic and treatment variables, cognitive complaints, depressive symptoms, quality of life, and NP functioning between those who received ET versus not. Multivariable linear regression models examined predictors of cognitive complaints at T2, including selected demographic variables, depressive symptoms, ET use, and other medical variables, along with NP domains that were identified in bivariate analyses. Seventy percent of the 173 MBS participants initiated ET, evenly distributed between tamoxifen or aromatase inhibitors. ET-treated participants reported significantly increased language and communication (LC) cognitive complaints at T2 (P = .003), but no significant differences in NP test performance. Multivariable regression on LC at T2 found higher LC complaints significantly associated with T1 LC score (P < .001), ET at T2 (P = .004), interaction between ET and past hormone therapy (HT) (P < .001), and diminished improvement in NP psychomotor function (P = .05). Depressive symptoms were not significant (P = .10). Higher LC complaints are significantly associated with ET 6 months after starting treatment and reflect diminished improvements in some NP tests. Past HT is a significant predictor of higher LC complaints after initiation of ET. © 2014 by American Society of Clinical Oncology.

Cognitive Function After the Initiation of Adjuvant Endocrine Therapy in Early-Stage Breast Cancer: An Observational Cohort Study

PubMed Central

Ganz, Patricia A.; Petersen, Laura; Castellon, Steven A.; Bower, Julienne E.; Silverman, Daniel H.S.; Cole, Steven W.; Irwin, Michael R.; Belin, Thomas R.

2014-01-01

Purpose This report examines cognitive complaints and neuropsychological (NP) testing outcomes in patients with early-stage breast cancer after the initiation of endocrine therapy (ET) to determine whether this therapy plays any role in post-treatment cognitive complaints. Patients and Methods One hundred seventy-three participants from the Mind Body Study (MBS) observational cohort provided data from self-report questionnaires and NP testing obtained at enrollment (T1, before initiation of ET), and 6 months later (T2). Bivariate analyses compared demographic and treatment variables, cognitive complaints, depressive symptoms, quality of life, and NP functioning between those who received ET versus not. Multivariable linear regression models examined predictors of cognitive complaints at T2, including selected demographic variables, depressive symptoms, ET use, and other medical variables, along with NP domains that were identified in bivariate analyses. Results Seventy percent of the 173 MBS participants initiated ET, evenly distributed between tamoxifen or aromatase inhibitors. ET-treated participants reported significantly increased language and communication (LC) cognitive complaints at T2 (P = .003), but no significant differences in NP test performance. Multivariable regression on LC at T2 found higher LC complaints significantly associated with T1 LC score (P < .001), ET at T2 (P = .004), interaction between ET and past hormone therapy (HT) (P < .001), and diminished improvement in NP psychomotor function (P = .05). Depressive symptoms were not significant (P = .10). Conclusion Higher LC complaints are significantly associated with ET 6 months after starting treatment and reflect diminished improvements in some NP tests. Past HT is a significant predictor of higher LC complaints after initiation of ET. PMID:25267747

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

PubMed Central

de Oliveira, Leandro Licursi; Coltri, Kely Cristine; Cardoso, Cristina Ribeiro Barros; Roque-Barreira, Maria-Cristina; Panunto-Castelo, Ademilson

2008-01-01

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans. PMID:18335066

Vaccine Adjuvants: from 1920 to 2015 and Beyond

PubMed Central

Di Pasquale, Alberta; Preiss, Scott; Tavares Da Silva, Fernanda; Garçon, Nathalie

2015-01-01

The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190

ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Govindan, Ramaswamy; Mandrekar, Sumithra J; Gerber, David E; Oxnard, Geoffrey R; Dahlberg, Suzanne E; Chaft, Jamie; Malik, Shakun; Mooney, Margaret; Abrams, Jeffrey S; Jänne, Pasi A; Gandara, David R; Ramalingam, Suresh S; Vokes, Everett E

2015-12-15

The treatment of patients with metastatic non-small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is an NCI-sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early-stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine whether their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)], making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively, after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture, clonal evolution, and mechanisms of resistance to therapy. In this review, we describe the concept, rationale, and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. Clin Cancer Res; 21(24); 5439-44. ©2015 AACR. ©2015 American Association for Cancer Research.

Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

PubMed

Cercek, Andrea; Roxburgh, Campbell S D; Strombom, Paul; Smith, J Joshua; Temple, Larissa K F; Nash, Garrett M; Guillem, Jose G; Paty, Philip B; Yaeger, Rona; Stadler, Zsofia K; Seier, Kenneth; Gonen, Mithat; Segal, Neil H; Reidy, Diane L; Varghese, Anna; Shia, Jinru; Vakiani, Efsevia; Wu, Abraham J; Crane, Christopher H; Gollub, Marc J; Garcia-Aguilar, Julio; Saltz, Leonard B; Weiser, Martin R

2018-03-22

Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases. To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC. A retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified. Of the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT). Treatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK. Of the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort. Our findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria

PubMed Central

Hiben, Mebrahtom Gebrelibanos; Sibhat, Gereziher Gebremedhin; Fanta, Biruk Sintayehu; Gebrezgi, Haile Desta; Tesema, Shewaye Belay

2015-01-01

The emergence of malarial resistance to most antimalarial drugs is the main factor driving the continued effort to identify/discover new agents for combating the disease. Moreover, the unacceptably high mortality rate in severe malaria has led to the consideration of adjuvant therapies. Senna singueana leaves are traditionally used against malaria and fever. Extracts from the leaves of this plant demonstrated in vitro and in vivo antioxidant activities, which in turn could reduce the severity of malaria. Extracts from the root bark of this plant exhibited antiplasmodial activity; however, the leaves are the more sustainable resource. Thus, S. singueana leaf was selected for in vivo evaluation as a potential alternative or adjuvant therapy for malaria. Using malaria [Plasmodium berghei ANKA, chloroquine (CQ) sensitive]-infected Swiss albino mice of both sexes, 70% ethanol extract of S. singueana leaves (alone and in combination with CQ) was tested for antimalarial activity and adjuvancy potential. The 4-day suppressive test was used to evaluate antimalarial activity. The dose of S. singueana extract administered was safe to mice and exhibited some parasite suppression effect: extract doses of 200 mg/kg/d, 400 mg/kg/d, and 800 mg/kg/d caused 34.54%, 44.52%, and 47.32% parasite suppression, respectively. Concurrent administration of the extract with CQ phosphate at varied dose levels indicated that the percentage of parasite suppression of this combination was higher than administering CQ alone, but less than the sum of the effects of the extract and CQ acting separately. In conclusion, the study indicated that 70% ethanol extract of S. singueana leaf was safe to mice and possessed some parasite suppression effect. Coadministration of the extract with CQ appeared to boost the overall antimalarial effect, indicating that the combination may have a net health benefit if used as an adjuvant therapy. PMID:26870688

Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria.

PubMed

Hiben, Mebrahtom Gebrelibanos; Sibhat, Gereziher Gebremedhin; Fanta, Biruk Sintayehu; Gebrezgi, Haile Desta; Tesema, Shewaye Belay

2016-01-01

The emergence of malarial resistance to most antimalarial drugs is the main factor driving the continued effort to identify/discover new agents for combating the disease. Moreover, the unacceptably high mortality rate in severe malaria has led to the consideration of adjuvant therapies. Senna singueana leaves are traditionally used against malaria and fever. Extracts from the leaves of this plant demonstrated in vitro and in vivo antioxidant activities, which in turn could reduce the severity of malaria. Extracts from the root bark of this plant exhibited antiplasmodial activity; however, the leaves are the more sustainable resource. Thus, S. singueana leaf was selected for in vivo evaluation as a potential alternative or adjuvant therapy for malaria. Using malaria [Plasmodium berghei ANKA, chloroquine (CQ) sensitive]-infected Swiss albino mice of both sexes, 70% ethanol extract of S. singueana leaves (alone and in combination with CQ) was tested for antimalarial activity and adjuvancy potential. The 4-day suppressive test was used to evaluate antimalarial activity. The dose of S. singueana extract administered was safe to mice and exhibited some parasite suppression effect: extract doses of 200 mg/kg/d, 400 mg/kg/d, and 800 mg/kg/d caused 34.54%, 44.52%, and 47.32% parasite suppression, respectively. Concurrent administration of the extract with CQ phosphate at varied dose levels indicated that the percentage of parasite suppression of this combination was higher than administering CQ alone, but less than the sum of the effects of the extract and CQ acting separately. In conclusion, the study indicated that 70% ethanol extract of S. singueana leaf was safe to mice and possessed some parasite suppression effect. Coadministration of the extract with CQ appeared to boost the overall antimalarial effect, indicating that the combination may have a net health benefit if used as an adjuvant therapy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morganti, Alessio G.; Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso; Falconi, Massimo

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462more » patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.« less

No effect of bipolar interferential electrotherapy and pulsed ultrasound for soft tissue shoulder disorders: a randomised controlled trial

PubMed Central

van der Heijden, G. J M G; Leffers, P.; Wolters, P.; Verheijden, J.; van Mameren, H.; Houben, J.; Bouter, L.; Knipschild, P.

1999-01-01

OBJECTIVE—To assess the efficacy of bipolar interferential electrotherapy (ET) and pulsed ultrasound (US) as adjuvants to exercise therapy for soft tissue shoulder disorders (SD).
METHODS—Randomised placebo controlled trial with a two by two factorial design plus an additional control group in 17 primary care physiotherapy practices in the south of the Netherlands. Patients with shoulder pain and/or restricted shoulder mobility, because of a soft tissue impairment without underlying specific or generalised condition, were enrolled if they had not recovered after six sessions of exercise therapy in two weeks. They were randomised to receive (1) active ET plus active US; (2) active ET plus dummy US; (3) dummy ET plus active US; (4) dummy ET plus dummy US; or (5) no adjuvants. Additionally, they received a maximum of 12 sessions of exercise therapy in six weeks. Measurements at baseline, 6 weeks and 3, 6, 9, and 12 months later were blinded for treatment. Outcome measures: recovery, functional status, chief complaint, pain, clinical status, and range of motion.
RESULTS—After written informed consent 180 patients were randomised: both the active treatments were given to 73 patients, both the dummy treatments to 72 patients, and 35 patients received no adjuvants. Prognosis of groups appeared similar at baseline. Blinding was successfully maintained. At six weeks seven patients (20%) without adjuvants reported very large improvement (including complete recovery), 17 (23%) and 16 (22%) with active and dummy ET, and 19 (26%) and 14 (19%) with active and dummy US. These proportions increased to about 40% at three months, but remained virtually stable thereafter. Up to 12 months follow up the 95% CI for differences between groups for all outcomes include zero.
CONCLUSION—Neither ET nor US prove to be effective as adjuvants to exercise therapy for soft tissue SD.

 PMID:10460185

Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy

PubMed Central

Derzko, C.; Elliott, S.; Lam, W.

2007-01-01

Treatment with aromatase inhibitors for postmenopausal women with breast cancer has been shown to reduce or obviate invasive procedures such as hysteroscopy or curettage associated with tamoxifen-induced endometrial abnormalities. The side effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar to that seen with the natural events of aging. The consequences often include vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn may result in cystitis and vaginitis. Not surprisingly, painful intercourse (dyspareunia) and loss of sexual interest (decreased libido) frequently occur as well. Various interventions, both non-hormonal and hormonal, are currently available to manage these problems. The purpose of the present review is to provide the practitioner with a wide array of management options to assist in treating the sexual consequences of aromatase inhibitors. The suggestions in this review are based on recent literature and on the recommendations set forth both by the North American Menopause Association and in the clinical practice guidelines of the Society of Gynaecologists and Obstetricians of Canada. The complexity of female sexual dysfunction necessitates a biopsychosocial approach to assessment and management alike, with interventions ranging from education and lifestyle changes to sexual counselling, pelvic floor therapies, sexual aids, medications, and dietary supplements—all of which have been reported to have a variable, but often successful, effect on symptom amelioration. Although the use of specific hormone replacement—most commonly local estrogen, and less commonly, systemic estrogen with or without an androgen, progesterone, or the additional of an androgen in an estrogenized woman (or a combination)—may be highly effective, the concern remains that in patients with estrogen-dependent breast cancer, including those receiving anti-estrogenic adjuvant therapies, the use of these hormones may be attended with potential risk. Therefore, non-hormonal alternatives should in all cases be initially tried with the expectation that symptomatic relief can often be achieved. First-line therapy for urogenital symptoms, notably vaginal dryness and dyspareunia, should be the non-hormonal group of preparations such as moisturizers and precoital vaginal lubricants. In patients with estrogen-dependent breast cancer (notably those receiving anti-estrogenic adjuvant therapies) and severely symptomatic vaginal atrophy that fails to respond to non-hormonal options, menopausal hormone replacement or prescription vaginal estrogen therapy may considered. Systemic estrogen may be associated with risk and thus is best avoided. Judicious use of hormones may be appropriate in the well-informed patient who gives informed consent, but given the potential risk, these agents should be prescribed only after mutual agreement of the patient and her oncologist. PMID:18087605

The role of adjuvant external beam radiation therapy for papillary thyroid carcinoma invading the trachea

PubMed Central

Kim, Young Suk; Choi, Jae Hyuck; Kim, Kwang Sik; Lim, Gil Chae; Kim, Jeong Hong; Kang, Ju Wan; Song, Hee-Sung; Lee, Sang Ah; Hyun, Chang Lim; Choi, Yunseon; Kim, Gwi Eon

2017-01-01

Purpose To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. Materials and Methods Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). Results The age range was 26–87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. Conclusion Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients. PMID:28712279

Results of NCCTG N0275 (Alliance) - a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma.

PubMed

Rule, William G; Allred, Jacob B; Pockaj, Barbara A; Markovic, Svetomir N; DiCaudo, David J; Erickson, Lori A; Deming, Richard L; Schild, Steven E

2016-08-01

To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Treatment decisions and the impact of adverse events before and during extended endocrine therapy in postmenopausal early breast cancer.

PubMed

Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

2018-05-01

Extended endocrine therapy beyond 5 years for postmenopausal breast cancer has been studied within multiple phase III trials. Treatment compliance in these trials is generally poor. In this analysis, we aimed to determine factors that were associated with participation in the phase III Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial and with early treatment discontinuation, and how this influenced survival outcome. In the IDEAL trial, postmenopausal patients were randomised between 2.5 or 5 years of extended letrozole, after completing 5 years of endocrine therapy for hormone receptor-positive early breast cancer. A subgroup of this population participated earlier in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in which we explored which factors were determinative for enrolment in the IDEAL study. In the IDEAL cohort, we evaluated which factors predicted for early treatment discontinuation and the effect of early treatment discontinuation on disease-free survival (DFS). Nodal status, younger age and adjuvant chemotherapy were significantly associated with higher enrolment in the IDEAL trial. In the IDEAL cohort, adverse events (AEs), the type of primary endocrine therapy and the interval between primary and extended therapy were associated with early treatment discontinuation. Among the reported AEs, depressive feelings (56%) were most frequently associated with early treatment discontinuation. Early treatment discontinuation was not associated with worse DFS (hazard ratio [HR] = 1.02, 95% confidence interval = 0.76-1.37). In this analysis, we found that risk factors were most strongly associated enrolment in the IDEAL trial. In contrast, patient experiences were the most significant factors leading to early treatment discontinuation, with no effect on DFS. Copyright © 2018 Elsevier Ltd. All rights reserved.

Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

PubMed

Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

2015-06-01

For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice. © 2015 by American Society of Clinical Oncology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Douillard, Jean-Yves; Rosell, Rafael; De Lena, Mario

Purpose: To study the impact of postoperative radiation therapy (PORT) on survival in the Adjuvant Navelbine International Trialist Association (ANITA) randomized study of adjuvant chemotherapy. Methods and Materials: ANITA is a randomized trial of adjuvant cisplatin and vinorelbine chemotherapy vs. observation in completely resected non-small-cell lung carcinoma (NSCLC) Stages IB to IIIA. Use of PORT was recommended for pN+ disease but was not randomized or mandatory. Each center decided whether to use PORT before initiation of the study. We describe here the survival of patients with and without PORT within each treatment group of ANITA. No statistical comparison of survivalmore » was performed because this was an unplanned subgroup analysis. Results: Overall, 232 of 840 patients received PORT (33.3% in the observation arm and 21.6% in the chemotherapy arm). In univariate analysis, PORT had a deleterious effect on the overall population survival. Patients with pN1 disease had an improved survival from PORT in the observation arm (median survival [MS] 25.9 vs. 50.2 months), whereas PORT had a detrimental effect in the chemotherapy group (MS 93.6 months and 46.6 months). In contrast, survival was improved in patients with pN2 disease who received PORT, both in the chemotherapy (MS 23.8 vs. 47.4 months) and observation arm (median 12.7 vs. 22.7 months). Conclusion: This retrospective evaluation suggests a positive effect of PORT in pN2 disease and a negative effect on pN1 disease when patients received adjuvant chemotherapy. The results support further evaluation of PORT in prospectively randomized studies in completely resected pN2 NSCLC.« less

Monitoring and evaluating the quality of cancer care in Japan using administrative claims data.

PubMed

Iwamoto, Momoko; Nakamura, Fumiaki; Higashi, Takahiro

2016-01-01

The importance of measuring the quality of cancer care has been well recognized in many developed countries, but has never been successfully implemented on a national level in Japan. We sought to establish a wide-scale quality monitoring and evaluation program for cancer by measuring 13 process-of-care quality indicators (QI) using a registry-linked claims database. We measured two QI on pre-treatment testing, nine on adherence to clinical guidelines on therapeutic treatments, and two on supportive care, for breast, prostate, colorectal, stomach, lung, liver and cervical cancer patients who were diagnosed in 2011 from 178 hospitals. We further assessed the reasons for non-adherence for patients who did not receive the indicated care in 26 hospitals. QI for pretreatment testing were high in most hospitals (above 80%), but scores on adjuvant radiation and chemoradiation therapies were low (20-37%), except for breast cancer (74%). QI for adjuvant chemotherapy and supportive care were more widely distributed across hospitals (45-68%). Further analysis in 26 hospitals showed that most of the patients who did not receive adjuvant chemotherapy had clinically valid reasons for not receiving the specified care (above 70%), but the majority of the patients did not have sufficient reasons for not receiving adjuvant radiotherapy (52-69%) and supportive care (above 80%). We present here the first wide-scale quality measurement initiative of cancer patients in Japan. Patients without clinically valid reasons for non-adherence should be examined further in future to improve care. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Geographic variation in the intended choice of adjuvant treatments for women diagnosed with screen-detected breast cancer in Queensland.

PubMed

Hsieh, Jeff Ching-Fu; Cramb, Susanna M; McGree, James M; Dunn, Nathan A M; Baade, Peter D; Mengersen, Kerrie L

2015-12-02

Although early diagnosis and improved treatment can reduce breast cancer mortality, there still appears to be a geographic differential in patient outcomes. This study aims to determine and quantify spatial inequalities in intended adjuvant (radio-, chemo- and hormonal) therapy usage among women with screen-detected breast cancer in Queensland, Australia. Linked population-based datasets from BreastScreen Queensland and the Queensland Cancer Registry during 1997-2008 for women aged 40-89 years were used. We adopted a Bayesian shared spatial component model to evaluate the relative intended use of each adjuvant therapy across 478 areas as well as common spatial patterns between treatments. Women living closer to a cancer treatment facility were more likely to intend to use adjuvant therapy. This was particularly marked for radiotherapy when travel time to the closest radiation facility was 4 + h (OR =0.41, 95 % CrI: [0.23, 0.74]) compared to <1 h. The shared spatial effect increased towards the centres with concentrations of radiotherapy facilities, in north-east (Townsville) and south-east (Brisbane) regions of Queensland. Moreover, the presence of residual shared spatial effects indicates that there are other unmeasured geographical barriers influencing women's treatment choices. This highlights the need to identify the additional barriers that impact on treatment intentions among women diagnosed with screen-detected breast cancer, particularly for those women living further away from cancer treatment centers.

Music as an adjuvant therapy in control of pain and symptoms in hospitalized adults: a systematic review.

PubMed

Cole, Linda C; LoBiondo-Wood, Geri

2014-03-01

The objective of this review is to evaluate the evidence regarding the use of music as an adjuvant therapy for pain control in hospitalized adults. The search terms music, music therapy, pain, adults, inpatient, and hospitalized were used to search the Cochrane Library, Cinahl, Medline, Natural Standard, and Scopus databases from January 2005 to March 2011. (A systematic review conducted by the Cochrane Collaboration has extensively covered the time frame from 1966 to 2004.) Seventeen randomized controlled trials met criteria for review and inclusion. Seven of the research studies were conducted with surgical patients, three with medical patients, one with medical-surgical patients, four with intensive care patients, and two with pregnant patients. The combined findings of these studies provide support for the use of music as an adjuvant approach to pain control in hospitalized adults. The use of music is safe, inexpensive, and an independent nursing function that can be easily incorporated into the routine care of patients. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Anne, E-mail: akim2@health-quest.org; Schreiber, David; Rineer, Justin

2011-11-15

Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: Wemore » identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.« less

The use of low output laser therapy to accelerate healing of diabetic foot ulcers: a randomized prospective controlled trial

NASA Astrophysics Data System (ADS)

Naidu, S. V. L. G.; Subapriya, S.; Yeoh, C. N.; Soosai, S.; Shalini, V.; Harwant, S.

2005-11-01

The aim of this study was to assess the effects of low output laser therapy as an adjuvant treatment in grade 1 diabetic foot ulcers. Methods: Sixteen patients were randomly divided equally into two groups. Group A had daily dressing only, while group B had low output laser therapy instituted five days a week in addition to daily dressing. Serial measurement of the ulcer was done weekly using digital photography and analyzed. Results: The rate of healing in group A was 10.42 mm2/week, and in group B was 66.14mm2/week. The difference in the rate of healing was statistically significant, p<0.05. Conclusion: Laser therapy as an adjuvant treatment accelerates diabetic ulcer healing by six times in a six week period.

Fighting cancers from within: augmenting tumor immunity with cytokine therapy.

PubMed

Pellegrini, Marc; Mak, Tak W; Ohashi, Pamela S

2010-08-01

The human immune system has successfully evolved to fight many pathogens. Through vaccination, we can harness and improve immune responses to eradicate infections. Despite this success, we are only now beginning to understand the natural tumor immune surveillance mechanisms and why, in some instances, our immune system fails to abrogate the development and growth of tumors. Encouraging results with the latest immunotherapies have renewed enthusiasm in the field. A central component of these therapies is the contribution of cytokines. Here we review our expanding knowledge of cytokine-induced effects as well as preclinical and clinical data that indicate adjuvant cytokine therapies may hold much promise in improving anti-tumor immunity. Further studies on optimal synergistic combinations, timing, duration and additional adjuvant therapies are required to realize the full potential of cytokines as immunotherapeutic agents. 2010 Elsevier Ltd. All rights reserved.

Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival.

PubMed

Sexe, R; Miedema, B W

1993-07-01

The risk of malignant disease arising in rectal mucosa is high. Surgery is the most effective form of treatment but results in cure in only 50% of patients. Adjuvant preoperative radiation therapy reduces the likelihood of local recurrence but does not improve survival rates. Fluorouracil is the most effective agent for adjuvant chemotherapy and slightly improves survival when given after surgery. Combining radiation therapy with chemotherapy appears to have a synergistic effect, and recent studies show that providing this combination after surgery improves survival. Future trends in the treatment of rectal cancer are expected to include expanded use of local excision to preserve anal sphincter function, preoperative use of a combination of radiation therapy and chemotherapy, perioperative use of chemotherapy combined with immunostimulating therapy, and use of tumor antibodies for diagnostic and therapeutic purposes.

Refining Post-Surgical Therapy for Women with Lymph Node-Positive Breast Cancer

Cancer.gov

In this trial, women with HER2-negative, HR-positive breast cancer and 1-3 positive lymph nodes with recurrence scores of 25 or lower will be randomized to undergo adjuvant chemotherapy before starting endocrine therapy or to begin endocrine therapy.

Accuracy of Computed Tomography for Predicting Pathologic Nodal Extracapsular Extension in Patients With Head-and-Neck Cancer Undergoing Initial Surgical Resection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prabhu, Roshan S., E-mail: roshansprabhu@gmail.com; Winship Cancer Institute, Emory University, Atlanta, Georgia; Magliocca, Kelly R.

2014-01-01

Purpose: Nodal extracapsular extension (ECE) in patients with head-and-neck cancer increases the loco-regional failure risk and is an indication for adjuvant chemoradiation therapy (CRT). To reduce the risk of requiring trimodality therapy, patients with head-and-neck cancer who are surgical candidates are often treated with definitive CRT when preoperative computed tomographic imaging suggests radiographic ECE. The purpose of this study was to assess the accuracy of preoperative CT imaging for predicting pathologic nodal ECE (pECE). Methods and Materials: The study population consisted of 432 consecutive patients with oral cavity or locally advanced/nonfunctional laryngeal cancer who underwent preoperative CT imaging before initialmore » surgical resection and neck dissection. Specimens with pECE had the extent of ECE graded on a scale from 1 to 4. Results: Radiographic ECE was documented in 46 patients (10.6%), and pECE was observed in 87 (20.1%). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 43.7%, 97.7%, 82.6%, and 87.3%, respectively. The sensitivity of radiographic ECE increased from 18.8% for grade 1 to 2 ECE, to 52.9% for grade 3, and 72.2% for grade 4. Radiographic ECE criteria of adjacent structure invasion was a better predictor than irregular borders/fat stranding for pECE. Conclusions: Radiographic ECE has poor sensitivity, but excellent specificity for pECE in patients who undergo initial surgical resection. PPV and NPV are reasonable for clinical decision making. The performance of preoperative CT imaging increased as pECE grade increased. Patients with resectable head-and-neck cancer with radiographic ECE based on adjacent structure invasion are at high risk for high-grade pECE requiring adjuvant CRT when treated with initial surgery; definitive CRT as an alternative should be considered where appropriate.« less

Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

PubMed

Mates, M; Fletcher, G G; Freedman, O C; Eisen, A; Gandhi, S; Trudeau, M E; Dent, S F

2015-03-01

This systematic review addresses the question "What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)-positive breast cancer?" The medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched. Sixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47). Taking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population.

Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

PubMed Central

Mates, M.; Fletcher, G.G.; Freedman, O.C.; Eisen, A.; Gandhi, S.; Trudeau, M.E.; Dent, S.F.

2015-01-01

Background This systematic review addresses the question “What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)–positive breast cancer?” Methods The medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched. Results Sixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47). Conclusions Taking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population. PMID:25848335

Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol.

PubMed

Gulati, Geeta; Heck, Siri Lagethon; Ree, Anne Hansen; Hoffmann, Pavel; Schulz-Menger, Jeanette; Fagerland, Morten W; Gravdehaug, Berit; von Knobelsdorff-Brenkenhoff, Florian; Bratland, Åse; Storås, Tryggve H; Hagve, Tor-Arne; Røsjø, Helge; Steine, Kjetil; Geisler, Jürgen; Omland, Torbjørn

2016-06-01

Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI -0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Psychosocial determinants and outcomes of chemotherapy in older women with breast cancer: what do we know? What do we need to know?

PubMed

Tallarico, Michelle; Figueiredo, Melissa; Goodman, Michelle; Kreling, Barbara; Mandelblatt, Jeanne

2005-01-01

With the aging of the U.S. population and rising breast cancer incidence with advancing age, the absolute number of women aged 65 years and older diagnosed with and surviving breast cancer will dramatically increase over the coming decades. Despite this demographic imperative, we know little about the impact of adjuvant therapies in this age group. We synthesized data to describe key findings and gaps in knowledge about the outcomes of adjuvant breast cancer treatment in women aged 65 years and and older ("older women"). We reviewed research published between 1995 and June 2005 on breast cancer outcomes among older women treated with adjuvant therapy for breast cancer. Outcomes included communication, emotional distress, satisfaction, and multiple quality-of-life domains. Only 16 articles focused exclusively on older women and chemotherapy; and only one included a large sample of older women (N = 1755). Most common domains included comorbidities, symptoms, and survival. Of the 13 clinical trials and three observational studies we reviewed, only one clinical trial measured quality of life and psychological factors such as coping. None of the studies examined patient preferences or patient-physician communication (processes of care) in older women. Few studies have been designed to specifically evaluate adjuvant therapy processes and outcomes among older women, especially interactions between treatment and comorbidity, and the impact of the processes of care on outcomes. In addition, only narrow segments of the older population with breast cancer (e.g., well-educated, nonminority women) have been included in trials to date. Thus, at present we do not have sufficient data to assist physicians and their older patients in developing adjuvant treatment decisions and plans tailored to older women's needs, preferences, and concerns.

Treatment Trends for Stage I Testicular Seminoma in an Equal-Access Medical System.

PubMed

Wingate, Jonathan T; Etzioni, Ruth; Macdonald, Dusten M; Brand, Timothy C

2016-10-01

The practice patterns for adjuvant therapies for stage I seminoma are rapidly evolving, and surveillance is currently preferred. How these recommendations have affected contemporary practice in an equal-access US population is unknown. A total of 436 men diagnosed with clinical stage IA-IB seminoma from 2001 to 2011 were identified in the Automated Central Tumor Registry (ACTUR). The ACTUR is the cancer registry system for the Department of Defense. Logistic regression models analyzed the association between patient characteristics and adjuvant therapy. Overall and recurrence-free survival were determined from Kaplan-Meier analysis. The use of adjuvant radiotherapy in this population decreased significantly from 2001 to 2011. In 2001, 83.9% of patients received radiotherapy compared with only 24.0% in 2011. During that period, a concomitant increase occurred in the use of chemotherapy from 0% to 38.0%. A later year of diagnosis was significantly associated with a greater rate of receiving chemotherapy relative to radiotherapy (P < .001 for 2006-2011 vs. 2001-2005; relative rate ratio, 19.3; 95% confidence interval [CI], 8.04-46.13). A later year of diagnosis was not significantly associated with the receipt of surveillance (P = .412 for 2006-2011 vs. 2001-2005; odds ratio, 0.83; 95% CI, 0.54-1.29). Black race or age was not significantly associated with adjuvant therapy. With a median follow-up period of 4.7 years, the 5-year overall and recurrence-free survival rates were 98.0% and 77.0%, respectively. The use of adjuvant radiotherapy has been replaced by chemotherapy for clinical stage I testicular seminoma in an equal-access system. The lack of an increase in active surveillance in our cohort might represent overtreatment of the population. Published by Elsevier Inc.

How does adjuvant chemotherapy affect menopausal symptoms, sexual function, and quality of life after breast cancer?

PubMed

Marino, Jennifer L; Saunders, Christobel M; Emery, Laura I; Green, Helena; Doherty, Dorota A; Hickey, Martha

2016-09-01

The aim of the study was to determine the association between adjuvant chemotherapy for breast cancer and menopausal symptoms, sexual function, and quality of life. Participants attended a menopause clinic with a dedicated service for cancer survivors at a large tertiary women's hospital. Information about breast cancer treatments including adjuvant chemotherapy was collected from medical records. Menopausal symptoms were recorded with the Greene Climacteric Scale and Functional Assessment of Cancer Therapy, Breast Cancer, and Endocrine Symptom Subscales. Sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. Quality of life was measured with Functional Assessment of Cancer Therapy scales. The severity of vasomotor, psychological, or sexual symptoms (apart from pain) did not differ between those who had received adjuvant chemotherapy (n = 339) and other breast cancer survivors (n = 465). After adjustment for current age, time since menopause, and current use of antiestrogen endocrine therapy, the risk of "severe pain" with sexual intercourse was twice as common after chemotherapy (31.6% vs 20.0%, odds ratio [OR] 2.18, 95% CI 1.25-3.79). Those treated with chemotherapy were more likely to report "severe problems" with physical well-being (OR 1.92, 95% CI 1.12-3.28) and lower breast cancer-specific quality of life (OR 1.89 95% CI 1.13-3.18), but did not differ in other quality of life measures. In this large study of breast cancer patients presenting to a specialty menopause clinic, previous chemotherapy was not associated with current vasomotor or psychological symptoms. Severe pain with intercourse was significantly more common in those treated with adjuvant chemotherapy.

Chondrosarcoma of the nasal septum.

PubMed

Magnano, Mauro; Boffano, Paolo; Machetta, Giacomo; Garibaldi, Elisabetta; Delmastro, Elena; Gabriele, Pietro

2015-03-01

Chondrosarcomas are non-epithelial malignant, slow growing tumors that usually involve pelvis, ribs, and long bones of extremities, scapula and sternum. Median age at diagnosis for head and neck chondrosarcomas is in the fourth decade. The etiopathogenesis of chondrosarcomas remains unknown. Treatment of choice is surgical, with adjuvant therapy having a limited role. In fact, radiation therapy and chemotherapy are reserved for residual or recurrent disease and palliation. As for surgery, several surgical procedures have been described. Recently, endoscopic surgery has allowed for the successful and less invasive treatment of inverting papillomas and even nasopharyngeal angiofibromas, lesions previously requiring extended external approaches. The aim of this paper was to present a case of nasal septal chondrosarcoma that was successfully treated with endoscopic surgery and radiation adjuvant therapy.

[Possibilities and results of "immunotherapy" in children with acute leucosis (author's transl)].

PubMed

Blau, H J; Schulz, M

1980-01-01

In the introduction we are giving an overview about the possibilities of treatment of acute leucemias in childhood with an adjuvant immunotherapeutic component. Our own ten-years-experiences from 25 a. 1.1. children with BCG-application are useful for testing this kind of adjuvant therapy under clinical conditions in future, too.

Evaluation of non-genomic, clinical risk and survival results in endocrine-sensitive, HER-2 negative, node negative breast cancer.

PubMed

Baena Cañada, José M; Gámez Casado, Salvador; Rodríguez Pérez, Lourdes; Quílez Cutillas, Alicia; Cortés Carmona, Cristina; Rosado Varela, Petra; Estalella Mendoza, Sara; Ramírez Daffós, Patricia; Benítez Rodríguez, Encarnación

2018-02-28

In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Gastrostomy Tube Use after Transoral Robotic Surgery for Oropharyngeal Cancer

PubMed Central

Al-khudari, Samer; Bendix, Scott; Lindholm, Jamie; Simmerman, Erin; Hall, Francis; Ghanem, Tamer

2013-01-01

Objective. To evaluate factors that influence gastrostomy tube (g-tube) use after transoral robotic surgery (TORS) for oropharyngeal (OP) cancer. Study Design/Methods. Retrospective review of TORS patients with OP cancer. G-tube presence was recorded before and after surgery at followup. Kaplan-Meier and Cox hazards model evaluated effects of early (T1 and T2) and advanced (T3, T4) disease, adjuvant therapy, and free flap reconstruction on g-tube use. Results. Sixteen patients had tonsillar cancer and 13 tongue base cancer. Of 22 patients who underwent TORS as primary therapy, 17 had T1 T2 stage and five T3 T4 stage. Seven underwent salvage therapy (four T1 T2 and three T3 T4). Nine underwent robotic-assisted inset free flap reconstruction. Seventeen received adjuvant therapy. Four groups were compared: primary early disease (PED) T1 and T2 tumors, primary early disease with adjunctive therapy (PEDAT), primary advanced disease (PAD) T3 and T4 tumors, and salvage therapy. Within the first year of treatment, 0% PED, 44% PEDAT, 40% PAD, and 57% salvage patients required a g-tube. Fourteen patients had a temporary nasoenteric tube (48.3%) postoperatively, and 10 required a g-tube (34.5%) within the first year. Four of 22 (18.2%) with TORS as primary treatment were g-tube dependent at one year and had received adjuvant therapy. Conclusion. PED can be managed without a g-tube after TORS. Similar feeding tube rates were found for PEDAT and PAD patients. Salvage patients have a high rate of g-tube need after TORS. PMID:23936676

The role of neratinib in HER2-driven breast cancer.

PubMed

Cherian, Mathew A; Ma, Cynthia X

2017-06-30

Up to 25% of patients with early-stage HER2+ breast cancer relapse despite adjuvant trastuzumab-based regimens and virtually all patients with metastatic disease eventually die from resistance to existing treatment options. In addition, recent studies indicate that activating HER2 mutations without gene amplification could drive tumor growth in a subset of HER2-ve breast cancer that is not currently eligible for HER2-targeted agents. Neratinib is an irreversible HER kinase inhibitor with activity as extended adjuvant therapy following standard trastuzumab-based adjuvant treatment in a Phase III trial. Phase II trials of neratinib demonstrate promising activity in combination with cytotoxic agents in trastuzumab resistant metastatic HER2+ breast cancer, and either as monotherapy or in combination with fulvestrant for HER2-mutated breast cancers. We anticipate a potential role for neratinib in the therapy of these patient populations.

Singapore Cancer Network (SCAN) Guidelines for Adjuvant Chemotherapy in Resected Non-Small Cell Lung Cancer.

PubMed

2015-10-01

The SCAN lung cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for the use of adjuvant systemic therapy for non-small cell lung cancer in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Comprehensive Cancer Network (2014), European Society of Medical Oncology (2014), National Institute of Clinical Excellence (2012), Scottish Intercollegiate Guidelines Network (2014), and the Cancer Care Council Australia (2012). Recommendations on the selection of patients, chemotherapy regimen, treatment for stage I disease, treatment for positive margins and treatment options for pN2 disease with negative margins were produced. These adapted guidelines form the SCAN Guidelines 2015 for adjuvant systemic therapy of non-small cell lung cancer.

Synthetic Studies of Complex Immunostimulants from Quillaja saponaria: Synthesis of the Potent Clinical Immunoadjuvant QS-21Aapi

PubMed Central

Kim, Yong-Jae; Wang, Pengfei; Navarro-Villalobos, Mauricio; Rohde, Bridget D.; Derryberry, JohnMark; Gin, David Y.

2008-01-01

QS-21 is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing vaccine therapy clinical trials involving QS-21 as a critical adjuvant component for immune response augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting both T-cell- and antibody-mediated immune responses with microgram doses. Herein is reported the synthesis of QS-21Aapi in a highly modular strategy, applying novel glycosylation methodologies to a convergent construction of the potent saponin immunostimulant. The chemical synthesis of QS-21 offers unique opportunities to probe its mode of biological action through the preparation of otherwise unattainable nonnatural saponin analogues. PMID:16953631

Mechanisms of, and Adjuvants for, Bone Pain.

PubMed

Figura, Nicholas; Smith, Joshua; Yu, Hsiang-Hsuan Michael

2018-06-01

Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

PubMed Central

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Practice patterns and long-term survival for early-stage rectal cancer.

PubMed

Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

2013-12-01

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

Design and Synthesis of Potent Quillaja Saponin Vaccine Adjuvants

PubMed Central

Adams, Michelle M.; Damani, Payal; Perl, Nicholas R.; Won, Annie; Hong, Feng

2010-01-01

The success of antitumor and antiviral vaccines often requires the use of an adjuvant, a substance that significantly enhances the immune response to a co-administered antigen. Only a handful of adjuvants have both sufficient potency and acceptable toxicity for clinical investigation. One promising adjuvant is QS-21, a saponin natural product that is the immunopotentiator of choice in many cancer and infectious disease vaccine clinical trials. However, the therapeutic promise of QS-21 adjuvant is curtailed by several factors, including its scarcity, difficulty in purification to homogeneity, dose-limiting toxicity, and chemical instability. Here we report the design, synthesis, and evaluation of chemically stable synthetic saponins. These novel, amide-modified, non-natural substances exhibit immunopotentiating effects in vivo that rival or exceed that of QS-21 in evaluations with the GD3-KLH melanoma conjugate vaccine. The highly convergent synthetic preparation of these novel saponins establishes new avenues for discovering improved molecular adjuvants for specifically tailored vaccine therapies. PMID:20088518

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers.

PubMed

Hequet, Delphine; Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna's assay information on physicians' adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians' opinion on the test results and the patients' degree of anxiety, difficulties with therapy and quality of life. Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36%) patients, an overall discordance rate of 25%. The availability of Prosigna assay results was significantly associated with the likelihood of change in treatment recommendations, with 34 patients (18%) having their treatment plan changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa (p<0.001, Fisher's exact test). Prosigna test results also decreased patients' anxiety about the chosen adjuvant therapy, and improved emotional well-being and measures of personal perceptions of uncertainty. The results of this prospective decision impact study are consistent with 2 previous, identically designed studies carried out in Spain and Germany. The availability of Prosigna test results increased the confidence of treating physicians in their adjuvant treatment decisions, and led to an 18% change in chemotherapy treatment plan (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna testing decreased anxiety and improved measures of health-related quality of life in patients facing adjuvant therapy. The 25% discordance between Prosigna test and IHC subtyping underlines the importance of molecular testing for optimal systemic therapy indications in early breast cancer.

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers

PubMed Central

Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

Purpose The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna’s assay information on physicians’ adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Methods Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians’ opinion on the test results and the patients’ degree of anxiety, difficulties with therapy and quality of life. Results Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36%) patients, an overall discordance rate of 25%. The availability of Prosigna assay results was significantly associated with the likelihood of change in treatment recommendations, with 34 patients (18%) having their treatment plan changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa (p<0.001, Fisher’s exact test). Prosigna test results also decreased patients’ anxiety about the chosen adjuvant therapy, and improved emotional well-being and measures of personal perceptions of uncertainty. Conclusions The results of this prospective decision impact study are consistent with 2 previous, identically designed studies carried out in Spain and Germany. The availability of Prosigna test results increased the confidence of treating physicians in their adjuvant treatment decisions, and led to an 18% change in chemotherapy treatment plan (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna testing decreased anxiety and improved measures of health-related quality of life in patients facing adjuvant therapy. The 25% discordance between Prosigna test and IHC subtyping underlines the importance of molecular testing for optimal systemic therapy indications in early breast cancer. PMID:29045452

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy in Japanese patients with locally advanced prostate cancer.

PubMed

Sakamoto, Masato; Mizowaki, Takashi; Mitsumori, Michihide; Takayama, Kenji; Sasai, Keisuke; Norihisa, Yoshiki; Kamoto, Toshiyuki; Nakamura, Eijiro; Ogawa, Osamu; Hiraoka, Masahiro

2010-12-01

The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with locally advanced prostate cancer who initiated salvage hormonal therapy (SHT) at a relatively early phase were evaluated. Between April 1998 and April 2003, 70 Japanese patients with T3N0M0 prostate cancer who received radical 3D-CRT treatment were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were 73 years old, 26.3 ng/ml, and 4 months, respectively. Seventy grays were given in 35 fractions that were confined to the prostate and seminal vesicles. Adjuvant hormonal therapy was not administered after 3D-CRT in any of the cases. The median follow-up period was 64.9 months. The median PSA value at the time of initiation of SHT was 5.0 ng/ml (range 0.1-21.6 ng/ml). Overall, disease-specific, PSA failure-free (based on the Phoenix definition) and SHT-free survival rates at 5 years were 90.3% (95% CI 86.5-94.0), 96.5% (94.0-98.9), 60.5% (48.2-72.7), and 63.5% (57.2-69.8), respectively. Therefore, two-thirds of the patients were still hormone-free at 5 years. PSA control rates in our series of Japanese patients with stage T3N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed higher than expected. This approach involving 3D-CRT combined with NAHT with the initiation of SHT at PSA values of around 5 ng/ml may be one option for Japanese patients with locally advanced prostate cancer, although further prospective study is required to confirm the validity.

Can mumps vaccine induce remission in recurrent respiratory papilloma?

PubMed

Pashley, Nigel R T

2002-07-01

To describe our experience using laser excision and locally injected mumps vaccine to induce remission in patients with recurrent respiratory papilloma (RRP). Tertiary care regional medical center. Initially, 11 children with RRP treated in a pilot study with laser excision at regular intervals for at least a year without adjuvant therapy; later, a series of 18 children and 20 adults with RRP, some of whom had used various adjuvant therapy with interval laser excision. Both patient groups continued their same interval laser excision with the same or similar laser, same clinical setting, and same surgeon. Locally injected mumps vaccine was then administered into the excision site after each laser removal of papilloma. Larynx and trachea were microphotographed with each treatment. Two consecutive disease-free intervals and a follow-up of at least 1 year were required criteria for remission. In the pilot study, remission was induced in 9 (82%) of 11 patients by 1 to 10 injections, with follow-up of 5 to 19 years. In the subsequent series, remission was induced in 29 (76%) of 38 patients by 4 to 26 injections, and follow-up was 2 to 5 years. Combined with serial laser excision, mumps vaccine positively influences induction of remission in children with RRP. The mechanisms of this effect are unclear, but the treatment is readily available, inexpensive, and has a low risk of adverse effects.

Histopathological features of endometrial carcinomas associated with POLE mutations: implications for decisions about adjuvant therapy.

PubMed

Bakhsh, Salwa; Kinloch, Mary; Hoang, Lien N; Soslow, Robert A; Köbel, Martin; Lee, Cheng-Han; McAlpine, Jessica N; McConechy, Melissa K; Gilks, C Blake

2016-05-01

To characterize the histomorphological features of endometrial carcinomas (ECs) harbouring polymerase ε (POLE) mutations. Forty-three ECs with POLE mutations were compared with a cohort of 202 ECs. Most POLE-mutated ECs were endometrioid [34/43 (79%)]; the remaining tumours were mixed [6/43 (14%)], serous [2/43 (5%)], and clear cell [1/43 (2%)]. The endometrioid carcinomas were predominantly International Federation of Gynecology and Obstetrics grade 3 (27/43, 63%). The histotype distribution did not differ from that of control ECs (P = 0.69), but the grade of the EC was higher (P < 0.0005). Both nuclear grade and mitotic index were significantly higher in POLE-mutated ECs than in the comparison cohort. POLE-mutated ECs were associated with peritumoral lymphocytes and numerous tumour-infiltrating lymphocytes. Lymphovascular invasion was present in 20 of 43 tumours. Adjuvant radiotherapy and adjuvant chemotherapy would be offered in up to 80% and 40% of patients, respectively, on the basis of stage, grade, lymphovascular invasion, and histotype. POLE-mutated ECs are typically of high grade, with prominent lymphocytic infiltration, but they are not sufficiently distinctive to allow accurate diagnosis based on routine haematoxylin and eosin staining. Even though POLE-mutated tumours are associated with an excellent prognosis, current guidelines for giving adjuvant treatment for EC result in most patients receiving adjuvant therapy. © 2015 John Wiley & Sons Ltd.

Dose density in adjuvant chemotherapy for breast cancer.

PubMed

Citron, Marc L

2004-01-01

Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d). The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.

Surgical resection of synchronously metastatic adrenocortical cancer.

PubMed

Dy, Benzon M; Strajina, Veljko; Cayo, Ashley K; Richards, Melanie L; Farley, David R; Grant, Clive S; Harmsen, William S; Evans, Doug B; Grubbs, Elizabeth G; Bible, Keith C; Young, William F; Perrier, Nancy D; Que, Florencia G; Nagorney, David M; Lee, Jeffrey E; Thompson, Geoffrey B

2015-01-01

Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.

Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method.

PubMed

Goodman, Karyn A; Patton, Caroline E; Fisher, George A; Hoffe, Sarah E; Haddock, Michael G; Parikh, Parag J; Kim, John; Baxter, Nancy N; Czito, Brian G; Hong, Theodore S; Herman, Joseph M; Crane, Christopher H; Hoffman, Karen E

2016-01-01

To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection. The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate. In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate. This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings. Ongoing trials may clarify areas of continuing uncertainty and allow further customization. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Phase II randomized trial comparing high-dose IFN-α2b with temozolomide plus cisplatin as systemic adjuvant therapy for resected mucosal melanoma.

PubMed

Lian, Bin; Si, Lu; Cui, Chuanliang; Chi, Zhihong; Sheng, Xinan; Mao, Lili; Li, Siming; Kong, Yan; Tang, Bixia; Guo, Jun

2013-08-15

Mucosal melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected mucosal melanoma to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy. Patients with mucosal melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 × 10(6) U/m(2)/d IFN-α2b, followed by 9 × 10(6) U IFN-α2b), and temozolomide (200 mg/m(2)/d) plus cisplatin (75 mg/m(2)) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities. One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS (P < 0.001) and OS (P < 0.01) than those treated with either HDI or surgery alone. Toxicities were generally mild to moderate. Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected mucosal melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected mucosal melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected mucosal melanoma. ©2013 AACR.

Letrozole in the extended adjuvant setting: MA.17

PubMed Central

2007-01-01

Relapse after completing adjuvant tamoxifen therapy is a persistent threat for women with hormone-responsive breast cancer. Third-generation aromatase inhibitors, such as letrozole, provide a new option for extended adjuvant hormonal therapy after 5 years of tamoxifen. MA.17 was conducted to determine whether letrozole improves outcome after discontinuation of tamoxifen. Postmenopausal women with hormone receptor-positive breast cancer (N = 5,187) were randomized to letrozole 2.5 mg or placebo once daily for 5 years. At a median follow-up of 30 months, letrozole significantly improved disease-free survival (DFS; P < 0.001), the primary end point, compared with placebo (hazard ratio [HR] for recurrence or contralateral breast cancer 0.58; 95% confidence interval [CI] 0.45, 0.76] P < 0.001). Furthermore, letrozole significantly improved distant DFS (HR = 0.60; 95% CI 0.43, 0.84; P = 0.002) and, in women with node-positive tumors, overall survival (HR = 0.61; 95% CI 0.38, 0.98; P = 0.04). Clinical benefits, including an overall survival advantage, were also seen in women who crossed over from placebo to letrozole after unblinding, indicating that tumors remain sensitive to hormone therapy despite a prolonged period since discontinuation of tamoxifen. The efficacy and safety of letrozole therapy beyond 5 years is being assessed in a re-randomization study, following the emergence of new data suggesting that clinical benefit correlates with the duration of letrozole. MA.17 showed that letrozole is extremely well-tolerated relative to placebo. Letrozole should be considered for all women completing tamoxifen; new results from the post-unblinding analysis suggest that letrozole treatment should also be considered for all disease-free women for periods up to 5 years following completion of adjuvant tamoxifen. PMID:17912635

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck.

PubMed

Weiss, Jared M; Grilley-Olson, Juneko E; Deal, Allison Mary; Zevallos, Jose P; Chera, Bhishamjit S; Paul, Jennifer; Knowles, Mary Fleming; Usenko, Dmitriy; Weissler, Mark C; Patel, Samip; Hayes, David N; Hackman, Trevor

2018-05-09

The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer. Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m 2 , and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility. Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow-up has recurred or died. Twenty-nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved. The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk-adapted adjuvant therapy resulted in high response rates and excellent long-term outcomes and should be further studied. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Cost-effectiveness of the 21-gene breast cancer assay in Mexico.

PubMed

Bargalló-Rocha, Juan Enrique; Lara-Medina, Fernando; Pérez-Sánchez, Victor; Vázquez-Romo, Rafael; Villarreal-Garza, Cynthia; Martínez-Said, Hector; Shaw-Dulin, Robin J; Mohar-Betancourt, Alejandro; Hunt, Barnaby; Plun-Favreau, Juliette; Valentine, William J

2015-03-01

The 21-gene breast cancer assay (Oncotype DX(®); Genomic Health, Inc.) is a validated diagnostic test that predicts the likelihood of adjuvant chemotherapy benefit and 10-year risk of distant recurrence in patients with hormone-receptor-positive, human epidermal growth receptor 2-negative, early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Mexico. A Markov model was developed to make long-term projections of distant recurrence, survival, and direct costs in scenarios using conventional diagnostic procedures or the 21-gene assay to inform adjuvant chemotherapy recommendations. Transition probabilities and risk adjustment were taken from published landmark trials. Costs [2011 Mexican Pesos (MXN)] were estimated from an Instituto Mexicano del Seguro Social perspective. Costs and clinical benefits were discounted at 5% annually. Following assay testing, approximately 66% of patients previously receiving chemotherapy were recommended to receive hormone therapy only after consideration of assay results. Furthermore, approximately 10% of those previously allocated hormone therapy alone had their recommendation changed to add chemotherapy. This optimized therapy allocation led to improved mean life expectancy by 0.068 years per patient and increased direct costs by MXN 1707 [2011 United States Dollars (USD) 129] per patient versus usual care. This is equated to an incremental cost-effectiveness ratio (ICER) of MXN 25,244 (USD 1914) per life-year gained. In early-stage breast cancer patients in Mexico, guiding decision making on adjuvant therapy using the 21-gene assay was projected to improve life expectancy in comparison with the current standard of care, with an ICER of MXN 25,244 (USD 1914) per life-year gained, which is within the range generally considered cost-effective.

Novel low-cost thermotherapy for cutaneous leishmaniasis in Peru.

PubMed

Valencia, Braulio M; Miller, David; Witzig, Richard S; Boggild, Andrea K; Llanos-Cuentas, Alejandro

2013-01-01

Thermotherapy is an accepted alternative therapy for new-world cutaneous leishmaniasis, but current heat-delivery modalities are too costly to be made widely available to endemic populations. We adapted a low-cost heat pack named the HECT-CL device that delivers safe, reliable, and renewable conduction heat. 25 patients with cutaneous leishmaniasis completed treatment with the device at an initial temperature of 52°C ± 2°C for 3 minutes to each lesion, repeated daily for 7 days, and were followed up for 6 months by direct observation. The overall definitive clinical cure rate was 60%. Concurrently, 13 patients meeting minimally significant exclusion criteria received identical compassionate use treatment with a cumulative definitive cure rate of 68.4%, 75% for those who had experienced CL relapse after prior antimonial treatment. Therapy was well tolerated. Reversible second-degree burns occurred in two patients and no bacterial super-infections were observed. HECT-CL is a promising treatment and deserves further study to verify its safety and efficacy as adjuvant and mono- therapy.

Novel Low-Cost Thermotherapy for Cutaneous Leishmaniasis in Peru

PubMed Central

Witzig, Richard S.; Boggild, Andrea K.; Llanos-Cuentas, Alejandro

2013-01-01

Thermotherapy is an accepted alternative therapy for new-world cutaneous leishmaniasis, but current heat-delivery modalities are too costly to be made widely available to endemic populations. We adapted a low-cost heat pack named the HECT-CL device that delivers safe, reliable, and renewable conduction heat. 25 patients with cutaneous leishmaniasis completed treatment with the device at an initial temperature of 52°C±2°C for 3 minutes to each lesion, repeated daily for 7 days, and were followed up for 6 months by direct observation. The overall definitive clinical cure rate was 60%. Concurrently, 13 patients meeting minimally significant exclusion criteria received identical compassionate use treatment with a cumulative definitive cure rate of 68.4%, 75% for those who had experienced CL relapse after prior antimonial treatment. Therapy was well tolerated. Reversible second-degree burns occurred in two patients and no bacterial super-infections were observed. HECT-CL is a promising treatment and deserves further study to verify its safety and efficacy as adjuvant and mono- therapy. PMID:23658851

Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects.

PubMed

Vyas, Purvi; Thakar, A B; Baghel, M S; Sisodia, Arvind; Deole, Yogesh

2010-10-01

Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy.

Physical Therapy Adjuvants to Promote Optimization of Walking Recovery after Stroke

PubMed Central

Bowden, Mark G.; Embry, Aaron E.; Gregory, Chris M.

2011-01-01

Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s) to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s) will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1) walking specific motor control; (2) dynamic balance; (3) cardiorespiratory fitness and (4) muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance. PMID:22013549

The IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration: Prospective Combined Analysis of Phase III Trials Investigating Duration of Adjuvant Therapy with the FOLFOX (FOLFOX4 or Modified FOLFOX6) or XELOX (3 versus 6 months) Regimen for Patients with Stage III Colon Cancer: Trial Design and Current Status.

PubMed

André, Thierry; Iveson, Timothy; Labianca, Roberto; Meyerhardt, Jeffrey A; Souglakos, Ioannis; Yoshino, Takayuki; Paul, James; Sobrero, Alberto; Taieb, Julien; Shields, Anthony F; Ohtsu, Atsushi; Grothey, Axel; Sargent, Daniel J

2013-01-01

The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration was established to prospectively combine and analyze data from several randomized trials conducted around the world to answer whether a three-month course of oxaliplatin-based adjuvant therapy (FOLFOX4/modified FOLFOX6 or XELOX) is non-inferior to the current standard six-month treatment for patients with stage III colon cancer, with a primary endpoint of three years disease-free survival. The IDEA steering committee comprises two members from each group coordinating an individual trial and two members from a secretariat who coordinate combining of the data and management of the joint analysis. Members of the IDEA agreed to combine the data from their individual trials to enable definitive analysis consisting of at least 10,500 patients. With accrual of 8,797 patients at the end of February 2013, the IDEA is on track to achieve its accrual objective of at least 10,500 patients by the end of 2013.

Effectiveness of repeated photodynamic therapy in the elimination of intracanal Enterococcus faecalis biofilm: an in vitro study.

PubMed

Prażmo, Ewa Joanna; Godlewska, Renata Alicja; Mielczarek, Agnieszka Beata

2017-04-01

The study aimed to investigate the effectiveness of photodynamic therapy in the elimination of intracanal Enterococcus faecalis biofilm and to analyse how a repeated light irradiation, replenishment of oxygen and photosensitiser affect the results of the photodynamic disinfecting protocol. After chemomechanical preparation, 46 single-rooted human teeth were infected with a clinical strain of E. faecalis and incubated for a week in microaerobic conditions. The experimental procedures included groups of single application of photodynamic therapy, two cycles of PDT, irrigation with 5.25% NaOCl solution and negative and positive control. The number of residing bacterial colonies in the root canals was determined based on the CFU/ml method. In the group of preparations irrigated with NaOCl, bacterial colonies were not observed. A single PDT eliminated 45% of the initial CFU/ml. Repeated PDT eradicated 95% of the intracanal bacterial biofilm. Photodynamic therapy has a high potential for the elimination of E. faecalis biofilm. There is a safe therapeutic window where photoinduced disinfection can be used as an adjuvant to conventional endodontic treatment, which remains the most effective.

History of myeloid-derived suppressor cells.

PubMed

Talmadge, James E; Gabrilovich, Dmitry I

2013-10-01

Tumour-induced granulocytic hyperplasia is associated with tumour vasculogenesis and escape from immunity via T cell suppression. Initially, these myeloid cells were identified as granulocytes or monocytes; however, recent studies have revealed that this hyperplasia is associated with populations of multipotent progenitor cells that have been identified as myeloid-derived suppressor cells (MDSCs). The study of MDSCs has provided a wealth of information regarding tumour pathobiology, has extended our understanding of neoplastic progression and has modified our approaches to immune adjuvant therapy. In this Timeline article, we discuss the history of MDSCs, their influence on tumour progression and metastasis, and the crosstalk between tumour cells, MDSCs and the host macroenvironment.

Emerging role of taxanes in adjuvant and neoadjuvant therapy for breast cancer: the potential and the questions.

PubMed

Goble, Sharon; Bear, Harry D

2003-08-01

Adjuvant chemotherapy has gained increasing prominence in the treatment of nonmetastatic breast cancer, producing gradual improvement in the survival of these patients. The taxanes offer great hope for adding to the progress in adjuvant treatment, but data have been conflicting. Early results of multi-center trials testing the sequential addition of paclitaxel to anthracycline-based adjuvant chemotherapy have perhaps been prematurely reported, but have already made a major impact on patterns of care for node-positive and even some node-negative patients. The early dramatic improvements in CALG 9344 are fading with time, however, and have not been confirmed by a second similar trial, NSABP B-28. Moreover, it cannot be stated with certainty whether the modest improvements observed by sequential addition of paclitaxel reflect the ability of this drug to kill anthracycline-resistant cancer cells or the increased total duration and amount of treatment. By contrast, the early results of the BCIRG 001 trial suggest that combining docetaxel with doxorubicin may significantly increase survival, but these early results should be viewed with caution and do not necessarily mean that docetaxel is superior to paclitaxel. The role of neoadjuvant chemotherapy for breast cancer has also expanded over the past 2 decades, from its initial use for inoperable locally advanced breast cancer (LABC) to its current use for patients with large operable tumors to make BCT feasible. The neoadjuvant approach also has an important role in clinical trials, where it will allow more rapid comparison of treatment regimens than can be accomplished in the adjuvant setting and provides an opportunity to analyze biologic markers as predictors of response. The value of this approach, however, will ultimately depend on a clear demonstration, not yet available, that a change in therapy that increases primary tumor response will also lead to improved long-term survival. The roles of docetaxel and paclitaxel in the neoadjuvant setting has been actively investigated over the past 5 to 10 years, and exciting results are beginning to emerge. Clearly, docetaxel has potent antitumor activity against breast cancer. Several preliminary results suggest that addition of docetaxel to an anthracycline-based regimen, particularly when added sequentially, as in NASBP B-27 and the Aberdeen trial, results in higher clinical and pathologic response rates. Whether this will translate into increased long-term survival, as suggested by the early results of the Aberdeen trial, remains to be seen. Whether sequential addition of docetaxel to doxorubicin is more or less effective than combining these drugs also has not been established. The results from M.D. Anderson suggesting that paclitaxel given on a weekly schedule was more effective than the same drug given every 3 weeks are particularly intriguing, and they may help to explain why the adjuvant studies with paclitaxel given every 3 weeks have not produced more dramatic results, whereas several studies with docetaxel (also given every 3 weeks) seem so positive. It may be that paclitaxel, with activity that is highly schedule-dependent and for which cell killing is more dependent on the duration of exposure, works best when given weekly, whereas the efficacy of docetaxel depends less on scheduling. If this is the case, then weekly paclitaxel may turn out to be equally effective as docetaxel appears to be even when given every 3 weeks. Alternatively, if docetaxel is simply a more active drug, then giving docetaxel weekly may be the most effective taxane regimen. Whether routine use of weekly chemotherapy administration in the adjuvant or neoadjuvant setting is practical or not is largely subjective, but at least it appears that the toxicity of this approach is acceptable. These issues are also being addressed in ongoing trials. Finally, taxanes have produced dramatic increases in response rates in the neoadjuvant setting, but, except for the Aberdeen trial, survival benefits have not yet been shown. If, however, the high pCR rates do translate into overall survival benefits that are greater than adding taxanes to postoperative adjuvant therapy, it might suggest that, unlike other drugs, taxanes are actually more effective before surgery than after, as predicted originally based on laboratory experiments. Clearly, much work remains to be done in this area of research on breast cancer therapy.

The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

PubMed Central

Lesiuk, Teresa

2016-01-01

Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients’ narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

PubMed

Zhu, Xin Yan; Liu, Fei

2017-04-01

Over 80% of individuals infected with Helicobacter pylori (H. pylori) are asymptomatic. Increased resistance to antibiotics and decreased compliance to the therapeutic regimens have led to the failure of eradication therapy. Probiotics, with direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials, have recently been used as a supplementary treatment in H. pylori eradication therapy. Probiotics have been considered useful because of the improvements in H. pylori eradication rates and therapy-related side effects although treatment outcomes using probiotics are controversial due to the heterogeneity of species, strains, doses and therapeutic duration of probiotics. Thus, despite the positive role of probiotics, several factors need to be further considered during their applications. Moreover, adverse events of probiotic use need to be noted. Further investigations into the safety of adjuvant probiotics to H. pylori eradication therapy are required. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Women's experiences of hormonal therapy for breast cancer: exploring influences on medication-taking behaviour.

PubMed

Cahir, Caitriona; Dombrowski, Stephan U; Kelly, Catherine M; Kennedy, M John; Bennett, Kathleen; Sharp, Linda

2015-11-01

Five to 10 years of adjuvant hormonal therapy is recommended to prevent breast cancer recurrence. This study investigated modifiable influences on adjuvant hormonal therapy medication-taking behaviour (MTB) in women with stage I-III breast cancer. Semi-structured face-to-face interviews among women with stage I-III breast cancer prescribed adjuvant hormonal therapy purposively sampled by their MTB at two cancer centres. Thematic analysis was conducted based on the Framework approach, with the Theoretical Domains Framework (TDF) informing the analysis framework; the TDF is an integrative framework consisting of 14 domains of behavioural change to inform intervention design. Thirty-one women participated in interviews (14 adherent/persistent; 7 non-adherent/persistent; 10 non-persistent). Three domains identified both barriers and enablers to hormonal therapy MTB across the three MTB strata: beliefs about consequences, intentions and goals and behaviour regulation, but their influence was different across the strata. Other domains influenced individual MTB strata. Key enablers for adherent/persistent women were identified within the domain beliefs about consequences (breast cancer recurrence), intentions and goals (high-priority), beliefs about capabilities (side effects) and behaviour regulation (managing medication). Barriers were identified within the domain behaviour regulation (no routine), memory, attention and decision processes (forgetting) and environmental context and resources (stressors) for non-adherent/persistent women and intentions and goals (quality of life), behaviour regulation (temporal self-regulation), reinforcement, beliefs about consequences (non-necessity) and social influences (clinical support) for non-persistent women. This study identified modifiable influences on hormonal therapy MTB. Targeting these influences in clinical practice may improve MTB and hence survival in this population.

[Treatment of non-small cell lung carcinoma in early stages].

PubMed

Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

2013-12-01

Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Adjuvant strategies for potentiation of antibiotics to overcome antimicrobial resistance.

PubMed

Pieren, Michel; Tigges, Marcel

2012-10-01

Alarming facts about the occurrence and spreading of multiple antibiotic resistant bacteria have caught the attention of global surveillance authorities and public media. The demand for novel effective antimicrobial drugs is high and on the rise while, at the same time, the supply of fresh 'magic bullets' is drying up. This review summarizes examples of recent strategies for development of adjunctive antibiotic therapies that overcome microbial resistance and thus rejuvenate the existing arsenal of drugs. Recent studies have demonstrated the potential of compounds that inhibit the action of the repressor protein implicated in ethionamide resistance, thus stimulating activation of the drug and thereby restoring the activity of the antibiotic for treatment of Mycobacterium tuberculosis. Such specific interference with regulators or signal transduction mechanisms involved in antibiotic resistance or virulence provides a new toolbox for novel combinations of antimicrobial drugs with adjuvant molecules lacking intrinsic antibiotic activity. In addition to the development of new antibiotics and vaccination initiatives this strategy of restoring or potentiating the activity of existing antibiotics may help to postpone the day when antibiotics are no longer generally efficacious. Copyright © 2012 Elsevier Ltd. All rights reserved.

Immunomodulatory effects of pidotimod in adults with community-acquired pneumonia undergoing standard antibiotic therapy.

PubMed

Trabattoni, D; Clerici, M; Centanni, S; Mantero, M; Garziano, M; Blasi, F

2017-06-01

The morbidity and mortality of community-acquired pneumonia (CAP) are still elevated and two aspects seem to contribute to a worse outcome: an uncontrolled inflammatory reaction and an inadequate immune response. Adjuvants, including corticosteroids and intravenous immunoglobulins, have been proposed to counterbalance these effects but their efficacy is only partial. We examined the immunomodulatory activity of Pidotimod (PDT), a synthetic dipeptide molecule in adult patients hospitalized for CAP. Sixteen patients with a diagnosis of CAP and a PSI score III or IV and/or a CURB-65 0-2 were randomized to receive either levofloxacin 500 mg b.i.d. alone or levofloxacin plus PDT (800mg, 2 daily doses). Blood samples were drawn at baseline (T0), before initiation of therapy, as well as 3 (T3), and 5 (T5) days after initiation of therapy. Immunologic and clinical parameters were analyzed at each time point. Supplementation of antibiotic therapy with PDT resulted in an upregulation of antimicrobial and of immunomodulatory proteins as well as in an increased percentage of Toll like receptor (TLR)2- and TLR4, and of CD80- and CD86-expressing immune cells. Notably, Pidotimod supplementation was also associated with a robust reduction of TNFα-producing immune cells. No significant differences were observed in clinical parameters. These results confirm that supplementation of antibiotic therapy with Pidotimod in patients with CAP results in a potentially beneficial modulation of innate immunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

A randomized trial of adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy for operable breast cancer stratified by estrogen receptors.

PubMed

Nomura, Y; Tashiro, H; Hisamatsu, K; Shinozuka, K

1988-06-01

Based on estrogen receptor (ER) status and menopausal status, operable breast cancer (International Union Against Cancer [UICC] Stage I, II, and III) patients were randomized for adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy, and the effects on the disease-free survival (DFS) and overall survival (OS) were compared. Adjuvant endocrine therapy was composed of tamoxifen (TAM) 20 mg/day orally for 2 years in postmenopausal patients. In premenopausal patients, oophorectomy (OVEX) was done before TAM administration. In the chemotherapy arm, the patients were given 0.06 mg/kg of body weight of mitomycin C (MMC) intravenously (IV) and then an oral administration of cyclophosphamide (CPA) 100 mg/body orally in an administration of a 3-month period and a 3-month intermission. This 6-month schedule was repeated four times in 2 years. As the chemoendocrine therapy arm, TAM with MMC + CPA chemotherapy was added. The patients were randomized according to ER and menopausal status. Estrogen receptor-positive (ER+) cancer patients were randomized to three arms: TAM +/- OVEX, MMC + CPA, or MMC + CPA + TAM. For estrogen receptor-negative (ER-) patients, there were two arms: MMC + CPA, or MMC + TAM. The study started in September 1978, and 692 patients entered until the end of 1984 were evaluated. The median follow-up was about 46 months. Totally, a 9.8% rate (68/692) of recurrence was noted, a 7.5% rate (52/692) of mortality. There were no significant differences in DFS or OS among the treatment arms in ER+ or ER- patients. There was significant differences in adverse effects such as bone marrow suppression, gastrointestinal disturbances, cystitis, hair loss between endocrine therapy and chemotherapy or chemoendocrine therapy groups. In this preliminary study, it was concluded that because of less adverse effects of endocrine therapy, it seems rational to select the operable breast cancer patients by the presence or absence of ER, namely, endocrine therapy for ER+ and chemotherapy for ER- cancer patients.

Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer

PubMed Central

Schiavon, Gaia; Hrebien, Sarah; Garcia-Murillas, Isaac; Cutts, Rosalind J; Pearson, Alex; Tarazona, Noelia; Fenwick, Kerry; Kozarewa, Iwanka; Lopez-Knowles, Elena; Ribas, Ricardo; Nerurkar, Ashutosh; Osin, Peter; Chandarlapaty, Sarat; Martin, Lesley-Ann; Dowsett, Mitch; Smith, Ian E; Turner, Nicholas C.

2016-01-01

Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AI). We developed ultra-high sensitivity multiplexed digital PCR assays for ESR1 mutations in circulating tumor DNA (ctDNA) and used these to investigate the clinical relevance and origin of ESR1 mutations in a cohort of 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies, and could be assessed in samples shipped at room temperature in preservative tubes without loss of accuracy. ESR1 mutations were found exclusively in patients with estrogen receptor positive breast cancer previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy (HR 3.1, 95%CI 1.9-23.1, log rank p=0.0041). ESR1 mutation prevalence differed markedly between patients that were first exposed to AI during the adjuvant and metastatic settings (5.8% (3/52) vs 36.4% (16/44) respectively, p=0.0002). In an independent cohort, ESR1 mutations were identified in 0% (0/32, 95%CI 0-10.9%) tumor biopsies taken after progression on adjuvant AI. In a patient with serial samples taken during metastatic treatment, ESR1 mutation was selected during metastatic AI therapy, to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI therapy, but are commonly selected by therapy for metastatic disease, providing evidence that the mechanisms of resistance to targeted therapy may be substantially different between the treatment of micro-metastatic and overt metastatic cancer. PMID:26560360

Add-ons in IVF programme – Hype or Hope?

PubMed Central

Datta, AK; Campbell, S; Deval, B; Nargund, G

2015-01-01

A series of new technologies and adjuvant therapies have been advocated in order to improve the success of IVF treatment. Dehydro-epiandrostenedione, growth hormones, Coenzyme Q 10, calcium ionosphores, immune therapy, heparin, low-dose aspirin, and vasodilators are among commonly prescribed pharmacological adjuvants. New technologies that are proposed to improve IVF outcomes include advanced sperm selection procedures, time- lapse embryo monitoring, preimplantation genetic screening, assisted hatching endometrial injury or embryo-glue. This review looked into current evidence to justify the use of these co-interventions and whether some of them can still be offered while awaiting more robust evidence to con rm or refute their role. PMID:27729969

Adjuvant electrochemotherapy for incompletely excised anal sac carcinoma in a dog.

PubMed

Spugnini, Enrico P; Dotsinsky, Ivan; Mudrov, Nikolay; Bufalini, Massimiliano; Giannini, Giovanni; Citro, Gennaro; Feroce, Florinda; Baldi, Alfonso

2008-01-01

Canine anal sac gland carcinoma (ASGC) is a frequently described neoplasm that is highly aggressive and can frequently lead to metastatic spread. In this paper, we describe the successful treatment of an incompletely excised ASGC by using cisplatin selectively driven within the tumor cells by trains of biphasic pulses. The dog received two courses of electrochemotherapy 14 days apart. Neither systemic nor local toxicities were detected during the whole course of therapy. The dog is still in complete remission after 18 months. Electrochemotherapy is a safe and efficacious adjuvant therapy for ASGC and warrants further investigation in order to standardize its protocols.

Speech-language therapy program for mouth opening in patients with oral and oropharyngeal cancer undergoing adjuvant radiotherapy: a pilot study.

PubMed

Marrafon, Caroline Somera; Matos, Leandro Luongo; Simões-Zenari, Marcia; Cernea, Claudio Roberto; Nemr, Katia

2018-01-01

Purpose Assess the effectiveness of an orofacial myofunctional therapeutic program in patients with oral or oropharyngeal cancer submitted to adjuvant radiotherapy through pre- and post-program comparison of maximum mandibular opening. Methods Prospective study involving five adult patients and five elderly patients postoperatively to oral cavity/oropharynx surgery who were awaiting the beginning of radiotherapy or had undergone fewer than five treatment sessions. The study participants had their maximum jaw opening measured using a sliding caliper at the beginning and end of the program. Two mobility exercises and three mandibular traction exercises were selected and weekly monitored presentially for 10 weeks. Descriptive data and pre- and post-therapy comparative measures were statistically analyzed using the Wilcoxon test. Results Ten patients (two women and eight men) with mean age of 58.4 years, median of 57.0 years, completed the therapeutic program. They presented mean maximum mandibular opening of 31.6 ± 11.7 and 36.4 ± 8.0 mm pre- and post-therapy, respectively (p =0.021). Conclusion The proposed orofacial myofunctional therapeutic program increased the maximum jaw opening of patients referred to adjuvant radiotherapy for oral cavity or oropharynx cancer treatment.

Role of Medicinal Plants for Liver-Qi Regulation Adjuvant Therapy in Post-stroke Depression: A Systematic Review of Literature.

PubMed

Zeng, Ling-Feng; Cao, Ye; Wang, Lu; Dai, Yun-Kai; Hu, Ling; Wang, Qi; Zhu, Li-Ting; Bao, Wen-Hu; Zou, Yuan-Ping; Chen, Yun-Bo; Xu, Wei-Hua; Liang, Wei-Xiong; Wang, Ning-Sheng

2017-01-01

Current evidence demonstrated certain beneficial effects of medicinal herbs as an adjuvant therapy for post-stroke depression (PSD) in China; Chai-hu (Chinese Thorowax Root, Radix Bupleuri) is an example of a medicinal plant for Liver-Qi regulation (MPLR) in the treatment of PSD. Despite several narrative reports on the antidepressant properties of MPLR, it appears that there are no systematic reviews to summarize its outcome effects. Therefore, the aim of this review was to assess the effectiveness and safety of MPLR adjuvant therapy in patients with PSD. Seven databases were extensively searched from January 2000 until July 2016. Randomized control trials (RCTs) involving patients with PSD that compared treatment with and without MPLR were taken into account. The pooled effect estimates were calculated based on Cochrane Collaboration's software RevMan 5.3. Finally, 42 eligible studies with 3612 participants were included. Overall, MPLR adjuvant therapy showed a significantly higher effective rate (RR = 1.23; 95% CI = 1.19, 1.27; p < 0.00001) compared to those without. Moreover, the administration of MPLR was superior to abstainers regarding Hamilton Depression Scale (HAMD) score changes after 3 weeks (WMD = -4.83; 95% CI = -6.82, -2.83; p < 0.00001), 4 weeks (WMD = -3.25; 95% CI = -4.10, -2.40; p < 0.00001), 6 weeks (WMD = -4.04; 95% CI = -5.24, -2.84; p < 0.00001), 8 weeks (WMD = -4.72; 95% CI = -5.57, -3.87; p < 0.00001), and 12 weeks (WMD = -3.07; 95% CI = -4.05, -2.09; p < 0.00001). In addition, there were additive benefits in terms of response changes for the National Institutes of Health Stroke Scale (NIHSS) and other self-rating scores. No frequently occurring or serious adverse events were reported. We concluded that there is supporting evidence that adjuvant therapy with MPLR is effective in reducing the depressive symptoms and enhancing quality of life for patients with PSD. More well-designed RCTs are necessary to explore the role of MPLR in the treatment of PSD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study.

PubMed

Kawashima, Atsunari; Nakai, Yasutomo; Nakayama, Masashi; Ujike, Takeshi; Tanigawa, Go; Ono, Yutaka; Kamoto, Akihito; Takada, Tsuyosi; Yamaguchi, Yuichiro; Takayama, Hitoshi; Nishimura, Kazuo; Nonomura, Norio; Tsujimura, Akira

2012-10-01

To determine through the analysis of our multi-institutional database whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma (UUTC) is beneficial. A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study. Clinical features evaluated were sex, tumor location, adjuvant chemotherapy status, tumor pathology (histology, grade, infiltrating growth, lymphovascular invasion (LVI)), and cause of death. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis. In pT3 patients, overall 5-year CSS rate was 68.4% and median CSS time was 31 months (range 3-114 months). In the adjuvant chemotherapy group, 5-year CSS rate was 80.8%, whereas 5-year CSS rate was 64.4% in the non-adjuvant chemotherapy group. By multivariate analysis, adjuvant chemotherapy status was significantly associated with CSS (P = 0.008) were sex, tumor grade, tumor histology, and LVI presence. This study, although it was retrospective study, revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis. Prospective studies evaluating adjuvant therapy regimens for UTTC are required.

Classical Hodgkin's lymphoma in adults: guidelines of the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation on initial work-up, management, and follow-up.

PubMed

Brusamolino, Ercole; Bacigalupo, Andrea; Barosi, Giovanni; Biti, Giampaolo; Gobbi, Paolo G; Levis, Alessandro; Marchetti, Monia; Santoro, Armando; Zinzani, Pier Luigi; Tura, Sante

2009-04-01

The Italian Society of Hematology (SIE), the Italian Society of Experimental Haematology (SIES) and the Italian Group for Bone Marrow Transplantation (GITMO) commissioned a project to develop practice guidelines for the initial work-up, therapy and follow-up of classical Hodgkin's lymphoma. Key questions to the clinical evaluation and treatment of this disease were formulated by an Advisory Committee, discussed and approved by an Expert Panel (EP) composed of senior hematologists and one radiotherapist. After a comprehensive and systematic literature review, the EP recommendations were graded according to their supporting evidence. An explicit approach to consensus methodologies was used for evidence interpretation and for producing recommendations in the absence of a strong evidence. The EP decided that the target domain of the guidelines should include only classical Hodgkin's lymphoma, as defined by the WHO classification, and exclude lymphocyte predominant histology. Distinct recommendations were produced for initial work-up, first-line therapy of early and advanced stage disease, monitoring procedures and salvage therapy, including hemopoietic stem cell transplant. Separate recommendations were formulated for elderly patients. Pre-treatment volumetric CT scan of the neck, thorax, abdomen, and pelvis is mandatory, while FDG-PET is recommended. As to the therapy of early stage disease, a combined modality approach is still recommended with ABVD followed by involved-field radiotherapy; the number of courses of ABVD will depend on the patient risk category (favorable or unfavorable). Full-term chemotherapy with ABVD is recommended in advanced stage disease; adjuvant radiotherapy in patients without initial bulk who achieved a complete remission is not recommended. In the elderly, chemotherapy regimens more intensive than ABVD are not recommended. Early evaluation of response with FDG-PET scan is suggested. Relapsed or refractory patients should receive high-dose chemotherapy and autologous hemopoietic stem cells transplant. Allogeneic transplant is recommended in patients relapsing after autologous transplant. All fertile patients should be informed of the possible effects of therapy on gonadal function and fertility preservation measures should be taken before the initiation of therapy.

Treatment of retroauricular keloids: Revision of cases treated at the ENT service of HC/UFPR.

PubMed

Carvalho, Bettina; Ballin, Annelyse Cristine; Becker, Renata Vecentin; Ribeiro, Talita Beithum; Cavichiolo, Juliana Benthien; Ballin, Carlos Roberto; Mocellin, Marcos

2012-04-01

 Keloids are benign tumors arising from abnormal healing of the skin, and there are several procedures available for their treatment.  The objective of this study was to evaluate the outcomes of patients undergoing treatment of keloids after ear, nose, and throat (ENT) surgeries at our service center.  We conducted thorough, retrospective and prospective analysis of records of patients undergoing treatment of retroauricular keloids at our center.  Nine patients were evaluated, and 6 underwent resection and adjuvant beta-therapy, 2 underwent resection with local application of corticosteroids, and only 1 underwent resection without adjuvant therapy. There was no recurrence of keloids in patients that were treated with beta-therapy in the early postoperative period. One patient had relapsed despite corticosteroid administration and late beta-therapy.  Several techniques have been used for the treatment of retroauricular keloids, and beta-therapy is thought to yield the best results, followed by the use of intralesional corticosteroids.  Treatment of retroauricular keloids remains a challenge. While new techniques are being developed, resection followed by early beta-therapy is still the best treatment option.

Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma.

PubMed

Long, Georgina V; Hauschild, Axel; Santinami, Mario; Atkinson, Victoria; Mandalà, Mario; Chiarion-Sileni, Vanna; Larkin, James; Nyakas, Marta; Dutriaux, Caroline; Haydon, Andrew; Robert, Caroline; Mortier, Laurent; Schachter, Jacob; Schadendorf, Dirk; Lesimple, Thierry; Plummer, Ruth; Ji, Ran; Zhang, Pingkuan; Mookerjee, Bijoyesh; Legos, Jeff; Kefford, Richard; Dummer, Reinhard; Kirkwood, John M

2017-11-09

Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety. At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P<0.001). The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group (hazard ratio for death, 0.57; 95% CI, 0.42 to 0.79; P=0.0006), but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma. Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov, NCT01682083 ; EudraCT number, 2012-001266-15 .).

Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

PubMed

Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

2016-12-01

Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P < .001). Of the 11 studies, 4 used a combination that included oxaliplatin, 2 included irinotecan, and 5 included a combination of both. Also, 7 studies used cetuximab and 4 bevacizumab. The overall progression-free survival was estimated at 14.4 months. Current evidence suggests that neoadjuvant chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Antigen-specific Immunotherapeutic Vaccine for Experimental Autoimmune Myasthenia Gravis

PubMed Central

Luo, Jie; Lindstrom, Jon

2014-01-01

Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are caused by antibody-mediated autoimmune responses to muscle nicotinic acetylcholine receptors (AChRs) that impair neuromuscular transmission thereby causing muscle weakness. Previously, we discovered that i. p. injection of a therapeutic vaccine consisting of bacterially-expressed cytoplasmic domains of human AChR subunits reduced development of chronic EAMG in rats. Here we show that immunization with the therapeutic vaccine in adjuvant does not induce EAMG, thus is safe. Potency and efficacy of the therapeutic vaccine were greatly increased by administering repeated low doses subcutaneously in incomplete Freund’s adjuvant. Onset of chronic EAMG could be prevented. Established chronic EAMG could be rapidly reversed, modeling therapy of chronic MG. Therapy reduced pathological antibodies assayed by immune precipitation of a main immunogenic region chimera. Successfully treated rats exhibited long-term resistance to re-induction of EAMG, modeling a lasting cure of MG. A long-term effect of therapy was to change isotype of the pathogenic antibody response from IgG2b that fixes complement to IgG1 that does not. Prevention and reversal of chronic EAMG was not caused by the isotype switch, but the isotype switch may contribute to resistance to reinduction of EAMG. Immunization with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG. PMID:25288571

Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality

PubMed Central

Munoz, Diego; Near, Aimee M.; van Ravesteyn, Nicolien T.; Lee, Sandra J.; Schechter, Clyde B.; Alagoz, Oguzhan; Berry, Donald A.; Burnside, Elizabeth S.; Chang, Yaojen; Chisholm, Gary; de Koning, Harry J.; Ali Ergun, Mehmet; Heijnsdijk, Eveline A. M.; Huang, Hui; Stout, Natasha K.; Sprague, Brian L.; Trentham-Dietz, Amy; Mandelblatt, Jeanne S.

2014-01-01

Background Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker. Methods We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy. Results In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13–21) and 5 per 100000 women (model range = 3–6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%–87.8% vs 85.7%–96.5%). Conclusion As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms. PMID:25255803

Levels of gemcitabine transport and metabolism proteins predict survival times of patients treated with gemcitabine for pancreatic adenocarcinoma.

PubMed

Maréchal, Raphaël; Bachet, Jean-Baptiste; Mackey, John R; Dalban, Cécile; Demetter, Pieter; Graham, Kathryn; Couvelard, Anne; Svrcek, Magali; Bardier-Dupas, Armelle; Hammel, Pascal; Sauvanet, Alain; Louvet, Christophe; Paye, François; Rougier, Philippe; Penna, Christophe; André, Thierry; Dumontet, Charles; Cass, Carol E; Jordheim, Lars Petter; Matera, Eva-Laure; Closset, Jean; Salmon, Isabelle; Devière, Jacques; Emile, Jean-François; Van Laethem, Jean-Luc

2012-09-01

Patients who undergo surgery for pancreatic ductal adenocarcinoma (PDAC) frequently receive adjuvant gemcitabine chemotherapy. Key determinants of gemcitabine cytotoxicity include the activities of the human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), and ribonucleotide reductase subunit 1 (RRM1). We investigated whether tumor levels of these proteins were associated with efficacy of gemcitabine therapy following surgery. Sequential samples of resected PDACs were retrospectively collected from 434 patients at 5 centers; 142 patients did not receive adjuvant treatment (33%), 243 received adjuvant gemcitabine-based regimens (56%), and 49 received nongemcitabine regimens (11%). We measured protein levels of hENT1, dCK, and RRM1 by semiquantitative immunohistochemistry with tissue microarrays and investigated their relationship with patients' overall survival time. The median overall survival time of patients was 32.0 months. Among patients who did not receive adjuvant treatment, levels of hENT1, RRM1, and dCK were not associated with survival time. Among patients who received gemcitabine, high levels of hENT1 and dCK were significantly associated with longer survival time (hazard ratios of 0.34 [P < .0001] and 0.57 [P = .012], respectively). Interaction tests for gemcitabine administration and hENT1 and dCK status were statistically significant (P = .0007 and P = .016, respectively). On multivariate analysis of this population, hENT1 and dCK retained independent predictive values, and those patients with high levels of each protein had the longest survival times following adjuvant therapy with gemcitabine. High levels of hENT1 and dCK in PDAC predict longer survival times in patients treated with adjuvant gemcitabine. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Tolerance of adjuvant letrozole outside of clinical trials.

PubMed

Fontaine, C; Meulemans, A; Huizing, M; Collen, C; Kaufman, L; De Mey, J; Bourgain, C; Verfaillie, G; Lamote, J; Sacre, R; Schallier, D; Neyns, B; Vermorken, J; De Grève, J

2008-08-01

Recently aromatase inhibitors have become a standard care as an adjuvant treatment for many postmenopausal patients with hormone receptor positive early breast cancer. Adjuvant letrozole was made available either immediately postoperative, after 2-3 years of tamoxifen, or as an extended treatment after 5 years of tamoxifen. Between October 2003 and October 2005, we analyzed the subjective tolerance in 185 postoperative early breast cancer patients receiving letrozole outside of a clinical trial. The most prominent toxicity was musculoskeletal pain. In addition hot flushes, increased fatigue, nausea, vomiting, anorexia, mood disturbances, vaginal dryness, hair loss and rash were also recorded. In contrast to the prospective randomized clinical trials, a high drop-out rate of 20% was documented, mainly due to aromatase inhibitor-associated arthralgia syndrome interfering significantly with the daily life of our patients. Although adjuvant aromatase inhibitors have proven to be generally superior to tamoxifen in the adjuvant setting, it is important to focus attention on the tolerance during the adjuvant therapy and to balance this against the potential benefit in individual patients. Alternative options including switching to tamoxifen remain available.

Retrospective study of adjuvant icotinib in postoperative lung cancer patients harboring epidermal growth factor receptor mutations

PubMed Central

Yao, Shuyang; Zhi, Xiuyi; Wang, Ruotian; Qian, Kun; Hu, Mu

2016-01-01

Background Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non‐small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR‐tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR‐mutated NSCLC patients undergoing resection of stage IB–IIIA. Methods Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy. Survival factors were evaluated by univariate and Cox regression analysis. Results The median follow‐up time was 30 months (range 24–41). At the data cut‐off, five patients (25%) had recurrence or metastasis and one patient had died of the disease. The two‐year disease‐free survival (DFS) rate was 85%. No recurrence occurred in the high‐risk stage IB subgroup during the follow‐up period. In univariate analysis, the micropapillary pattern had a statistically significant effect on DFS (P = 0.040). Multivariate logistic regression analysis showed that there was no independent predictor. Drug related adverse events (AEs) occurred in nine patients (45.0%). The most common AEs were skin‐related events and diarrhea, but were relatively mild. No grade 3 AEs or occurrences of intolerable toxicity were observed. Conclusions Icotinib as adjuvant therapy is effective in patients harboring EGFR mutations after complete resection, with an acceptable AE profile. Further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. PMID:27766784

[Practical neoadjuvant and adjuvant therapies for rectal cancer. How many patients are actually recruited in multimodality therapy concepts? An analysis of the Tumour Centre Schwerin].

PubMed

Sauer, J; Sobolewski, K; Dommisch, K

2009-09-01

For rectal cancer in UICC stage II or III, a neoadjuvant chemoradiotherapy or short-course radiotherapy is established to reduce the incidence of local relapses. It has been documented that the neoadjuvant therapy is superior to the adjuvant therapy. In spite of the formulation of therapeutic principles in guidelines, they are not consistently applied. The actual rate of application and the reasons for a change from the recommended treatment strategy have been investigated. The data of the tumour centre West Mecklenburg were analysed. Data concerning the type and stage of rectal cancer, multimodal treatment (surgery with or without neoadjuvant therapy or adjuvant therapy) and treatment according to the level of medical care of hospitals were recorded from 2000 to 2008. In addition, in our clinic prospectively collected data of patients with rectal cancer (September 2006 until December 2008) were used to find out the reasons for the denial of neoadjuvant therapy. During the observation period we detected 348 patients with rectal cancer in UICC stage II or III in the area of the tumour centre West Mecklenburg. 16 % of these patients were treated pre-operatively. An increase in the preoperative multimodal treatment from 3 % to 39 % was observed. Hospitals with higher provisions of medical care applied the multimodal treatment 4-fold more frequently during this period of time. 55 patients of our own clinic were found to be of UICC stage II or III. 6 patients were emergency cases. The carcinoma was found in the lower or middle third of the rectum in 38 of our patients. The endosonographical examination could not adequately show the tumour or was falsely negative in 16 of these patients. A neoadjuvant treatment was started for 58 % of the patients. Overall, 76 of patients with rectal carcinoma were treated adjuvant or neoadjuvant, 62 of them with a complete treatment scheme. The application of neoadjuvant treatment for rectal carcinoma in UICC stage II or III in West Mecklenburg was unexpectedly low during the observation period. However, an increase in treatment frequency was detected. During the same period of time the number of patients treated in hospitals of basic and standard medical care decreased by half. This is the reason for the regional increase of neoadjuvant treatment. 47 % of the patients of our clinic received neoadjuvant chemoradiotherapy or a short-course radiotherapy. Including the adjuvant treatment, 76 % of all patients were treated multimodally. An increase in neoadjuvant treatment can only be achieved by shifting patients to centres with an appropriate diagnostic facility and a regular tumour board for rectal cancer. (c) Georg Thieme Verlag Stuttgart-New York.

Adjuvant helical IMRT by tomotherapy for bulky adrenocortical carcinoma operated with positive margins: a case report.

PubMed

Delmastro, Elena; Garibaldi, Elisabetta; Gabriele, Domenico; Bresciani, Sara; Cattari, Gabriella; Dia, Amalia Di; Manini, Claudia; Collura, Devis; Redda, Maria Grazia Ruo; Gabriele, Pietro

2016-11-11

Adrenocortical carcinoma (ACC) is a rare tumor in the adult. The main therapy is surgery but in some cases radiotherapy may be needed to control the disease locally. A patient with a surgically removed bulky ACC and pathologic finding of a positive margin was treated at our center by adjuvant mitotane and radiotherapy using an intensity-modulated radiation therapy (IMRT)/image-guided radiotherapy (IGRT) technique by tomotherapy. Dose prescriptions were 63 Gy on the surgical bed and 50.4 Gy on the lymphatic drainage in 28 sessions. Patient compliance was good with no evidence of acute or late toxicities. Thirty months after radiotherapy, the patient is alive without evidence of disease checked by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and without any complication. In patients with adverse prognostic features, the delivery of adequate adjuvant radiotherapy doses with IMRT and daily IGRT is feasible and safe and could result in an improved outcome for patients with ACC.

Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

PubMed Central

Liao, Guo-Shiou; Shyur, Lie-Fen

2013-01-01

Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM) used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy. PMID:23840256

Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study.

PubMed

Borgquist, Signe; Giobbie-Hurder, Anita; Ahern, Thomas P; Garber, Judy E; Colleoni, Marco; Láng, István; Debled, Marc; Ejlertsen, Bent; von Moos, Roger; Smith, Ian; Coates, Alan S; Goldhirsch, Aron; Rabaglio, Manuela; Price, Karen N; Gelber, Richard D; Regan, Meredith M; Thürlimann, Beat

2017-04-10

Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor-positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer-free interval, and distant recurrence-free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer-free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence-free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor-positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.

Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.

PubMed

Yamazaki, Naoya; Uhara, Hisashi; Wada, Hidefumi; Matsuda, Kenji; Yamamoto, Keiko; Shimamoto, Takashi; Kiyohara, Yoshio

2016-10-01

In the adjuvant setting for malignant melanoma, interferon (IFN)-α-2b and pegylated (PEG) IFN-α-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-α-2b. As with a previously reported phase III study, patients were to receive PEG IFN-α-2b 6 μg/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 μg/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-α-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial. © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer.

PubMed

Lutz, Manfred P; Zalcberg, John R; Ducreux, Michel; Aust, Daniela; Bruno, Marco J; Büchler, Markus W; Delpero, Jean-Robert; Gloor, Beat; Glynne-Jones, Rob; Hartwig, Werner; Huguet, Florence; Laurent-Puig, Pierre; Lordick, Florian; Maisonneuve, Patrick; Mayerle, Julia; Martignoni, Marc; Neoptolemos, John; Rhim, Andrew D; Schmied, Bruno M; Seufferlein, Thomas; Werner, Jens; van Laethem, Jean-Luc; Otto, Florian

2017-07-01

The primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations. It was generally accepted that radical surgical resection followed by adjuvant chemotherapy offers the only evidence-based treatment with a chance for cure. Initial staging should classify localised tumours as resectable or unresectable (i.e. locally advanced pancreatic cancer) although there remains a large grey-zone of potentially resectable disease between these two categories which has recently been named as borderline resectable, a concept which was generally accepted by the panel members. However, the definition of these borderline-resectable (BR) tumours varies between classifications due to their focus on either (i) technical hurdles (e.g. the feasibility of vascular resection) or (ii) oncological outcome (e.g. predicting the risk of a R1 resection and/or occult metastases). The resulting expert discussion focussed on imaging standards as well as the value of pretherapeutic laparoscopy. Indications for biliary drainage were seen especially before neoadjuvant therapy. Following standard resection, the panel unanimously voted for the use of adjuvant chemotherapy after R0 resection and considered it as a reasonable standard of care after R1 resection, even though the optimal pathologic evaluation and the definition of R0/R1 was the issue of an ongoing debate. The general concept of BR tumours was considered as a good basis to select patients for preoperative therapy, albeit its current impact on the therapeutic strategy was far less clear. Main focus of the conference was to discuss the limits of surgical resection and to identify ways to standardise procedures and to improve curative outcome, including adjuvant and perioperative treatment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of outcomes in early stage uterine carcinosarcoma and uterine serous carcinoma.

PubMed

Desai, Neil B; Kollmeier, Marisa A; Makker, Vicky; Levine, Douglas A; Abu-Rustum, Nadeem R; Alektiar, Kaled M

2014-10-01

To assess whether contemporary adjuvant management of early stage uterine carcinosarcoma (CS) produces equal outcomes as in uterine serous carcinoma (USC). We reviewed 172 women treated from 2000 to 2011 for stage I-II USC (n=112, 65%) or CS (n=60, 35%). Adjuvant therapy was initiated in 154 (90%) patients, with 111 patients receiving intravaginal radiotherapy (IVRT)/chemotherapy. Median follow up was 4.6 years for surviving patients. Characteristics for USC vs. CS did not differ significantly by age ≥60, pelvic or para-aortic node sampling, stage, lymphovascular invasion, chemotherapy use, RT use or omission of adjuvant therapy. Outcomes were better for USC vs. CS in 5-year actuarial rates of recurrence [17% (C.I. 10-25%) vs. 45% (C.I. 31-59%), p<0.001],disease-related mortality (DRM) [11% (5-17%) vs. 30% (16-44%), p=0.016], and all-cause mortality [12% (C.I. 6-18%) vs. 34% (C.I. 20-48%), p=0.007]. In multivariable analysis, CS histology remained a significant predictor of risk for recurrence [HR 3.1 (C.I. 1.7-5.7), p<0.001], DRM [HR 2.4 (C.I. 1.1-5.1), p=0.024], and all-cause mortality [HR 2.4 (C.I. 1.2-4.8), p=0.012]. On sub-group analysis of 111 patients (77 USC, 34 CS) able to receive IVRT/chemotherapy, CS no longer was associated significantly with increased recurrence (29% vs. 15%, p=0.18), DRM (22% vs. 10%, p=0.39), or all-cause mortality (22% vs. 10%, p=0.45). CS was associated with worse outcomes than USC. However, that difference was not maintained in patients able to receive IVRT and chemotherapy. While intriguing, this result may be due in part to selection against rapid early relapsing CS patients in this group. Copyright © 2014 Elsevier Inc. All rights reserved.

A Neuroprotective Effect of the Glutamate Receptor Antagonist MK801 on Long-Term Cognitive and Behavioral Outcomes Secondary to Experimental Cerebral Malaria.

PubMed

de Miranda, Aline Silva; Brant, Fátima; Vieira, Luciene Bruno; Rocha, Natália Pessoa; Vieira, Érica Leandro Marciano; Rezende, Gustavo Henrique Souza; de Oliveira Pimentel, Pollyana Maria; Moraes, Marcio F D; Ribeiro, Fabíola Mara; Ransohoff, Richard M; Teixeira, Mauro Martins; Machado, Fabiana Simão; Rachid, Milene Alvarenga; Teixeira, Antônio Lúcio

2017-11-01

Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection, which can result in long-term cognitive and behavioral deficits despite successful anti-malarial therapy. Due to the substantial social and economic burden of CM, the development of adjuvant therapies is a scientific goal of highest priority. Apart from vascular and immune responses, changes in glutamate system have been reported in CM pathogenesis suggesting a potential therapeutic target. Based on that, we hypothesized that interventions in the glutamatergic system induced by blockage of N-methyl-D-aspartate (NMDA) receptors could attenuate experimental CM long-term cognitive and behavioral outcomes. Before the development of evident CM signs, susceptible mice infected with Plasmodium berghei ANKA (PbA) strain were initiated on treatment with dizocilpine maleate (MK801, 0.5 mg/kg), a noncompetitive NMDA receptor antagonist. On day 5 post-infection, mice were treated orally with a 10-day course chloroquine (CQ, 30 mg/kg). Control mice also received saline, CQ or MK801 + CQ therapy. After 10 days of cessation of CQ treatment, magnetic resonance images (MRI), behavioral and immunological assays were performed. Indeed, MK801 combined with CQ prevented long-term memory impairment and depressive-like behavior following successful PbA infection resolution. In addition, MK801 also modulated the immune system by promoting a balance of TH1/TH2 response and upregulating neurotrophic factors levels in the frontal cortex and hippocampus. Moreover, hippocampus abnormalities observed by MRI were partially prevented by MK801 treatment. Our results indicate that NMDA receptor antagonists can be neuroprotective in CM and could be a valuable adjuvant strategy for the management of the long-term impairment observed in CM.

Improved outcome in solitary bone plasmacytomata with combined therapy.

PubMed

Avilés, A; Huerta-Guzmán, J; Delgado, S; Fernández, A; Díaz-Maqueo, J C

1996-09-01

Solitary bone plasmacytoma (SBP) is a rare presentation of plasma cell dyscrasias. Radiotherapy has been considered the treatment of choice, however, most patients will develop multiple myeloma, 3 to 10 years after initial diagnosis and treatment. No innovations have been introduced in the treatment of SBP in the last 30 years. We began a prospective clinical trial to assess the efficacy and toxicity of adjuvant chemotherapy with low doses of melphalan and prednisone administered to patients with SBP after radiation therapy in an attempt to improve the disease-free survival and overall survival. Between 1982 and 1989, 53 patients with SBP were randomly assigned to be treated with either local radiotherapy with doses ranged from 4000 to 5000 cGy to achieve local control of disease (28 patients) or the same radiotherapy schedule followed by melphalan and prednisone given every 6 weeks for 3 years (25 patients). After a median follow-up of 8.9 years, disease-free survival and overall survival were improved in patients who were treated with combined therapy, 22 patients remain alive and free of disease in the combined treatment group compared to only 13 patients in the radiotherapy group (p < 0.01). Treatment was well tolerated; planned doses were administered in all cases; no delays in treatment or acute side-effects were observed during treatment. Long-term secondary toxicities including secondary neoplasms and acute leukaemia, have not been observed. We felt that the use of adjuvant chemotherapy after adequate doses of radiotherapy in patients with SBP improved duration of remission and survival without severe side-effects. However, as with other studies in SBP, the group was too small to draw definitive conclusions and more controlled clinical trials are necessary to define the role of this therapeutic approach in patients with SBP.

Radiation Therapy-First Strategy After Surgery With or Without Adjuvant Chemotherapy in Stage IIIA-N2 Non-Small Cell Lung Cancer.

PubMed

Lee, Hyun Woo; Noh, O Kyu; Oh, Young-Taek; Choi, Jin-Hyuk; Chun, Mison; Kim, Hwan-Ik; Heo, Jaesung; Ahn, Mi Sun; Park, Seong Yong; Park, Rae Woong; Yoon, Dukyong

2016-03-01

Postoperative radiation therapy (PORT) and postoperative chemotherapy (POCT) can be administered as adjuvant therapies in patients with non-small cell lung cancer (NSCLC). The aim of this study was to present the clinical outcomes in patients treated with PORT-first with or without subsequent POCT in stage IIIA-N2 NSCLC. From January 2002 to November 2014, the conditions of 105 patients with stage IIIA-N2 NSCLC who received PORT-first with or without subsequent POCT were analyzed. PORT was initiated within 4 to 6 weeks after surgical resection. Platinum-based POCT was administered 3 to 4 weeks after the completion of PORT. We analyzed the outcomes and the clinical factors affecting survival. Of 105 patients, 43 (41.0%) received POCT with a median of 4 cycles (range, 2-6 cycles). The follow-up times ranged from 3 to 123 months (median, 30 months), and the 5-year overall survival (OS) was 40.2%. The 5-year OS of patients treated with PORT and POCT was significantly higher than that of patients with PORT (61.3% vs 29.2%, P<.001). The significant prognostic factors affecting OS were the use of POCT (hazard ratio [HR] = 0.453, P=.036) and type of surgery (pneumonectomy/lobectomy; HR = 2.845, P<.001). PORT-first strategy after surgery appeared not to compromise the clinical outcomes in the treatment of stage IIIA-N2 NSCLC. The benefit of POCT on OS was preserved even in the PORT-first setting. Further studies are warranted to compare the sequencing of PORT and POCT, guaranteeing the proper use of POCT. Copyright © 2016 Elsevier Inc. All rights reserved.

Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

PubMed Central

Stitzenberg, Karyn B.; Sanoff, Hanna K.; Penn, Dolly C.; Meyers, Michael O.; Tepper, Joel E.

2013-01-01

Purpose Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. Methods All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. Results LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Conclusion Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE. PMID:24166526

Trametes versicolor Mushroom Immune Therapy in Breast Cancer

PubMed Central

Standish, Leanna J.; Wenner, Cynthia A.; Sweet, Erin S.; Bridge, Carly; Nelson, Ana; Martzen, Mark; Novack, Jeffrey; Torkelson, Carolyn

2009-01-01

Data from multiple epidemiologic and clinical studies on immune effects of conventional cancer treatment and the clinical benefits of polysaccharide immune therapy suggest that immune function has a role in breast cancer prevention. Immune therapy utilizing the polysaccharide constituents of Trametes versicolor (Tv) as concurrent adjuvant cancer therapy may be warranted as part of a comprehensive cancer treatment and secondary prevention strategy. PMID:19087769

Harnessing system models of cell death signalling for cytotoxic chemotherapy: towards personalised medicine approaches?

PubMed

Huber, Heinrich J; McKiernan, Ross G; Prehn, Jochen H M

2014-03-01

Most cytotoxic chemotherapeutics are believed to kill cancer cells by inducing apoptosis. Understanding the factors that contribute to impairment of apoptosis in cancer cells is therefore critical for the development of novel therapies that circumvent the widespread chemoresistance. Apoptosis, however, is a complex and tightly controlled process that can be induced by different classes of chemotherapeutics targeting different signalling nodes and pathways. Moreover, apoptosis initiation and apoptosis execution strongly depend on patient-specific, genomic and proteomic signatures. Here, we will review recent translational studies that suggest a critical link between the sensitivity of cancer cells to initiate apoptosis and clinical outcome. Next we will discuss recent advances in the field of system modelling of apoptosis pathways for the prediction of treatment responses. We propose that initiation of mitochondrial apoptosis, defined as the process of mitochondrial outer membrane permeabilisation (MOMP), is a dose-dependent decision process that allows for a prediction of individual therapy responses and therapeutic windows. We provide evidence in contrast that apoptosis execution post-MOMP may be a binary decision that dictates whether apoptosis is executed or not. We will discuss the implications of this concept for the future use of novel adjuvant therapeutics that specifically target apoptosis signalling pathways or which may be used to reduce the impact of cell-to-cell heterogeneity on therapy responses. Finally, we will discuss the technical and regulatory requirements surrounding the use and implications of system-based patient stratification tools for the future of personalised oncology.

Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

PubMed

Bluethmann, Shirley M; Alfano, Catherine M; Clapp, Jonathan D; Luta, George; Small, Brent J; Hurria, Arti; Cohen, Harvey J; Sugarman, Steven; B Muss, Hyman; Isaacs, Claudine; Mandelblatt, Jeanne S

2017-10-01

To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (<1 year); midpoint (1-3 years); and late discontinuation (>3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p < 0.001), considering covariates, but cognition was not related to discontinuation in the other periods. Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

Esophageal cancer management controversies: Radiation oncology point of view

PubMed Central

Tai, Patricia; Yu, Edward

2014-01-01

Esophageal cancer treatment has evolved from single modality to trimodality therapy. There are some controversies of the role, target volumes and dose of radiotherapy (RT) in the literature over decades. The present review focuses primarily on RT as part of the treatment modalities, and highlight on the RT volume and its dose in the management of esophageal cancer. The randomized adjuvant chemoradiation (CRT) trial, intergroup trial (INT 0116) enrolled 559 patients with resected adenocarcinoma of the stomach or gastroesophageal junction. They were randomly assigned to surgery plus postoperative CRT or surgery alone. Analyses show robust treatment benefit of adjuvant CRT in most subsets for postoperative CRT. The Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) used a lower RT dose of 41.4 Gray in 23 fractions with newer chemotherapeutic agents carboplatin and paclitaxel to achieve an excellent result. Target volume of external beam radiation therapy and its coverage have been in debate for years among radiation oncologists. Pre-operative and post-operative target volumes are designed to optimize for disease control. Esophageal brachytherapy is effective in the palliation of dysphagia, but should not be given concomitantly with chemotherapy or external beam RT. The role of brachytherapy in multimodality management requires further investigation. On-going studies of multidisciplinary treatment in locally advanced cancer include: ZTOG1201 trial (a phase II trial of neoadjuvant and adjuvant CRT) and QUINTETT (a phase III trial of neoadjuvant vs adjuvant therapy with quality of life analysis). These trials hopefully will shed more light on the future management of esophageal cancer. PMID:25132924

Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

PubMed

Gao, Sarah J; Park, Henry S; Corso, Christopher D; Rutter, Charles E; Kim, Anthony W; Johung, Kimberly L

2017-07-01

The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN + disease stratified by margin status. We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. Among cT1-2 N0 pN + esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Significance of Ovarian Function Suppression in Endocrine Therapy for Breast Cancer in Pre-Menopausal Women

PubMed Central

Scharl, A.; Salterberg, A.

2016-01-01

Ovarian function suppression (OFS) for treating breast cancer in pre-menopausal women was introduced for the first time in the late 19th century as bilateral oophorectomy. It was not until the 1960s that the oestrogen receptor was identified and a test for detecting endocrine sensitivity of the breast cancer was developed. A weakness of early trials on OFS for breast cancer treatment is therefore their failure to take receptor sensitivity into account when selecting participants. A meta-analysis performed in the early 1990s first proved that adjuvant OFS significantly improved the cure rate of oestrogen receptor-positive breast cancer in pre-menopausal women regardless of whether it was carried out through oophorectomy, radiation-induced ablation or drug therapy. In the 1970s, tamoxifen was synthesized. It became one of the most important cancer drugs and today constitutes the gold standard for endocrine adjuvant therapy. Taking tamoxifen for a five-year period lowers mortality by 30 % over 15 years. Ten years of tamoxifen therapy reduces mortality even further, with increased side effects, however. Research over the past ten years has proven that for post-menopausal women, aromatase inhibitors have benefits over tamoxifen. Current trial results have rekindled the debate about the combination of OFS with tamoxifen or with aromatase inhibitors for adjuvant breast cancer treatment of pre-menopausal women. These trials have reported an improvement in disease-free survival in patients with a high risk of recurrence when they are treated with a combination of OFS plus tamoxifen or aromatase inhibitors, especially in women younger than 35. However, combination therapy causes significantly more side effects, which could negatively impact compliance. Endocrine treatments administered over a period of many years show waning compliance, which tends to be only around 50 % after five years. Inadequate compliance compromises efficacy and increases the risk of mortality. For this reason, when indicating and supporting endocrine adjuvant therapy, physicians must ensure that compliance will be good. To prevent recurrence in the long run, it is much more effective to prescribe a somewhat less effective therapy that will actually be carried out than to prescribe one that is theoretically more effective, but is not adhered to consistently. PMID:27239060

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

DTIC Science & Technology

2016-10-01

subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO...within the proposed time frame. 15. SUBJECT TERMS Breast cancer, adjuvant treatment, aspirin, randomized controlled trial 16. SECURITY...propose a randomized controlled trial to test that promise. There is compelling epidemiologic, in-vitro, and in-vivo, evidence of aspirin’s potential

Febrile neutropaenia and chemotherapy discontinuation in women aged 70 years or older receiving adjuvant chemotherapy for early breast cancer.

PubMed

Adjogatse, D; Thanopoulou, E; Okines, A; Thillai, K; Tasker, F; Johnston, S R D; Harper-Wynne, C; Torrisi, E; Ring, A

2014-11-01

Low rates of adjuvant chemotherapy use are frequently reported in older women with early breast cancer. One of the reasons for this may be the risk of febrile neutropaenia or the perception that older patients will probably not complete the chemotherapy course prescribed. There are no data regarding these adverse outcomes in routine clinical practice. We identified 128 patients aged 70 years or over who received neoadjuvant or adjuvant chemotherapy for early breast cancer in seven UK cancer centres between 2006 and 2012. Data were collected regarding standard clinical and pathological variables and treatment toxicity and outcomes. Twenty-four patients (19%) had an episode of febrile neutropaenia. Overall, 27 patients (21%) did not complete their planned therapy. Chemotherapy discontinuation was more common in those patients with an episode of febrile neutropaenia (46% versus 16%, P = 0.004). Thirty patients (23%) were admitted with chemotherapy-related complications. There were no treatment-related deaths. The rates of febrile neutropaenia and treatment discontinuation are high in women aged 70 years or over receiving adjuvant chemotherapy for breast cancer. Close attention should be paid to the choice or regimen and the use of supportive therapies in this patient population. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer.

PubMed

Schiavon, Gaia; Hrebien, Sarah; Garcia-Murillas, Isaac; Cutts, Rosalind J; Pearson, Alex; Tarazona, Noelia; Fenwick, Kerry; Kozarewa, Iwanka; Lopez-Knowles, Elena; Ribas, Ricardo; Nerurkar, Ashutosh; Osin, Peter; Chandarlapaty, Sarat; Martin, Lesley-Ann; Dowsett, Mitch; Smith, Ian E; Turner, Nicholas C

2015-11-11

Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies and was accurately assessed in samples shipped at room temperature in preservative tubes. ESR1 mutations were found exclusively in estrogen receptor-positive breast cancer patients previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy [hazard ratio, 3.1; 95% confidence interval (CI), 1.9 to 23.1; P = 0.0041]. ESR1 mutation prevalence differed markedly between patients who were first exposed to AI during the adjuvant and metastatic settings [5.8% (3 of 52) versus 36.4% (16 of 44), respectively; P = 0.0002]. In an independent cohort, ESR1 mutations were identified in 0% (0 of 32; 95% CI, 0 to 10.9) tumor biopsies taken after progression on adjuvant AI. In a patient with serial sampling, ESR1 mutation was selected during metastatic AI therapy to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI but are commonly selected by therapy for metastatic disease, providing evidence that mechanisms of resistance to targeted therapy may be substantially different between the treatment of micrometastatic and overt metastatic cancer. Copyright © 2015, American Association for the Advancement of Science.

Critical decision-making in radiotherapy for early stage breast cancer in a neo-adjuvant treatment era.

PubMed

De Felice, Francesca; Osti, Mattia Falchetto; De Sanctis, Vitaliana; Musio, Daniela; Tombolini, Vincenzo

2017-05-01

In breast cancer management, the role of adjuvant radiation therapy (RT) has been the subject of intense controversy over the past several years, due to the improvement in neoadjuvant chemotherapy (NACT) prescription. One of the most controversial questions regarding indication for adjuvant RT is whether or not RT is essential in patients with early stage disease at diagnosis. The value of adjuvant RT remains highly debatable in those patients with clinically negative nodes at the completion of NACT. Areas covered: This review is focused on this gray area and is intended to assist with clinical decision-making. We provide a comprehensive review using PubMed and meeting proceedings of San Antonio Breast Cancer Symposium, European Society for Radiotherapy & Oncology, European Society of Medical Oncology and American Society of Clinical Oncology. Expert commentary: The identification of potential prognostic factors may lead to novel adjuvant RT indications. Phase III clinical trials are underway and their results will help guide treatment decisions.

Optimal Timing of Chemotherapy and Surgery in Patients with Muscle-Invasive Bladder Cancer and Upper Urinary Tract Urothelial Carcinoma.

PubMed

Tabayoyong, William; Li, Roger; Gao, Jianjun; Kamat, Ashish

2018-05-01

Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for patients with clinically localized muscle-invasive bladder cancer. Survival after radical cystectomy is associated with final pathologic staging. Survival decreases with increasing pT stage because of the presence of occult micrometastases, indicating the need for systemic chemotherapy. Systemic chemotherapy is delivered as either neoadjuvant therapy preoperatively, or as adjuvant therapy postoperatively. This article reviews the evidence for neoadjuvant and adjuvant chemotherapy for the treatment of muscle-invasive bladder and upper tract urothelial cancer and offers recommendations based on these data and recently updated clinical guidelines. Copyright © 2018 Elsevier Inc. All rights reserved.

Interventions to improve reproductive outcomes in women with elevated natural killer cells undergoing assisted reproduction techniques: a systematic review of literature.

PubMed

Polanski, L T; Barbosa, M A P; Martins, W P; Baumgarten, M N; Campbell, B; Brosens, J; Quenby, S; Raine-Fenning, N

2014-01-01

Is there any scientific evidence to support the routine use of adjuvant therapies for women with elevated natural killer (NK) cells undergoing assisted reproduction techniques (ARTs) in order to improve live birth rate? Due to the poor quality evidence, this review does not support the use of described adjuvant treatments in women found to have elevated absolute numbers or activity of NK cells undergoing ART. Deregulation in the numbers of NK cells and/or their activity, in the blood as well as in the endometrium, has been associated with various manifestations of reproductive failure. NK cell analysis is becoming increasingly popular as a test offered to investigate the causes of reproductive failure. Adjuvant therapies influencing the NK cells have been postulated as therapeutic options for couples where deregulation of this component of the maternal immune system is suspected as the cause of infertility or implantation failure. Systematic review. Embase, LILACS, MEDLINE, PsycINFO, CENTRAL and CINAHL databases from 1946 to present were searched with no language restrictions. Studies evaluating the use of adjuvant therapies in women undergoing ART where NK cell numbers and/or activity were assessed were considered eligible for inclusion. Only three studies (one in abstract form only) meeting the inclusion criteria were identified: two reported the use of intravenous immunoglobulins (IVIg) and one the use of oral prednisolone. All studies demonstrated a beneficial effect of the interventions on clinical pregnancy rates with a risk ratio (RR) of 1.63 [95% confidence interval (CI) 1.00-2.66] for prednisolone and 3.41 (95%CI 1.90-6.11) for IVIg. Studies assessing the efficacy of IVIg have also reported live birth rate with an RR of 3.94 (95% CI 2.01-7.69) favoring the intervention. Data heterogeneity was substantial however (I(2) = 66%) suggesting a cautious interpretation of the results. Differing study populations, lack of statistical power, method of data presentation (per couple or per cycle), the use of additional medications and differing dosage regimes contribute to data heterogeneity and suggest a cautious approach to data interpretation. This review identified some data showing that adjuvant therapies (mainly IVIg) in this selected population seem to confer some benefit on ART outcome. However, overall, the review does not support the use of prednisolone, IVIg or any other adjuvant treatment in women undergoing ART who are found to have elevated absolute numbers or activity of NK cells, purely due to the paucity of, or poor quality of, the evidence. Agreement as to the most reliable NK cell testing method must be made by the scientific community as well as 'normal' NK cell levels unequivocally defined. Well designed, sufficiently powered RCTs with an appropriate population selection and using the same NK cell testing methodology are required to ascertain the actual benefit of using adjuvant therapy treatment for elevated NK cell levels or activity in the context of pregnancy outcome following IVF. None.

Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer.

PubMed

Deva, Sanjeev; Jameson, Michael

2012-08-15

Anecdotal reports of tumour regression with histamine type 2 receptor antagonists (H(2)RAs) have lead to a series of trials with this class of drug as adjuvant therapy to try and improve outcomes in patients with resected colorectal cancers. There was a plausible scientific rationale suggesting merit in this strategy. This included improved immune surveillance (by way of increasing tumour infiltrating lymphocytes), inhibiting the direct proliferative effect of histamine as a growth factor for colorectal cancer and, in the case of cimetidine, inhibiting endothelial expression of E-selectin (a cell adhesion molecule thought to be critical for metastatic spread). To determine if H(2)RAs improve overall survival when used as pre- and/or postoperative therapy in colorectal cancer patients who have had surgical resection with curative intent. We also stratified the results to see if there was an improvement in overall survival in terms of the specific H(2)RA used. Randomised controlled trials were identified using a sensitive search strategy in the following databases: MEDLINE (1964 to present), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2009), EMBASE (1980 to present) and Cancerlit (1983 to present). Criteria for study selection included: patients with colorectal cancer surgically resected with curative intent; H(2)RAs used i) at any dose, ii) for any length of time, iii) with any other treatment modality and iv) in the pre-, peri- or post-operative period. The results were stratified for the H(2)RA used. The literature search retrieved 142 articles. There were six studies included in the final analysis, published from 1995 to 2007, including a total of 1229 patients. All patients were analysed by intention to treat according to their initial allocation. Log hazard ratios and standard errors of treatment effects (on overall survival) were calculated using the Cochrane statistical package RevMan Version 5. Hazard ratios and standard errors were recorded from trial publications or, if not provided, were estimated from published actuarial survival curves using a spreadsheet designed for this purpose (http://www.biomedcentral.com/content/supplementary/1745-6215-8-16-S1.xls). Of the six identified trials, five used cimetidine as the experimental H(2)RA, whereas one used ranitidine. There was a trend towards improved survival when H(2)RAs were utilised as adjuvant therapy in patients having curative-intent surgery for colorectal cancer (HR 0.70; 95% CI 0.48-1.03, P = 0.07). Analysis of the five cimetidine trials (n = 421) revealed a statistically significant improvement in overall survival (HR 0.53; 95% CI 0.32 to 0.87). Of the H(2)RAs evaluated cimetidine appears to confer a survival benefit when given as an adjunct to curative surgical resection of colorectal cancers. The trial designs were heterogeneous and adjuvant therapy has evolved since these trials were performed. Further prospective randomised studies are warranted.

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

PubMed

Giusti, M; Caorsi, V; Mortara, L; Caputo, M; Monti, E; Schiavo, M; Bagnara, M C; Minuto, F; Bagnasco, M

2014-03-01

In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 ± 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 ± 3.8 ml; group 1), while 13 patients (74.1 ± 7.9 year) had non-autoimmune pre-toxic (TSH <0.3 mIU/l) MNG (TV: 82.6 ± 14.4 ml; group 2). TSH, thyroid hormones, TV (by ultrasonography), body mass index (BMI), symptoms and quality of life (QoL) were evaluated. Treatment induced short-term thyrotoxicosis in both groups, but this was slightly more marked in group 2 than in group 1. The number and severity of adverse events were similar. The follow-up period was 55.3 ± 4.1 months in group 1 and 57.2 ± 5.1 months in group 2. The final TV reduction was similar in groups 1 (63.4 ± 3.6%) and 2 (57.2 ± 4.6%) and TV reduction positively correlated only with initial TV. At the last examination, 14 group-1 subjects were on L-T4 therapy, while 2 group-2 subjects were on methimazole. An increase in BMI was noted only in group 2. MNG-related symptoms were significantly reduced in both groups. Symptoms related to sub-clinical hyperthyroidism improved in group 2, while no significant changes in QoL were noted in either group. This study confirms the effectiveness of rhTSH adjuvant treatment in reducing TV after low RAI activities, irrespective of baseline thyroid status. TSH levels <0.3 mIU/l proved to be predictive of a more severe thyrotoxic phase after rhTSH and RAI, while initial TSH levels >0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects.

How do I deal with the axilla in patients with a positive sentinel lymph node?

PubMed

Falkson, Conrad B

2011-12-01

Optimal management of the axilla in a patient with a positive sentinel node biopsy is not yet defined.These patients usually have Breast Conserving Surgery and receive adjuvant systemic therapy and whole breast radiation.Treatment options for the axilla include: no further surgery with or without radiation completion axillary nodal dissection with or without radiation Radiation options in addition to whole breast radiation include axillary and supraclavicular nodal irradiation regional nodal irradiationincludes supraclavicular and internal mammary nodes Completion axillary dissection has been standard practice in patients with positive sentinel nodes. the number of involved nodes provides prognostic information. theoretically improves local control, but may be obviated by systemic chemotherapy. but avoidance of dissection may not adversely affect locoregional control or survival. dissection has significant morbidity so safe avoidance is desirable. There is little worldwide concordance on the use of radiation: whole breast radiation (commonly used after breast conserving surgery) may radiate the lower axilla supraclavicular radiation is most commonly recommended for patients with four or more nodes but may confer a survival benefit on patients with lower risk disease. adding nodal irradiation reduces local recurrence with only modest toxicity. Adjuvant systemic therapy provides a survival benefit for patients with nodal disease. Most will receive cytostatic chemotherapy containing an anthracycline and a taxane. Hormone therapy is appropriate for estrogen receptor positive disease. The extent to which systemic therapy controls microscopic nodal disease is unknown. Node positive patients should generally receive adjuvant chemotherapy.A small group of patients benefit from specific nodal therapy. Further studies are needed to better identify these patients.

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

PubMed Central

2013-01-01

Abstract Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis. Antioxid. Redox Signal. 19, 2129–2140. PMID:23682970

Use of adjuvant trastuzumab in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer by race/ethnicity and education within the National Comprehensive Cancer Network.

PubMed

Freedman, Rachel A; Hughes, Melissa E; Ottesen, Rebecca A; Weeks, Jane C; He, Yulei; Wong, Yu-Ning; Theriault, Richard; Keating, Nancy L

2013-02-15

Trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive breast cancer is highly efficacious yet costly and time-intensive, and few data are available about its use. The authors of this report examined receipt and completion of adjuvant trastuzumab by race/ethnicity and education for women with HER2-positive disease. The National Comprehensive Cancer Network Breast Cancer Outcomes Database was used to identify 1109 women who were diagnosed with stage I through III, HER2-positive breast cancer during September 2005 through December 2008 and were followed for ≥1 year. The authors used multivariable logistic regression to assess the association of race/ethnicity and education with the receipt of trastuzumab and, among those women who initiated trastuzumab, with the completion of > 270 days of therapy. The cohort was 75% white, 8% black, and 9% Hispanic; and 20% of women had attained a high school degree or less. Most women (83%) received trastuzumab, and no significant differences were observed according to race/ethnicity or socioeconomic status. Among the women who initiated trastuzumab, 73% of black women versus 87% of white women (P = .007) and 70% of women with less than a high school education versus 90% of women with a college degree completed > 270 days of therapy (P = .006). In adjusted analyses, black women (vs white women) and women without a high school degree (vs those with a college degree) had lower odds of completing therapy (black women: odds ratio, 0.45; 95% confidence interval, 0.27-074; white women: odds ratio, 0.27, 95% confidence interval, 0.14-0.51). Differences in completing trastuzumab therapy were observed according to race and educational attainment among women who received treatment at National Comprehensive Cancer Network centers. Efforts to assure the appropriate use of trastuzumab and to understand treatment barriers are needed and may lead to improved outcomes. The authors report differences in the rate at which patients complete treatment with trastuzumab according to race and education among women who receive treatment at National Comprehensive Cancer Network centers. Efforts to assure the appropriate use of trastuzumab and to understand treatment barriers are needed and may lead to improved outcomes. Copyright © 2012 American Cancer Society.

Effectiveness of Mechanical Debridement Combined With Adjunctive Therapies for Nonsurgical Treatment of Periimplantitis: A Systematic Review.

PubMed

de Almeida, Juliano Milanezi; Matheus, Henrique Rinaldi; Rodrigues Gusman, David Jonathan; Faleiros, Paula Lazilha; Januário de Araújo, Nathália; Noronha Novaes, Vivian Cristina

2017-02-01

This study aimed to perform a systematic review of the effectiveness of nonsurgical treatment associated with different adjuvant therapies on periimplantitis. Different individuals, following a research process, performed a network research of controlled and randomized controlled clinical trials on PubMed, Embase/MEDLINE, with 20 years' time constraint and the last search in January 2016. From 108 articles found by the first search, they analyzed 10 full texts, and in none did they find a standard control group. When compared, mechanical therapies combined with adjuvant therapy decreased prevalence of periimplant ratios; however, some groups showed unsatisfactory results, mainly related to the probing depth and bleeding index. When comparing debridement with other nonsurgical therapies (Er:YAG, Vector, air abrasive with amino acid glycine powder), increased periimplant levels were noticed in the test and control groups, although in different periods. Despite the improvement in the periimplant indices, there is no sufficient evidence to score the best results or even to choose the best association for nonsurgical treatment of periimplantitis; hence, more trials are necessary to answer this question.

Progress in Rectal Cancer Treatment

PubMed Central

Ceelen, Wim P.

2012-01-01

The dramatic improvement in local control of rectal cancer observed during the last decades is to be attributed to attention to surgical technique and to the introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse remains frequent and is currently insufficiently addressed. Intensification of neoadjuvant therapy by incorporating chemotherapy with or without targeted agents before the start of (chemo)radiation or during the waiting period to surgery may present an opportunity to improve overall survival. An increasing number of patients can nowadays undergo sphincter preserving surgery. In selected patients, local excision or even a “wait and see” approach may be feasible following active neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative imaging techniques may in the future allow better selection of patients for this treatment option. Controversy persists concerning the selection of patients for adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The currently available evidence suggests that in complete pathological responders long-term outcome is excellent and adjuvant therapy may be omitted. The results of ongoing trials will help to establish the ideal tailored approach in resectable rectal cancer. PMID:22970381

Perivascular epithelioid cell tumor located retroperitoneally with pulmonary lymphangioleiomyomatosis: report of a case.

PubMed

Pata, Giacomo; Tironi, Andrea; Solaini, Leonardo; Tiziano, Travaglia; Ragni, Fulvio

2014-03-01

Perivascular epithelioid cell neoplasms, also known as "PEComas", are unusual mesenchymal tumors, exhibiting perivascular epithelioid cell differentiation and characterized by a mixed myogenic and melanocytic phenotype. "PEComas not otherwise specified" (PEComas-NOS) are especially rare; consequently, there are no published large series, but only case reports. These tumors are rarely located retroperitoneally, with only about 15 such cases reported. We report a case of pulmonary diffuse lymphangioleiomyomatosis with large retroperitoneal PEComa-NOS in a 66-year-old woman. Treatment consisted only of tumor resection, without additional adjuvant therapy. We emphasize the importance of correct immunohistochemistry diagnosis, initiation of recommended treatment, and surveillance of this unique family of tumors.

History of myeloid derived suppressor cells (MDSCs) in the macro- and micro-environment of tumour-bearing hosts

PubMed Central

Talmadge, James E.; Gabrilovich, Dmitry I.

2015-01-01

Tumour-induced granulocytic hyperplasia is associated with tumour vasculogenesis and escape from immunity via T-cell suppression. Initially, these myeloid cells were identified as granulocytes or monocytes; however, recent studies revealed that this hyperplasia was associated with populations of multi-potent progenitor cells identified as myeloid-derived suppressor cells (MDSCs). The discovery and study of MDSCs have provided a wealth of information regarding tumour pathobiology, extended our understanding of neoplastic progression, and modified our approaches to immune adjuvant therapy. In this perspective, we discuss the history of MDSCs, their influence on tumour progression and metastasis, and the crosstalk between tumour cells, MDSCs, and the host macroenvironment. PMID:24060865

AHNS Series: Do you know your guidelines?Principles of radiation therapy for head and neck cancer: A review of the National Comprehensive Cancer Network guidelines.

PubMed

Gooi, Zhen; Fakhry, Carole; Goldenberg, David; Richmon, Jeremy; Kiess, Ana P

2016-07-01

This article is a continuation of the "Do You Know Your Guidelines" series, an initiative of the American Head and Neck Society's Education Committee to increase awareness of current best practices pertaining to head and neck cancer. The National Comprehensive Cancer Network guidelines for radiotherapy in the treatment for head and neck cancers are reviewed here in a systematic fashion according to site and stage. These guidelines outline indications for primary and adjuvant treatment, as well as general principles of radiotherapy. © 2016 Wiley Periodicals, Inc. Head Neck 38: 987-992, 2016. © 2016 Wiley Periodicals, Inc.

[Bacterial meningitis in adults in emergency and rescue services].

PubMed

Klein, M; Pfister, H-W

2016-10-01

The cardinal symptoms of bacterial meningitis are headache, fever, impaired consciousness and nuchal stiffness (meningism); however, the diagnosis of acute bacterial meningitis can only be confirmed or ruled out by investigation of cerebrospinal fluid. The recommended empirical antibiotic regimen for community-acquired acute bacterial meningitis in adults in Germany is a combination of ceftriaxone and ampicillin plus adjuvant dexamethasone. An important influenceable factor for treatment success of acute bacterial meningitis is a rapid induction of antibiotic therapy, which must be initiated directly after lumbar puncture. When this is delayed for any reason, e. g. because of the necessity of cerebral computed tomography imaging before lumbar puncture, antibiotics should be started even before acquisition of cerebrospinal fluid.

[Conversion Therapy of Initially Unresectable Rectal Cancer with Perforation via FOLFOX4 Chemotherapy].

PubMed

Yamada, Chizu; Ishikawa, Fumihiko; Nitta, Hiroshi; Fujita, Yoshihisa; Omoto, Hideyuki; Kamata, Shigeyuki; Ito, Hiroshi

2015-11-01

We describe a case of perforated rectal cancer that became curatively resectable after FOLFOX4 chemotherapy. An 81- year-old woman was transferred to our hospital with a diagnosis of bowel perforation. She underwent emergency transverse colostomy, peritoneal lavage, and the insertion of indwelling drainage tubes, because the perforated rectal cancer was considered unresectable. After recuperation, she received chemotherapy consisting of FOLFOX4 and bevacizumab. Owing to a good response to the treatment after 4 months, rectal resection was achieved curatively. Wound dehiscence occurred as a postoperative complication. The patient chose not to receive adjuvant chemotherapy. Currently, she has been alive for more than 1 year 3 months after resection without recurrence.

Colchicine in therapy. State of the art and new perspectives for an old drug.

PubMed

Famaey, J P

1988-01-01

Colchicine is the most specific treatment in acute gouty attacks. In several European countries, oral colchicine is still used for routine treatment of acute gout. Its selectivity is used as a diagnostic tool. It is also active in the treatment of acute crises of chondrocalcinosis and more occasionally of other arthritic crises (e.g. sarcoidosis). Colchicine appears to be the necessary adjuvant prophylactic drug when starting a hypouricemic treatment with uricosuric or uricolytic drugs for avoiding acute gouty crisis due to sudden mobilisation of the uric acid pool. Besides gout, colchicine is the drug of choice for treating familial mediterranean fever. It appears to be helpful in the treatment of Behçet's disease. It seems also useful for treating fibrosing conditions such as liver cirrhosis and scleroderma. As an adjuvant therapy, it helps treating dermatological disorders which are associated with leucocyte migration as an essential pathogenic factor (e.g. psoriasis, dermatitis herpetiformis, necrotising vasculitis ...). It has been advocated as an adjuvant therapy in malignant diseases as a support in radiotherapy and as an useful drug in various other diseases where it has been tried occasionally (e.g. Paget's disease of the bone, idiopathic thrombocytopenic purpura, disc syndrome). This very old drug remains a modern therapeutic agent.

Management of salivary gland tumors.

PubMed

Andry, Guy; Hamoir, Marc; Locati, Laura D; Licitra, Lisa; Langendijk, Johannes A

2012-09-01

Surgery after proper imaging (MRI or CT scan) is the main stay of treatment for salivary gland tumors. Although excision margins should be ≥5 mm for malignant tumors in cases of parotid gland carcinoma, the facial nerve should be preserved whenever it is not infiltrated. Adjuvant external radiation is indicated for malignant tumors with high-risk features such as close (or invaded) margins, perineural speed, lymphatic and/or vascular invasion, lymph-node involvement and high-grade histology. A Phase II trial testing adjuvant concomitant cisplatin plus radiation therapy versus adjuvant radiation therapy alone after surgery is currently under investigation for high-risk salivary gland cancer. For inoperable cancers, photons combined with proton boost seem to be a valuable option. Even if protons or carbon ions are promising, access to the latter is limited for usual treatment. For recurrent and/or metastatic cancer, polychemotherapy (cisplatin based) gives a 25% response rate in adenoid cystic carcinoma and should be used when the disease is overtly in progression. Targeted therapies with anti-EGF receptor molecules, antiangiogenic agents and tyrosine kinase inhibitors are ongoing, but more trials are needed to establish their efficacy, as is the use of bortezomib followed by doxorubicin. The products of fusion oncogenes, which have a pathogenic role in some adenoid cystic carcinoma and mucoepidermoid carcinomas, are of interest as potential therapeutic targets.

ASCO 2016: highlights in breast cancer.

PubMed

Bartsch, Rupert; Bergen, Elisabeth

2016-01-01

At the 2016 ASCO Annual Meeting, several pertinent studies in the field of breast cancer were presented. MA17.R was the first randomized phase III trial to evaluate the prolongation of adjuvant aromatase-inhibitor (AI) therapy from 5 to 10 years; while a significant reduction of disease-free survival events was observed in the extended treatment group, the absolute difference was relatively small and longer endocrine therapy resulted in a higher fracture rate. A combined analysis of three North American trials emphasized the superiority of anthracycline containing adjuvant chemotherapy regimens compared with docetaxel/cyclophosphamide (TC), while the PANTHER trial investigated dose-dense tailored adjuvant treatment. In metastatic breast cancer, the main interest was on cyclin-dependent kinase (CDK) 4/6 inhibitors. In PALOMA-2, the addition of palbociclib to letrozole prolonged progression-free survival (PFS) from 14.5 to 24.8 months resulting in the longest PFS data ever reported in the first-line setting. A subgroup analysis of premenopausal patients accrued to PALOMA-3 indicated that in this patient subset, ovarian function suppression plus fulvestrant and palbociclib yielded results comparable to the postmenopausal population. ESR1 mutations were another focus of interest as these activating mutations in the gene coding for the estrogen receptor alpha apparently evolve under the selection pressure of AI therapy.

A redox-sensitive, oligopeptide-guided, self-assembling, and efficiency-enhanced (ROSE) system for functional delivery of microRNA therapeutics for treatment of hepatocellular carcinoma.

PubMed

Hu, Qida; Wang, Kai; Sun, Xu; Li, Yang; Fu, Qihan; Liang, Tingbo; Tang, Guping

2016-10-01

Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for adjuvant treatment of HCC. We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supramolecular complex self-assembled from polycations and functional adamantyl modules. The ROSE system condensing tumor suppressor microRNA-34a (miR-34a) therapeutics becomes ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/miR-34a enables approximately higher affinity for LM3 HCC cells than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles significantly inhibits HCC cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. ROSE/miR-34a, featuring redox-responsiveness, oligopeptide-guided specificity, self-assembly, and enhanced transfection, is therefore a potential therapeutic agent in future adjuvant therapy for HCC treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: is there a standard of care?

PubMed

Almhanna, Khaldoun; Shridhar, Ravi; Meredith, Kenneth L

2013-04-01

Carcinoma of the esophagus is an aggressive and lethal disease with an increasing incidence worldwide. Despite changes in the treatment approach over the past two decades and even following complete resection, most patients will eventually relapse and die as a result of their disease. Several clinical trials evaluated different modalities in treating locally advanced esophageal cancer; however, because of stage migration and the changes in disease epidemiology, applying these trials to clinical practice has become a daunting task. We searched Medline and conference abstracts for randomized studies published in the past three decades. We restricted our search to articles published in English. Neoadjuvant chemoradiotherapy followed by surgical resection is an accepted standard of care in the United States for patients with locally advanced esophageal cancer. Esophagectomy remains an essential component of treatment and can lead to improved overall survival, especially when performed at high-volume institutions. The role of adjuvant chemotherapy following curative resection in patients who underwent neoadjuvant chemotherapy and radiation remains unclear. Several questions still need to be answered regarding the use of neoadjuvant or adjuvant therapy for patients with resectable esophageal cancer. The optimal chemotherapy regimen has not yet been identified for these patients, although newer therapies show promise.

Evaluation of Trends in the Cost of Initial Cancer Treatment

PubMed Central

Yabroff, K. Robin; Meekins, Angela; Topor, Marie; Lamont, Elizabeth B.; Brown, Martin L.

2008-01-01

Background Despite reports of increases in the cost of cancer treatment, little is known about how costs of cancer treatment have changed over time and what services have contributed to the increases. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database for 306 709 persons aged 65 and older and diagnosed with breast, lung, colorectal, or prostate cancer between 1991 and 2002 to assess the number of patients assigned to initial cancer care, from 2 months before diagnosis to 12 months after diagnosis, and mean annual Medicare payments for this care according to cancer type and type of treatment. Mutually exclusive treatment categories were cancer-related surgery, chemotherapy, radiation therapy, and other hospitalizations during the period of initial cancer care. Linear regression models were used to assess temporal trends in the percentage of patients receiving treatment and costs for those treated. We extrapolated our results based on the SEER data to the US Medicare population to estimate national Medicare payments by cancer site and treatment category. All statistical tests were two-sided. Results For patients diagnosed in 2002, Medicare paid an average of $39 891 for initial care for each lung cancer patient, $41 134 for each colorectal cancer patient, and $20 964 for each breast cancer patient, corresponding to inflation-adjusted increases from 1991 of $7139, $5345, and $4189, respectively. During the same interval, the mean Medicare payment for initial care for prostate cancer declined by $196 to $18261 in 2002. Costs for any hospitalization accounted for the largest portion of payments for all cancers. Chemotherapy use increased markedly for all cancers between 1991 and 2002, as did radiation therapy use (except for colorectal cancers). Total 2002 Medicare payments for initial care for these four cancers exceeded $6.7 billion, with colorectal and lung cancers being the most costly overall. Conclusions The statistically significant increase in costs of initial cancer treatment reflects more patients receiving surgery and adjuvant therapy and rising prices for these treatments. These trends are likely to continue in the near future, although more efficient targeting of costly therapies could mitigate the overall economic impact of this trend. PMID:18544740

New advances in focal therapy for early stage prostate cancer.

PubMed

Tay, Kae Jack; Schulman, Ariel A; Sze, Christina; Tsivian, Efrat; Polascik, Thomas J

2017-08-01

Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years. Areas covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized. A literature search of major databases was performed using the search terms 'focal therapy', 'focal ablation', 'partial ablation', 'targeted ablation', 'image guided therapy' and 'prostate cancer'. Expert commentary: Advanced radiological tools such as multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS), prostate-specific-membrane-antigen positron emission tomography (PSMA-PET) represent a revolution in the ability to understand cancer function and biology. Advances in ablative technologies now provide a menu of modalities that can be rationalized based on lesion location, size and perhaps in the near future, pre-determined resistance to therapy. However, these need to be carefully studied to establish their safety and efficacy parameters. Adjuvant strategies to enhance focal ablation are under development.

Improved long-term outcomes after resection of pancreatic adenocarcinoma: a comparison between two time periods.

PubMed

Serrano, Pablo E; Cleary, Sean P; Dhani, Neesha; Kim, Peter T W; Greig, Paul D; Leung, Kenneth; Moulton, Carol-Anne; Gallinger, Steven; Wei, Alice C

2015-04-01

Despite reduced perioperative mortality and routine use of adjuvant therapy following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), improvement in long-term outcome has been difficult to ascertain. This study compares outcomes in patients undergoing resection for PDAC within a single, high-volume academic institution over two sequential time periods. Retrospective review of patients with resected PDAC, in two cohorts: period 1 (P1), 1991-2000; and period 2 (P2), 2001-2010. Univariate and multivariate analyses using the Cox proportional hazards model were performed to determine prognostic factors associated with long-term survival. Survival was evaluated using Kaplan-Meier analyses. A total of 179 pancreatectomies were performed during P1 and 310 during P2. Perioperative mortality was 6.7 % (12/179) in P1 and 1.6 % (5/310) in P2 (p = 0.003). P2 had a greater number of lymph nodes resected (17 [0-50] vs. 7 [0-31]; p < 0.001), and a higher lymph node positivity rate (69 % [215/310] vs. 58 % [104/179]; p = 0.021) compared with P1. The adjuvant therapy rate was 30 % (53/179) in P1 and 63 % (195/310) in P2 (p < 0.001). By multivariate analysis, node and margin status, tumor grade, adjuvant therapy, and time period of resection were independently associated with overall survival (OS) for both time periods. Median OS was 16 months (95 % confidence interval [CI] 14-20) in P1 and 27 months (95 % CI 24-30) in P2 (p < 0.001). Factors associated with improved long-term survival remain comparable over time. Short- and long-term survival for patients with resected PDAC has improved over time due to decreased perioperative mortality and increased use of adjuvant therapy, although the proportion of 5-year survivors remains small.

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

DTIC Science & Technology

2017-10-01

Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR...TERMS Breast cancer, adjuvant treatment, aspirin, randomized controlled trial 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

Health promotion for young patients with haemophilia. Counselling, adjuvant exercise therapy and school sports.

PubMed

Sondermann, Judith; Herbsleb, Marco; Stanek, Frank-Detlef; Gabriel, Holger; Kentouche, Karim

2017-05-10

The haemophilia treatment centre of the Clinic for Children and Youth Medicine in Jena extends medical care by health-promotion measures, namely: health counselling, adjuvant exercise therapy and school sports. In addition to the regular medical checks at the treatment centre patients are examined regarding physical fitness, joint situation, quality of life in general and disease-specific manner, as well as psycho-social and nutritional behaviour. Findings and medical results of the examinations are integrated into an individual advice on therapy, school sports, and health recommendations. This aimed at strengthening health-related resources and minimizing potential injuries. First long-term evaluation shows an increase of activity behaviour and physical fitness without increasing bleeding rate and maintained joint function. Combining functional prevention diagnostics and individual health counselling shows signs of improved patient's health knowledge, self-competence and physical fitness.

Update on primary head and neck mucosal melanoma

PubMed Central

López, Fernando; Rodrigo, Juan P.; Cardesa, Antonio; Triantafyllou, Asterios; Devaney, Kenneth O.; Mendenhall, William M.; Haigentz, Missak; Strojan, Primož; Pellitteri, Phillip K.; Bradford, Carol R.; Shaha, Ashok R.; Hunt, Jennifer L.; de Bree, Remco; Takes, Robert P.; Rinaldo, Alessandra; Ferlito, Alfio

2016-01-01

Primary mucosal melanomas (PMMs) of the head and neck are uncommon malignancies that arise mainly in the nasal cavity and paranasal sinuses, followed by the oral cavity. The mainstay of treatment is radical surgical resection followed by adjuvant radiotherapy in selected patients with high-risk features. Multimodality therapy has not been well studied and is not standardized. Adjuvant radiotherapy seems to improve locoregional control but does not improve overall survival (OS). Elective neck dissection is advocated in patients with oral PMM. Systemic therapy should be considered only for patients with metastatic or unresectable locoregional disease. Despite improvements in the field of surgery, radiotherapy, and systemic therapy, patients with PMM still face a very unfavorable prognosis (5-year disease-free survival [DFS] <20%) with high rates of locoregional recurrence and distant metastasis. The present review aims to summarize the current state of knowledge on the molecular biology, pathological diagnosis, and management of this disease. PMID:25242350

Postoperative radiation therapy of pT2-3N0M0 esophageal carcinoma-a review.

PubMed

Luo, Yijun; Wang, Xiaoli; Yu, Jinming; Zhang, Bin; Li, Minghuan

2016-11-01

Esophageal cancer is one of the most malignant gastrointestinal cancers worldwide. Despite advances in surgical technique, 5-year survival in pathologic stage T2-3N0M0 esophageal squamous cell carcinoma patients who are treated with surgery alone is still poor. The addition of adjuvant radiotherapy may confer a benefit for these patients. However, not all patients could get a benefit from radiotherapy and patients with esophageal squamous cell carcinoma receiving radiotherapy seem to have a disparity in treatment response. Thus, identifying effective prognostic indicator to complement current clinical staging approaches is extremely important. Those prognostic factors could give rise to a novel prognostic stratification system, which serve as criteria for selecting patients for adjuvant therapy. Consequently, it may help to define the subgroups who are more likely to benefit from postoperative radiation therapy.

Metformin as add-on to intensive insulin therapy in type 1 diabetes mellitus.

PubMed

Staels, Frederik; Moyson, Carolien; Mathieu, Chantal

2017-10-01

We aimed to evaluate the effect of adjuvant metformin to intensive insulin therapy in patients with type 1 diabetes mellitus (T1DM). A 10-year retrospective study in 2 cohorts was performed: the MET cohort (n = 181) consisted of patients with T1DM on adjuvant metformin for ≥6 months and the CTR cohort (n = 62) consisted of patients with T1DM who refused metformin (n = 25) or adhered to metformin for <6 months (n = 36). Data on glycated haemoglobin (HbA1c), body mass index (BMI) and daily insulin dose were recorded yearly. A third cross-sectional cohort, the REF cohort (n = 961), consisting of patients with T1DM not offered adjuvant metformin, was used as a reference for baseline comparison. At the study start, BMI was significantly higher and insulin doses were lower in patients in the MET cohort, while HbA1c levels were similar. In the first years of metformin therapy, small but non-significant decreases were seen in BMI and insulin dose in patients in the MET cohort, while after 10 years no persistent effect on HbA1c, insulin dose or BMI was seen. In conclusion, although metformin may have short-term effects on BMI and insulin dose when used as adjunct therapy in patients with T1DM, no long-term beneficial effects were observed when patients were followed for 10 years. © 2017 John Wiley & Sons Ltd.

Evaluation of the Effectiveness of a Multimodal Complementary Medicine Program for Improving the Quality of Life of Cancer Patients during Adjuvant Radiotherapy and/or Chemotherapy or Outpatient Aftercare.

PubMed

Domnick, Martin; Domnick, Manju; Wiebelitz, Karl-Rüdiger; Beer, André-Michael

2017-01-01

Evidence for complementary therapies as important strategies to relieve cancer treatment-associated symptoms is increasing. Mostly, these complementary therapies start at the end of adjuvant treatments, resulting in a long delay until the well-being of patients is addressed. Further, long distances between the rehabilitation center and the patients' residence hinder patients' compliance. The multimodal outpatient LOTUS Care Cure Project (LCCP) was tested in a randomized controlled trial including patients of various cancer entities and stages while on adjuvant chemotherapy and/or radiotherapy or outpatient aftercare. The intervention group received the LCCP additionally to the conventional treatment (LCCP group, n = 50). The control group (CG) was split into 2 groups, with (CG1, n = 33) and without (CG2, n = 17) weekly talks. The primary endpoint was quality of life (QoL) after 3 months. In the LCCP group, QoL significantly improved after 3 months compared to CG2 (p = 0.022) but not compared to CG1. Other parameters showing a significant improvement were cognitive (p < 0.05, vs. CG1 and CG2) and social function (p < 0.05, vs. CG2). This pilot study describes a multimodal outpatient complementary therapy program conducted in parallel with conventional therapies and its potential to significantly improve QoL and reduce treatment-associated side effects. To substantiate these data, multicenter trials are needed. © 2017 S. Karger AG, Basel.

Letrozole as upfront endocrine therapy for postmenopausal women with hormone-sensitive breast cancer: BIG 1-98

PubMed Central

Thuerlimann, Beat

2007-01-01

The BIG 1-98 trial is a large, randomized, independently conducted clinical trial designed to compare the efficacy of upfront letrozole versus tamoxifen monotherapy and to compare sequential or up-front use of letrozole and/or tamoxifen as an early adjuvant therapy for patients with early breast cancer. We report on the results from the primary core analysis of the BIG 1-98 trial of 8,010 patients, which compares monotherapy with letrozole versus tamoxifen. This pre-planned core analysis allowed the use of patient data from the monotherapy arms of letrozole and tamoxifen and from the sequential arms prior to the drug switch point. Patients randomized to letrozole had a 19% improved disease-free survival (hazard ratio [HR] = 0.81; P = 0.003), due especially to reduced distant metastases (HR = 0.73; P = 0.001). A 14% risk reduction of fatal events in favor of letrozole was also observed (P = NS). The results from the monotherapy arms alone confirmed the findings from the primary core analysis. Based on the results from this trial, the aromatase inhibitor letrozole (Femara®) is currently recommended as a part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer and has recently been approved in the early adjuvant setting in both Europe and the United States. A subsequent analysis after additional follow-up will address the question of monotherapy versus sequential therapy. PMID:17912636

Decision-making by surgeons about referral for adjuvant therapy for patients with non-small-cell lung, breast or colorectal cancer: a qualitative study

PubMed Central

Urquhart, Robin; Kendell, Cynthia; Buduhan, Gordon; Rayson, Daniel; Sargeant, Joan; Johnson, Paul; Grunfeld, Eva; Porter, Geoffrey A.

2016-01-01

Background: Because surgeons are the main gatekeepers to oncology services, understanding how they make decisions related to referral for adjuvant therapies is important to optimize referral rates and use of oncology services for patients with potentially curable disease. We examined decision-making by surgeons related to referral to oncology services for patients having undergone curative-intent surgery for non-small-cell lung, breast or colorectal cancer. Methods: We conducted a qualitative study, whose design was guided by the principles of grounded theory. Semi-structured interviews were held with 29 surgeons who performed non-small-cell lung, breast or colorectal cancer surgery in the province of Nova Scotia. Data were collected and analyzed concurrently. Analysis involved an inductive, grounded approach using constant comparative analysis. Data collection and analysis continued until theoretical saturation was reached. Results: Seven factors influenced the surgeons' decision-making related to referral to oncology services: indications and contraindications for therapy; patients' beliefs and preferences; a belief that oncologists are the experts; knowledge of local standards of care; consultation with oncology colleagues; navigating patient logistics (e.g., lodging, caregiving responsibilities, insurance coverage); and system resources and capacity. Interpretation: Our study's findings provide a novel understanding of how surgeons make decisions about oncology referral and point to potential areas for intervention to promote referral to oncology services for patients for whom adjuvant therapy is recommended. PMID:27570760

Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.

2009-12-01

Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m{sup 2} intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m{sup 2} intravenously on Days 1 and 8 or capecitabine 1500 mg/m{sup 2} orallymore » in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m{sup 2} orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of >=180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.« less

A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants

PubMed Central

Olschewski, Jessica; Braicu, Ioana; Sehouli, Jalid

2015-01-01

Background. Treatment of borderline ovarian tumors (BOTs) remains contentious, and there is no consensus regarding therapy for BOTs with invasive implants (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in patients with BOTi at primary diagnosis. Methods. The PubMed database was systematically searched for articles using the following terms: ((borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment) OR (surgery) OR (surgical treatment)). Results. We identified 27 articles including 3,124 patients, 181 with invasive implants. All studies provided information regarding mortality or recurrence rates. Central pathological examination was performed in 19 studies. Eight studies included more than 75% stage I patients; 7 included only advanced-stage patients, and 14 included only serous BOT. The pooled recurrence estimates for both treatment groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ significantly (p = .114). A meta-analysis of the 6 studies providing separate mortality data for both treatment groups favored surgical treatment only, but this difference did not reach statistical significance (.05 < p < .1; odds ratio: 0.33; 95% confidence interval: 0.09–1.71; p = .086). We were unable to pool the results of the included studies because not all studies registered events in both treatment groups. Egger’s regression indicated low asymmetry of the studies (p = .39), and no heterogeneity was found (I2 = 0%). Conclusion. We did not find evidence supporting platinum-based adjuvant therapy for BOT with invasive implants. PMID:25601963

Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

PubMed

Lu, Sharon M; Chang-Halpenny, Christine; Hwang-Graziano, Julie

2015-04-01

To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with C3d as a molecular adjuvant.

PubMed

Xu, Gui-lian; Zhang, Ke-qin; Guo, Bo; Zhao, Ting-ting; Yang, Fei; Jiang, Man; Wang, Qing-hong; Shang, Yu-hang; Wu, Yu-zhang

2010-10-18

Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer therapies is unclear. In this study, we have engineered a DNA vaccine that expresses extracellular region of murine VEGFR-2 (FLK1(265-2493)) and 3 copies of C3d (C3d3), a component of complement as a molecular adjuvant, designed to increase antitumor immunity. VEGFR-2 has a more restricted expression on endothelial cells and is upregulated once these cells proliferate during angiogenesis in the tumor vasculature. Immunization of mice with vector encoding FLK1(265-2493) alone generated only background levels of anti-VEGFR-2 antibodies and slight inhibitory effect on tumor growth. However, the addition of C3d3 to the vaccine construct significantly augmented the anti-VEGFR-2 humoral immune response and inhibited the tumor growth. The antitumor activity induced by vaccination with vector encoding FLK1(265-2493)-C3d3 fusion protein was also demonstrated via growth inhibition of established tumors following passive transfer of immune serum from vaccinated mice. Our results suggest that vaccination with vector encoding FLK1(265-2493) with C3d3 as a molecular adjuvant induces adaptive humoral activity, which is directed against the murine VEGFR-2 and can significantly inhibit tumor growth, and that administration of C3d as a molecular adjuvant to increase antibodies levels to VEGFR-2 may provide an alternative treatment modality for cancer therapies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Retrospective study of adjuvant icotinib in postoperative lung cancer patients harboring epidermal growth factor receptor mutations.

PubMed

Yao, Shuyang; Zhi, Xiuyi; Wang, Ruotian; Qian, Kun; Hu, Mu; Zhang, Yi

2016-09-01

Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR-mutated NSCLC patients undergoing resection of stage IB-IIIA. Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy. Survival factors were evaluated by univariate and Cox regression analysis. The median follow-up time was 30 months (range 24-41). At the data cut-off, five patients (25%) had recurrence or metastasis and one patient had died of the disease. The two-year disease-free survival (DFS) rate was 85%. No recurrence occurred in the high-risk stage IB subgroup during the follow-up period. In univariate analysis, the micropapillary pattern had a statistically significant effect on DFS ( P = 0.040). Multivariate logistic regression analysis showed that there was no independent predictor. Drug related adverse events (AEs) occurred in nine patients (45.0%). The most common AEs were skin-related events and diarrhea, but were relatively mild. No grade 3 AEs or occurrences of intolerable toxicity were observed. Icotinib as adjuvant therapy is effective in patients harboring EGFR mutations after complete resection, with an acceptable AE profile. Further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Adjuvant therapy decisions based on magnetic resonance imaging of extramural venous invasion and other prognostic factors in colorectal cancer

PubMed Central

Swift, RI; Chau, I; Heald, RJ; Tekkis, PP; Brown, G

2014-01-01

Introduction There remains a lack of high quality randomised trial evidence for the use of adjuvant chemotherapy in stage II rectal cancer, particularly in the presence of high risk features such as extramural venous invasion (EMVI). The aim of this study was to explore this issue through a survey of colorectal surgeons and gastrointestinal oncologists. Methods An electronic survey was sent to a group of colorectal surgeons who were members of the Association of Coloproctology of Great Britain and Ireland. The survey was also sent to a group of gastrointestinal oncologists through the Pelican Cancer Foundation. Reminder emails were sent at 4 and 12 weeks. Results A total of 142 surgeons (54% response rate) and 99 oncologists (68% response rate) responded to the survey. The majority in both groups of clinicians thought EMVI was an important consideration in adjuvant treatment decision making and commented routinely on this in their multidisciplinary team meeting. Although both would consider treating patients on the basis of EMVI detected by magnetic resonance imaging, oncologists were more selective. Both surgeons and oncologists were prepared to offer patients with EMVI adjuvant chemotherapy but there was lack of consensus on the benefit. Conclusions This survey reinforces the evolution in thinking with regard to adjuvant therapy in stage II disease. Factors such as EMVI should be given due consideration and the prognostic information we offer patients must be more accurate. Historical data may not accurately reflect today’s practice and it may be time to consider an appropriately designed trial to address this contentious issue. PMID:25245736

Determination of Patients’ Breast Tumor-Specific Immunity and Its Enhancement with In Vitro Stimulation and Gene Therapy

DTIC Science & Technology

1998-03-01

cancer therapy. Am. J. Clin. Oncol., 22:368-380. Overgaard, J., Gonzalez Gonzalez, D., Hulshof , M.C.C.M., Arcangeli, G., Dahl, O., Mella, O., and... Hulshof , M.C.C.M., Arcangeli, G., Dahl, O., Mella, O., and Bentzen, S.M. (1996) Hyperthermia as an adjuvant to radiation therapy of recurrent or

Analysis of different therapeutic protocols for osteonecrosis of the jaw associated with oral and intravenous bisphpsphonates

PubMed Central

Bermúdez-Bejarano, Elena-Beatriz; Serrera-Figallo, María-Ángeles; Gutiérrez-Corrales, Aida; Romero-Ruiz, Manuel-María; Castillo-de-Oyagüe, Raquel; Gutiérrez-Pérez, José-Luis; Machuca-Portillo, Guillermo

2017-01-01

Introduction Chemotherapy-associated osteonecrosis of the jaw caused by bisphosphonates is an exposure of necrotic bone with more than eight weeks of evolution that is attributable to bisphosphonates and no prior radiation therapy. Its etiopathogenesis remains unknown, although there are two hypotheses that may explain it: the drug’s mechanism of action, and the risk factors that can lead to osteonecrosis. There is a wide range of treatment options for managing chemotherapy-associated osteonecrosis of the jaw, from conservative treatments to surgical procedures of varying levels of invasiveness, which are sometimes supplemented with adjuvant therapies. Objectives The objective of this article is to group the therapeutic options for osteonecrosis of the jaw (ONJ) into seven different protocols and to evaluate their effectiveness in relation to stage of ONJ. Material and Methods A literature review was carried out in PubMed following the PRISMA criteria. A total of 47 were collected after compiling a series of variables that define ONJ, applied treatments, and the clinical results obtained. Results and Discussion The 47 articles selected have a low to average estimated risk of bias and are of moderate to good quality. According to the data obtained, Protocol 3 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and adjuvant therapies) is the most favorable approach for ONJ lesions caused by oral bisphosphonates. For lesions caused by intravenous bisphosphonates, Protocol 2 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and no adjuvant therapies) is the best approach. When comparing the different stages of ONJ, Protocol 1 (conservative treatment, clinical and radiological follow-up) promotes better healing of Stage 1 ONJ lesions caused by orally administered bisphosphonates, and Protocol 3 is recommended for Stage II. For ONJ lesions attributable to intravenous bisphosphonates, Protocol 7 (conservative treatment, clinical and radiological follow-up, and adjuvant therapies) provides the best results in Stage 0; in Stages I, II, and III, Protocol 1 gives better results. Key words:Bisphosphonates, bronj, therapeutic protocol, clinical result. PMID:27918742

Distal Cholangiocarcinoma and Pancreas Adenocarcinoma: Are They Really the Same Disease? A 13-Institution Study from the US Extrahepatic Biliary Malignancy Consortium and the Central Pancreas Consortium.

PubMed

Ethun, Cecilia G; Lopez-Aguiar, Alexandra G; Pawlik, Timothy M; Poultsides, George; Idrees, Kamran; Fields, Ryan C; Weber, Sharon M; Cho, Clifford; Martin, Robert C; Scoggins, Charles R; Shen, Perry; Schmidt, Carl; Hatzaras, Ioannis; Bentrem, David; Ahmad, Syed; Abbott, Daniel; Kim, Hong Jin; Merchant, Nipun; Staley, Charles A; Kooby, David A; Maithel, Shishir K

2017-04-01

Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as 1 entity, yet direct comparisons are lacking. Our aim was to use 2 large multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases. This study included patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000 to 2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums. Primary endpoint was disease-specific survival (DSS). Of 1,463 patients, 224 (15%) had DC and 1,239 (85%) had PDAC. Compared with PDAC, DC patients were less likely to be margin-positive (19% vs 25%; p = 0.005), lymph node (LN)-positive (55% vs 69%; p < 0.001), and receive adjuvant therapy (57% vs 71%; p < 0.001). Of DC patients treated with adjuvant therapy, 62% got gemcitabine alone and 16% got gemcitabine/cisplatin. Distal cholangiocarcinoma was associated with improved median DSS (40 months) compared with PDAC (22 months; p < 0.001), which persisted on multivariable analysis (hazard ratio 0.65; 95% CI 0.50 to 0.84; p = 0.001). Lymph node involvement was the only factor independently associated with decreased DSS for both DC and PDAC. The DC/LN-positive patients had similar DSS as PDAC/LN-negative patients (p = 0.74). Adjuvant therapy (chemotherapy ± radiation) was associated with improved median DSS for PDAC/LN-positive patients (21 vs 13 months; p = 0.001), but not for DC patients (38 vs 40 months; p = 0.62), regardless of LN status. Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are distinct entities. Distal cholangiocarcinoma has a favorable prognosis compared with PDAC, yet current adjuvant therapy regimens are only associated with improved survival in PDAC, not DC. Therefore, treatment paradigms used for PDAC should not be extrapolated to DC, despite similar operative approaches, and novel therapies for DC should be explored. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Treatment of retroauricular keloids: Revision of cases treated at the ENT service of HC/UFPR

PubMed Central

Carvalho, Bettina; Ballin, Annelyse Cristine; Becker, Renata Vecentin; Ribeiro, Talita Beithum; Cavichiolo, Juliana Benthien; Ballin, Carlos Roberto; Mocellin, Marcos

2012-01-01

Summary Introduction: Keloids are benign tumors arising from abnormal healing of the skin, and there are several procedures available for their treatment. Objective: The objective of this study was to evaluate the outcomes of patients undergoing treatment of keloids after ear, nose, and throat (ENT) surgeries at our service center. Method: We conducted thorough, retrospective and prospective analysis of records of patients undergoing treatment of retroauricular keloids at our center. Results: Nine patients were evaluated, and 6 underwent resection and adjuvant beta-therapy, 2 underwent resection with local application of corticosteroids, and only 1 underwent resection without adjuvant therapy. There was no recurrence of keloids in patients that were treated with beta-therapy in the early postoperative period. One patient had relapsed despite corticosteroid administration and late beta-therapy. Discussion: Several techniques have been used for the treatment of retroauricular keloids, and beta-therapy is thought to yield the best results, followed by the use of intralesional corticosteroids. Conclusion: Treatment of retroauricular keloids remains a challenge. While new techniques are being developed, resection followed by early beta-therapy is still the best treatment option. PMID:25991935

Outcomes of curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma of long bone.

PubMed

Kim, Wanlim; Han, Ilkyu; Kim, Eo Jin; Kang, Seungcheol; Kim, Han-Soo

2015-06-01

Low-grade chondrosarcoma of long bones can be treated successfully with extended intralesional curettage using adjuvants. However, there is no study reporting the use of anhydrous alcohol as an adjuvant in the treatment of low-grade chondrosarcoma. We asked (1) whether intralesional curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma is associated with good oncologic outcomes; and we report (2) the complications of the procedure. Thirty-six patients (13 men, 23 women) with a mean age of 46 years (range, 18-67 years) were treated for low-grade chondrosarcoma and followed up for a median of 62 months (range, 24-169 months). After intralesional curettage, and additional burring, anhydrous alcohol was used as an adjuvant therapy. At the time of last follow-up, there were no local recurrences or distant metastases. Six patients developed complications: 4 postoperative fractures (11%), 1 intra-articular loose body (3%) and 1 postoperative joint stiffness (3%). Anhydrous alcohol is a reasonable adjuvant for the curettage of low-grade chondrosarcoma of long bones. A long-term follow-up study is necessary, considering the slow biological progression of low-grade chondrosarcoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toxicity of aggressive multimodality therapy including cisplatinum, bleomycin and methotrexate with radiation and/or surgery for advanced head and neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weichselbaum, R.R.; Posner, M.R.; Ervin, T.J.

1982-05-01

A combined modality regimen employing induction chemotherapy with cisplatinum, bleomycin and methotrexate followed by surgery and/or radiation therapy was initiated in patients with advanced squamous cell carcinoma of the head and neck. In the first 23 patients treated with this program there was a 90% response rate to induction chemotherapy (9% CR and 81% PR). Toxicity associated with radiotherapy, but not surgery, was increased with 11 of 23 patients (48%) who experienced some toxicity during or immediately after radiotherapy. Mucositis was worse than expected and severe delayed mucositis was seen in 2 patients, one of whom required hospitalization. Late complications,more » possibly related to therapy included one myocardial infarction and one episode of hypoglycemia, both of which were fatal. One other patient voluntarily failed to take prescribed oral leucovorin, dying of unrescued methotrexate toxicity during adjuvant therapy, a questionable suicide. Further follow-up analysis of failure will be necessary to determine if the value of a combined modality regimen in producing an increased cure rate and long term survival will out weigh increased toxicity.« less

Deconstructing Decisions to Initiate, Maintain, or Discontinue Adjuvant Endocrine Therapy in Breast Cancer Survivors: A Mixed-Methods Study

PubMed Central

Bluethmann, Shirley M.; Murphy, Caitlin C.; Tiro, Jasmin A.; Mollica, Michelle A.; Vernon, Sally W.; Bartholomew, Leona Kay

2017-01-01

Purpose/Objectives Adjuvant endocrine therapy (AET) has been shown to improve survival in hormone receptor–positive breast cancer survivors, but as many as half do not complete recommended treatment. Management of medication-related side effects and engagement with providers are two potentially modifiable factors, but their associations with adherence are not well understood. The aims were to build on survey results to qualitatively explore survivors’ experiences with prescribed AET to (a) describe appraisal and management of AET side effects and (b) deconstruct decisions to initiate, discontinue, or maintain AET. Research Approach The authors used a mixed-methods explanatory sequence research design with a qualitative emphasis. Setting Survivors were recruited from a clinical cancer registry maintained at the University of Texas Southwestern Medical Center, which includes the Harold C. Simmons Comprehensive Cancer Center (National Cancer Institute–designated), in Dallas. Participants 452 survivors completed a survey, and 30 took part in telephone interviews. Methodologic Approach Qualitative methods were used in which the authors recorded and transcribed interviews for analysis and used open coding to reduce data into themes. Findings Among adherent survivors, the themes of tolerance of side effects and perseverance were strong. Nonadherent survivors expressed more difficulty managing side effects and perceived fewer benefits when side effects were bothersome. The most common side effects mentioned by all survivors were menopausal symptoms and joint pain; less common side effects were cognitive decline and cardiac distress. Some sought advice from their oncology team. Nonadherent survivors appeared initially motivated to maintain AET but identified a tolerance limit for side effects after which a provider’s recommendation was less influential in their decision to maintain or discontinue AET. Interpretation This study elucidated adherence as a complex continuum of behaviors, appraisals, and decision points. These insights may be particularly useful in counseling survivors taking AET and promoting timely delivery of clinical interventions to enhance adherence. Implications for Nursing Nurses should be involved in the planning and implementation of clinical interventions to manage side effects and other barriers to AET adherence. PMID:28635973

Association between African American race and outcomes in patients with nonmetastatic triple-negative breast cancer: a retrospective analysis by using results from the Georgia Cancer Specialist Database.

PubMed

Christiansen, Neal; Chen, Lei; Gilmore, James; Pechar, David; Szabo, Stephen

2012-08-01

The objective of this study was to evaluate, in a real-world context, the impact of race on disease recurrence and survival in patients with nonmetastatic triple-negative breast cancer (TNBC) treated with adjuvant chemotherapy. The study selected patients from the 2003-2008 Georgia Cancer Specialist Database with stage I-III confirmed TNBC who had received adjuvant chemotherapy. These patients were followed-up from initial diagnosis to death, cancer recurrence, or loss to follow-up. The primary outcome was disease-free survival (DFS). Kaplan-Meier curves compared DFS and recurrence between African American and non-African American groups. The impact of African American status was examined further through multivariate Cox models by adjusting for age, comorbidity, body mass index (BMI), smoking status, initial TNBC stage, surgery, and radiation therapy. Among 209 patients with TNBC, 89 (42.6%) were African American. The 2 groups (African American vs. non-African American) were similar in mean age at diagnosis (53.2 vs. 54.4 years; P =.487) and with surgery and radiation rates (98.9% vs. 100%; P = .244; 68.5% vs. 62.5%; P = .365, respectively). Compared with non-African Americans, African American patients had a higher BMI (30.4 vs. 28.6 kg/m(2); P = .0477) and were less likely to be diagnosed at stage I (31.5% vs. 51.7%; P = .0107). The African American patients had a lower 5-year DFS rate (45.2% vs. 79.7%; P = .0005) and a higher 5-year recurrence rate (42.5% vs. 7.0%; P = .0005) compared with the non-African American patients. Among patients with TNBC treated with adjuvant chemotherapy, African American race was associated with a worse outcome irrespective of later stage at presentation or higher BMI. Copyright © 2012 Elsevier Inc. All rights reserved.

Adenoid cystic carcinoma of the skull base: results with an aggressive multidisciplinary approach.

PubMed

Ramakrishna, Rohan; Raza, Shaan M; Kupferman, Michael; Hanna, Ehab; DeMonte, Franco

2016-01-01

OBJECT Adenoid cystic carcinoma (ACC) is a locally aggressive tumor of salivary gland origin. Little data exist to guide treatment when this tumor extends to involve the structures of the skull base. METHODS Fifty-one patients with a diagnosis of ACC affecting the skull base were identified from a prospective database at MD Anderson Cancer Center (from 1992 to 2010). RESULTS Median follow-up for study patients was 6.75 years. The 5- and 10-year overall survival (OS) rates were 78% and 50%, respectively. Sixty-six percent of patients had progression of their disease. The 5- and 10-year progression-free survival (PFS) rates were 46.7% and 21.0%, respectively. Gross-total resection was achieved in 75% of patients, with 49% having microscopically negative margins at the time of first operation. On univariate analysis, resections with microscopically negative margins were associated with a significant OS advantage (20.1 ± 3.3 years) compared with resections that left residual disease, even if microscopic (10.3 ± 1.6 years, p = 0.035). In patients who underwent reoperation, the effect persisted, with improved OS in those with negative margins (21.4 ± 0.0 vs 16.7 ± 4.0 years, p = 0.06). The use of adjuvant radiotherapy was associated with an OS advantage (16.2 ± 2.5 vs 5.5 ± 2.2 years, p = 0.03) at initial diagnosis and improved PFS (7.8 ± 1.0 vs 2.1 ± 0.62 years, p = 0.005), whereas repeat irradiation provided no benefit. The use of adjuvant chemotherapy at diagnosis or at recurrence was not associated with any significant advantage. Multivariate analysis revealed margin-negative resection at initial operation and at recurrence retained OS significance, even after controlling for age, radiation therapy, and T stage. CONCLUSIONS ACC of the skull base is best treated with a multidisciplinary approach aimed at maximal, safe resection. Adjuvant radiotherapy should be offered, whereas chemotherapy does not confer benefit.

Toward the development of a stable, freeze-dried formulation of Helicobacter pylori killed whole cell vaccine adjuvanted with a novel mutant of E. coli heat-labile toxin

PubMed Central

Summerton, Nancy A.; Welch, Richard W.; Bondoc, Laureano; Yang, Huei-Hsiung; Pleune, Brett; Ramachandran, Naryaswamy; Harris, Andrea M.; Bland, Desiree; Jackson, W. James; Park, Sukjoon; Clements, John D.; Nabors, Gary S.

2009-01-01

No vaccine exists for the prevention of infection with the ubiquitous gastric pathogen Helicobacter pylori, and drug therapy for the infection is complicated by poor patient compliance, the high cost of treatment, and ineffectiveness against drug resistant strains. A new medical advancement is required to reduce the incidence of peptic ulcer disease and stomach cancer, two conditions caused by infection with H. pylori. Clinical trials have been performed with a formalin-inactivated Helicobacter pylori Whole Cell (HWC) vaccine, given orally in combination with the mucosal adjuvant mLT(R192G), a mutant of E. coli heat-labile toxin. Following the initial dose of this vaccine, some subjects experienced gastrointestinal side effects. To reduce side effects and potentially further increase the amount of adjuvant that can safely be administered with the HWC vaccine, experiments were performed with a form of LT that carried two mutations in the A subunit, a substitution of G for R at position 192, and A for L at position 211. The double-mutant LT (dmLT) adjuvant stimulated immune responses as effectively as the single mutant LT in mice. Additionally, following a challenge infection, the dmLT-adjuvanted vaccine was as effective as single mutant LT in reducing gastric urease levels (diagnostic for H. pylori infection), and H. pylori colonization in the stomach as assessed by quantitative analysis of stomach homogenates. A lyophilized formulation of HWC was developed to improve stability and to potentially reduce reliance on cold chain maintenance. It was observed that a dmLT-adjuvanted lyophilized vaccine was equally as protective in the mouse model as the liquid formulation as assessed by gastric urease analysis and analysis of stomach homogenates for viable H. pylori. No readily detectable effect of tonicity or moisture content was observed for the lyophilized vaccine within the formulation limits evaluated. In an accelerated stability study performed at 37°C the lyophilized vaccine remained equally as protective as vaccine stored at 2–8°C. The formulation selected for clinical development consisted of 2.5×1010 formalin-inactivated cells per ml in 6.5% trehalose, 0.5% mannitol, and 10 mM citrate buffer at pH 6.8. PMID:19897067

Natural products: a hope for glioblastoma patients.

PubMed

Vengoji, Raghupathy; Macha, Muzafar A; Batra, Surinder K; Shonka, Nicole A

2018-04-24

Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB). Cancer stem cells (CSCs) have intrinsic resistance to initial chemoradiation therapy (CRT) and acquire further resistance via deregulation of many signaling pathways. Due to the failure of classical chemotherapies and targeted drugs, research efforts focusing on the use of less toxic agents have increased. Interestingly, multiple natural compounds have shown antitumor and apoptotic effects in TMZ resistant and p53 mutant GBM cell lines and also displayed synergistic effects with TMZ. In this review, we have summarized the current literature on natural products or product analogs used to modulate the BBB permeability, induce cell death, eradicate CSCs and sensitize GBM to CRT.

Natural products: a hope for glioblastoma patients

PubMed Central

Vengoji, Raghupathy; Macha, Muzafar A.; Batra, Surinder K.; Shonka, Nicole A.

2018-01-01

Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB). Cancer stem cells (CSCs) have intrinsic resistance to initial chemoradiation therapy (CRT) and acquire further resistance via deregulation of many signaling pathways. Due to the failure of classical chemotherapies and targeted drugs, research efforts focusing on the use of less toxic agents have increased. Interestingly, multiple natural compounds have shown antitumor and apoptotic effects in TMZ resistant and p53 mutant GBM cell lines and also displayed synergistic effects with TMZ. In this review, we have summarized the current literature on natural products or product analogs used to modulate the BBB permeability, induce cell death, eradicate CSCs and sensitize GBM to CRT. PMID:29774132

Liposarcoma: multimodality management and future targeted therapies

PubMed Central

Crago, Aimee M.; Dickson, Mark A.

2016-01-01

SYNOPSIS There are three biologic groups of liposarcoma: well- and dedifferentiated liposarcoma (WD/DDLS), myxoid/round cell liposarcoma (M/RCLS) and pleomorphic liposarcoma. WD/DDLS is characterized by amplification of 12q13-15 (including the oncogenes MDM2 and CDK4), M/RCLS by FUS-DDIT3 translocations, and pleomorphic liposarcoma by loss of p53 and Rb. In all three groups, complete surgical resection is central in treatment aimed at cure and is based on grade. Radiation can reduce risk of local recurrence in high-grade lesions or minimize surgical morbidity in the highly radiosensitive M/RCLS group. The biologic groups differ greatly in their chemosensitivity, so adjuvant chemotherapy is selectively utilized in chemosensitive histologies with metastatic potential (i.e. round cell and pleomorphic liposarcomas) but not in the relatively resistant subtype DDLS. An improved understanding of the genetic aberrations that lead to liposarcoma initiation is also allowing for the rapid development of targeted therapies for liposarcoma. Among such therapies are CDK4 inhibitors in WD/DDLS and trabectedin, which prevents FUS-DDIT3 binding to DNA, in M/RCLS. PMID:27591497

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma.

PubMed

Weber, Jeffrey; Mandala, Mario; Del Vecchio, Michele; Gogas, Helen J; Arance, Ana M; Cowey, C Lance; Dalle, Stéphane; Schenker, Michael; Chiarion-Sileni, Vanna; Marquez-Rodas, Ivan; Grob, Jean-Jacques; Butler, Marcus O; Middleton, Mark R; Maio, Michele; Atkinson, Victoria; Queirolo, Paola; Gonzalez, Rene; Kudchadkar, Ragini R; Smylie, Michael; Meyer, Nicolas; Mortier, Laurent; Atkins, Michael B; Long, Georgina V; Bhatia, Shailender; Lebbé, Celeste; Rutkowski, Piotr; Yokota, Kenji; Yamazaki, Naoya; Kim, Tae M; de Pril, Veerle; Sabater, Javier; Qureshi, Anila; Larkin, James; Ascierto, Paolo A

2017-11-09

Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population. At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment. Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906 ; Eudra-CT number, 2014-002351-26 .).

How do surgeons decide to refer patients for adjuvant cancer treatment? Protocol for a qualitative study

PubMed Central

2012-01-01

Background Non-small cell lung cancer, breast cancer, and colorectal cancer are commonly diagnosed cancers in Canada. Patients diagnosed with early-stage non-small cell lung, breast, or colorectal cancer represent potentially curable populations. For these patients, surgery is the primary mode of treatment, with (neo)adjuvant therapies (e.g., chemotherapy, radiotherapy) recommended according to disease stage. Data from our research in Nova Scotia, as well as others’, demonstrate that a substantial proportion of non-small cell lung cancer and colorectal cancer patients, for whom practice guidelines recommend (neo)adjuvant therapy, are not referred for an oncologist consultation. Conversely, surveillance data and clinical experience suggest that breast cancer patients have much higher referral rates. Since surgery is the primary treatment, the surgeon plays a major role in referring patients to oncologists. Thus, an improved understanding of how surgeons make decisions related to oncology services is important to developing strategies to optimize referral rates. Few studies have examined decision making for (neo)adjuvant therapy from the perspective of the cancer surgeon. This study will use qualitative methods to examine decision-making processes related to referral to oncology services for individuals diagnosed with potentially curable non-small cell lung, breast, or colorectal cancer. Methods A qualitative study will be conducted, guided by the principles of grounded theory. The study design is informed by our ongoing research, as well as a model of access to health services. The method of data collection will be in-depth, semi structured interviews. We will attempt to recruit all lung, breast, and/or colorectal cancer surgeons in Nova Scotia (n ≈ 42), with the aim of interviewing a minimum of 34 surgeons. Interviews will be audiotaped and transcribed verbatim. Data will be collected and analyzed concurrently, with two investigators independently coding and analyzing the data. Analysis will involve an inductive, grounded approach using constant comparative analysis. Discussion The primary outcomes will be (1) identification of the patient, surgeon, institutional, and health-system factors that influence surgeons’ decisions to refer non-small cell lung, breast, and colorectal cancer patients to oncology services when consideration for (neo)adjuvant therapy is recommended and (2) identification of potential strategies that could optimize referral to oncology for appropriate individuals. PMID:23098262

The impact of extended release exenatide as adjuvant therapy on hemoglobin A1C, weight, and total daily dose of insulin in patients with type 2 diabetes mellitus using U-500 insulin.

PubMed

Farwig, Phillip A; Zielinski, Angela J; Accursi, Mallory L; Burant, Christopher J

2017-12-01

To evaluate the efficacy and safety of adjuvant exenatide extended release (ER) therapy in patients treated with regular U-500 insulin. In this retrospective chart review at an ambulatory care center in the Midwest, 18 patients with type 2 diabetes being treated with regular U-500 insulin and adjuvant exenatide ER were identified. These patients were evaluated for outcomes following the addition of exenatide ER. The primary outcome was change in HbA 1C from baseline to 3, 6, and 12months. Secondary outcomes included change in weight, total daily dose (TDD) of insulin, and hypoglycemia. Repeated measures ANOVA was performed to assess the differences in mean scores over four time periods. A total of 18 of 50 patients met inclusion criteria with sufficient data to be included in analysis. HbA 1C showed non-significant findings from baseline to 12months (8.08% vs. 8.23%; p=0.75). A non-significant, modest weight loss occurred (146.4kgvs. 144.2kg; -2.2kg; p=0.31). A significant decrease in TDD of insulin was observed (378 units vs. 326 units; p<0.001). There was a trend towards hypoglycemia from baseline to month 3 post addition of exenatide ER (0.33 events vs. 1.33 events; p=0.055). In patients treated with regular U-500 insulin, adjuvant exenatide ER therapy showed no significant improvement in HbA 1C , but did show modest weight loss as well as decreased insulin requirements to achieve a HbA 1C that was comparable to baseline. Published by Elsevier B.V.

Sentinel Lymph Node Biopsy in Endometrial Cancer: a New Standard of Care?

PubMed

Sullivan, Stephanie A; Rossi, Emma C

2017-09-18

Lymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment in endometrial cancer (EMCA). Unfortunately, full lymphadenectomy bears significant surgical and postoperative risks. The majority of patients with clinical stage I disease will not have metastatic disease; thus, a full lymphadenectomy only increases morbidity in this population of patients. The use of the sentinel lymph node (SLN) biopsy has emerged as an alternative to complete lymphadenectomy in EMCA. By removing the highest yield lymph nodes, the SLN biopsy has the same diagnostic ability as lymphadenectomy while minimizing morbidity. The sensitivity of sentinel lymph node identification with robotic fluorescence imaging for detecting metastatic endometrial and cervical cancer (FIRES) trial published this year is the largest prospective, multi-institution trial investigating the accuracy of the SLN biopsy for endometrial and cervical cancer. Results of this trial found an excellent sensitivity (97.2%) and false negative rate (3%) with the technique. The conclusions from the FIRES trial and those of a recent meta-analysis are that SLN biopsy has an acceptable diagnostic accuracy in detecting lymphatic metastases, and can replace lymphadenectomy for this diagnostic purpose. There remains controversy surrounding the SLN biopsy in high-risk disease and the use of adjuvant therapy in the setting of low volume disease detected with ultrastaging. Current data suggests that the technique is accurate in high-risk disease and that the increased detection of metastasis helps guide adjuvant therapy such that oncologic outcomes are likely not affected by forgoing a full lymphadenectomy. Further prospective study is needed to investigate the impact of low volume metastatic disease on oncologic outcomes and the need for adjuvant therapy in these patients.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trifiletti, Daniel M.; Swisher-McClure, Samuel; Showalter, Timothy N.

Purpose: To review the National Cancer Database (NCDB) to evaluate postoperative high-risk cervical cancer patients for factors associated with a benefit from chemoradiation therapy (CRT) over external beam radiation therapy alone (EBRT). Methods and Materials: The National Cancer Database was queried for women with cervical cancer treated with hysterectomy and adjuvant EBRT from 2002 to 2012. Only patients with pathologic lymph node involvement (LN+), positive surgical margins, and/or parametrial invasion were included in our analysis (on the basis of Peter's criteria). Univariable and multivariable analyses (MVA) were performed, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigatemore » for factors associated with of CRT utilization and overall survival (OS). Results: A total of 3053 patients met inclusion criteria, and 2479 received adjuvant CRT (81%), whereas 574 (19%) received EBRT alone. Factors associated with increased CRT utilization on MVA included age <69 years, year of diagnosis ≥2008, non-adenocarcinoma histology, and LN+. Use of CRT improved OS among the entire cohort on MVA (HR 0.76, CI 0.601-0.962; P=.022). On MVA, CRT improved OS in patients with LN+ as their sole Peter's criteria (HR 0.58, CI 0.413-0.814; P=.002). Chemoradiation therapy did not improve OS in patients with only positive margins (P=.73), only parametrial invasion (P=.95), or any combination of these 2 factors without LN+ (P=.63). Conclusions: The use of adjuvant CRT after hysterectomy improves OS in patients with high-risk cervical cancer compared with EBRT alone, but this benefit seems to be restricted to patients with LN+. The benefits of adjuvant CRT over EBRT alone in patients with parametrial invasion and/or positive margins (without nodal involvement) are unknown.« less

Nipple-Sparing Mastectomy is Not Associated with a Delay of Adjuvant Treatment.

PubMed

Albright, Emily L; Schroeder, Mary C; Foster, Kendra; Sugg, Sonia L; Erdahl, Lillian M; Weigel, Ronald J; Lizarraga, Ingrid M

2018-07-01

High-volume single-institution studies support the oncologic safety of nipple sparing mastectomy (NSM). Concerns remain regarding the increased potential for complications, recurrence, and delays to subsequent adjuvant therapy. A national database was used to examine treatment and outcomes for NSM patients. Women undergoing unilateral NSM or skin sparing mastectomy (SSM) for stage 0-4 breast cancer from 2004 to 2013 were identified from the National Cancer Database. Demographic and oncologic characteristics, short-term outcomes and time to local and systemic treatment were compared. NSM was performed on 8173 patients: 8.7% were node positive, and for stage 1-4 disease, 10.6% were triple negative (TN) and 15.3% were HER2-positive. NSM patients were less likely than SSM patients to receive chemotherapy [CT] (37.4 vs. 43.4%) or radiation [PMRT] (15.6 vs. 16.9%), and were also more likely to present with clinically early-stage disease. NSM patients with high-risk features were more likely to receive CT in the neoadjuvant [NCT] than adjuvant setting [AC] (OR 3.76, 1.81, and 1.99 for clinical N2/3, TN, and HER2-positive disease, all p < 0.001). On multivariate analysis, NSM patients had a higher rate of pathologic complete response [pCR] (OR 1.41, p < 0.001). Readmission rate, positive margin rate and time to CT, PMRT or hormonal therapy were not increased for NSM compared to SSM patients. Over one third of NSM patients received chemotherapy and/or radiation. NSM patients with high-risk features were more likely to receive NAC and obtain a pCR. NSM patients did not experience worse outcomes or delayed adjuvant therapy compared to SSM.

Effects of Adjuvant Mental Practice on Affected Upper Limb Function Following a Stroke: Results of Three-Dimensional Motion Analysis, Fugl-Meyer Assessment of the Upper Extremity and Motor Activity Logs.

PubMed

Oh, Hyun Seung; Kim, Eun Joo; Kim, Doo Young; Kim, Soo Jeong

2016-06-01

To investigate the effects of adjuvant mental practice (MP) on affected upper limb function following a stroke using three-dimensional (3D) motion analysis. In this AB/BA crossover study, we studied 10 hemiplegic patients who had a stroke within the past 6 months. The patients were randomly allocated to two groups: one group received MP combined with conventional rehabilitation therapy for the first 3 weeks followed by conventional rehabilitation therapy alone for the final 3 weeks; the other group received the same therapy but in reverse order. The MP tasks included drinking from a cup and opening a door. MP was individually administered for 20 minutes, 3 days a week for 3 weeks. To assess the tasks, we used 3D motion analysis and three additional tests: the Fugl-Meyer Assessment of the upper extremity (FMA-UE) and the motor activity logs for amount of use (MAL-AOU) and quality of movement (MAL-QOM). Assessments were performed immediately before treatment (T0), 3 weeks into treatment (T1), and 6 weeks into treatment (T2). Based on the results of the 3D motion analysis and the FMA-UE index (p=0.106), the MAL-AOU scale (p=0.092), and MAL-QOM scale (p=0.273), adjuvant MP did not result in significant improvements. Adjuvant MP had no significant effect on upper limb function following a stroke, according to 3D motion analysis and three clinical assessment tools (the FMA-UE index and the two MAL scales). The importance of this study is its use of objective 3D motion analysis to evaluate the effects of MP. Further studies will be needed to validate these findings.

A pan-inhibitor of DASH family enzymes induces immune-mediated regression of murine sarcoma and is a potent adjuvant to dendritic cell vaccination and adoptive T-cell therapy.

PubMed

Duncan, Brynn B; Highfill, Steven L; Qin, Haiying; Bouchkouj, Najat; Larabee, Shannon; Zhao, Peng; Woznica, Iwona; Liu, Yuxin; Li, Youhua; Wu, Wengen; Lai, Jack H; Jones, Barry; Mackall, Crystal L; Bachovchin, William W; Fry, Terry J

2013-10-01

Multimodality therapy consisting of surgery, chemotherapy, and radiation will fail in approximately 40% of patients with pediatric sarcomas and result in substantial long-term morbidity in those who are cured. Immunotherapeutic regimens for the treatment of solid tumors typically generate antigen-specific responses too weak to overcome considerable tumor burden and tumor suppressive mechanisms and are in need of adjuvant assistance. Previous work suggests that inhibitors of DASH (dipeptidyl peptidase IV activity and/or structural homologs) enzymes can mediate tumor regression by immune-mediated mechanisms. Herein, we demonstrate that the DASH inhibitor, ARI-4175, can induce regression and eradication of well-established solid tumors, both as a single agent and as an adjuvant to a dendritic cell (DC) vaccine and adoptive cell therapy (ACT) in mice implanted with the M3-9-M rhabdomyosarcoma cell line. Treatment with effective doses of ARI-4175 correlated with recruitment of myeloid (CD11b) cells, particularly myeloid DCs, to secondary lymphoid tissues and with reduced frequency of intratumoral monocytic (CD11bLy6-CLy6-G) myeloid-derived suppressor cells. In immunocompetent mice, combining ARI-4175 with a DC vaccine or ACT with tumor-primed T cells produced significant improvements in tumor responses against well-established M3-9-M tumors. In M3-9-M-bearing immunodeficient (Rag1) mice, ACT combined with ARI-4175 produced greater tumor responses and significantly improved survival compared with either treatment alone. These studies warrant the clinical investigation of ARI-4175 for treatment of sarcomas and other malignancies, particularly as an adjuvant to tumor vaccines and ACT.

Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

PubMed

Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

2017-06-01

This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

Contemporary adjuvant polymethyl methacrylate cementation optimally limits recurrence in primary giant cell tumor of bone patients compared to bone grafting: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Reports of recurrence following restructuring of primary giant cell tumor (GCT) defects using polymethyl methacrylate (PMMA) bone cementation or allogeneic bone graft with and without adjuvants for intralesional curettage vary widely. Systematic review and meta-analysis were conducted to investigate efficacy of PMMA bone cementation and allogeneic bone grafting following intralesional curettage for GCT. Methods Medline, EMBASE, Google Scholar, and Cochrane databases were searched for studies reporting GCT of bone treatment with PMMA cementation and/or bone grafting with or without adjuvant therapy following intralesional curettage of primary GCTs. Pooled risk ratios and 95% confidence intervals (CIs) for local recurrence risks were calculated by fixed-effects methods. Results Of 1,690 relevant titles, 6 eligible studies (1,293 patients) spanning March 2008 to December 2011 were identified in published data. Treatment outcomes of PMMA-only (n = 374), bone graft-only (n = 436), PMMA with or without adjuvant (PMMA + adjuvant; n = 594), and bone graft filling with or without adjuvant (bone graft + adjuvant; n = 699) were compared. Bone graft-only patients exhibited higher recurrence rates than PMMA-treated patients (RR 2.09, 95% CI (1.64, 2.66), Overall effect: Z = 6.00; P <0.001), and bone graft + adjuvant patients exhibited higher recurrence rates than PMMA + adjuvant patients (RR 1.66, 95% CI (1.21, 2.28), Overall effect: Z = 3.15, P = 0.002). Conclusions Local recurrence was minimal in PMMA cementation patients, suggesting that PMMA is preferable for routine clinical restructuring in eligible GCT patients. Relationships between tumor characteristics, other modern adjuvants, and recurrence require further exploration. PMID:23866921

Comparison of the Prognostic and Predictive Utilities of the 21-Gene Recurrence Score Assay and Adjuvant! for Women with Node-Negative, ER-Positive Breast Cancer: Results from NSABP B-14 and NSABP B-20

PubMed Central

Tang, Gong; Shak, Steven; Paik, Soonmyung; Anderson, Stewart J.; Costantino, Joseph P.; Geyer, Charles E.; Mamounas, Eleftherios P.; Wickerham, D. Lawrence; Wolmark, Norman

2012-01-01

The Oncotype DX® Recurrence Score® (RS) is a validated genomic predictor of outcome and response to adjuvant chemotherapy in ER-positive breast cancer. Adjuvant! was developed using SEER registry data and results from the Early Breast Cancer Clinical Trialists’ overview analyses to estimate outcome and benefit from adjuvant hormonal therapy and chemotherapy. In this report we compare the prognostic and predictive utility of these two tools in node-negative, ER-positive breast cancer. RS and Adjuvant! results were available from 668 tamoxifen-treated NSABP B-14 patients: 227 tamoxifen-treated NSABP B-20 patients, and 424 chemotherapy-plus-tamoxifen-treated B-20 patients. Adjuvant! results were also available from 1952 B-20 patients. The primary endpoint was distant recurrence-free interval (DRFI). Cox proportional hazards models were used to compare the prognostic and predictive utility of RS and Adjuvant!. Both RS (p<0.001) and Adjuvant! (p=0.002) provided strong independent prognostic information in tamoxifen-treated patients. Combining RS and individual clinicopathologic characteristics provided greater prognostic discrimination than combining RS and the composite Adjuvant!. In the B-20 cohort with RS results (n=651), RS was significantly predictive of chemotherapy benefit (interaction p=0.031 for DRFI, p=0.011 for overall survival [OS], p=0.082 for disease-free survival [DFS]), but Adjuvant! was not (interaction p=0.99, p=0.311 and p=0.357, respectively). However, in the larger B-20 sub-cohort (n=1952), Adjuvant! was significantly predictive of chemotherapy benefit for OS (interaction p=0.009) but not for DRFI (p=0.219) or DFS (p=0.099). Prognostic estimates can be optimized by combining RS and clinicopathologic information instead of simply combining RS and Adjuvant!. RS should be used for estimating relative chemotherapy benefit. PMID:21221771

Comparison of the prognostic and predictive utilities of the 21-gene Recurrence Score assay and Adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20.

PubMed

Tang, Gong; Shak, Steven; Paik, Soonmyung; Anderson, Stewart J; Costantino, Joseph P; Geyer, Charles E; Mamounas, Eleftherios P; Wickerham, D Lawrence; Wolmark, Norman

2011-05-01

The Oncotype DX Recurrence Score (RS) is a validated genomic predictor of outcome and response to adjuvant chemotherapy in ER-positive breast cancer. Adjuvant! was developed using SEER registry data and results from the Early Breast Cancer Clinical Trialists' overview analyses to estimate outcome and benefit from adjuvant hormonal therapy and chemotherapy. In this report we compare the prognostic and predictive utility of these two tools in node-negative, ER-positive breast cancer. RS and Adjuvant! results were available from 668 tamoxifen-treated NSABP B-14 patients, 227 tamoxifen-treated NSABP B-20 patients, and 424 chemotherapy plus tamoxifen-treated B-20 patients. Adjuvant! results were also available from 1952 B-20 patients. The primary endpoint was distant recurrence-free interval (DRFI). Cox proportional hazards models were used to compare the prognostic and predictive utility of RS and Adjuvant!. Both RS (P < 0.001) and Adjuvant! (P = 0.002) provided strong independent prognostic information in tamoxifen-treated patients. Combining RS and individual clinicopathologic characteristics provided greater prognostic discrimination than combining RS and the composite Adjuvant!. In the B-20 cohort with RS results (n = 651), RS was significantly predictive of chemotherapy benefit (interaction P = 0.031 for DRFI, P = 0.011 for overall survival [OS], P = 0.082 for disease-free survival [DFS]), but Adjuvant! was not (interaction P = 0.99, P = 0.311, and P = 0.357, respectively). However, in the larger B-20 sub-cohort (n = 1952), Adjuvant! was significantly predictive of chemotherapy benefit for OS (interaction P = 0.009) but not for DRFI (P = 0.219) or DFS (P = 0.099). Prognostic estimates can be optimized by combining RS and clinicopathologic information instead of simply combining RS and Adjuvant!. RS should be used for estimating relative chemotherapy benefit.

[Prognostic factors of early breast cancer].

PubMed

Almagro, Elena; González, Cynthia S; Espinosa, Enrique

2016-02-19

Decision about the administration of adjuvant therapy for early breast cancer depends on the evaluation of prognostic factors. Lymph node status, tumor size and grade of differentiation are classical variables in this regard, and can be complemented by hormonal receptor status and HER2 expression. These factors can be combined into prognostic indexes to better estimate the risk of relapse or death. Other factors are less important. Gene profiles have emerged in recent years to identify low-risk patients who can forgo adjuvant chemotherapy. A number of profiles are available and can be used in selected cases. In the future, gene profiling will be used to select patients for treatment with new targeted therapies. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Sinonasal hemangiopericytomas: a clinicopathologic and immunohistochemical study of seven cases.

PubMed

Catalano, P J; Brandwein, M; Shah, D K; Urken, M L; Lawson, W; Biller, H F

1996-01-01

Sinonasal hemangiopericytoma (SNHPC) is a rare lesion usually of low-grade malignant potential. Aggressive and metastatic cases are uncommon, and experience using adjuvant therapy on these cases has been limited. Tumor-induced osteomalacia has a very rare association with SNHPC. Further, the diagnosis of SNHPC remains one of histologic-pattern recognition. Traditionally, immunohistochemistry has aided in excluding other diagnoses; only vimentin has been consistently expressed by the tumor spindle cells of HPC. Recent studies have shown that Factor XIIIa is also expressed by HPC, (as well as tumors of fibrohistiocytic differentiation) and hence may be yet another helpful positive marker in establishing an immunohistochemical profile. We identified 7 patients at this institution with SNHPC from 1990 to 1994. Immunohistochemistry was performed on seven formalin-fixed paraffin-embedded tumors utilizing antibodies to factor XIIIa as well as antibodies to vimentin, factor VIII, muscle-specific antigen, cytokeratin, and S-100. All 7 patients were initially seen with nasal obstruction or epistaxis and underwent surgical resection. The period of follow-up was from 3 months to 14 years (mean 54 months) for 7 patients. Three patients had recurrent disease after 3, 5, and 10 years. The first 2 were known to have been originally treated by polypectomy. One patient required adjuvant radiotherapy for metastatic disease and local extension. One patient was initially seen with tumor-induced osteomalacia which dramatically improved following resection of the lesion. The immunohistochemical profile revealed strong expression of vimentin in 7/7 cases, and of factor XIIIa in 4/7 cases; tumor cells did not express the other markers studied. Adequate surgical resection with negative margins appears to be the appropriate therapy for SNHPC. Our 1 case associated with tumor-induced osteomalacia was reversible after surgical excision of the tumor. The immunohistochemical results suggest that the pattern of vimentin and factor XIIIa positivity, as well as lack of expression of other markers, is consistent with the diagnosis of HPC, which still remains in the domain of histopathology.

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study.

PubMed

Basu, Reshma; Pathak, Sunjay; Goyal, Jyoti; Chaudhry, Rajeev; Goel, Rati B; Barwal, Anil

2014-12-01

CytoSorb(®) (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb(®) in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb(®) hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock.

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study

PubMed Central

Basu, Reshma; Pathak, Sunjay; Goyal, Jyoti; Chaudhry, Rajeev; Goel, Rati B.; Barwal, Anil

2014-01-01

CytoSorb® (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb® in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb® hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock. PMID:25538418

Anthrax prevention and treatment: utility of therapy combining antibiotic plus vaccine.

PubMed

Klinman, Dennis M; Yamamoto, Masaki; Tross, Debra; Tomaru, Koji

2009-12-01

The intentional release of anthrax spores in 2001 confirmed this pathogen's ability to cause widespread panic, morbidity and mortality. While individuals exposed to anthrax can be successfully treated with antibiotics, pre-exposure vaccination can reduce susceptibility to infection-induced illness. Concern over the safety and immunogenicity of the licensed US vaccine (Anthrax Vaccine Adsorbed (AVA)) has fueled research into alternatives. Second-generation anthrax vaccines based on purified recombinant protective antigen (rPA) have entered clinical trials. These rPA vaccines induce neutralizing antibodies that prevent illness, but the magnitude and duration of the resultant protective response is modest. Efforts are underway to bolster the immunogenicity of rPA by combining it with adjuvants and other immunostimulatory agents. Third generation vaccines are under development that utilize a wide variety of immunization platforms, antigens, adjuvants, delivery methods and routes of delivery to optimize the induction of a protective immunity. For the foreseeable future, vaccination will rely on first and second generation vaccines co-administered with immune adjuvants. Optimal post-exposure treatment of immunologically naive individuals should include a combination of vaccine plus antibiotic therapy.

Imatinib as the first and only treatment in Europe for adult patients at significant risk of relapse following gastrointestinal stromal tumor removal

PubMed Central

Duffaud, F; Salas, S; Huyn, T; Deville, JL

2010-01-01

Mutations of the KIT gene are the molecular hallmark of most gastrointestinal stromal tumors (GISTs). GIST has become a model for targeted treatment of solid tumors, imatinib becoming the standard first-line treatment of these tumors in the advanced/metastatic phase. Because of the efficacy of imatinib treatment in the advanced setting, its role following resection of a primary non-metastatic GIST was investigated. The recently published phase III, double-blind, placebo-controlled, multicenter ACOSOG Z9001 study showed that adjuvant therapy is safe, and significantly improves recurrence-free survival compared to placebo when given after resection. To what extent imatinib will improve overall survival has yet to be answered. What is clear is that high-risk GIST patients definitely need adjuvant therapy, and that 1 year of imatinib is not enough for the patients who do need it. The questions of optimal duration of imatinib treatment in the adjuvant setting, adequate selection of risk patients and effect of imatinib on overall survival are currently being studied. PMID:21694845

Optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer.

PubMed

Kowalczyk, Keith J; Gu, Xiangmei; Nguyen, Paul L; Lipsitz, Stuart R; Trinh, Quoc-Dien; Lynch, John H; Collins, Sean P; Hu, Jim C

2014-04-01

Although post-radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the outcomes and optimal timing of early vs. delayed ART. From the Surveillance, Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3N0 disease receiving early (<4 mo after RP, n = 419) vs. delayed (4-12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we compared overall mortality, prostate cancer-specific mortality (PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the most significant effect on outcomes of interest in men with pT3N0 disease. When compared with delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042). Initiating ART less than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP, respectively. However, ART administered later than 9 months after RP is associated with fewer urethral strictures. Our population-based findings complement randomized trials designed with fixed ART timing. © 2013 Published by Elsevier Inc.

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer.

PubMed Central

Saarto, T.; Blomqvist, C.; Rissanen, P.; Auvinen, A.; Elomaa, I.

1997-01-01

Two hundred and eleven patients with node-positive stage II and III breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (DI), dose intensity of the two initial cycles (DI2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P = 0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy. PMID:9010042

Generation of “Virtual” Control Groups for Single Arm Prostate Cancer Adjuvant Trials

PubMed Central

Koziol, James A.; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M.; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-guo; McLaren, Christine E.; Gurley, Michael J.; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W.; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. PMID:24465467

Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

PubMed

Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

Salvage topical therapy for upper tract urothelial carcinoma.

PubMed

Balasubramanian, Adithya; Metcalfe, Michael J; Wagenheim, Gavin; Xiao, Lianchun; Papadopoulos, John; Navai, Neema; Davis, John W; Karam, Jose A; Kamat, Ashish M; Wood, Christopher G; Dinney, Colin P; Matin, Surena F

2018-05-26

Topical therapy (TT) for upper tract urothelial carcinoma (UTUC) has been explored as a kidney sparing approach to treat carcinoma in situ (CIS) and as adjuvant for endoscopically treated Ta/T1 tumors. In bladder cancer, data support use of salvage TT for repeat induction. We investigate the outcomes of salvage TT for UTUC in patients ineligible for or refusing nephroureterectomy. A single-center retrospective review on patients receiving salvage TT via percutaneous nephrostomy tube or cystoscopically placed ureteral catheters was performed. Primary outcome was response to therapy based on International Bladder Cancer Group criteria. 51 patients with 58 renal units (RUs) received TT. Of these, 17 patients with 18 RUs received the second-line TT, with a median follow-up of 36.5 months (IQR 24.5-67 months). 44% (8/18) received salvage TT for refractory disease and 56% (10/18) as reinduction. 5 RUs with CIS were unresponsive to initial TT and went on to receive salvage TT, of which 20% (1/5) responded. 13 RUs recurred or relapsed following initial TT and received salvage TT for papillary tumors, with 62% (8/13) responding. Our data provide preliminary clinical rationale for the second-line TT for refractory and recurrent, endoscopically managed papillary UTUC in patients ineligible for or refusing nephroureterectomy. However, refractory upper tract CIS appears to have poor response to salvage TT.

Cost-effectiveness analysis of high-dose omeprazole infusion as adjuvant therapy to endoscopic treatment of bleeding peptic ulcer.

PubMed

Lee, Kenneth K C; You, Joyce H S; Wong, Ian C K; Kwong, Sunny K S; Lau, James Y W; Chan, Thomas Y K; Lau, Joseph T F; Leung, Wilson Y S; Sung, Joseph J Y; Chung, Sydney S C

2003-02-01

Intravenous administration of proton pump inhibitors after endoscopic treatment of bleeding peptic ulcers has been shown to decrease the rate of recurrent bleeding and the need for subsequent surgery. Yet there is a relative lack of formal assessment of this practice. The aim of this study was to examine the cost-effectiveness of this therapy by using standard pharmacoeconomic methods. The present study was performed in conjunction with a randomized controlled clinical trial that included 232 patients who received either omeprazole (80 mg intravenous bolus followed by infusion at 8 mg/hour for 72 hours) or placebo after hemostasis was achieved endoscopically. A cost-effectiveness analysis was performed to evaluate the different outcomes of the trial. All related direct medical costs were identified from patient records. Cost-effectiveness ratios were calculated. Analysis by the Kolmogorov-Smirnov test showed that the direct medical cost in the omeprazole group was lower than that for the placebo group. Cost-effectiveness ratios for omeprazole and placebo groups were, respectively, HK$ 28,764 (US$ 3688) and HK$ 36,992 (US$ 4743) in averting one episode of recurrent bleeding in one patient after initial hemostasis was achieved endoscopically. Intravenous administration of high-dose omeprazole appears to be a cost-effective therapy in reducing the recurrence of bleeding and need for surgery in patients with active bleeding ulcer after initial hemostasis is obtained endoscopically.

Capecitabine treatment patterns in patients with gastroesophageal cancer in the United States

PubMed Central

Saif, Muhammad Wasif; Shi, Nianwen; Zelt, Susan

2009-01-01

AIM: To assess the use of capecitabine-based therapy and associated complication rates in patients with gastroesophageal cancer (GEC) in a real-world treatment setting. METHODS: Patients with claims between 2004 and 2005 were identified from the Thomson Reuters MarketScan® databases. Capecitabine regimens were compared with 5-fluorouracil (5-FU) and other chemotherapy regimens, and were stratified by treatment setting. RESULTS: We identified 1013 patients with GEC: approximately half had treatment initiated with a 5-FU regimen, whereas 11% had therapy initiated with a capecitabine regimen. The mean capecitabine dose overall was 2382 ± 1118 mg/d, and capecitabine was used as monotherapy more often than in combination. Overall, 5-FU regimens were the most common treatment option in neoadjuvant and adjuvant settings, while other non-capecitabine regimens were used more widely in first- and second-line settings. The overall unadjusted complication rate for capecitabine regimens was about half of that seen with 5-FU regimens. In multivariate analyses, capecitabine recipients had a 51% (95% CI: 26%-81%) lower risk of developing any complication than 5-FU recipients did. The risk of developing bone marrow, constitutional, gastrointestinal tract, infectious, or skin complications was lower with capecitabine therapy than with 5-FU. CONCLUSION: Capecitabine appeared to have a favorable side effect profile compared with 5-FU, which indicates that it may be a treatment option for GEC. PMID:19764093

Laser vaccine adjuvants. History, progress, and potential.

PubMed

Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

2014-01-01

Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines.

Laser vaccine adjuvants

PubMed Central

Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

2014-01-01

Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

Effectiveness of Oncologist-Referred Exercise and Healthy Eating Programming as a Part of Supportive Adjuvant Care for Early Breast Cancer.

PubMed

Kirkham, Amy A; Van Patten, Cheri L; Gelmon, Karen A; McKenzie, Donald C; Bonsignore, Alis; Bland, Kelcey A; Campbell, Kristin L

2018-01-01

Randomized trials have established efficacy of supervised exercise training during chemotherapy for breast cancer for numerous health outcomes. The purpose of this study was to assess reach, effectiveness, maintenance, and implementation of an evidence-based exercise and healthy eating program offered within an adjuvant care setting. Women receiving adjuvant chemotherapy for breast cancer were given a prescription by their oncologist to participate in the Nutrition and Exercise during Adjuvant Treatment (NExT) program. The NExT program consisted of supervised, moderate-intensity, aerobic and resistance exercise three times a week during adjuvant therapy, followed by a step-down in supervised sessions per week for 20 additional weeks, plus one group-based healthy eating session. Usual moderate-to-vigorous physical activity (MVPA) and health-related quality of life (HRQoL) were assessed by questionnaire at baseline, program completion, and one year later, along with measures of satisfaction and safety. Program reach encompassed referral of 53% of eligible patients, 78% uptake ( n  = 73 enrolled), and 78% retention for the 45.0 ± 8.3-week program. During the program, MVPA increased (116 ± 14 to 154 ± 14 minutes per week, p  = .014) and HRQoL did not change. One year later, MVPA (171 ± 24 minutes per week, p  = .014) and HRQoL (44 ± 1 to 49 ± 1, p  < .001) were significantly higher than baseline. Exercise adherence was 60% ± 26% to three sessions per week during treatment. No major adverse events occurred and injury prevalence did not change relative to baseline. Participants were highly satisfied. This oncologist-referred exercise and healthy eating supportive-care program for breast cancer patients receiving chemotherapy was safe, successful in reaching oncologists and patients, and effective for improving MVPA and maintaining HRQoL. Despite evidence that exercise is both safe and efficacious at improving physical fitness, quality of life, and treatment side effects for individuals with cancer, lifestyle programming is not offered as standard of cancer care. This study describes an oncologist-referred, evidence-based exercise and healthy eating program offered in collaboration with a university as supportive care to women with breast cancer receiving chemotherapy. The program was well received by oncologists and patients, safe, and relatively inexpensive to operate. Importantly, there was a significant positive impact on physical activity levels and health-related quality of life lasting for 2 years after initiation of therapy. © AlphaMed Press 2017.

Adjuvant ovarian function suppression and cognitive function in women with breast cancer

PubMed Central

Phillips, Kelly-Anne; Regan, Meredith M; Ribi, Karin; Francis, Prudence A; Puglisi, Fabio; Bellet, Meritxell; Spazzapan, Simon; Karlsson, Per; Budman, Daniel R; Zaman, Khalil; Abdi, Ehtesham A; Domchek, Susan M; Feng, Yang; Price, Karen N; Coates, Alan S; Gelber, Richard D; Maruff, Paul; Boyle, Frances; Forbes, John F; Ahles, Tim; Fleming, Gini F; Bernhard, Jürg

2016-01-01

Background: To examine the effect on cognitive function of adjuvant ovarian function suppression (OFS) for breast cancer. Methods: The Suppression of Ovarian Function (SOFT) trial randomised premenopausal women with hormone receptor-positive breast cancer to 5 years adjuvant endocrine therapy with tamoxifen+OFS, exemestane+OFS or tamoxifen alone. The Co-SOFT substudy assessed objective cognitive function and patient reported outcomes at randomisation (T0), and 1 year later (T1); the primary endpoint was change in global cognitive function, measured by the composite objective cognitive function score. Data were compared for the pooled tamoxifen+OFS and exemestane+OFS groups vs the tamoxifen alone group using the Wilcoxon rank-sum test. Results: Of 86 participants, 74 underwent both T0 and T1 cognitive testing; 54 randomised to OFS+ either tamoxifen (28) or exemestane (26) and 20 randomised to tamoxifen alone. There was no significant difference in the changes in the composite cognitive function scores between the OFS+ tamoxifen or exemestane groups and the tamoxifen group (mean±s.d., −0.21±0.92 vs −0.04±0.49, respectively, P=0.71, effect size=−0.20), regardless of prior chemotherapy status, and adjusting for baseline characteristics. Conclusions: The Co-SOFT study, although limited by small samples size, provides no evidence that adding OFS to adjuvant oral endocrine therapy substantially affects global cognitive function. PMID:27092785

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

PubMed Central

Gaß, Paul; Fasching, Peter A.; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W.; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M.; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y.; Beckmann, Matthias W.; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R.

2016-01-01

Background Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues. PMID:27920623

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

PubMed

Gaß, Paul; Fasching, Peter A; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y; Beckmann, Matthias W; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R

2016-10-01

Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

Leptin-based Adjuvants: An Innovative Approach to Improve Vaccine Response

PubMed Central

White, Sarah J.; Taylor, Matthew J.; Hurt, Ryan; Jensen, Michael D.; Poland, Gregory A.

2013-01-01

Leptin is a pleiotropic hormone with multiple direct and regulatory immune functions. Leptin deficiency or resistance hinders the immunologic, metabolic, and neuroendocrinologic processes necessary to thwart infections and their associated complications, and to possibly protect against infectious diseases following vaccination. Circulating leptin levels are proportional to body fat mass. High circulating leptin concentrations, as observed in obesity, are indicative of the development of leptin transport saturation/signaling desensitization. Leptin bridges nutritional status and immunity. Although its role in vaccine response is currently unknown, over-nutrition has been shown to suppress vaccine-induced immune responses. For instance, obesity (BMI ≥ 30 kg/m2) is associated with lower antigen-specific antibody titers following influenza, hepatitis B, and tetanus vaccinations. This suggests that obesity, and possibly saturable leptin levels, are contributing factors to poor vaccine immunogenicity. While leptin-based therapies have not been investigated as vaccine adjuvants thus far, leptin’s role in immunity suggests that application of these therapies is promising and worth investigation to enhance vaccine response in people with leptin signaling impairments. This review will examine the possibility of using leptin as a vaccine adjuvant by: briefly reviewing the distribution and signal transduction of leptin and its receptors; discussing the physiology of leptin with emphasis on its immune functions; reviewing the causes of attenuation of leptin signaling; and finally, providing plausible inferences for the innovative use of leptin-based pharmacotherapies as vaccine adjuvants. PMID:23370154

The Effect of Mindfulness-Based Music Therapy on Attention and Mood in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Study.

PubMed

Lesiuk, Teresa

2015-05-01

To explore the efficacy of mindfulness-
based music therapy (MBMT) to improve attention and decrease mood distress experienced by women with breast cancer receiving adjuvant chemotherapy. Quantitative, descriptive, longitudinal approach. A comprehensive cancer hospital and a university in southern Florida. 15 women with a diagnosis of breast cancer, stages I-III, receiving adjuvant chemotherapy. Participants individually received MBMT for one hour per week for four weeks. The sessions consisted of varied music activities accompanied by mindfulness attitudes, or mental strategies that enhance moment-to-moment awareness, and weekly homework. Demographic information was collected at baseline. Attention was measured using Conners' Continuous Performance Test II. Mood was measured using the Profile of Mood States-Brief Form. Narrative comments collected from the homework assignments served to reinforce quantitative data. Repeated measures analysis of variance showed that attention improved significantly over time. Although all mood states significantly improved from the beginning to the end of each MBMT session, the mood state of fatigue decreased significantly more than the other mood states. MBMT enhances attention and mood, particularly the mood state of fatigue, in women with breast cancer receiving adjuvant chemotherapy. 
. A preferred music listening and mindfulness exercise may be offered to women with breast cancer who experience attention problems and mood distress.

Efficacy and safety of platinum combination chemotherapy re-challenge for relapsed patients with non-small-cell lung cancer after postoperative adjuvant chemotherapy of cisplatin plus vinorelbine.

PubMed

Imai, Hisao; Shukuya, Takehito; Yoshino, Reiko; Muraki, Keiko; Mori, Keita; Ono, Akira; Akamatsu, Hiroaki; Taira, Tetsuhiko; Kenmotsu, Hirotsugu; Naito, Tateaki; Murakami, Haruyasu; Tomizawa, Yoshio; Takahashi, Toshiaki; Takahashi, Kazuhisa; Saito, Ryusei; Yamamoto, Nobuyuki

2013-01-01

There is no standard therapy for relapsed patients who have received postoperative platinum-based adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of platinum combination chemotherapy re-challenge for such patients. Medical records from 3 institutes from April 2005 to July 2012 were retrospectively reviewed. Patients who underwent complete surgical resection were eligible if they received postoperative adjuvant chemotherapy consisting of cisplatin plus vinorelbine once and then re-challenge with platinum combination chemotherapy. Sixteen patients were enrolled in this study. After re-challenge with platinum combination chemotherapy, we observed an overall response rate of 31.2% (5/16) and a disease control rate of 81.2% (13/16). Median progression-free survival and overall survival from the start of the re-administration of platinum combination chemotherapy were 6.5 and 28.0 months, respectively. Frequently observed severe adverse events (≥grade 3) included neutropenia (31.2%), thrombocytopenia (31.2%), leukopenia (12.5%) and hyponatremia (12.5%). Frequently observed non-hematological toxicities (≥grade 2) were anorexia (37.5%) and nausea (37.5%). Re-challenge with platinum combination chemotherapy was effective and safe; therefore, this therapy should be considered as a treatment option for relapsed patients after postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC. © 2014 S. Karger AG, Basel.

A 16 Yin Yang gene expression ratio signature for ER+/node- breast cancer.

PubMed

Xu, Wayne; Jia, Gaofeng; Cai, Nianguang; Huang, Shujun; Davie, James R; Pitz, Marshall; Banerji, Shantanu; Murphy, Leigh

2017-03-15

Breast cancer is one of the leading causes of cancer death in women. It is a complex and heterogeneous disease with different clinical outcomes. Stratifying patients into subgroups with different outcomes could help guide clinical decision making. In this study, we used two opposing groups of genes, Yin and Yang, to develop a prognostic expression ratio signature. Using the METABRIC cohort we identified a16-gene signature capable of stratifying breast cancer patients into four risk levels with intention that low-risk patients would not undergo adjuvant systemic therapy, intermediate-low-risk patients will be treated with hormonal therapy only, and intermediate-high- and high-risk groups will be treated by chemotherapy in addition to the hormonal therapy. The 16-gene signature for four risk level stratifications of breast cancer patients has been validated using 14 independent datasets. Notably, the low-risk group (n = 51) of 205 estrogen receptor-positive and node negative (ER+/node-) patients from three different datasets who had not had any systemic adjuvant therapy had 100% 15-year disease-specific survival rate. The Concordance Index of YMR for ER+/node negative patients is close to the commercially available signatures. However, YMR showed more significance (HR = 3.7, p = 8.7e-12) in stratifying ER+/node- subgroup than OncotypeDx (HR = 2.7, p = 1.3e-7), MammaPrint (HR = 2.5, p = 5.8e-7), rorS (HR = 2.4, p = 1.4e-6), and NPI (HR = 2.6, p = 1.2e-6). YMR signature may be developed as a clinical tool to select a subgroup of low-risk ER+/node- patients who do not require any adjuvant hormonal therapy (AHT). © 2016 UICC.

Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker.

PubMed

Sgroi, Dennis C; Carney, Erin; Zarrella, Elizabeth; Steffel, Lauren; Binns, Shemeica N; Finkelstein, Dianne M; Szymonifka, Jackie; Bhan, Atul K; Shepherd, Lois E; Zhang, Yi; Schnabel, Catherine A; Erlander, Mark G; Ingle, James N; Porter, Peggy; Muss, Hyman B; Pritchard, Katherine I; Tu, Dongsheng; Rimm, David L; Goss, Paul E

2013-07-17

Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)-positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph node-negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole. A prospective-retrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided. High H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio [OR] = 0.35; 95% confidence interval [CI] = 0.16 to 0.75; P = .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR = 0.33; 95% CI = 0.15 to 0.73; P = .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P = .007). The interaction between H/I and letrozole treatment was statistically significant (P = .03). In the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence.

Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients.

PubMed

Perez, Cédric; Huttner, Angela; Assal, Mathieu; Bernard, Louis; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

2010-05-01

No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (7 days). Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with 14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

Adjuvant breast cancer therapy: current status and future strategies--growth kinetics and the improved drug therapy of breast cancer.

PubMed

Norton, L

1999-02-01

It is well-established that the adjuvant treatment of breast cancer is effective in prolonging both disease-free and overall survival. The pressing questions are how to improve on existing treatment, whether new agents should be incorporated into adjuvant regimens, and, if so, how they should best be utilized. The application of log-kill principles to the sigmoid growth curve characteristic of human cancers suggests that the chances of eradicating tumor will be increased by dose-dense schedules. If the tumor is composed of several cell lines with different sensitivities, the optimum therapy is likely to consist of several drugs given in sequence at a good dose and on a dense schedule. Such sequential chemotherapy, rather than the use of drugs given in combination at longer intervals, should maximize log-kill at the same time as minimizing tumor regrowth. There is now evidence that the actions of chemotherapy may involve Ras, tyrosine kinases (epidermal growth factor receptor, HER2), TC21, or similar molecules. This concept may provide important clues for optimizing the clinical applications of drug therapy and for designing new therapeutic approaches. It might also explain the reason why dose density may be more effective than other schedules of administration. New blood vessel formation is an obligatory step in the establishment of a tumor in its sigmoid growth course and there is evidence that taxanes adversely affect this process. Major practical advances in the curative drug therapy of cancer should follow the demonstration of better ways to maximize cell kill, the development of predictive in vitro methods of selecting active agents, the discovery of techniques to minimize both drug resistance and host-cell toxicity, and the improved understanding of cancer-stromal interactions and their therapeutic perturbation.

Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest

PubMed Central

YAMATSUJI, TOMOKI; FUJIWARA, YASUHIRO; MATSUMOTO, HIDEO; HATO, SHINJI; NAMIKAWA, TSUTOMU; HANAZAKI, KAZUHIRO; TAKAOKA, MUNENORI; HAYASHI, JIRO; SHIGEMITSU, KAORI; YOSHIDA, KAZUHIRO; URAKAMI, ATSUSHI; UNO, FUTOSHI; NISHIZAKI, MASAHIKO; KAGAWA, SHUNSUKE; NINOMIYA, MOTOKI; FUJIWARA, TOSHIYOSHI; HIRAI, TOSHIHIRO; NAKAMURA, MASAFUMI; HAISA, MINORU; NAOMOTO, YOSHIO

2015-01-01

In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer. PMID:26137261

Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: does this improve pain control and reduce opioid requirements?

PubMed

Shinde, Shivani; Gordon, Pamela; Sharma, Prashant; Gross, James; Davis, Mellar P

2015-03-01

Cancer pain is complex, and despite the introduction of the WHO cancer pain ladder, few studies have looked at the prevalence of adjuvant medication use in an inpatient palliative medicine unit. In this study, we evaluate the use of adjuvant pain medications in patients admitted to an inpatient palliative care unit and whether their use affects pain scores or opiate dosing. In this retrospective observational study, patients admitted to the inpatient palliative care unit over a 3-month period with a diagnosis of cancer on opioid therapy were selected. Data pertaining to demographics, diagnosis, oral morphine dose equivalent of the opioid at the time of discharge, adjuvant analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and pain scores as reported by nurses and physicians were collected. Seventy-seven patients were eligible over a 3-month period, out of which 65 (84 %) were taking an adjuvant medication. The most commonly prescribed adjuvant was gabapentin (70 %). Fifty-seven percent were taking more than one adjuvant. There were more women in the group receiving adjuvants (57 vs. 17%, p = 0.010). Those without adjuvants compared with those on adjuvants did not have worse pain scores on discharge as reported by physicians (0.8 ± 0.8 vs. 1.0 ± 0.7, p = 0.58) or nurses (2.0 ± 2.7 vs. 2.1 ± 2.6, p = 0.86). There was no difference in morphine equivalent doses of the opioid in both groups (median (min, max); 112 (58, 504) vs. 200 (30, 5,040)) at the time of discharge; 75-80 % of patients had improvement in pain scores as measured by a two-point reduction in numerical rating scale (NRS). This study shows that adjuvant medications are commonly used for treating pain in patients with cancer. More than half of study population were on two adjuvants or an adjuvant plus NSAID along with an opioid. We did not demonstrate any benefit in terms of improved pain scores or opioid doses with adjuvants, but this could reflect confounding variables and physician choice. Larger prospective studies are needed to define the opioid-sparing effects of adjuvants. Adjuvant agents are used in over 80 % of those treated for cancer pain.

High frequency of brain metastases after adjuvant therapy for high-risk melanoma.

PubMed

Samlowski, Wolfram E; Moon, James; Witter, Merle; Atkins, Michael B; Kirkwood, John M; Othus, Megan; Ribas, Antoni; Sondak, Vernon K; Flaherty, Lawrence E

2017-11-01

The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Adjuvant chemotherapy for early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

PubMed Central

Gandhi, S.; Fletcher, G.G.; Eisen, A.; Mates, M.; Freedman, O.C.; Dent, S.F.; Trudeau, M.E.

2015-01-01

Background The Program in Evidence-Based Care (pebc) of Cancer Care Ontario recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question “What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?” The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (her2)–directed therapy. Methods For the systematic review, the medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were “breast cancer” and “systemic therapy” (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. Results Several hundred documents that met the inclusion criteria were retrieved. The Early Breast Cancer Trialists’ Collaborative Group meta-analyses encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite–based regimens (for example, cyclophosphamide–methotrexate–5-fluorouracil), anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline–taxane-based polychemotherapy regimens are, overall, considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes. Regimens with varying anthracycline and taxane doses and schedules are options; in general, paclitaxel given every 3 weeks is inferior. Evidence does not support the use of bevacizumab in the adjuvant setting; other systemic therapy agents such as metformin and vaccines remain investigatory. Adjuvant bisphosphonates for menopausal women will be discussed in later work. Conclusions The results of this systematic review constitute a comprehensive compilation of the high-level evidence that is the basis for the 2014 pebc guideline on systemic therapy for early breast cancer. Use of cytotoxic chemotherapy is presented here; the results addressing endocrine therapy and her2-targeted treatment, and the final clinical practice recommendations, are published separately in this supplement. PMID:25848343

Safety and effectiveness of MF-59 adjuvanted influenza vaccines in children and adults.

PubMed

Black, Steven

2015-06-08

The squalene oil-in-water emulsion MF-59 adjuvant was developed initially to enhance the immunogenicity of influenza vaccines in populations such as children and adults with known suboptimal response. Developed in the 1990s, it was initially licensed in Europe for use in seasonal influenza vaccine in the elderly. Since that time, both Avian and p2009H1N1 vaccines have also been developed. Overall, more than 30,000 individuals have participated in clinical trials of MF-59 adjuvanted vaccine and more than 160 million doses of licensed vaccine have been administered. Safety and effectiveness data from clinical trials and observation studies attest to the safety of MF-59 and to its ability to enhance the effectiveness of influenza vaccines in children and the elderly. Copyright © 2014 Elsevier Ltd. All rights reserved.

Early initiation of low-dose hydrocortisone treatment for septic shock in adults: A randomized clinical trial.

PubMed

Lv, Qing-Quan; Gu, Xiao-Hua; Chen, Qi-Hong; Yu, Jiang-Quan; Zheng, Rui-Qiang

2017-12-01

Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock. However, the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear. Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone. Thus we designed a placebo-controlled, randomized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome. A total of 118 patients with septic shock were recruited in the study. All eligible patients were randomized to receive hydrocortisone (n=58) or normal saline (n=60). The study medication (hydrocortisone and normal saline) was initiated simultaneously with vasopressors. The primary end-point was 28-day mortality. The secondary end-points were the reversal of shock, in-hospital mortality and the duration of ICU and hospital stay. The proportion of patients with reversal of shock was similar in the two groups (P=0.602); There were no significant differences in 28-day or hospital all-cause mortality; length of stay in the ICU or hospital between patients treated with hydrocortisone or normal saline. The early initiation of low-dose of hydrocortisone did not decrease the risk of mortality, and the length of stay in the ICU or hospital in adults with septic shock. www.clinicaltrials.govNCT02580240. Copyright © 2017 Elsevier Inc. All rights reserved.

Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer.

PubMed

Martín, Miguel; González-Rivera, Milagros; Morales, Serafín; de la Haba-Rodriguez, Juan; González-Cortijo, Lucía; Manso, Luis; Albanell, Joan; González-Martín, Antonio; González, Sónia; Arcusa, Angels; de la Cruz-Merino, Luis; Rojo, Federico; Vidal, María; Galván, Patricia; Aguirre, Elena; Morales, Cristina; Ferree, Sean; Pompilio, Kristen; Casas, Maribel; Caballero, Rosalía; Goicoechea, Uxue; Carrasco, Eva; Michalopoulos, Steven; Hornberger, John; Prat, Aleix

2015-06-01

Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p < 0.05). Though this study does not include evaluation of the impact of GEP on long-term outcomes, it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection. Patients' anxiety about the selected adjuvant therapy decreased with use of the GEP.

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no; Department of Oncology, Haukeland University Hospital, Bergen; Engellau, Jacob

2013-08-01

Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence intervalmore » [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.« less

Piercing Ear Keloid: Excision Using Loupe Magnification and Topical Liquid Silicone Gel as Adjuvant

PubMed Central

Ramesh, Bellam A.; Mohan, J.

2018-01-01

Background: Keloid is an abnormal growth of scar at the site of skin injury, which usually does not regress. It proliferates beyond the original scar. The ear keloid usually develops after piercing injury to wear ornaments. A patient usually asks for removal of keloid, as it is aesthetically unpleasant. Patient may sometimes complain of itching and pain. Aim: The study was conducted to analyze results following excision of keloid with its tract and topical silicone gel as the postsurgical adjuvant. Materials and Methods: Ear keloids measuring less than 0.5cm or more than 5cm in maximum dimension were excluded from the study. Nonpiercing causes such as burns, trauma, and recurrent keloid were excluded from the study. The study was carried out on 22 patients who had keloid because of piercing injury, including 4 cases with both ear keloids. Of 26 ear keloids, 19 had the tract or connecting tissue. The lesion was excised under anesthesia using magnification. For all the operated cases, topical liquid silicone gel was used as postsurgical adjuvant therapy. The method of application of topical silicone gel was taught to each patient and was considered significant. Result: The magnification helped in identification of tract in 73% of the cases in this study. Twenty patients had successfully responded to proposed treatment, and two patients developed recurrence while using topical silicone gel as the adjuvant. These two patients were managed with conventional triamcinolone injection. Conclusion: The topical silicone gel as postsurgical adjuvant therapy avoided the use of painful postsurgical injection or radiotherapy for the 1–3cm primary ear keloids. The advantages of magnification were better clearance of keloid tissue, easier identification of tract and removal of keloid pseudopods, meticulous suturing, and comfortable elevation of a small local flap. PMID:29731586

Prognostic factors and treatment outcomes in surgically-staged non-invasive uterine clear cell carcinoma: a Turkish Gynecologic Oncology Group study

PubMed Central

2017-01-01

Objective To assess the prognosis of surgically-staged non-invasive uterine clear cell carcinoma (UCCC), and to determine the role of adjuvant therapy. Methods A multicenter, retrospective department database review was performed to identify patients with UCCC who underwent surgical treatment between 1997 and 2016 at 8 Gynecologic Oncology Centers. Demographic, clinicopathological, and survival data were collected. Results A total of 232 women with UCCC were identified. Of these, 53 (22.8%) had surgically-staged non-invasive UCCC. Twelve patients (22.6%) were upstaged at surgical assessment, including a 5.6% rate of lymphatic dissemination (3/53). Of those, 1 had stage IIIA, 1 had stage IIIC1, 1 had stage IIIC2, and 9 had stage IVB disease. Of the 9 women with stage IVB disease, 5 had isolated omental involvement indicating omentum as the most common metastatic site. UCCC limited only to the endometrium with no extra-uterine disease was confirmed in 41 women (73.3%) after surgical staging. Of those, 13 women (32%) were observed without adjuvant treatment whereas 28 patients (68%) underwent adjuvant therapy. The 5-year disease-free survival rates for patients with and without adjuvant treatment were 100.0% vs. 74.1%, respectively (p=0.060). Conclusion Extra-uterine disease may occur in the absence of myometrial invasion (MMI), therefore comprehensive surgical staging including omentectomy should be the standard of care for women with UCCC regardless of the depth of MMI. Larger cohorts are needed in order to clarify the necessity of adjuvant treatment for women with UCCC truly confined to the endometrium. PMID:28541637

The Role of Vaginal Brachytherapy in the Treatment of Surgical Stage I Papillary Serous or Clear Cell Endometrial Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barney, Brandon M., E-mail: barney.brandon@mayo.edu; Petersen, Ivy A.; Mariani, Andrea

2013-01-01

Objectives: The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. Methods and Materials: From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic andmore » paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. Results: At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal + pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. Conclusions: VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.« less

Alginate Particles with Ovalbumin (OVA) Peptide Can Serve as a Carrier and Adjuvant for Immune Therapy in B16-OVA Cancer Model.

PubMed

Zhu, Longbao; Ge, Fei; Yang, Liangjun; Li, Wanzhen; Wei, Shenghua; Tao, Yugui; Du, Guocheng

2017-04-28

BACKGROUND Alginate is a natural polysaccharide obtained from brown algae and has been shown to have numerous applications in biomedical science, such as wound healing, delivery of bioactive agents, and cell transplantation. Ovalbumin (OVA) peptide 323-339 has been reported to be involved in immune response.  MATERIAL AND METHODS This work investigated the use of alginate particles as a carrier and adjuvant for the immune therapy of cancer. Alginate particles loaded with OVA peptide were produced via emulsion. A tumor model was established in C57BL/6J mice via subcutaneous injection of 3×105 B16-OVA tumor cells. The effect of alginate/OVA peptide on cell viability was analyzed by use of the CCK-8 assay kit. Activation of macrophages was examined by checking cell surface makers CD40 and CD86 by FACs. RESULTS Alginate/OVA peptide inhibited tumor progression more effectively than using the peptide alone. The viability and uptake study illustrated that this particle is safe and non-toxic. The activation study demonstrated that alginate particles can promote the activation of surface markers on macrophages. ELISA assay showed that the particles with peptide can promote the secretion of inflammatory and effector cytokines from macrophages.  CONCLUSIONS This study demonstrated that alginate has dual functions in immune therapy of cancer, serving both as a carrier and an adjuvant.

[The clinical efficacy of allergen-specific immunotherapy with water-salt extracts and adjuvant allergens for atopic asthma with household sensitization].

PubMed

Ushakova, D V; Nikonov, E L

To evaluate the clinical and economic efficiency of allergen-specific immunotherapy (ASIT); to comparatively analyze the efficiency of various therapy regimens for atopic asthma. The clinical and economic efficiency of asthma therapy using ASIT with water-salt allergen extracts or the adjuvant drug alustal 'mite allergen' and only with medicines were comparatively analyzed. The investigation enrolled 156 patients with mild and moderate atopic asthma, household allergy. In Group 1 (n = 57), ASIT was performed using the classical scheme by subcutaneous injection of house dust mite allergen (JSC 'I.I. Mechnikov Biomed', Russia). In Group 2 (n = 43), ASIT was conducted using the alustal 'mite allergen' (Stallergenes, France). Group 3 (n = 56) received only medical therapy. ASIT with both water-salt allergen extracts and the adjuvant allergen alustal is an effective treatment for mild and moderate atopic asthma. ASIT greatly reduces the need for anti-inflammatory treatment and the use of symptomatic drugs and improves the physical and psychoemotional indicators of quality of life in patients. The economic benefit of ASIT is delayed, but its use significantly reduces financing costs. ASIT is a reasonable, highly effective and ultimately cost-effective treatment in patients with atopic asthma. A variety of drugs for ASIT can choose schemes that are convenient and acceptable for each patient, which allows wider use of this treatment.

Immunological monitoring for prediction of clinical response to antitumor vaccine therapy.

PubMed

Mikhaylova, Irina N; Shubina, Irina Zh; Chkadua, George Z; Petenko, Natalia N; Morozova, Lidia F; Burova, Olga S; Beabelashvili, Robert Sh; Parsunkova, Kermen A; Balatskaya, Natalia V; Chebanov, Dmitrii K; Pospelov, Vadim I; Nazarova, Valeria V; Vihrova, Anastasia S; Cheremushkin, Evgeny A; Molodyk, Alvina A; Kiselevsky, Mikhail V; Demidov, Lev V

2018-05-11

Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease. We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment. The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.

A pilot randomized controlled trial of D-cycloserine and distributed practice as adjuvants to constraint-induced movement therapy after stroke.

PubMed

Nadeau, Stephen E; Davis, Sandra E; Wu, Samuel S; Dai, Yunfeng; Richards, Lorie G

2014-01-01

Background. Phase III trials of rehabilitation of paresis after stroke have proven the effectiveness of intensive and extended task practice, but they have also shown that many patients do not qualify, because of severity of impairment, and that many of those who are treated are left with clinically significant deficits. Objective. To test the value of 2 potential adjuvants to normal learning processes engaged in constraint-induced movement therapy (CIMT): greater distribution of treatment over time and the coadministration of d-cycloserine, a competitive agonist at the glycine site of the N-methyl-D-aspartate glutamate receptor. Methods. A prospective randomized single-blind parallel-group trial of more versus less condensed therapy (2 vs 10 weeks) and d-cycloserine (50 mg) each treatment day versus placebo (in a 2 × 2 design), as potential adjuvants to 60 hours of CIMT. Results. Twenty-four participants entered the study, and 22 completed it and were assessed at the completion of treatment and 3 months later. Neither greater distribution of treatment nor treatment with d-cycloserine significantly augmented retention of gains achieved with CIMT. Conclusions. Greater distribution of practice and treatment with d-cycloserine do not appear to augment retention of gains achieved with CIMT. However, concentration of CIMT over 2 weeks ("massed practice") appears to confer no advantage either. © The Author(s) 2014.

The Evolving Role of Radiation Therapy in the Management of Malignant Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, Niloufer; Khan, Mohammad K., E-mail: drkhurram2000@gmail.com; Almasan, Alex

2011-07-01

The incidence of melanoma is rising in the United States, leading to an estimated 68,720 new diagnoses and 8,650 deaths annually. The natural history involves metastases to lymph nodes, lung, liver, brain, and often to other sites. Primary treatment for melanoma is surgical excision of the primary tumor and affected lymph nodes. The role of adjuvant or definitive radiation therapy in the treatment of melanoma remains controversial, because melanoma has traditionally been viewed as a prototypical radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, there may be a significant role for radiation therapy in melanoma treatment. Stereotacticmore » radiosurgery for brain metastases has shown effective local control. High dose per fraction radiation therapy has been associated with a lower rate of locoregional recurrence of sinonasal melanoma. Plaque brachytherapy has evolved into a promising alternative to enucleation at the expense of moderate reduction in visual acuity. Adjuvant radiation therapy following lymphadenectomy in node-positive melanoma prevents local and regional recurrence. The newer clinical data along with emerging radiobiological data indicate that radiotherapy is likely to play a greater role in melanoma management and should be considered as a treatment option.« less

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update

PubMed Central

Krop, Ian; Ismaila, Nofisat; Andre, Fabrice; Bast, Robert C.; Barlow, William; Collyar, Deborah E.; Hammond, M. Elizabeth; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Wolff, Antonio C.; Stearns, Vered

2018-01-01

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor–positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki. PMID:28692382

Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527

PubMed Central

Foster, Jared C.; Seisler, Drew K.; Lafky, Jacqueline M.; Muss, Hyman B.; Cohen, Harvey J.; Mandelblatt, Jeanne; Winer, Eric P.; Hudis, Clifford A.; Partridge, Ann H.; Carey, Lisa A.; Cirrincione, Constance; Moreno-Aspitia, Alvaro; Kimmick, Gretchen; Jatoi, Aminah; Hurria, Arti

2017-01-01

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years (v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population. PMID:27992272

Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527.

PubMed

Freedman, Rachel A; Foster, Jared C; Seisler, Drew K; Lafky, Jacqueline M; Muss, Hyman B; Cohen, Harvey J; Mandelblatt, Jeanne; Winer, Eric P; Hudis, Clifford A; Partridge, Ann H; Carey, Lisa A; Cirrincione, Constance; Moreno-Aspitia, Alvaro; Kimmick, Gretchen; Jatoi, Aminah; Hurria, Arti

2017-02-01

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.

Breast-cancer adjuvant therapy with zoledronic acid.

PubMed

Coleman, Robert E; Marshall, Helen; Cameron, David; Dodwell, David; Burkinshaw, Roger; Keane, Maccon; Gil, Miguel; Houston, Stephen J; Grieve, Robert J; Barrett-Lee, Peter J; Ritchie, Diana; Pugh, Julia; Gaunt, Claire; Rea, Una; Peterson, Jennifer; Davies, Claire; Hiley, Victoria; Gregory, Walter; Bell, Richard

2011-10-13

Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients. In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed. At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths--243 in the zoledronic acid group and 276 in the control group--were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups. These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.).

Adjuvant radiation therapy and lymphadenectomy in esophageal cancer: a SEER database analysis.

PubMed

Shridhar, Ravi; Weber, Jill; Hoffe, Sarah E; Almhanna, Khaldoun; Karl, Richard; Meredith, Kenneth

2013-08-01

This study seeks to determine the effects of postoperative radiation therapy and lymphadenectomy on survival in esophageal cancer. An analysis of patients with surgically resected esophageal cancer from the SEER database between 2004 and 2008 was performed to determine association of adjuvant radiation and lymph node dissection on survival. Survival curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. We identified 2109 patients who met inclusion criteria. Radiation was associated with increased survival in stage III patients (p = 0.005), no benefit in stage II (p = 0.075) and IV (p = 0.913) patients, and decreased survival in stage I patients (p < 0.0001). Univariate analysis revealed that radiation therapy was associated with a survival benefit node positive (N1) patients while it was associated with a detriment in survival for node negative (N0) patients. Removing >12 and >15 lymph nodes was associated with increased survival in N0 patients, while removing >8, >10, >12, >15, and >20 lymph nodes was associated with a survival benefit in N1 patients. MVA revealed that age, gender, tumor and nodal stage, tumor location, and number of lymph nodes removed were prognostic for survival in N0 patients. In N1 patients, MVA showed the age, tumor stage, number of lymph nodes removed, and radiation were prognostic for survival. The number of lymph nodes removed in esophageal cancer is associated with increased survival. The benefit of adjuvant radiation therapy on survival in esophageal cancer is limited to N1 patients.

The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients.

PubMed

Fagerholm, Rainer; Schmidt, Marjanka K; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A; Fasching, Peter A; Janni, Wolfgang; Weinshilboum, Richard; Loehberg, Christian R; Hopper, John L; Southey, Melissa C; Keeman, Renske; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Chenevix-Trench, Georgia; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Seibold, Petra; Couch, Fergus J; Olson, Janet E; Andrulis, Irene L; Knight, Julia A; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J; Jager, Agnes; Shah, Mitul; Perkins, Barbara J; Luben, Robert; Hamann, Ute; Kabisch, Maria; Czene, Kamila; Hall, Per; Easton, Douglas F; Pharoah, Paul D P; Liu, Jianjun; Eccles, Diana; Blomqvist, Carl; Nevanlinna, Heli

2015-04-10

We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.

Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays

PubMed Central

Schuur, Eric; Angel Aristizabal, Javier; Bargallo Rocha, Juan Enrique; Cabello, Cesar; Elizalde, Roberto; García‐Estévez, Laura; Gomez, Henry L.; Katz, Artur; Nuñez De Pierro, Aníbal

2017-01-01

Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision‐making. This review details the development and validation of six multi‐gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use. PMID:28211064

Optimized Hyperthermia Treatment of Prostate Cancer Using a Novel Intracavitary Ultrasound Array

DTIC Science & Technology

2006-01-01

Overgaard J, Gonzalez GD, Hulshof MC, Arcangeli G, Dahl O, Mella O, et al. 1995. Randomised trial of hyperthermia as adjuvant to radiotherapy for...Gonzalez, G. D., Hulshof , M. C., Arcangeli, G., Dahl, O., Mella, O., and Bentzen, S. M., "Hyperthermia as an adjuvant to radiation therapy of recurrent or...25 pp. 79-85, 1993. 9. Overgaard, J., Gonzalez, G. D., Hulshof , M. C., Arcangeli, G., Dahl, O., Mella, O., and Bentzen, S. M.: Hyperthermia as an

Antifungal adjuvants: Preserving and extending the antifungal arsenal

PubMed Central

Butts, Arielle; Palmer, Glen E.; Rogers, P. David

2017-01-01

ABSTRACT As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance. PMID:27459018

[Retrospective analysis of 24 recurrent glioblastoma after chemoradiation and treated with nitrosoureas or irinotecan and bevacizumab].

PubMed

Vauleon, Elodie; Mesbah, Habiba; Gedouin, Daniel; Lecouillard, Isabelle; Louvel, Guillaume; Hamlat, Abderrahmane; Riffaud, Laurent; Carsin, Béatrice; Quillien, Véronique; Audrain, Odile; Lesimple, Thierry

2012-02-01

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

Periodontal Health in Women With Early-Stage Postmenopausal Breast Cancer Newly on Aromatase Inhibitors: A Pilot Study.

PubMed

Taichman, L Susan; Inglehart, Marita R; Giannobile, William V; Braun, Thomas; Kolenic, Giselle; Van Poznak, Catherine

2015-07-01

Aromatase inhibitor (AI) use results in low estrogen levels, which in turn affect bone mineral density (BMD). Periodontitis, alveolar bone loss, and tooth loss are associated with low BMD. The goal of this study is to assess the prevalence of periodontitis and perceived oral health and evaluate salivary biomarkers in postmenopausal women who are survivors of early-stage (I to IIIA) breast cancer (BCa) and receive adjuvant AI therapy. Participants included 58 postmenopausal women: 29 with BCa on AIs and 29 controls without BCa diagnoses. Baseline periodontal status was assessed with: 1) periodontal probing depth (PD); 2) bleeding on probing (BOP); and 3) attachment loss (AL). Demographic and dental utilization information was gathered by questionnaire. Linear regression modeling was used to analyze the outcomes. No differences were found in mean PD or number of teeth. The AI group had significantly more sites with BOP (27.8 versus 16.7; P = 0.02), higher worst-site AL (5.2 versus 4.0 mm; P <0.01), and more sites with dental calculus (18.2 versus 6.4; P <0.001) than controls. Linear regression adjusted for income, tobacco use, dental insurance, and previous radiation and chemotherapy exposure demonstrated that AI use increased AL by >2 mm (95% confidence interval, 0.46 to 3.92). Median salivary osteocalcin and tumor necrosis factor-α levels were significantly higher in the AI group than the control group. This first investigation of the periodontal status of women initiating adjuvant AI therapy identifies this population as having an increased risk for periodontitis.

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.

PubMed

Kawamura, Junichiro; Sugiura, Fumiaki; Sukegawa, Yasushi; Yoshioka, Yasumasa; Hida, Jin-Ichi; Hazama, Shoichi; Okuno, Kiyotaka

2018-02-23

We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination-induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA-masked fashion. After the disclosure of HLA, 28 patients were in the HLA-A*2402-matched and 16 were in the unmatched group. In the HLA-matched group, 14 patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides after 2 cycles of treatment and 9 had negative responses; in the HLA-unmatched group, 10 CTL responses were positive and 2 negative. In the HLA-matched group, 3-year relapse-free survival (RFS) was significantly better in the positive CTL subgroup than in the negative-response subgroup. Patients with negative vaccination-induced CTL responses showed a significant trend towards shorter RFS than those with positive responses. Moreover, in the HLA-unmatched group, the positive CTL response subgroup showed an equally good 3-year RFS as in the HLA-matched group. In conclusion, vaccination-induced CTL response to peptide vaccination could predict survival in the adjuvant setting for stage III CRC. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.

PubMed

Leow, Jeffrey J; Orsola, Anna; Chang, Steven L; Bellmunt, Joaquim

2015-04-01

Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Although the main treatment is radical nephroureterectomy (NU), oncologic outcomes are not comparable to lower tract urothelial cancers. Identifying prognostic factors can help guide management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC. A comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed. Preoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits. Minimally invasive surgery has equivalent oncologic and better peri-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease. Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of nandrolone decanoate as an adjuvant for erythropoietin dose reduction in treating anemia in patients on hemodialysis.

PubMed

Sheashaa, Hussein; Abdel-Razek, Waleed; El-Husseini, Amr; Selim, Amal; Hassan, Nabil; Abbas, Tarek; El-Askalani, Hassan; Sobh, Mohamed

2005-01-01

Use of androgen as an adjuvant therapy to treat anemia in patients on hemodialysis is debated. Our target is to assess the safety and the efficacy of nandrolone decanoate (ND) as an effective adjunctive therapy to treat such anemia. This study included 32 anemic adult hemodialysis patients who had adequate iron stores. They were randomized into two equal groups: the first group received subcutaneously a low dose of erythropoietin (EPO) 1,000 U three times weekly combined with ND, 50 mg intramuscularly twice weekly, and the second group received only the same low dose of EPO for the 6-month study period. All patients were subjected to a serial follow-up of hemoglobin (Hb), hematocrit % (Hct%), iron store indices, serum insulin-like growth factor-1 (IGF-1) concentration and liver function tests. A significant rise of both Hb and Hct in both groups was found at the end of the study (p < 0.001). Although the rise of both Hb and Hct was higher in the androgen group, it was not rated as being statistically significant. Both groups showed a significant rise of serum IGF-1 concentration at the end of the study in comparison to its initial value. Moreover, the androgen group attained a more statistically significant rise of IGF-1 serum concentration. Four female patients discontinued ND because of related adverse effects, principally distressing hirsutism and hepatic dysfunction. Addition of ND to a low-dose EPO regimen does not offer a significant benefit. Androgen-related side effects limit its use in female patients.

Adjuvant Radiation is Associated with Improved Survival for Select Patients with Non-metastatic Adrenocortical Carcinoma.

PubMed

Nelson, Daniel W; Chang, Shu-Ching; Bandera, Brad C; Fischer, Trevan D; Wollman, Robert; Goldfarb, Melanie

2018-07-01

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy for which surgery is the mainstay of treatment and for which adjuvant radiation is infrequently employed; however, small, single-institution series suggest adjuvant radiation may improve outcomes. All patients with non-metastatic ACC treated with either surgery alone or surgery followed by adjuvant radiation were identified in the 2004-2013 National Cancer Database. Factors associated with receipt of radiation and the impact of adjuvant radiation on survival were determined by multivariable analysis. Of 1184 patients, 171 (14.4%) received adjuvant radiation. Patient demographics were similar between the two groups, but those receiving radiation were more likely to have had positive margins following surgery (37.4 vs. 14.6%; p < 0.001), evidence of vascular invasion (14.0 vs. 5.1%; p = 0.05), and receive concurrent chemotherapy (57.3 vs. 28.8%; p < 0.001). After adjustment for tumor and other treatment factors, only positive margins following surgery was associated with an increased likelihood of receiving adjuvant radiation (odds ratio 3.84, 95% confidence interval [CI] 1.95-7.56). Radiation therapy did not confer a difference in median overall survival in the general cohort. However, for patients with positive margins, adjuvant radiation was associated with a 40% decreased yearly risk of death after adjustment for concurrent chemotherapy (hazard ratio 0.60, 95% CI 0.40-0.92; p = 0.02). This survival advantage was not evident for other traditional high-risk features. Adjuvant radiation appears to decrease the risk of death in ACC patients with positive margins following surgical resection, but only a small percentage are currently receiving radiation. Multidisciplinary treatment with surgery and radiation should be considered for these patients.

Craniopharyngioma: a roadmap for scientific translation.

PubMed

Gupta, Saksham; Bi, Wenya Linda; Giantini Larsen, Alexandra; Al-Abdulmohsen, Sally; Abedalthagafi, Malak; Dunn, Ian F

2018-06-01

OBJECTIVE Craniopharyngiomas are among the most challenging of intracranial tumors to manage because of their pattern of growth, associated morbidities, and high recurrence rate. Complete resection on initial encounter can be curative, but it may be impeded by the risks posed by the involved neurovascular structures. Recurrent craniopharyngiomas, in turn, are frequently refractory to additional surgery and adjuvant radiation or chemotherapy. METHODS The authors conducted a review of primary literature. RESULTS Recent advances in the understanding of craniopharyngioma biology have illuminated potential oncogenic targets for pharmacotherapy. Specifically, distinct molecular profiles define two histological subtypes of craniopharyngioma: adamantinomatous and papillary. The discovery of overactive B-Raf signaling in the adult papillary subtype has led to reports of targeted inhibitors, with a growing acceptance for refractory cases. An expanding knowledge of the biological underpinnings of craniopharyngioma will continue to drive development of targeted therapies and immunotherapies that are personalized to the molecular signature of each individual tumor. CONCLUSIONS The rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other challenging neurooncological diseases.

The Effect of Complementary and Alternative Medicine on Subfertile Women with In Vitro Fertilization

PubMed Central

Zhang, Yuehui; Fu, Yiman; Han, Fengjuan; Kuang, Hongying; Hu, Min; Wu, Xiaoke

2014-01-01

About 10–15% of couples have difficulty conceiving at some point in their reproductive lives and thus have to seek specialist fertility care. One of the most commonly used treatment options is in vitro fertilization (IVF) and its related expansions. Despite many recent technological advances, the average IVF live birth rate per single initiated cycle is still only 30%. Consequently, there is a need to find new therapies to promote the efficiency of the procedure. Many patients have turned to complementary and alternative medical (CAM) treatments as an adjuvant therapy to improve their chances of success when they undergo IVF treatment. At present, several CAM methods have been used in infertile couples with IVF, which has achieved obvious effects. However, biologically plausible mechanisms of the action of CAM for IVF have not been systematically reviewed. This review briefly summarizes the current progress of the impact of CAM on the outcomes of IVF and introduces the mechanisms. PMID:24527047

Diffuse low-grade glioma: a review on the new molecular classification, natural history and current management strategies.

PubMed

Delgado-López, P D; Corrales-García, E M; Martino, J; Lastra-Aras, E; Dueñas-Polo, M T

2017-08-01

The management of diffuse supratentorial WHO grade II glioma remains a challenge because of the infiltrative nature of the tumor, which precludes curative therapy after total or even supratotal resection. When possible, functional-guided resection is the preferred initial treatment. Total and subtotal resections correlate with increased overall survival. High-risk patients (age >40, partial resection), especially IDH-mutated and 1p19q-codeleted oligodendroglial lesions, benefit from surgery plus adjuvant chemoradiation. Under the new 2016 WHO brain tumor classification, which now incorporates molecular parameters, all diffusely infiltrating gliomas are grouped together since they share specific genetic mutations and prognostic factors. Although low-grade gliomas cannot be regarded as benign tumors, large observational studies have shown that median survival can actually be doubled if an early, aggressive, multi-stage and personalized therapy is applied, as compared to prior wait-and-see policy series. Patients need an honest long-term therapeutic strategy that should ideally anticipate neurological, cognitive and histopathologic worsening.

[Pain Management in Palliative Care].

PubMed

Steins, Martin B; Eschbach, Corinna; Villalobos, Matthias; Thomas, Michael

2017-05-01

A consistent pain management together with treatment of dyspnoea belongs to the main issues in symptom control in particular in palliative thoracic oncology. Together with the medicamentous therapy the psychologic and social circumstances of the affected patients have to be considered as factors influencing the experience of pain. The therapeutic fundament according to the WHO guideline for cancer pain is the opiate based medicamentous adjustment combined with non-opioids. In principle, this should be performed preferably orally, as simply as possible, according to a fix drug schedule and individually adjusted to the needed dosage. Breakthrough pain has to be treated with rapidly efficacious, non-retarded analgetics. The typical adverse reaction profile for opiates like constipation and initial nausea should be considered prophylactically by applying concurrent medication with adjuvants. Co-analgesic drugs like anticonvulsiva or corticosteroids could support the analgetic effect and are used preferably in case of neuropathic pain. Primary aim in analgesic therapy is to achieve the best possible pain reduction and hence to safeguard quality of life. © Georg Thieme Verlag KG Stuttgart · New York.

Experiences and perspectives on the GIST patient journey.

PubMed

Macdonald, Nancy; Shapiro, Ari; Bender, Christina; Paolantonio, Marc; Coombs, John

2012-01-01

The tyrosine kinase inhibitor (TKI) imatinib has improved outcomes for patients with unresectable or metastatic gastrointestinal stromal tumors (GIST), and for patients receiving adjuvant therapy following GIST resection. This qualitative study explored the experiences and emotions of patients through GIST diagnosis, treatment initiation, disease control, and in some patients, loss of response and therapy switch. Ethnographic investigations were conducted, including semi- structured qualitative interviews of patients with resected or metastatic/unresectable GIST and their caregivers, from Canada (n = 15); the United States (n = 10); and Brazil, France, Germany, Russia, and Spain (n = 5 each). Some interviewees also kept 7-day photo journals. Responses were qualitatively analyzed to identify gaps and unmet needs where communication about disease, treatments, and adherence could be effective. Patients shared common experiences during each stage of disease management (crisis, hope, adaptation, new normal, and uncertainty). Patients felt a sense of crisis during diagnosis, followed by hope upon TKI therapy initiation. Over time, they came to adapt to their new lives (new normal) with cancer. With each follow-up, patients confronted the uncertainty of becoming TKI resistant and the possible need to switch therapy. During uncertainty many patients sought new information regarding GIST. Cases of disease progression and drug switching caused patients to revert to crisis and restart their emotional journey. Patients with primary or unresectable/metastatic GIST shared similar journeys, especially regarding uncertainty, although differences in the scope and timing of phases were observed. Strategies patients used to remain adherent included obtaining family support, setting reminder mechanisms, taking medicine at routine times, and storing medicine in prominent places. Physicians and support staff can manage patient expectations and encourage adherence to therapy, which may facilitate optimal patient outcomes. Patient education about current GIST developments and adherence across all phases of the patient journey are of benefit.

Hepatic resection with or without adjuvant iodine-131-lipiodol for hepatocellular carcinoma: a comparative analysis.

PubMed

Chua, Terence C; Saxena, Akshat; Chu, Francis; Butler, S Patrick; Quinn, Richard J; Glenn, Derek; Morris, David L

2011-04-01

Resection of hepatocellular carcinoma (HCC) is potentially curative; however, recurrence is common. To date, few or no effective adjuvant therapies have been adequately investigated. This study evaluates the efficacy of adjuvant iodine-131-lipiodol after hepatic resection through the experience of a single-center hepatobiliary service of managing this disease. All patients who underwent hepatic resection for HCC and received adjuvant iodine-131-lipiodol between January 1991 and August 2009 were selected for inclusion into the experimental group. A group composed of patients treated during the same time period without adjuvant iodine-131-lipiodol was identified through the unit's HCC surgery database for comparison. The endpoints of this study were disease-free survival and overall survival. Forty-one patients who received adjuvant iodine-131-lipiodol after hepatic resection were compared with a matched group of 41 patients who underwent hepatic resection only. The median disease-free and overall survival were 24 versus 10 months (P = 0.032) and 104 versus 19 months (P = 0.001) in the experimental and control groups, respectively. Rates of intrahepatic-only recurrences (73 vs. 37%; P = 0.02) and surgical and nonsurgical treatments for recurrences (84 vs. 56%; P = 0.04) were higher in the experimental group compared to the control group. The finding of this study corroborates the current evidence from randomized and nonrandomized trials that adjuvant iodine-131-lipiodol improves disease-free and overall survival in patients with HCC after hepatic resection. The lengthened disease-free survival after adjuvant iodine-131-lipiodol allows for further disease-modifying treatments to improve the overall survival.

Racial Disparities in Cancer Therapy

PubMed Central

Gross, Cary P.; Smith, Benjamin D.; Wolf, Elizabeth; Andersen, Martin

2012-01-01

BACKGROUND The purpose of this study was to determine whether racial disparities in cancer therapy had diminished since the time they were initially documented in the early 1990s. METHODS The authors identified a cohort of patients in the SEER-Medicare linked database who were ages 66 to 85 years and who had a primary diagnosis of colorectal, breast, lung, or prostate cancer during 1992 through 2002. The authors identified 7 stage-specific processes of cancer therapy by using Medicare claims. Candidate covariates in multivariate logistic regression included year, clinical, and sociodemographic characteristics, and physician access before cancer diagnosis. RESULTS During the full study period, black patients were significantly less likely than white patients to receive therapy for cancers of the lung (surgical resection of early stage, 64.0% vs 78.5% for blacks and whites, respectively), breast (radiation after lumpectomy, 77.8% vs 85.8%), colon (adjuvant therapy for stage III, 52.1% vs 64.1%), and prostate (definitive therapy for early stage, 72.4% vs 77.2%, respectively). For both black and white patients, there was little or no improvement in the proportion of patients receiving therapy for most cancer therapies studied, and there was no decrease in the magnitude of any of these racial disparities between 1992 and 2002. Racial disparities persisted even after restricting the analysis to patients who had physician access before their diagnosis. CONCLUSIONS There has been little improvement in either the overall proportion of Medicare beneficiaries receiving cancer therapies or the magnitude of racial disparity. Efforts in the last decade to mitigate cancer therapy disparities appear to have been unsuccessful. PMID:18181101

Adjuvant Chemotherapy Improves Prostate Cancer Survival

Cancer.gov

Giving some men with prostate cancer chemotherapy after standard treatment with radiation and hormone therapy modestly improves how long they live, according to results from a new NCI-funded clinical trial.

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib.

PubMed

Park, Youngmok; Kim, Hyemin; Kim, Eui-Hyun; Suh, Chang-Ok; Lee, Soohyeon

2016-01-01

Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2-positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.

[Choroid plexus tumours in childhood: Experience in Sant Joan de Déu hospital].

PubMed

Del Río-Pérez, Clara Maria; Suñol-Capella, Mariona; Cruz-Martinez, Ofelia; Garcia-Fructuoso, Gemma

2016-01-01

Choroid plexus tumours are rare, with a peak incidence in the first two years of life. The most common location is the lateral ventricle in children, while in adults it is the fourth ventricle. The most common clinical manifestation is the signs and symptoms of intracranial hypertension. They are histologically classified as plexus papilloma, atypical plexus papilloma, and plexus carcinoma. A review is presented on choroid plexus tumours treated in the Hospital Sant Joan de Déu between 1980 and 2014. A total of 18 patients have been treated. An analysis was made of the demographic, clinical, histological data, treatment, and recurrences. The treatment of choice is complete resection, accompanied by adjuvant therapy in carcinomas. In atypical papillomas, the use of adjuvant therapies is controversial, reserving radiation therapy for recurrences. Papillomas have a good outcome, whereas atypical papillomas and carcinomas outcome is poor. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Leptin-based adjuvants: an innovative approach to improve vaccine response.

PubMed

White, Sarah J; Taylor, Matthew J; Hurt, Ryan T; Jensen, Michael D; Poland, Gregory A

2013-03-25

Leptin is a pleiotropic hormone with multiple direct and regulatory immune functions. Leptin deficiency or resistance hinders the immunologic, metabolic, and neuroendocrinologic processes necessary to thwart infections and their associated complications, and to possibly protect against infectious diseases following vaccination. Circulating leptin levels are proportional to body fat mass. High circulating leptin concentrations, as observed in obesity, are indicative of the development of leptin transport saturation/signaling desensitization. Leptin bridges nutritional status and immunity. Although its role in vaccine response is currently unknown, over-nutrition has been shown to suppress vaccine-induced immune responses. For instance, obesity (BMI ≥30 kg/m(2)) is associated with lower antigen-specific antibody titers following influenza, hepatitis B, and tetanus vaccinations. This suggests that obesity, and possibly saturable leptin levels, are contributing factors to poor vaccine immunogenicity. While leptin-based therapies have not been investigated as vaccine adjuvants thus far, leptin's role in immunity suggests that application of these therapies is promising and worth investigation to enhance vaccine response in people with leptin signaling impairments. This review will examine the possibility of using leptin as a vaccine adjuvant by: briefly reviewing the distribution and signal transduction of leptin and its receptors; discussing the physiology of leptin with emphasis on its immune functions; reviewing the causes of attenuation of leptin signaling; and finally, providing plausible inferences for the innovative use of leptin-based pharmacotherapies as vaccine adjuvants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Financial Implication of Radioactive Iodine Therapy for Early-Stage Papillary Thyroid Cancer.

PubMed

Al-Qurayshi, Zaid; Bu Ali, Daniah; Srivastav, Sudesh; Kandil, Emad

2017-01-01

The aim of this study was to evaluate disease-specific survival and cost related to radioactive iodine therapy (RAI) utilization in patients with early-stage papillary thyroid carcinoma (PTC). This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2012. A total of 38,374 patients with PTC were identified. Of those, 56.3% had adjuvant RAI. RAI administration was not associated with a survival advantage in patients with PTC stage I (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.11, 14.54; p = 0.85) or stage II (HR 0.50, 95% CI 0.05, 4.88; p = 0.55). Patients with PTC stage III who underwent adjuvant RAI had an improved survival (HR 0.30, 95% CI 0.10, 0.91; p = 0.033). In 2012, RAI was used in 45.5% of patients with stage I and in 71.4% of patients with stage II. The total expenditure on adjuvant RAI for PTC stage I throughout the study period was estimated to be USD 82.3 million with an annual average of USD 9.1 (±2.0) million/year. If the decline rate in the utilization of RAI continued, the model projected that the annual expenditure would decrease by USD 0.14 million/year. There is a high prevalence of adjuvant RAI utilization for early-stage PTC that is causing financial burden on the health system with no evidence of survival benefit. © 2017 S. Karger AG, Basel.

Adjuvant Vaginal Brachytherapy for Early Stage Endometrial Cancer: A Comprehensive Review

PubMed Central

Harkenrider, Matthew M; Block, Alec M; Alektiar, Kaled M; Gaffney, David K; Jones, Ellen; Klopp, Ann; Viswanathan, Akila N; Small, William

2017-01-01

This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the post-operative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early stage endometrial cancer patients results in very low rates of vaginal recurrence (0–3.1%) with low rates of late toxicity which are primarily vaginal in nature. PORTEC-2 supports that VBT results in non-inferior rates of vaginal recurrence compared to external beam radiotherapy (EBRT) for the treatment of high-intermediate risk patients. VBT as a boost following EBRT, in combination with chemotherapy, and for high-risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians both prefer joint decision-making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multi-disciplinary setting and patients should be counseled properly regarding the risks and benefits of adjuvant therapy. PMID:27260082

Adjuvant Gemcitabine and Gemcitabine-based Chemoradiotherapy Versus Gemcitabine Alone After Pancreatic Cancer Resection: The Indiana University Experience.

PubMed

Khawaja, Muhammad R; Kleyman, Svetlana; Yu, Zhangsheng; Howard, Thomas; Burns, Matthew; Nakeeb, Attila; Loehrer, Patrick J; Cardenes, Higinia R; Chiorean, Elena Gabriela

2017-02-01

Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy. Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement. The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement. Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer.

Esophageal Dose Tolerance to Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors for Late Toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stephans, Kevin L., E-mail: stephak@ccf.org; Djemil, Toufik; Diaconu, Claudiu

2014-09-01

Purpose: To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). Methods and Materials: This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. Results: The median esophageal point dose andmore » 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Conclusions: Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy should be considered when delivering SBRT near the esophagus.« less

Esophageal dose tolerance to hypofractionated stereotactic body radiation therapy: risk factors for late toxicity.

PubMed

Stephans, Kevin L; Djemil, Toufik; Diaconu, Claudiu; Reddy, Chandana A; Xia, Ping; Woody, Neil M; Greskovich, John; Makkar, Vinit; Videtic, Gregory M M

2014-09-01

To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. The median esophageal point dose and 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy should be considered when delivering SBRT near the esophagus. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katayama, Sonja, E-mail: sonja.katayama@med.uni-heidelberg.de; Striecker, Thorbjoern; Kessel, Kerstin

Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy inmore » 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.« less

Reasons for underuse of recommended therapies for colorectal and lung cancer in the Veterans Health Administration.

PubMed

Landrum, Mary Beth; Keating, Nancy L; Lamont, Elizabeth B; Bozeman, Samuel R; McNeil, Barbara J

2012-07-01

Many studies have documented low rates of effective cancer therapies, particularly in older or minority populations. However, little is known about why effective therapies are underused in these populations. The authors examined medical records of 584 patients with cancer diagnosed or treated in Department of Veterans Affairs facilities to assess reasons for lack of 1) surgery for stage I/II nonsmall cell lung cancer, 2) surgery for stage I/II/III rectal cancer, 3) adjuvant radiation therapy for stage II/III rectal cancer, and 4) adjuvant chemotherapy for stage III colon cancer. They also assessed differences in reasons for underuse by patient age and race. Across the 4 guideline-recommended treatments, 92% to 99% of eligible patients were referred to the appropriate cancer specialist; however, therapy was recommended in only 74% to 92% of eligible cases. Poor health was cited in the medical record as the reason for lack of therapy in 15% to 61% of underuse cases; patient refusal explained 26% to 58% of underuse cases. African American patients were more likely to refuse surgery. Older patients were more likely to refuse treatments. Recommendation against therapy was a primary factor in underuse of effective therapies in older and sicker patients. Patients' refusal of therapy contributed to age and racial disparities in care. Improved data on the effectiveness of cancer therapies in community populations and interventions aimed at improved communication of known risks and benefits of therapy to cancer patients could be effective tools to reduce underuse and lingering disparities in care. Copyright © 2011 American Cancer Society.

The evolution of anti-angiogenic therapy for kidney cancer

PubMed Central

Lee, Chung-Han; Motzer, Robert J.

2017-01-01

Tyrosine kinase inhibitors that target pro-angiogenic pathways improve progression-free and overall survival in patients with metastatic kidney cancer and were thus tested in the adjuvant setting in studies published this past year. 2016 also saw the emergence of new inhibitors of pro-angiogenic pathways that might represent the next step in kidney cancer therapy. PMID:28100904

The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKCδ-dependent inhibition of the AKT pathway.

PubMed

Assad Kahn, Suzana; Costa, Silvia Lima; Gholamin, Sharareh; Nitta, Ryan T; Dubois, Luiz Gustavo; Fève, Marie; Zeniou, Maria; Coelho, Paulo Lucas Cerqueira; El-Habr, Elias; Cadusseau, Josette; Varlet, Pascale; Mitra, Siddhartha S; Devaux, Bertrand; Kilhoffer, Marie-Claude; Cheshier, Samuel H; Moura-Neto, Vivaldo; Haiech, Jacques; Junier, Marie-Pierre; Chneiweiss, Hervé

2016-05-01

A variety of drugs targeting monoamine receptors are routinely used in human pharmacology. We assessed the effect of these drugs on the viability of tumor-initiating cells isolated from patients with glioblastoma. Among the drugs targeting monoamine receptors, we identified prazosin, an α1- and α2B-adrenergic receptor antagonist, as the most potent inducer of patient-derived glioblastoma-initiating cell death. Prazosin triggered apoptosis of glioblastoma-initiating cells and of their differentiated progeny, inhibited glioblastoma growth in orthotopic xenografts of patient-derived glioblastoma-initiating cells, and increased survival of glioblastoma-bearing mice. We found that prazosin acted in glioblastoma-initiating cells independently from adrenergic receptors. Its off-target activity occurred via a PKCδ-dependent inhibition of the AKT pathway, which resulted in caspase-3 activation. Blockade of PKCδ activation prevented all molecular changes observed in prazosin-treated glioblastoma-initiating cells, as well as prazosin-induced apoptosis. Based on these data, we conclude that prazosin, an FDA-approved drug for the control of hypertension, inhibits glioblastoma growth through a PKCδ-dependent mechanism. These findings open up promising prospects for the use of prazosin as an adjuvant therapy for glioblastoma patients. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

PubMed

Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

2016-02-01

This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P < .001). These findings suggest that the combined use of botulinum toxin A and a low dose of tizanidine in treating children with cerebral palsy appears to be more effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A. © The Author(s) 2015.

Optimal management for surgically Stage 1 serous cancer of the uterus.

PubMed

Elit, L; Kwon, J; Bentley, J; Trim, K; Ackerman, I; Carey, M

2004-01-01

To describe the outcomes of patients who have undergone well-conducted surgery and found to have Stage 1 serous uterine cancer. This retrospective cohort study includes women who have been treated for Stage 1 serous cancer of the uterus from 1985 to 2001. Cases were included from the regional cancer centers in Hamilton, London, Sunnybrook Toronto and Cancer Care Manitoba. Forty-three women met the inclusion criteria: Complete surgical staging (n = 27), surgery followed by pelvic radiation therapy (n = 4), surgery followed by whole abdominal radiation therapy (n = 6), surgery followed by adjuvant chemotherapy (n = 6). Patient age or depth of invasion did not influence survival. Progression free interval was 22 months (SD = 14.29). Recurrence rate was highest for adjuvant chemotherapy (66%). Survival was assessed by treatment modality and a statistically significant poorer survival was seen in the adjuvant chemotherapy group (OR 17.5; 95% CI 1.3-227.6). No comment can be made on a superior treatment regimen given the small numbers in each treatment strata. This study supports the findings of others in the literature. In a group of patients where surgical staging shows limited disease (i.e., surgically Stage 1 disease), then surgery alone appears to be adequate treatment.

[Smoothing Gan Reinforcing Shen Method Adjuvantly Treated Poor Response of Diminished Ovari- an Reserve Patients in in vitro Fertilization and Embryo Transfer: a Clinical Study].

PubMed

Zhang, Zheng; Zhang, Xue-hong; He, Tian-you

2015-10-01

To study clinical efficacy of smoothing Gan reinforcing Shen (SGRS) method in treating poor response of diminished ovarian reserve (DOR) patients in in vitro fertilization and embryo, transfer (IVF-ET). Totally 84 DOR patients undergoing IVF-ET were assigned to the experimental group (SGRS Chinese herbs as adjuvant therapy) and the control group according to random digit table, 42 in each group. Patients in the control group received controlled ovarian hyperstimulation (COH) and IVF-ET. Those in the experimental group additionally received basic formula of SGRS method, one dose per day. The dose and use time of recombinant follicle-stimulating hormone (r-FSH) were recorded during ovarian stimulation process. On the injection day of human chorionic gonadotropin (HCG) and serum levels of estradiol (E2) on the oocyte retrieval day were determined using chemiluminescent method. E2 contents in the follicular fluid on the oocyte retrieval day were detected using ELISA. The total number of retrieved oocytes, the number of mature oocytes in metaphase II (M II), the number of normal fertilization [with two pronucleus (2PN)], the number of portable embryos, and the number of good quality embryos were recorded. The correlation between Chinese medical adjuvant therapy and the aforesaid indices were observed. The clinical pregnancy rate and the abortion rate were finally compared between the two groups. The total dose of r-FSH, the E2 level on HCG injection day, the serum E2 level on the oocyte retrieval day, the number of retrieved oocyte, the number of oocytes in M II the number of oocytes with 2PN, the number of portable embryos, and the number of good quality embryos were all positively correlated with Chinese medical adjuvant therapy (P < 0.05, P < 0.01). Compared with the control group, serum E2 levels on the HCG injection day and the oocyte retrieval day obviously increased, the number of retrieved oocytes, the number of oocytes in M II, and the number of portable embryos were increased more in the experimental group with statistical difference (P < 0.05, P < 0.01). There was no statistical significance in the clinical pregnancy rate or the abortion rate between the two groups (P > 0.05). SGRS Chinese herbs as adjuvant therapy could improve ovarian responsiveness of DOR patients undergoing IVF-ET, increase the number of retrieved oocytes, elevate the quality of oocytes and the number of embryos.