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Sample records for adjuvant cancer therapy

  1. Adjuvant therapy in pancreatic cancer.

    PubMed

    Jones, Owain Peris; Melling, James Daniel; Ghaneh, Paula

    2014-10-28

    Pancreatic cancer remains one of the leading causes of cancer related death worldwide with an overall five-year survival of less than 5%. Potentially curative surgery, which alone can improve 5-year survival to 10%, is an option for only 10%-20% of patients at presentation owing to local invasion of the tumour or metastatic disease. Adjuvant chemotherapy has been shown to improve 5-year survival to 20%-25% but conflicting evidence remains with regards to chemoradiation. In this article we review the current evidence available from published randomised trials and discuss ongoing phase III trials in relation to adjuvant therapy in pancreatic cancer.

  2. 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.

  3. Adjuvant therapy of resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-08-01

    The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined modality therapy and preoperative combined modality therapy followed by surgery and postoperative chemotherapy. Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy are in progress.

  4. [Adjuvant therapy of breast cancer with trastuzumab].

    PubMed

    Beneder, Christine; Marth, Christian

    2008-01-01

    With the approval of trastuzumab (Herceptin) in 1998, a new era of breast cancer treatment has been heralded. This antibody is directed at the intracellular domain of a member of the epidermal growth factor receptor family, the so-called HER2 receptor. About 25-30% of all breast cancers overexpress this factor, which is associated with a more unfavorable prognosis. Trastuzumab is indicated for patients whose tumor overexpresses HER2. All previous studies on the adjuvant therapy with trastuzumab show very consistent results and provide evidence that the risk of recurrence can be reduced by half by the antibody. Nevertheless, there are still numerous open and controversially discussed questions concerning the use of trastuzumab in adjuvant therapy.

  5. Overview of adjuvant systemic therapy in early stage breast cancer.

    PubMed

    Newman, Lisa A; Singletary, S Eva

    2007-04-01

    The benefits of adjuvant systemic therapy in reducing risk of distant relapse from breast cancer have been recognized for several decades. The intent of adjuvant therapy is to eliminate the occult micrometastatic breast cancer burden before it progresses into clinically apparent disease. Successful delivery of effective adjuvant systemic therapy as a complement to surgical management of breast cancer has contributed to the steady declines in breast cancer mortality observed internationally over the past 2 decades. Ongoing clinical and translational research in breast cancer seeks to improve the efficacy of systemic agents for use in the conventional postoperative (adjuvant) setting.

  6. Adjuvant therapy for colon cancer in the new millenium.

    PubMed

    Rao, S; Cunningham, D

    2003-01-01

    A significant proportion of patients with colon cancer who undergo curative surgical resection develop metastatic disease. Over the last 20 years large prospective randomised studies have demonstrated a clear survival benefit for patients with stage III colon cancer who are treated with adjuvant 5FU based chemotherapy. At the present time 6 months of 5FU and leucovorin is generally considered the standard adjuvant therapy. For stage II disease the routine use of adjuvant treatment remains controversial. Newer drugs such as oxaliplatin, irinotecan, and the oral fluoropyrimidines have proven active in advanced colorectal cancer and are currently being evaluated in the adjuvant setting. Molecular markers for this disease are being identified and may help define those patients who would benefit from therapy. The integration of adjuvant immunotherapy with conventional chemotherapy offers the potential to improve the long-term outcome for surgically resected colon cancer.

  7. NCCN Task Force Report: Adjuvant Therapy for Breast Cancer.

    PubMed

    Carlson, Robert W; Brown, Elizabeth; Burstein, Harold J; Gradishar, William J; Hudis, Clifford A; Loprinzi, Charles; Mamounas, Eleftherios Paul; Perez, Edith A; Pritchard, Kathleen; Ravdin, Peter; Recht, Abram; Somlo, George; Theriault, Richard L; Winer, Eric P; Wolff, Antonio C

    2006-03-01

    The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.

  8. Radiation plus chemotherapy as adjuvant therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-04-01

    The most common neo-adjuvant therapy for rectal cancer is chemotherapy and concurrent radiation therapy. In general, it is delivered pre-operatively for patients with clinical evidence of T(3-4) disease or post-operatively in patients who have undergone surgery and have T(3) and/or N(1-2) disease. This chapter reviews the rationale and results for neo-adjuvant therapy, the selection process for pre-operative versus post-operative treatment, and new approaches and controversies.

  9. Postoperative adjuvant therapy of breast cancer. Oncology Overview

    SciTech Connect

    Not Available

    1984-12-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Postoperative chemotherapy; Postoperative radiotherapy; Postoperative hormone therapy; Postoperative immunotherapy and chemoimmunotherapy; Postoperative multimodal therapy; Prognostic factors in postoperative adjuvant therapy.

  10. Management of adjuvant mitotane therapy following resection of adrenal cancer.

    PubMed

    Terzolo, M; Ardito, A; Zaggia, B; Laino, F; Germano, A; De Francia, S; Daffara, F; Berruti, A

    2012-12-01

    Whenever adrenal cancer (ACC) is completely removed we should face the dilemma to treat by means of adjuvant therapy or not. In our opinion, adjuvant mitotane is the preferable approach in most cases because the majority of patients following radical removal of an ACC have an elevated risk of recurrence. A better understanding of factors that influence prognosis and response to treatment will help in stratifying patients according to their probability of benefiting from adjuvant mitotane, with the aim of sparing unnecessary toxicity to patients who are likely unresponsive. However, until significant advancements take place, we have to deal with uncertainty using our best clinical judgement and personal experience in the clinical decision process. In the present paper, we present the current evidence on adjuvant mitotane treatment and describe the management strategies of patients with ACC after complete surgical resection. We acknowledge the limit that most recommendations are based on personal experience rather than solid evidence.

  11. Redefining Adjuvant Therapy for Colon Cancer

    Cancer.gov

    In this trial, patients with resected stage III colon cancer are being randomly assigned to receive FOLFOX chemotherapy for either 3 or 6 months and to take either a pill called celecoxib or a matching placebo pill for 3 years.

  12. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Cancer.gov

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  13. Selective glucocorticoid receptor-activating adjuvant therapy in cancer treatments

    PubMed Central

    Sundahl, Nora; Clarisse, Dorien; Bracke, Marc; Offner, Fritz; Berghe, Wim Vanden; Beck, Ilse M.

    2016-01-01

    Although adverse effects and glucocorticoid resistance cripple their chronic use, glucocorticoids form the mainstay therapy for acute and chronic inflammatory disorders, and play an important role in treatment protocols of both lymphoid malignancies and as adjuvant to stimulate therapy tolerability in various solid tumors. Glucocorticoid binding to their designate glucocorticoid receptor (GR), sets off a plethora of cell-specific events including therapeutically desirable effects, such as cell death, as well as undesirable effects, including chemotherapy resistance, systemic side effects and glucocorticoid resistance. In this context, selective GR agonists and modulators (SEGRAMs) with a more restricted GR activity profile have been developed, holding promise for further clinical development in anti-inflammatory and potentially in cancer therapies. Thus far, the research into the prospective benefits of selective GR modulators in cancer therapy limped behind. Our review discusses how selective GR agonists and modulators could improve the therapy regimens for lymphoid malignancies, prostate or breast cancer. We summarize our current knowledge and look forward to where the field should move to in the future. Altogether, our review clarifies novel therapeutic perspectives in cancer modulation via selective GR targeting. PMID:27713909

  14. Adjuvant therapy use among Appalachian breast cancer survivors.

    PubMed

    Tan, Xi; Marshall, Vincent D; Anderson, Roger T; Donohoe, Joseph; Camacho, Fabian; Balkrishnan, Rajesh

    2015-07-01

    There is a paucity of literature systemically examining the effects of access to cancer care resources on adjuvant endocrine therapy (AET) use behaviors, especially in underserved regions such as the Appalachian region in the United States, where gaps in healthcare access are well documented. The objectives of this study were to explore AET adherence and persistence in Appalachia, delineate the effects of access to care cancer on adherence/persistence, and evaluate the influences of adherence and persistence on overall survival.A retrospective cohort study from 2006 to 2008 was conducted among female breast cancer survivors living in the Appalachian counties of 4 states (PA, OH, KY, and NC). We linked cancer registries to Medicare claims data and included patients with invasive, nonmetastatic, hormone-receptor-positive breast cancer who received guideline-recommended AET. Medication adherence was defined as corresponding to a Medication Possession Ratio (MPR) ≥0.8 and logistic regression was utilized to assess predictors of adherence. Medication nonpersistence was defined as the discontinuation of drugs after exceeding a 60-day medication gap, and multivariate adjusted estimates of nonpersistence were obtained using the Cox proportional hazards (PH) model.About 31% of the total 428 patients were not adherent to AET, and 30% were not persistent over an average follow-up period of 421 days. Tamoxifen, relative to aromatase inhibitors, was associated with higher odds of adherence (odds ratio = 2.82, P < 0.001) and a lower risk of nonpersistence (hazard ratio = 0.40, P < 0.001). Drug-related side effects like pain may be an important factor leading to nonadherence and early discontinuation. In addition, aromatase inhibitor (AI) adherence and persistence were significantly influenced by out-of-pocket drug costs, dual eligibility status, and coverage gaps. Nonadherence to and nonpersistence with AET were associated with higher risks of all-cause mortality.Our findings

  15. The role of targeted agents in adjuvant therapy for non-small cell lung cancer.

    PubMed

    Kelly, Karen

    2005-07-01

    The recent survival benefit of adjuvant chemotherapy in early stage non-small cell lung cancer provides optimism for the future success of targeted therapy in this setting. It is important that we begin to explore molecularly targeted agents in the adjuvant arena, but how best to accomplish this in the face of these new findings presents a challenge. Criteria for selecting promising targeted therapies and optimal trial designs to evaluate them expeditiously in the adjuvant setting are clearly needed.

  16. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    NASA Astrophysics Data System (ADS)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  17. Menopausal status and adjuvant hormonal therapy for breast cancer patients: a practical guideline.

    PubMed

    De Vos, F Y F L; van Laarhoven, H W M; Laven, J S E; Themmen, A P N; Beex, L V A M; Sweep, C G J; Seynaeve, C; Jager, A

    2012-11-01

    Breast cancer is the most common malignancy amongst women in the developed world. For patients with hormone-sensitive breast cancer eligible for adjuvant hormonal therapy, it is important to know if the ovaries are (still) functional or not. Indeed, the choice for a specific adjuvant hormonal treatment depends on the menopausal status of an individual woman. The currently available measures to determine the menopausal status are conflicting. Until better measures become available, we propose a practical guideline enabling an optimal choice of adjuvant hormonal therapy for women with a hormone receptor positive breast cancer taking into account uncertainties about their menopausal status.

  18. Adjuvant Therapy: Treatment to Keep Cancer from Returning

    MedlinePlus

    ... or neoadjuvant therapy doesn't come without a price — the side effects can be more than minor ... chemotherapy. Radiation therapy. Radiation therapy uses high-powered energy beams, such as X-rays, to kill cancer ...

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

    SciTech Connect

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    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 from 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.

  20. Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.

    PubMed

    Carlson, Robert W; Henderson, I Craig

    2003-01-01

    The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that

  1. Cell membrane modulation as adjuvant in cancer therapy.

    PubMed

    Zalba, Sara; Ten Hagen, Timo L M

    2017-01-01

    Cancer is a complex disease involving numerous biological processes, which can exist in parallel, can be complementary, or are engaged when needed and as such can replace each other. This redundancy in possibilities cancer cells have, are fundamental to failure of therapy. However, intrinsic features of tumor cells and tumors as a whole provide also opportunities for therapy. Here we discuss the unique and specific makeup and arrangement of cell membranes of tumor cells and how these may help treatment. Interestingly, knowledge on cell membranes and associated structures is present already for decades, while application of membrane modification and manipulation as part of cancer therapy is lagging. Recent developments of scientific tools concerning lipids and lipid metabolism, opened new and previously unknown aspects of tumor cells and indicate possible differences in lipid composition and membrane function of tumor cells compared to healthy cells. This field, coined Lipidomics, demonstrates the importance of lipid components in cell membrane in several illnesses. Important alterations in cancer, and specially in resistant cancer cells compared to normal cells, opened the door to new therapeutic strategies. Moreover, the ability to modulate membrane components and/or properties has become a reality. Here, developments in cancer-related Lipidomics and strategies to interfere specifically with cancer cell membranes and how these affect cancer treatment are discussed. We hypothesize that combination of lipid or membrane targeted strategies with available care to improve chemotherapy, radiotherapy and immunotherapy will bring the much needed change in treatment in the years to come.

  2. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    SciTech Connect

    McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  3. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review.

    PubMed

    Murphy, Caitlin C; Bartholomew, L Kay; Carpentier, Melissa Y; Bluethmann, Shirley M; Vernon, Sally W

    2012-07-01

    Adjuvant hormonal therapy significantly improves long-term survival of breast cancer patients with hormone receptor-positive disease. Despite the proven clinical efficacy of tamoxifen and aromatase inhibitors, many breast cancer survivors either fail to take the correct dosage at the prescribed frequency (adherence) or discontinue therapy (persistence). This systematic review aims to: (1) determine the prevalence of adherence and persistence to adjuvant hormonal therapy among breast cancer survivors in clinical practice, and (2) identify correlates of adherence and persistence. We searched Medline, PubMed, PsycINFO, and CINAHL for studies that measured rates and/or correlates of adherence and/or persistence to adjuvant hormonal therapy. Studies were reviewed in a multi-step process: (1) the lead author screened titles and abstracts of all potentially eligible studies; (2) each coauthor reviewed a random 5 % sample of abstracts; and (3) two sets of coauthors each reviewed half of all "maybe" abstracts. Any disagreements were discussed until consensus was reached. Twenty-nine studies met inclusion criteria. Prevalence of adherence ranged from 41 to 72 % and discontinuation (i.e., nonpersistence) ranged from 31 to 73 %, measured at the end of 5 years of treatment. Extremes of age (older or younger), increasing out-of-pocket costs, follow-up care with a general practitioner (vs. oncologist), higher CYP2D6 activity, switching from one form of therapy to another, and treatment side effects were negatively associated with adherence and/or persistence. Taking more medications at baseline, referral to an oncologist, and earlier year at diagnosis were positively associated with adherence and/or persistence. Adherence and persistence to adjuvant hormonal therapy among breast cancer survivors is suboptimal. Many of the correlates of adherence and persistence studied to date are not modifiable. Our review reveals a critical need for further research on modifiable factors

  4. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    PubMed Central

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  5. Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents.

    PubMed

    Patel, Seema

    2016-01-01

    Propolis is a bee-metabolized resinous substance (bee glue) from plant sap and gums. It has been in usage as a healing agent since antiquity, yet has not garnered global popularity as a health promoter. Its biological effects, which range from antimicrobial, antioxidant, anti-inflammatory, antidiabetic, dermatoprotective, anti-allergic, laxative and immunomodulatory to anticancer, have been validated. Propolis has shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The inhibition of matrix metalloproteinases, anti-angiogenesis, prevention of metastasis, cell-cycle arrest, induction of apoptosis and moderation of the chemotherapy-induced deleterious side effects have been deduced as the key mechanisms of cancer manipulation. The components conferring antitumor potentials have been identified as caffeic acid phenethyl ester, chrysin, artepillin C, nemorosone, galangin, cardanol, etc. These compounds target various genetic and biochemical pathways of cancer progression. Depending on the botanical sources and the geographical origin, biological activities of propolis vary. Despite phenomenal development in cancer research, conventional therapy falls short in complete malignancy management. The findings obtained so far build hope that propolis as a complementary medicine may address the lacunae. This review documents the recent advances and scope of amendement in cancer remediation with adequate emphasis on the mechanistic aspect of propolis.

  6. Adjuvant hormonal therapy for breast cancer and risk of hormone receptor-specific subtypes of contralateral breast cancer.

    PubMed

    Li, Christopher I; Daling, Janet R; Porter, Peggy L; Tang, Mei-Tzu C; Malone, Kathleen E

    2009-09-01

    Compared with the breast cancer risk women in the general population have, breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer. Adjuvant hormonal therapy reduces this risk, but preliminary data indicate that it may also increase risk of hormone receptor-negative contralateral tumors. We conducted a population-based nested case-control study including 367 women diagnosed with both first primary estrogen receptor (ER)-positive invasive breast cancer and second primary contralateral breast cancer and 728 matched control women diagnosed only with a first breast cancer. Data on adjuvant hormonal therapy, other treatments, and breast cancer risk factors were ascertained through telephone interviews and medical record abstractions. Two-sided statistical tests using conditional logistic regression were conducted to quantify associations between adjuvant hormonal therapy and risk of hormone receptor-specific subtypes of contralateral breast cancer (n = 303 ER+ and n = 52 ER- cases). Compared with women not treated with hormonal therapy, users of adjuvant tamoxifen for >or=5 years had a reduced risk of ER+ contralateral breast cancer [odds ratio, 0.4; 95% confidence interval (CI), 0.3-0.7], but a 4.4-fold (95% CI, 1.03-19.0) increased risk of ER- contralateral breast cancer. Tamoxifen use for <5 years was not associated with ER- contralateral breast cancer risk. Although adjuvant hormonal therapy has clear benefits, risk of the relatively uncommon outcome of ER- contralateral breast cancer may now need to be tallied among its risks. This is of clinical concern given the poorer prognosis of ER- compared with ER+ tumors.

  7. Chinese herbal medicines as adjuvant treatment during chemo- or radio-therapy for cancer.

    PubMed

    Qi, Fanghua; Li, Anyuan; Inagaki, Yoshinori; Gao, Jianjun; Li, Jijun; Kokudo, Norihiro; Li, Xiao-Kang; Tang, Wei

    2010-12-01

    Numerous studies have indicated that in cancer treatment Chinese herbal medicines in combination with chemo- or radio-therapy can be used to enhance the efficacy of and diminish the side effects and complications caused by chemo- and radio-therapy. Therefore, an understanding of Chinese herbal medicines is needed by physicians and other health care providers. This review provides evidence for use of Chinese herbal medicines as adjuvant cancer treatment during chemo- or radio-therapy. First, Chinese herbal medicines (e.g. Astragalus, Turmeric, Ginseng, TJ-41, PHY906, Huachansu injection, and Kanglaite injection) that are commonly used by cancer patients for treating the cancer and/or reducing the toxicity induced by chemo- or radio-therapy are discussed. Preclinical and clinical studies have shown that these Chinese herbal medicines possess great advantages in terms of suppressing tumor progression, increasing the sensitivity of chemo- and radio-therapeutics, improving an organism's immune system function, and lessening the damage caused by chemo- and radio-therapeutics. Second, clinical trials of Chinese herbal medicines as adjuvant cancer treatment are reviewed. By reducing side effects and complications during chemo- and radio-therapy, these Chinese herbal medicines have a significant effect on reducing cancer-related fatigue and pain, improving respiratory tract infections and gastrointestinal side effects including diarrhea, nausea, and vomiting, protecting liver function, and even ameliorating the symptoms of cachexia. This review should contribute to an understanding of Chinese herbal medicines as adjuvant treatment for cancer and provide useful information for the development of more effective anti-cancer drugs.

  8. Dose-dense and sequential strategies in adjuvant breast cancer therapy.

    PubMed

    Untch, M; Von Koch, F; Crohns, C; Sobotta, K; Kahlert, S; Konecny, G; Hepp, H

    2001-05-01

    Several attempts have been made to improve the survival rates of breast cancer patients. The benefit of adjuvant chemotherapy was clearly shown, but the absolute difference of 2% to 11% in overall survival, depending on the patient group, is disappointingly small. In particular, high-risk patients, such as those with > or = 10 involved lymph nodes, extracapsular spread, or vascular invasion, still have an excessive risk of recurrence even after standard adjuvant chemotherapy. To increase the survival rates after adjuvant therapy, new chemotherapeutic agents and new strategies of application are currently being evaluated in clinical trials. Chemotherapy with cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil (CMF) seems to be safe and effective in patients with breast cancer. In addition, in metastatic patients, dose-intensified chemotherapy is being investigated. The introduction of epirubicin (Ellence), an agent less cardiotoxic and equally active compared to doxorubicin, enabled the escalation of anthracyclines in adjuvant therapy without serious cardiotoxic effects. The combination of dose-intensified chemotherapy and sequential application in the treatment of breast cancer is reviewed.

  9. Adjuvant Hormonal Therapy in Women with Early-stage Breast Cancer.

    PubMed

    Lumachi, Franco; Santeufemia, Davide A; Fadda, Giovanni M; Tozzoli, Renato; Chiara, Giordano B; Basso, Stefano M M

    2016-01-01

    For decades, adjuvant hormonal therapy has become the standard treatment of patients with estrogen receptor-positive breast cancer. Currently, the drugs available are GnRH agonists, selective estrogen receptor modulators, and aromatase inhibitors. The use of GnRH agonists represents a potentially reversible treatment that can restore ovarian function after chemotherapy. In premenopausal women, systemic therapy based on selective estrogen receptor modulators administration (e.g., tamoxifen) usually represents the standard adjuvant treatment. There are not sufficient data to recommend the routine addition of GnRH agonists to other endocrine therapies. In postmenopausal women, the disease-free survival was significantly prolonged in patients treated with aromatase inhibitor compared with those treated with tamoxifen, but the survival benefit was modest. Better results were obtained when the two drugs were administered sequentially. According to the ASCO guidelines, after 5 years of tamoxifen treatment, either tamoxifen or aromatase inhibitors therapy should be suggested for an additional 5 years. Unfortunately, most adverse events are consistent with estrogen deprivation and are common to all therapies, and the cumulative toxicity causes discontinuation and nonadherence to therapy in up to 50% of patients. Switching tamoxifen to an aromatase inhibitor may reduce adverse event incidence. Molecular-targeted therapy is useful in patients with advanced, relapsed or hormonal therapy-resistant tumors, usually as second- or third-line treatment. These drugs are usually added to aromatase inhibitors; however, currently, they have not yet been used in patients with early breast cancer.

  10. Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

    PubMed Central

    Tham, Chee Kian; Choo, Su Pin; Poon, Donald Yew Hee; Toh, Han Chong; Ong, Simon Yew Kuang; Tan, Sze Huey; Wang, Michael Lian Chek; Foo, Kian Fong

    2010-01-01

    AIM: To analyze the outcome of patients who received concurrent capecitabine (Xeloda) and radiation (XRT) compared to the established concurrent 5-fluorouracil (5-FU) with radiation (5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers. METHODS: All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed. Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers. RESULTS: A total of 108 patients were reviewed. Median age at diagnosis was 60. The majority of the patients (64.8%) had advanced stage III and IV disease (with no distant metastasis). All except 4 patients had D2 gastrectomy. Twenty one patients (19.4%) had positive surgical resection margins. Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone. For the patients in the chemotherapy-only group, all had fluoropyrimidine-based therapy, with added cisplatin in 7 patients and epirubicin in 2 patients. Median recurrence-free survival was longer for the XRT group (52 mo) compared to the 5FU-RT (35 mo) and chemotherapy-only groups (25 mo) (P = 0.48). The patients in the XRT group achieved similar median overall survival (53 mo) as the 5FU-RT (54 mo) and the chemotherapy-only groups (44 mo) (P = 0.5). CONCLUSION: Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers. PMID:20677345

  11. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  12. Positive effect of tamoxifen as part of adjuvant chemo-endocrine therapy for breast cancer. Hokkaido Adjuvant Chemo-Endocrine Therapy for Breast Cancer Study Group.

    PubMed Central

    Uchino, J.; Samejima, N.; Tanabe, T.; Hayasaka, H.; Mito, M.; Hata, Y.; Asaishi, K.

    1994-01-01

    A prospective randomised multicentre clinical study was undertaken for 2 years and 3 months from November 1982, with the aim of examining the significance of using a combination of ftorafur (FT) and tamoxifen (TAM) for post-operative adjuvant therapy of breast cancer. Patients had either stage II or stage IIIa disease, were age 75 or below and had undergone radical mastectomy. Patients were divided into two groups and received one of the following treatment protocols: treatment A, intravenous administration of doxorubicin (DOX), 20 mg on the day of surgery and 10 mg the next day, followed by oral FT 50 mg day-1 for 2 years from the 14th day; treatment B, the same pattern of DOX administration for the first 2 days, followed by a combined therapy of FT and TAM 20 mg day-1 for 2 years. The number of patients was 546 (treatment A 274 and treatment B 272), of whom 34 (6%) were ineligible. The remaining 512 patients (treatment A 254 and treatment B 258) were followed up for 5 years for analysis. Significantly higher 5 year disease-free rate and 5 year survival rates were observed with treatment B compared with treatment A. When seen in terms of background factors, node-positive patients appeared to derive more benefit from tamoxifen than node-negative patients, but the oestrogen receptor-negative and premenopausal subgroups appeared to derive about the same benefit as those who were oestrogen receptor positive and post-menopausal. Indeed, survival in the premenopausal group was significantly better with tamoxifen (P = 0.04). No increase in side-effects was seen by combining TAM with FT. The study results demonstrate that concomitant administration of FT and TAM is better than FT alone for post-operative adjuvant therapy for breast cancer. PMID:8142265

  13. Understanding Breast Cancer Survivors' Beliefs and Concerns About Adjuvant Hormonal Therapy: Promoting Adherence.

    PubMed

    Hurtado-de-Mendoza, Alejandra; Jensen, Roxanne E; Jennings, Yvonne; Sheppard, Vanessa B

    2017-02-15

    Adjuvant hormonal therapy is recommended for women with hormone receptor (HR)-positive breast cancer. Though critical, many patients are non-adherent to this therapy. Few scales have been developed to specifically address beliefs about adjuvant hormonal therapy. This study explores the clarity and relevance of the Beliefs about Medicine Questionnaire (BMQ) in the context of adherence behaviors to hormonal therapy in Black and White breast cancer survivors. We recruited women diagnosed with HR-positive cancer from the Washington, DC, area. An interviewer administered a standardized survey and conducted a cognitive interview. Participants rated the BMQ across three areas: relevance, difficulty, and clarity. We coded whether the comments identified item level issues: limited applicability, unclear reference, unclear perspective, or wording or tone. In-depth interviews were conducted with women who prematurely discontinued hormone therapy. The sample (n = 30) was equally split between Black and White survivors. On average, women were 57.9 years old (SD = 9.0). Overall 77% rated scale as relevant. Cognitive interviews revealed areas of perceived limited acceptability such as the notion of becoming too dependent or the notion of becoming worse if not taking the medication. Women who discontinued hormonal therapy (n = 2) felt ambivalent towards hormonal therapy as they reported having both positive and negative beliefs about the medication. Our study findings suggest new areas for further research and instrument development to accurately measure self-reported beliefs about hormonal therapy by HR-positive breast cancer survivors.

  14. 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 m

  15. Tamoxifen as the First Targeted Long Term Adjuvant Therapy for Breast Cancer

    PubMed Central

    Jordan, V. Craig

    2014-01-01

    Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine has continued to surprise us, perform and save lives for the past 40 years. Unlike any other medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ, male breast cancer, pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that “longer was going to be better” when tamoxifen was being considered as an adjuvant therapy (Jordan 1978 Use of the DMBA-induced rat mammary carcinoma system for the evaluation of tamoxifen as a potential adjuvant therapy Reviews in Endocrine Related Cancer. October Supplement: 49–55.). This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. “Science is adventure, discovery, new horizons, insight into our world, a means of predicting the future and enormous power to help others”(Hoagland 1990).- Mahlon Hoagland, MD. Director, Worcester Foundation for Experimental Biology (1970–85) PMID:24659478

  16. Tailoring Adjuvant Radiation Therapy by Intraoperative Imaging to Detect Residual Cancer

    PubMed Central

    Whitley, Melodi J.; Weissleder, Ralph; Kirsch, David G.

    2015-01-01

    For many solid cancers, radiation therapy is offered as an adjuvant to surgical resection in order to lower rates of local recurrence and improve survival. However, a subset of patients treated with surgery alone will not have a local recurrence. Currently, there is no way to accurately determine which patients have microscopic residual disease in the tumor bed after surgery and therefore are most likely to benefit from adjuvant radiation therapy. To address this problem, a number of technologies have been developed to try to improve margin assessment of resected tissue and to detect residual cancer in the tumor bed. Moreover, some of these approaches have been translated from the preclinical arena into clinical trials. Here, we review different types of intraoperative molecular imaging systems for cancer. Optical imaging techniques like epi-illumination, fluorescence molecular tomography and optoacoustic imaging can be coupled with exogenous fluorescent imaging probes that accumulate in tumors passively via the enhanced permeability and retention effect or are targeted to tumor tissues based on affinity or enzyme activity. In these approaches, detection of fluorescence in the tumor bed may indicate residual disease. Protease activated probes have generated great interest because of their potential for leading to high tumor to normal contrast. Recently, the first Phase I clinical trial to assess the safety and activation of a protease activated probe was conducted. Spectroscopic methods like radiofrequency spectroscopy and Raman spectroscopy, which are based on energy absorption and scattering respectively, have also been tested in humans and are able to distinguish between normal and tumors tissues intraoperatively. Most recently, multi-modal contrast agents have been developed that target tumors and contain both fluorescent dyes and MRI contrast agents, allowing for preoperative planning and intraoperative margin assessment with a single contrast agent. Further

  17. Does adjuvant radiation therapy benefit women with small mammography-detected breast cancers?

    PubMed Central

    Jerzak, K.; Dudalski, N.; Pritchard, K.; Sun, P.; Narod, S.A.

    2017-01-01

    Background Women with small nonpalpable breast tumours have an excellent prognosis. The benefit of radiotherapy in this group of low-risk women is unknown. Methods A cohort of 1595 women with stages i–iii invasive breast cancer treated with breast-conserving surgery were followed for local recurrence. Using t-tests, baseline demographic data and tumour characteristics were compared for the women who had palpable (n = 1023) and mammography-detected (n = 572) breast cancers. The 15-year actuarial risk of local recurrence was estimated using a Kaplan–Meier method, stratified for adjuvant radiation therapy (yes or no), tumour palpability (palpable or not), and tumour size (≤1 cm or >1 cm). Hazard ratios (hrs) and 95% confidence intervals (95% cis) were calculated using a multivariate Cox regression model. Results were considered statistically significant if 2-tailed p values were less than 0.05. Results Among women with a nonpalpable tumour, the 15-year actuarial rates of local recurrence were, respectively, 13.9% and 18.3% for those treated and not treated with adjuvant radiation therapy (hr: 0.65; 95%ci: 0.40 to 1.06; p = 0.08). Among women with small nonpalpable breast cancers (≤1.0 cm), the rates were 14.6% and 13.4% respectively (p = 0.67). The absolute reduction in 15-year local recurrence was 11.0% for women with palpable tumours. Conclusions Our results suggest that women with small (<1 cm) screen-detected nonpalpable breast cancers likely derive little benefit from adjuvant radiotherapy; however, an adequately powered randomized trial would be required to make definitive conclusions. PMID:28270722

  18. 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

  19. Clinical and immunological assessment in breast cancer patients receiving anticancer therapy and bovine dialyzable leukocyte extract as an adjuvant.

    PubMed

    Lara, Humberto H; Turrent, Liliana Ixtepan; Garza-Treviño, Elsa N; Tamez-Guerra, Reyes; Rodriguez-Padilla, Cristina

    2010-05-01

    Dialyzable leukocyte extract (DLE) is one of the immunological agents used as an adjuvant in cancer therapy; it has been associated with improved quality of life during cancer chemotherapy. Based on these previous findings and on the observed clinical benefits attributed to DLE in other types of cancer, we investigated its clinical and immunological effects as a therapy adjuvant on breast cancer patients who received only chemotherapy, as compared to patients administered bovine DLE (bDLE) as an adjuvant. This study included 43 breast cancer patients who were about to begin chemotherapy. This group was divided as follows: 25 received chemotherapy and bDLE as an adjuvant therapy, and 18 received only chemotherapy without the adjuvant. All patient clinical and immunological responses were monitored. Among patients in the group that received bDLE as adjuvant, 60% showed a complete response, 32% showed a partial response and 8% did not respond. By contrast, in the group without the adjuvant, 39% showed a complete response, 50% displayed a partial response and 11% were non-responders. In addition, bDLE treatment in combination with chemotherapy resulted in the enhancement of the Karnofsky performance scale during chemotherapy. Even though patients underwent several cycles of chemotherapy without bDLE, the lymphocyte population dropped to below the reference value. On the other hand, in patients with bDLE as adjuvant, the CD4(+) and CD8(+) lymphocytes and the B lymphocytes were maintained within the median range of the reference value. The number of natural killer cells also increased after chemotherapy treatment with bDLE as an adjuvant. In conclusion, bDLE treatment contributes to significant immunological recovery in patients that have undergone heavy chemotherapy, increasing the clinical response and quality of life during chemotherapy.

  20. Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation

    PubMed Central

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

    2016-01-01

    The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment) have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i) would have decreased resting endothelial function; and ii) altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment) and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT) on a cycle ergometer during which pulmonary V˙O2 and changes in near-infrared spectroscopy (NIRS)-derived microvascular tissue oxygenation (TOI), total hemoglobin concentration ([Hb]total), and muscle deoxygenation ([HHb] ≈ fractional O2 extraction) were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98). During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01) The rate of change for TOI (ΔTOIΔ/V˙O2) and [HHb] (Δ[HHb]/ΔV˙O2) relative to ΔV˙O2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively). In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V˙O2 and O2 delivery during exercise. PMID:26807572

  1. Novel adjuvant therapies for pancreatic adenocarcinoma

    PubMed Central

    Oyasiji, Tolutope

    2015-01-01

    Contemporary adjuvant therapy for pancreatic cancer patients following surgical resection includes chemotherapy and chemoradiotherapy. However, the median survival remains approximately 20 months despite multi-modality treatment using gemcitabine or fluoropyrimidine systemic chemotherapy. Adjuvant randomized trials are currently underway to evaluate cytotoxic combinations found to be active in advanced disease including FOLFIRINOX, gemcitabine/nab-paclitaxel and gemcitabine/capecitabine. Immunotherapy using genetically engineered cell-based vaccines had shown promise in resected pancreatic cancer patients during early phase trials, and algenpantucel-L vaccine is currently being evaluated in adjuvant setting in a randomized trial. This review focuses on novel adjuvant therapies currently in clinical evaluation. PMID:26261729

  2. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    PubMed

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p < .001) and VEGF expression (r = .35, p < .001). For the prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies.

  3. Cyclophosphamide and tamoxifen as adjuvant therapies in the management of breast cancer. CRC Adjuvant Breast Trial Working Party.

    PubMed Central

    1988-01-01

    In 1980 the Cancer Research Campaign launched a multi-centre breast cancer trial; aimed at repeating the Scandinavian Chemotherapy Study Group's cyclophosphamide trial, and the NATO tamoxifen study; thereby further evaluating the role of these two adjuvant regimens in patients with early breast cancer. Two thousand two hundred and thirty women were randomized into this trial between 1980 and 1985 and preliminary analyses demonstrate a significant improvement in event-free survival for both regimens. Results from this study closely parallel the two trials it set out to repeat. PMID:2900646

  4. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    PubMed Central

    Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

  5. [Recurrent micro-satellite stable colonic cancer: prolonged survival of 16 years without adjuvant therapy].

    PubMed

    Grothe, D; Kasperk, R

    2004-10-01

    Long-term survival in malignant disease is often linked to intensified therapeutic interventions. We report the case of a colonic cancer in a 78 years old female patient, who underwent her first operation in 1987 for a symptomatic T4 carcinoma. Since then, the patient has always denied any form of follow-up examination and adjuvant therapy. Recently, she has undergone her fourth operation, which for the first time demonstrated peritoneal carcinosis, and is still in very good health.Clinical experience shows that in some cases standard therapies may unexpectedly produce extremely long survival times. This has to be kept in mind when the value of prognostic markers is discussed and limits the validity of survival data in the context of small scale studies dealing with especially extended therapeutic protocols.

  6. Neoadjuvant or adjuvant therapy for resectable gastric cancer? A practice guideline

    PubMed Central

    Earle, Craig C.; Maroun, Jean; Zuraw, Lisa

    2002-01-01

    Objective To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer (T1–4, N1–2, M0). Options Neoadjuvant or adjuvant treatments compared with “curative” surgery alone. Outcomes Overall survival, disease-free survival, and adverse effects. Evidence The MEDLINE, CANCERLIT and Cochrane Library databases and relevant conference proceedings were searched to identify randomized trials. Values Evidence was selected and reviewed by one member of the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI) Gastrointestinal Cancer Disease Site Group and methodologists. A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. This report has been reviewed and approved by the Gastrointestinal Cancer Disease Site Group, comprising medical oncologists, radiation oncologists, surgeons, a pathologist and 2 community representatives. Benefits, harms and costs When compared with surgery alone, at 3 years adjuvant chemoradiotherapy has been shown to increase overall survival by 9% (50% v. 41%, p = 0.005) and to improve relapse-free survival from 31% to 48% (p = 0.001). At 5 years, it has been shown to increase overall survival by 11.6% (40% v. 28.4%) and to improve relapse-free survival from 25% to 38% (p < 0.001). Treatment has been associated with toxic deaths in 1% of patients. The most frequent adverse effects (> grade 3 [Southwest Oncology Group toxicity scale] are hematologic (54%), gastrointestinal (33%), influenza-like (9%), infectious (6%) and neurologic (4%). The radiation fields used can possibly damage the left kidney, resulting in hypertension and other renal problems. Furthermore, this therapy could increase the demand on radiation resources. Physicians and patients should understand the tradeoffs between survival benefit

  7. Positive esophageal proximal resection margin: an important prognostic factor for esophageal cancer that warrants adjuvant therapy

    PubMed Central

    Wang, Yun-Cang; Deng, Han-Yu; Wang, Wen-Ping; He, Du; Ni, Peng-Zhi; Hu, Wei-Peng; Wang, Zhi-Qiang

    2016-01-01

    Background Positive esophageal proximal resection margin (ERM+) following esophagectomy was considered as incomplete or R1 resection. The clinicopathological data and long-term prognosis of esophageal cancer (EC) patients with ERM+ after esophagectomy were still unknown. Therefore, the aim of this study was to assess the clinical significance of ERM+ and its therapeutic option. Methods From November 2008 to December 2014, 3,594 patients with histologically confirmed EC underwent radical resection in our department. Among them there were 37 patients (1.03%) who had ERM+. ERM+ was defined as carcinoma or atypical hyperplasia (severe or moderate) at the residual esophageal margin in our study. For comparison, another 74 patients with negative esophageal proximal resection margin (ERM−) were propensity-matched at a ratio of 1:2 as control group according to sex, age, tumor location and TNM staging. The relevant prognostic factors were investigated by univariate and multivariate regression analysis. Results In this large cohort of patients, the rate of ERM+ was 1.03%. The median survival time was 35.000 months in patients with ERM+, significantly worse than 68.000 months in those with ERM− (Chi-square =4.064, P=0.044). Survival in patients with esophageal residual atypical hyperplasia (severe or moderate) was similar to those with esophageal residual carcinoma. Survival rate in stage I–II was higher than that in stage III–IV (Chi-square =27.598, P=0.000) in ERM−; But there was no difference between the two subgroups of patients in ERM+. Furthermore, in those patients with ERM+, survival was better in those who having adjuvant therapy, compared to those without adjuvant therapy (Chi-square =5.480, P=0.019). And the average survival time which was improved to a well situation for ERM+ patients who have adjuvant therapy was 68.556 months which is comparable to average survival time (65.815 months) of ERM− for those patients who are at earlier stages

  8. 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

  9. Do Patients with Luminal A Breast Cancer Profit from Adjuvant Systemic Therapy? A Retrospective Multicenter Study

    PubMed Central

    Blettner, Maria; Häusler, Sebastian; Janni, Wolfgang; Kreienberg, Rolf; Stein, Roland; Stüber, Tanja; Schwentner, Lukas; Bartmann, Catharina; Wöckel, Achim

    2016-01-01

    Background Luminal A breast cancers respond well to anti-hormonal therapy (HT), are associated with a generally favorable prognosis and constitute the majority of breast cancer subtypes. HT is the mainstay of treatment of these patients, accompanied by an acceptable profile of side effects, whereas the added benefit of chemotherapy (CHT), including anthracycline and taxane-based programs, is less clear-cut and has undergone a process of critical revision. Methods In the framework of the BRENDA collective, we analyzed the benefits of CHT compared to HT in 4570 luminal A patients (pts) with primary diagnosis between 2001 and 2008. The results were adjusted by nodal status, age, tumor size and grading. Results There has been a progressive reduction in the use of CHT in luminal A patients during the last decade. Neither univariate nor multivariate analyses showed any statistically significant differences in relapse free survival (RFS) with the addition of CHT to adjuvant HT, independent of the nodal status, age, tumor size or grading. Even for patients with more than 3 affected lymph nodes, there was no significant difference (univariate: p = 0.865; HR 0.94; 95% CI: 0.46–1.93; multivariate: p = 0.812; HR 0.92; 95% CI: 0.45–1.88). Conclusions The addition of CHT to HT provides minimal or no clinical benefit at all to patients with luminal A breast cancer, independent of the RFS-risk. Consequently, risk estimation cannot be the initial step in the decisional process. These findings–that are in line with several publications–should encourage the critical evaluation of applying adjuvant CHT to patients with luminal A breast cancer. PMID:27992550

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

    SciTech Connect

    Strauss, Joshua; Hershman, Dawn L.; Buono, Donna; McBride, Russell; Clark-Garvey, Sean; Woodhouse, Shermian A.; Abrams, Julian A.

    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 combined 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.

  11. Adjuvant endocrine therapy of premenopausal women with early breast cancer: an overview.

    PubMed

    Hubalek, Michael; Brantner, Christine; Marth, Christian

    2010-04-01

    Tamoxifen is currently the standard of care for premenopausal women with hormone receptor-positive early breast cancers. However, endocrine strategies in premenopausal women include not only estrogen receptor blockade with tamoxifen but also temporary suppression of ovarian estrogen synthesis by luteinizing hormone-releasing hormone (LHRH) agonists, or permanent interruption of ovarian estrogen synthesis with oophorectomy or radiotherapy. Luteinizing hormone-releasing hormone agonists have proven to be as effective as surgical oophorectomy in adjuvant treatment of premenopausal breast cancer. The addition of LHRH agonists compared to no therapy reduces the annual odds of recurrence and death in premenopausal women aged less than 50 years with estrogen receptor-positive tumors. Luteinizing hormone-releasing hormone agonists alone or in combination with tamoxifen have shown disease-free survival rates similar to chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) and other second-generation chemotherapies. The role of aromatase inhibitors in combination with ovarian suppression is still not established, especially as a large phase III randomized study (Austrian Breast and Colorectal Cancer Study Group Trial 12) did not show superior efficacy compared with ovarian suppression plus tamoxifen in premenopausal early stage disease. Patients currently continue to receive ovarian suppression and tamoxifen. CYP2D6 status may become an important discriminator for the type of endocrine therapy for the premenopausal patient in the future.

  12. The treatment outcomes and the use of adjuvant therapies in breast cancer patients with severe co-morbidities

    PubMed Central

    Han, Jaihong; Lee, Han-Byoel; Lee, Eun-Shin; Kang, Young Joon; Kim, Yumi; Choi, Jihye; Rhu, Jiyoung; Shin, Hee-Chul; Han, Wonshik; Noh, Dong-Young

    2017-01-01

    Purpose Studies have suggested a potential role of patient’s co-morbidity in determining the survival outcomes of breast cancer. In this study, we examined the long-term oncologic outcomes in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions and analyzed the association between the co-morbidity and the use of adjuvant therapies. Methods The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. Results There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA I, II, and III, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of deaths (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA I, II and III group, respectively, p<0.001). The ASA 3 patients also showed significantly higher rate of breast cancer recurrence when compared to other groups (180 (10.0%), 80 (12.0%) and 9 (20.5%) in ASA I, II, and III, respectively, p = 0.041). Significantly fewer patients in the high co-morbidity group received adjuvant therapies (77 (4.3%), 44 (6.6%) and 8 (18.2%) in ASA I, II, and III, respectively, p<0.001). The increased recurrence of breast cancer in the high morbidity group was mostly seen in patients who did not receive adjuvant therapies. The incidence of serious adverse effect during the adjuvant therapy did not differ according to the co-morbidity conditions. Conclusions In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high

  13. 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

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

    PubMed

    Derzko, C; Elliott, S; Lam, W

    2007-12-01

    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

  15. The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive, pT1a-b pN0 Breast Cancer

    PubMed Central

    Gori, Stefania; Inno, Alessandro; Fiorio, Elena; Foglietta, Jennifer; Ferro, Antonella; Gulisano, Marcella; Pinotti, Graziella; Gubiotti, Marta; Cavazzini, Maria Giovanna; Turazza, Monica; Duranti, Simona; De Simone, Valeria; Iezzi, Laura; Bisagni, Giancarlo; Spazzapan, Simon; Cavanna, Luigi; Saggia, Chiara; Bria, Emilio; Cretella, Elisabetta; Vici, Patrizia; Santini, Daniele; Fabi, Alessandra; Garrone, Ornella; Frassoldati, Antonio; Amaducci, Laura; Saracchini, Silvana; Evangelisti, Lucia; Barni, Sandro; Gamucci, Teresa; Mentuccia, Lucia; Laudadio, Lucio; Zoboli, Alessandra; Marchetti, Fabiana; Bogina, Giuseppe; Lunardi, Gianluigi; Boni, Luca

    2015-01-01

    Background The management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients. Methods Data of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres. Analysis of contingency tables and multivariate generalized logit models were used to investigate the association between the baseline clinical and biological features and the treatment strategy adopted. Results Among 303 enrolled patients, 204 received adjuvant systemic therapy with trastuzumab, 65 adjuvant systemic therapy without trastuzumab and 34 did not receive adjuvant systemic therapy. At the multivariate analysis age, tumor size, proliferation index and hormone receptor status were significantly associated with the treatment choice. Five-year disease-free survival (DFS) probability was 95%, 94.3% and 69.6% for patients treated with adjuvant systemic therapy and trastuzumab, with adjuvant systemic therapy without trastuzumab and for patients who did not receive adjuvant systemic therapy, respectively (p<0.001). Conclusions The majority of patients (66%) with pT1a-b pN0 HER2-positive breast cancer enrolled in this retrospective study received adjuvant systemic therapy with trastuzumab, whereas only 11% patients did not receive any adjuvant systemic therapy. The choice of treatment type seems to be mainly influenced by tumor size, proliferation index, hormone receptor status and age. The 5-year DFS probability was significantly higher for patients receiving adjuvant systemic therapy with trastuzumab compared with patients not receiving adjuvant

  16. A Prospective Cohort Study on Cardiotoxicity of Adjuvant Trastuzumab Therapy in Breast Cancer Patients

    PubMed Central

    Matos, Erika; Jug, Borut; Blagus, Rok; Zakotnik, Branko

    2016-01-01

    Background Cardiotoxicity is an important side effect of trastuzumab therapy and cardiac surveillance is recommended. Objectives The aim of our study was to prospectively assess baseline patients' characteristics, level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic parameters as possible predictors of trastuzumab-related cardiac dysfunction. Methods In a prospective cohort study, clinical, echocardiographic and neurohumoral assessment was performed at baseline, after 4, 8 and 12 months in breast cancer patients undergoing post-anthracycline (3-4 cycles) adjuvant therapy with trastuzumab. Trastuzumab-related cardiac dysfunction was defined as a decline of ≥ 10% in left ventricular ejection fraction (LVEF). Results 92 patients (mean age, 53.6 ± 9.0 years) were included. Patients who developed trastuzumab-related LVEF decline ≥ 10% (20.6%) during treatment had significantly higher baseline LVEF (70.7 ± 4.4%) than those without (64.8 ± 5.5%) (p = 0.0035). All other measured baseline parameters (age, body mass index, arterial hypertension, level of NT-proBNP and other echocardiographic parameters) were not identified as significant. Conclusions Our findings suggest that baseline patient' characteristics, level of NT-proBNP and echocardiographic parameters, as long as they are within normal range, are not a reliable tool to predict early trastuzumab-related cardiac dysfunction in patients undergoing post-low dose anthracycline adjuvant trastuzumab therapy. A LVEF decline in patients with high-normal baseline level although statistically significant is not clinically relevant. PMID:27305108

  17. Racial/ethnic differences in initiation of adjuvant hormonal therapy among women with hormone receptor-positive breast cancer.

    PubMed

    Livaudais, Jennifer C; Hershman, Dawn L; Habel, Laurel; Kushi, Lawrence; Gomez, Scarlett Lin; Li, Christopher I; Neugut, Alfred I; Fehrenbacher, Louis; Thompson, Beti; Coronado, Gloria D

    2012-01-01

    Mortality after breast cancer diagnosis is known to vary by race/ethnicity even after adjustment for differences in tumor characteristics. As adjuvant hormonal therapy decreases risk of recurrence and increases overall survival among women with hormone receptor-positive tumors, treatment disparities may play a role. We explored racial/ethnic differences in initiation of adjuvant hormonal therapy, defined as two or more prescriptions for tamoxifen or aromatase inhibitor filled within the first year after diagnosis of hormone receptor-positive localized or regional-stage breast cancer. The sample included women diagnosed with breast cancer enrolled in Kaiser Permanente Northern California (KPNC). Odds ratios [OR] and 95% confidence intervals [CI] compared initiation by race/ethnicity (Hispanic, African American, Chinese, Japanese, Filipino, and South Asian vs. non-Hispanic White [NHW]) using logistic regression. Covariates included age and year of diagnosis, area-level socioeconomic status, co-morbidities, tumor stage, histology, grade, breast cancer surgery, radiation and chemotherapy use. Our sample included 13,753 women aged 20-79 years, diagnosed between 1996 and 2007, and 70% initiated adjuvant hormonal therapy. In multivariable analysis, Hispanic and Chinese women were less likely than NHW women to initiate adjuvant hormonal therapy ([OR] = 0.82; [CI] 0.71-0.96 and [OR] = 0.78; [CI] 0.63-0.98, respectively). Within an equal access, insured population, lower levels of initiation of adjuvant hormonal therapy were found for Hispanic and Chinese women. Findings need to be confirmed in other insured populations and the reasons for under-initiation among these groups need to be explored.

  18. Anti-metastatic functions of type 1 interferons: Foundation for the adjuvant therapy of cancer.

    PubMed

    Ortiz, Angélica; Fuchs, Serge Y

    2017-01-01

    The anti-tumorigenic effects that type 1 interferons (IFN1) elicited in the in vitro studies prompted consideration of IFN1 as a potent candidate for clinical treatment. Though not all patients responded to IFN1, clinical trials have shown that patients with high risk melanoma, a highly refractory solid malignancy, benefit greatly from intermediate IFN1 treatment in regards to relapse-free and distant-metastasis-free survival. The mechanisms by which IFN1 treatment at early stages of disease suppress tumor recurrence or metastatic incidence are not fully understood. Intracellular IFN1 signaling is known to affect cell differentiation, proliferation, and apoptosis. Moreover, recent studies have revealed specific IFN1-regulated genes that may contribute to IFN1-mediated suppression of cancer progression and metastasis. In concert, expression of these different IFN1 stimulated genes may impede numerous mechanisms that mediate metastatic process. Though, IFN1 treatment is still utilized as part of standard care for metastatic melanoma (alone or in combination with other therapies), cancers find the ways to develop insensitivity to IFN1 treatment allowing for unconstrained disease progression. To determine how and when IFN1 treatment would be most efficacious during disease progression, we must understand how IFN1 signaling affects different metastasis steps. Here, we specifically focus on the anti-metastatic role of endogenous IFN1 and parameters that may help to use pharmaceutical IFN1 in the adjuvant treatment to prevent cancer recurrence and metastatic disease.

  19. Frailty and Adherence to Adjuvant Hormonal Therapy in Older Women With Breast Cancer: CALGB Protocol 369901

    PubMed Central

    Sheppard, Vanessa B.; Faul, Leigh Anne; Luta, George; Clapp, Jonathan D.; Yung, Rachel L.; Wang, Judy Huei-yu; Kimmick, Gretchen; Isaacs, Claudine; Tallarico, Michelle; Barry, William T.; Pitcher, Brandelyn N.; Hudis, Clifford; Winer, Eric P.; Cohen, Harvey J.; Muss, Hyman B.; Hurria, Arti; Mandelblatt, Jeanne S.

    2014-01-01

    Purpose Most patients with breast cancer age ≥ 65 years (ie, older patients) are eligible for adjuvant hormonal therapy, but use is not universal. We examined the influence of frailty on hormonal therapy noninitiation and discontinuation. Patients and Methods A prospective cohort of 1,288 older women diagnosed with invasive, nonmetastatic breast cancer recruited from 78 sites from 2004 to 2011 were included (1,062 had estrogen receptor–positive tumors). Interviews were conducted at baseline, 6 months, and annually for up to 7 years to collect sociodemographic, health care, and psychosocial data. Hormonal initiation was defined from records and discontinuation from self-report. Baseline frailty was measured using a previously validated 35-item scale and grouped as prefrail or frail versus robust. Logistic regression and proportional hazards models were used to assess factors associated with noninitiation and discontinuation, respectively. Results Most women (76.4%) were robust. Noninitiation of hormonal therapy was low (14%), but in prefrail or frail (v robust) women the odds of noninitiation were 1.63 times as high (95% CI, 1.11 to 2.40; P = .013) after covariate adjustment. Nonwhites (v whites) had higher odds of noninitiation (odds ratio, 1.71; 95% CI, 1.04 to 2.80; P = .033) after covariate adjustment. Among initiators, the 5-year continuation probability was 48.5%. After adjustment, the risk of discontinuation was higher with increasing age (P = .005) and lower for stage ≥ IIB (v stage I) disease (P = .003). Conclusion Frailty is associated with noninitiation of hormonal therapy, but it does not seem to be a major predictor of early discontinuation in older patients. PMID:24934786

  20. Adjuvant Radiation Therapy Alone for HPV Related Oropharyngeal Cancers with High Risk Features

    PubMed Central

    Su, William; Liu, Jerry; Miles, Brett A.; Genden, Eric M.; Misiukiewicz, Krzysztof J.; Posner, Marshall; Gupta, Vishal; Bakst, Richard L.

    2016-01-01

    Background Current standard of care for oropharyngeal cancers with positive surgical margins and/or extracapsular extension is adjuvant chemoradiotherapy. It is unknown whether HPV+ oropharyngeal cancer benefits from this treatment intensification. Objective To investigate the outcomes of HPV+ patients treated with adjuvant radiotherapy alone when chemoradiotherapy was indicated based on high risk pathological features. They were compared with high risk HPV+ patients treated with adjuvant chemoradiotherapy. Methods All high risk HPV+ oropharyngeal cancer patients (9) who received radiotherapy alone were identified. We also identified 17 patients who received chemoradiotherapy as a comparison group. Median follow up time was 37.3 months. Results No local failures developed in adjuvant radiotherapy group. There was 1 distant recurrence in this cohort and 3 in CRT cohort. Regarding toxicity, 8 (47.1%) chemoradiotherapy patients had >10 lb. weight loss (p = 0.013), despite 75% of them having a percutaneous endoscopic gastrostomy tube placed. No individuals in radiotherapy group experienced a >10 lb. weight loss and none required a gastrostomy tube. Conclusions This series provides preliminary evidence suggesting that the omission of concurrent chemotherapy to adjuvant radiotherapy may offer comparative local control rates with a lower toxicity profile in the setting of HPV+ patients with traditional high risk features. PMID:27930732

  1. Cutaneous adverse effects of hormonal adjuvant therapy for breast cancer: a case of localised urticarial vasculitis following anastrozole therapy and a review of the literature.

    PubMed

    Bock, Vanessa L; Friedlander, Michael; Waring, Dale; Kossard, Steven; Wood, Glenda K

    2014-11-01

    Hormonal therapy with either tamoxifen or aromatase inhibitors is commonly used to treat women with breast cancer in both the adjuvant and recurrent disease setting. Cutaneous adverse reactions to these drugs have been rarely reported in the literature. We report an unusual case of urticarial vasculitis following the aromatase inhibitor anastrozole that localised to the unilateral trunk and mastectomy scar, and review the literature on the cutaneous adverse effects of hormonal therapy for breast cancer.

  2. 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.

  3. Survival in gastric cancer in relation to postoperative adjuvant therapy and determinants

    PubMed Central

    Ozden, Sevgi; Ozgen, Zerrin; Ozyurt, Hazan; Gemici, Cengiz; Yaprak, Gokhan; Tepetam, Huseyin; Mayadagli, Alpaslan

    2015-01-01

    AIM: To evaluate survival data in patients with gastric cancer in relation to postoperative adjuvant therapy and survival determinants METHODS: A total of 201 patients (mean ± SD age: 56.0 ± 11.9 years, 69.7% were males) with gastric carcinoma who were operated and followed up at Lutfi Kirdar Kartal Training and Research Hospital between 1998 and 2010 were included in this retrospective study. Follow up was evaluated divided into two consecutive periods (before 2008 and 2008-2010, respectively) based on introduction of 3-D conformal technique in radiotherapy at our clinic in 2008. Data on patient demographics, clinical and histopathological characteristics of gastric carcinoma and the type of treatment applied after surgery [postoperative adjuvant treatment protocols including chemoradiotherapy (CRT) and chemotherapy (CT), supportive therapy or follow up without any treatment] were recorded. The median duration and determinants of local recurrence free (LRF) survival, distant metastasis free (DMF) survival and overall survival were evaluated in the overall population as well as with respect to follow up years [1998-2008 (n = 127) vs 2008-2010 (n = 74)]. RESULTS: Median duration for LRF survival, DMF survival and overall survival were 31.9, 24.1 and 31.9 mo, respectively in patients with postoperative adjuvant CRT. No significant difference was noted in median duration for LRF survival, DMF survival and overall survival with respect to treatment protocols in the overall population and also with respect to followed up periods. In the overall population, CT protocols FUFA [5-fluorouracil (400 mg/m2) and leucovorin-folinic acid (FA, 20 mg/m2)] (29.9 mo) and UFT® + Antrex® [a fixed combination of the oral FU prodrug tegafur (flouroprymidine, FT, 300 mg/m2 per day) with FA (Antrex®), 15 mg tablet, two times a day] (42.5 mo) was significantly associated with longer LRF survival times than other CT protocols (P = 0.036), while no difference was noted between CT

  4. Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy.

    PubMed

    De Sanctis, Vitaliana; Agolli, Linda; Visco, Vincenzo; Monaco, Flavia; Muni, Roberta; Spagnoli, Alessandra; Campanella, Barbara; Valeriani, Maurizio; Minniti, Giuseppe; Osti, Mattia F; Amanti, Claudio; Pellegrini, Patrizia; Brunetti, Serena; Costantini, Anna; Alfò, Marco; Torrisi, Maria Rosaria; Marchetti, Paolo; Enrici, Riccardo Maurizi

    2014-01-01

    We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

  5. Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity.

    PubMed

    Chlebowski, R T; Haque, R; Hedlin, H; Col, N; Paskett, E; Manson, J E; Kubo, J T; Johnson, K C; Wactawski-Wende, J; Pan, K; Anderson, G

    2015-12-01

    In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.

  6. 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.

  7. Elapsed time from breast cancer detection to first adjuvant therapy in a Canadian province, 1999–2000

    PubMed Central

    Rayson, Daniel; Chiasson, Darrell; Dewar, Ron

    2004-01-01

    Background A number of studies have examined time intervals between care steps in breast cancer diagnosis and treatment. The objective of this study was to document the elapsed time from first clinical or mammographic detection of breast abnormality to initiation of first adjuvant therapy in women with invasive breast cancer in Nova Scotia and to examine the effect of age, disease stage and place of residence on these intervals. Methods All dates were abstracted from patient charts and the Oncology Patient Information System. Eligible women were those with invasive breast cancer detected by Sept. 1, 1999, who were referred to 1 of 2 provincial cancer treatment centres by Sept. 1, 2000. All time intervals were calculated in days, and only patients experiencing both care events defining an interval were included in the analysis of time to event for that interval. We used proportional hazards regression analysis to evaluate the influence of patient age, disease stage and place of residence on times between care events. Results A total of 776 new diagnoses of breast cancer were reported to the Nova Scotia Cancer Registry over the study period. Of the 776, 467 met the inclusion criteria, and 364 patients were eligible for analysis. The overall median time from clinical or mammographic detection of breast cancer to initiation of first adjuvant therapy was 91 days (interquartile range 72–123 days). Disease stage was the strongest predictor of elapsed time: the median interval from disease detection to initiation of first adjuvant therapy for patients with stage I disease was 118 days, as compared with 85 days for those with stage II disease and 75 days for those with stage III disease (adjusted hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.6–2.8). Patients aged 70 years or more at diagnosis experienced longer elapsed times (median interval 98 days) than did younger patients (93 days for those aged 50–69 years and 82 days for those aged 49 years or less

  8. Adjuvant chemotherapy and HER-2-directed therapy for early-stage breast cancer in the elderly

    PubMed Central

    Sun, J; Chia, S

    2017-01-01

    There is a lack of sufficient evidence-based data defining the optimal adjuvant systemic therapies in older women. Recommendations are mainly based on retrospective studies, subgroup analyses within larger randomised trials and expert opinion. Treatment decisions should consider the functional fitness of the patient, co-morbidities, in addition to chronological age with the aim to balance risks and potential benefits from treatment(s). In this review, we discuss assessment tools to aid clinicians to select elderly patients who are ‘fit' for chemotherapy, and review the literature on the use of chemotherapy and of the anti-HER 2 antibody trastuzumab in this population. We will also review two commonly used prediction models to assess their accuracy in predicting survival outcomes in elderly patients. Ongoing clinical trials specifically focusing on older patients may help to clarify the absolute benefits and risks of adjuvant systemic therapy in this age group. PMID:27875517

  9. Limited Advantages of Intensity-Modulated Radiotherapy Over 3D Conformal Radiation Therapy in the Adjuvant Management of Gastric Cancer

    SciTech Connect

    Alani, Shlomo; Soyfer, Viacheslav; Strauss, Natan; Schifter, Dan; Corn, Benjamin W.

    2009-06-01

    Purpose: Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. Methods and Materials: Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 deg., 53 deg., 107 deg., 158 deg., 204 deg., 255 deg., and 306 deg.. Beam arrangement 2 consisted of gantry angles of 30 deg., 90 deg., 315 deg., and 345 deg.; a gantry angle of 320 deg./couch, 30 deg.; and a gantry angle of 35{sup o}/couch, 312{sup o}. Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. Results: Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. Conclusions: IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

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

    PubMed

    Lesiuk, Teresa

    2016-08-09

    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.

  11. 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

  12. A hard pill to swallow: a qualitative study of women's experiences of adjuvant endocrine therapy for breast cancer

    PubMed Central

    Harrow, Alison; Dryden, Ruth; McCowan, Colin; Radley, Andrew; Parsons, Mark; Thompson, Alastair M; Wells, Mary

    2014-01-01

    Objective To explore women's experiences of taking adjuvant endocrine therapy as a treatment for breast cancer and how their beliefs about the purpose of the medication, side effects experienced and interactions with health professionals might influence adherence. Design Qualitative study using semistructured, one-to-one interviews. Setting 2 hospitals from a single health board in Scotland. Participants 30 women who had been prescribed tamoxifen or aromatase inhibitors (anastrozole or letrozole) and had been taking this medication for 1–5 years. Results Women clearly wished to take their adjuvant endocrine therapy medication as prescribed, believing that it offered them protection against breast cancer recurrence. However, some women missed tablets and did not recognise that this could reduce the efficacy of the treatment. Women did not perceive that healthcare professionals were routinely or systematically monitoring their adherence. Side effects were common and impacted greatly on the women’s quality of life but did not always cause women to stop taking their medication, or to seek advice about reducing the side effects they experienced. Few were offered the opportunity to discuss the impact of side effects or the potential options available. Conclusions Although most women in this study took adjuvant endocrine therapy as prescribed, many endured a range of side effects, often without seeking help. Advice, support and monitoring for adherence are not routinely offered in conventional follow-up settings. Women deserve more opportunity to discuss the pros, cons and impact of long-term adjuvant endocrine therapy. New service models are needed to support adherence, enhance quality of life and ultimately improve survival. These should ideally be community based, in order to promote self-management in the longer term. PMID:24928595

  13. Desmoplasia Influenced Recurrence of Disease and Mortality in Stage III Colorectal Cancer within Five Years after Surgery and Adjuvant Therapy

    PubMed Central

    Zippi, Maddalena; De Toma, Giorgio; Minervini, Giovanni; Cassieri, Claudio; Pica, Roberta; Colarusso, Diodoro; Stock, Simon; Crispino, Pietro

    2017-01-01

    Background/Aims: In patients with colon cancer who undergo resection for potential cure, 40–60% have advanced locoregional disease (stage III). Those who are suitable for adjuvant treatment had a definite disease-free-survival benefit. The aim of the present study was to demonstrate whether the presence of desmoplasia influenced the mortality rate of stage III colorectal cancer (CRC) within 5 years from the surgery and adjuvant therapy. Patients and Methods: Sixty-five patients with stage III CRC underwent resection and adjuvant therapy. Qualitative categorization of desmoplasia was obtained using Ueno's stromal CRC classification. Desmoplasia was related to mortality using Spearman correlation and stratified with other histological variables (inflammation, grading) that concurred to the major determinant of malignancy (venous invasion and lymph nodes) using the Chi-square test. Result: The 5-year survival rate was 65% and the relapse rate was 37%. The mortality rate in patients with immature desmoplasia was 86%, 27% in intermediate desmoplasia, and 0% in mature desmoplasia (Spearman correlation coefficient: −0.572, P = 0.05). Conclusion: Immature desmoplasia appears to be associated with disease recurrence and mortality in stage III CRC patients. PMID:28139499

  14. Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breast cancer patients.

    PubMed

    Eggemann, Holm; Ignatov, Atanas; Smith, Bobbie J; Altmann, Udo; von Minckwitz, Gunter; Röhl, Freidrich W; Jahn, Mark; Costa, Serban-Dan

    2013-01-01

    To determine the impact of adjuvant treatment with tamoxifen and aromatase inhibitors (AI) on the survival of men with breast cancer. We analyzed 257 male patients with hormone-receptor-positive breast cancer from numerous German population-based cancer registries treated with tamoxifen (N = 207) or aromatase inhibitors (N = 50). The median follow-up was 42.2 (range 2-115) months. Median age at diagnosis was 68 (range 36-91) years. Thirty-seven (17.9 %) patients treated with tamoxifen and 16 (32.0 %) patients treated with AI died (log rank p = 0.007). After the adjustment for the patient's age, tumor size, node status, and tumor grading, the AI treatment was linked to a 1.5-fold increase in risk of mortality compared to tamoxifen (HR 1.55; 95 % CI: 1.13-2.13; p = 0.007). The overall survival in male breast cancer was significantly better after adjuvant treatment with tamoxifen compared to an aromatase inhibitor. Tamoxifen should be considered as the treatment of choice for hormone-receptor-positive male breast cancer.

  15. Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial: overview of efficacy, safety, and cost-effectiveness.

    PubMed

    Twelves, Chris J

    2006-11-01

    The X-ACT (Xeloda in Adjuvant Colon Cancer Therapy) trial compared the efficacy and safety of the oral fluoropyrimidine capecitabine with bolus 5-fluorouracil (5-FU)/leucovorin (LV; Mayo Clinic regimen) as adjuvant therapy for stage III colon cancer. A total of 1987 patients were enrolled at 164 centers worldwide. Disease-free survival (primary study endpoint) in the capecitabine arm was at least equivalent to that in the 5-FU/LV arm; the upper limit of the hazard ratio was significantly (P < 0.001) below the predefined margins for noninferiority. Capecitabine was also associated with significantly fewer fluoropyrimidine-related grade 3/4 adverse events (AEs; P < 0.001) and fewer AE-related hospital admissions/days than 5-FU/LV. Pharmacoeconomic analyses performed in several countries show that the savings in direct costs (drug administration and AE-related costs) associated with capecitabine versus 5-FU/LV offset the acquisition costs of the drug. Furthermore, capecitabine reduces patient travel time and costs, making it a "dominant" strategy (ie, less costly and more effective) in the adjuvant setting. In conclusion, efficacy, safety, convenience, and cost findings from the X-ACT trial show that capecitabine offers at least equivalent clinical benefit compared with bolus 5-FU/LV and can replace intravenous 5-FU/LV in the adjuvant treatment of stage III colon cancer. The X-ACT trial has not only helped to better define the role of capecitabine but has also broadened the options available to patients with early-stage disease to include a uniquely effective oral outpatient treatment.

  16. Second non-breast primary cancer following adjuvant therapy for early breast cancer: A report from the International Breast Cancer Study Group

    PubMed Central

    Gianni, Lorenzo; Gelber, Shari; Ravaioli, Alberto; Price, Karen N.; Panzini, Ilaria; Fantini, Manuela; Castiglione-Gertsch, Monica; Pagani, Olivia; Simoncini, Edda; Gelber, Richard D.; Coates, Alan S.; Goldhirsch, Aron

    2009-01-01

    The incidence of second non-breast primary cancer following adjuvant treatment was evaluated using data from patients enrolled from 1978 to 1999 in four International Breast Cancer Study Group (IBCSG) trials. The occurrence of these tumours as sites of first failure was assessed separately for two treatment comparisons: toremifene versus tamoxifen for five years in 1035 patients in IBCSG Trials 12-93 and 14-93 with a median follow-up of eight years and endocrine therapy (toremifene or tamoxifen) versus chemoendocrine therapy (CMF or AC plus toremifene or tamoxifen) in 1731 patients from IBCSG Trials III, VII and 12-93, with a combined median follow-up of 14 years. No significant differences in second non-breast primary tumours were observed in either comparison. In particular the incidences of second primary uterine tumours with toremifene and tamoxifen were similar and no significant increase of secondary leukaemias was observed with chemoendocrine therapy compared with endocrine therapy. PMID:19062268

  17. 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

  18. 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.

  19. Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer

    SciTech Connect

    Andersson, M.; Storm, H.H.; Mouridsen, H.T. )

    1991-07-17

    The incidence of new primary cancers was evaluated in 3538 postmenopausal patients who had received surgical treatment for primary breast cancer. Of these patients, 1828 with a low risk of recurrence received no further treatment. High-risk patients were randomly assigned to one of two groups. The first group (n = 846) received postoperative radiotherapy, while the second group (n = 864) received radiotherapy plus tamoxifen at a dose of 30 mg given daily for 48 weeks. The median observation time was 7.9 years. In comparison with the number of new cancers in the general population, the number of new cancers in the three groups was elevated mostly due to a high number of cancers of the contralateral breast and of colorectal cancers in the high-risk groups. The cumulative risk of nonlymphatic leukemia was increased among patients who received postoperative radiotherapy (P = .04). Cancer incidence in the high-risk tamoxifen-treated group relative to that in the high-risk group not treated with tamoxifen was not significant (1.3). No protective effect of tamoxifen on the opposite breast was seen (rate ratio for breast cancer = 1.1), but a tendency to an elevated risk of endometrial cancer was observed (rate ratio = 3.3; 95% confidence interval = 0.6-32.4). Continued and careful follow-up of women treated with tamoxifen is necessary to clarify the potential cancer-suppressive or cancer-promoting effects of this drug.

  20. Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

    SciTech Connect

    Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.; Simeone, Diane; Greenson, Joel K.; Francis, Isaac R.; Hampton, Janet; Colletti, Lisa; Chang, Alfred E.; Lawrence, Theodore S.; Zalupski, Mark M.

    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} orally 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.

  1. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27767031

  3. Influence of definitive radiation therapy for primary breast cancer on ability to deliver adjuvant chemotherapy

    SciTech Connect

    Lippman, M.E.; Edwards, B.K.; Findlay, P.; Danforth, D.W. Jr.; MacDonald, H.; D'Angelo, T.; Gorrell, C.

    1986-01-01

    Primary radiotherapy as a means of managing stage I and II breast cancer is receiving increasing attention. In a prospectively randomized trial comparing modified radical mastectomy to lumpectomy followed by definitive radiotherapy, we evaluated whether radiotherapy has a deleterious effect on the ability to administer adjuvant doxorubicin and cyclophosphamide to patients with histologically positive axillary lymph nodes. All patients were treated with an identical regimen, and doses were escalated to the same degree until myelosuppression occurred. There were no significant differences in the amount of chemotherapy administered to either treatment group. Patients in both groups received approximately 100% of the predicted dose of doxorubicin and approximately 117% of the predicted dose of cyclophosphamide. At present, we have no evidence that there are differences in recurrence rates as a function of the quantity of drug received, although longer follow-up is required.

  4. Identification of high-risk factors as indicators for adjuvant therapy in stage II colon cancer patients treated at a single institution

    PubMed Central

    YAMAGUCHI, KEIZO; OGATA, YUTAKA; AKAGI, YOSHITO; SHIROUZU, KAZUO

    2013-01-01

    Although post-operative adjuvant chemotherapy (ACT) is only recommended for patients with stage II colon cancer who are at a high risk of recurrence, the definition of high risk remains unclear. The present study aimed to identify the risk factors for recurrence, which may also be indicators for adjuvant therapy, using a retrospective analysis of clinicopathological data obtained from stage II colon cancer patients who had undergone a curative resection. The present study also investigated the effects of ACT in patients who displayed the risk factors for recurrence. Univariate and multivariate analyses of the data collected from 377 stage II colon cancer patients, treated at Kurume University Hospital (Fukuoka, Japan) between 1982 and 2005, was conducted in order to determine and compare the risk factors for recurrence between the 163 patients who had undergone adjuvant therapy and the 214 patients who had not undergone adjuvant therapy. The risk factors for recurrence in patients who had not undergone adjuvant therapy were a serum carcinoembryonic antigen (CEA) level that was twice the cut-off value and pre-operative bowel obstruction. Adjuvant therapy provided no benefit to patients who presented with neither risk factor, but significantly decreased the recurrence rate in patients presenting with one or both risk factors. Based on these findings, serum CEA levels of twice the cut-off value and pre-operative bowel obstruction were proposed as indicators in the assessment for adjuvant chemotherapy following a curative resection for stage II colon cancer. These results warrant further clinical study of ACT in patients with one or both risk factors. PMID:24137386

  5. Non-initiation of adjuvant hormonal therapy in women with hormone receptor-positive breast cancer: The Breast Cancer Quality of Care Study (BQUAL).

    PubMed

    Neugut, Alfred I; Hillyer, Grace Clarke; Kushi, Lawrence H; Lamerato, Lois; Leoce, Nicole; Nathanson, S David; Ambrosone, Christine B; Bovbjerg, Dana H; Mandelblatt, Jeanne S; Magai, Carol; Tsai, Wei-Yann; Jacobson, Judith S; Hershman, Dawn L

    2012-07-01

    Adjuvant hormonal therapy for non-metastatic hormone receptor (HR)-positive breast cancer decreases risk of breast cancer recurrence and increases survival. However, some women do not initiate this life-saving treatment. We used a prospective cohort design to investigate factors related to non-initiation of hormonal therapy among women with newly diagnosed, non-metastatic HR-positive breast cancer recruited from three U.S. sites. Serial interviews were conducted at baseline and during treatment to examine sociodemographic factors, tumor characteristics, and treatment decision-making factors. Multivariate modeling assessed associations between variables of interest and hormonal therapy initiation. Of 1,050 breast cancer patients recruited, 725 (69%) had HR-positive breast cancer, of whom 87 (12.0%) based on self-report and 122 (16.8%) based on medical record/pharmacy fill rates did not initiate hormonal therapy. In a multivariable analysis, non-initiation of hormonal therapy, defined by medical record/pharmacy, was associated with having greater negative beliefs about efficacy of treatment (OR 1.42, 95% CI 1.18-1.70). Non-initiation was less likely in those who found the quality of patient/physician communication to be higher (OR 0.96, 95% CI 0.93-0.99), the hormonal therapy treatment decision an easy one to make (OR 0.45, 95% CI 0.23-0.90) or neither easy nor difficult (OR 0.34, 95% CI 0.20-0.58); and had more positive beliefs about hormonal therapy efficacy (OR 0.40, 95% CI 0.34-0.62). Factors influencing non-initiation of adjuvant hormonal therapy are complex and influenced by patient beliefs regarding treatment efficacy and side effects. Educational interventions to women about the benefits of hormonal therapy may decrease negative beliefs and increase hormone therapy initiation.

  6. ω3 Polyunsaturated Fatty Acids as Immunomodulators in Colorectal Cancer: New Potential Role in Adjuvant Therapies

    PubMed Central

    Miccadei, Stefania; Masella, Roberta; Mileo, Anna Maria; Gessani, Sandra

    2016-01-01

    Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabolic pathways. Colorectal cancer (CRC) is one of the leading causes of death worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug resistance and/or off-target toxicity limit their efficacy. Dietary ω3 polyunsaturated fatty acids (PUFA) have been gaining great interest in recent years as possible anti-inflammatory and anticancer agents, especially in areas such as the large bowel, where the pro-inflammatory context promotes virtually all steps of colon carcinogenesis. Growing epidemiological, experimental, and clinical evidence suggests that ω3 PUFA may play a role in several stages of CRC management exhibiting antineoplastic activity against human CRC cells, improving the efficacy of radiation and chemotherapy, ameliorating cancer-associated secondary complications, and preventing CRC recurrence. These effects are most likely related to the immunomodulatory activities of ω3 PUFA that are able to influence several aspects of the inflammatory process ranging from inflammasome activation, leukocyte recruitment, production of immune mediators to differentiation, and activation of immune cells. In this review, we will focus on the potential use of ω3 PUFA as adjuvant agents together with chemo/radiotherapy, highlighting the immunomodulatory effects most likely responsible for their beneficial effects in different stages of CRC management. PMID:27895640

  7. Adjuvant pamidronate therapy prevents the development of bone metastases in breast cancer patients with four or more positive nodes.

    PubMed

    Kokufu, Ikuo; Kohno, Norio; Yamamoto, Masayuki; Takao, Shintaro

    2010-03-01

    Bisphosphonates are strongly efficacious in inhibiting osteoclast bone resorption and have beneficial effects on bone metastasis. Due to their mechanism of action, bisphosphonates are expected to prevent the development of bone metastases in breast cancer patients. Pamidronate is a potent inhibitor of osteoclast activity. We examined whether pamidronate was able to prevent the development of bone metastases in breast cancer patients at high risk for bone metastasis. Between 1997 and 2001, 90 patients with primary breast cancer with ≥4 positive nodes were assigned to receive 45 mg pamidronate 4 times every 2 weeks (33 patients) or standard follow-up (57 patients) based on patient self-preference. Patients underwent surgery and adjuvant therapy. The characteristics of the patients in the two groups were well-balanced. The median follow-up period was 5 years. Bone metastases were detected in 12.1% of patients in the pamidronate group and 40.4% in the control group (p=0.005). Distant metastases (36.4 vs. 56.1%, p=0.071) and non-osseous metastases (33.3 vs. 52.6%, p=0.077) were detected at a lower frequency in the pamidronate group. Thus, the rate of bone metastasis-free survival was significantly higher in the pamidronate group (85.9 vs. 64.0% at 5 years, p=0.023). Overall and disease-free survival rates did not differ between the two groups. In the pamidronate group, the incidence of bone metastases was significantly reduced and bone metastasis-free survival was significantly higher. Adjuvant pamidronate therapy therefore prevents the development of bone metastases in breast cancer patients with ≥4 positive nodes.

  8. Drug switch because of treatment-related adverse side effects in endocrine adjuvant breast cancer therapy: how often and how often does it work?

    PubMed

    Güth, Uwe; Myrick, Mary Elizabeth; Schötzau, Andreas; Kilic, Nerbil; Schmid, Seraina Margaretha

    2011-10-01

    Therapy-related adverse side effects are a main reason for non-persistence to adjuvant endocrine breast cancer therapy. This study reports frequency of drug-related adverse side effects that were so severe that a modification of the therapy was necessary. We evaluated how many patients discontinued adjuvant endocrine therapy because of these side effects (non-persistence). Last, we analyzed how often a drug switch was undertaken for this reason and how often this measure led to the patient successfully continuing their endocrine therapy. Data concerning all postmenopausal breast cancer patients (≤ 80 years), who initiated endocrine adjuvant therapy between 1998 and 2008 in a Swiss breast center (n = 400), were analyzed. Out of these 400 women, 37 (9.3%) were defined as being non-persistent to the therapy; out of these, 24 (64.9%) because of therapy-related side effects. About 78 patients (19.5%) suffered from severe therapy-related side effects that made a modification of therapy necessary. Out of these 78 cases, 14 patients (17.9%) stopped the therapy without attempting a drug switch (non-persistence). In 64 patients (82.1%; 16% of all women who started endocrine therapy), a drug switch was undertaken. Out of these 64 cases, in 52 cases (81.3%) endocrine therapy was completed after therapy modification. Patients who reported one major adverse effect were more likely to continue the endocrine therapy after a drug switch (P = 0.048) compared with those who suffered from at least two different side effects. In 10 of the 64 cases (15.6%), modification of the therapy was not successful and the patients stopped the treatment prematurely (non-persistence) because of ongoing side effects. In cases when therapy-related side effects occur, a drug switch is a promising step to further improve persistence and, by doing so, the outcome of breast cancer patients.

  9. Racial differences in receipt of adjuvant hormonal therapy among Medicaid enrollees in South Carolina diagnosed with breast cancer.

    PubMed

    Felder, Tisha M; Do, D Phuong; Lu, Z Kevin; Lal, Lincy S; Heiney, Sue P; Bennett, Charles L

    2016-05-01

    Several factors contribute to the pervasive Black-White disparity in breast cancer mortality in the U.S., such as tumor biology, access to care, and treatments received including adjuvant hormonal therapy (AHT), which significantly improves survival for hormone receptor-positive breast cancers (HR+). We analyzed South Carolina Central Cancer Registry-Medicaid linked data to determine if, in an equal access health care system, racial differences in the receipt of AHT exist. We evaluated 494 study-eligible, Black (n = 255) and White women (n = 269) who were under 65 years old and diagnosed with stages I-III, HR+ breast cancers between 2004 and 2007. Bivariate and multivariate analyses were conducted to assess receipt of ≥1 AHT prescriptions at any point in time following (ever-use) or within 12 months of (early-use) breast cancer diagnosis. Seventy-two percent of the participants were ever-users (70 % Black, 74 % White) and 68 % were early-users (65 % Black, 71 % White) of AHT. Neither ever-use (adjusted OR (AOR) = 0.75, 95 % CI 0.48-1.17) nor early-use (AOR = 0.70, 95 % CI 0.46-1.06) of AHT differed by race. However, receipt of other breast cancer-specific treatments was independently associated with ever-use and early-use of AHT [ever-use: receipt of surgery (AOR = 2.15, 95 % CI 1.35-3.44); chemotherapy (AOR = 1.97, 95 % CI 1.22-3.20); radiation (AOR = 2.33, 95 % CI 1.50-3.63); early-use: receipt of surgery (AOR = 2.03, 95 % CI 1.30-3.17); chemotherapy (AOR = 1.90, 95 % CI 1.20-3.03); radiation (AOR = 1.73, 95 % CI 1.14-2.63)]. No racial variations in use of AHT among women with HR+ breast cancers insured by Medicaid in South Carolina were identified, but overall rates of AHT use by these women is low. Strategies to improve overall use of AHT should include targeting breast cancer patients who do not receive adjuvant chemotherapy and/or radiation.

  10. The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer

    PubMed Central

    Théret, Nathalie; Brenner, Catherine; Jouan, Elodie; Le Moigne-Muller, Gwénaëlle; Dimanche-Boitrel, Marie-Thérèse

    2016-01-01

    TNF-Related Apoptosis-Inducing Ligand (TRAIL) is a well-known apoptosis inducer, which activates the extrinsic death pathway. TRAIL is pro-apoptotic on colon cancer cells, while not cytotoxic towards normal healthy cells. However, its clinical use is limited by cell resistance to cell death which occurs in approximately 50% of cancer cells. Short Chain Fatty Acids (SCFA) are also known to specifically induce apoptosis of cancer cells. In accordance, we have shown that food grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via the production and release of SCFA (propionate and acetate) acting on mitochondria. Here, we investigated possible synergistic effect between Propionibacterium freudenreichii and TRAIL. Indeed, we hypothesized that acting on both extrinsic and intrinsic death pathways may exert a synergistic pro-apoptotic effect. Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial metabolites (propionate and acetate), in combination with TRAIL, increased pro-apoptotic gene expression (TRAIL-R2/DR5) and decreased anti-apoptotic gene expression (FLIP, XIAP) in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on both death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and caspases (caspase-8, -9 and -3) activation, was lethal on cancer cells but not on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented by P. freudenreichii induced HT29 cells apoptosis and enhanced TRAIL cytotoxic activity, as did P. freudenreichii DMEM culture supernatants or its SCFA metabolites. These results open new perspectives for food grade P. freudenreichii-containing products in order to potentiate TRAIL-based cancer therapy in colorectal cancer. PMID:26771233

  11. Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005.

    PubMed

    Chang, Kun; Qin, Xiao-Jian; Zhang, Hai-Liang; Dai, Bo; Zhu, Yao; Shi, Guo-Hai; Shen, Yi-Jun; Zhu, Yi-Ying; Ye, Ding-Wei

    2016-01-01

    The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage  or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

  12. The association between population-based treatment guidelines and adjuvant therapy for node-negative breast cancer. British Columbia/Ontario Working Group.

    PubMed Central

    Sawka, C.; Olivotto, I.; Coldman, A.; Goel, V.; Holowaty, E.; Hislop, T. G.

    1997-01-01

    This study evaluated the impact of province-wide treatment guidelines on consistency of adjuvant therapy for node-negative breast cancer. A retrospective population-based cohort study was conducted in the Canadian provinces of British Columbia, which has province-wide guidelines, and Ontario, which does not. All eligible 1991 incident cases of node-negative breast cancer in British Columbia (n = 942) and a similar number of randomly selected 1991 incident cases in Ontario (n = 938) were reviewed. Consistency of adjuvant therapy received was evaluated by stratifying cases into discrete diagnostic groups using several grouping systems, and by then comparing the distribution of treatments received within each diagnostic group in the two provinces. Recursive partitioning was also performed. We observed that patterns of pathology reporting were consistent with awareness of the factors used in the British Columbia guidelines to define indications for adjuvant therapy. Consistency of care was greater in British Columbia than in Ontario by all diagnostic grouping systems and by recursive partitioning (P < 0.001), and the observed patterns in British Columbia corresponded to the British Columbia guidelines. We conclude that population-based treatment guidelines can play a role in promoting consistent patterns of adjuvant therapy for women with node-negative breast cancer. PMID:9166950

  13. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  14. Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer

    ClinicalTrials.gov

    2016-05-24

    Estrogen Receptor-positive Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Male Breast Cancer; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

  15. Adjuvant and neoadjuvant treatment in pancreatic cancer.

    PubMed

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

    2012-04-14

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes "standard" adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  16. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

    PubMed Central

    Biondi, Alberto; Lirosi, Maria C; D’Ugo, Domenico; Fico, Valeria; Ricci, Riccardo; Santullo, Francesco; Rizzuto, Antonia; Cananzi, Ferdinando CM; Persiani, Roberto

    2015-01-01

    In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules. PMID:26690252

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

    SciTech Connect

    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

    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 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). 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.

  18. Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward

    PubMed Central

    Papadimitriou, Konstantinos; Antoniou, Georgios; Bronte, Giuseppe; Vassiliou, Vassilios; Papamichael, Demetris; Peeters, Marc; Kountourakis, Panteleimon

    2015-01-01

    Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targeting well-designed future approaches. PMID:26101524

  19. Adjuvant therapy of Dukes' C colon cancer by intra-arterial P-32 colloid for internal radiation therapy of the liver

    SciTech Connect

    Grady, E.D.

    1984-09-01

    To prevent probable occult metastatic liver cancer from progressing to clinical disease, the author used internal radiation therapy as an effective adjuvant to surgical excision of primary Dukes' C colonic cancer. A calculated radiation dose of 5000 rads was delivered to the liver by injecting radioactive 32-P chromic phosphate colloid through the superior mesenteric and celiac arteries. When this was done, the colloid passed through the intestines and was mixed thoroughly with the blood and delivered to the liver by the portal vein. The Kupffer cells in the liver trapped the colloid, and a minimum amount passed through the liver and got into the general circulation. This kept the amount of colloid deposited in the bone marrow to a minimum. In a phase-I pilot study in which nine patients were treated, no serious side effects were noted. In eight patients, the liver has remained free of cancer for more than 1 year.

  20. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received

    PubMed Central

    Dawson, S-J; Makretsov, N; Blows, F M; Driver, K E; Provenzano, E; Le Quesne, J; Baglietto, L; Severi, G; Giles, G G; McLean, C A; Callagy, G; Green, A R; Ellis, I; Gelmon, K; Turashvili, G; Leung, S; Aparicio, S; Huntsman, D; Caldas, C; Pharoah, P

    2010-01-01

    Background: Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL2), an antiapoptotic protein, has been proposed as a prognostic marker, but this effect is considered to relate to oestrogen receptor (ER) status. This study aimed to test the clinical validity of BCL2 as an independent prognostic marker. Methods: Five studies of 11 212 women with early-stage breast cancer were analysed. Individual patient data included tumour size, grade, lymph node status, endocrine therapy, chemotherapy and mortality. BCL2, ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) levels were determined in all tumours. A Cox model incorporating the time-dependent effects of each variable was used to explore the prognostic significance of BCL2. Results: In univariate analysis, ER, PR and BCL2 positivity was associated with improved survival and HER2 positivity with inferior survival. For ER and PR this effect was time dependent, whereas for BCL2 and HER2 the effect persisted over time. In multivariate analysis, BCL2 positivity retained independent prognostic significance (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.66–0.88, P<0.001). BCL2 was a powerful prognostic marker in ER− (HR 0.63, 95% CI 0.54–0.74, P<0.001) and ER+ disease (HR 0.56, 95% CI 0.48–0.65, P<0.001), and in HER2− (HR 0.55, 95% CI 0.49–0.61, P<0.001) and HER2+ disease (HR 0.70, 95% CI 0.57–0.85, P<0.001), irrespective of the type of adjuvant therapy received. Addition of BCL2 to the Adjuvant! Online prognostic model, for a subset of cases with a 10-year follow-up, improved the survival prediction (P=0.0039). Conclusions: BCL2 is an independent indicator of favourable prognosis for all types of early-stage breast cancer. This study establishes the rationale for introduction of BCL2 immunohistochemistry to improve prognostic stratification. Further work

  1. Oncologist-patient discussion of adjuvant hormonal therapy in breast cancer: results of a linguistic study focusing on adherence and persistence to therapy.

    PubMed

    Davidson, Brad; Vogel, Victor; Wickerham, Lawrence

    2007-03-01

    Although studies have proven the benefit of 5+ years of adjuvant hormonal therapy (AHT) for breast cancer, data show adherence and persistence with therapy are suboptimal. This observational linguistic study analyzed communication between breast cancer patients and their oncologists to determine how adherence was addressed and to identify areas where communication could be improved. Community-based oncologists were recruited by letter to participate. Researchers visited oncologists (n = 14) to record patient-oncologist interactions and conduct separate post-visit interviews. Comprehensive linguistic analyses of visits between 28 postmenopausal, early-stage breast cancer patients on or initiating hormonal therapy and their oncologists were conducted to determine the nature of discussions of adherence and persistence to therapy. Oncologist-patient discussions about AHT were generally good but did not address potential difficulties of remaining adherent with long-term therapy. Discussions of persistence were usually monologues addressing the current state of "study data" and were not linked to the patient, the importance of persistence, or how the study data related to her situation. Because the patient's cancer was framed as being "in the past," discussions resembled those of chronic management in preventive medicine. This more ad-hoc approach to adherence and persistence is a potential stumbling block for motivating patients to stay on hormonal therapy. Additionally, the oncologists participating in this study recognized that adherence to therapy is a problem but did not feel "their patients" fell into this pattern. In this office-based evaluation, minimal nurse interactions were observed, which increases the importance of oncologist-patient communication. The authors recommend that oncologists leverage the existing good communication with their patients by increasing the amount and quality of discussions around the importance of adherence and persistence to AHT.

  2. Adjuvant chemotherapy in elderly patients with pancreatic cancer

    PubMed Central

    Nagrial, A M; Chang, D K; Nguyen, N Q; Johns, A L; Chantrill, L A; Humphris, J L; Chin, V T; Samra, J S; Gill, A J; Pajic, M; Pinese, M; Colvin, E K; Scarlett, C J; Chou, A; Kench, J G; Sutherland, R L; Horvath, L G; Biankin, A V

    2014-01-01

    Background: Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer. Methods: We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative. Results: The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ⩾70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8% P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27–2.78, P=0.002). Conclusion: Patients aged ⩾70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer. PMID:24263063

  3. Adjuvant photodynamic therapy (PDT) with photosensitizer photosens for superficial bladder cancer: experimental investigations to treat prostate cancer by PDT with photosens

    NASA Astrophysics Data System (ADS)

    Apolikhin, Oleg I.; Chernishov, Igor V.; Sivkov, Andrey V.; Altunin, Denis V.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

    2007-07-01

    14 patients with transional-cell bladder cancer in stage T1N0M0G2 after transurethral bladder resection were offered adjuvant treatment with PDT. Adjuvant PDT was performed 1-1.5 months after transurethral bladder resection for superficial bladder cancer. Prior to PDT conventional and fluorescent cystoscopy were performed. In the absence of inflammation and after full epitalisation of postoperative wound a session of therapy was performed. 24 hours prior to PDT-session photosensitizer Photosens was injected intravenously in the dose of 0.8 mg per kg of body weight. Prior to PDT local anesthesia of urethra with lidocain-gel was performed. Cystoscopy was carried out. PDT was performed with diode laser "Biospec" (675 nm). During the session the place of standing diffuser and the volume of a bladder were controlled. After 7 months of observation no tumor recidivists were observed. Registered side effects were not life-threatened. 5 patients had pain or discomfort in suprapubic area, ceasing spontaneously or requiring administration of analgetics. No systemic side-effects or allergic reactions were observed. The method can be used in out-patient practice. Absence of early recidivists shows efficiency of PDT in the treatment of superficial bladder cancer. Further study is necessary to estimate optimal regimen of PDT. The further controlling of condition on the patients in this group is required. At the laboratory animals' experiment, we conducted the explorations devoted to the influence of the photodynamic effect at the prostate's tissues.

  4. Exploring the role of physician communication about adjuvant endocrine therapy among breast cancer patients on active treatment: a qualitative analysis

    PubMed Central

    Farias, Albert J.; Ornelas, India J.; Hohl, Sarah D.; Zeliadt, Steven B.; Hansen, Ryan N.; Li, Christopher I.; Thompson, Beti

    2016-01-01

    Purpose To better understand how physicians communicate with breast cancer patients about adjuvant endocrine therapy (AET), we explored, from the breast cancer patient’s perspective, dimensions of the patient-provider communication among women who were on active AET treatment. Methods Qualitative methods using semi-structured in-depth interviews were conducted with breast cancer patients (n = 22) who filled a prescription for AET in the previous 12 months. Interview questions aimed to elicit experiences with AET. We reviewed and coded interview transcripts using qualitative principles of inductive reasoning to identify concepts and themes from interview data. Results We grouped emergent themes into four major functions of physician-patient communication: (1) information exchange, (2) decision-making to take and continue AET, (3) enabling patient self-management and monitoring potential side effects, and (4) emotional support. Physicians exchanged information with patients in a way that they understood and enhanced patient’s health literacy regarding the benefits and knowledge of AET. Physicians empowered patients to make decisions about their care. Patients expressed trust and confidence in their physician which helped them seek care when needed. Patients reported a high degree of self-efficacy to self-manage AET and were continuing treatment despite potential side effects. Conclusions The results from our study suggest that women’s interactions and communication with their physician may be an important factor that contributes to the continued use of AET. Physicians who can communicate information about AET treatment benefits, purpose, and expectations in a way that patients can understand is a critical aspect of care that needs to be further studied. PMID:27557832

  5. [Adjuvant dermato-cosmetic acne therapy].

    PubMed

    Bayerl, Christiane; Degitz, Klaus; Meigel, Eva; Kerscher, Martina

    2010-03-01

    Adjuvant dermato-cosmetic therapy in acne is an essential part of the concept of treating acne after initiation and during maintenance therapy. Those are mechanical peeling, chemical peeling and its combination. It needs supervision by an experienced dermatologist.

  6. Biotherapy in the Adjuvant Treatment of Colorectal Cancer

    PubMed Central

    Tazi, El Mehdi; Essadi, Ismail; Boutayeb, Saber; M’rabti, Hind; Errihani, Hassan

    2011-01-01

    The use of adjuvant chemotherapy has improved survival in early-stage colon cancer. Ongoing adjuvant clinical trials are evaluating the addition of targeted therapies to standard chemotherapy regimen. Preliminary results with bevacizumab were disappointing. Also, cetuximab added to chemotherapy does not seem to be better than chemotherapy alone, even in selected wild-type KRAS populations. A better understanding of mechanisms of action of drugs, tumor biology, and predictive biomarkers are needed to design future adjuvant trials. PMID:27942334

  7. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    SciTech Connect

    Song, Changhoon; Kim, Kyubo; Chie, Eui Kyu; Kim, Jin Ho; Jang, Jin-Young; Kim, Sun Whe; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W.

    2013-11-01

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

  8. Adjuvant radiation therapy for bladder cancer: A dosimetric comparison of techniques

    SciTech Connect

    Baumann, Brian C.; Noa, Kate; Wileyto, E. Paul; Bekelman, Justin E.; Deville, Curtiland; Vapiwala, Neha; Kirk, Maura; Both, Stefan; Dolney, Derek; Kassaee, Ali; Christodouleas, John P.

    2015-01-01

    Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to compare plans for bowel and rectal volumes exposed to 35% (V{sub 35%}), 65% (V{sub 65%}), and 95% (V{sub 95%}) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V{sub 35%} {sub rectum}, V{sub 65%} {sub rectum}, and V{sub 95%} {sub rectum}; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V{sub 95%} {sub bowel}, V{sub 65%} {sub bowel}, or V{sub 35%} {sub bowel}). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V{sub 65%} {sub bowel} and V{sub 95%} {sub bowel} for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation

  9. Adjuvant radiation therapy for bladder cancer: a dosimetric comparison of techniques.

    PubMed

    Baumann, Brian C; Noa, Kate; Wileyto, E Paul; Bekelman, Justin E; Deville, Curtiland; Vapiwala, Neha; Kirk, Maura; Both, Stefan; Dolney, Derek; Kassaee, Ali; Christodouleas, John P

    2015-01-01

    Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to compare plans for bowel and rectal volumes exposed to 35% (V35%), 65% (V65%), and 95% (V95%) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V35% rectum, V65% rectum, and V95% rectum; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V95% bowel, V65% bowel, or V35% bowel). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V65% bowel and V95% bowel for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation. Using the IMRT or the SFUD plans instead of the 3-D conformal plan may improve both bowel and rectal toxicity.

  10. Adjuvant treatment strategies for early colon cancer.

    PubMed

    Waterston, Ashita M; Cassidy, Jim

    2005-01-01

    Colon cancer remains a major cause of death; however, in the last 3 years a number of trials have been published that have led to changes in the treatment of patients with this disease. Initially, the adjuvant treatment of patients following curative resection was based on their Dukes staging; this is now being refined by consideration of other pathological factors, as well as the investigation of newer prognostic markers such as p53, Ki67 and a number of genes on chromosome 18. Tumours generally develop from the progressive accumulation of genetic events, although some develop through mutation or inactivation of DNA mismatch repair proteins leading to microsatellite instability; this is particularly important in Lynch's syndrome. The loss of gene expression can occur by deletion or mutation of genes or by aberrant methylation of CpG islands. In patients with Dukes C colon cancer the standard of care for adjuvant chemotherapy was previously based on bolus fluorouracil (5-fluorouracil) and folinic acid (leucovorin) administered 5 days per month or weekly for 6 months. Recent studies with a combination of infusional fluorouracil, folinic acid and oxaliplatin have been found to be superior. A further study replacing fluorouracil with oral capecitabine has also demonstrated equivalent disease-free survival. Although some debate remains regarding the benefit of adjuvant treatment for patients with Dukes B colon cancer, the emerging consensus is that, for those patients who are younger and have high-risk features, chemotherapy should be discussed. A number of large vaccine trials have also been conducted in the adjuvant setting and, overall, these have been disappointing. This is a rapidly advancing area of therapy and the results of new trials are awaited to determine whether additional benefits can be achieved with biological therapies such as anti-vascular endothelial growth factor and anti-epithelial growth factor receptor monoclonal antibodies, which have already

  11. Locoregional Failure in Early-Stage Breast Cancer Patients Treated With Radical Mastectomy and Adjuvant Systemic Therapy: Which Patients Benefit From Postmastectomy Irradiation?

    SciTech Connect

    Trovo, Marco; Durofil, Elena; Polesel, Jerry; Roncadin, Mario; Perin, Tiziana; Mileto, Mario; Piccoli, Erica; Quitadamo, Daniela; Massarut, Samuele; Carbone, Antonino; Trovo, Mauro G.

    2012-06-01

    Purpose: To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). Methods and Materials: Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. Results: Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. Conclusions: A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.

  12. Adjuvant cytostatic therapy of breast cancer as an important factor in the postponing of a relapse and longer survival period.

    PubMed

    Stula, N

    1992-01-01

    This prospective clinical study shows the results of the adjuvant cytostatic therapy (ACT) in breast cancer applied to patients in the premenopausal age. Cyclophosphamide, methotrexate, 5-fluorouracil (CMF) group (70 patients): after operative and radiotherapeutic treatment the ACT is applied over the period of six months (six cycles). Control group (71 patients): only operative and radiotherapeutic treatment. Protocol of the ACT: cyclophosphamide, methotrexate, 5-fluorouracil (CMF) over 5 days with a 4-week break. Total 6 cycles. Control period: 10 years. Stratification of patients was made on the basis of the following risk factors: size of the tumour, number of positive lymph nodes of ipsilateral axilla, grade of the differentiation of the tumour, hormonal dependence of the tumour. Statistical method of analysis: actuary calculation, the Hi square test. The results show that the application of the ACT is statistically significant (P < 0.05) in regard to the disease-free interval. However, concerning the survival, the usefulness of its application is present but not statistically significant on the significance level of 5%. The usefulness of the ACT application as regards high risk factors (T3, T4 > or = 4 lymph nodes, grade of differentiation II, III, ER-PR-) is statistically significant (P < 0.05) both in regard to the DFI and survival. Regarding low risk factors the ACT application adversely influenced the results in the control group. This is probably the result of the ACT toxicity. The patients have a favourable prognosis in this subgroup in regard to the staging and biological nature of the tumour. The ACT in the premenopausal age of patients with high risk factors gives a significantly better results concerning the procrastination of relapse and the length of the survival period.

  13. Adjuvant therapy after surgical stone management.

    PubMed

    Ferrandino, Michael N; Monga, Manoj; Preminger, Glenn M

    2009-01-01

    The aim of this article was to review the most widely researched adjuvant medical therapies for the surgical management of urolithiasis. Articles were identified and reviewed from PubMed and Medline databases with MeSH headings focusing on the various surgical treatments of urolithiasis and adjuvant therapy. Additional articles were retrieved from references and conference proceedings. Surgical treatments reviewed included shockwave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy. Adjuvant therapy was considered medical or complementary therapy as an adjunct to these surgical interventions. Adjuvant therapy for the surgical management of urolithiasis has been documented to increase stone-free rates, reduce stone remission rates, prevent renal damage, and decrease postoperative morbidity. A variety of agents have been studied, ranging from antioxidants to alpha-blockers and to alkalinizing agents. Additionally, there is increasing interest in complementary adjuvant therapy (ie, acupuncture). Adjuvant therapy is a fertile area for research in the surgical management of urolithiasis. The optimal agents have yet to be determined and therefore further investigation is warranted and necessary.

  14. Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial

    PubMed Central

    Phillips, Kelly-Anne; Aldridge, Julie; Ribi, Karin; Sun, Zhuoxin; Thompson, Alastair; Harvey, Vernon; Thürlimann, Beat; Cardoso, Fatima; Pagani, Olivia; Coates, Alan S.; Goldhirsch, Aron; Price, Karen N.; Gelber, Richard D.

    2011-01-01

    Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1 year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change = 0.22, effect size = 0.53, P < 0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P = 0.0006 and P = 0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment. PMID:21046229

  15. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer

    SciTech Connect

    Burstein, Harold J. . E-mail: hburstein@partners.org; Bellon, Jennifer R.; Galper, Sharon; Lu, H.-M.; Kuter, Irene; Wong, Julia; Gelman, Rebecca; Bunnell, Craig A.; Parker, Leroy M.; Garber, Judy E.; Winer, Eric P.; Harris, Jay R.; Powell, Simon N.

    2006-02-01

    Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly x 12 weeks (60 mg/m{sup 2}), or every 3 weeks x 4 cycles (135-175 mg/m{sup 2}). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m{sup 2} per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m{sup 2}. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.

  16. Vaccine adjuvants as potential cancer immunotherapeutics

    PubMed Central

    Temizoz, Burcu; Kuroda, Etsushi

    2016-01-01

    Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund’s adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID:27006304

  17. 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

    PubMed Central

    Harris, Lyndsay N.; McShane, Lisa M.; Andre, Fabrice; Collyar, Deborah E.; Gonzalez-Angulo, Ana M.; Hammond, Elizabeth H.; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Bast, Robert C.; Hayes, Daniel F.

    2016-01-01

    Purpose To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. Methods A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. Recommendations In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. PMID:26858339

  18. Genomic predictor of residual risk of recurrence after adjuvant chemotherapy and endocrine therapy in high risk estrogen receptor-positive breast cancers.

    PubMed

    Khan, Sabrina S; Karn, Thomas; Symmans, W Fraser; Rody, Achim; Müller, Volkmar; Holtrich, Uwe; Becker, Sven; Pusztai, Lajos; Hatzis, Christos

    2015-02-01

    A subset of early stage estrogen receptor (ER)-positive breast cancers considered "high risk" for recurrence with endocrine therapy alone by current genomic prognostic predictors, such as Oncotype DX, is no longer high risk after receiving adjuvant chemotherapy. We hypothesized that a recently described gene expression-based outcome predictor adjuvant chemotherapy and endocrine therapy sensitivity (ACES) could re-stratify these patients into high and low risk groups for relapse when treated with both chemo- and endocrine therapies. ACES involves four separate modules (endocrine sensitivity, chemotherapy sensitivity, chemotherapy resistance, and survival prediction) that yield a prediction for good or poor outcome with current standard of care multimodality therapy. ACES was applied to Affymetrix gene expression data from 2 retrospectively collected ER-positive and HER2-negative patient cohorts that were uniformly treated with adjuvant endocrine and chemotherapy (n = 250). Each sample was first risk stratified by a genomic surrogate of Oncotype DX, and the high risk patients (n = 76) were re-stratified by ACES. Recurrence-free survival (RFS) was evaluated with ACES risk categories. The Oncotype DX high risk but ACES good prognosis patients (n = 24, 32%) had an RFS of 95% compared to 76% in the poor prognosis group (n = 52; log-rank p = 0.033) at 5 years. ACES risk category remained an independent predictor in multivariate analysis after adjusting for age, T-stage, and lymph node involvement at diagnosis (hazard ratio 0.15; p = 0.072). Tertiary risk prediction that takes into account chemotherapy and endocrine sensitivity, and baseline prognosis may help identify high risk ER-positive patients who have excellent survival after chemotherapy.

  19. Adjuvant analgesics in cancer pain: a review.

    PubMed

    Mitra, Raj; Jones, Stephanie

    2012-02-01

    Adjuvant analgesics (co-analgesics) are medications whose primary indication is the management of a medical condition with secondary effects of analgesia. Cancer pain is multifactorial and often involves inflammatory, nociceptive, and neuropathic pain subtypes. Adjuvant analgesics used in conjunction with opioids have been found to be beneficial in the management of many cancer pain syndromes; however, they are currently underutilized. Antidepressants, anticonvulsants, local anesthetics, topical agents, steroids, bisphosphonates, and calcitonin are all adjuvants which have been shown to be effective in the management of cancer pain syndromes. When utilizing analgesic adjuvants in the treatment of cancer pain, providers must take into account the particular side effect profile of the medication. Ideally, adjuvant analgesics will be initiated at lower dosages and escalated as tolerated until efficacy or adverse effects are encountered.

  20. (Neo)adjuvant systemic therapy for melanoma.

    PubMed

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M

    2017-03-01

    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  1. 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

  2. Adjuvant Therapy for Resected Gastric Cancer-Rapid, Yet Incomplete Adoption Following Results of Intergroup 0116 Trial

    SciTech Connect

    Coburn, Natalie G. Guller, Ulrich; Baxter, Nancy N.; Kiss, Alex; Ringash, Jolie; Swallow, Carol J.; Law, Calvin H.L.

    2008-03-15

    Purpose: The Southwest Oncology Group/Intergroup 0116 (INT-0116) trial showed that adjuvant chemoradiotherapy improves survival in high-risk gastric adenocarcinoma patients. This study examined the adoption of adjuvant treatment following the trial results and the factors associated with its use. Methods and Materials: Between 1996 and 2003, patients aged 18-85 years with resected gastric adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database and classified as diagnosed before (January 1996 to April 2000) or after (May 2000 to December 2003) presentation of the INT-0116 trial findings. Univariate and multivariable models were used to determine the factors associated with use of adjuvant radiotherapy (RT). Results: Of 10,230 patients studied, 14.6% were given adjuvant RT before the INT-0116 trial, increasing to 30.4% afterward (p < 0.001). Significant increases in adjuvant RT from before to after INT-0116 were seen in all demographic categories. Younger patients were significantly more likely to receive adjuvant RT (44.5%, 18-59 years; 31.0%, 60-74 years; and 12.6%, 75-85 years, p < 0.0001). Married patients were significantly more likely to receive adjuvant RT (30.9%) than were unmarried patients (23.6%, p < 0.001). A greater depth of tumor invasion, worse nodal status, and more lymph nodes assessed were associated with adjuvant RT (p < 0.0001). The rate of adjuvant RT varied from 22.9-44.2% across SEER regions. On multiple logistic regression analysis, age, SEER region, marital status, assessed lymph nodes, tumor depth, and nodal status were all significant independent predictors of the use of adjuvant RT. Conclusion: Use of adjuvant RT doubled after the INT-0116 trial results became public; however, the fraction of patients receiving adjuvant RT is still low. Additional examination of the statistically significant and clinically relevant variability between different SEER regions, tumor characteristics, and patient

  3. The Adoption of New Adjuvant Radiation Therapy Modalities Among Medicare Beneficiaries With Breast Cancer: Clinical Correlates and Cost Implications

    SciTech Connect

    Roberts, Kenneth B.; Soulos, Pamela R.; Herrin, Jeph; Yu, James B.; Long, Jessica B.; Dostaler, Edward; and others

    2013-04-01

    Purpose: New radiation therapy modalities have broadened treatment options for older women with breast cancer, but it is unclear how clinical factors, geographic region, and physician preference affect the choice of radiation therapy modality. Methods and Materials: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify women diagnosed with stage I-III breast cancer from 1998 to 2007 who underwent breast-conserving surgery. We assessed the temporal trends in, and costs of, the adoption of intensity modulated radiation therapy (IMRT) and brachytherapy. Using hierarchical logistic regression, we evaluated the relationship between the use of these new modalities and patient and regional characteristics. Results: Of 35,060 patients, 69.9% received conventional external beam radiation therapy (EBRT). Although overall radiation therapy use remained constant, the use of IMRT increased from 0.0% to 12.6% from 1998 to 2007, and brachytherapy increased from 0.7% to 9.0%. The statistical variation in brachytherapy use attributable to the radiation oncologist and geographic region was 41.4% and 9.5%, respectively (for IMRT: 23.8% and 22.1%, respectively). Women undergoing treatment at a free-standing radiation facility were significantly more likely to receive IMRT than were women treated at a hospital-based facility (odds ratio for IMRT vs EBRT: 3.89 [95% confidence interval, 2.78-5.45]). No such association was seen for brachytherapy. The median radiation therapy cost per treated patient increased from $5389 in 2001 to $8539 in 2007. Conclusions: IMRT and brachytherapy use increased substantially from 1998 to 2007; overall, radiation therapy costs increased by more than 50%. Radiation oncologists played an important role in treatment choice for both types of radiation therapy, whereas geographic region played a bigger role in the use of IMRT than brachytherapy.

  4. Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

    SciTech Connect

    Gold, Douglas G.; Miller, Robert C. Haddock, Michael G.; Gunderson, Leonard L.; Quevedo, Fernando; Donohue, John H.; Bhatia, Sumita; Nagorney, David M.

    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. On 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.

  5. Impact of intratumoral expression levels of fluoropyrimidine-metabolizing enzymes on treatment outcomes of adjuvant S-1 therapy in gastric cancer.

    PubMed

    Kim, Ji-Yeon; Shin, Eun; Kim, Jin Won; Lee, Hye Seung; Lee, Dae-Won; Kim, Se-Hyun; Lee, Jeong-Ok; Kim, Yu Jung; Kim, Jee Hyun; Bang, Soo-Mee; Ahn, Sang-Hoon; Park, Do Joong; Lee, Jong Seok; Lee, Ju-Seog; Kim, Hyung-Ho; Lee, Keun-Wook

    2015-01-01

    We analyzed the expression levels of fluoropyrimidine-metabolizing enzymes (thymidylate synthase [TS], dihydropyrimidine dehydrogenase [DPD], thymidine phosphorylase [TP] and orotate phosphoribosyltransferase [OPRT]) to identify potential biomarkers related to treatment outcomes in gastric cancer (GC) patients receiving adjuvant S-1 chemotherapy. In this study, 184 patients who received curative gastrectomy (D2 lymph node dissection) and adjuvant S-1 were included. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were performed to measure the protein and mRNA levels of TS, DPD, TP, and OPRT in tumor tissue. In univariate analysis, low intratumoral DPD protein expression was related to poorer 5-year disease-free survival (DFS; 78% vs. 88%; P = 0.068). Low intratumoral DPD mRNA expression (1st [lowest] quartile) was also related to poorer DFS (69% vs. 90%; P < 0.001) compared to high intratumoral DPD expression (2nd to 4th quartiles). In multivariate analyses, low intratumoral DPD protein or mRNA expression was related to worse DFS (P < 0.05), irrespective of other clinical variables. TS, TP, and OPRT expression levels were not related to treatment outcomes. Severe non-hematologic toxicities (grade ≥ 3) had a trend towards more frequent development in patients with low intratumoral DPD mRNA expression (29% vs. 16%; P = 0.068). In conclusion, GC patients with high intratumoral DPD expression did not have inferior outcome following adjuvant S-1 therapy compared with those with low DPD expression. Instead, low intratumoral DPD expression was related to poor DFS.

  6. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    PubMed Central

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  7. Overexpression of CRM1: A Characteristic Feature in a Transformed Phenotype of Lung Carcinogenesis and a Molecular Target for Lung Cancer Adjuvant Therapy.

    PubMed

    Gao, Weimin; Lu, Chuanwen; Chen, Lixia; Keohavong, Phouthone

    2015-05-01

    Our previous study showed that chromosome region maintenance 1 (CRM1), a nuclear export receptor for various cancer-associated "cargo" proteins, was important in regulating lung carcinogenesis in response to a tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The objectives of this study are to comprehensively evaluate the significance of CRM1 in lung cancer development and investigate the therapeutic potential of targeting CRM1 for lung cancer treatment using both in vitro and in vivo models. We showed that CRM1 was overexpressed not only in lung tumor tissues from both lung cancer patients and mice treated with NNK but also in NNK-transformed BEAS-2B human bronchial epithelial cells. Furthermore, stable overexpression of CRM1 in BEAS-2B cells by plasmid vector transfection led to malignant cellular transformation. Moreover, a decreased CRM1 expression level in A549 cells by short hairpin siRNA transfection led to a decreased tumorigenic activity both in vitro and in nude mice, suggesting the potential to target CRM1 for lung cancer treatment. Indeed, we showed that the cytotoxic effects of cisplatin on A549 cells with CRM1 down-regulated by short hairpin siRNA were significantly increased, compared with A549 cells, and the cytotoxic effects of cisplatin became further enhanced when the drug was used in combination with leptomycin B, a CRM1 inhibitor, in both in vitro and in vivo models. Cancer target genes were significantly involved in these processes. These data suggest that CRM1 plays an important role in lung carcinogenesis and provides a novel target for lung cancer adjuvant therapy.

  8. Regulation of the CCN genes by vitamin D: A possible adjuvant therapy in the treatment of cancer and fibrosis.

    PubMed

    Piszczatowski, Richard T; Lents, Nathan H

    2016-10-01

    The CCN family is composed of six cysteine-rich, modular, and conserved proteins whose functions span a variety of tissues and include cell proliferation, adhesion, angiogenesis, and wound healing. Roles for the CCN proteins throughout the entire body including the skin, kidney, brain, blood vessels, hematopoietic compartment and others, are continuously being elucidated. Likewise, an understanding of the regulation of this important gene family is constantly becoming clearer, through identification of transcription factors that directly activate, repress, or respond to upstream cell signaling pathways, as well as other forms of gene expression control. Vitamin D (1,25-dihydroxyvitamin D3 or calcitriol), a vitamin essential for numerous biological processes, acts as a potent gene expression modulator. The regulation of the CCN gene family members by calcitriol has been described in many contexts. Here, we provide a concise and thorough overview of what is known about calcitriol and its regulation of the CCN genes, and argue that its regulation is of physiological importance in a wide breadth of tissues in which CCN genes function. In addition, we highlight the effects of vitamin D on CCN gene expression in the setting of two common pathologic conditions, fibrosis and cancer, and propose that the therapeutic effects of vitamin D3 described in these disease states may in part be attributable to CCN gene modulation. As vitamin D is perfectly safe in a wide range of doses and already showing promise as an adjuvant therapeutic agent, a deeper understanding of its control of CCN gene expression may have profound implications in clinical management of disease.

  9. Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

    SciTech Connect

    Creutzberg, Carien L.; Stiphout, Ruud G.P.M. van; Nout, Remi A.; Lutgens, Ludy C.H.W.; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T.H.B.M.; Lambin, Philippe

    2015-03-01

    Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variables which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT

  10. Barriers and facilitators of adjuvant hormone therapy adherence and persistence in women with breast cancer: a systematic review

    PubMed Central

    Moon, Zoe; Moss-Morris, Rona; Hunter, Myra S; Carlisle, Sophie; Hughes, Lyndsay D

    2017-01-01

    Purpose Nonadherence to hormone therapy in breast cancer survivors is common and associated with increased risk of mortality. Consistent predictors of nonadherence and nonpersistence are yet to be identified, and little research has examined psychosocial factors that may be amenable to change through intervention. This review aimed to identify predictors of nonadherence and nonpersistence to hormone therapy in breast cancer survivors in order to inform development of an intervention to increase adherence rates. Methods Studies published up to April 2016 were identified through MEDLINE, Embase, Web of Science, PsycINFO, CINAHL and gray literature. Studies published in English measuring associations between adherence or persistence and any predictor variables were included. Eligible studies were assessed for methodological quality, data were extracted and a narrative synthesis was conducted. Results Sixty-one eligible articles were identified. Most studies focused on clinical and demographic factors with inconsistent results. Some evidence suggested that receiving specialist care and social support were related to increased persistence, younger age and increased number of hospitalizations were associated with nonadherence, and good patient–physician relationship and self-efficacy for taking medication were associated with better adherence. A small amount of evidence suggested that medication beliefs were associated with adherence, but more high-quality research is needed to confirm this. Conclusion Some psychosocial variables were associated with better adherence and persistence, but the results are currently tentative. Future high-quality research should be carried out to identify psychosocial determinants of nonadherence or nonpersistence that are modifiable through intervention. PMID:28260867

  11. Hepatic toxicity caused by adjuvant CMF/CNF in breast cancer patients and reversal by tamoxifen.

    PubMed

    Hirvikoski, P P; Kumpulainen, E J; Johansson, R T

    1997-07-01

    The purpose of the study was to determine the effect of adjuvant chemotherapy on liver enzymes in breast cancer patients. Furthermore, the effect of tamoxifen on liver enzymes was analyzed. Liver function tests from 194 breast cancer patients who received adjuvant chemotherapy with or without tamoxifen (TAM) were reviewed. Statistically very significant increases were seen in alkaline phosphatase, aspartate acetyl transferase, and gamma glutamyl transferase levels in these patients receiving adjuvant chemotherapy. No statistical changes were noticed in bilirubin levels. If tamoxifen was given together with adjuvant chemotherapy, no changes in liver function tests were detected. Hepatic toxicity was induced in breast cancer patients by adjuvant CMF/CNF therapy (cyclophosphamide, methotrexate, 5-fluorouracil, mitoxantrone). These changes were mostly mild. Adjuvant tamoxifen reduced the increase in liver enzymes caused by adjuvant chemotherapy.

  12. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    NASA Astrophysics Data System (ADS)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  13. Adjuvant chemotherapy in early breast cancer.

    PubMed

    Ejlertsen, Bent

    2016-05-01

    of epirubicin and the presence of TOP2A, but not the presence of HER2 aberrations. The results obtained in the 89D trial regarding TOP2A have been reproduced by others, but not consistently. However, a recent individual-patient pooled analysis of five adjuvant trials demonstrated that patients with either TOP2A or centromere 17 aberrations, but not with HER2 amplification, benefit from anthracycline-containing adjuvant chemotherapy. Anthracyclins have additional distinct biological mechanisms; and results from the DBCG 89D suggested that tumours with normal TOP2A were only non-responsive to anthracyclines if they were TIMP1 immunoreactive. The DBCG READ trial (N = 2,015) prospectively included patients without TOP2A-aberrated breast cancers, and its results are awaited for prospective confirmation of the results from the DBCG 89D and the individual-patient pooled analysis. Adjuvant chemotherapy substantially reduces the risk of recurrence and mortality of breast cancer, but is also associated with significant toxicity. However, according to a large cohort study from DBCG, chemotherapy can safely be withheld in one fourth of postmenopausal patients who will be without excess mortality following sufficient adjuvant endocrine therapy for ER positive breast cancer. A prognostic standard mortality rate index (PSI) was constructed using regression coefficients obtained in a multivariate fractional polynomials model, and most accurately identified those who could be spared chemotherapy. In addition to age, tumour size, nodal status, histological type and malignancy grade, the PSI also includes ER level addressed as a continuous variable in the MFP model. In the MFP model, absence of LVI was sufficient to counteract the impact of other risk factors, while that could not be achieved with a categorical multivariate model in a prior study. An evaluation of whether the addition of results from a molecular assay may improve the clinical utility of the PSI is on-going, but when

  14. Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

    SciTech Connect

    Damast, Shari; Alektiar, Kaled M.; Goldfarb, Shari; Eaton, Anne; Patil, Sujata; Mosenkis, Jeffrey; Bennett, Antonia; Atkinson, Thomas; Jewell, Elizabeth; Leitao, Mario; Barakat, Richard; Carter, Jeanne; Basch, Ethan

    2012-10-01

    Purpose: We used the Female Sexual Function Index (FSFI) to investigate the prevalence of sexual dysfunction (SD) and factors associated with diminished sexual functioning in early stage endometrial cancer (EC) patients treated with simple hysterectomy and adjuvant brachytherapy. Methods and Materials: A cohort of 104 patients followed in a radiation oncology clinic completed questionnaires to quantify current levels of sexual functioning. The time interval between hysterectomy and questionnaire completion ranged from <6 months to >5 years. Multivariate regression was performed using the FSFI as a continuous variable (score range, 1.2-35.4). SD was defined as an FSFI score of <26, based on the published validation study. Results: SD was reported by 81% of respondents. The mean ({+-} standard deviation) domain scores in order of highest-to-lowest functioning were: satisfaction, 2.9 ({+-}2.0); orgasm, 2.5 ({+-}2.4); desire, 2.4 ({+-}1.3); arousal, 2.2 ({+-}2.0); dryness, 2.1 ({+-}2.1); and pain, 1.9 ({+-}2.3). Compared to the index population in which the FSFI cut-score was validated (healthy women ages 18-74), all scores were low. Compared to published scores of a postmenopausal population, scores were not statistically different. Multivariate analysis isolated factors associated with lower FSFI scores, including having laparotomy as opposed to minimally invasive surgery (effect size, -7.1 points; 95% CI, -11.2 to -3.1; P<.001), lack of vaginal lubricant use (effect size, -4.4 points; 95% CI, -8.7 to -0.2, P=.040), and short time interval (<6 months) from hysterectomy to questionnaire completion (effect size, -4.6 points; 95% CI, -9.3-0.2; P=.059). Conclusions: The rate of SD, as defined by an FSFI score <26, was prevalent. The postmenopausal status of EC patients alone is a known risk factor for SD. Additional factors associated with poor sexual functioning following treatment for EC included receipt of laparotomy and lack of vaginal lubricant use.

  15. Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma

    PubMed Central

    Aizer, Ayal A.; Arvold, Nils D.; Catalano, Paul; Claus, Elizabeth B.; Golby, Alexandra J.; Johnson, Mark D.; Al-Mefty, Ossama; Wen, Patrick Y.; Reardon, David A.; Lee, Eudocia Q.; Nayak, Lakshmi; Rinne, Mikael L.; Beroukhim, Rameen; Weiss, Stephanie E.; Ramkissoon, Shakti H.; Abedalthagafi, Malak; Santagata, Sandro; Dunn, Ian F.; Alexander, Brian M.

    2014-01-01

    Background The impact of adjuvant radiation in patients with atypical meningioma remains poorly defined. We sought to determine the impact of adjuvant radiation therapy in this population. Methods We identified 91 patients with World Health Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and Women's Cancer Center between 1997 and 2011. A propensity score model incorporating age at diagnosis, gender, Karnofsky performance status, tumor location, tumor size, reason for diagnosis, and era of treatment was constructed using logistic regression for the outcome of receipt versus nonreceipt of radiation therapy. Propensity scores were then used as continuous covariates in a Cox proportional hazards model to determine the adjusted impact of adjuvant radiation therapy on both local recurrence and the combined endpoint of use of salvage therapy and death due to progressive meningioma. Results The median follow-up in patients without recurrent disease was 4.9 years. After adjustment for pertinent confounding variables, radiation therapy was associated with decreased local recurrence in those undergoing gross total resection (hazard ratio, 0.25; 95% CI, 0.07–0.96; P = .04). No differences in overall survival were seen in patients who did and did not receive radiation therapy. Conclusion Patients who have had a gross total resection of an atypical meningioma should be considered for adjuvant radiation therapy given the improvement in local control. Multicenter, prospective trials are required to definitively evaluate the potential impact of radiation therapy on survival in patients with atypical meningioma. PMID:24891451

  16. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    PubMed Central

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS

  17. Combined modality therapy for esophageal cancer.

    PubMed

    Minsky, Bruce D

    2003-08-01

    Treatment approaches for esophageal cancer include primary treatment (surgical or nonsurgical) or adjuvant treatment (preoperative or postoperative). Primary treatments include surgery alone, radiation therapy alone, and radiation therapy plus chemotherapy (combined modality therapy). Adjuvant therapies include preoperative or postoperative radiation therapy, preoperative chemotherapy, and preoperative combined modality therapy. There is considerable controversy as to the ideal therapeutic approach. This review will examine the results of these approaches as well as combined modality therapy using novel regimens.

  18. Second Malignancies After Adjuvant Radiation Therapy for Early Stage Breast Cancer: Is There Increased Risk With Addition of Regional Radiation to Local Radiation?

    SciTech Connect

    Hamilton, Sarah Nicole; Tyldesley, Scott; Li, Dongdong; Olson, Robert; McBride, Mary

    2015-04-01

    Purpose: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT). Materials and Methods: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates. Results: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: −8.7 to 9.9). Conclusions: No statistically significant increased risk of second malignancy was detected after LRRT relative to

  19. Adjuvant chemotherapy in patients with completely resected non-small cell lung cancer

    PubMed Central

    2014-01-01

    Adjuvant chemotherapy has been established as a standard for patients with completely resected non-small cell lung cancer (NSCLC). Adjuvant chemotherapy increased the 5-year survival rates by 4% to 15% within randomized trials and, based on a meta-analysis of five cisplatin-based trials, by 5.4%. Adjuvant chemotherapy consists of a cisplatin-based doublet, preferentially cisplatin plus vinorelbine. Future improvements in outcome of adjuvant therapy are expected by customized chemotherapy and the integration of targeted therapies or immunotherapy. PMID:25806316

  20. Intravesical chemotherapy for intermediate risk non-muscle invasive bladder cancer recurring after a first cycle of intravesical adjuvant therapy

    PubMed Central

    Serretta, Vincenzo; Sommatino, Francesco; Gesolfo, Cristina Scalici; Franco, Vito; Cicero, Giuseppe; Allegro, Rosalinda

    2015-01-01

    Context: The therapeutic strategy in intermediate risk (IR) non-muscle invasive bladder cancer (NMIBC) recurring after intravesical therapy (IT) is not well defined. Most patients are usually retreated by Bacillus Calmette-Guerin (BCG). Aims: To evaluate the efficacy of intravesical chemotherapy (ICH) given at recurrence after the first cycle of ICH in IR-NMIBC recurring 6 months or later. Settings and Design: Retrospective analysis of the efficacy of ICH given after previous IT. Materials and Methods: The clinical files of IR-NMIBC patients recurring later than 6 months after transurethral resection (TUR) and IT and retreated by IT were reviewed. The patients should be at intermediate risk both initially and at the first recurrence. BCG should have been given at full dose. Cytology and cystoscopy were performed 3 monthly for 2 years and then 6 monthly. Statistical Analysis: The RFS was estimated by the Kaplan-Meier method and the differences between treatment groups were compared by log-rank test. Mann Whitney U-test was used to compare the parameters’ distribution for median time to recurrence. Multivariate Cox proportional hazards models were used. Results: The study included 179 patients. The first IT was ICH in 146 (81.6%) and BCG in 33 (18.4%), re-IT was ICH in 112 (62.6%) and BCG in 67 (37.4%) patients. Median time to recurrence was 18 and 16 months after first and second IT (P = 0.32). At 3 years, 24 (35.8%) and 49 (43.8%) patients recurred after BCG and ICH, respectively (P = 0.90). No difference in RFS was found between BCG and ICH given after a first cycle of ICH (P = 0.23). Conclusions: Re-treatment with ICH could represent a legitimate option to BCG in patients harboring IR-NMIBC recurring after TUR and previous ICH. Prospective trials are needed. PMID:25657538

  1. Does Adjuvant Radiation Therapy Improve Outcomes In pT1-3N0 Oral Cavity Cancer With Tumor-Free Margins and Perineural Invasion?

    SciTech Connect

    Liao, C.-T.; Chang, J.T.-C.; Wang, H.-M.; Ng, S.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2008-06-01

    Purpose: The criteria for administration of adjuvant radiation therapy (RT) in oral cavity squamous cell carcinoma (OSCC) remain controversial, and it is unclear whether patients with pT1-3N0 disease benefit from adjuvant radiation in the presence of free margins and perineural invasion. The goal of this report was to determine whether this group would benefit from adjuvant radiation therapy in terms of 5-year local control rate and overall survival rate. Methods and Materials: We retrospectively reviewed our case records from January 1996 to May 2005. In all, 460 pT1-3N0 OSCC patients had tumor-free margins, of whom 68 had perineural invasion. Postoperative adjuvant RT was performed in patients with pT4 tumors, positive lymph nodes, or close margins ({<=}4 mm). In addition, selected OSCC patients with large pT3 tumors or perineural invasion received postoperative adjuvant RT. Local control and overall survival rates were plotted by Kaplan-Meier analysis. Results: There were no significant differences in 5-year local control (p 0.1936) and overall survival (p = 0.5580) rates between patients with perineural invasion compared with those without. Among patients with perineural invasion, the addition of adjuvant radiotherapy did not significantly alter the 5-year local control rate (p = 0.3170) or the overall survival rate (p = 0.0935). Conclusion: Altogether, these data seem to indicate that radical surgical resection alone should be considered a sufficient treatment for OSCC patients with pT1-3N0 disease, even in the presence of perineural invasion.

  2. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

    PubMed Central

    2010-01-01

    Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM®) to BCG in patients after transurethral resection (TURB) of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p < 0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p < 0.001). Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130. PMID:20529333

  3. Mitomycin C as an adjuvant in resected gastric cancer.

    PubMed Central

    Alcobendas, F; Milla, A; Estape, J; Curto, J; Pera, C

    1983-01-01

    As a result of their previous experience with mitomycin C at high discontinuous doses in advanced gastric cancer, the authors studied its role as an adjuvant for locally advanced cases after surgical complete resection. Results from 70 evaluable patients are presented. Patients were allocated randomly to receive mitomycin C, 20 mg/m2 I.V. direct once every 6 weeks, four courses, or a placebo. After a follow-up period of 250 weeks, seven patients of treatment arm and 23 controls have already relapsed (p less than 0.001). Toxicity was moderate and controllable by symptomatic measures. The authors consider this investigation a positive contribution in the field of adjuvant therapy of gastric cancer. PMID:6407408

  4. Natural zeolite clinoptilolite: new adjuvant in anticancer therapy.

    PubMed

    Pavelić, K; Hadzija, M; Bedrica, L; Pavelić, J; Dikić, I; Katić, M; Kralj, M; Bosnar, M H; Kapitanović, S; Poljak-Blazi, M; Krizanac, S; Stojković, R; Jurin, M; Subotić, B; Colić, M

    2001-01-01

    Natural silicate materials, including zeolite clinoptilolite, have been shown to exhibit diverse biological activities and have been used successfully as a vaccine adjuvant and for the treatment of diarrhea. We report a novel use of finely ground clinoptilolite as a potential adjuvant in anticancer therapy. Clinoptilolite treatment of mice and dogs suffering from a variety of tumor types led to improvement in the overall health status, prolongation of life-span, and decrease in tumors size. Local application of clinoptilolite to skin cancers of dogs effectively reduced tumor formation and growth. In addition, toxicology studies on mice and rats demonstrated that the treatment does not have negative effects. In vitro tissue culture studies showed that finely ground clinoptilolite inhibits protein kinase B (c-Akt), induces expression of p21WAF1/CIP1 and p27KIP1 tumor suppressor proteins, and blocks cell growth in several cancer cell lines. These data indicate that clinoptilolite treatment might affect cancer growth by attenuating survival signals and inducing tumor suppressor genes in treated cells.

  5. Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy.

    PubMed

    Mast, Natalia; Lin, Joseph B; Pikuleva, Irina A

    2015-09-01

    Cytochrome P450 CYP27A1 is the only enzyme in humans converting cholesterol to 27-hydroxycholesterol, an oxysterol of multiple functions, including tissue-specific modulation of estrogen and liver X receptors. Both receptors seem to mediate adverse effects of 27-hydroxycholesterol in breast cancer when the levels of this oxysterol are elevated. The present work assessed druggability of CYP27A1 as a potential antibreast cancer target. We selected 26 anticancer and noncancer medications, most approved by the Food and Drug Administration, and evaluated them first in vitro for inhibition of purified recombinant CYP27A1 and binding to the enzyme active site. Six strong CYP27A1 inhibitors/binders were identified. These were the two antibreast cancer pharmaceuticals anastrozole and fadrozole, antiprostate cancer drug bicalutamide, sedative dexmedetomidine, and two antifungals ravuconazole and posaconazole. Anastrozole was then tested in vivo on mice, which received subcutaneous drug injections for 1 week. Mouse plasma and hepatic 27-hydroxycholesterol levels were decreased 2.6- and 1.6-fold, respectively, whereas plasma and hepatic cholesterol content remained unchanged. Thus, pharmacologic CYP27A1 inhibition is possible in the whole body and individual organs, but does not negatively affect cholesterol elimination. Our results enhance the potential of CYP27A1 as an antibreast cancer target, could be of importance for the interpretation of Femara versus Anastrozole Clinical Evaluation Trial, and bring attention to posaconazole as a potential complementary anti-breast cancer medication. More medications on the US market may have unanticipated off-target inhibition of CYP27A1, and we propose strategies for their identification.

  6. Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy

    PubMed Central

    Mast, Natalia; Lin, Joseph B.

    2015-01-01

    Cytochrome P450 CYP27A1 is the only enzyme in humans converting cholesterol to 27-hydroxycholesterol, an oxysterol of multiple functions, including tissue-specific modulation of estrogen and liver X receptors. Both receptors seem to mediate adverse effects of 27-hydroxycholesterol in breast cancer when the levels of this oxysterol are elevated. The present work assessed druggability of CYP27A1 as a potential antibreast cancer target. We selected 26 anticancer and noncancer medications, most approved by the Food and Drug Administration, and evaluated them first in vitro for inhibition of purified recombinant CYP27A1 and binding to the enzyme active site. Six strong CYP27A1 inhibitors/binders were identified. These were the two antibreast cancer pharmaceuticals anastrozole and fadrozole, antiprostate cancer drug bicalutamide, sedative dexmedetomidine, and two antifungals ravuconazole and posaconazole. Anastrozole was then tested in vivo on mice, which received subcutaneous drug injections for 1 week. Mouse plasma and hepatic 27-hydroxycholesterol levels were decreased 2.6- and 1.6-fold, respectively, whereas plasma and hepatic cholesterol content remained unchanged. Thus, pharmacologic CYP27A1 inhibition is possible in the whole body and individual organs, but does not negatively affect cholesterol elimination. Our results enhance the potential of CYP27A1 as an antibreast cancer target, could be of importance for the interpretation of Femara versus Anastrozole Clinical Evaluation Trial, and bring attention to posaconazole as a potential complementary anti-breast cancer medication. More medications on the US market may have unanticipated off-target inhibition of CYP27A1, and we propose strategies for their identification. PMID:26082378

  7. Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients.

    PubMed

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p < 0.001), had Karnofsky Performance Status >70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income ≥$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease.

  8. Current adjuvant treatment modalities for gastric cancer: From history to the future.

    PubMed

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-05-15

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients.

  9. Current adjuvant treatment modalities for gastric cancer: From history to the future

    PubMed Central

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-01-01

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  10. Adjuvant Endocrine Therapy in Breast Cancer: A Novel e-Health Approach in Optimizing Treatment for Seniors (OPTIMUM): A Two-Group Controlled Comparison Pilot Study

    PubMed Central

    Tamblyn, Robyn; Meterissian, Sarkis; Law, Susan; Prchal, Jaroslav; Winslade, Nancy; Stern, Donna

    2016-01-01

    Background In women with hormone receptor positive breast cancer, adjuvant endocrine therapy (AET) is associated with a significant survival advantage. Nonadherence is a particular challenge in older women, even though they stand to benefit the most from AET. Therefore, a novel eHealth tool (OPTIMUM) that integrates real-time analysis of health administrative claims data was developed to provide point-of-care decision support for clinicians. Objectives The objectives of the study are to determine the effectiveness of a patient-specific, real-time eHealth alert delivered at point-of-care in reducing rates of AET discontinuation and to understand patient-level factors related to AET discontinuation as well as to assess integration of eHealth alerts regarding deviations from best practices in administration of AET by cancer care teams. Methods A prospective, 2-group controlled comparison pilot study will be conducted at 2 urban, McGill University–affiliated hospitals, the Royal Victoria Hospital and St. Mary’s Hospital. A minimum of 43 patients per study arm will be enrolled through site-level allocation. Follow-up is 1.5 years. Health care professionals at the intervention site will have access to the eHealth tool, which will report to them in real-time medical events with known associations to AET discontinuation, an AET adherence monitor, and a discontinuation alert. Cox proportional hazard ratios with 95% confidence intervals will estimate risks of AET discontinuation. Tests for significance will be 2-sided with a significance level of P<.05. Results This protocol has been approved and funded by the Canadian Institutes of Health Research. The study will evaluate site-level differences between AET discontinuation and AET adherence and assess care team actions at the intervention site. Participant enrollment into this project is expected to start September 2016 with primary data ready to present by June 2018. Conclusion This study will offer an opportunity to

  11. Examples of adjuvant treatment enhancing the antitumor effect of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Cecic, Ivana; Sun, Jinghai; Chaplin, David J.

    1999-07-01

    Strategies for improving the clinical efficacy of photodynamic therapy (PDT) in treatment of solid cancers include applications of different types of adjuvant treatments in addition to this modality that may result in superior therapeutic outcome. Examples of such an approach investigated using mouse tumor models are presented in this report. It is shown that the cures of PDT treated subcutaneous tumors can be substantially improved by adjuvant therapy with: metoclopramide (enhancement of cancer cell apoptosis), combretastatin A-4 (selective destruction of tumor neovasculature), Roussin's Black Salt (light activated tumor localized release of nitric oxide), or dendritic cell-based adoptive immunotherapy (immune rejection of treated tumor).

  12. The Na⁺/H⁺ exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells.

    PubMed

    Amith, Schammim Ray; Wilkinson, Jodi Marie; Baksh, Shairaz; Fliegel, Larry

    2015-01-20

    Dysregulation of Na⁺/H⁺ exchanger isoform one (NHE1) activity is a hallmark of cells undergoing tumorigenesis and metastasis, the leading cause of patient mortality. The acidic tumor microenvironment is thought to facilitate the development of resistance to chemotherapy drugs and to promote extracellular matrix remodeling leading to metastasis. Here, we investigated NHE1 as a co-adjuvant target in paclitaxel chemotherapy of metastatic breast cancer. We generated a stable NHE1-knockout of the highly invasive, triple-negative, MDA-MB-231 breast cancer cells. The NHE1-knockout cells proliferated comparably to parental cells, but had markedly lower rates of migration and invasion in vitro. In vivo xenograft tumor growth in athymic nude mice was also dramatically decreased compared to parental MDA-MB-231 cells. Loss of NHE1 expression also increased the susceptibility of knockout cells to paclitaxel-mediated cell death. NHE1 inhibition, in combination with paclitaxel, resulted in a dramatic decrease in viability, and migratory and invasive potential of triple-negative breast cancer cells, but not in hormone receptor-positive, luminal MCF7 cells. Our data suggest that NHE1 is critical in triple-negative breast cancer metastasis, and its chemical inhibition boosts the efficacy of paclitaxel in vitro, highlighting NHE1 as a novel, potential co-adjuvant target in breast cancer chemotherapy.

  13. [Neoadjuvant or Adjuvant Chemotherapy for Bladder Cancer?].

    PubMed

    Hupe, M C; Kramer, M W; Kuczyk, M A; Merseburger, A S

    2015-05-01

    Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.

  14. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I–III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue

    PubMed Central

    Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

    2016-01-01

    This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t0) and after the intervention (t1) as well as 3 months after finishing intervention (t2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t0 to t2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t0 to t1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t1 and t2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t1 nor for t2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase. PMID:27019663

  15. Propensity Scoring after Multiple Imputation in a Retrospective Study on Adjuvant Radiation Therapy in Lymph-Node Positive Vulvar Cancer

    PubMed Central

    Suling, Anna; Neuser, Petra; Reuss, Alexander; Canzler, Ulrich; Fehm, Tanja; Luyten, Alexander; Hellriegel, Martin; Woelber, Linn; Mahner, Sven

    2016-01-01

    Propensity scoring (PS) is an established tool to account for measured confounding in non-randomized studies. These methods are sensitive to missing values, which are a common problem in observational data. The combination of multiple imputation of missing values and different propensity scoring techniques is addressed in this work. For a sample of lymph node-positive vulvar cancer patients, we re-analyze associations between the application of radiotherapy and disease-related and non-related survival. Inverse-probability-of-treatment-weighting (IPTW) and PS stratification are applied after multiple imputation by chained equation (MICE). Methodological issues are described in detail. Interpretation of the results and methodological limitations are discussed. PMID:27802342

  16. Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer.

    PubMed

    Waltersson, Marie Ahnström; Askmalm, Marie Stenmark; Nordenskjöld, Bo; Fornander, Tommy; Skoog, Lambert; Stål, Olle

    2009-02-01

    Cyclin E and the retinoblastoma protein (Rb) are both important regulators of the G1 phase in the cell cycle. Overexpression of cyclin E and lost expression of Rb has previously been observed in breast tumours at frequencies of 10-50% and 20-30%, respectively. We explored the prognostic role of cyclin E and Rb in breast cancer patients randomised for tamoxifen (TAM), CMF (cyclophosphamide, metotrexate, 5-fluorouracil) chemotherapy and radiotherapy (RT) and how their expression affects the patients' response to treatment. Protein expression was assessed with immunohistochemistry. We found overexpression of cyclin E in 32.1% (71/221) of the tumours and loss of Rb expression in 25.0% (59/236). Increased expression of cyclin E correlated to dysfunctional p53 (P=0.003) while loss of Rb correlated to normal p53 status (P=0.001). Our results suggest that patients with high cyclin E tumours have less benefit from tamoxifen (ER+, TAM vs. no TAM; RR=0.97; 95% CI, 0.36-2.60) than patients whose tumours show low expression (ER+, TAM vs. no TAM; RR =0.41; 95% CI, 0.24-0.72). Cyclin E also tended to predict the benefit from radiotherapy with a local recurrence rate of 0.31 (RT vs. CMF; 95% CI, 0.12-0.83) for patients with low expression and 0.68 (RT vs. CMF; 95% CI, 0.2-2.32) for patients with high expression of cyclin E. When the p53 status was taken in consideration the results showed that patients with both normal p53 and normal Rb expression had considerably lower locoregional recurrence rate when treated with radiotherapy instead of CMF (RR=0.17; 95% CI, 0.052-0.58) as compared to patients with either altered Rb or p53 or both (RR=0.70; 95% CI, 0.28-1.73).

  17. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    PubMed

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  18. Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy Is More Effective in Triple-Negative, Node-Negative Breast Cancer: Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

    PubMed Central

    Colleoni, Marco; Cole, Bernard F.; Viale, Giuseppe; Regan, Meredith M.; Price, Karen N.; Maiorano, Eugenio; Mastropasqua, Mauro G.; Crivellari, Diana; Gelber, Richard D.; Goldhirsch, Aron; Coates, Alan S.; Gusterson, Barry A.

    2010-01-01

    Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer. PMID:20458051

  19. Dose Dense Cyclophosphamide, Methotrexate, Fluorouracil is Feasible at 14-Day Intervals: A Pilot Study of Every-14-Day Dosing as Adjuvant Therapy for Breast Cancer

    PubMed Central

    Drullinsky, Pamela; Sugarman, Steven M.; Fornier, Monica N.; D’Andrea, Gabriella; Gilewski, Teresa; Lake, Diana; Traina, Tiffany; Wasserheit-Lieblich, Carolyn; Sklarin, Nancy; Atieh-Graham, Deena; Mills, Nancy; Troso-Sandoval, Tiffany; Seidman, Andrew D.; Yuan, Jeffrey; Patel, Hamangi; Patil, Sujata; Norton, Larry; Hudis, Clifford

    2012-01-01

    Purpose Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule. Patients and Methods Thirty-eight patients with early-stage breast cancer were accrued from March 2008 through June 2008. They were treated every 14 days with C 600, M 40, F 600 (all mg/m2) with PEG-filgrastim (Neulasta®) support on day 2 of each cycle. The primary endpoint was tolerability using a Simon’s 2-stage optimal design. The design would effectively discriminate between true tolerability (as protocol-defined) rates of ≤ 60% and ≥ 80%. Results The median age was 52-years-old (range, 38–78 years of age). Twenty-nine of the 38 patients completed 8 cycles of CMF at 14-day intervals. Conclusion Dose-dense adjuvant CMF is tolerable and feasible at 14-day intervals with PEG-filgrastim support. PMID:21147686

  20. Herbal medicines as adjuvants for cancer therapeutics.

    PubMed

    Wang, Chong-Zhi; Calway, Tyler; Yuan, Chun-Su

    2012-01-01

    In the United States, many patients, including cancer patients, concurrently take prescription drugs and herbal supplements. Co-administration of prescription medicines and herbal supplements may have negative outcomes via pharmacodynamic and pharmacokinetic herb-drug interactions. However, multiple constituents in botanicals may also yield beneficial pharmacological activities. Botanicals could possess effective anticancer compounds that may be used as adjuvants to existing chemotherapy to improve efficacy and/or reduce drug-induced toxicity. Herbal medicines, such as ginseng, potentiated the effects of chemotherapeutic agents via synergistic activities, supported by cell cycle evaluations, apoptotic observations, and computer-based docking analysis. Since botanicals are nearly always administrated orally, the role of intestinal microbiota in metabolizing ginseng constituents is presented. Controlled clinical studies are warranted to verify the clinical utility of the botanicals in cancer chemoprevention.

  1. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

    PubMed Central

    Delishaj, Durim; Fabrini, Maria Grazia; Gonnelli, Alessandra; Morganti, Riccardo; Perrone, Franco; Tana, Roberta; Paiar, Fabiola; Gadducci, Angiolo

    2016-01-01

    Purpose The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT). Material and methods Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity. PMID:28115957

  2. Immunohistochemical Markers as Predictors of Histopathologic Response and Prognosis in Rectal Cancer Treated with Preoperative Adjuvant Therapy: State of the Art

    PubMed Central

    2017-01-01

    We explain the state of the art of the immunohistochemical markers of response in rectal cancers treated with neoadjuvant medical therapies and its implication with prognosis. Neoadjuvant chemoradiotherapy is widely used to improve the outcome of patients with locally advanced rectal cancer, and the evaluation of the effects of medical therapy is to date based on histomorphological examination by applying four grading systems of response to therapy (tumor regression grade (TRG)). The need to identify immunohistochemical markers that could ensure a better assessment of response and possibly provide additional prognostic information has emerged. We identified p53, p27kip1, Ki67, matrix metalloprotease-9, survivin, Ki67 proliferative index, CD133, COX2, CD44v6, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase as the most common markers studied in literature to date, and we explained their prognostic potential and their implications in the evaluation of the response to preoperative therapies in rectal cancers. PMID:28326100

  3. Patterns and Predictors of Early Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiation Therapy in Men With pT{sub 3}N{sub 0} Prostate Cancer: Implications for Multimodal Therapies

    SciTech Connect

    Briganti, Alberto; Joniau, Steven; Gandaglia, Giorgio; Cozzarini, Cesare; Sun, Maxine; Tombal, Bertrand; Haustermans, Karin; Hinkelbein, Wolfgang; Shariat, Shahrokh F.; Karakiewicz, Pierre I.; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas

    2013-12-01

    Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT{sub 3}N{sub 0} prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 years after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT{sub 3}N{sub 0} PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to a

  4. Salvage interstitial brachytherapy based on computed tomography for recurrent cervical cancer after radical hysterectomy and adjuvant radiation therapy: case presentations and introduction of the technique

    PubMed Central

    Liu, Zhong-Shan; Guo, Jie; Zhao, Yang-Zhi; Lin, Xia; Chen, Bin; Zhang, Ming; Li, Jiang-Ming; Ren, Xiao-Jun; Zhang, Bing-Ya

    2016-01-01

    Purpose Locally recurring cervical cancer after surgery and adjuvant radiotherapy remains a major therapeutic challenge. This paper presents a new therapeutic technique for such patients: interstitial brachytherapy (BT) guided by real-time three-dimensional (3D) computed tomography (CT). Material and methods Sixteen patients with recurrent cervical cancer after radical surgery and adjuvant external-beam radiotherapy (EBRT) were included in this study. These patients underwent high-dose-rate (HDR) interstitial BT with free-hand placement of metal needles guided by real-time 3D-CT. Six Gy in 6 fractions were prescribed for the high-risk clinical target volume (HR-CTV). D90 and D100 for HR-CTV of BT, and the cumulative D2cc for the bladder, rectum, and sigmoid, including previous EBRT and present BT were analyzed. Treatment-related complications and 3-month tumor-response rates were investigated. Results The mean D90 value for HR-CTV was 52.5 ± 3.3 Gy. The cumulative D2cc for the bladder, rectum, and sigmoid were 85.6 ± 5.8, 71.6 ± 6.4, and 69.6 ± 5.9 Gy, respectively. The mean number of needles was 6.1 ± 1.5, with an average depth of 3.5 ± 0.9 cm for each application. Interstitial BT was associated with minor complications and passable tumor-response rate. Conclusions Interstitial BT guided by real-time 3D-CT for recurrent cervical cancer results in good dose-volume histogram (DVH) parameters. The current technique may be clinically feasible. However, long-term clinical outcomes should be further investigated. PMID:27895683

  5. The use of adjuvant bisphophonates in the treatment of early-stage breast cancer.

    PubMed

    Mathew, Aju; Brufsky, Adam M

    2014-11-01

    Adjuvant treatment of breast cancer has resulted in significant improvement in breast cancer-related outcomes. In addition to chemotherapy and endocrine therapy, the bone-protective agents known as bisphosphonates have been extensively investigated for their putative antitumor effect. Backed by strong preclinical data from in vitro and in vivo models, several randomized clinical trials have evaluated the role of bisphosphonates in an adjuvant setting. The recent NSABP B-34 (National Surgical Adjuvant Breast and Bowel Project protocol B-34) and AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) studies found no disease-free survival benefit with clodronate and zoledronate, respectively, whereas the ABCSG-12 (Austrian Breast and Colorectal Cancer Study Group trial 12) study found improvement in disease-free survival with zoledronate. Data from these trials suggested a beneficial effect of bisphosphonates in older, postmenopausal women and in premenopausal women treated with ovarian suppression. Given the acceptable toxicity profile of bisphosphonates, these agents could be a useful adjunct to adjuvant chemotherapy or endocrine treatment for early-stage breast cancer in a carefully selected subset of patients. This review aims to critically synthesize the results of clinical trials of adjuvant bisphosphonates in early-stage breast cancer, and to provide guidelines for the use of these agents in early-stage breast cancer.

  6. Cancer of the Prostate Risk Assessment (CAPRA) Preoperative Score Versus Postoperative Score (CAPRA-S): ability to predict cancer progression and decision-making regarding adjuvant therapy after radical prostatectomy.

    PubMed

    Seo, Won Ik; Kang, Pil Moon; Kang, Dong Il; Yoon, Jang Ho; Kim, Wansuk; Chung, Jae Il

    2014-09-01

    The University of California, San Francisco, announced in 2011 Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score which included pathologic data, but there were no results for comparing preoperative predictors with the CAPRA-S score. We evaluated the validation of the CAPRA-S score in our institution and compare the result with the preoperative progression predictor, CAPRA score. Data of 130 patients were reviewed who underwent radical prostatectomy for localized prostate cancer from 2008 to 2013. Performance of CAPRA-S score in predicting progression free probabilities was assessed through Kaplan Meier analysis and Cox proportional hazards regression test. Additionally, prediction probability was compared with preoperative CAPRA score by logistic regression analysis. Comparing CAPRA score, the CAPRA-S score showed improved prediction ability for 5 yr progression free survival (concordance index 0.80, P = 0.04). After risk group stratification, 3 group model of CAPRA-S was superior than 3 group model of CAPRA for 3-yr progression free survival and 5-yr progression free survival (concordance index 0.74 vs. 0.70, 0.77 vs. 0.71, P < 0.001). Finally the CAPRA-S score was the more ideal predictor concerned with adjuvant therapy than the CAPRA score through decision curve analysis. The CPARA-S score is a useful predictor for disease progression after radical prostatectomy.

  7. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    SciTech Connect

    Bhatia, Sumita; Miller, Robert C. . E-mail: miller.robert@mayo.edu; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

    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 included 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.

  8. Targeted Therapies for Kidney Cancer

    MedlinePlus

    ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  9. 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.

  10. Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials.

    PubMed

    Regan, Meredith M; Pagani, Olivia; Francis, Prudence A; Fleming, Gini F; Walley, Barbara A; Kammler, Roswitha; Dell'Orto, Patrizia; Russo, Leila; Szőke, János; Doimi, Franco; Villani, Laura; Pizzolitto, Stefano; Öhlschlegel, Christian; Sessa, Fausto; Peg Cámara, Vicente; Rodríguez Peralto, José Luis; MacGrogan, Gaëtan; Colleoni, Marco; Goldhirsch, Aron; Price, Karen N; Coates, Alan S; Gelber, Richard D; Viale, Giuseppe

    2015-11-01

    The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-negative disease. Of 5707 women enrolled, 4115 with HER2-negative (HR+/HER2-) disease had ER, PgR, and Ki-67 centrally assessed by immunohistochemistry. Breast cancer-free interval (BCFI) was defined from randomization to first invasive local, regional, or distant recurrence or contralateral breast cancer. The prognostic and predictive values of ER, PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology. In this HR+/HER2- population, the median ER, PgR, and Ki-67 expressions were 95, 90, and 18 % immunostained cells. As most patients had strongly ER-positive tumors, the predictive value of ER levels could not be investigated. Lower PgR and higher Ki-67 expression were associated with reduced BCFI. There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels, though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression (OFS) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67. Women with poor prognostic features of low PgR and/or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone, but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2- early breast cancer.

  11. Adjuvant photodynamic therapy in surgical management of cerebral tumors

    NASA Astrophysics Data System (ADS)

    Chen, Zong-Qian; Wu, Si-En; Zhu, Shu-Gan

    1993-03-01

    We have performed high dose photoradiation therapy in patients with cerebral tumors. Twenty-seven patients had gliomas, two had metastatic cancer of the brain, one had malignant meningioma. Hematoporphyrin derivative was administered intravenously. All patients underwent a craniotomy with a radical or partial excision of the tumor. There was no evidence of increased cerebral edema and other toxicity from the therapy, and all patients were discharged from the hospital within 15 days after surgery. On the basis of animal experiments our institute started using photodynamic therapy (PDT) as an adjuvant measure to the operative therapy in 30 cases of cerebral tumors. Ten of these patients were excluded from this group because of the short postoperative following time. Here, the details of our experiences are presented as follows: 106 of C6 type glioma cell strain were implanted into the frontal lobe of a Chinese hamster. Fourteen days later intracranial gliomas developed, which were larger than 4 mm in diameter, HpD in a dosage of 4 mg/kg was injected into the tail vein of the animals. The fluorescence was seen 5 minutes later. The diagnostic laser used was He-Ca (Hc-type 15A, made at Shanghai Laser Institute) with a wavelength of 441.6 nm, power of 30 mw. The fluorescence reached its peak point 24 hours later, and the normal tissue can be identified by the lack of fluorescence. Then, the tumor tissue was further radiated with an Ar laser (made in Nanjing Electronic Factory, type 360), pumped dye-laser (made in Changchun Optic Machinery Institute, type 901) with a wavelength of 630 nm, and an energy density of more than 200 Joules/cm2, which might get the tumor cells destroyed selectively. The effect of photoradiation may reach as deep as 4 - 7 mm into the brain tissue without cerebral edema or necrosis.

  12. Cancer Therapy

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The patient shown is undergoing cancer radiation treatment in a hospital-like atmosphere but he is not in a hospital. The treatment room is at NASA's Lewis Research Center, Cleveland, Ohio. It is a converted portion of the Center's cyclotron facility, originally designed for radiation studies related to nuclear propulsion for aircraft and spacecraft. Under an agreement between the Center and the Cleveland Clinic Foundation, the 50 million volt cyclotron is now being used to evaluate the effectiveness of "fast neutron" therapy in the treatment of cancerous tumors.

  13. Adjuvant radiotherapy following radical hysterectomy for patients with stage IB and IIA cervical cancer

    SciTech Connect

    Soisson, A.P.; Soper, J.T.; Clarke-Pearson, D.L.; Berchuck, A.; Montana, G.; Creasman, W.T. )

    1990-06-01

    From 1971 through 1984, 320 women underwent radical hysterectomy as primary therapy of stage IB and IIA cervical cancer. Two hundred forty-eight patients (78%) were treated with surgery alone and 72 patients (22%) received adjuvant postoperative external-beam radiotherapy. Presence of lymph node metastasis, large lesion (greater than 4 cm in diameter), histologic grade, race (noncaucasian), and age (greater than 40 years) were significant poor prognostic factors for the entire group of patients. Patients treated with surgery alone had a better disease-free survival than those who received combination therapy (P less than 0.001). However, patients receiving adjuvant radiation therapy had a higher incidence of lymphatic metastases, tumor involvement of the surgical margin, and large cervical lesions. Adjuvant pelvic radiation therapy did not improve the survival of patients with unilateral nodal metastases or those who had a large cervical lesion with free surgical margins and the absence of nodal involvement. Radiation therapy appears to reduce the incidence of pelvic recurrences. Unfortunately, 84% of patients who developed recurrent tumor after combination therapy had a component of distant failure. The incidence of severe gastrointestinal or genitourinary tract complications was not different in the two treatment groups. However, the incidence of lymphedema was increased in patients who received adjuvant radiation therapy. Although adjuvant radiation therapy appears to be tolerated without a significant increase in serious complications, the extent to which it may improve local control rates and survival in high-risk patients appears to be limited. In view of the high incidence of distant metastases in high-risk patients, consideration should be given to adjuvant systemic chemotherapy in addition to radiation therapy.

  14. Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: 10-Year Follow-Up

    SciTech Connect

    Kim, Tae-Won; Lee, Je-Hwan; Lee, Jung-Hee; Ahn, Jin-Hee; Kang, Yoon-Koo; Lee, Kyoo-Hyung; Yu, Chang-Sik; Kim, Jong-Hoon; Ahn, Seung-Do; Kim, Woo-Kun; Kim, Jin-Cheon; Lee, Jung-Shin

    2011-11-15

    Purpose: To determine the optimal sequence of postoperative adjuvant chemotherapy and radiotherapy in patients with Stage II or III rectal cancer. Methods and Materials: A total of 308 patients were randomized to early (n = 155) or late (n = 153) radiotherapy (RT). Treatment included eight cycles of chemotherapy, consisting of fluorouracil 375 mg/m{sup 2}/day and leucovorin 20 mg/m{sup 2}/day, at 4-week intervals, and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on Day 1 of the first chemotherapy cycle in the early RT arm and on Day 1 of the third chemotherapy cycle in the late RT arm. Results: At a median follow-up of 121 months for surviving patients, disease-free survival (DFS) at 10 years was not statistically significantly different between the early and late RT arms (71% vs. 63%; p = 0.162). A total of 36 patients (26.7%) in the early RT arm and 49 (35.3%) in the late RT arm experienced recurrence (p = 0.151). Overall survival did not differ significantly between the two treatment groups. However, in patients who underwent abdominoperineal resection, the DFS rate at 10 years was significantly greater in the early RT arm than in the late RT arm (63% vs. 40%; p = 0.043). Conclusions: After the long-term follow-up duration, this study failed to show a statistically significant DFS advantage for early radiotherapy with concurrent chemotherapy after resection of Stage II and III rectal cancer. Our results, however, suggest that if neoadjuvant chemoradiation is not given before surgery, then early postoperative chemoradiation should be considered for patients requiring an abdominoperineal resection.

  15. Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

    SciTech Connect

    Chan, Elisa K.; Woods, Ryan; McBride, Mary L.; Virani, Sean; Nichol, Alan; Speers, Caroline; Wai, Elaine S.; Tyldesley, Scott

    2014-03-15

    Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiac risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast

  16. Adjuvant Therapy for Renal Cell Carcinoma: Past, Present, and Future

    PubMed Central

    Pal, Sumanta K.

    2014-01-01

    At the present time, the standard of care for patients who have received nephrectomy for localized renal cell carcinoma (RCC) is radiographic surveillance. With a number of novel targeted agents showing activity in the setting of metastatic RCC, there has been great interest in exploring the potential of the same agents in the adjuvant setting. Herein, we discuss the evolution of adjuvant trials in RCC, spanning from the immunotherapy era to the targeted therapy era. Pitfalls of current studies are addressed to provide a context for interpreting forthcoming results. Finally, we outline avenues to incorporate promising investigational agents, such as PD-1 (programmed death-1) inhibitors and MNNG transforming gene inhibitors, in future adjuvant trials. PMID:24969163

  17. Adjuvant Cancer Biotherapy by Viscum Album Extract Isorel: Overview of Evidence Based Medicine Findings.

    PubMed

    Sunjic, Suzana Borovic; Gasparovic, Ana Cipak; Vukovic, Tea; Weiss, Thomas; Weiss, Elisabeth Sussman; Soldo, Ivo; Djakovic, Nikola; Zarkovic, Tomislav; Zarkovic, Neven

    2015-09-01

    Within the integrative medicine one of the most frequently used adjuvant cancer biotherapies is based on aqueous mistletoe (Viscum album) extracts. Tumor growth inhibition, stimulation of host immune response and improvement of the quality of life are the positive effects of mistletoe therapy described in several preclinical and clinical studies. However, cumulative results of the evidence based medicine findings on such treatments are rarely given. Therefore, this paper evaluates the evidence based findings describing effects of the Viscum album extract Isorel in cancer therapy with respect to the type of therapy, stage and type of illness. This study presents cumulated data for 74 patients with different types and stages of cancer treated by Viscum album extract as adjuvant treatment to different conventional therapies, mostly combined surgery and radiotherapy. The biotherapy effectiveness was evaluated according to the outcome as (1) no major therapeutic improvement (15% of patients), (2) prevention of tumor recurrence (47% of patients) and (3) regression of cancer (38% of patients). Notably, there was no obvious health worsening during the follow up period at all. Thus, the results obtained for conventional anticancer therapies combined with adjuvant biotherapy based on Viscum album extract seem to be beneficial for the majority of cancer patients (85%) without serious side effects.

  18. Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)

    SciTech Connect

    Wang, Xin; Li, Guangjun; Zhang, Yingjie; Bai, Sen; Xu, Feng; Wei, Yuquan; Gong, Youling

    2013-01-01

    To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patient's case, the parameters were compared based on the dose-volume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMAT plans successfully achieved better target dose conformity, reduced the V{sub 20/30}, and mean dose of the left kidney, as well as the V{sub 20/30} of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V{sub 20} of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6 Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future.

  19. External beam boost versus interstitial high-dose-rate brachytherapy boost in the adjuvant radiotherapy following breast-conserving therapy in early-stage breast cancer: a dosimetric comparison

    PubMed Central

    Melchert, Corinna; Kovács, György

    2016-01-01

    Purpose This study aims to compare the dosimetric data of local tumor's bed dose escalation (boost) with photon beams (external beam radiation therapy – EBRT) versus high-dose-rate interstitial brachytherapy (HDR-BT) after breast-conserving treatment in women with early-stage breast cancer. Material and methods We analyzed the treatment planning data of 136 irradiated patients, treated between 2006 and 2013, who underwent breast-conserving surgery and adjuvant whole breast irradiation (WBI; 50.4 Gy) and boost (HDR-BT: 10 Gy in one fraction [n = 36]; EBRT: 10 Gy in five fractions [n = 100]). Organs at risk (OAR; heart, ipsilateral lung, skin, most exposed rib segment) were delineated. Dosimetric parameters were calculated with the aid of dose-volume histograms (DVH). A non-parametric test was performed to compare the two different boost forms. Results There was no difference for left-sided cancers regarding the maximum dose to the heart (HDR-BT 29.8% vs. EBRT 29.95%, p = 0.34). The maximum doses to the other OAR were significantly lower for HDR-BT (Dmax lung 47.12% vs. 87.7%, p < 0.01; rib 61.17% vs. 98.5%, p < 0.01; skin 57.1% vs. 94.75%, p < 0.01; in the case of right-sided breast irradiation, dose of the heart 6.00% vs. 16.75%, p < 0.01). Conclusions Compared to EBRT, local dose escalation with HDR-BT presented a significant dose reduction to the investigated OAR. Only left-sided irradiation showed no difference regarding the maximum dose to the heart. Reducing irradiation exposure to OAR could result in a reduction of long-term side effects. Therefore, from a dosimetric point of view, an interstitial boost complementary to WBI via EBRT seems to be more advantageous in the adjuvant radiotherapy of breast cancer. PMID:27648082

  20. 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

  1. Future of therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2013-06-01

    Since 2004, the standard of care for patients with cT3 and/or N+ rectal cancer has been preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. A number of advances have occurred and are defining the future of rectal cancer therapy. Among these are short course radiation, the impact of postoperative adjuvant chemotherapy, selective radiation and selective surgery, and new chemoradiation regimens with novel agents. This review will examine these developments and assess their impact on the future therapy of rectal cancer.

  2. Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery

    ClinicalTrials.gov

    2013-02-26

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer; Stage IVA Rectal Cancer; Stage IVB Rectal Cancer

  3. Neoadjuvant and adjuvant chemotherapy approaches for invasive bladder cancer.

    PubMed

    Raghavan, Derek; Burgess, Earle; Gaston, Kris E; Haake, Michael R; Riggs, Steven B

    2012-10-01

    Deeply invasive bladder cancer, representing approximately 20% of incident cases, is cured by radical cystectomy or radiotherapy in less than 50% of cases. In an effort to improve cure rates, based on objective response rates in metastatic disease of 40%-70% from combination chemotherapy regimens, systemic chemotherapy has been incorporated into programs of definitive treatment for this disease. Several randomized trials and a meta-analysis have confirmed a survival benefit from neoadjuvant chemotherapy followed by definitive local treatment, reflecting both median survival figures and cure rates. Despite several promising phase II trials, no randomized trial of classical adjuvant chemotherapy for bladder cancer has demonstrated an overall survival benefit, despite increments in disease-free survival. Molecular prognostication has been studied in an effort to improve the utility of systemic therapy for invasive non-metastatic bladder cancer, but randomized trials have not shown associated survival benefit. Despite level 1 evidence of a survival benefit from neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin], cisplatin) or cisplatin, methotrexate, and vinblastine (CMV) chemotherapy, more than 50% of incident cases do not receive such treatment.

  4. Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

    PubMed

    Zhu, Xinyan; Liu, Fei

    2017-03-10

    Over 80% population with Helicobacter pylori (H. pylori) infection is asymptomatic. H. pylori was considered as a primary reason for various natural gastric physiopathology. Increased antibiotic resistance and less medication compliance lead to the failure of antibiotic eradication therapy. Probiotics have been applied as a supplementary treatment in H. pylori eradication therapy in recent years. They have direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials. Because of the improvement in eradication rates and therapy-related side effects, probiotics have been considered as the useful supplementation to current eradication therapy although the treatment outcomes were controversial due to the heterogeneity of probiotics in species, strains, doses and therapeutic duration. Despite the positive role of probiotics, several factors need to be further considered during the application of probiotics. At last, the adverse effects of probiotics are notable. Further investigation into the safety of adjuvant probiotics to present H. pylori eradication therapy is still needed.

  5. A Model to Estimate the Risk of Breast Cancer-Related Lymphedema: Combinations of Treatment-Related Factors of the Number of Dissected Axillary Nodes, Adjuvant Chemotherapy, and Radiation Therapy

    SciTech Connect

    Kim, Myungsoo; Kim, Seok Won; Lee, Sung Uk; Lee, Nam Kwon; Jung, So-Youn; Kim, Tae Hyun; Lee, Eun Sook; Kang, Han-Sung; Shin, Kyung Hwan

    2013-07-01

    Purpose: The development of breast cancer-related lymphedema (LE) is closely related to the number of dissected axillary lymph nodes (N-ALNs), chemotherapy, and radiation therapy. In this study, we attempted to estimate the risk of LE based on combinations of these treatment-related factors. Methods and Materials: A total of 772 patients with breast cancer, who underwent primary surgery with axillary lymph node dissection from 2004 to 2009, were retrospectively analyzed. Adjuvant chemotherapy (ACT) was performed in 677 patients (88%). Among patients who received radiation therapy (n=675), 274 (35%) received supraclavicular radiation therapy (SCRT). Results: At a median follow-up of 5.1 years (range, 3.0-8.3 years), 127 patients had developed LE. The overall 5-year cumulative incidence of LE was 17%. Among the 127 affected patients, LE occurred within 2 years after surgery in 97 (76%) and within 3 years in 115 (91%) patients. Multivariate analysis showed that N-ALN (hazard ratio [HR], 2.81; P<.001), ACT (HR, 4.14; P=.048), and SCRT (HR, 3.24; P<.001) were independent risk factors for LE. The total number of risk factors correlated well with the incidence of LE. Patients with no risk or 1 risk factor showed a significantly lower 5-year probability of LE (3%) than patients with 2 (19%) or 3 risk factors (38%) (P<.001). Conclusions: The risk factors associated with LE were N-ALN, ACT, and SCRT. A simple model using combinations of these factors may help clinicians predict the risk of LE.

  6. Role of Adjuvant Chemoradiotherapy for Resected Extrahepatic Biliary Tract Cancer

    SciTech Connect

    Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae Lee, Woo Jin; Woo, Sang Myung; Moon, Sung Ho; Yoo, Tae; Kim, Sang Soo; Kim, Seong Hoon; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-12-01

    Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. Methods and Materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p = .007; 32.1% vs. 26.1%, p = .041; 36.5% vs. 28.2%, p = .049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p < .05). Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.

  7. Chemotherapy in recurrent advanced non-small-cell lung cancer after adjuvant chemotherapy

    PubMed Central

    Valdes, M.; Nicholas, G.; Goss, G.D.; Wheatley-Price, P.

    2016-01-01

    Introduction Despite adjuvant systemic therapy in patients with completely resected non-small-cell lung cancer (nsclc), many will subsequently relapse. We investigated treatment choices at relapse and assessed the effect of palliative platinum doublet systemic therapy in this population. Methods With research ethics board approval, we performed a retrospective chart review of all patients with resected nsclc who received adjuvant systemic therapy from January 2002 until December 2008 at our institution. The primary outcome was the response rate to first-line palliative systemic therapy among patients who relapsed. Results We identified 176 patients who received adjuvant platinum doublet systemic therapy (82% received cisplatin–vinorelbine). In the 85 patients who relapsed (48%), median time to relapse was 18.5 months (95% confidence interval: 15 months to 21.3 months). Palliative systemic therapy was given in 43 patients. Of those 43 patients, 25 (58%) were re-challenged with platinum doublet systemic therapy, with a response rate of 29% compared with 18% in 18 patients who received other systemic therapy (p = 0.48). We observed a trend toward an increased clinical benefit rate (complete response + partial response + stable disease) in patients who were treated with a platinum doublet (67% vs. 41%, p = 0.12). Median overall survival (os) from relapse was 15.3 months in patients receiving palliative systemic therapy and 7.8 months in those receiving best supportive care alone. Compared with patients treated with non-platinum regimens, the platinum-treated group experienced longer survival after relapse (18.4 months vs. 9.7 months, p = 0.041). Conclusions In patients previously treated with adjuvant systemic therapy, re-treatment with platinum doublet chemotherapy upon relapse is feasible. Moreover, compared with patients receiving other first-line systemic therapy, patients receiving platinum doublets experienced higher response rates and significantly longer

  8. Breast cancer follow-up in the adjuvant setting.

    PubMed

    Khatcheressian, James; Swainey, Craig

    2008-01-01

    Breast cancer may recur through 15 years and beyond after diagnosis; thus, breast cancer patients require long-term follow-up after adjuvant treatment to detect recurrent disease. History taking, physical examination, and regular mammography are still the foundation of appropriate breast cancer follow-up in the adjuvant setting. Clearly, breast MRI has a role in certain high-risk patients, but in moderate-risk patients, the decision to use MRI must be based on the complexity of the clinical scenario. Other routine imaging studies (CT, positron emission tomography, and bone scans) and laboratory testing--including tumor marker assessments--in asymptomatic patients have not demonstrated an improvement in survival, quality of life, toxicity, or cost-effectiveness. Survivorship issues are also an inherent part of breast cancer follow-up; physicians should make every effort to address supportive care issues unique to breast cancer survivors including hot flashes, bone health, neuropathy, and risk-reduction strategies.

  9. MiR-4653-3p and its target gene FRS2 are prognostic biomarkers for hormone receptor positive breast cancer patients receiving tamoxifen as adjuvant endocrine therapy

    PubMed Central

    Wang, Zhu; Wang, Yu; Wang, YanPing; Qiu, Yan; Li, Li; Bu, Hong; Li, JiaYuan; Zheng, Hong

    2016-01-01

    Long-term tamoxifen treatment significantly improves the survival of hormone receptor-positive (HR+) breast cancer (BC) patients. However, tamoxifen resistance remains a challenge. We aimed to identify prognostic biomarkers for tamoxifen resistance and reveal the underlying mechanism. From March 2001 to September 2013, 400 HR+ BC women (stage I~III) were treated with adjuvant tamoxifen for 5 years or until relapse in West China Hospital. We included a discovery set of 6 patients who were refractory to tamoxifen, and a validation cohort of 88 patients including 35 cases with relapse. In the discovery set, microRNA microarray showed that miR-4653-3p decreased in recurrent/metastatic lesions compared to the matched primary lesions. In the validation cohort, real-time RT-PCR demonstrated that, following tamoxifen treatment, miR-4653-3p overexpression in the primary tumors decreased the risk of relapse (adjusted hazard ratio [HR] = 0.17, 95% confidence interval [CI] = 0.05~0.57, P = 0.004). Conversely, high expression of FRS2, the key adaptor protein required by FGFR signaling, predicted poor disease-free survival (DFS) (adjusted HR = 2.70, 95% CI = 1.11~6.56, P = 0.03). MiR-4653-3p down regulated FRS2 by binding to its 3′ untranslated region. Either overexpressing miR-4653-3p or attenuating FRS2 expression could restore TAM sensitivity in two tamoxifen-resistant BC cell lines. In conclusion, high miR-4653-3p level was the potential predictor for favorable DFS, while FRS2 overexpression was potential high-risk factor for relapse in HR+ BC patients receiving TAM adjuvant therapy. FGFR/FRS2 signaling might be a promising target for reversing tamoxifen resistance. PMID:27533459

  10. Herpes virus infection and uterine cervix carcinoma. General considerations, personal experimental data and suggestions for a specific antiherpes adjuvant therapy.

    PubMed

    Nastac, E; Hozoc, M; Stoian, M

    1982-01-01

    The authors review some data of the literature and results of personal investigations that point out a relationship between human herpes simplex virus infection and the etiopathogeny of uterine cervix carcinoma. On the ground of these data the authors suggest a "specific antiherpes" adjuvant therapy in this form of human cancer.

  11. [Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].

    PubMed

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

    Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy.

  12. Adjuvant chemotherapy for gastric cancer in Japan: global and Japanese perspectives.

    PubMed

    Sakamoto, Junichi; Morita, Satoshi; Kodera, Yasuhiro; Rahman, Mahbubur; Nakao, Akimasa

    2004-09-01

    Adjuvant therapy for gastric cancer after surgical resection has been under clinical investigation for decades. However, up until now, consistent and concrete evidence has not been generated either in Japan or other countries in favor of adjuvant therapy in terms of survival compared to surgery alone. Meta-analyses reported from Western countries have shown either no or borderline benefit for chemotherapy after surgical resection of gastric cancer. A recent trial showed significant benefit for chemoradiotherapy. However, Japanese specialists believe that their perspectives are different from those in the West due to the following: (1) gastric cancer incidence is several times higher in Japan; (2) more stringent screening programs are emphasized in Japan, thus baseline conditions of cancer patients are different; (3) specific operative techniques are used; and (4) Japanese surgeons have probably acquired additional experience in gastric cancer resection techniques. From the 1960s to the 1980s first mitomycin (MMC) and, later, a combination of oral fluorinated pyrimidines (o-FP) and MMC showed improved survival benefit in Japan compared to surgery alone. However, in the late 1980s, an expert group re-examined the results of previous trials, questioned them, and suggested fresh trials. Since then, the Japanese Clinical Oncology Group (JCOG) has conducted relevant trials to re-examine the effect of MMC and/or o-FP as adjuvant chemotherapy. The results of trials JCOG 8801 and JCOG 9206 have already been reported, and the accrual of patients for another trial (NSAS-GC trial) has just been completed. A pooled analysis of the two preceding trials showed a borderline survival benefit for o-FP compared to surgery alone. If o-FP treatment shows a 5% difference in survival benefit in the NSAS-GC trial, a meta-analysis of the three trials would probably reveal overall significant results. In conclusion, this therapy could become the standard adjuvant treatment regimen for

  13. Endocrine therapy of breast cancer

    SciTech Connect

    Cavalli, F.

    1986-01-01

    This book results from a meeting of the ESO (European School of Oncology) Task Force on endocrine aspects of breast cancer. The contributions stem from some of the most outstanding researchers in Europe and highlight mainly methodological issues and new avenues for future research. The chapters on basic research deal primarily with experimental strategies for studying the relationship between steroid hormones, growth factors, and oncongenes. The clinically oriented chapters treat the methodology of clinical trials. Provocative questions are raised, such as: What are the pitfalls in endocrine trials. What does statistical proof mean. How can we consider a quality of life endpoint in the adjuvant setting. Two special reports deal with the controversial issues of chemoprevention in high-risk normal women and the optimization of the hormonal contribution to the adjuvant therapy of breast cancer. Topics considered included oncogenic transformations, radiotherapy, steroid hormones, cell proliferation, tamoxifen, and preventive medicine.

  14. Randomized Phase II Study of 5-Fluorouracil Hepatic Arterial Infusion with or without Antineoplastons as an Adjuvant Therapy after Hepatectomy for Liver Metastases from Colorectal Cancer

    PubMed Central

    Ogata, Yutaka; Matono, Keiko; Tsuda, Hideaki; Ushijima, Masataka; Uchida, Shinji; Akagi, Yoshito; Shirouzu, Kazuo

    2015-01-01

    Background Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplaston A10 and AS2-1 reportedly control neoplastic growth and do not significantly inhibit normal cell growth. Antineoplastons contain 3-phenylacetylamino-2, 6-piperidinedione (A10), phenylacetylglutamine plus phenylacetylisoglutamine (A10-I), and phenylacetylglutamine plus phenylacetate (AS2-1). This open label, non- blinded randomized phase II study compared the efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil,with or without antineoplastons as a postoperative therapy for colorectal metastasis to the liver. Methods Sixty-five patients with histologically confirmed metastatic colon adenocarcinoma in liver, who had undergone hepatectomy, and/or thermal ablation for liver metastases were enrolled between 1998- 2004 in Kurume University Hospital. Patients were randomly assigned to receive systemic antineoplastons (A10-I infusion followed by per-oral AS2-1) plus HAI (AN arm) or HAI alone (control arm) based on the number of metastases and presence/ absence of extra-hepatic metastasis at the time of surgery. Primary endpoint was cancer-specific survival (CSS); secondary endpoints were relapse-free survival (RFS), status and extent of recurrence, salvage surgery (rate) and toxicity. Findings Overall survival was not statistically improved (p=0.105) in the AN arm (n=32). RFS was not significant (p=0.343). Nevertheless, the CSS rate was significantly higher in the AN arm versus the control arm (n=33) with a median survival time 67 months (95%CI 43-not calculated) versus 39 months (95%CI 28-47) (p=0.037) and 5 year CSS rate 60% versus 32% respectively. Cancer recurred more often in a single organ than in multiple organs in the AN arm versus the control arm. The limited extent of recurrent tumours in the AN arm meant more patients remained eligible for salvage surgery. Major adverse effects of antineoplastons were fullness of the

  15. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma.

    PubMed

    Jianyong, Lei; Jinjing, Zhong; Lunan, Yan; Jingqiang, Zhu; Wentao, Wang; Yong, Zeng; Bo, Li; Tianfu, Wen; Jiaying, Yang

    2017-02-03

    Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients.

  16. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma

    PubMed Central

    Jianyong, Lei; Jinjing, Zhong; Lunan, Yan; Jingqiang, Zhu; Wentao, Wang; Yong, Zeng; Bo, Li; Tianfu, Wen; Jiaying, Yang

    2017-01-01

    Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients. PMID:28155861

  17. [Criteria of efficacy of adjuvant immunotherapy of surface cancer of the urinary bladder].

    PubMed

    Loran, O B; Medvedev, V L; Budnik, N V

    2005-01-01

    Assessment of prognostic significance of interleukine-8 (L-8) urine levels was made in 12 patients with verified surface cancer of the urinary bladder (SCUB) on adjuvant intravesical immunotherapy. Quantitative enzyme immunoassay identified IL-8 in the urine before intravesical injection of BCG vaccine and 6 hours later. A total of 192 urine samples were studied ("Multiskan-Jems", 405 nm). Adjuvant immunotherapy raises an L-8 level in the urine of the patients. After 8-week immunotherapy IL-8 elevated from 169.4 pg/ml to 326 pg/ml. Four patients with minimal difference in IL-8 urine levels (120 pg/ml, on the average) before and 6 hours after intravesical injection of BCG vaccine developed recurrence. Thus, quantitative assessment of IL-8 in urine of SCUB patients given intravesical BCG therapy can serve as one of prognostic criteria of adjuvant immunotherapy efficacy.

  18. [Postoperative adjuvant chemotherapy using NCS (neocarzinostatin) and 5-FU in the treatment of gastric cancer. First report--A comparison with the 5-year survival rate of patients undergoing combined therapy with MMC and 5-FU].

    PubMed

    Yokomori, T; Taniguchi, T; Iesato, H; Sakata, Y; Watanabe, T; Kawabe, K

    1987-11-01

    As a postoperative adjuvant chemotherapy for gastric cancer, we have administered a combination of NCS (Neocarzinostatin) and 5-FU (NF treatment method) and in this paper we have compiled the results obtained in patients who were treated for 5 years in an attempt to compare the 5-year survival rate with that of patients administered a combination of MMC and 5-FU (MF treatment group) and a control group administered no anticancer agents. As the selection of either NF or MF treatment was conducted on an annual basis, this study can be considered an historical controlled study. The results obtained are summarized as follows. On comparing the survival rate of the NF treatment group and the control group, the 5-year survival rate for all patients who underwent curative resection and all patients with histological stage III cancers and the curative resection PS (+) group, as well as the survival period of the non-resected patients, showed a statistically significant difference, indicating that the survival rate was higher in the NF group. On comparing the NF group and the MF group, although no statistically significant difference was observed between then based on a stratified analysis of all resected cases, histological stage differences and n.ps factors, etc., certain values tended to indicate a higher survival rate for the NF group. Moreover, the survival rate of the non-resected patients was more favorable in the NF group. These results confirm that NCS is useful for the treatment of stomach cancer and compares favorably with MMC. The appearance of side-effects was significantly lower in the NF group in comparison with the MF group and the number of patients who had to discontinue therapy was extremely low.

  19. [HER-2/neu positive breast cancer: how to prescribe adjuvant trastuzumab (Herceptin)?].

    PubMed

    Belkacémi, Yazid; Gligorov, Joseph; Mauriac, Louis; Azria, David

    2006-10-01

    One of the most recent advances in the management of Her-2/neu positive breast cancer is the validation of a targeted therapy from bench to the clinic, particularly towards the adjuvant setting. The recommended dose of trastuzumab (Herceptin), a humanized monoclonal antibody targeting the HER-2 antigen, has been determined in phase I studies. In the metastatic patients two randomised trials have demonstrated its efficacy when associated to taxanes. In less than 10 years, trastuzumab became the standard of care in the adjuvant treatment of HER-2/neu positive breast cancer. In this setting, two combinations regimen with chemotherapy (concomitant or sequential) have been recently published. The concomitant schedule has been used in three studies (North American Group, BCIRG, FinHer), whereas in the Hera trial trastuzumab was started after the end of neo-adjuvant and adjuvant chemotherapy. In this article, the advantages and uncertainties on efficacy and toxicities of the trastuzumab administration modalities, associated or not to chemotherapy and radiation therapy, are discussed.

  20. Targeted Therapy for Cancer

    Cancer.gov

    Targeted therapy is a type of cancer treatment that targets the changes in cancer cells that help them grow, divide, and spread. Learn how targeted therapy works against cancer and about side effects that may occur.

  1. Neo-adjuvant radiotherapy in rectal cancer

    PubMed Central

    Glimelius, Bengt

    2013-01-01

    In rectal cancer treatment, attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence. Several large randomized trials have also shown that combinations of surgery, radiotherapy and chemotherapy have markedly reduced the risk of a loco-regional recurrence, but this has not yet had any major influence on overall survival. The best results have been achieved when the radiotherapy has been given preoperatively. Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance, i.e., when a total mesorectal excision has been performed. The relative reduction is then 50%-70%. The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance, as practised in some Asian countries. Many details about how the radiotherapy is performed are still open for discussion, and practice varies between countries. A highly fractionated radiation schedule (5 Gy × 5), proven efficacious in many trials, has gained much popularity in some countries, whereas a conventionally fractionated regimen (1.8-2.0 Gy × 25-28), often combined with chemotherapy, is used in other countries. The additional therapy adds morbidity to the morbidity that surgery causes, and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high. The best integration of the weakest modality, to date the drugs (conventional cytotoxics and biologicals) is not known. A new generation of trials exploring the best sequence of treatments is required. Furthermore, there is a great need to develop predictors of response, so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging. PMID:24379566

  2. Adjuvant therapy for intrahepatic cholangiocarcinoma: the debate continues.

    PubMed

    Zhu, Andrew X; Knox, Jennifer J

    2012-01-01

    lymph nodes were obtained, all of which were negative, consistent with a stage T2, N0, MX intrahepatic cholangiocarcinoma. The tumor was positive for CK7, CK19, and CA19-9 and negative for CK20, CDX2, CA125, ER, PR, GCDFP-15, synaptophysin, and chromogranin (Table 1). The uninvolved liver was unremarkable and a trichrome stain showed no fibrosis. Following an uneventful postoperative recovery, she was referred for consideration of adjuvant therapy.

  3. miR-21 Expression in Cancer Cells may Not Predict Resistance to Adjuvant Trastuzumab in Primary Breast Cancer.

    PubMed

    Nielsen, Boye Schnack; Balslev, Eva; Poulsen, Tim Svenstrup; Nielsen, Dorte; Møller, Trine; Mortensen, Christiane Ehlers; Holmstrøm, Kim; Høgdall, Estrid

    2014-01-01

    Trastuzumab is established as standard care for patients with HER2-positive breast cancer both in the adjuvant and metastatic setting. However, 50% of the patients do not respond to the trastuzumab therapy, and therefore new predictive biomarkers are highly warranted. MicroRNAs (miRs) constitute a new group of biomarkers and their cellular expression can be determined in tumor samples by in situ hybridization (ISH) analysis. miR-21 is highly prevalent and up-regulated in breast cancer and has been linked to drug resistance in clinical and in vitro settings. To determine expression patterns of miR-21 in high-grade breast cancers, we examined miR-21 expression in 22 HER2-positive tumors and 15 HER2-negative high-grade tumors by ISH. The histological examination indicated that patient samples could be divided into three major expression patterns: miR-21 predominantly in tumor stroma, predominantly in cancer cells, or in both stromal and cancer cells. There was no obvious difference between the HER2-positive and HER2-negative tumors in terms of the miR-21 expression patterns and intensities. To explore the possibility that miR-21 expression levels and/or cellular localization could predict resistance to adjuvant trastuzumab in HER2-positive breast cancer patients, we analyzed additional 16 HER2-positive tumors from patients who were treated with trastuzumab in the adjuvant setting. Eight of the 16 patients showed clinical recurrence and were considered resistant. Examination of the miR-21 expression patterns and intensities revealed no association between the miR-21 scores in the cancer cell population (p = 0.69) or the stromal cells population (p = 0.13) and recurrent disease after adjuvant trastuzumab. Thus, our findings show that elevated miR-21 expression does not predict resistance to adjuvant trastuzumab.

  4. Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

    PubMed Central

    Emmons, Russell; Niemiro, Grace M.; De Lisio, Michael

    2016-01-01

    Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers. PMID:27123008

  5. Role of Adjuvant Chemoradiotherapy for Ampulla of Vater Cancer

    SciTech Connect

    Kim, Kyubo; Chie, Eui Kyu Jang, Jin-Young; Kim, Sun Whe; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W.

    2009-10-01

    Purpose: To evaluate the role of adjuvant chemoradiotherapy for ampulla of Vater cancer. Methods and Materials: Between January 1991 and December 2002, 118 patients with ampulla of Vater cancer underwent en bloc resection. Forty-one patients received adjuvant chemoradiotherapy [RT(+) group], and 77 did not [RT(-) group]. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes, for a total dose of up to 40 Gy delivered in 2-Gy fractions, with a planned 2-week rest period halfway through the treatment period. Intravenous 5-fluorouracil (500 mg/m{sup 2}/day) was given on Days 1 to 3 of each split course. The median follow-up was 65 months. Results: The 5-year overall survival rate in the RT(-) and RT(+) groups was 66.9% and 52.8%, respectively (p = 0.2225). The 5-year locoregional relapse-free survival rate in the RT(-) and RT(+) groups was 79.9% and 80.2%, respectively (p = 0.9582). When age, type of operation, T stage, N stage, histologic differentiation, and the use of adjuvant chemoradiotherapy were incorporated into the Cox proportional hazard model, there was an improvement in the locoregional relapse-free survival rate (p = 0.0050) and a trend toward a longer overall survival (p = 0.0762) associated with the use of adjuvant chemoradiotherapy. Improved overall survival (p = 0.0235) and locoregional relapse-free survival (p = 0.0095) were also evident in patients with nodal metastasis. In contrast, enhanced locoregional control (p = 0.0319) did not result in longer survival in patients with locally advanced disease (p = 0.4544). Conclusions: Adjuvant chemoradiotherapy may enhance locoregional control and overall survival in patients with ampulla of Vater cancer after curative resection, especially in those with nodal involvement.

  6. Design, conduct, and analyses of Breast International Group (BIG) 1-98: A randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer

    PubMed Central

    Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

    2010-01-01

    Background Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. Purpose To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. Methods From 1998–2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. Results The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Limitations Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. Conclusions BIG 1-98 is an example of an enriched design, involving

  7. Adjuvant chemotherapy for resected colorectal cancer metastases: Literature review and meta-analysis

    PubMed Central

    Brandi, Giovanni; De Lorenzo, Stefania; Nannini, Margherita; Curti, Stefania; Ottone, Marta; Dall’Olio, Filippo Gustavo; Barbera, Maria Aurelia; Pantaleo, Maria Abbondanza; Biasco, Guido

    2016-01-01

    Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials. PMID:26811604

  8. Adjuvant Everolimus for Resected Kidney Cancer

    Cancer.gov

    In this clinical trial, patients with renal cell cancer who have undergone partial or complete nephrectomy will be randomly assigned to take everolimus tablets or matching placebo tablets daily for 54 weeks.

  9. Evolution of Long-Term Adjuvant Anti-hormone Therapy: Consequences and Opportunities. The St. Gallen Prize Lecture

    PubMed Central

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

    2012-01-01

    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 nor-epinephrine 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

  10. 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

  11. [Adjuvant treatment of breast cancer by concomitant hormonotherapy and radiotherapy: state of the art].

    PubMed

    Azria, D; Lemanski, C; Zouhair, A; Gutowski, M; Belkacémi, Y; Dubois, J B; Romieu, G; Ozsahin, M

    2004-06-01

    Combining radiation and hormone therapy has become common clinical practice in recent years for locally advanced prostate cancer. The use of such concomitant therapy in the treatment of breast disease has been very infrequently reported in the literature, but such an application seems justified given the common hormonal dependence of breast cancer and the potential synergetic effect of these two treatment modalities. As adjuvant therapy, tamoxifen is the key drug in the hormonal treatment arsenal, providing a significant improvement in both local control and global survival rates. Aromatase inhibitors are currently being evaluated in this setting, and initial results are promising. In vitro, tamoxifen does not seem to offer a protective effect against radiation. In clinical use, the few available published studies confirm the superiority of the association of radiation with tamoxifen as opposed to radiation therapy alone in decreasing local recurrences of surgically removed breast tumors. Toxicity associated with such concomitant therapy includes mainly subcutaneous and pulmonary fibroses. However, subcutaneous fibrosis and its cosmetic impact on the treated breast are frequently described side effects of radiation therapy, and their incidence may actually be reduced when tamoxifen is associated. The evidence is less controversial for pulmonary fibrosis, which is more common with the concomitant therapy. The association of radiation and aromatase inhibitors has as of yet rarely been reported. Letrozole (Femara) has a radiosensitizing effect on breast-cancer cell lines transfected with the aromatase gene. Clinical data assessing this effect in vivo are not available. The FEMTABIG study (letrozole vs. tamoxifen vs. sequential treatment) did not specify the sequence of radiation and hormonal therapy. The ATAC study comparing the adjuvant use of anastrozole (Arimidex) and tamoxifen does not provide any information on the number of patients receiving radiation

  12. The association of adjuvant therapy with survival at the population level following pancreatic adenocarcinoma resection

    PubMed Central

    Kagedan, Daniel J.; Raju, Ravish S.; Dixon, Matthew E.; Shin, Elizabeth; Li, Qing; Liu, Ning; Elmi, Maryam; El-Sedfy, Abraham; Paszat, Lawrence; Kiss, Alexander; Earle, Craig C.; Mittmann, Nicole; Coburn, Natalie G.

    2016-01-01

    Background Using a retrospective observational cohort approach, the overall survival (OS) following curative-intent resection of pancreatic adenocarcinoma (PC) was defined at the population level according to adjuvant treatment, and predictors of OS were identified. Methods Patients undergoing resection of PC in the province of Ontario between 2005 and 2010 were identified using the provincial cancer registry, and linked to databases that include all treatments received and outcomes experienced in the province. Pathology reports were abstracted for staging and margin status. Patients were identified as having received chemotherapy (CT), chemoradiation therapy (CRT), or no adjuvant treatment (NAT). Kaplan–Meier survival analysis of patients surviving ≥6 months was performed, and predictors of OS identified by log-rank test. Cox multivariable analysis was used to define independent predictors of OS. Results Among the 473 patients undergoing PC resection, the median survival was 17.8 months; for the 397 who survived ≥6 months following surgery, the 5-year OS for the CT, CRT, and NAT groups was 21%, 16%, and 17%, respectively (p = 0.584). Lymph node-negative patients demonstrated improved OS associated with chemotherapy on multivariable analysis (HR = 2.20, 95% CI = 1.25–3.83 for NAT vs. CT). Conclusions Following PC resection, only patients with negative lymph nodes demonstrated improved OS associated with adjuvant chemotherapy. PMID:27037203

  13. The iBRA-2 (immediate breast reconstruction and adjuvant therapy audit) study: protocol for a prospective national multicentre cohort study to evaluate the impact of immediate breast reconstruction on the delivery of adjuvant therapy

    PubMed Central

    Dave, Rajiv; O'Connell, Rachel; Rattay, Tim; Tolkien, Zoe; Barnes, Nicola; Skillman, Joanna; Williamson, Paula; Conroy, Elizabeth; Gardiner, Matthew; Harnett, Adrian; O'Brien, Ciara; Blazeby, Jane; Holcombe, Chris

    2016-01-01

    Introduction Immediate breast reconstruction (IBR) is routinely offered to improve quality of life for women with breast cancer requiring a mastectomy, but there are concerns that more complex surgery may delay the delivery of adjuvant oncological treatments and compromise long-term oncological outcomes. High-quality evidence, however, is lacking. iBRA-2 is a national prospective multicentre cohort study that aims to investigate the effect of IBR on the delivery of adjuvant therapy. Methods and analysis Breast and plastic surgery centres in the UK performing mastectomy with or without (±) IBR will be invited to participate in the study through the trainee research collaborative network. All women undergoing mastectomy ± IBR for breast cancer between 1 July and 31 December 2016 will be included. Patient demographics, operative, oncological and complication data will be collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR will be compared to determine the impact that IBR has on the time of delivery of adjuvant therapy. Prospective data on 3000 patients from ∼50 centres are anticipated. Ethics and dissemination Research ethics approval is not required for this study. This has been confirmed using the online Health Research Authority decision tool. This novel study will explore whether IBR impacts the time to delivery of adjuvant therapy. The study will provide valuable information to help patients and surgeons make more informed decisions about their surgical options. Dissemination of the study protocol will be via the Mammary Fold Academic and Research Collaborative (MFAC) and the Reconstructive Surgery Trials Network (RSTN), the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS). Participating units will have access to their own data and collective results will be presented at relevant surgical conferences and

  14. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    PubMed

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  15. Survival After Chemoradiation in Resected Pancreatic Cancer: The Impact of Adjuvant Gemcitabine

    SciTech Connect

    Baschnagel, Andrew; Shah, Chirag; Margolis, Jeffrey; Nadeau, Laura; Stein, Julie; Jury, Robert; Robertson, John M.

    2012-07-01

    Purpose: To evaluate survival in patients with resected pancreatic cancer treated with concurrent chemoradiation with or without adjuvant gemcitabine (Gem). Methods and Materials: From 1998 to 2010, 86 patients with pancreatic adenocarcinoma who underwent resection were treated with adjuvant concurrent chemoradiation. Thirty-four patients received concurrent 5-fluorouracil-based chemoradiation (5-FU/RT) with traditional field radiation (range, 45-61.2 Gy; median, 50.4 Gy) without further adjuvant therapy. Thirty patients received traditional field 5-FU/RT (range, 45-60.4 Gy; median, 50.4 Gy) with Gem (1,000 mg/m{sup 2} weekly) either before and after radiotherapy or only after radiotherapy. Twenty-two patients received concurrent full-dose Gem (1,000 mg/m{sup 2} weekly)-based chemoradiation (Gem/RT), consisting of involved-field radiation (range, 27-38 Gy; median, 36 Gy) followed by further adjuvant Gem. Results: The median age of the cohort was 65 years (range, 40-80 years). Of the patients, 58 had T3 tumors (67%), 22 had T2 tumors (26%), and 6 had T1 tumors (7%). N1 disease was present in 61 patients (71%), whereas 18 patients (21%) had R1 resections. Performance status, lymph node status, and margin status were all similar among the treatment groups. Median follow-up was 19.0 months. Median overall survival (OS) (19.2 months, 19.0 months, and 21.0 months) and 3-year OS rates (26.5%, 27.2%, and 32.1%) were similar among patients with 5-FU/RT with no adjuvant Gem, those with 5-FU/RT with adjuvant Gem, and those with Gem/RT with adjuvant Gem, respectively (p = 0.88). Patients who received adjuvant Gem had a similar median OS (22.1 months) and 3-year OS rate (29%) compared to patients who did not (19.2 months and 26.5%, respectively) (p = 0.62). There was a trend for improved 3-year OS rates in patients with R0 vs. R1 resections (28.1% vs. 14.2%, p = 0.06) and in patients with T1 and T2 vs. T3 tumors (38% vs. 20%, p = 0.09). Node-negative patients had an improved 3

  16. Targeted therapies for cancer

    MedlinePlus

    ... disables the cancer cells so they cannot spread. How Does Targeted Therapy Work? Targeted therapy drugs work in a few different ways. They may: Turn off the process in cancer cells that causes them to grow and spread Trigger cancer cells to die on their own Kill cancer cells directly People ...

  17. Laser therapy for cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

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

    PubMed Central

    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

    2012-01-01

    Background: 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). Methods: 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. Results: 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. Conclusion: 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. PMID:22531635

  19. Biologic Therapy (Immunotherapy) for Kidney Cancer

    MedlinePlus

    ... Stage for Kidney Cancer Kidney Cancer Treating Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer The goal of biologic therapy ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  20. Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy.

    PubMed

    Khouri, Michel G; Hornsby, Whitney E; Risum, Niels; Velazquez, Eric J; Thomas, Samantha; Lane, Amy; Scott, Jessica M; Koelwyn, Graeme J; Herndon, James E; Mackey, John R; Douglas, Pamela S; Jones, Lee W

    2014-02-01

    Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimensional echocardiography (3DE) and global longitudinal strain (GLS), have potential for early identification of chemotherapy-related myocardial injury. Exercise "stress" is an established method to uncover impairments in cardiac function but has received limited attention in the adult oncology setting. We evaluated the utility of an integrated approach using 3DE, GLS, and exercise stress echocardiography for detecting subclinical cardiac dysfunction in early breast cancer patients treated with DOX-containing chemotherapy. Fifty-seven asymptomatic women with early breast cancer (mean 26 ± 22 months post-chemotherapy) and 20 sex-matched controls were studied. Resting left ventricular (LV) function was assessed by LVEF using 2-dimensional echocardiography (2DE) and 3DE and by GLS using 2-dimensional speckle-tracking echocardiography (2D-STE). After resting assessments, subjects completed cardiopulmonary exercise testing with stress 2DE. Resting LVEF was lower in patients than controls by 3DE (55 ± 4 vs. 59 ± 5 %; p = 0.005) but not 2DE (56 ± 4 vs. 58 ± 3 %; p = 0.169). 10 of 51 (20 %) patients had GLS greater than or equal to -17 %, which was below the calculated lower limit of normal (control mean 2SD); this patient subgroup had a mean 20 % impairment in GLS (-16.1 ± 0.9 vs. -20.1 ± 1.5 %; p < 0.001), despite similar LVEF by 2DE and 3DE compared to controls (p > 0.05). Cardiopulmonary function (VO2peak) was 20 % lower in patients than controls (p < 0.001). Exercise stress 2DE assessments of stroke volume (61 ± 11 vs. 69 ± 15 ml; p = 0.018) and cardiac index (2.3 ± 0.9 vs. 3.1 ± 0.8 l min(-1) m(-2) mean increase; p = 0.003) were lower in patients than controls. Post-exercise increase in cardiac index predicted VO2peak (r = 0.429, p = 0

  1. Significant Effect of Polymorphisms in CYP2D6 and ABCC2 on Clinical Outcomes of Adjuvant Tamoxifen Therapy for Breast Cancer Patients

    PubMed Central

    Kiyotani, Kazuma; Mushiroda, Taisei; Imamura, Chiyo K.; Hosono, Naoya; Tsunoda, Tatsuhiko; Kubo, Michiaki; Tanigawara, Yusuke; Flockhart, David A.; Desta, Zeruesenay; Skaar, Todd C.; Aki, Fuminori; Hirata, Koichi; Takatsuka, Yuichi; Okazaki, Minoru; Ohsumi, Shozo; Yamakawa, Takashi; Sasa, Mitsunori; Nakamura, Yusuke; Zembutsu, Hitoshi

    2010-01-01

    Purpose The clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism, and elimination of its active forms. We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen. Patients and Methods We studied 282 patients with hormone receptor–positive, invasive breast cancer receiving tamoxifen monotherapy, including 67 patients who have been previously reported. We investigated the effects of allelic variants of CYP2D6 and haplotype-tagging single nucleotide polymorphisms (tag-SNPs) of ABCB1, ABCC2, and ABCG2 on recurrence-free survival using the Kaplan-Meier method and Cox regression analysis. Plasma concentrations of tamoxifen metabolites were measured in 98 patients receiving tamoxifen 20 mg/d. Results CYP2D6 variants were significantly associated with shorter recurrence-free survival (P = .000036; hazard ratio [HR] = 9.52; 95% CI, 2.79 to 32.45 in patients with two variant alleles v patients without variant alleles). Among 51 tag-SNPs in transporter genes, a significant association was found at rs3740065 in ABCC2 (P = .00017; HR = 10.64; 95% CI, 1.44 to 78.88 in patients with AA v GG genotypes). The number of risk alleles of CYP2D6 and ABCC2 showed cumulative effects on recurrence-free survival (P = .000000055). Patients carrying four risk alleles had 45.25-fold higher risk compared with patients with ≤ one risk allele. CYP2D6 variants were associated with lower plasma levels of endoxifen and 4-hydroxytamoxifen (P = .0000043 and .00052), whereas no significant difference was found among ABCC2 genotype groups. Conclusion Our results suggest that polymorphisms in CYP2D6 and ABCC2 are important predictors for the prognosis of patients with breast cancer treated with tamoxifen. PMID:20124171

  2. Lack of long-lasting effects of mitotane adjuvant therapy in a mouse xenograft model of adrenocortical carcinoma.

    PubMed

    Doghman, Mabrouka; Lalli, Enzo

    2013-12-05

    Mitotane is a widely used drug in the therapy of adrenocortical carcinoma (ACC). It is important to set up preclinical protocols to study the possible synergistic effects of its association with new drugs for ACC therapy. We assessed the efficacy of different routes of administration of mitotane (i.p. and oral) in inhibiting growth of H295R ACC cell xenografts in an adjuvant setting. Both formulations of mitotane could inhibit H295R xenografts growth only at short times after carcinoma cells inoculation, even though plasma mitotane levels approached or fell within the therapeutic range in humans. Our results show that mitotane adjuvant therapy is inadequate to antagonize long-term growth of H295R cancer cells xenografts and that care should then be taken in the design of preclinical protocols to evaluate the performance of new drugs in association with mitotane.

  3. Combined modality therapy for rectal cancer.

    PubMed

    Minsky, Bruce D; Röedel, Claus; Valentini, Vincenzo

    2010-01-01

    The standard adjuvant treatment for cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These include the role of short course radiation, whether postoperative adjuvant chemotherapy necessary for all patients and whether the type of surgery after chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.

  4. The effects of genomic polymorphisms in one-carbon metabolism pathways on survival of gastric cancer patients received fluorouracil-based adjuvant therapy

    PubMed Central

    Zhao, Tingting; Xu, Zhi; Gu, Dongying; Wu, Peng; Huo, Xinying; Wei, Xiaowei; Tang, Yongfei; Gong, Weida; He, Ming-Liang; Chen, Jinfei

    2016-01-01

    5-fluorouracil (5-FU) is widely used to treat patients with gastric cancer (GC). However, the response rate is quite heterogeneous. The single nucleotide polymorphisms (SNPs) and their interactions of genes in the one-carbon metabolism (OCM) pathway, including Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), Methionine synthase (MTR), and Thymidylate synthase (TS), significantly affect 5-FU metabolism. In this study, 650 stage II-III patients were recruited from 1998 to 2006. Among them, 251 received 5-FU treatment and other 399 patients were untreated. The Cox regression analysis, log-rank tests and Kaplan–Meier plots were adopted. In the chemotherapy cohort, MTRR 66 GA + GG genotypes decreased death risk, however, the protect effect of MTRR 66 GA + GG disappeared when GC patients simultaneously had MTHFR 677TT + TC or MTR 2756GG + GA genotypes. TS 5′-UTR 2R3R + 3R3R genotypes also prolonged overall survival of patients treated with 5-FU. And this favorable prognosis obviously enhanced when GC patients simultaneously had TS 3′-UTR DD + DI and TS 5′-UTR 2R3R + 3R3R genotypes. Our findings showed that the polymorphisms of MTRR 66 A > G and TS 5′-UTR 3R > 2R may be potential prognostic factors for GC patients receiving 5-FU. PMID:27456431

  5. Endometrial carcinoma--relative effectiveness of adjuvant irradiation vs therapy reserved for relapse.

    PubMed

    Ackerman, I; Malone, S; Thomas, G; Franssen, E; Balogh, J; Dembo, A

    1996-02-01

    Fifty-four patients with recurrent endometrial carcinoma were identified from a retrospective review of charts of 304 endometrial cancer patients seen between 1983 and 1989 at our center. A review was undertaken to identify the patterns of relapse, to determine the outcome of salvage treatment, to examine the factors predictive of effective salvage, and, if salvage is effective, to assess an alternative strategy to routine adjuvant postoperative pelvic radiotherapy. Forty percent of the entire recurrent population are long-term survivors. Of the 54 relapsing patients, primary therapy had been surgery alone in 32 and surgery and adjuvant radiotherapy (rt) in 22. Isolated pelvic recurrence was the predominate relapse site in those who had not received adjuvant pelvic RT as primary therapy (23 of 32 or 72%). Distant relapse predominated in those who received adjuvant RT (17 or 22 or 77%). Twenty-eight (54%) failed in the pelvis alone, and 26 (46%) had a component of distant failure. Of the 28 with isolated pelvic relapse, 16 had vaginal mucosal disease involvement only and 12 had disease in the parametrium and/or the pelvic sidewall. With a minimum follow-up for the survivors of 5 years, 21 of the 28 with isolated pelvic relapse received radical radiotherapy and 14 or 67% had maintained pelvic control until death or last follow-up. Eleven of 14 (79%) with disease confined to the mucosa had pelvic control, whereas only 3 of 7 (43%) with extramucosal disease were controlled. No patient experienced major treatment-related toxicity. Tumor size, anatomic extent of pelvic recurrence, RT dose, and disease-free interval were examined for prognostic significance for pelvic control and survival by univariate analysis. Only anatomic extent of pelvic recurrence showed a nonstatistically significant trend as a predictor for control with P = 0.08. In conclusion, a significant proportion of patients with disease recurrence confined to the pelvis can be rendered disease-free long

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

    SciTech Connect

    Sher, David J.; Thotakura, Vijaya; Balboni, Tracy A.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen; Goguen, Laura A.; Annino, Donald J.; Tishler, Roy B.

    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 distribution 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

  7. Advances in management of adjuvant chemotherapy in rectal cancer: Consequences for clinical practice.

    PubMed

    Netter, Jeanne; Douard, Richard; Durdux, Catherine; Landi, Bruno; Berger, Anne; Taieb, Julien

    2016-11-01

    More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the 'gold standard' for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer remain justified in future to achieve a high level of proof in keeping with evidence-based medical standards.

  8. Evaluation of monophosphoryl lipid A as an immune adjuvant for photodynamic therapy in a rat sarcoma model: preliminary results

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Edwards, Benjamin F.; Griffey, Stephen M.; Madewell, Bruce R.

    1999-06-01

    Photodynamic therapy (PDT) is a treatment option for several forms of human cancer, and like traditional chemotherapy and ionizing radiation therapy, PDT alone is not curative for some cases. Recent efforts have aimed at developing strategies for adjuvant therapy for PDT. Given the nature of PDT-mediated cell damage, immunotherapy is a promising adjuvant for long-term control of solid tumors. A candidate immune stimulant for use with PDT is monophosphoryl lipid A (MLA), a non-toxic fraction of the endotoxin molecule. The hypothesis is that adjuvant MLA immunotherapy with PDT will improve local tumor control and prevent growth of subsequently implanted tumor cells when compared to PDT alone. To date, no significant differences in circulating leukocyte populations or tumor infiltrating lymphocyte populations have been identified in 9L tumor-bearing F344 rats after systemic administrations of MLA. Likewise, no significant difference has been identified in local tumor control following PDT of 9L tumors with or without adjuvant MLA. Further results are pending.

  9. Molecular Markers Predict Distant Metastases After Adjuvant Chemoradiation for Rectal Cancer

    SciTech Connect

    Kim, Jun Won; Kim, Yong Bae; Choi, Jun Jeong; Koom, Woong Sub; Kim, Hoguen; Kim, Nam-Kyu; Ahn, Joong Bae; Lee, Ikjae; Cho, Jae Ho; Keum, Ki Chang

    2012-12-01

    Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant

  10. [Radiation therapy of pancreatic cancer].

    PubMed

    Huguet, F; Mornex, F; Orthuon, A

    2016-09-01

    Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In adjuvant setting, the standard treatment is 6 months of chemotherapy with gemcitabine and capecitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This should be confirmed by a prospective trial. Neoadjuvant CRT is a promising treatment especially for patients with borderline resectable tumors. For patients with locally advanced tumors, there is no a standard. An induction chemotherapy followed by CRT for non-progressive patients reduces the rate of local relapse. Whereas in the first trials of CRT large fields were used, the treated volumes have been reduced to improve tolerance. Tumor movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique is not recommended.

  11. Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer

    PubMed Central

    Karlsson, P.; Sun, Z.; Braun, D.; Price, K. N.; Castiglione-Gertsch, M.; Rabaglio, M.; Gelber, R. D.; Crivellari, D.; Collins, J.; Murray, E.; Zaman, K.; Colleoni, M.; Gusterson, B. A.; Viale, G.; Regan, M. M.; Coates, A. S.; Goldhirsch, A.

    2011-01-01

    Background: The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer. Patients and methods: From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of ‘classical’ CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMF→ goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years. Results: For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMF→ goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS). Conclusions: For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhea. PMID:21325445

  12. [The role of Lactobacillus acidophilus in the prevention and adjuvant therapy of certain infectious diseases].

    PubMed

    Halmy, C; Halmy, L

    1998-09-27

    Authors call attention to the role of lactic acid bacteria in the prevention and adjuvant therapy of certain infective diseases. It has special importance in the prevention and adjuvant therapy of new-born and childhood enteritis, different urogenital inflammations and antibiotic associated diarrhoea. Administration of lactic acid bacteria create eubiosis between the human organism and the world of bacteria, that is, eubacteriosis is developed instead of a pathogen flora, assuring normal physiologic functions for the well-being of the organism.

  13. Radiation Therapy for Cancer

    Cancer.gov

    Radiation therapy is a type of cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Learn about the types of radiation, why side effects happen, which ones you might have, and more.

  14. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    PubMed Central

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  15. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis

    PubMed Central

    Coyle, C.; Cafferty, F. H.; Vale, C.; Langley, R. E.

    2016-01-01

    Background Metformin use has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates in meta-analyses, but, to date, evidence to support the use of metformin as an adjuvant therapy in individual cancer types has not been presented. Patients and methods We systematically searched research databases, conference abstracts and trial registries for any studies reporting cancer outcomes for individual tumour types in metformin users compared with non-users, and extracted data on patients with early-stage cancer. Studies were assessed for design and quality, and a meta-analysis was conducted to quantify the adjuvant effect of metformin on recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS), to inform future trial design. Results Of 7670 articles screened, 27 eligible studies were identified comprising 24 178 participants, all enrolled in observational studies. In those with early-stage colorectal cancer, metformin use was associated with a significant benefit in all outcomes [RFS hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.47–0.85; OS HR 0.69, CI 0.58–0.83; CSS HR 0.58, CI 0.39–0.86]. For men with early-stage prostate cancer, metformin was associated with significant, or borderline significant, benefits in all outcomes (RFS HR 0.83, CI 0.69–1.00; OS HR 0.82, CI 0.73–0.93; CSS HR 0.58, CI 0.37–0.93); however, there was significant heterogeneity between studies. The data suggest that prostate cancer patients treated with radical radiotherapy may benefit more from metformin (RFS HR 0.45, CI 0.29–0.70). In breast and urothelial cancer, no significant benefits were identified. Sufficient data were not available to conduct analyses on the impact of metformin dose and duration. Conclusions Our findings suggest that metformin could be a useful adjuvant agent, with the greatest benefits seen in colorectal and prostate cancer, particularly in those receiving radical

  16. Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: a pilot study.

    PubMed

    Kahn, S Anthony; Mullin, Christine M; de Lorimier, Louis-Philippe; Burgess, Kristine E; Risbon, Rebecca E; Fred, Rogers M; Drobatz, Kenneth; Clifford, Craig A

    2013-03-01

    Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA.

  17. Targeted Radiation Therapy for Cancer Initiative

    DTIC Science & Technology

    2014-09-01

    routine clinical use, 2) whether the use of Vac-Lok® immobilization devices are necessary when patients are treated using the Calypso system, 3...using breath-hold technique for left-sided breast cancer patients treated with adjuvant radiation therapy, with the benefit of confirmatory tracking...required for each patient thereby reducing the cost of care and increasing treatment capacity within the military delivery system; enabling research to

  18. Aflibercept and Ang1 supplementation improve neoadjuvant or adjuvant chemotherapy in a preclinical model of resectable breast cancer

    PubMed Central

    Wu, Florence T. H.; Paez-Ribes, Marta; Xu, Ping; Man, Shan; Bogdanovic, Elena; Thurston, Gavin; Kerbel, Robert S.

    2016-01-01

    Phase III clinical trials evaluating bevacizumab (an antibody to the angiogenic ligand, VEGF-A) in breast cancer have found improved responses in the presurgical neoadjuvant setting but no benefits in the postsurgical adjuvant setting. The objective of this study was to evaluate alternative antiangiogenic therapies, which target multiple VEGF family members or differentially modulate the Angiopoietin/Tie2 pathway, in a mouse model of resectable triple-negative breast cancer (TNBC). Neoadjuvant therapy experiments involved treating established orthotopic xenografts of an aggressive metastatic variant of the MDA-MB-231 human TNBC cell line, LM2-4. Adjuvant therapies were given after primary tumor resections to treat postsurgical regrowths and distant metastases. Aflibercept (‘VEGF Trap’, which neutralizes VEGF-A, VEGF-B and PlGF) showed greater efficacy than nesvacumab (an anti-Ang2 antibody) as an add-on to neoadjuvant/adjuvant chemotherapy. Concurrent inhibition of Ang1 and Ang2 signaling (through an antagonistic anti-Tie2 antibody) was not more efficacious than selective Ang2 inhibition. In contrast, short-term perioperative BowAng1 (a recombinant Ang1 variant) improved the efficacy of adjuvant chemotherapy. In conclusion, concurrent VEGF pathway inhibition is more likely than Ang/Tie2 pathway inhibition (e.g., anti-Ang2, anti-Ang2/Ang1, anti-Tie2) to improve neoadjuvant/adjuvant chemotherapies for TNBC. Short-term perioperative Ang1 supplementation may also have therapeutic potential in conjunction with adjuvant chemotherapy for TNBC. PMID:27841282

  19. A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902

    SciTech Connect

    Rosenthal, Seth A.; Hunt, Daniel; Sartor, A. Oliver; Pienta, Kenneth J.; Gomella, Leonard; Grignon, David; Rajan, Raghu; Kerlin, Kevin J.; Jones, Christopher U.; Dobelbower, Michael; Shipley, William U.; Zeitzer, Kenneth; Hamstra, Daniel A.; Donavanik, Viroon; Rotman, Marvin; Hartford, Alan C.; Michalski, Jeffrey; Seider, Michael; Kim, Harold; and others

    2015-10-01

    Purpose: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). Methods and Materials: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥7 or clinical stage ≥T2 and GS ≥8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. Results: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). Conclusions: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for

  20. Review of Adjuvant Radiochemotherapy for Resected Pancreatic Cancer and Results From Mayo Clinic for the 5th JUCTS Symposium

    SciTech Connect

    Miller, Robert C. Iott, Matthew J.; Corsini, Michele M.

    2009-10-01

    Purpose: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. Methods and Materials: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4Gy in 28 fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. Results: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). Conclusions: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.

  1. Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82 cases

    SciTech Connect

    Kassam, Zahra |; Lockwood, Gina |; O'Brien, Catherine; Brierley, James |; Swallow, Carol ||; Oza, Amit |; Siu, Lillian |; Knox, Jennifer J. |; Wong, Rebecca |; Cummings, Bernard; Kim, John |; Moore, Malcolm |; Ringash, Jolie |. E-mail: jolie.ringash@rmp.uhn.on.cag

    2006-07-01

    Background: The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT). Methods and Materials: Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial. Results: Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years. Conclusion: Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.

  2. Controversies of adjuvant endocrine treatment for breast cancer and recommendations of the 2007 St Gallen conference.

    PubMed

    Rabaglio, Manuela; Aebi, Stefan; Castiglione-Gertsch, Monica

    2007-10-01

    Endocrine treatment for breast cancer was introduced more than a century ago. The discovery of hormone receptors has allowed targeting of endocrine treatment to patients whose primary tumours express these receptors. In the adjuvant setting, different approaches are used in premenopausal or postmenopausal women. In premenopausal patients, suppression of ovarian function and the use of tamoxifen are the most important therapeutic options, even though questions on timing, duration, and combination of these compounds remain unanswered. The use of aromatase inhibitors in combination with ovarian-function suppression is currently under investigation in the premenopausal setting. In postmenopausal patients, aromatase inhibitors given after 2-3 years or 5 years of tamoxifen have shown a significant benefit over tamoxifen alone. However, questions on this treatment also remain unanswered. For example, whether all patients should receive an aromatase inhibitor or whether some subgroups of patients might be optimally treated by tamoxifen alone is yet to be established. In this paper we review the published work on adjuvant endocrine treatment in breast cancer and provide recommendations from the 2007 St Gallen International Conference on Primary Therapy of Early Breast Cancer.

  3. Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

    PubMed Central

    Meyers, B.M.; Cosby, R.; Quereshy, F.; Jonker, D.

    2016-01-01

    Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken. Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline. Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer. Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer. PMID:28050138

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

    SciTech Connect

    Kim, Anne; Schreiber, David; Rineer, Justin; Choi, Kwang; Rotman, Marvin

    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: We 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.

  5. Neutron therapy of cancer

    NASA Technical Reports Server (NTRS)

    Frigerio, N. A.; Nellans, H. N.; Shaw, M. J.

    1969-01-01

    Reports relate applications of neutrons to the problem of cancer therapy. The biochemical and biophysical aspects of fast-neutron therapy, neutron-capture and neutron-conversion therapy with intermediate-range neutrons are presented. Also included is a computer program for neutron-gamma radiobiology.

  6. [A case of early gastric cancer completely responding to adjuvant chemotherapy for advanced colon cancer].

    PubMed

    Tanaka, Ryo; Kameyama, Hitoshi; Nakano, Mae; Ichikawa, Hiroshi; Hanyu, Takaaki; Nakano, Masato; Ishikawa, Takashi; Shimada, Yoshifumi; Sakata, Jun; Kobayashi, Takashi; Kosugi, Shinichi; Minagawa, Masahiro; Koyama, Yu; Wakai, Toshifumi

    2014-11-01

    A 70-year-old man was referred to our hospital with ascending colon cancer (cT3N1M0, Stage IIIa), which was found during examinations following a positive fecal occult blood test. The patient was also diagnosed with early gastric cancer (cT1a, N0, M0, Stage IA)during a preoperative gastroscopy examination. A laparoscopically assisted right colectomy and D3 lymphadenectomy was performed for the ascending colon cancer. The postoperative pathological diagnosis was Stage IIIb (pT3N2), he was administered in combination with capecitabine plus oxaliplatin (CapeOX) as adjuvant chemotherapy before the treatment for the colon cancer. After 6 months of adjuvant chemotherapy, we were unable to detect any gastric lesions at the same location using gastroscopy, and so diagnosed a clinical complete response. A follow-up gastroscopy 6 months later showed the same findings. The patient has had no recurrence of gastric cancer for 18 months after the initial operation. He will continue to be followed up closely using gastroscopy. In this case, CapeOX as adjuvant chemotherapy for advanced colon cancer was also effective for early gastric cancer.

  7. Proteomics as a Guide for Personalized Adjuvant Chemotherapy in Patients with Early Breast Cancer.

    PubMed

    Lumachi, Franco; Chiara, Giordano B; Foltran, Luisa; Basso, Stefano M M

    2015-01-01

    Proteomics allows for better understanding of the function and regulation of cancer cells mediated by intra- and extracellular signaling networks. Integrating such information with clinicopathological characteristics of the tumor may lead to either detection of disease biomarkers useful to differentiate high-from low-risk patients, or to identification of new drug targets. Adjuvant chemotherapy is currently a personalized treatment strategy, especially for breast cancer (BC) patients, and the risk assessment of each patient influences its use because the benefit strictly correlates with the level of risk. Luminal A BCs are endocrine therapy (ET)-sensitive but exhibit low sensitivity to chemotherapy, while luminal B cancers, according to the Ki-67 proliferation rate may require for chemotherapy in addition to ET, and HER2-positive tumors derive benefit from adjuvant chemotherapy containing an anthracycline, a taxane and trastuzumab for one year. Triple-negative BCs have a high degree of genomic instability exhibiting a more aggressive clinical course with respect to other types of BC, and the anthracycline-taxane regimen constitutes the standard approach. Studies considering the use of targeted approaches (drugs), including poly (ADP-ribose) polymerase (PARP-1), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) inhibitors, or EFGR and HER2 blockers, are still under evaluation. In the genomic era, promising new targeted-therapies are worthy of further investigation, and mTOR inhibitors have been used for patients with high-risk ER-positive and HER2-negative tumors. In the near future, genetic and molecular profiling of BC will help to better-categorize patients, determine the choice of chemotherapy in low-risk, or intensify the treatment in high-risk cancer patients, eventually revealing new targeted agents.

  8. Timing of radiotherapy and outcome in patients receiving adjuvant endocrine therapy

    PubMed Central

    Karlsson, Per; Cole, Bernard F.; Colleoni, Marco; Roncadin, Mario; Chua, Boon; Murray, Elizabeth; Price, Karen N.; Castiglione-Gertsch, Monica; Goldhirsch, Aron; Gruber, Günther

    2010-01-01

    Purpose To evaluate the association between time from breast-conserving surgery (BCS) to radiotherapy and clinical outcome among patients treated with adjuvant endocrine therapy. Methods Patient information was obtained from three International Breast Cancer Study Group trials. Analysis was restricted to 964 patients treated with BCS and adjuvant endocrine therapy. Patients were divided into two groups based on the median number of days between BCS and radiotherapy and into 4 groups based on the quartile of time between BCS and radiotherapy. Endpoints were time to local recurrence (TLR), disease-free survival (DFS) and overall survival (OS). Proportional hazards regression analysis was used to perform comparisons after adjustment for baseline factors. Results The median time between BCS and radiotherapy was 77 days. Radiotherapy timing was significantly associated with age, menopausal status, and estrogen receptor status. After adjustment for these factors no significant effect of radiotherapy delay of up to 20 weeks was found. Adjusted hazard ratios (HRs) (radiotherapy within 77 days vs. after 77 days) were 0.94 (95% CI 0.47–1.87) for TLR, 1.05 (95% CI 0.82–1.34) for DFS and 1.07 (95% CI 0.77–1.49) for OS. For TLR the adjusted HRs for ≤48 days, 49–77 days, and 78–112 days were 0.90 (CI 95% 0.34–2.37), 0.89 (95% CI, 0.33–2.25), and 0.89 (95% CI, 0.33–2.41), respectively relative to ≥ 113 days. Conclusions Radiotherapy delay of up to 20 weeks was significantly associated with baseline factors such as age, menopausal status, and estrogen-receptor status. After adjustment for these factors, timing of radiotherapy was not significantly associated with TLR, DFS, or OS. PMID:20729007

  9. Timing of Radiotherapy and Outcome in Patients Receiving Adjuvant Endocrine Therapy

    SciTech Connect

    Karlsson, Per; Cole, Bernard F.; Colleoni, Marco; Roncadin, Mario; Chua, Boon H.; Murray, Elizabeth; Price, Karen N.; Castiglione-Gertsch, Monica; Goldhirsch, Aron; Gruber, Guenther

    2011-06-01

    Purpose: To evaluate the association between the interval from breast-conserving surgery (BCS) to radiotherapy (RT) and the clinical outcome among patients treated with adjuvant endocrine therapy. Patients and Methods: Patient information was obtained from three International Breast Cancer Study Group trials. The analysis was restricted to 964 patients treated with BCS and adjuvant endocrine therapy. The patients were divided into two groups according to the median number of days between BCS and RT and into four groups according to the quartile of time between BCS and RT. The endpoints were the interval to local recurrence, disease-free survival, and overall survival. Proportional hazards regression analysis was used to perform comparisons after adjustment for baseline factors. Results: The median interval between BCS and RT was 77 days. RT timing was significantly associated with age, menopausal status, and estrogen receptor status. After adjustment for these factors, no significant effect of a RT delay {<=}20 weeks was found. The adjusted hazard ratio for RT within 77 days vs. after 77 days was 0.94 (95% confidence interval [CI], 0.47-1.87) for the interval to local recurrence, 1.05 (95% CI, 0.82-1.34) for disease-free survival, and 1.07 (95% CI, 0.77-1.49) for overall survival. For the interval to local recurrence the adjusted hazard ratio for {<=}48, 49-77, and 78-112 days was 0.90 (95% CI, 0.34-2.37), 0.86 (95% CI, 0.33-2.25), and 0.89 (95% CI, 0.33-2.41), respectively, relative to {>=}113 days. Conclusion: A RT delay of {<=}20 weeks was significantly associated with baseline factors such as age, menopausal status, and estrogen-receptor status. After adjustment for these factors, the timing of RT was not significantly associated with the interval to local recurrence, disease-free survival, or overall survival.

  10. Adjuvant intraoperative photodynamic therapy (AIOPDT) after photosensitization with mTHPC in a CC531 colon carcinoma model in mice

    NASA Astrophysics Data System (ADS)

    Winkler, Steffi; Prosst, Ruediger L.; Stern, Josef; Rheinwald, Markus; Haase, Thomas; Herfarth, Christian; Gahlen, Johannes

    2001-01-01

    The effectiveness of PDT as an adjuvant alternative therapy method for diverse malignant tumors has been investigated in numerous studies. The therapeutic benefit and extent of side effects is mainly determined by the applied photoactive substance. The second generation photosensitizer (PS) mTHPC is capable of causing selective tumor cell death in colon carcinoma when combined with laser irradiation of a PS specific wavelength. Our study revealed PDT with mTHPC as an efficient adjuvant intraoperative modality after R1/R2 resection of a subcutaneously implanted colon tumor. There was a significant increase of postoperative recurrence-free survival time using PDT compared to a control group in a colon cancer model in nude mice. The accumulation of the PS determined by point spectrometry showed a high tumor-selectivity in the tumor, tumor bed, and overlying skin compared to muscle tissue as reference parameter.

  11. Unproven (questionable) cancer therapies.

    PubMed Central

    Brigden, M L

    1995-01-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects of questionable therapies that make these treatments attractive to patients and that may be perceived as being deficient in the practice of conventional health care professionals. Physicians with patients with cancer should always make sure that unproven therapies are discussed early in the therapeutic relationship. They should also attempt to be aware of alternative therapies that are in vogue in their particular geographic area. PMID:8533410

  12. Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

    PubMed Central

    Findlay, John M.; Castro-Giner, Francesc; Makino, Seiko; Rayner, Emily; Kartsonaki, Christiana; Cross, William; Kovac, Michal; Ulahannan, Danny; Palles, Claire; Gillies, Richard S.; MacGregor, Thomas P.; Church, David; Maynard, Nicholas D.; Buffa, Francesca; Cazier, Jean-Baptiste; Graham, Trevor A.; Wang, Lai-Mun; Sharma, Ricky A.; Middleton, Mark; Tomlinson, Ian

    2016-01-01

    How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful. PMID:27045317

  13. Overview on cardiac, pulmonary and cutaneous toxicity in patients treated with adjuvant radiotherapy for breast cancer.

    PubMed

    Meattini, Icro; Guenzi, Marina; Fozza, Alessandra; Vidali, Cristiana; Rovea, Paolo; Meacci, Fiammetta; Livi, Lorenzo

    2017-01-01

    Conservative management of breast cancer represents the standard treatment for early disease. Breast conserving surgery associated with radiotherapy for stage I-II has been proven to be as equally effective as mastectomy in term of local control, distant disease, and overall survival. The growing minimal invasive surgical approach on the axillary region, and the new breast reconstructive techniques, will probably lead to a significant decrease of the rate of side-effects related to mastectomy. Therefore, the adverse events caused by adjuvant radiation still remain a challenge. Cutaneous, pulmonary and cardiac toxicity represent the main toxicities of adjuvant radiotherapy for breast cancer. Safety profile of radiation is strongly dependent on the multidisciplinary management of the single case (systemic treatment, endocrine therapy, surgery), individual characteristics (i.e., co-morbidities, age, habits), and radiation-related aspects. Radiation techniques development, and facilities implementation concerning organs-at-risk sparing systems (i.e., image-guided radiotherapy, tracking systems, respiratory gating), represent brand new tools for the clinical oncologist, that would certainly minimize toxicity profile in the next future. However, data reported from published literature will greatly help physicians, to give to the patients appropriate counseling regarding the efficacy and potential adverse events of treatments, thus optimizing the informed decision-making process.

  14. Glioblastoma multiforme in conus medullaris with intracranial metastasis after postoperative adjuvant therapy

    PubMed Central

    Yan, Chengrui; Kong, Xiangyi; Yin, Hua; Wang, Yu; He, Huayu; Zhang, Hui; Gao, Jun; Li, Yongning; Ma, Wenbin

    2017-01-01

    Abstract Spinal glioblastoma multiforme is not common among spinal cord tumors. According to our literature review, only 27 cases originating from the conus medullaris were reported. We herein reported a case of a 10-year-old child diagnosed with glioblastoma multiforme. The patient received adjuvant radiotherapy and standard temozolomide chemotherapy after total excision. Intracranial lesions were found 1 month after postoperative adjuvant therapy. We described the clinical characteristics and postoperative therapy of the patient, and reviewed all of the published cases of conus medullaris glioblastoma. Location, age, leptomeningeal spread, and secondary hydrocephalus may be predictive factors. Immunohistochemical factors such as p53 and Ki-67 are also important. Combined treatment of surgery and postoperative adjuvant therapy is commonly used, but is controversial. PMID:28353599

  15. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    SciTech Connect

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

    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. 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.

  16. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    SciTech Connect

    Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.; and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

  17. Adjuvants and myeloid-derived suppressor cells: enemies or allies in therapeutic cancer vaccination.

    PubMed

    Fernández, Audry; Oliver, Liliana; Alvarez, Rydell; Fernández, Luis E; Lee, Kelvin P; Mesa, Circe

    2014-01-01

    Adjuvants are a critical but largely overlooked and poorly understood component included in vaccine formulations to stimulate and modulate the desired immune responses to an antigen. However, unlike in the protective infectious disease vaccines, adjuvants for cancer vaccines also need to overcome the effect of tumor-induced suppressive immune populations circulating in tumor-bearing individuals. Myeloid-derived suppressor cells (MDSC) are considered to be one of the key immunosuppressive populations that inhibit tumor-specific T cell responses in cancer patients. This review focuses on the different signals for the activation of the immune system induced by adjuvants, and the close relationship to the mechanisms of recruitment and activation of MDSC. This work explores the possibility that a cancer vaccine adjuvant may either strengthen or weaken the effect of tumor-induced MDSC, and the crucial need to address this in present and future cancer vaccines.

  18. Enzyme and combination therapy with cyclosporin A in the rat developing adjuvant arthritis.

    PubMed

    Rovenská, E; Svík, K; Stancíková, M; Rovenský, J

    1999-01-01

    Recent knowledge of the pathophysiology of rheumatoid arthritis and the mechanism of drug effects have enabled the use of new drugs and drug combinations in rheumatoid arthritis therapy. This study investigates the efficacy of both enzyme therapy and combined therapy with cyclosporin in rats with adjuvant arthritis. Rats with adjuvant-induced arthritis were administered either cyclosporin A (2.5 or 5.0 mg/kg/day per os), a mixture of enzymes (Phlogenzym (PHL); 45 mg/kg twice daily intrarectally), or a combination of 2.5 mg cyclosporin A and 90 mg PHL for a period of 40 days from the adjuvant application. Levels of serum albumin, changes in hind paw swelling and bone erosions were measured in rats as variables of inflammation and arthritis-associated destructive changes. Treatment with 5 mg of cyclosporin A, as well as with the combination therapy with cyclosporin A plus PHL, significantly inhibited both the inflammation and destructive arthritis-associated changes. However, 2.5 mg of cyclosporin A and PHL alone inhibited these disease markers, although to a lesser extent and at a later stage of arthritis development. The results show the inhibitory effect of enzyme therapy on rat adjuvant arthritis, as well as the efficacy of a low dose of cyclosporin A given in combination with enzyme therapy, which may be useful in the treatment of rheumatoid arthritis.

  19. Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2008-12-01

    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 median 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

  20. Radiation therapy of esophageal cancer

    SciTech Connect

    Hancock, S.L.; Glatstein, E.

    1984-06-01

    Radiation therapy has been used extensively in the management of patients with cancer of the esophagus. It has demonstrated an ability to cure a small minority of patients. Cure is likely to be limited to patients who have lesions less than 5 cm in length and have minimal, if any, involvement of lymph nodes. Esophagectomy is likely to cure a similar, small percentage of patients with the same presentation of minimal disease but has a substantial acute postoperative mortality rate and greater morbidity than irradiation. Combining surgery and either preoperative or postoperative irradiation may cure a small percentage of patients beyond the number cured with either modality alone. Radiation has demonstrated benefit as an adjuvant to surgery following the resection of minimal disease. However, radiation alone has never been compared directly with surgery for the highly select, minimal lesions managed by surgery. Radiation provides good palliation of dysphagia in the majority of patients, and roughly one third may have adequate swallowing for the duration of their illness when ''radical'' doses have been employed. Surgical bypass procedures have greater acute morbidity but appear to provide more reliable, prolonged palliation of dysphagia. Several approaches to improving the efficacy of irradiation are currently under investigation. These approahces include fractionation schedules, radiosensitizers, neutron-beam therapy, and helium-ion therapy.

  1. Successful management of chronic multifocal Q fever Osteomyelitis with adjuvant interferon-gamma therapy.

    PubMed

    Neth, Olaf Werner; Falcon, Dolores; Peromingo, Estrella; Soledad Camacho, Maria; Rodríguez-Gallego, Carlos; Obando, Ignacio

    2011-09-01

    We present a 3-year-old girl who had chronic recurrent multifocal osteomyelitis caused by Coxiella burnetii despite long-term dual antibiotic therapy. Excellent clinical response was achieved and sustained when immunomodulatory therapy with interferon-γ was initiated. This is the case of a first child who was successfully treated with interferon-γ as adjuvant therapy for chronic multifocal Q fever osteomyelitis.

  2. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  3. Anti-Vascular Endothelial Growth Factor Therapy in Breast Cancer

    PubMed Central

    Kristensen, Tina Bøgelund; Knutsson, Malin L. T.; Wehland, Markus; Laursen, Britt Elmedal; Grimm, Daniela; Warnke, Elisabeth; Magnusson, Nils E.

    2014-01-01

    Neo-angiogenesis is a critical process for tumor growth and invasion and has become a promising target in cancer therapy. This manuscript reviews three currently relevant anti-angiogenic agents targeting the vascular endothelial growth factor system: bevacizumab, ramucirumab and sorafenib. The efficacy of anti-angiogenic drugs in adjuvant therapy or as neo-adjuvant treatment has been estimated in clinical trials of advanced breast cancer. To date, the overall observed clinical improvements are unconvincing, and further research is required to demonstrate the efficacy of anti-angiogenic drugs in breast cancer treatments. The outcomes of anti-angiogenic therapy have been highly variable in terms of tumor response. New methods are needed to identify patients who will benefit from this regimen. The development of biomarkers and molecular profiling are relevant research areas that may strengthen the ability to focus anti-angiogenic therapy towards suitable patients, thereby increase the cost-effectiveness, currently estimated to be inadequate. PMID:25514409

  4. Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.

    PubMed

    Tsen, Andrew R; Long, Patrick M; Driscoll, Heather E; Davies, Matthew T; Teasdale, Benjamin A; Penar, Paul L; Pendlebury, William W; Spees, Jeffrey L; Lawler, Sean E; Viapiano, Mariano S; Jaworski, Diane M

    2014-03-15

    Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA-induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors.

  5. Concurrent chemoradiotherapy in adjuvant treatment of breast cancer

    PubMed Central

    Ismaili, Nabil; Mellas, Nawfel; Masbah, Ouafae; Elmajjaoui, Sanaa; Arifi, Samia; Bekkouch, Imane; Ahid, Samir; Bazid, Zakaria; Tazi, Mohammed Adnane; Erraki, Abdelouahed; El Mesbahi, Omar; Benjaafar, Noureddine; El Gueddari, Brahim El Khalil; Ismaili, Mohammed; Afqir, Said; Errihani, Hassan

    2009-01-01

    Background The optimal sequencing of chemotherapy and radiotherapy after breast surgery was largely studied but remains controversial. Concurrent chemo-radiotherapy is a valuable method for adjuvant treatment of breast cancer which is under ongoing research program in our hospital. We are evaluating the feasibility of the concomitant use of chemotherapy retrospectively. Methods Two hundred forty four women having breast cancer were investigated in a retrospective study. All patients were either treated by radical surgery or breast conservative surgery. The study compares two adjuvant treatments associating concomitant chemotherapy and radiotherapy. In the first group (group A) the patients were treated by chemotherapy and radiotherapy in concomitant way using anthracycline (n = 110). In the second group (group B) the patients were treated by chemotherapy and radiotherapy in concomitant way using CMF treatment (n = 134). Chemotherapy was administered in six cycles, one each 3 weeks. Radiotherapy delivered a radiation dose of 50 Gy on the whole breast (or on the external wall) and/or on the lymphatic region. The Kaplan-Meier method was used to estimate the rates of disease free survival, loco-regional recurrence-free survival and overall survival. The Pearson Khi2 test was used to analyse the homogeneity between the two groups. The log-rank test was used to evaluate the differences between the two groups A and B. Results After 76.4 months median follow-up (65.3 months mean follow up), only one patient relapsed to loco-regional breast cancer when the treatment was based on anthracycline. However, 8 patients relapsed to loco-regional breast cancer when the treatment was based on CMF. In the anthracycline group, the disease free survival after 5 years, was 80.4% compared to 76.4% in the CMF group (Log-rank test: p = 0.136). The overall survival after 5 years was 82.5% and 81.1% in the anthracycline and CMF groups respectively (Log-rank test: p = 0.428). The loco

  6. Tamoxifen therapy in breast cancer control worldwide.

    PubMed Central

    Love, R. R.; Koroltchouk, V.

    1993-01-01

    In most developed and many developing countries, breast cancer is the most frequent cancer and the leading cause of cancer death among women. At least 50% of all breast cancer patients worldwide would survive longer, however, if public awareness about and early detection of the condition were increased and greater use were made of efficient treatment of proven value. With early-stage, localized breast cancer, local treatment combined with adjuvant hormonal therapy with tamoxifen, a synthetic estrogen, could save the lives of 6 women out of 100 compared with local treatment alone. Tamoxifen has anti-estrogenic effects not only on breast cancer cells but also on liver metabolism and bone, with concomitant decreases in risk factors for chronic skeletal and vascular system diseases. Long-term tamoxifen treatment causes major adverse clinical effects in < 5% of women; menopausal and vasomotor symptoms occur in the majority of treated women, but their severity lessens over time. Tamoxifen is being considered as a standard therapy and is included in the WHO list of essential drugs for the treatment of breast cancer patients in both developing and developed countries. For the control of breast cancer more successfully worldwide, one challenge is to make tamoxifen therapy available to greater numbers of women. PMID:8313498

  7. Adjuvant Therapy for a Microscopically Incomplete Resection Margin after an Esophagectomy for Esophageal Squamous Cell Carcinoma

    PubMed Central

    Qiu, Bo; Li, JiaXiang; Wang, Bin; Wang, ZhiQiang; Liang, Ying; Cai, Peiqiang; Chen, ZhaoLin; Liu, MengZhong; Fu, JianHua; Yang, Hong; Liu, Hui

    2017-01-01

    Purpose: To investigate the prognosis of esophageal squamous cell carcinoma with a microscopically incomplete (R1) resection margin following an esophagectomy, as well as the impact of adjuvant treatment on survival. Methods: Data obtained from 124 patients with R1-resected ESCC were reviewed. The impact of clinicopathological factors and adjuvant treatment on the overall survival, locoregional recurrence, and distant recurrence were explored. Results: For a median follow-up time of 16.8 months, the median overall survival of 124 patients was 25.6 months. The 1, 3, and 5-year overall survival rates were 75.6%±4.0%, 35.9%±5.1%, and 23.2%±5.0%, respectively. Adjuvant therapy was administered in 78 patients. In the univariate analyses, patients with a pN0 stage (log rank, p=0.028) and adjuvant chemotherapy (log rank, p=0.032) exhibited more favorable overall survival. In the multivariate analyses, the pN stage (HR=2.192, p=0.004) and adjuvant chemotherapy (HR=0.032, p=0.004) were independent prognostic factors for overall survival. Locoregional recurrence was the main failure pattern after R1 resection. The pN stage (HR=2.567, p=0.009) and adjuvant radiotherapy (HR=0.278, p=0.000) were independent prognostic factors for locoregional recurrence. Conclusion: In R1-resected esophageal squamous cell carcinoma, adjuvant radiotherapy reduced locoregional recurrence; however, it did not improve overall survival. Adjuvant chemotherapy demonstrated benefits for overall survival. The pN stage was an independent prognostic factor for locoregional recurrence and overall survival. PMID:28243329

  8. Could Adjuvant Chemotherapy after Surgery Benefit Elderly Patients with Advanced Gastric Cancer?

    PubMed Central

    Jeong, Jin Woon; Kwon, In Gyu; Son, Young-Gil

    2016-01-01

    Purpose The aim of this study was to evaluate tolerance to adjuvant chemotherapy, and to compare survival between treatments using only surgery and using surgery with adjuvant chemotherapy, in elderly patients with advanced gastric cancer who were ≥75 years of age. Materials and Methods Patients ≥75 years of age who were diagnosed with pathological stage II or III gastric cancer were identified retrospectively and categorized into the surgery only and surgery with adjuvant chemotherapy groups. Clinicopathological and survival data were compared between these two groups. Results Among the 130 patients studied, 67 patients underwent curative surgery only, and 63 patients received adjuvant chemotherapy after curative surgery. In the latter group, adverse events were reported in 24 patients (38.1%). The treatments were discontinued in 19 patients (30.2%) owing to any reason. The overall 5-year survival rates of the surgery only and the surgery with adjuvant chemotherapy groups did not differ significantly (44.1% vs. 30.7%, respectively; P=0.804). Among 90 death events, deaths from recurrences of gastric cancer occurred in 42 patients. Multivariate analyses revealed that the American Society of Anesthesiologists score and the depths of tumor invasions were related to survival, and the addition of adjuvant chemotherapy after surgery did not influence survival. Conclusions The decision for the addition of adjuvant chemotherapy for elderly patients should be taken after considering the condition of individual patients and their life expectancies. PMID:28053813

  9. New possibilities for cancer therapy with advances in cancer immunology.

    PubMed

    MacLean, G D; Longenecker, B M

    1994-04-01

    There has been progress over the last decade in addressing three questions: Are there cancer-associated antigens that could be targets for immunotherapy? Can the human immune system recognize cancer-associated antigens? Can an anti-cancer immune response affect cancer cells and lead to increased survival? Results from animal model studies have been interpreted by optimists as encouraging, and by pessimists as being irrelevant to human cancer. Earlier studies on "cancer vaccines" utilized heterogeneous cell extracts of cell components. Monoclonal antibodies have enabled identification of relevant cancer-associated antigens or epitopes, such as the ganglioside GM2, the carbohydrates TF and STn, and the peptide sequences of MUC-1. In parallel with research on immune adjuvants and measures designed to inhibit suppressor activity, these epitopes are being tested for their potential in the immunotherapy of solid tumors. It is clear that some of these cancer-associated epitopes are immunogenic in humans. Mixed responses may relate to cancer heterogeneity and may indicate the importance of multi-epitopic vaccines. Responses are encouraging, but are they relevant? Prolonged disease stability challenges us to re-think the goals of cancer therapy. Recent advances in the knowledge of the effect of cytokines on tumor antigen expression and the regulation of the immune response, coupled with advances in active specific immunotherapy, provide hope that biomodulation may become an important part of the therapy of solid tumors in the next century.

  10. Real-world experience with adjuvant fec-d chemotherapy in four Ontario regional cancer centres

    PubMed Central

    Madarnas, Y.; Dent, S.F.; Husain, S.F.; Robinson, A.; Alkhayyat, S.; Hopman, W.M.; Verreault, J.L.; Vandenberg, T.

    2011-01-01

    Background The efficacy of adjuvant chemotherapy with fec-d (5-fluorouracil–epirubicin–cyclophosphamide followed by docetaxel) is superior to that with fec-100 alone in women with early-stage breast cancer. As the use of fec-d increased in clinical practice, health care providers anecdotally noted higher-than-expected toxicity rates and frequent early treatment discontinuations because of toxicity. In the present study, we compared the rates of serious adverse events in patients who received adjuvant fec-d chemotherapy in routine clinical practice with the rates reported in the pacs-01 trial. Methods We retrospectively reviewed all patients prescribed adjuvant fec-d for early-stage breast cancer at 4 regional cancer centres in Ontario. Information was collected from electronic and paper charts by a physician investigator from each centre. Data were analyzed using chi-square tests, independent samples t-tests, one-way analysis of variance, and univariate regression. Results The 671 electronic and paper patient records reviewed showed a median patient age of 52.2 years, 229 patients (34.1%) with N0 disease, 508 patients (75.7%) with estrogen or progesterone receptor–positive disease (or both), and 113 patients (26%) with her2/neu–overexpressing breast cancer. Febrile neutropenia occurred in 152 patients (22.7%), most frequently at cycle 4, coincident with the initiation of docetaxel [78/152 (51.3%)]. Primary prophylaxis with hematopoietic growth factor support was used in 235 patients (35%), and the rate of febrile neutropenia was significantly lower in those who received prophylaxis than in those who did not [15/235 (6.4%) vs. 137/436 (31.4%); p < 0.001; risk ratio: 0.20]. Conclusions In routine clinical practice, treatment with fec-d is associated with a higher-than-expected rate of febrile neutropenia, in light of which, primary prophylaxis with growth factor should be considered, per international guidelines. Adoption based on clinical trial reports of

  11. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.

    PubMed

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim; Millikan, Randall E; Stadler, Walter; De Mulder, Pieter; Sherif, Amir; von der Maase, Hans; Tsukamoto, Taiji; Soloway, Mark S

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients

  12. [Neoadjuvant, inductive or adjuvant chemotherapy of bladder cancer].

    PubMed

    Ohlmann, C-H; De Santis, M

    2013-11-01

    Perioperative chemotherapy is a standard treatment for patients with muscle-invasive bladder carcinoma undergoing radical cystectomy; however, direct comparisons of neoadjuvant and adjuvant chemotherapy are lacking. Evidence-based data and implementation into daily clinical practice favor neoadjuvant chemotherapy; nevertheless, neoadjuvant chemotherapy is still underused in daily practice compared to adjuvant chemotherapy. If neoadjuvant chemotherapy has not been used and patients are fit enough to receive cisplatin, adjuvant chemotherapy should be considered in patients with pT3-pT4 and/or lymph node metastases.

  13. TARGETED THERAPY IN CANCER

    PubMed Central

    Tsimberidou, Apostolia-Maria

    2015-01-01

    Purpose To describe the emergence of targeted therapies that have led to significant breakthroughs in cancer therapy and completed or ongoing clinical trials of novel agents for the treatment of patients with advanced cancer. Methods The literature was systematically reviewed, based on clinical experience and the use of technologies that improved our understanding of carcinogenesis. Results Genomics and model systems have enabled the validation of novel therapeutic strategies. Tumor molecular profiling has enabled the reclassification of cancer, and elucidated some mechanisms of disease progression or resistance to treatment, the heterogeneity between primary and metastatic tumors, and the dynamic changes of tumor molecular profiling over time. Despite the notable technologic advances, there is a gap between the plethora of preclinical data and the lack of effective therapies, which is attributed to suboptimal drug development for “driver” alterations of human cancer, the high cost of clinical trials and available drugs, and limited access of patients to clinical trials. Bioinformatic analyses of complex data to characterize tumor biology, function, and the dynamic tumor changes in time and space may improve cancer diagnosis. The application of discoveries in cancer biology in clinic holds the promise to improve the clinical outcomes in a large scale of patients with cancer. Increased harmonization between discoveries, policies, and practices will expedite the development of anticancer drugs and will accelerate the implementation of precision medicine. Conclusions Combinations of targeted, immunomodulating, antiangiogenic, or chemotherapeutic agents are in clinical development. Innovative adaptive study design is used to expedite effective drug development. PMID:26391154

  14. Clinical Role of Adjuvant Chemotherapy after Radical Hysterectomy for FIGO Stage IB-IIA Cervical Cancer: Comparison with Adjuvant RT/CCRT Using Inverse-Probability-of-Treatment Weighting

    PubMed Central

    Jung, Phill-Seung; Kim, Dae-Yeon; Lee, Shin-Wha; Park, Jeong-Yeol; Suh, Dae-Shik; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun

    2015-01-01

    Objective To evaluate the clinical role of adjuvant chemotherapy (AC) in FIGO stage IB-IIA cervical cancer patients. Study Design A cohort of 262 patients with cervical cancer who received radical hysterectomy (RH) and adjuvant therapy at Asan Medical Center between 1992 and 2012 was enrolled. In this cohort, 85 patients received adjuvant chemotherapy (AC), and 177 received adjuvant radiotherapy or concurrent chemoradiation therapy (AR). Oncologic outcomes and adverse events in both treatment arms were compared using weighted Cox proportional hazards regression models with inverse-probability-of-treatment weighting (IPTW) to reduce the impact of treatment selection bias and potential confounding factors. Results During a 46.8-month median follow-up duration, 39 patients (14.9%) had recurrences, and 18 patients (6.9%) died of disease. In multivariate analysis, the hazard ratio (HR) for recurrence and death was not significantly different in patients in either treatment arm (p=0.62 and 0.12, respectively). Also, after IPTW matching, the HR for recurrence did not significantly differ between the arms (HR 1.57, 95% CI 0.68-3.62, p=0.29). Similarly, disease-free survival and overall survival were not significantly different between the arms (p=0.47 and 0.13, respectively). In addition, patients with AC had a much lower prevalence of long-term complications (lymphedema: n=8 (9.4%) vs. 46 (26.0%), p=0.03; ureteral stricture: n=0 vs. 9 (6.2%), p=0.05). Conclusion Patients with FIGO stage IB-IIA cervical cancer can benefit from AC after RH with fewer long-term complications and non-inferior therapeutic effect to AR. Chemotherapy may therefore be an alternative adjuvant treatment option for cervical cancer, particularly in younger patients. PMID:26176626

  15. Efficacy of adjuvant chemotherapy using oral fluorinated pyrimidines for curatively resected gastric cancer: a meta-analysis of centrally randomized controlled clinical trials in Japan.

    PubMed

    Oba, K; Morita, S; Tsuburaya, A; Kodera, Y; Kobayashi, M; Sakamoto, J

    2006-06-01

    Adjuvant chemotherapy for gastric cancer has been extensively explored in Japan since the 1950s, and a combination of oral fluorinated pyrimidines (o-FP) and mitomycin C (MMC) has been mainly utilized for adjuvant chemotherapy. However, there is no sufficient evidence for the efficacy of adjuvant therapy. Therefore, we assessed the efficacy of o-FPs over surgery alone (control) by means of a meta-analysis of Japanese centrally randomized controlled clinical trials conducted between 1980 and 2005. For inclusion in this study, studies had to compare adjuvant chemotherapy for curatively resected gastric cancer with surgery alone, mainly targeting o-FP, and central randomization designed to comply with contemporary standards for clinical trials in Japan. For the 4 trials that met the eligibility criteria, the estimated hazard ratio was 0.73 (95%CI=0.60-0.89). Our findings show that in Japan adjuvant chemotherapy using o-FP for long-term maintenance therapy appears to be effective for gastric cancer patients after curative resection.

  16. Ablation and Other Local Therapy for Kidney Cancer

    MedlinePlus

    ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  17. Phase III Multi-Institutional Trial of Adjuvant Chemotherapy With Paclitaxel, Estramustine, and Oral Etoposide Combined With Long-Term Androgen Suppression Therapy and Radiotherapy Versus Long-Term Androgen Suppression Plus Radiotherapy Alone for High-Risk Prostate Cancer: Preliminary Toxicity Analysis of RTOG 99-02

    SciTech Connect

    Rosenthal, Seth A. Bae, Kyoungwha; Pienta, Kenneth J.; Sobczak, Mark L.; Asbell, Sucha O.; Rajan, Raghu; Kerlin, Kevin J.; Michalski, Jeff M.; Sandler, Howard M.

    2009-03-01

    Purpose: Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity. Methods and Materials: High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score {>=}7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began. Results: The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2. Conclusion: TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.

  18. 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

  19. Sleep Aid Use During and Following Breast Cancer Adjuvant Chemotherapy

    PubMed Central

    Moore, Tiffany A.; Berger, Ann M.; Dizona, Paul

    2010-01-01

    Background Knowledge of sleep aid use is limited despite the high prevalence of insomnia among women before, during, and following breast cancer adjuvant chemotherapy treatments (CTX). This study's purpose was to 1) determine the frequency and characteristics of participants taking sleep aid(s); 2) identify the frequency and percent of sleep aid use by category (prescription sedative/hypnotics, prescription anti-depressants, prescription analgesics, prescription anti-emetics, over-the-counter (OTC) analgesics, OTC cold/flu/sinus, OTC sleep, alcohol, and herbal supplements); and 3) compare sleep aid use by category in the experimental and control groups within a randomized-controlled clinical trial RCT). Methods Longitudinal, descriptive, secondary RCT data analysis of women (n=219) receiving out-patient CTX, and at 30, 60, and 90 days following the last CTX and 1 year following CTX1. Participants recorded daily sleep aid use on a Sleep Diary. Analyses included descriptives, chi-square, and RM-ANOVA. Results Approximately 20% of participants took at least one sleep aid before CTX1; usage decreased over time (12-18%); a 2nd sleep aid was used infrequently. Prescription sedative/hypnotics (46%) and OTC analgesics (24%) were used most frequently. OTC sleep aids were most commonly used as a 2nd aid. Prescription sedative/hypnotics [F(7,211)=4.26, p=0.00] and OTC analgesics [F(7,211)=2.38, p=0.023] use decreased significantly over time. Conclusions Results reflect the natural course of CTX, recovery, and healing. Comprehensive screening for sleep-wake disturbances and sleep aid use may lead to a better understanding of the risks and benefits of pharmacologic and non-pharmacologic interventions, and ultimately lead to selection of the safest and most effective treatment. PMID:20878849

  20. Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial.

    PubMed

    Cassidy, J; Douillard, J-Y; Twelves, C; McKendrick, J J; Scheithauer, W; Bustová, I; Johnston, P G; Lesniewski-Kmak, K; Jelic, S; Fountzilas, G; Coxon, F; Díaz-Rubio, E; Maughan, T S; Malzyner, A; Bertetto, O; Beham, A; Figer, A; Dufour, P; Patel, K K; Cowell, W; Garrison, L P

    2006-04-24

    Oral capecitabine (Xeloda) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings pound3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings pound1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

  1. Radiation Therapy for Testicular Cancer

    MedlinePlus

    ... Therapy for Testicular Cancer Radiation therapy uses a beam of high-energy rays (such as gamma rays or x-rays) or particles (such as electrons, protons, or neutrons) to destroy cancer cells or ...

  2. Bile Duct (Cholangiocarcinoma) Cancer: Radiation Therapy

    MedlinePlus

    ... Situation Bile Duct Cancer Treating Bile Duct Cancer Radiation Therapy for Bile Duct Cancer Radiation therapy uses ... of radiation for bile duct cancer. External beam radiation therapy (EBRT) This type of radiation therapy uses ...

  3. Adjuvant Stereotactic Radiosurgery and Radiation Therapy for the Treatment of Intracranial Chordomas

    PubMed Central

    Choy, Winward; Terterov, Sergei; Ung, Nolan; Kaprealian, Tania; Trang, Andy; DeSalles, Antonio; Chung, Lawrance K.; Martin, Neil; Selch, Michael; Bergsneider, Marvin; Yong, William; Yang, Isaac

    2015-01-01

    Objective Chordomas are locally aggressive, highly recurrent tumors requiring adjuvant radiotherapy following resection for successful management. We retrospectively reviewed patients treated for intracranial chordomas with adjuvant stereotactic radiosurgery (SRS) and stereotactic radiation therapy (SRT). Methods A total of 57 patients underwent 83 treatments at the UCLA Medical Center between February 1990 and August 2011. Mean follow-up was 57.8 months. Mean tumor diameter was 3.36 cm. Overall, 8 and 34 patients received adjuvant SRS and SRT, and the mean maximal dose of radiation therapy was 1783.3 cGy and 6339 cGy, respectively. Results Overall rate of recurrence was 51.8%, and 1- and 5-year progression-free survival (PFS) was 88.2% and 35.2%, respectively. Gross total resection was achieved in 30.9% of patients. Adjuvant radiotherapy improved outcomes following subtotal resection (5-year PFS 62.5% versus 20.1%; p = 0.036). SRS and SRT produced comparable rates of tumor control (p = 0.28). Higher dose SRT (> 6,000 cGy) (p = 0.013) and younger age (< 45 years) (p = 0.03) was associated with improved rates of tumor control. Conclusion Adjuvant radiotherapy is critical following subtotal resection of intracranial chordomas. Adjuvant SRT and SRS were safe and improved PFS following subtotal resection. Higher total doses of SRT and younger patient age were associated with improved rates of tumor control. PMID:26949587

  4. Combined-modality therapy for rectal cancer using irinotecan.

    PubMed

    Minsky, Bruce D

    2002-05-01

    Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease. Irinotecan (CPT-11, Camptosar)-based regimens have improved survival in patients with metastatic disease and are being actively investigated in combination with pelvic radiation therapy for patients with rectal cancer.

  5. Accelerators for Cancer Therapy

    DOE R&D Accomplishments Database

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  6. Prospective evaluation of mitotane toxicity in adrenocortical cancer patients treated adjuvantly.

    PubMed

    Daffara, Fulvia; De Francia, Silvia; Reimondo, Giuseppe; Zaggia, Barbara; Aroasio, Emiliano; Porpiglia, Francesco; Volante, Marco; Termine, Angela; Di Carlo, Francesco; Dogliotti, Luigi; Angeli, Alberto; Berruti, Alfredo; Terzolo, Massimo

    2008-12-01

    Toxicity of adjuvant mitotane treatment is poorly known; thus, our aim was to assess prospectively the unwanted effects of adjuvant mitotane treatment and correlate the findings with mitotane concentrations. Seventeen consecutive patients who were treated with mitotane after radical resection of adrenocortical cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory evaluation, monitoring of mitotane concentrations, and a hormonal work-up at baseline and every 3 months till ACC relapse or study end (December 2007). Mitotane toxicity was graded using NCI CTCAE criteria. All biochemical measurements were performed at our center and plasma mitotane was measured by an in-house HPLC assay. All the patients reached mitotane concentrations >14 mg/l and none of them discontinued definitively mitotane for toxicity; 14 patients maintained consistently elevated mitotane concentrations despite tapering of the drug. Side effects occurred in all patients but were manageable with palliative treatment and adjustment of hormone replacement therapy. Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS than aldosterone. Mitotane induced either perturbation of thyroid function mimicking central hypothyroidism or, in male patients, inhibition of testosterone secretion. The discrepancy between salivary and serum cortisol, as well as between total and free testosterone, is due to the mitotane-induced increase in hormone-binding proteins which complicates interpretation of hormone measurements. A low-dose monitored regimen of mitotane is tolerable and able to maintain elevated drug concentrations in the long term. Mitotane exerts a complex effect on the endocrine system that may require multiple hormone replacement therapy.

  7. Role of toll-like receptors and their adaptors in adjuvant immunotherapy for cancer.

    PubMed

    Seya, Tsukasa; Akazawa, Takashi; Uehori, Junji; Matsumoto, Misako; Azuma, Ichiro; Toyoshima, Kumao

    2003-01-01

    The potentiation of immune responses to tumor-associated antigen (Ag) is a pivotal issue in immunotherapy for cancer and thus requires the use of adjuvants, which are involved in efficient antibody (Ab) production and killer cell induction. The efficacy for tumor regression of a number of adjuvants that have been applied to immunotherapy in humans and tumor-bearing animal models has been tested without understanding of the function of adjuvants. Recent findings on the function of Toll-like receptors (TLRs) and their adaptors facilitated the elucidation of the molecular basis of adjuvant activity. TLR signaling was found to induce interferons (IFNs), chemokines and proinflammatory cytokines and mature dendritic cells (DCs) for enhanced efficiency in antigen presentation. The mediators then play a crucial role in the organization of acquired immunity and, together with matured DCs, activate cytotoxic T cells (CTL) and NK cells. These TLR outputs vary among adjuvants, which may depend on adjuvant-specific selection of appropriate sets of TLRs and their adaptors. Here we review how a variety of host immune responses are induced by an individual adjuvant to confer an adjuvant-specific anti-tumor immunity. We elaborate specifically on two adjuvants, BCG-cell wall skeleton and double-stranded RNA (dsRNA). The former activates TLR2/4 on DCs and induces tumor-specific CTL allowing general application to patients with surgically dissected cancer and improving prognosis, while the latter activates TLR3 on DCs to release type 1 IFN that induces tumor cell apoptosis and NK-mediated tumor cytotoxicity.

  8. Exosome removal as a therapeutic adjuvant in cancer.

    PubMed

    Marleau, Annette M; Chen, Chien-Shing; Joyce, James A; Tullis, Richard H

    2012-06-27

    Exosome secretion is a notable feature of malignancy owing to the roles of these nanoparticles in cancer growth, immune suppression, tumor angiogenesis and therapeutic resistance. Exosomes are 30-100 nm membrane vesicles released by many cells types during normal physiological processes. Tumors aberrantly secrete large quantities of exosomes that transport oncoproteins and immune suppressive molecules to support tumor growth and metastasis. The role of exosomes in intercellular signaling is exemplified by human epidermal growth factor receptor type 2 (HER2) over-expressing breast cancer, where exosomes with the HER2 oncoprotein stimulate tumor growth and interfere with the activity of the therapeutic antibody Herceptin®. Since numerous observations from experimental model systems point toward an important clinical impact of exosomes in cancer, several pharmacological strategies have been proposed for targeting their malignant activities. We also propose a novel device strategy involving extracorporeal hemofiltration of exosomes from the entire circulatory system using an affinity plasmapheresis platform known as the Aethlon ADAPT™ (adaptive dialysis-like affinity platform technology) system, which would overcome the risks of toxicity and drug interactions posed by pharmacological approaches. This technology allows affinity agents, including exosome-binding lectins and antibodies, to be immobilized in the outer-capillary space of plasma filtration membranes that integrate into existing kidney dialysis systems. Device therapies that evolve from this platform allow rapid extracorporeal capture and selective retention of target particles < 200 nm from the entire circulatory system. This strategy is supported by clinical experience in hepatitis C virus-infected patients using an ADAPT™ device, the Hemopurifier®, to reduce the systemic load of virions having similar sizes and glycosylated surfaces as cancer exosomes. This review discusses the possible

  9. Effect of a randomized controlled exercise trial on bone outcomes: influence of adjuvant endocrine therapy.

    PubMed

    Knobf, M Tish; Jeon, Sangchoon; Smith, Barbara; Harris, Lyndsay; Kerstetter, Jane; Thompson, A Siobhan; Insogna, Karl

    2016-02-01

    Bone loss is a significant clinical problem for female cancer survivors (FCS) and increases fracture risk. The aim of the Yale Fitness Intervention Trial (Yale FIT) was to determine the effects of a 12-month aerobic-resistance exercise intervention compared to a home-based physical activity group on bone outcomes [bone mineral density (BMD)] and biomarkers bone turnover). Early postmenopausal FCS (N = 154) were randomized to the exercise intervention (3 times/week) or to a home-based physical activity group. Calcium (1200 mg) and Vitamin D (400 IU) supplements were provided to both groups. BMD was measured at baseline and 12 months. No significant difference in BMD was observed for the exercise vs home-based group. However, subjects on Tamoxifen or no endocrine therapy did not significantly lose BMD, with the exception of the femoral neck (FN). In contrast subjects on aromatase inhibitors (AIs) had significant BMD loss at all sites. The majority of subjects had sufficient serum levels of Vitamin D (>20 ng/mL) but there was significantly less bone loss in subjects in the 20-29 ng/mL range at the LS (p = 0.01), hip (p = 0.03), and GT (p = 0.008) compared to lower or higher levels. Exercise stimulates bone remodeling but the intervention was not superior for BMD outcomes at one year. The dose of the osteogenic stimulus in the intervention has been effective in preserving BMD in healthy postmenopausal women but it may be inadequate for survivors with chemotherapy-induced menopause and for those on adjuvant AI therapy.

  10. A prospective cohort study of early discontinuation of adjuvant chemotherapy in women with breast cancer: the breast cancer quality of care study (BQUAL).

    PubMed

    Neugut, Alfred I; Hillyer, Grace Clarke; Kushi, Lawrence H; Lamerato, Lois; Buono, Donna L; Nathanson, S David; Bovbjerg, Dana H; Mandelblatt, Jeanne S; Tsai, Wei-Yann; Jacobson, Judith S; Hershman, Dawn L

    2016-07-01

    For many women with non-metastatic breast cancer, adjuvant chemotherapy prevents recurrence and extends survival. Women who discontinue chemotherapy early may reduce those benefits, but little is known about what predicts early discontinuation. We sought to determine prospectively the rate and reasons for early discontinuation of adjuvant chemotherapy in women with breast cancer. We conducted a prospective cohort study among three U.S. health care organizations. Of 1158 women with newly diagnosed non-metastatic breast cancer, 2006-2010, we analyzed 445 (38.4 %) patients who initiated standard adjuvant chemotherapy as defined by accepted guidelines. We interviewed patients at baseline and twice during treatment regarding sociodemographic/psychosocial factors and treatment decision-making and collected clinical data. They were categorized according to the number of cycles required by the chemotherapy regimen they had initiated. The outcome was early discontinuation (<80 % of planned cycles). Of patients analyzed, 392 (88.1 %) completed the prescribed therapy. The strongest predictor was receipt of a regimen entailing >4 cycles of therapy (18.1 % for longer regimens, 7.4 % for 4 cycles) (odds ratio [OR] 2.59, 95 % CI 1.32-5.08), controlling for race, age, stage, hormone receptor status, social support, optimism, spirituality, stress, and physical symptoms. Higher levels of psychological symptoms on the Memorial symptom assessment scale also increased the odds of early discontinuation (OR 1.92, 95 % CI 0.998-3.68). The large majority of patients who initiated adjuvant chemotherapy for breast cancer completed their prescribed regimens, but early discontinuation was associated with lengthier regimens and, with borderline statistical significance, for those with psychological side effects.

  11. Adjuvant Chemotherapy for Elderly Patients with Gastric Cancer after D2 Gastrectomy

    PubMed Central

    Zhang, Dong-sheng; Ren, Chao; Bai, Long; Luo, Hui-yan; Wang, Zhi-qiang; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2013-01-01

    Background A phase III clinical trial has already shown the survival benefits of postoperative chemotherapy in gastric cancer. However, there are limited published data concerning the elderly. This study aims to investigate the use of adjuvant chemotherapy for gastric cancer after D2 gastrectomy among the elderly and identify its impact on survival. Methods We retrospectively reviewed 360 patients who had undergone D2 gastrectomy, aged 65 years or older, with non-metastatic gastric cancer in a single institution. We analyzed the predictors and survival benefits of adjuvant chemotherapy use in the elderly. Further, we analyzed the survival benefits of adjuvant chemotherapy by dividing the patients into groups according to disease stages and chemotherapeutic regimens. Results Among the 360 patients, only 34.7% of patients received adjuvant chemotherapy. Age, tumor location, lymph node involvement and tumor invasion were associated with the receipt of adjuvant chemotherapy. Adjuvant chemotherapy improved the overall survival for non-metastatic elderly patients (HR 0.60, 95%CI 0.42–0.83, P = 0.003). Significant survival benefits were found with adjuvant chemotherapy in stage III patients (HR 0.67, 95%CI 0.47–0.97, P = 0.033), but not in stage I patients or in stage II patients (HR 0.52, 95%CI 0.21–1.30 P = 0.161). Compared to adjuvant chemotherapy without platinum, no significant survival benefits were observed with platinum-containing chemotherapy (HR 0.84, 95%CI 0.49–1.45, P = 0.530). Besides adjuvant chemotherapy, other independent prognostic factors of survival included tumor location, tumor size, histologic grade, depth of tumor invasion, and lymph node status. Conclusions This study demonstrated the survival benefits of adjuvant fluoropyrimidine-based chemotherapy among the elderly patients with non-metastatic gastric cancer after D2 gastrectomy. However, due to the limitations of this study, further well-designed prospective studies with

  12. Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial

    PubMed Central

    Takayama, Tadatoshi; Miyagawa, Shinichi; Yamamoto, Junji; Ijichi, Masayoshi; Teruya, Masanori; Yoshimi, Fuyo; Kawasaki, Seiji; Koyama, Hiroto; Oba, Masaru; Takahashi, Michiro; Mizunuma, Nobuyuki; Watanabe, Toshiaki

    2016-01-01

    Background The high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV). Methods In the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75mg/day for 28 days followed by a 7-day rest per cycle). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS). Results Between February 2004 and December 2010, 180 patients (90 in each group) were enrolled into the study. Of these, 3 patients (2 in the UFT/LV group and 1 in the surgery alone group) were excluded from the efficacy analysis. Median follow-up was 4.76 (range, 0.15–9.84) years. The RFS rate at 3 years was higher in the UFT/LV group (38.6%, n = 88) than in the surgery alone group (32.3%, n = 89). The median RFS in the UFT/LV and surgery alone groups were 1.45 years and 0.70 years, respectively. UFT/LV significantly prolonged the RFS compared with surgery alone with the hazard ratio of 0.56 (95% confidence interval, 0.38–0.83; P = 0.003). The hazard ratio for death of the UFT/LV group against the surgery alone group was not significant (0.80; 95% confidence interval, 0.48–1.35; P = 0.409). Conclusion Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice. Trial Registration UMIN Clinical Trials Registry C000000013 PMID:27588959

  13. Postoperative hormonal therapy prevents recovery of neurological damage after surgery in patients with breast cancer

    PubMed Central

    Sekiguchi, Atsushi; Sato, Chiho; Matsudaira, Izumi; Kotozaki, Yuka; Nouchi, Rui; Takeuchi, Hikaru; Kawai, Masaaki; Tada, Hiroshi; Ishida, Takanori; Taki, Yasuyuki; Ohuchi, Noriaki; Kawashima, Ryuta

    2016-01-01

    Cancer survivors are exposed to several risk factors for cognitive dysfunction, such as general anesthesia, surgical trauma, and adjuvant therapies. In our recent study we showed that thalamic volume reduction and attentional dysfunction occurred shortly after surgery. Here, we examined the 6-month prognosis of the 20 patients with breast cancer who underwent surgery. Seven patients did not receive any adjuvant therapy after the surgery and 13 patients received a hormonal therapy after the surgery. We assessed their attentional functions, and thalamic volumes shortly after and 6 months after surgery. We found a significant group x time interaction in the attentional functions (p = 0.033) and the right thalamus (p <  0.05, small volume correction), suggesting the thalamic volume reduction and attentional dysfunction recovered in patients without adjuvant therapy. Our findings provide a better understanding of the potential role of hormonal therapy in relation to the cognitive dysfunction of cancer survivors. PMID:27708377

  14. Medical factors influencing decision making regarding radiation therapy for breast cancer

    PubMed Central

    Dilaveri, Christina A; Sandhu, Nicole P; Neal, Lonzetta; Neben-Wittich, Michelle A; Hieken, Tina J; Mac Bride, Maire Brid; Wahner-Roedler, Dietlind L; Ghosh, Karthik

    2014-01-01

    Radiation therapy is an important and effective adjuvant therapy for breast cancer. Numerous health conditions may affect medical decisions regarding tolerance of breast radiation therapy. These factors must be considered during the decision-making process after breast-conserving surgery or mastectomy for breast cancer. Here, we review currently available evidence focusing on medical conditions that may affect the patient–provider decision-making process regarding the use of radiation therapy. PMID:25429241

  15. Estrogen therapy in gynecological cancer survivors.

    PubMed

    Guidozzi, F

    2013-12-01

    Treatment of gynecological cancer has significant impact on a woman's quality of life because it commonly includes removal of the uterus and ovaries, both being the core of a woman's femininity, whilst irradiation and chemotherapy, be they as primary therapy or when indicated as postoperative adjuvant therapy, will lead to ablation of ovarian function if the ovaries had not been removed. This will lead to an acute onset of menopausal symptoms, which may be more debilitating than those occurring as a result of natural aging, and of which hot flushes, night sweats, insomnia, mood swings, vaginal dryness, decreased libido, malaise and a general feeling of apathy are the most common. About 25% of gynecological cancers will occur in pre- and perimenopausal women, a large percentage of whom will become menopausal as a result of their treatment. There are also the gynecological cancer survivors who are not rendered menopausal as a result of the treatment strategy but who will become menopausal because of natural aging. Concern among the medical attendants of these women is whether use of estrogen therapy or estrogen and progestogens for their menopausal symptoms will reactivate tumor deposits and therefore increase the rate of recurrence and, as a result, decrease overall survival among these women. Yet the data that are available do not support this concern. There are eight retrospective studies and only one randomized study that have analyzed outcome in endometrial cancer survivors who used hormone therapy after their surgery, whilst, among ovarian cancer survivors, there are four retrospective studies and one randomized study. The studies do suffer from small numbers and, although the studies pertaining to endometrial cancer analyze mostly women with early-stage disease, a number of the studies in both the endometrial and ovarian cancer survivors do have a sizeable follow-up. These studies seem to support that estrogen therapy after the treatment for gynecological

  16. Health-related Quality of Life in Metastatic and Adjuvant Breast Cancer Patients

    PubMed Central

    Wallwiener, M.; Simoes, E.; Sokolov, A. N.; Brucker, S. Y.; Fasching, P. A.; Graf, J.

    2016-01-01

    Introduction: When cancer patients have advanced disease and a primary cure is no longer possible, the focus is on maintaining the patientʼs quality of life. Recent therapeutic advances in breast cancer treatment mean that even patients with metastatic disease can remain stable for long periods of time. The aim of this study was to look at the health-related quality of life (HRQL) of these patients and compare it with data for the general population and to show the differences in outcomes for different survey instruments used to measure quality of life. Material and Methods: A total of 96 breast cancer patients with metastatic disesae or receiving adjuvant therapy were questioned about their quality of life. Patients were investigated using the established survey instruments EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5L and EQ VAS. All patients filled out questionnaires. Statistical analysis was done using MS Excel and SPSS. Results: Although the questionnaires were completed at the same time, the different questionnaires showed significant differences with regard to the level of stress experienced by the patient. When the EQ VAS questionnaire was used, the patientʼs current state of health was assessed as significantly better than with the EORTC QLQ-C30. Overall, all aspects of patientsʼ quality of life were found to be in need of optimization and HRQL of patients was significantly poorer in all areas compared to the reference population. Conclusion: To improve the quality of life of patients with metastatic disease, it is necessary to continuously monitor the success of therapy. The choice of survey tools is highly relevant as assessments differ considerably depending on the choice of questionnaire. PMID:27761027

  17. Prognostic values of DLK1 for surgery and imatinib mesylate adjuvant therapy in gastrointestinal stromal tumors

    PubMed Central

    Xu, Jia; Wang, Ming; Zhang, Zizhen; Zhao, Wenyi; Wang, Chaojie; Tu, Lin; Zhang, Yeqian; Cao, Hui

    2016-01-01

    The Delta-like 1 homolog (DLK1) gene is a paternal imprinting gene located on human chromosome 14q32, a site associated with frequent chromosomal mutations in GIST. The expression level of DLK1 is closely associated with the outcome of tumours. However, no study has reported the DLK1 expression in GIST. Here, we demonstrated that DLK1 showed low expression in GIST patients with low risk according to the modified National Institute of Health (NIH) criteria. With increasing tumour risk level, DLK1 gene and protein expression levels gradually increased. In the test cohort, tissue microarray data showed that DLK1 protein expression was significantly associated with tumour size, mitotic figure count, NIH risk level, and Ki67 expression. In terms of either disease-free survival (DFS) or overall survival (OS), the long-term outcome was significantly better in DLK1-negative patients than in DLK1-positive patients. Univariate and multivariate analyses suggested that DLK1 expression was an independent risk factor influencing tumour DFS. Additionally, for intermediate/high-risk GIST patients received postoperative IM adjuvant therapy, Kaplan-Meier analysis showed that IM adjuvant therapy was associated with a better outcome in DLK1-negative patients than in DLK1-positive patients. All of the above results were verified in the validation cohort. Taken together, DLK1 is a promising prognostic biomarker for GISTs that may help to predict surgical outcomes and guide adjuvant IM therapy. PMID:27904782

  18. Adjuvant combined ozone therapy for extensive wound over tibia.

    PubMed

    Shah, Prasham; Shyam, Ashok K; Shah, Sambhav

    2011-07-01

    Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15(th) day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  19. Adjuvant combined ozone therapy for extensive wound over tibia

    PubMed Central

    Shah, Prasham; Shyam, Ashok K; Shah, Sambhav

    2011-01-01

    Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15th day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability. PMID:21772635

  20. 5-Fluorouracil Adjuvant Chemotherapy Does Not Increase Survival in Patients with CpG Island Methylator Phenotype Colorectal Cancer

    PubMed Central

    Jover, Rodrigo; Nguyen, Thuy-Phuong; Pérez-Carbonell, Lucía; Zapater, Pedro; Payá, Artemio; Alenda, Cristina; Rojas, Estefanía; Cubiella, Joaquín; Balaguer, Francesc; Morillas, Juan D.; Clofent, Juan; Bujanda, Luis; Reñé, Josep M; Bessa, Xavier; Xicola, Rosa M.; Nicolás-Pérez, David; Castells, Antoni; Andreu, Montserrat; Llor, Xavier; Boland, C. Richard; Goel, Ajay

    2011-01-01

    Background & Aims 5-FU-based adjuvant chemotherapy does not increase survival times of patients with colorectal tumors with microsatellite instability. We determined the response of patients with colorectal tumors with the CpG island methylator phenotype (CIMP) to 5-FU-based therapy. Methods We analyzed a population-based cohort of 302 patients with colorectal cancer (CRC) for a median follow-up time of 50.7 months. CIMP status was determined by analysis of the CACNAG1, SOCS1, RUNX3, NEUROG1, and MLH1 promoters; tumors were considered to be CIMP-positive (CIMP+) if at least 3 promoters were methylated. Results Tumors from 29.5% (89/302) of patients were CIMP+; this did not influence disease-free survival (log rank=.26). Of tumors of TNM stages II–III (n=196), 32.7% were CIMP+. Among patients with CRC stages II–III who did not receive adjuvant 5-FU chemotherapy, those with CIMP+ tumors had longest times of disease-free survival (log rank=.04); patients with CIMP+ tumors who received chemotherapy had shorter times of disease-free survival (log rank=0.02). In patients with CIMP-negative tumors, adjuvant 5-FU chemotherapy significantly increased time of disease-free survival (log-rank=.00001). However, in patients with CIMP+ tumors, adjuvant 5-FU chemotherapy did not affect time of disease-free survival (log rank=.7). Multivariate analysis showed a significant, independent interaction between 5-FU treatment and CIMP status (hazard ratio [HR]=0.6; 95% confidence interval [CI], .5–.8). Among patients with CIMP+ tumors, adjuvant chemotherapy was not an independent predictor of outcome (HR=0.8; 95% CI, 0.3–2.0). In patients who did not receive adjuvant 5-FU chemotherapy, CIMP status was the only independent predictor of survival (HR=2.0; 95% CI, 1.1–3.8) Conclusion Patients with CIMP+ colorectal tumors do not benefit from 5-FU–based adjuvant chemotherapy. PMID:21185836

  1. Renal Toxicity of Adjuvant Chemoradiotherapy With Cisplatin in Gastric Cancer

    SciTech Connect

    Welz, Stefan Hehr, Thomas; Kollmannsberger, Christian; Bokemeyer, Carsten; Belka, Claus; Budach, Wilfried

    2007-12-01

    Purpose: Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods: Between December 2000 and September 2003, 27 patients were treated at Tuebingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m{sup 2}), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m{sup 2}/24 h). A dose constraint of {<=}12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results: The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m{sup 2} in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range. Conclusions: Using a dose constraint of {<=}12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m{sup 2} administered before and after simultaneous 5-FU and radiotherapy.

  2. Nipple-sparing mastectomy in breast cancer patients: The role of adjuvant radiotherapy (Review).

    PubMed

    Janssen, Stefan; Holz-Sapra, Edna; Rades, Dirk; Moser, Alexander; Studer, Gabriela

    2015-06-01

    The present study aimed to evaluate the role of adjuvant radiotherapy (RT) following nipple-sparing mastectomy (NSM) for patients with ductal carcinoma in situ and invasive breast cancer, based on the published literature. Currently, there is no standard for RT following NSM. NSM aims to spare the nipple areola complex (NAC) without compromising locoregional control. Long-term follow-up studies have begun to show promising results. A search of the English literature was performed using the Medline database and Cochrane central library, with the keywords 'nipple/areola-sparing mastectomy', 'whole skin mastectomy' and 'NAC preservation'. A total of 32 original studies with data on NSM in terms of locoregional control, NAC control, NAC necrosis and adjuvant RT were identified. The median locoregional and NAC recurrence rates were 3.2 and 1.4% (range, 0-28.4% and 0-3.7%), respectively. The volume of remaining breast tissue following NSM was reported inconsistently. In 15 studies, RT was not mentioned. In the remaining 17 studies, RT was administered in 0-100% of patients. Only 7 studies provided detailed information regarding the use of adjuvant RT. Adjuvant thoracic wall irradiation was not used in certain studies, not even for locoregionally advanced tumors. Overall, NSM appears a feasible treatment without increased risk of locoregional recurrence for selected patients. The role of adjuvant RT following NSM requires further clarification. The decision regarding adjuvant RT must be made in interdisciplinary tumor boards and with consideration of the individual situation of the patient.

  3. Integrative oncology: managing cancer pain with complementary and alternative therapies.

    PubMed

    Running, Alice; Seright, Teresa

    2012-08-01

    For the projected 1,638,910 patients with a diagnosis of cancer this year, the great majority of them (75-90 %) will experience cancer-related pain. A growing number of these patients will turn to complementary and alternative therapies to assist with the management of their pain and other cancer-related symptoms. The World Health Organization's suggested approach to pain management begins with the use of time honored opioids, but recommends the use of adjuvant therapies early in the management process. Complementary and alternative therapies are being used by more patients each year to assist with the management of their pain. Practitioners and researchers must be aware of the evidence that exists to support or refute the use of these therapies. In this manuscript we review evidence from the recent past on complementary and alternative therapies for pain with emphasis on more common modalities including acupuncture, bio-energy, massage, and music.

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

    SciTech Connect

    Pinkham, Mark B.; Foote, Matthew C.; Burmeister, Elizabeth; Thomas, Janine; Meakin, Janelle; Smithers, B. Mark; Burmeister, Bryan H.

    2013-07-15

    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 therapy 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.

  5. [Current status of adjuvant chemotherapy for resected lung cancer at our institute--focus on clinical trial enrollment].

    PubMed

    Sawada, Shigeki; Yamashita, Motohiro; Komori, Eisaku; Suehiro, Hiroshi; Ogino, Atsuko; Nogami, Hiroyuki; Segawa, Yoshihiko; Shinkai, Tetsu

    2010-03-01

    Adjuvant chemotherapy after complete resection in Stage I B-III A non-small cell lung cancer is recommended. Several clinical trials of adjuvant chemotherapy are now underway in Japan. Our institute also participates in adjuvant clinical trials, but slow patient recruitment is a problem. In this paper, we reported the current status of adjuvant chemotherapy and recruitment for clinical trials at our institute. Between August 2001 and December 2008, candidates for adjuvant chemotherapy were 315 patients. Among them 186 who received adjuvant chemotherapy were younger and had less co-morbidity than those who did not receive adjuvant chemotherapy. Twenty-five of the 186 patients participated in the clinical trials. The major reason of refusal of a clinical trial was that patients preferred to choose their own treatment and disliked randomized trials.

  6. Linking Estrogen-Induced Apoptosis With Decreases in Mortality Following Long-term Adjuvant Tamoxifen Therapy

    PubMed Central

    2014-01-01

    The impressive first results of the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) and the adjuvant Tamoxifen To offer more (aTTom) trials both demonstrate that 10 years of tamoxifen is superior to five years of treatment. Tamoxifen is a nonsteroidal antiestrogen that blocks estrogen-stimulated tumor growth. Paradoxically, mortality decreases dramatically only in the decade after long-term tamoxifen is stopped. It is proposed that the evolution and clonal selection of micrometastases that acquire tamoxifen resistance now become increasingly vulnerable to endogenous estrogen-induced apoptosis. Laboratory and clinical studies confirm the concept, and supporting clinical evidence from the estrogen-alone trial in the Women’s Health Initiative (WHI), demonstrate that long-term estrogen-deprived women given exogenous physiologic estrogen have a decreased incidence of breast cancer and decreased mortality. It is proposed that a natural process of apoptosis is recruited to execute the long-term survival benefit of stopping ten years of adjuvant tamoxifen, but only after clonal selection of vulnerable breast cancer cells in an estrogen-deprived environment. PMID:25269699

  7. Single Nucleotide Polymorphisms as Prognostic and Predictive Factors of Adjuvant Chemotherapy in Colorectal Cancer of Stages I and II

    PubMed Central

    Horvat, Matej; Potočnik, Uroš; Repnik, Katja; Kavalar, Rajko; Štabuc, Borut

    2016-01-01

    Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant. PMID:26884752

  8. Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

    SciTech Connect

    Vargas, Carlos; Kestin, Larry L. . E-mail: lkestin@beaumont.edu; Weed, Dan W.; Krauss, Daniel; Vicini, Frank A.; Martinez, Alvaro A.

    2005-03-01

    Purpose: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. Methods and materials: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level {>=}0.1 ng/mL and any postoperative PSA level {>=}0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. Results: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA < 0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the

  9. Why a D2 gastrectomy plus adjuvant chemotherapy is insufficient in locally advanced gastric cancer

    PubMed Central

    Sebastián Solé, Z; Larsen, Francisco E; Solé, Claudio V

    2016-01-01

    This review discusses all the important published evidence regarding adjuvant treatments in locally advanced gastric cancer. In this process it revealed facts that demonstrate the superiority of radiotherapy and concomitant chemotherapy to chemotherapy alone. Some outstanding work that has not yet been published is also discussed. PMID:28105077

  10. Why a D2 gastrectomy plus adjuvant chemotherapy is insufficient in locally advanced gastric cancer.

    PubMed

    Sebastián Solé, Z; Larsen, Francisco E; Solé, Claudio V

    2016-01-01

    This review discusses all the important published evidence regarding adjuvant treatments in locally advanced gastric cancer. In this process it revealed facts that demonstrate the superiority of radiotherapy and concomitant chemotherapy to chemotherapy alone. Some outstanding work that has not yet been published is also discussed.

  11. Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice*

    PubMed Central

    Zhao, Ming; Ding, Xian-feng; Shen, Jian-yu; Zhang, Xi-ping; Ding, Xiao-wen; Xu, Bin

    2017-01-01

    Breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs. Being effective for enhancing drug efficacy and reducing side effects, they have been widely used for developing anticancer drugs. As a kind of anthracycline with high anticancer activity, doxorubicin can treat or alleviate a variety of malignant tumors effectively when it is used on its own or in combination with other anticancer drugs. Although liposomal doxorubicin has been extensively used in the adjuvant chemotherapy of breast cancer, its exact therapeutic efficacy and side effects have not been definitely proven. Various clinical studies have adopted different combined regimes, dosages, and staging, so their findings differ to certain extent. This paper reviews the clinical application of liposomal doxorubicin in the adjuvant chemotherapy of breast cancer and illustrates therapeutic effects and side effects of pegylated liposomal doxorubicin (PLD) and non-PLD (NPLD) in clinical research, in order to discuss the strategies for applying these drugs in such adjuvant chemotherapy, looking forward to providing references for related research and clinical treatment in terms of dosage, staging, combined regimes, and analysis methods and so on. PMID:28070993

  12. Phase 1 study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases.

    PubMed

    Takahashi, Michiro; Hasegawa, Kiyoshi; Oba, Masaru; Saiura, Akio; Arita, Junichi; Sakamoto, Yoshihiro; Shinozaki, Eiji; Mizunuma, Nobuyuki; Matsuyama, Yutaka; Kokudo, Norihiro

    2016-08-01

    of Background Data The effectiveness of adjuvant chemotherapy in patients with stage II/III colorectal cancer has been confirmed in various studies. However, no adjuvant chemotherapy for colorectal liver metastasis (CLM) classified to stage IV has been established. Objectives We conducted a phase 1 study of S-1 and oxaliplatin to determine the recommended dose (RD) in patients with CLM as adjuvant therapy in two institutes. Methods S-1 and oxaliplatin were administered from day 1 to day 14 of a 3-week cycle as a 2-h infusion every 3 weeks, respectively. The initial doses of S-1 and oxaliplatin were fixed to 80 mg/m(2) and 100 mg/m(2), respectively (level 1). We scheduled in the protocol a dose change of S-1 and oxaliplatin to level 2 (S-1: 80 mg/m(2) and oxaliplatin: 130 mg/m(2)) or level 0 (S-1: 65 mg/m(2) and oxaliplatin: 100 mg/m(2)) depending on the incidence of dose-limiting toxicity (DLT) at level 1 in six patients. Results Because DLT occurred in one among the initial six patients at level 1, the doses were increased to level 2 in the next six patients. At level 2, grade 3 leukopenia and neutropenia occurred in one (16.7 %) and two (33.3 %) patients, respectively, in the absence of non-hematological event. Because no DLT occurred at level 2, we suggest that the RD can be set to the level 2 dose. The median number of cycles delivered at RD was 8. The mean relative dose intensity of S-1 and oxaliplatin at RD was 0.90 and 0.63, respectively. Conclusion In a patient undergoing hepatectomy for CLM, 80 mg/m(2) of S-1 and 130 mg/m(2) of oxaliplatin are recommended as adjuvant therapy. A further study is required to confirm the efficacy and safety of this regimen on a larger scale.

  13. NANOTECHNOLOGY IN CANCER THERAPY

    PubMed Central

    Aslan, Burcu; Ozpolat, Bulent; Sood, Anil K.; Lopez-Berestein, Gabriel

    2014-01-01

    Cancer is one of the major causes of mortality worldwide and advanced techniques for therapy are urgently needed. The development of novel nanomaterials and nanocarriers has allowed a major drive to improve drug delivery in cancer. The major aim of most nanocarrier applications has been to protect the drug from rapid degradation after systemic delivery and allowing it to reach tumor site at therapeutic concentrations, meanwhile avoiding drug delivery to normal sites as much as possible to reduce adverse effects. These nanocarriers are formulated to deliver drugs either by passive targeting, taking advantage of leaky tumor vasculature or by active targeting using ligands that increase tumoral uptake potentially resulting in enhanced antitumor efficacy, thus achieving a net improvement in therapeutic index. The rational design of nanoparticles plays a critical role since structural and physical characteristics, such as size, charge, shape, and surface characteristics determine the biodistribution, pharmacokinetics, internalization and safety of the drugs. In this review, we focus on several novel and improved strategies in nanocarrier design for cancer therapy. PMID:24079419

  14. Prediction of metastatic relapse in node-positive breast cancer: establishment of a clinicogenomic model after FEC100 adjuvant regimen.

    PubMed

    Campone, Mario; Campion, Loïc; Roché, Henry; Gouraud, Wilfried; Charbonnel, Catherine; Magrangeas, Florence; Minvielle, Stéphane; Genève, Jean; Martin, Anne-Laure; Bataille, Régis; Jézéquel, Pascal

    2008-06-01

    Breast cancer is a very heterogeneous disease, and markers for disease subtypes and therapy response remain poorly defined. For that reason, we employed a retrospective study in node-positive breast cancer to identify molecular signatures of gene expression correlating with metastatic free survival. Patients were primarily included in FEC100 (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2)) arms of two multicentric prospective adjuvant clinical trials (PACS01 and PEGASE01-FNCLCC cooperative group). Data from nylon microarrays containing 8,032 cDNA unique sequences, representing 5,776 distinct genes, have been used to develop a predictive model for treatment outcome. We obtained the gene expression profiles for 150 of these patients, and used stringent univariate selection techniques based on Cox regression combined with principal component analysis to identify a genomic signature of metastatic relapse after adjuvant FEC100 regimen. Most of the 14 selected genes have a clear role in breast cancer, carcinogenesis or chemotherapy resistance. Six genes have been previously described in other genomic studies (UBE2C, CENPF, C16orf61 [DC13], STMN1, CCT5 and BCL2A1). Furthermore, we showed the interest of combining transcriptomic data with clinical data into a clinicogenomic model for patients subtyping. The described model adds predictive accuracy to that provided by the well-established Nottingham prognostic index or by our genomic signature alone.

  15. Continued value of adjuvant anthracyclines as treatment for early breast cancer.

    PubMed

    Turner, Natalie; Biganzoli, Laura; Di Leo, Angelo

    2015-07-01

    Anthracyclines are frequently used in the adjuvant treatment of early-stage breast cancer. However, with the increasing use of other active drugs--mainly taxanes and trastuzumab in HER2-positive disease--coupled with concerns about anthracycline-associated toxic effects, there is debate about whether anthracyclines are still needed. Three major factors should be taken into consideration with the investigation of the role of anthracyclines in management of early breast cancer; specifically, the proven efficacy of anthracyclines in breast cancer, the absence of superiority of non-anthracycline-based chemotherapy over anthracycline-taxane regimens, and the low risk of toxic effects associated with the cumulative doses of anthracyclines used in contemporary regimens. The risks remain substantially outweighed by the benefits of treatment with anthracyclines, and thus, they maintain an important role in adjuvant treatment of breast cancer, particularly in women with high-risk disease.

  16. [Hormonal therapy for prostatic cancer--state of the art].

    PubMed

    Miyakita, Hideshi

    2005-02-01

    Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high dose estrogen. Labrie et al introduced combined use of a LHRH agonist and an androgen antagonist for prostatic cancer. Various reports demonstrated a beneficial effect for combined androgen blockade using nonsteroidal antiandrogens for advanced prostatic cancer through meta-analysis of published randomized control trials. In Japanese status, a combined androgen blockade is popular for advanced prostatic cancer as well as local cancer by J-Cap survey. There is a lot of controversy about adjuvant hormonal therapy for prostatic cancer including intermittent hormonal therapy, but the results are not gotten yet.

  17. Radiation Therapy for Skin Cancer

    MedlinePlus

    ... than in African-Americans. TYPES OF SKIN CANCER Basal cell carcinoma: This is the most common form of skin ... epidermis ). Radiation therapy is very effective for treating basal cell cancers that have not spread elsewhere. Other common treatments ...

  18. Optimal adjuvant treatment for patients with HER2-positive breast cancer in 2015.

    PubMed

    Zardavas, Dimitrios; Fouad, Tamer M; Piccart, Martine

    2015-11-01

    The introduction of trastuzumab as adjuvant treatment for patients with HER2-positive breast cancer changed the natural course of early-stage disease. Currently, one year of trastuzumab given concurrently with a taxane and following an anthracycline regimen is the preferred standard of care in Europe. The first attempt to escalate this approach, though the implementation of dual HER2 blockade with lapatinib added to trastuzumab, as assessed by the ALTTO trial, failed to improve further clinical outcomes; clinical assessment of the adjuvant trastuzumab/pertuzumab regimen is still ongoing in the APHINITY trial. Negative results were also reported for the addition of bevacizumab to adjuvant trastuzumab treatment within the context of the BETH study. Similarly, efforts to de-escalate through shortening the duration of adjuvant trastuzumab treatment failed (the PHARE trial), whereas others are still ongoing. Of note, evidence supports the use of lighter chemotherapy regimens with one year of adjuvant trastuzumab as backbone, for women with small HER2-positive breast tumors, where the omission of anthracyclines did not compromise the clinical outcome. Despite the successes achieved so far, a proportion of women with early-stage HER2-positive breast cancer, will still experience disease recurrence. The identification of these women is urgently needed, as well as the identification of predictive biomarkers to dictate the optimal treatment strategy. So far, HER2 expression status has been the only validated predictive biomarker for this patient population. Despite the clear association of pCR achieved through neoadjuvant trastuzumab-based chemotherapy with clinical outcome, results from neoadjuvant trials have not been always consistent with what was seen in the adjuvant setting. Similarly, inconsistent results have been reported for the predictive ability of alterations affecting the PI3K signaling pathway or the quantification of tumor infiltrating lymphocytes. In the era

  19. Biological Therapies for Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  20. Photodynamic Therapy for Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  1. Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy

    PubMed Central

    Granja, Andreia; Pinheiro, Marina; Reis, Salette

    2016-01-01

    Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (−)-Epigallocatechin-3-gallate (EGCG) is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG’s properties and potentiate its anti-tumoral activity. PMID:27213442

  2. Early versus delayed initiation of adjuvant treatment for pancreatic cancer

    PubMed Central

    Kim, Hyoung Woo; Lee, Jong-Chan; Lee, Jongchan; Kim, Jin Won; Kim, Jaihwan; Hwang, Jin-Hyeok

    2017-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC. Methods We retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20–83 days]). Results Patient baseline characteristics were comparable in both groups, except for grade III or IV postoperative complications (5.4% in the early group vs. 22.8% in the delayed group). With a median 20.3-month follow-up, the overall survival (OS) and disease-free survival (DFS) times were 29.5 and 14.7 months, respectively. The early group had significantly prolonged OS (39.1 vs. 21.1 months, p = 0.018) and DFS (18.8 vs. 10.0 months, p = 0.034), compared to the delayed group. Among 71 patients who completed planned adjuvant treatment, patients in the early group tended to have longer, though not statistically significant, OS and DFS times than those in the delayed group. In 67 patients without postoperative complications, patients in the early group had longer OS (42.8 vs. 20.5 months, p = 0.002) and DFS (19.6 vs. 9.1 months, p = 0.005) than those in the delayed group. By multivariate analysis, incompletion of treatment (hazard ratio [HR]: 4.039, 95% confidence interval [CI]: 2.334–6.992), delayed treatment initiation (HR: 1.822, 95% CI: 1.081–3.070), and positive angiolymphatic invasion (HR: 2.116, 95% CI: 1.160–3.862) were significantly associated with shorter OS. Conclusions Adjuvant treatment should be delivered earlier and completed for better outcomes in resected PDAC patients, especially without postoperative complications. PMID:28301556

  3. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer.

    PubMed

    Scheiermann, Julia; Klinman, Dennis M

    2014-11-12

    Synthetic oligonucleotides (ODN) that express unmethylated "CpG motifs" trigger cells that express Toll-like receptor 9. In humans this includes plasmacytoid dendritic cells and B cells. CpG ODN induce an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. Their utility as vaccine adjuvants was evaluated in a number of clinical trials. Results indicate that CpG ODN improve antigen presentation and the generation of vaccine-specific cellular and humoral responses. This work provides an up-to-date overview of the utility of CpG ODN as adjuvants for vaccines targeting infectious agents and cancer.

  4. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer

    PubMed Central

    Scheiermann, Julia; Klinman, Dennis M.

    2014-01-01

    Synthetic oligonucleotides (ODN) that express unmethylated “CpG motifs” trigger cells that express Toll-like receptor 9. In humans this includes plasmacytoid dendritic cells and B cells. CpG ODN induce an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. Their utility as vaccine adjuvants was evaluated in a number of clinical trials. Results indicate that CpG ODN improve antigen presentation and the generation of vaccine-specific cellular and humoral responses. This work provides an up-to-date overview of the utility of CpG ODN as adjuvants for vaccines targeting infectious agents and cancer. PMID:24975812

  5. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  6. [Is there alternative to FOLFOX adjuvant chemotherapy for stage III colorectal cancer patients?].

    PubMed

    Esch, Anouk; Coriat, Romain; Perkins, Géraldine; Brezault, Catherine; Chaussade, Stanislas

    2012-01-01

    Being the second cancer for men and the third cancer for women in France, colorectal cancer represents a serious public health issue. Its incidence has increased these last years and despite new therapeutics being developed, it still has a bad prognostic. Thanks in part to Hemoccult national mass screening program, its diagnosis is made possible at an earlier stage, which makes a surgical curative resection and the carrying out of adjuvant chemotherapy possible. For stage III colic cancer that has been surgically removed, adjuvant chemotherapy by FOLFOX 4 has to be offered. Nevertheless, because of its toxicities, the patient's high age, important comorbidities or post-surgical complications, this chemotherapy occasionally cannot be done. What are the colorectal cancer prognostic factors which would guide the chemotherapy? TNM classification, number of examined lymph nodes, MSI status, and presence or not of a perforation or a perinervous, lymphatic or venous invasion is recognized prognostic factors. Also, what are the alternatives of FOLFOX 4 regimen as colorectal cancer adjuvant treatment?

  7. 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.

  8. Toll-like receptor agonists in cancer therapy

    PubMed Central

    Adams, Sylvia

    2010-01-01

    Toll-like receptors (TLRs) are pattern-recognition receptors related to the Drosophila Toll protein. TLR activation alerts the immune system to microbial products and initiates innate and adaptive immune responses. The naturally powerful immunostimulatory property of TLR agonists can be exploited for active immunotherapy against cancer. Antitumor activity has been demonstrated in several cancers, and TLR agonists are now undergoing extensive clinical investigation. This review discusses recent advances in the field and highlights potential opportunities for the clinical development of TLR agonists as single agent immunomodulators, vaccine adjuvants and in combination with conventional cancer therapies. PMID:20563267

  9. Successful treatment of accessory breast cancer with endocrine therapy#

    PubMed Central

    Wang, Chun-Xi; Guo, Shu-Li; Han, Li-Na

    2017-01-01

    Accessory breast cancers in males are extremely rare, and only a few cases have been reported in the literature. In this paper, an 87-year-old male patient was diagnosed with an accessory breast cancer by means of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and immunohistochemistry based on needle biopsy, and has undergone successful resection and postoperative adjuvant endocrine therapy. He was the oldest male patient with an accessory breast cancer reported in the Chinese Hospital Knowledge Database and PubMed literature from 1975 to 2015. PMID:28070998

  10. Pre-adjuvant chemotherapy leukocyte count may predict the outcome for advanced gastric cancer after radical resection.

    PubMed

    Pei, Dong; Zhu, Fang; Chen, Xiaofeng; Qian, Jing; He, Shaohua; Qian, Yingying; Shen, Hua; Liu, Yiqian; Xu, Jiali; Shu, Yongqian

    2014-03-01

    Gastric cancer (GC) has a high morbidity worldwide each year especially in China and advanced GC is well known with poor prognosis, for which surgical resection combine adjuvant chemotherapy is the optimal choice for therapy. Leukocyte is an important index during the treatment for its influence on drugs' dosage and tolerance. Therefore, peripheral blood leukocyte and its subsets during adjuvant chemotherapy may have great clinical value for predicting prognostic. In this retrospective study, we showed the distribution of white blood cell and its subsets in the baseline period before adjuvant chemotherapy in 399 patients who underwent radical resection for advanced GC from January 1, 2008 to August 31, 2012. We investigated the relationship between leukocyte count and overall survival (OS) as well as disease-free survival (DFS). In these patients, females were more likely to have less white blood cells after operation (P=0.016). Patients with pre-chemotherapy leukocyte count less than 4×10(9)/L got worse DFS (P=0.028) and OS (P=0.016). In multivariate analysis, tumor size ≥ 6cm (P=0.033), TNM stage IV (P=0.024), vascular or nerval invasion (P=0.005) and leukocyte count less than 4.0×10(9)/L (P=0.019) was associated with poor DFS. TNM stage IV (P=0.008), vascular or nerval invasion (P=0.001) and lower leukocyte count (P=0.045) were independent risk factors for poor OS. Taken together, our findings suggest that pre-adjuvant chemotherapy peripheral blood leukocyte count correlates with clinical outcome of patients with advanced GC after radical resection.

  11. Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab

    PubMed Central

    Olson, E. M.; Abdel-Rasoul, M.; Maly, J.; Wu, C. S.; Lin, N. U.; Shapiro, C. L.

    2013-01-01

    Background Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab. Methods Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models. Results A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02–1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed. Conclusions Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients. PMID:23463626

  12. Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor.

    PubMed

    Ohara, Masahiro; Akimoto, Etsushi; Noma, Midori; Matsuura, Kazuo; Doi, Mihoko; Kagawa, Naoki; Itamoto, Toshiyuki

    2015-11-01

    Aromatase inhibitors have played a central role in endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer in postmenopausal patients. However, prognostic factors for recurrence following such treatment have not been identified. The current study aimed to validate the prognostic value of endocrine-related progesterone receptor (PgR) status combined with body mass index (BMI). Among 659 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2012, 184 postmenopausal patients with ER-positive (ER+) and human epidermal growth factor receptor type 2-negative (HER2-) breast cancer who were treated with adjuvant aromatase inhibitor therapy were assessed. The patients were assigned to groups based on BMI, according to the WHO cut-off value: ≥25 kg/m(2) (high, H) or <25 kg/m(2) (low, L). Positive nodal status, negative PgR status, BMI-H and a high Ki-67 labeling index (≥20%) were found to be significantly associated with a short recurrence-free interval (RFI) upon univariate analysis (P=0.048, 0.007, 0.027, and 0.012, respectively). The patients were further grouped based on their combined PgR/BMI status. The RFI was significantly shorter in the PgR- and/or BMI-H group compared with that of the PgR+/BMI-L group (P=0.012). Multivariate analysis revealed PgR- tumors and/or BMI-H and positive nodal status to be independent prognostic factors (P=0.012 and 0.020, respectively). The present findings indicate that PgR/BMI status may serve as a practical tool in the management of ER+ and HER2- breast cancer in patients treated with adjuvant aromatase inhibitors.

  13. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

    SciTech Connect

    Li Baoqing; Chen, Margaret; Nori, Dattatreyudu; Chao, K.S. Clifford; Chen, Allen M.; Chen, Steven L.

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

  14. Photodynamic therapy for cancer

    MedlinePlus

    ... Cancer of the esophagus-photodynamic; Esophageal cancer-photodynamic; Lung cancer-photodynamic ... the light at the cancer cells. PDT treats cancer in the: Lungs, using a bronchoscope Esophagus, using upper endoscopy Doctors ...

  15. Adjuvant radiotherapy for pathological high-risk muscle invasive bladder cancer: time to reconsider?

    PubMed Central

    Baumann, Brian C.; Eapen, Libni J.; Bahl, Amit; Murthy, Vedang; Roubaud, Guilhem; Orré, Mathieu; Efstathiou, Jason A.; Shariat, Shahrokh; Larré, Stephane; Richaud, Pierre; Christodouleas, John P.

    2016-01-01

    Radical cystectomy with extended pelvic lymph-node dissection, associated with neo-adjuvant chemotherapy, remains the standard of care for advanced, non-metastatic muscle-invasive bladder cancer (MIBC). Loco-regional control is a key factor in the outcome of patients since it is related to overall survival (OS), disease-free survival (DFS) and cause-specific survival. The risk of loco-regional recurrence (LRR) is correlated to pathological factors as well as the extent of the lymphadenectomy. In addition, neither pre- nor post-operative chemotherapy have shown a clear impact on LRR-free survival. Several recent publications have led to the development of a nomogram predicting the risk of LRR, in order to identify patients most likely to benefit from adjuvant radiotherapy. Given the high risk of LRR for selected patients and improvements in radiation techniques that can reduce toxicity, there is a growing interest in adjuvant radiotherapy; international cooperative groups have come together to provide the rationale in favor of adjuvant radiotherapy. Clinical trials in order to reduce the risk of pelvic relapse are opened based on this optimizing patient selection. The aim of this critical literature review is to provide an overview of the rationale supporting the studies of adjuvant radiation for patients with pathologic high-risk MIBC. PMID:27785427

  16. Enhancing Immunogenicity of Cancer Vaccines: QS-21 as an Immune Adjuvant

    PubMed Central

    Gin, David Y.; Slovin, Susan F.

    2014-01-01

    Saponins comprise a class of plant natural products that incorporate a lipophilic terpenoid core, to which is appended one or more carbohydrate residues. They are amphiphilic molecules and often exhibit toxic biological profiles, likely as a result of their roles as vital components in protective coatings to defend against phytopathogen infection and insect predation. The most notable of adjuvant-active saponins investigated for vaccine development come from the Chilean Soapbark Tree, Quillaja saponaria (i.e., QS). More than 30 years ago, semi-purified extracts (i.e., Quil A) from the cortex of Quillaja saponaria were found to be highly effective as adjuvants in veterinary vaccines. However, due to significant and variable toxicity effects, Quil A was not deemed appropriate for human vaccines. More refined purification methods have led to multiple fractions which are derived from the original plant extract. As such, QS-21 to date appears to be one of the more scientifically interesting and robust adjuvants in use in vaccinology. The role of QS-21 as an adjuvant for use in a variety of cancer vaccine trials and its comparison to other adjuvants is discussed in this review. PMID:25473385

  17. Clinical Characteristics, Surgical Management and Adjuvant Therapy of Patients with Uterine Carcinosarcoma: A Retrospective Case Series

    PubMed Central

    Wallwiener, C.; Hartkopf, A.; Kommoss, S.; Joachim, C.; Wallwiener, M.; Taran, F. A.; Brucker, S.

    2016-01-01

    Purpose: To review a single-center experience over a 27-year period of managing uterine carcinosarcoma (UCS), focusing on surgical practice, adjuvant therapy and clinical outcome. Material and Methods: This was a retrospective study of women with histologically proven UCS treated at the Department of Obstetrics and Gynecology, University of Tübingen, Germany, between 1983 and 2010. Inpatient and outpatient records were reviewed; follow-up and survival data were ascertained. Results: The study population comprised 18 patients with UCS. Primary surgical treatment consisted of total abdominal hysterectomy in 12 patients (67 %) and laparoscopic total hysterectomy in 4 patients (22 %). Bilateral salpingo-oophorectomy was performed in 94 % of patients (17/18). Lymph nodes were evaluated in 15 patients (83 %). Positive pelvic lymph nodes were present in 2 patients (11 %). A total of 17 patients (94 %) received adjuvant therapy. Disease recurred in 7 (39 %) patients of our study group, with no recurrence noted in the 4 patients who underwent laparoscopic surgical staging. Median disease-free survival (DFS) was 48.7 months (95 % CI: 0.0–157.3) and median overall survival (OS) was 49.9 months (95 % CI: 0.0–108.2). The 5-year survival rate was 40 %. Conclusion: UCS is a rare and aggressive uterine neoplasm with high recurrence rates and metastatic potential. Surgical staging consisting of total hysterectomy with bilateral salpingo-oophorectomy and systematic lymphadenectomy is the most important treatment for patients with UCS. Adjuvant radiation therapy appears to decrease pelvic recurrence, but there is a high incidence of distant recurrence, indicating the need for additional systemic treatment. PMID:26941453

  18. Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum

    SciTech Connect

    Thomas, P.R.; Lindblad, A.S.; Stablein, D.M.; Knowlton, A.H.; Bruckner, H.W.; Childs, D.S.; Mittelman, A.

    1986-03-15

    An adjuvant rectal carcinoma study compared four postoperative treatment regimens: (1) control (no adjuvant therapy); (2) chemotherapy alone consisting of pulses of 5-fluorouracil and methyl CCNU for 18 months; (3) pelvic and perineal radiotherapy using parallel opposed fields with 4000 rad in 4.5 to 5 weeks or 4800 rad in 5 to 5.5 weeks; and (4) a combination of both modalities. The results of this study are published elsewhere and show a significantly reduced recurrence rate and prolonged disease-free survival time for the combined modality arm compared with the no therapy arm. Severe toxicity in the combined therapy arm was significantly worse (P less than 0.001) than in either single modality arm. Most of the differences in toxicity experienced between the three regimens involved diarrhea, thrombocytopenia, and leukopenia. Analysis of all parameters of radiotherapy quality assurance data was not significantly associated with toxicity. Radiation enteritis was noted in 5 patients of 96 (5.2%) in the two arms containing irradiation. All five required laparotomy. The two enteritis fatalities occurred late at 605 and 1000 days after start of combined modality treatment, respectively. One other patient on the chemotherapy arm died of acute nonlymphocytic leukemia. The authors conclude that combined radiotherapy and chemotherapy, although significantly more effective in reducing recurrence than no therapy, is significantly more toxic than single-modality therapy in many parameters, although most of the toxicity is transient and therefore not limiting. Late complications, which are less reversible and therefore much more important than early reactions, and radiation enteritis in this study were relatively uncommon. This schedule of combined modality therapy is not only effective but appears to have tolerable toxicity, because of the relative lack of late effects.

  19. Hadron Therapy for Cancer Treatment

    SciTech Connect

    Lennox, Arlene

    2003-09-10

    The biological and physical rationale for hadron therapy is well understood by the research community, but hadron therapy is not well established in mainstream medicine. This talk will describe the biological advantage of neutron therapy and the dose distribution advantage of proton therapy, followed by a discussion of the challenges to be met before hadron therapy can play a significant role in treating cancer. A proposal for a new research-oriented hadron clinic will be presented.

  20. Is the toxicity of adjuvant aromatase inhibitor therapy underestimated? Complementary information from patient-reported outcomes (PROs).

    PubMed

    Oberguggenberger, Anne; Hubalek, Michael; Sztankay, Monika; Meraner, Verena; Beer, Beate; Oberacher, Herbert; Giesinger, Johannes; Kemmler, Georg; Egle, Daniel; Gamper, Eva-Maria; Sperner-Unterweger, Barbara; Holzner, Bernhard

    2011-07-01

    Adjuvant endocrine treatment-related adverse effects have a strong impact on patients' quality of life and thereby limit therapy's risk benefit ratio resulting in morbidity and treatment discontinuation. Still, many AI adverse effects remain untreated given that they are unrecognized by conservative methods (e.g., proxy ratings). The ability of complementary patient-reported outcomes (PROs) to provide a more comprehensive assessment of side-effects is to be explored. A cross-sectional study sample of 280 postmenopausal, early stage breast cancer patients was subjected to a comprehensive PRO assessment (FACT-B/+ES) at their after-care appointment. Prevalence and severity of patient-reported physical side-effects and psychosocial burden related to adjuvant AI therapy were compared with prevalences derived from pivotal phase IV trials (ATAC 2005, BIG1-98 2005). Across all symptom categories, highest prevalence rates were found for joint pain (59.6%), hot flushes (52%), lost interest in sexual intercourse (51.4%), and lack of energy (40.3%). Overall, PROs resulted in significantly higher prevalence rates as compared to physician ratings for all symptoms published in pivotal clinical trials except vaginal bleeding and nausea. The treatment duration exerted no significant impact on symptom frequency (P > 0.05). Established prevalence rates of endocrine treatment-related toxicity seem to be underestimated. The incorporation of PRO data should be mandatory or at least highly recommended in clinical treatment planning to arrive at a more accurate assessment of a patient's actual symptom burden enabling improved individualized management of side-effects and mediating the preservation of treatment adherence.

  1. Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy

    PubMed Central

    Cao, Lu; Cai, Gang; Xu, Fei; Yang, Zhao-Zhi; Yu, Xiao-Li; Ma, Jin-Li; Zhang, Qian; Wu, Jiong; Guo, Xiao-Mao; Chen, Jia-Yi

    2016-01-01

    Abstract The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2–positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT. Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed. At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor–positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR−/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07–15.35; P = 0.039). Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer. PMID:27512838

  2. Postoperative adjuvant chemotherapy combined with intracavitary brachytherapy in early-stage cervical cancer patients with intermediate risk factors

    PubMed Central

    Yu, Hao; Zhang, Linlin; Du, Xuelian; Sheng, Xiugui

    2016-01-01

    Objective To investigate the impact of postoperative adjuvant therapy on survival of patients with intermediate risk early-stage cervical squamous cell carcinoma. Methods A total of 133 consecutive patients with intermediate risk early-stage cervical squamous cell carcinoma treated at Shandong Cancer Hospital and Institute from February 2010 to March 2014 were enrolled in our study. All patients received adjuvant therapy and were subdivided into three groups: pelvic radiotherapy (RT; N=42), adjuvant chemotherapy + intracavitary radiotherapy (CT+ICRT; N=47), or concurrent chemoradiation (CCRT; N=44). Disease-free survival (DFS) and therapeutic complications were evaluated. Results There were no significant differences in DFS for patients treated with RT, CT+ICRT, and CCRT (P>0.05) with 3-year rates of 94.0%, 93.4%, and 97.6%, respectively. Frequencies of grade III–IV acute toxicities were higher in patients treated with CCRT (34.1%) than those treated with RT (9.5%) or CT+ICRT (16.7%; P<0.05), with no significant differences observed between RT and CT+ICRT groups (P>0.05). Grade I–II late toxicities were higher in CCRT (25%), followed by RT (19.0%), and finally, the CT+ICRT group (4.3%; P<0.05); with no significant differences observed between CCRT and RT groups (P>0.05). Conclusion Treatment with CT+ICRT or RT resulted in the equivalent of 3-year DFS compared to CCRT, but fewer therapeutic complications were observed with CT for patients with intermediate risk early-stage cervical squamous cell carcinoma. PMID:27942225

  3. HER2 drives luminal breast cancer stem cells in the absence of HER2 amplification: Implications for efficacy of adjuvant trastuzumab

    PubMed Central

    Ithimakin, Suthinee; Day, Kathleen C.; Malik, Fayaz; Zen, Qin; Dawsey, Scott J.; Bersano-Begey, Tom F.; Quraishi, Ahmed A.; Ignatoski, Kathleen Woods; Daignault, Stephanie; Davis, April; Hall, Christopher L.; Palanisamy, Nallasivam; Heath, Amber N.; Tawakkol, Nader; Luther, Tahra K.; Clouthier, Shawn G.; Chadwick, Whitney A.; Day, Mark L.; Kleer, Celina G.; Thomas, Dafydd G.; Hayes, Daniel F.; Korkaya, Hasan; Wicha, Max S.

    2013-01-01

    Although current breast cancer treatment guidelines limit the use of HER2 blocking agents to tumors with HER2 gene amplification, recent retrospective analyses suggest that a wider group of patients may benefit from this therapy. Utilizing breast cancer cell lines, mouse xenograft models and matched human primary and metastatic tissues, we demonstrate that HER2 is selectively expressed in and regulates self-renewal of the cancer stem cell population in ER+, HER2− luminal breast cancers. Although trastuzumab had no effects on the growth of established luminal breast cancer mouse xenografts, administration after tumor inoculation blocked subsequent tumor growth. HER2 expression is increased in luminal tumors grown in mouse bone xenografts, as well as in bone metastases from breast cancer patients compared to matched primary tumors. Furthermore this increase in HER2 protein expression was not due to gene amplification but rather was mediated by RANK-ligand in the bone microenvironment. These studies suggest that the clinical efficacy of adjuvant trastuzumab may relate to the ability of this agent to target the cancer stem cell population in a process that does not require HER2 gene amplification. Furthermore these studies support a cancer stem cell model in which maximal clinical benefit is achieved when cancer stem cell targeting agents are administered in the adjuvant setting. PMID:23442322

  4. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2005-06-01

    breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy . Unfortunately...response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies , e.g., -40% of tumors...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  5. Electrophysiological correlates of information processing in breast-cancer patients treated with adjuvant chemotherapy.

    PubMed

    Kreukels, Baudewijntje P C; Schagen, Sanne B; Ridderinkhof, K Richard; Boogerd, Willem; Hamburger, Hans L; van Dam, Frits S A M

    2005-11-01

    Cognitive deficits are found in a number of breast-cancer patients who have undergone adjuvant (Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF)) chemotherapy, but the underlying mechanisms are still unclear. The objective of this study is to investigate information processing in these patients with concurrent registration of brain activity. Twenty-six breast-cancer patients treated with adjuvant CMF chemotherapy and a control group of 23 stage I breast-cancer patients not treated with chemotherapy were examined. Mean time since treatment for the CMF patients was 5.1 years after the last CMF course, and for the control patients 3.6 years after termination of radiotherapy. An information processing task was administered with concurrent EEG registration. Reaction times and the amplitudes and latencies of an Event Related Potential component (P3) in different task conditions related to input, central, and output processing of information were studied. Significant differences in latency and amplitude of the P3 component were found between the treatment groups with an earlier and reduced P3 in the chemotherapy group. Patients treated with chemotherapy had longer reaction times (although not significantly different) than the control group on all task conditions. Our data provide further evidence for long-term neurocognitive problems in breast-cancer patients treated with adjuvant (CMF) chemotherapy and offer new information regarding abnormalities in brain functioning in these patients.

  6. [Effect of adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants and its action characteristics].

    PubMed

    Sun, Hai-Feng; Gao, Yan-Yun; An, Cui-Hong; Li, Yu-Lan; Duan, Li-Jun; Yu, Yu-Hong; Ren, Wu-Xian

    2014-07-01

    The applicator therapy is a unique method to treat infant diarrhea in traditional Chinese medicines and widely applied in clinical practice. Currently, many researchers have proved the rationality of the therapy based on the traditional Chinese medicine mechanism and on the data from clinical practice, but its action mechanism is uncertain at present. In this study, with the assistance of pediatric practitioners, the automated ribosomal intergenic-spacer analysis (ARISA) was adopted to study the effect of the adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants, in which Dingguier umbilical paste served as the adjuvant therapy in oral traditional Chinese medicines and fecal samples of infants with different diarrhea symptoms were collected and used as the study materials. The results showed that the adjuvant therapy had a significant effect on the shift of intestinal flora, which was associated with the decrease in the similarity difference to the normal control group and the increase in the number of operational taxonomic units (OTUs) shared with the normal control group. Additionally, adjuvant therapy with Dingguier umbilical paste also showed long action duration and increased OTUs number. These results indicated that Dingguier umbilical paste has the effect in restoring the micro-ecosystem of unbalanced intestinal bacteria. Intestinal flora may be one of major targets for the applicator therapy for the infant diarrhea, but not for the single oral traditional Chinese medicine for infant diarrhea.

  7. Functional Alteration of Tumor-infiltrating Myeloid Cells in RNA Adjuvant Therapy.

    PubMed

    Seya, Tsukasa; Shime, Hiroaki; Matsumoto, Misako

    2015-08-01

    Macrophages, as well as dendritic cells (DCs), are derived from myeloid progenitor cells. Recent evidence suggests that tumor-infiltrating macrophages differ in many aspects from conventional tissue macrophages, including nature, function and markers. Tumors usually contain various myeloid lineage cells in their non-parenchymal environment. In immunotherapy for cancer, tumor cells and non-parenchymal cells are exposed to tumor-associated antigens (TAA) and tumor-cell-derived nucleic acids. In addition, a dsRNA mimic, polyinosinic:polycytidylic acid (polyI:C), exhibits strong adjuvant activity, which acts both on the immune system and tumor constituents. Herein we discuss the RNA recognition system and unique cellular output in tumor-associated myeloid cells in response to immunotherapy. We especially focus on the mechanism by which RNA adjuvant alters the tumor-supportive nature of tumor-infiltrated myeloid cells to those with tumoricidal activity. We discuss how RNA administration makes tumor cells collapse and its significance of evoking cell death signals in tumor cells and macrophages. This knowledge will be applicable to the development of an alternative immunotherapy for cancer.

  8. Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data

    PubMed Central

    Delorenzi, Mauro; Jensen, Thomas; Jensen, Peter Buhl; Bosman, Fred; Tejpar, Sabine; Roth, Arnaud; Brunner, Nils; Hansen, Anker; Knudsen, Steen

    2016-01-01

    Purpose This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. Methods To test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. Results There was no statistically significant association between the irinotecan or SN-38 profiles and benefit from irinotecan. The 5-FU sensitivity profile showed a statistically significant association with relapse free survival (RFS) (hazard ratio (HR) = 0.54 (0.41–0.71), p<1e-05) and overall survival (HR = 0.47 (0.34–0.63), p<1e-06) in the PETACC-3 subpopulation. The effect of the 5-FU profile remained significant in a multivariable Cox Proportional Hazards model, adjusting for several relevant clinicopathological parameters. No statistically significant effect of the 5-FU profile was observed in the untreated cohort of 359 patients (relapse free survival, p = 0.671). Conclusion The irinotecan predictor had no predictive value. The 5-FU predictor was prognostic in stage III patients in PETACC-3 but not in stage II patients with no adjuvant therapy. This suggests a potential predictive ability of the 5-FU sensitivity profile to identify colon cancer patients who may benefit from 5-FU, however, any biomarker predicting benefit for adjuvant 5-FU must be rigorously evaluated in independent cohorts. Given differences

  9. [Value of adjuvant basic therapy in chronic recurrent skin diseases. Neurodermatitis atopica/psoriasis vulgaris].

    PubMed

    Schöpf, E; Mueller, J M; Ostermann, T

    1995-07-01

    Atopic dermatitis and psoriasis vulgaris belong to the most common diseases in dermatology. Since these chronical diseases progress over years and decades, they may lead to restrictions in private and professional life as well as to psychological stress of concerned patients. Therefore, a lasting, stabilising, stage-adjusted topical treatment is necessary. Main component of this treatment in a complete therapeutical concept consists in an adjuvant basic therapy with oil baths and with emollients containing urea or no drug additives at all. Thus the vehicle itself is therapeutically effective. Altered structure and function of the skin measured by increased transepidermal water loss, dysfunction of skin lipid barrier, augmented skin permeability and skin roughness can be improved. Due to this treatment clinical symptoms can be diminished and relapses can be avoided. Corticosteroids and other specific medications can be reduced by using basic therapeutics with little side effects. This means economical benefit as well. So far adjuvant basic treatment is an essential part in the therapy of chronic inflammatory skin diseases.

  10. Detection of sentinel lymph node in breast cancer recurrence may change adjuvant treatment decision in patients with breast cancer recurrence and previous axillary surgery.

    PubMed

    Cordoba, Octavi; Perez-Ceresuela, Francesc; Espinosa-Bravo, Martin; Cortadellas, Tomas; Esgueva, Antonio; Rodriguez-Revuelto, Robert; Peg, Vicente; Reyes, Victoria; Xercavins, Jordi; Rubio, Isabel T

    2014-08-01

    Use of sentinel lymph node dissection in patients with ipsilateral breast cancer recurrence is still controversial. The objective of this study is to evaluate the feasibility of the sentinel lymph node in breast cancer recurrence (SLNBR) and whether the positivity had impact in the adjuvant treatment. Between 2008 and 2012 we performed SLNBR in patients with ipsilateral breast tumor recurrence. We included 53 patients in a prospective study. Forty-three patients (81%) had a previous axillary lymph node dissection (ALND) and ten (19%) had a previous sentinel lymph node biopsy (SLNB). Identification rate after SLNB was 50% and after ALND was 60.5% (p = 0.4). Nine patients (26%) had a positive SLNBR. Adjuvant systemic treatment was given to all the patients with a positive SLNBR and to 23 (85%) with a negative SLNBR (p = 0.29). Six patients (66%) with positive SLNBR and 4 patients (14%) with negative SLNBR underwent radiation therapy (p < 0.01). As conclusions of our study we conclude that sentinel lymph node biopsy in breast tumor recurrence is feasible and significant differences were found in the use of radiation therapy in patients with a positive SLNBR.

  11. ALCHEMIST: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials

    Cancer.gov

    ALCHEMIST represents three integrated, precision medicine trials that are designed to identify people with early-stage lung cancer who have tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those mol

  12. Scalp cooling has no place in the prevention of alopecia in adjuvant chemotherapy for breast cancer.

    PubMed

    Tollenaar, R A; Liefers, G J; Repelaer van Driel, O J; van de Velde, C J

    1994-01-01

    35 patients were studied to determine the effectiveness of scalp hypothermia in the prevention of alopecia caused by adjuvant chemotherapy for breast cancer. Scalp hypothermia was induced by the newly developed Theracool cooling machine. The chemotherapeutic regimen consisted of one perioperative course of doxorubicin 50 mg/m2, cyclophosphamide 600 mg/m2 and 5-fluorouracil 600 mg/m2 (EORTC protocol 10854). Only 4 (11%) patients showed acceptable hair preservation (no or minor alopecia). 12 patients (34%) had moderate alopecia, all requiring a wig. 19 patients (54%) had complete alopecia. No scalp metastases were observed after scalp cooling. These results and a review of the literature suggest that scalp hypothermia to prevent alopecia may only be effective in a cytotoxic regimen containing an anthracycline as the sole alopecia-inducing agent. With current adjuvant chemotherapy for breast cancer, in which a combination of cyclophosphamide and an anthracycline is often used, there is no place for scalp hypothermia.

  13. Plasmapheresis as adjuvant therapy in Stevens-Johnson syndrome and hepatic encephalopathy.

    PubMed

    Hung, Po-Cheng; Wang, Huei-Shyong; Hsia, Shao-Hsuan; Wong, Alex M-C

    2014-04-01

    Stevens-Johnson syndrome (SJS) is a severe idiosyncratic reaction, most commonly triggered by medications, which is characterized by fever and mucocutaneous lesions, leading to necrosis and sloughing of the epidermis. Aside from skin and mucosal manifestations, SJS may also compromise heart, liver, kidney, lung, and gastrointestinal tract. Although cholestatic liver disease has been reported to occur in SJS, hepatic encephalopathy (HE) as a delayed complication has never been reported. We report a 4-year-old female child with anticonvulsant-induced SJS complicated by HE who was completely cured with a combination of systemic corticosteroid, intravenous immunoglobulin (IVIG), and plasmapheresis therapy. We suggested that plasmapheresis may be used as an adjuvant therapy for SJS with HE.

  14. Buffer Therapy for Cancer

    PubMed Central

    Ribeiro, Maria de Lourdes C; Silva, Ariosto S.; Bailey, Kate M.; Kumar, Nagi B.; Sellers, Thomas A.; Gatenby, Robert A.; Ibrahim-Hashim, Arig; Gillies, Robert J.

    2013-01-01

    Oral administration of pH buffers can reduce the development of spontaneous and experimental metastases in mice, and has been proposed in clinical trials. Effectiveness of buffer therapy is likely to be affected by diet, which could contribute or interfere with the therapeutic alkalinizing effect. Little data on food pH buffering capacity was available. This study evaluated the pH and buffering capacity of different foods to guide prospective trials and test the effect of the same buffer (lysine) at two different ionization states. Food groups were derived from the Harvard Food Frequency Questionnaire. Foods were blended and pH titrated with acid from initial pH values until 4.0 to determine “buffering score”, in mmol H+/pH unit. A “buffering score” was derived as the mEq H+ consumed per serving size to lower from initial to a pH 4.0, the postprandial pH of the distal duodenum. To differentiate buffering effect from any metabolic byproduct effects, we compared the effects of oral lysine buffers prepared at either pH 10.0 or 8.4, which contain 2 and 1 free base amines, respectively. The effect of these on experimental metastases formation in mice following tail vein injection of PC-3M prostate cancer cells were monitored with in vivo bioluminescence. Carbohydrates and dairy products’ buffering score varied between 0.5 and 19. Fruits and vegetables showed a low to zero buffering score. The score of meats varied between 6 and 22. Wine and juices had negative scores. Among supplements, sodium bicarbonate and Tums® had the highest buffering capacities, with scores of 11 and 20 per serving size, respectively. The “de-buffered” lysine had a less pronounced effect of prevention of metastases compared to lysine at pH 10. This study has demonstrated the anti-cancer effects of buffer therapy and suggests foods that can contribute to or compete with this approach to manage cancer. PMID:24371544

  15. Utility of PET/CT Imaging Performed Early After Surgical Resection in the Adjuvant Treatment Planning for Head and Neck Cancer

    SciTech Connect

    Shintani, Stephanie A.; Foote, Robert L. Lowe, Val J.; Brown, Paul D.; Garces, Yolanda I.; Kasperbauer, Jan L.

    2008-02-01

    Purpose: To evaluate the utility of positron emission tomography (PET)/computed tomography (CT) early after surgical resection and before postoperative adjuvant radiation therapy. Methods and Materials: We studied a prospective cohort of 91 consecutive patients referred for postoperative adjuvant radiation therapy after complete surgical resection. Tumor histologies included 62 squamous cell and 29 non-squamous cell cancers. Median time between surgery and postoperative PET/CT was 28 days (range, 13-75 days). Findings suspicious for persistent/recurrent cancer or distant metastasis were biopsied. Correlation was made with changes in patient care. Results: Based on PET/CT findings, 24 patients (26.4%) underwent biopsy of suspicious sites. Three patients with suspicious findings did not undergo biopsy because the abnormalities were not easily accessible. Eleven (45.8%) biopsies were positive for cancer. Treatment was changed for 14 (15.4%) patients (11 positive biopsy and 3 nonbiopsied patients) as a result. Treatment changes included abandonment of radiation therapy and switching to palliative chemotherapy or hospice care (4), increasing the radiation therapy dose (6), extending the radiation therapy treatment volume and increasing the dose (1), additional surgery (2), and adding palliative chemotherapy to palliative radiation therapy (1). Treatment for recurrent cancer and primary skin cancer were significant predictors of having a biopsy-proven, treatment-changing positive PET/CT (p < 0.03). Conclusions: Even with an expectedly high rate of false positive PET/CT scans in this early postoperative period, PET/CT changed patient management in a relatively large proportion of patients. PET/CT can be recommended in the postoperative, preradiation therapy setting with the understanding that treatment-altering PET/CT findings should be biopsied for confirmation.

  16. Adjuvant therapy after primary surgery for stage I-IIA carcinoma of the cervix.

    PubMed

    Thomas, G M

    1996-01-01

    Radical hysterectomy and bilateral pelvic lymph node dissection is commonly used as a primary management option for treatment of stage IB/IIA carcinoma of the cervix. Overall cure rates approach 85%. However, a spectrum of relapse risk exists, depending on the presence or absence of primary tumor and nodal-related prognostic factors. Known factors include number and location of lymph nodes; size of primary, deep invasion in the cervix; capillary lymphatic space involvement; occult parametrial involvement; and positive or close surgical margins. Biologic determinants have yet to be identified. No systematic analysis has examined various combinations of prognostic factors to precisely define associated levels of risk and to predict the sites of relapse. Decreased local control and survival rates in some high-risk subgroups, usually those with nodal positivity, has led to the exploration of adjuvant therapies. Compiled data from retrospective series have defined the overall patterns of failure. Seventy-two percent of those relapsing have a component of pelvic failure, while 42% experience relapse in the pelvis alone. Fifty-eight percent have a component of distant failure but only 28% have distant disease alone. Adjuvant treatment options include pelvic radiotherapy, extended-field radiotherapy, chemoradiotherapy, and chemotherapy. Trials of adjuvant chemotherapy are too few to evaluate the use of available agents. Pelvic radiotherapy has been shown to reduce the relapse risk when surgical margins are close or positive. It also reduces the risk of pelvic relapse and improves the relapse-free interval but has no apparent impact on overall survival in the groups that have been selected for treatment. The apparent lack of benefit may relate to the choice of patients with nodal involvement who, despite high risk of pelvic failure, most likely have a predominant pattern of distant failure. Maximization of the survival benefit of pelvic radiotherapy requires the

  17. Study protocol of the SACURA trial: a randomized phase III trial of efficacy and safety of UFT as adjuvant chemotherapy for stage II colon cancer

    PubMed Central

    2012-01-01

    Background Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy, but the usefulness of adjuvant chemotherapy for stage II colon cancer remains controversial. The major Western guidelines recommend adjuvant chemotherapy for “high-risk stage II” cancer, but this is not clearly defined and the efficacy has not been confirmed. Methods/design SACURA trial is a multicenter randomized phase III study which aims to evaluate the superiority of 1-year adjuvant treatment with UFT to observation without any adjuvant treatment after surgery for stage II colon cancer in a large population, and to identify “high-risk factors of recurrence/death” in stage II colon cancer and predictors of efficacy and adverse events of the chemotherapy. Patients aged between 20 and 80 years with curatively resected stage II colon cancer are randomly assigned to a observation group or UFT adjuvant therapy group (UFT at 500–600 mg/day as tegafur in 2 divided doses after meals for 5 days, followed by 2-day rest. This 1-week treatment cycle is repeated for 1 year). The patients are followed up for 5 years until recurrence or death. Treatment delivery and adverse events are entered into a web-based case report form system every 3 months. The target sample size is 2,000 patients. The primary endpoint is disease-free survival, and the secondary endpoints are overall survival, recurrence-free survival, and incidence and severity of adverse events. In an additional translational study, the mRNA expression of 5-FU-related enzymes, microsatellite instability and chromosomal instability, and histopathological factors including tumor budding are assessed to evaluate correlation with recurrences, survivals and adverse events. Discussion A total of 2,024 patients were enrolled from October 2006 to July 2010. The results of this study will provide important information that help to improve the therapeutic strategy for

  18. The Two Faces of Fractionated Photodynamic Therapy: Increasing Efficacy With Light Fractionation or Adjuvant Use of Fractional Laser Technology.

    PubMed

    Juhasz, Margit L W; Levin, Melissa K; Marmur, Ellen S

    2016-11-01

    "Fractionated photodynamic therapy (PDT)" is a new term being used by dermatologists to describe advances in PDT technology including fractionated light or the adjuvant use of fractional lasers. Although dermatologists have used PDT since the early 1990s for the treatment of photodamage and precancerous lesions, newer developments in technology have allowed for the treatment of non-melanoma skin cancers (NMSCs), in ammatory disorders, and even uses in the eld of anti-aging. Recent developments in fractionated light therapy have allowed for PDT with dark intervals and two-fold illumination schemes to increase cellular damage and apoptosis. Combining PDT with fractional laser technology has allowed for enhanced dermal penetration of topical photosensitizers including 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL), as well as increased ef cacy of treatment. These advances in PDT technology will allow for increased convenience, decreased treatment time, only one application of topical photosensitizer, and decreased cost to the patient and dermatologist. J Drugs Dermatol. 2016;15(11):1324-1328..

  19. Contribution of Early Detection and Adjuvant Treatments to Breast Cancer Mortality Reduction in Catalonia, Spain

    PubMed Central

    Vilaprinyo, Ester; Puig, Teresa; Rue, Montserrat

    2012-01-01

    Background Reductions in breast cancer (BC) mortality in Western countries have been attributed to the use of screening mammography and adjuvant treatments. The goal of this work was to analyze the contributions of both interventions to the decrease in BC mortality between 1975 and 2008 in Catalonia. Methodology/Principal Findings A stochastic model was used to quantify the contribution of each intervention. Age standardized BC mortality rates for calendar years 1975–2008 were estimated in four hypothetical scenarios: 1) Only screening, 2) Only adjuvant treatment, 3) Both interventions, and 4) No intervention. For the 30–69 age group, observed Catalan BC mortality rates per 100,000 women-year rose from 29.4 in 1975 to 38.3 in 1993, and afterwards continuously decreased to 23.2 in 2008. If neither of the two interventions had been used, in 2008 the estimated BC mortality would have been 43.5, which, compared to the observed BC mortality rate, indicates a 46.7% reduction. In 2008 the reduction attributable to screening was 20.4%, to adjuvant treatments was 15.8% and to both interventions 34.1%. Conclusions/Significance Screening and adjuvant treatments similarly contributed to reducing BC mortality in Catalonia. Mathematical models have been useful to assess the impact of interventions addressed to reduce BC mortality that occurred over nearly the same periods. PMID:22272292

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

    SciTech Connect

    Valicenti, Richard K.; Thompson, Ian; Albertsen, Peter; Davis, Brian J.; Goldenberg, S. Larry; Wolf, J. Stuart; Sartor, Oliver; Klein, Eric; Hahn, Carol; Michalski, Jeff; Roach, Mack; Faraday, Martha M.

    2013-08-01

    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 biochemical 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.

  1. Testosterone Therapy and Prostate Cancer.

    PubMed

    Davidson, Emily; Morgentaler, Abraham

    2016-05-01

    Changes in understanding regarding the relationship of androgens and prostate cancer have led to changes in the use of testosterone therapy. The evidence supports a finite ability of androgens to stimulate prostate cancer growth, with a maximum achieved at low testosterone concentrations, called the saturation model. The saturation point corresponds with maximal androgenic stimulation at 250 ng/dL. Evidence is reviewed herein regarding the relationship of testosterone to prostate cancer and the relatively new practice of offering testosterone therapy to men with a history of prostate cancer. Although no prospective controlled trials have been performed, results have been reassuring.

  2. Intraperitoneal therapy for peritoneal cancer

    PubMed Central

    Lu, Ze; Wang, Jie; Wientjes, M Guillaume; Au, Jessie L-S

    2011-01-01

    Cancers originating from organs in the peritoneal cavity (e.g., ovarian, pancreatic, colorectal, gastric and liver) account for approximately 250,000 new cancer cases annually in the USA. Peritoneal metastases are common owing to locoregional spread and distant metastases of extraperitoneal cancers. A logical treatment is intraperitoneal therapy, as multiple studies have shown significant targeting advantage for this treatment, including significant survival benefits in stage III, surgically debulked ovarian cancer patients. However, the clinical use of intraperitoneal therapy has been limited, in part, by toxicity, owing to the use of indwelling catheters or high drug exposure, by inadequate drug penetration into bulky tumors (>1 cm) and by the lack of products specifically designed and approved for intraperitoneal treatments. This article provides an overview on the background of peritoneal metastasis, clinical research on intraperitoneal therapy, the pharmacokinetic basis of drug delivery in intraperitoneal therapy and our development of drug-loaded tumor-penetrating microparticles. PMID:21062160

  3. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... cancer, surgery has been the standard. However, in patients medically not able to tolerate surgery, focused radiation, called stereotactic body radiation therapy (SBRT) is a good treatment option. For large ...

  4. Therapeutic usefulness of postoperative adjuvant chemotherapy with Tegafur-Uracil (UFT) in patients with breast cancer: focus on the results of clinical studies in Japan.

    PubMed

    Nakayama, Takahiro; Noguchi, Shinzaburo

    2010-01-01

    In Japan, the history of postoperative chemotherapy for breast cancer started with 5-fluorouracil (5-FU), launched in the 1980s. Currently, oral fluoropyrimidine-based regimens indicated for the treatment of breast cancer in Japan include tegafur plus uracil (UFT); tegafur, gimeracil, and oteracil (TS-1); doxifluridine; and capecitabine. In particular, UFT represents an important option for long-term treatment because of minimal adverse events and the potential for long-term maintenance of effective plasma concentrations of 5-FU to inhibit micrometastasis after surgery. Therefore, various clinical studies of postoperative adjuvant chemotherapy with UFT have been conducted in patients with completely resected tumors. Recent studies have shown that UFT prolongs survival after tumor resection in patients with gastric cancer, colorectal cancer, and lung cancer. In patients with breast cancer, large clinical trials of UFT-based postoperative chemotherapy conducted in Japan have shown that UFT is useful for the treatment of intermediate-risk patients with no lymph node metastasis. This paper reviews the results of clinical studies of UFT conducted in Japan to assess the therapeutic usefulness of this oral 5-FU. The types of patients most likely to benefit from UFT are discussed on the basis of currently available evidence and a global consensus of treatment recommendations. The optimal timing of endocrine therapy and strategies for postoperative adjuvant chemotherapy with UFT in patients with breast cancer are also discussed.

  5. Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.

    PubMed

    Finocchiaro, L M E; Glikin, G C

    2008-02-01

    We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.

  6. Chemosensory alterations and cancer therapies

    SciTech Connect

    Bartoshuk, L.M. )

    1990-01-01

    Taste and olfaction provide sensory information and sensory pleasure. Cancer therapies affect both. Chemotherapy has not been shown to produce dramatic losses of taste or smell, but systematic studies on various chemotherapeutic agents and types of cancer are lacking. Radiation therapy does produce clear losses of both taste and smell. Both chemotherapy and radiation therapy alter the pleasure produced by taste and smell through the formation of conditioned aversions. That is, foods consumed in proximity with the nausea of therapy come to be unpleasant. The impact of conditioned aversions can be diminished by providing a scapegoat food just before therapy. Alterations in foods may be beneficial to the cancer patient. Increasing the concentrations of flavor ingredients can compensate for sensory losses, and providing pureed foods that retain the cognitive integrity of a meal can benefit the patient who has chewing or swallowing problems.

  7. Antimetabolites: established cancer therapy.

    PubMed

    Tiwari, Manjul

    2012-01-01

    Cell death has been divided into two main types: programmed cell death, in which the cell plays an active role, and passive (necrotic) cell death. Senescence arrest, accelerated senescence and differentiation are also responses that can be induced in response to DNA-damaging agents. Apoptosis may occur as a primary event following chemotherapy, in which genes that regulate apoptosis will influence the outcome of therapy or, alternatively, as an event secondary to the induction of lethal damage that involves the subsequent processing of cellular damage. The particular type of response induced is highly dependent on the agent and dose employed, the type of DNA damage induced as well as the genetic and cellular phenotypes. It has been proposed that apoptosis may play a lesser role in tumor response to radiation in comparison with the induction of cell death through mitotic catastrophe or a senescence-like irreversible growth arrest. However, in comparison with the induction of apoptosis, there is a lack of as much definitive information on other cell death processes that occur in cancer cells in response to chemotherapeutic agents, including antimetabolites. This article reviews what is known about these processes at the present time in response to experimental or clinically used agents that are analogs of 5-fluorouracil, cytidine or purines, hydroxyurea, or that belong to the family of folate antagonists.

  8. Loco-regional control after neo-adjuvant chemotherapy and conservative treatment for locally advanced breast cancer patients.

    PubMed

    Levy, Antonin; Borget, Isabelle; Bahri, Manel; Arnedos, Monica; Rivin, Eleonor; Vielh, Philippe; Balleyguier, Corinne; Rimareix, Françoise; Bourgier, Céline

    2014-01-01

    Breast-conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco-regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo-adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty-four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p < 0.001). Patients receiving mastectomy had more invasive lobular carcinoma (p = 0.007) and a higher American Joint Committee on Cancer (AJCC) stage (p < 0.001) at diagnosis than those with BCT. At a median follow-up of 6.3 years, the loco-regional control rate was 91% (95% CI: 86-94%). The 10-year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9-16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9-15.2%]; p = 0.8). Ten-year overall survival (OS) rates (63% [95% CI: 46-79%] in the BCT group; 60% [95% CI: 47-73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2-5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2-30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1-5.9; p = 0.03) were independent predictors of LRR. Ten-year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely

  9. DETERMINANTS OF ADJUVANT OXALIPLATIN RECEIPT AMONG OLDER STAGE II AND III COLORECTAL CANCER PATIENTS

    PubMed Central

    Lund, Jennifer L; Stürmer, Til; Sanoff, Hanna K; Brookhart, Alan; Sandler, Robert S; Warren, Joan L

    2013-01-01

    Purpose Controversy exists regarding adjuvant oxaliplatin treatment among older stage II and III colorectal cancer (CRC) patients. We sought to identify patient/tumor, physician, hospital, and geographic factors associated with oxaliplatin use among older patients. Methods Individuals diagnosed at age>65 with stage II/III CRC from 2004–2007 undergoing surgical resection and receiving adjuvant chemotherapy were identified using the Surveillance, Epidemiology and End Results program (SEER)-Medicare, a database including patient/tumor and hospital characteristics. Physician information was obtained from the American Medical Association. We used Poisson regression to identify independent predictors of oxaliplatin receipt. The discriminatory ability of each category of characteristics to predict oxaliplatin receipt was assessed by comparing the area under the receiver operating curve (AUC) from logistic regression models. Results We identified 4,388 individuals who underwent surgical resection at 773 hospitals and received chemotherapy from 1,517 physicians. Adjuvant oxaliplatin use was higher among stage III (colon=56%, rectum=51%) compared to stage II patients (colon=37%, rectum=35%). Overall, patients who were older, diagnosed before 2006, separated, divorced or widowed, living in a higher poverty census tract or in the East or Midwest, or with higher levels of comorbidity were less likely to receive oxaliplatin. Patient factors and calendar year accounted for most of the variation in oxaliplatin receipt (AUC=75.8%). Conclusion Adjuvant oxaliplatin use increased rapidly from 2004–2007 despite uncertainties regarding its effectiveness in older patients. Physician and hospital characteristics had little influence on adjuvant oxaliplatin receipt among older patients. PMID:23512326

  10. Proton therapy for prostate cancer.

    PubMed

    Hoppe, Bradford; Henderson, Randal; Mendenhall, William M; Nichols, Romaine C; Li, Zuofeng; Mendenhall, Nancy P

    2011-06-01

    Proton therapy has been used in the treatment of cancer for over 50 years. Due to its unique dose distribution with its spread-out Bragg peak, proton therapy can deliver highly conformal radiation to cancers located adjacent to critical normal structures. One of the important applications of its use is in prostate cancer, since the prostate is located adjacent to the rectum and bladder. Over 30 years of data have been published on the use of proton therapy in prostate cancer; these data have demonstrated high rates of local and biochemical control as well as low rates of urinary and rectal toxicity. Although before 2000 proton therapy was available at only a couple of centers in the United States, several new proton centers have been built in the last decade. With the increased availability of proton therapy, research on its use for prostate cancer has accelerated rapidly. Current research includes explorations of dose escalation, hypofractionation, and patient-reported quality-of-life outcomes. Early results from these studies are promising and will likely help make proton therapy for the treatment of prostate cancer more cost-effective.

  11. [Adjuvant radiotherapy for bladder cancer in patients with risk of locoregional recurrence: Who, what and how?

    PubMed

    Sargos, P; Larré, S; Chapet, O; Latorzeff, I; Fléchon, A; Roubaud, G; Orré, M; Belhomme, S; Richaud, P

    2017-02-01

    Radical cystectomy with extended pelvic lymph node dissection remains the standard of care for non-metastatic muscle-invasive bladder cancer. Locoregional control is a key factor in the outcome of patients since it is related to overall survival, metastasis-free survival and specific survival. Locoregional recurrence rate is directly correlated to pathological results and the quality of lymphadenectomy. In addition, while pre- or postoperative chemotherapy improved overall survival, it showed no impact on locoregional recurrence-free survival. Several recent publications have led to the development of a nomogram that predicts the risk of locoregional recurrence, in order to identify patients for which adjuvant radiotherapy could be beneficial. International cooperative groups have then come together to provide the rational for adjuvant radiotherapy, reinforced by recent technical developments limiting toxicity, and to develop prospective studies to reduce the risk of relapse. The aim of this critical literature review is to provide an overview of the elements in favor of adjuvant radiation for patients treated for muscle-invasive bladder cancer.

  12. Personalized therapy for urothelial cancer: review of the clinical evidence

    PubMed Central

    Guancial, Elizabeth A.; Chowdhury, Dipanjan; Rosenberg, Jonathan E.

    2012-01-01

    Despite a detailed understanding of the molecular aberrations driving the development of urothelial cancers, this knowledge has not translated into advances for the treatment of this disease. Urothelial cancers are chemosensitive, and platinum-based combination chemotherapy remains the standard of care for advanced disease, as well as neoadjuvant and adjuvant therapy for locally advanced disease. However, nearly half of patients who undergo resection of locally advanced urothelial cancer will relapse and eventually develop platinum-resistant disease. Clinical trials of targeted agents against angiogenesis and growth factors, as well as novel chemotheraputics, have generally been unsuccessful in urothelial cancers. Improvements in the theraputic arsenal for urothelial cancer depend upon identification of new targets and strategies to overcome platinum resistance. PMID:22754656

  13. Evaluation of adjuvant postoperative radiotherapy for lung cancer

    SciTech Connect

    Chung, C.K.; Stryker, J.H.; O'Neill, M. Jr.; DeMuth, W.E. Jr.

    1982-11-01

    One hundred eighteen patients with lung cancer were retrospectively analyzed to determine whether postoperative radiotherapy (RT) improves survival. Patterns of treatment failure and three year NED (no evidence of disease) survival rates were assessed according to extent of tumor spread, histology, and treatment method. Patients with hilar or mediastinal node metastases were at higher risk of local failure compared to those with negative nodes. Postoperative RT reduced local recurrence and improved 3 year survival among patients with positive nodes. However, postoperative RT did not improve survival among those with negative nodes. Our data indicated that patients with positive hilar or mediastinal nodes may require postoperative RT to improve survival.

  14. Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

    SciTech Connect

    Morganti, Alessio G.; Falconi, Massimo; Stiphout, Ruud G.P.M. van; Mattiucci, Gian-Carlo; Alfieri, Sergio; Calvo, Felipe A.; Dubois, Jean-Bernard; Fastner, Gerd; Herman, Joseph M.; Maidment, Bert W.; Miller, Robert C.; Regine, William F.; Reni, Michele; Sharma, Navesh K.; Ippolito, Edy; and others

    2014-11-15

    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 462 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.

  15. Gene therapy in pancreatic cancer.

    PubMed

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

    2014-10-07

    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC.

  16. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach

    PubMed Central

    Jiang, Meng-jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-01-01

    Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common. Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes. Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID:26356712

  17. Vascular dysfunction as a target for adjuvant therapy in cerebral malaria

    PubMed Central

    Carvalho, Leonardo José de Moura; Moreira, Aline da Silva; Daniel-Ribeiro, Cláudio Tadeu; Martins, Yuri Chaves

    2014-01-01

    Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum malaria that continues to be a major global health problem. Brain vascular dysfunction is a main factor underlying the pathogenesis of CM and can be a target for the development of adjuvant therapies for the disease. Vascular occlusion by parasitised red blood cells and vasoconstriction/vascular dysfunction results in impaired cerebral blood flow, ischaemia, hypoxia, acidosis and death. In this review, we discuss the mechanisms of vascular dysfunction in CM and the roles of low nitric oxide bioavailability, high levels of endothelin-1 and dysfunction of the angiopoietin-Tie2 axis. We also discuss the usefulness and relevance of the murine experimental model of CM by Plasmodium berghei ANKA to identify mechanisms of disease and to screen potential therapeutic interventions. PMID:25185000

  18. Selective Thrombolysis in Acute Deep Vein Thrombosis: Evaluation of Adjuvant Therapy In Vivo

    SciTech Connect

    Roy, Sumit; Brosstad, Frank; Sakariassen, Kjell S.

    1999-09-15

    Purpose: To evaluate in a porcine model of acute deep vein thrombosis (DVT) the efficacy of dalteparin and antithrombin with respect to heparin for local adjuvant therapy during selective thrombolysis, and the utility of nitroglycerin and iloprost as heparin supplements. Methods: DVT was induced in both hind limbs using a previously described technique (n = 20). Thirty minutes later, the animal was heparinized (2500 IU IV), and bilateral sequestrated thrombolysis was performed using 8 mg alteplase: both external iliac veins were endoluminally occluded with Swan-Ganz catheters, and a multi-sideport infusion wire coaxially introduced through each catheter and advanced into the ipsilateral popliteal vein. In the control limbs, tissue plasminogen activator (tPA) 8 mg was injected as 0.8-ml boluses at 3-min intervals for 2 hr as a 0.25-mg/ml solution containing heparin 50 IU/ml (n 20). On the contralateral side, heparin was substituted with either dalteparin 50 IU/ml (n = 5) or antithrombin 12.5 IU/ml (n = 5), or supplemented with either nitroglycerin 0.075 mg/ml (n = 5) or iloprost (150 ng/ml) (n = 5). Blood samples were taken at predetermined intervals to measure the activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen concentration. At autopsy, the thrombus mass in the iliofemoral veins was measured, and the extent of residual thrombosis in the venous tributaries graded at four sites. Results: Bilateral thrombolysis was successfully completed in all animals. The median thrombus mass in the iliofemoral veins after thrombolysis was 0.48 g (range 0.06-1.58 g), 0.95 g (0.59-1.29 g), 0.74 g (0.52-0.96 g), and 0.29 g (0.0-0.77 g) for dalteparin, antithrombin, iloprost, and nitroglycerin respectively, as compared with 0.53 g (0.18-0.88 g) (p = 0.69), 0.97 g (0.46-1.15 g) (p = 0.69), 0.53 g (0.48-1.10 g) (p = 0.69), and 0.18 g (0.13-1.04 g) (p = 0.5) for the respective controls. Likewise, the severity of residual thrombosis in the venous

  19. Ki67 proliferation in core biopsies versus surgical samples - a model for neo-adjuvant breast cancer studies

    PubMed Central

    2011-01-01

    Background An increasing number of neo-adjuvant breast cancer studies are being conducted and a novel model for tumor biological studies, the "window-of-opportunity" model, has revealed several advantages. Change in tumor cell proliferation, estimated by Ki67-expression in pre-therapeutic core biopsies versus post-therapeutic surgical samples is often the primary end-point. The aim of the present study was to investigate potential differences in proliferation scores between core biopsies and surgical samples when patients have not received any intervening anti-cancer treatment. Also, a lack of consensus concerning Ki67 assessment may raise problems in the comparison of neo-adjuvant studies. Thus, the secondary aim was to present a novel model for Ki67 assessment. Methods Fifty consecutive breast cancer cases with both a core biopsy and a surgical sample available, without intervening neo-adjuvant therapy, were collected and tumor proliferation (Ki67, MIB1 antibody) was assessed immunohistochemically. A theoretical model for the assessment of Ki67 was constructed based on sequential testing of the null hypothesis 20% Ki67-positive cells versus the two-sided alternative more or less than 20% positive cells.. Results Assessment of Ki67 in 200 tumor cells showed an absolute average proliferation difference of 3.9% between core biopsies and surgical samples (p = 0.046, paired t-test) with the core biopsies being the more proliferative sample type. A corresponding analysis on the log-scale showed the average relative decrease from the biopsy to the surgical specimen to be 19% (p = 0.063, paired t-test on the log-scale). The difference was significant when using the more robust Wilcoxon matched-pairs signed-ranks test (p = 0.029). After dichotomization at 20%, 12 of the 50 sample pairs had discrepant proliferation status, 10 showed high Ki67 in the core biopsy compared to two in the surgical specimen (p = 0.039, McNemar's test). None of the corresponding results for 1000

  20. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2006-06-01

    or TAM should be given as first line endocrine therapy . Unfortunately, response rates are lower, and response durations are shorter, on crossover than...when these agents are given as first line therapies , e.g., ~40% of tumors show cross resistance to TAM or an aromatase inhibitor on crossover. Only...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  1. Surface engineering tumor cells with adjuvant-loaded particles for use as cancer vaccines.

    PubMed

    Ahmed, Kawther K; Geary, Sean M; Salem, Aliasger K

    2017-02-28

    Cell surface engineering is an expanding field and whilst extensive research has been performed decorating cell surfaces with biomolecules, the engineering of cell surfaces with particles has been a largely unexploited area. This study reports on the assembly of cell-particle hybrids where irradiated tumor cells were surface engineered with adjuvant-loaded, biodegradable, biocompatible, polymeric particles, with the aim of generating a construct capable of functioning as a therapeutic cancer vaccine. Successfully assembled cell-particle hybrids presented here comprised either melanoma cells or prostate cancer cells stably adorned with Toll-like receptor-9 ligand-loaded particles using streptavidin-biotin cross-linking. Both cell-particle assemblies were tested in vivo for their potential as therapeutic cancer vaccines yielding promising therapeutic results for the prostate cancer model. The ramifications of results obtained for both tumor models are openly discussed.

  2. Randomized Trial of Neuroprotective Effects of Erythropoietin in Patients Receiving Adjuvant Chemotherapy for Breast Cancer: Positron Emission Tomography and Neuropsychological Study

    DTIC Science & Technology

    2008-09-01

    Effects of Erythropoietin in Patients Receiving Adjuvant Chemotherapy for Breast Cancer : Positron Emission Tomography and Neuropsychological Study...Neuroprotective Effects of Erythropoietin in Patients 5a. CONTRACT NUMBER Receiving Adjuvant Chemotherapy for Breast Cancer : Positron Emission Tomography...11 Introduction In the United States approximately 60-80% of patients diagnosed with breast cancer will receive

  3. Cancer Alternative Therapies

    MedlinePlus

    You have many choices to make about your cancer treatment. One choice you might be thinking about ... are acupuncture, chiropractic, and herbal medicines. People with cancer may use CAM to Help cope with the ...

  4. Targeted Cancer Therapies

    MedlinePlus

    ... targets is to determine whether cancer cells produce mutant (altered) proteins that drive cancer progression . For example, ... V600E) in many melanomas . Vemurafenib (Zelboraf®) targets this mutant form of the BRAF protein and is approved ...

  5. Interpreting breast international group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer

    PubMed Central

    2011-01-01

    The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG -98 enrolled 8,010 women. The enhanced design f the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments. Clinicaltrials.gov ID: NCT00004205. PMID:21635709

  6. 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.

  7. Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies.

    PubMed

    Fan, Weimin; Chang, Jinjia; Fu, Peifeng

    2015-08-01

    Endocrine therapy has become one of most effective forms of targeted adjuvant therapy for hormone-sensitive breast cancer and may be given after surgery or radiotherapy, and also prior, or subsequent to chemotherapy. Current commonly used drugs for adjuvant endocrine therapy can be divided into following three classes: selective estrogen receptor modulators, aromatase inhibitors and selective estrogen receptor downregulators. Tumor cells can develop resistance to endocrine therapy, a major obstacle limiting the success of breast cancer treatment. The complicated crosstalk, both genomic and nongenomic, between estrogen receptors and growth factors was considered to be a crucial factor contributing to endocrine resistance. However, resistance to this therapy is thought to be a progressive, step-wise process, and the underlying mechanism remains unclear. In this review, we summarize the possible biological and molecular mechanisms that underlie endocrine resistance, and discuss some novel strategies to overcoming these issues.

  8. [Postoperative adjuvant chemotherapy for gastric cancer after the adjuvant chemotherapy trial of S-1 for gastric cancer in Hiroshima prefecture: results from a questionnaire survey and future challenges].

    PubMed

    Yamaguchi, Kakuhiro; Hirabayashi, Naoki; Ninomiya, Motoki; Shinozaki, Katsunori; Hatanaka, Nobutaka; Matsuda, Hiroyuki; Tanabe, Kazuaki

    2013-12-01

    A questionnaire survey on postoperative adjuvant chemotherapy for gastric cancer was conducted for 76 hospitals affiliated with the Hiroshima Oncology Group of Gastric Cancer in Hiroshima prefecture in January 2011. Responses were obtained from 29 hospitals, including 12 core cancer treatment hospitals, and the following results were obtained. The percentage of patients completing 1 year of oral S-1 was >70%, affecting approximately 75% of the entire hospital cohort. Dose reduction was conducted in approximately 30% of patients because of age, poor PS, and renal insufficiency. The standard S-1 regimen (4 weeks of S-1 treatment followed by 2 weeks of rest)was adopted in almost half of the patients, whereas the rest of the patients received another treatment schedule such as 2 weeks of treatment followed by 1 week of rest. Dose reduction and withdrawal of S-1 due to adverse events were conducted more frequently in hospitals with low completion rates of 1-year S- 1 treatment than those with a high completion rate. S-1 was most commonly discontinued because of subjective adverse events and patient request, although the discontinuation rate according to objective adverse events such as bone marrow depression was not very high. The fact that some hospitals had high completion rates suggested the importance of supplementary tools for patient IC.

  9. Intralesional lymphokine-activated killer cells as adjuvant therapy for primary glioblastoma.

    PubMed

    Dillman, Robert Owen; Duma, Christopher Michael; Ellis, Robin Anne; Cornforth, Andrew Nimitz; Schiltz, Patric Michael; Sharp, Shari Lynn; DePriest, Madeline Carol

    2009-01-01

    Despite recent advances, median survival for patients with resectable glioblastoma multiforme (GBM) is only 12 to 15 months. We previously observed minimal toxicity and a 9.0-month median survival after treatment with intralesional autologous lymphokine-activated killer (LAK) cells in 40 patients with recurrent GBM. In this study, GBM patients were treated with adjuvant intralesional LAK cells. Eligible patients had completed primary therapy for GBM without disease progression. LAK cells were produced by incubating autologous peripheral blood mononuclear cells with interleukin-2 for 3 to 7 days and then placed into the surgically exposed tumor cavity by a neurosurgeon. The 19 men and 14 women had a median age of 57 years. Prior therapy included surgical resection (97%), partial brain irradiation (97%), gamma knife radiosurgery (97%), and temozolomide chemotherapy (70%). Median time from diagnosis to LAK cell therapy was 5.3 months (range: 3.0 to 11.1 mo). LAK cell treatment was well tolerated; average length of hospitalization was 3 days. At the time of this analysis, 27 patients have died; the median survival from the date of original diagnosis is 20.5 months with a 1-year survival rate of 75%. In subset analyses, superior survival was observed for patients who received higher numbers of CD3+/CD16+/CD56+ (T-LAK) cells in the cell products, which was associated with not taking corticosteroids in the month before leukopheresis. Intralesional LAK cell therapy is safe and the survival sufficiently encouraging to warrant further evaluation in a randomized phase 2 trial of intralesional therapies with LAK or carmustine-impregnated wafers.

  10. Subclinical Myocardial Impairment Occurred in Septal and Anterior LV Wall Segments After Anthracycline-Embedded Chemotherapy and did not Worsen During Adjuvant Trastuzumab Treatment in Breast Cancer Patients.

    PubMed

    Lange, Stefan Andreas; Jung, Jens; Jaeck, Almut; Hitschold, Thomas; Ebner, Bernd

    2016-04-01

    In a previous study of breast cancer patients, we found changes in cardiac function and size during the early stages of adjuvant trastuzumab (Herceptin(®)) therapy. Here we present a subgroup analysis of this patient cohort. This subgroup received a anthracycline-embedded chemotherapy followed by at least 3 months up to 6 months of adjuvant Herceptin(®) therapy. Twenty-seven female breast cancer patients with Her-2/-neu overexpression were studied using conventional echocardiography and 2D speckle tracking. These methods were done before anthracycline-embedded chemotherapy, before adjuvant trastuzumab therapy, and both 3 and 6 months after the start of the therapy (T3, T6). The LV-EF (Simpson biplane) decreased significantly from before the chemotherapy to after the chemotherapy and further decreased after 3 months of trastuzumab therapy (66.2 ± 1.5 vs. 58.7 ± 1.2 vs. 55.6 ± 1.3 vs. 55.9 ± 1.5 %; p < 0.05). The stroke volume index remained constant after chemotherapy (22.0 ± 0.8 vs. 22.6 ± 1.3 ml/m(2); p = 0.9), but increased significantly during trastuzumab therapy (26.7 ± 1.1 and 27.3 ± 1.0 ml/m(2); p < 0.01). Global longitudinal strain exclusively decreased during chemotherapy (-21.0 ± 0.5 vs. -18.9 ± 0.5 %, p < 0.001). Regional longitudinal strain decreased significantly after chemotherapy in septal, anteroseptal, anterolateral, and apex segments. Mitral valve regurgitation increased during the whole treatment, but especially during trastuzumab. Right ventricular function decreased exclusively during chemotherapy. Anthracycline-embedded chemotherapy in patients with breast cancer led to a decrease in LV function, especially of the septal and anterior segments, and did not worsen during adjuvant trastuzumab treatment.

  11. Is Adjuvant Chemoradiotherapy Overtreatment in Cervical Cancer Patients With Intermediate Risk Factors?

    SciTech Connect

    Ryu, Sang-Young; Park, Sang-Il; Nam, Byung-Ho; Cho, Chul-Koo; Kim, Kidong; Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol; Lee, Eui-Don; Lee, Kyoung-Hee

    2011-03-01

    Purpose: To determine whether adjuvant chemoradiotherapy (CRT) improves the outcome of cervical cancer patients with intermediate risk factors. Methods and Materials: Between January 2000 and June 2006, the medical records of 735 patients who had undergone radical surgery for Stage IB-IIA cervical cancer were reviewed retrospectively. Of the 735 patients, 172 with two or more intermediate risk factors (i.e., lymphovascular space involvement, deep stromal invasion, and tumor size {>=}2 cm) were grouped as follows according to the adjuvant treatment received: 34 patients, no further treatment; 49 patients, RT; and 89 patients, CRT. The significance of the clinical parameters and recurrence-free survival of each group were analyzed. Results: Of the 172 patients with any of the intermediate risk factors, 137 (79.6%) had two or more intermediate risk factors. Of the 172 patients, 12 developed recurrences (6.4%)->(7.0%), with 6 in the pelvis and 6 in distant sites. All 12 recurrences occurred in those who had two or more intermediate risk factors (sensitivity, 100%); however, only six recurrences were detected in patients who met the Gynecologic Oncology Group criteria for the intermediate-risk group (sensitivity, 50%; Z test, p < .05). A statistically significant difference was found in the 3-year recurrence-free survival rate among the no further treatment, RT, and CRT groups (67.5%, 90.5%, and 97.5%, respectively; p < .05). The incidence of Grade 3-4 hematologic and gastrointestinal toxicities was not significantly different statistically between the RT and CRT groups (6.1% and 13.4%, respectively; p > .05). Conclusion: Postoperative adjuvant CRT can improve the outcome of cervical cancer patients with intermediate risk factors, with low increase in toxicity.

  12. Relationship Between Topoisomerase 2A RNA Expression and Recurrence after Adjuvant Chemotherapy for Breast Cancer

    PubMed Central

    Sparano, Joseph A.; Goldstein, Lori J.; Childs, Barrett H.; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L.; Bugarini, Roberto; Rowley, Steve; Perez, Edith; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Sledge, George W.; Gray, Robert

    2009-01-01

    Purpose To perform an exploratory analysis of the relationship between gene expression and recurrence in operable hormone receptor (HR)-positive, HER2-normal breast cancer patients treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design RNA was extracted from archived tumor samples derived from 378 patients with stage I–III HR-positive, HER2-normal breast cancer and analyzed by RT-PCR for a panel of 374 genes, including the 21 gene Recurrence Score (RS). Patients were randomized to receive adjuvant doxorubicin plus cyclophosphamide or docetaxel in trial E2197, with no difference in recurrence seen in the treatment arms. All available recurrent cases were selected plus a non-recurrent cohort. Cox proportional hazard models were used to identify relationships between gene expression and recurrence. Results TOP2A expression exhibited the strongest association with increased recurrence risk (p=0.01), and was significantly associated with recurrence (p=0.008) in a multivariate analysis adjusted for clinicopathological features. Elevated TOP2A expression above the median was associated with a 2.6-fold increase (95% confidence intervals [CI], 1.3, 5.2 p=0.008) in risk of recurrence if the RS was less than 18, and a 2.0-fold increase (95% CI, 1.2, 3.2, p=0.003) if there was an intermediate RS of 18–30. Conclusions In patients with HR-positive, HER2-normal breast cancer, a population known to have a low incidence of TOP2A gene alterations thought to be predictive of anthracycline benefit, there is a range of TOP2A RNA expression that is strongly associated with recurrence after adjuvant anthracyclines which provides information complementary to RS, indicating that it merits further evaluation as a prognostic and predictive marker. PMID:19996222

  13. Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer

    SciTech Connect

    Solhjem, Matthew C. . E-mail: petersen.ivy@mayo.edu; Petersen, Ivy A.; Haddock, Michael G.

    2005-08-01

    Purpose To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. Methods and Materials Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic {+-} paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. Results With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. Conclusion Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer.

  14. Start strong or switch? Adjuvant endocrine strategies for postmenopausal women with hormone-sensitive breast cancer.

    PubMed

    Tusquets Trías de Bes, Ignasi; Tormo, Sònia Servitja; Mestres, Joan Albanell

    2009-01-01

    Women are at considerable risk of recurrence in the first few years following initial treatment for early breast cancer. To reduce the risk of recurrence, including distant metastases, those with hormone-sensitive breast cancer receive adjuvant endocrine treatment. Lymph node metastases are a predictor of high risk of early recurrence and distant metastases; however, a significant number of women with node-negative disease will also develop distant metastases. This is of concern, because the development of distant metastases is associated with a high risk of breast cancer death. Studies in postmenopausal women showed that an aromatase inhibitor (AI) as initial, upfront treatment reduces early recurrence, including distant metastases, compared with tamoxifen. The three available AIs (letrozole, anastrozole, and exemestane) are approved for adjuvant use. Upfront letrozole or anastrozole improved time to distant metastasis in patients included in the Breast International Group 1-98 and Arimidex, Tamoxifen, Alone or in Combination trials, respectively. Of note, the beneficial effects of letrozole on distant disease were already observed in the first report at 2 years of follow-up and confirmed in the updated results with 50 months of follow-up. Here, we discuss the available data for all AIs and strategies to be taken into account for patient management, with a special focus on the effects of available options on early recurrences and metastasis risk.

  15. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab.

    PubMed

    Gündüz, Seyda; Göksu, Sema Sezgin; Arslan, Deniz; Tatli, Ali Murat; Uysal, Mükremin; Gündüz, Umut Riza; Sevinç, Mert Mahsuni; Coşkun, Hasan Senol; Bozcuk, Hakan; Mutlu, Hasan; Savas, Burhan

    2015-09-01

    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20-30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×10(3)/mm(3) (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer.

  16. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab

    PubMed Central

    GÜNDÜZ, SEYDA; GÖKSU, SEMA SEZGIN; ARSLAN, DENIZ; TATLI, ALI MURAT; UYSAL, MÜKREMIN; GÜNDÜZ, UMUT RIZA; SEVINÇ, MERT MAHSUNI; COŞKUN, HASAN SENOL; BOZCUK, HAKAN; MUTLU, HASAN; SAVAS, BURHAN

    2015-01-01

    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20–30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×103/mm3 (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer. PMID:26623060

  17. Tuberculosis axillary lymph node coexistent breast cancer in adjuvant treatment: case report

    PubMed Central

    Bromberg, Silvio Eduardo; do Amaral, Paulo Gustavo Tenório

    2015-01-01

    Coexistence of breast cancer and tuberculosis is rare. In most cases, involvement by tuberculosis occurs in axillary lymph nodes. We report a case of a 43-years-old patient who had undergone adenomastectomy and left sentinel lymph node biopsy due to a triple negative ductal carcinoma. At the end of adjuvant treatment, the patient had an atypical lymph node in the left axilla. Lymph node was excised, and after laboratory analysis, the diagnosis was ganglion tuberculosis. The patient underwent treatment for primary tuberculosis. The development of these two pathologies can lead to problems in diagnosis and treatment. An accurate diagnosis is important to avoid unnecessary surgical procedures. PMID:26018148

  18. Transcutaneous electrical nerve stimulation therapy: An adjuvant pain controlling modality in TMD patients — A clinical study

    PubMed Central

    Shanavas, Muhammad; Chatra, Laxmikanth; Shenai, Prashanth; Rao, Prasanna Kumar; Jagathish, Veena; Kumar, Sreeja Prasanna; Naduvakkattu, Bilahari

    2014-01-01

    Background: The use of transcutaneous electrical nerve stimulation (TENS) in dentistry was first described in 1967, by Shane and Kessler, but it has yet to gain widespread acceptance in dentistry. A study was undertaken to evaluate the effectiveness of TENS therapy as an adjuvant modality and to compare it with the conventional medication in controlling pain in temporomandibular disorder (TMD) patients. Materials and Methods: The study was carried out in the Department of Oral Medicine and Radiology, Yenepoya Dental College and Hospital, Mangalore. A total of 40 patients with the clinical symptom of pain associated with TMDs were randomly divided into two groups. Group A (control) patients were treated with medication (analgesics and muscle relaxants) alone, while group B patients were treated with TENS therapy in combination with medication. The intensity of the pain was assessed using the Visual Analog Scale (VAS). The results were analyzed with the student's ‘t’ test. A P-value < 0.05 was considered as significant. Results: A significant improvement was observed in both the TENS and the control group in terms of pain control. On comparative analysis, adjuvant TENS therapy was found to be more effective than medication alone, in controlling pain. (P value = 0.019). Conclusion: The observed data suggest that TENS therapy can be used as an adjuvant modality in the management of pain associated with TMDs. This study justifies the use of TENS therapy in the management of TMD. PMID:25540662

  19. Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic efficacy against glioma.

    PubMed

    Munson, Jennifer M; Fried, Levi; Rowson, Sydney A; Bonner, Michael Y; Karumbaiah, Lohitash; Diaz, Begoña; Courtneidge, Sara A; Knaus, Ulla G; Brat, Daniel J; Arbiser, Jack L; Bellamkonda, Ravi V

    2012-03-28

    The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts chemotherapeutic access and complicates surgical resection. Here, we test the hypothesis that an effective anti-invasive agent can "contain" GBM and increase the efficacy of chemotherapy. We report a new anti-invasive small molecule, Imipramine Blue (IB), which inhibits invasion of glioma in vitro when tested against several models. IB inhibits NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-mediated reactive oxygen species generation and alters expression of actin regulatory elements. In vivo, liposomal IB (nano-IB) halts invasion of glioma, leading to a more compact tumor in an aggressively invasive RT2 syngeneic astrocytoma rodent model. When nano-IB therapy was followed by liposomal doxorubicin (nano-DXR) chemotherapy, the combination therapy prolonged survival compared to nano-IB or nano-DXR alone. Our data demonstrate that nano-IB-mediated containment of diffuse glioma enhanced the efficacy of nano-DXR chemotherapy, demonstrating the promise of an anti-invasive compound as an adjuvant treatment for glioma.

  20. Bisphosphonates in the adjuvant treatment of young women with breast cancer: the estrogen rich is a poor candidate!

    PubMed

    Azim, Hamdy A; Kamal, Nermine S; Malak, Rafaat A

    2013-06-01

    During the last 2 decades the role of bisphosphonates (BPs) to reduce skeletal-related events from bone metastases in breast cancer has been well defined. Several preclinical studies have strongly suggested that BPs may also provide an anti-cancer effect in early breast cancer. Indeed, the use of adjuvant BPs represents a unique approach that attempts at eradicating occult tumor micro-metastases residing in the bone marrow via targeting the bone microenvironment to render it less favorable for cancer cell growth. Although, this concept has been tested clinically for more than 15 years, no final consensus has been reached as for the routine use of BPs in the adjuvant phase of breast cancer, owing to conflicting results of randomized studies. Nevertheless, accumulating evidence from recent trials has indicated a therapeutic benefit of adjuvant BPs-particularly zoledronic acid-in women with established menopause, with no or perhaps detrimental effects in premenopausal women. Indeed, this hypothesis has opened a new chapter on the role of estrogen-poor microenvironment as a potential pre-requisite for the anti-tumor effects of BPs in the adjuvant phase of breast cancer. In this review, we will emphasize the biological rational of using BPs to target bone microenvironment in patients with early breast cancer and we will explore mechanistic differences; related to bisphosphonates effects in premenopausal versus postmenopausal women and how the endocrine environment would influence the anticancer potential of these compounds.

  1. High miR-21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer.

    PubMed

    Oue, Naohide; Anami, Katsuhiro; Schetter, Aaron J; Moehler, Markus; Okayama, Hirokazu; Khan, Mohammed A; Bowman, Elise D; Mueller, Annett; Schad, Arno; Shimomura, Manabu; Hinoi, Takao; Aoyagi, Kazuhiko; Sasaki, Hiroki; Okajima, Masazumi; Ohdan, Hideki; Galle, Peter R; Yasui, Wataru; Harris, Curtis C

    2014-04-15

    Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR-21 was measured by quantitative reverse transcriptase-polymerase chain reaction in a Japanese cohort (stage I-IV, n = 156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors was associated with poor survival in both the stage II/III Japanese (p = 0.0008) and stage II German (p = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR-21 in either cohort. In the Japanese cohort, high miR-21 expression was significantly associated with poor therapeutic outcome (p = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR-21 (p = 0.001). These results suggest that miR-21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR-21 may also identify patients who will benefit from adjuvant chemotherapy.

  2. Oral targeted therapy for cancer

    PubMed Central

    Carrington, Christine

    2015-01-01

    SUMMARY Oral targeted therapies are increasingly being used to treat cancer. They work by interfering with specific molecules or pathways involved in tumour growth. It is essential that health professionals managing patients taking these drugs have appropriate training and skills. They should be aware of potential adverse effects and drug interactions, and be able to manage toxicities when they occur. Despite the selectivity of these targeted therapies, they still have serious adverse effects including skin reactions, diarrhoea and altered organ function. PMID:26648656

  3. Esophagus Cancer: Palliative Therapy

    MedlinePlus

    ... in our document Guide to Controlling Cancer Pain . Nutritional support Nutrition is another concern for many patients ... and nutritionists can work with you to provide nutritional supplements and information about your individual nutritional needs. ...

  4. Treatment outcomes after adjuvant radiotherapy following surgery for patients with stage I endometrial cancer

    PubMed Central

    Kim, Jiyoung; Lee, Kyung-Ja; Park, Kyung-Ran; Ha, Boram; Kim, Yi-Jun; Jung, Wonguen; Lee, Rena; Kim, Seung Cheol; Moon, Hye Sung; Ju, Woong; Kim, Yun Hwan; Lee, Jihae

    2016-01-01

    Purpose The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. Materials and Methods The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0–50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. Results The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Conclusion Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery. PMID:27703126

  5. Radiation Therapy for Cancer

    MedlinePlus

    ... being studied as potential radioprotectors. The use of carbon ion beams in radiation therapy is being investigated ... time, the use of these beams remains experimental. Carbon ion beams are available at only a few ...

  6. Prostate Cancer (Radiation Therapy)

    MedlinePlus

    ... to three years. If I choose surgery, will radiation treatment still be required? If your surgery is ... option with your physician team. If I choose radiation therapy, will surgical treatment still be an option? ...

  7. Adjuvant Chemotherapy for Stage II Right- and Left-Sided Colon Cancer: Analysis of SEER-Medicare Data

    PubMed Central

    Weiss, Jennifer M.; Schumacher, Jessica; Allen, Glenn O.; Neuman, Heather; Lange, Erin O’Connor; LoConte, Noelle K.; Greenberg, Caprice C.; Smith, Maureen A.

    2014-01-01

    Purpose Survival benefit from adjuvant chemotherapy is established for stage III colon cancer; however, uncertainty exists for stage II patients. Tumor heterogeneity, specifically microsatellite instability (MSI) which is more common in right-sided cancers, may be the reason for this observation. We examined the relationship between adjuvant chemotherapy and overall 5-year mortality for stage II colon cancer by location (right- versus left-side) as a surrogate for MSI. Methods Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified Medicare beneficiaries from 1992 to 2005 with AJCC stage II (n=23,578) and III (n=17,148) primary adenocarcinoma of the colon who underwent surgery for curative intent. Overall 5-year mortality was examined with Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting. Results Eighteen percent (n=2,941) of stage II patients with right-sided cancer and 22% (n=1,693) with left-sided cancer received adjuvant chemotherapy. After adjustment, overall 5-year survival benefit from chemotherapy was observed only for stage III patients (right-sided: HR 0.64; 95% CI, 0.59–0.68, p<0.001 and left-sided: HR 0.61; 95% CI, 0.56–0.68, p<0.001). No survival benefit was observed for stage II patients with either right-sided (HR 0.97; 95% CI, 0.87–1.09, p=0.64) or left-sided cancer (HR 0.97; 95% CI, 0.84–1.12, p=0.68). Conclusions Among Medicare patients with stage II colon cancer, a substantial number receive adjuvant chemotherapy. Adjuvant chemotherapy did not improve overall 5-year survival for either right- or left-sided colon cancers. Our results reinforce existing guidelines and should be considered in treatment algorithms for older adults with stage II colon cancer. PMID:24643898

  8. Adjuvant Anti-Angiogenesis Drugs Are No Benefit in Kidney Cancer

    Cancer.gov

    Results from a recent clinical trial show that post-surgical therapy with two anti-angiogenesis drugs does not improve progression-free survival for patients with kidney cancer and may cause serious side effects.

  9. Long term survival of HER2-positive early breast cancer treated with trastuzumab-based adjuvant regimen: a large cohort study from clinical practice.

    PubMed

    Bonifazi, Martina; Franchi, Matteo; Rossi, Marta; Zambelli, Alberto; Moja, Lorenzo; Zambon, Antonella; Corrao, Giovanni; La Vecchia, Carlo; Zocchetti, Carlo; Negri, Eva

    2014-10-01

    Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ≥70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.

  10. Prognostic nutritional index before adjuvant chemotherapy predicts chemotherapy compliance and survival among patients with non-small-cell lung cancer

    PubMed Central

    Shimizu, Katsuhiko; Okita, Riki; Saisho, Shinsuke; Yukawa, Takuro; Maeda, Ai; Nojima, Yuji; Nakata, Masao

    2015-01-01

    Background Adjuvant chemotherapy after the complete resection of non-small-cell lung cancer (NSCLC) is now the standard of care. To improve survival, it is important to identify risk factors for the continuation of adjuvant chemotherapy. In this study, we analyzed chemotherapy compliance and magnitude of the prognostic impact of the prognostic nutritional index (PNI) before adjuvant chemotherapy. Methods We conducted a retrospective review of data from 106 patients who had received adjuvant chemotherapy. The adjuvant chemotherapy consisted of an oral tegafur agent (OT) or platinum-based chemotherapy (PB). The correlations between the PNI values and recurrence-free survival (RFS) were then evaluated. Results In the PB group, the percentage of patients who completed the four planned cycles of chemotherapy was not correlated with the PNI. In the OT group, however, a significant difference was observed in the percentage of patients who completed the planned chemotherapy according to the PNI before adjuvant chemotherapy. The RFS of patients with a PNI <50 before adjuvant chemotherapy was significantly poorer than that of the patients with a PNI ≥50. A multivariate analysis showed that nodal metastasis and PNI before chemotherapy were independent predictors of the RFS. However, PNI before surgery was not a predictor of the RFS. In the subgroup analysis, PNI before chemotherapy was independent predictor of the RFS in the OT group (P=0.019), but not in the PB group (P=0.095). Conclusion The PNI before adjuvant chemotherapy influenced the treatment compliance with the planned chemotherapy in the OT group, but not the PB group. In addition, a low PNI before adjuvant chemotherapy was associated with a poor RFS in a multivariate analysis, especially in the OT group. PMID:26504397

  11. Zingiber officinale Roscoe (ginger) as an adjuvant in cancer treatment: a review.

    PubMed

    Pereira, M M; Haniadka, R; Chacko, P P; Palatty, P L; Baliga, M S

    2011-01-01

    Despite acquiring a strong understanding of the molecular basis and advances in treatment, cancer is the second major cause of death in the world. In clinics, the stagedependent treatment strategies may include surgery, radiotherapy and systemic treatments like hormonotherapy and chemotherapy, which are associated with side effects. The use of traditional herbal medicine in cancer patients is on a rise, as it is believed that these medications are non toxic and alleviate the symptoms of cancer, boost the immune system, or may tackle the cancer itself. Since antiquity the rhizome of Zingiber officinale Roscoe commonly known as ginger (family Zingiberaceae) have widely been used as a spice and condiment in different societies. Additionally, ginger also has a long history of medicinal use in various cultures for treating common colds, fever, to aid digestion, treat stomach upset, diarrhoea, nausea, rheumatic disorders, gastrointestinal complications and dizziness. Preclinical studies have also shown that ginger possesses chemopreventive and antineoplastic properties. It is also reported to be effective in ameliorating the side effects of γ-radiation and of doxorubicin and cisplatin; to inhibit the efflux of anticancer drugs by P-glycoprotein (P-gp) and to possess chemosensitizing effects in certain neoplastic cells in vitro and in vivo. The objective of this review is to address observations on the role of ginger as adjuvant to treatment modalities of cancer. Emphasis is also placed on the drawbacks and on future directions for research that will have a consequential effect on cancer treatment and cure.

  12. Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy

    NASA Technical Reports Server (NTRS)

    Headley, J. A.; Theriault, R. L.; LeBlanc, A. D.; Vassilopoulou-Sellin, R.; Hortobagyi, G. N.

    1998-01-01

    The objective of this cross-sectional study was to determine lumbar spine bone mineral density (BMD) in breast cancer patients previously treated with adjuvant chemotherapy. Sixteen of 27 patients who received adjuvant chemotherapy became permanently amenorrheic as a result of chemotherapy. BMD was measured at the lumbar spine using dual energy X-ray absorptiometry (DEXA). Chemotherapy drugs and dosages along with a history of risk factors for reduced bone density including activity level, tobacco and/or alcohol use, metabolic bone disease, family history, and hormone exposure were identified. Results showed that women who became permanently amenorrheic as a result of chemotherapy had BMD 14% lower than women who maintained menses after chemotherapy. Chemotherapy-treated women who maintained ovarian function had normal BMD. This study suggests that women who have premature menopause as a result of chemotherapy for breast cancer are at increased risk of bone loss and may be at risk for early development of osteoporosis. Women who maintain menses do not appear to be at risk for accelerated trabecular bone loss.

  13. Cancer therapy and vaccination.

    PubMed

    Aly, Hamdy A A

    2012-08-31

    Cancer remains one of the leading causes of death worldwide, both in developed and in developing nations. It may affect people at all ages, even fetuses, but the risk for most varieties increases with age. Current therapeutic approaches which include surgery, chemotherapy and radiotherapy are associated with adverse side effects arising from lack of specificity for tumors. The goal of any therapeutic strategy is to impact on the target tumor cells with limited detrimental effect to normal cell function. Immunotherapy is cancer specific and can target the disease with minimal impact on normal tissues. Cancer vaccines are capable of generating an active tumor-specific immune response and serve as an ideal treatment due to their specificity for tumor cells and long lasting immunological memory that may safeguard against recurrences. Cancer vaccines are designed to either prevent (prophylactic) or treat established cancer (therapeutic). Identification of tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) has led to increased efforts to develop vaccination strategies. Vaccines may be composed of whole cells or cell extracts, genetically modified tumor cells to express costimulatory molecules, dendritic cells (DCs) loaded with TAAs, immunization with soluble proteins or synthetic peptides, recombinant viruses or bacteria encoding tumor-associated antigens, and plasmid DNA encoding TSAs or TAAs in conjunction with appropriate immunomodulators. All of these antitumor vaccination approaches aim to induce specific immunological responses and localized to TAAs, destroying tumor cells alone and leaving the vast majority of other healthy cells of the body untouched.

  14. Corpus uteri cancer: the results of surgical, combined and complex therapy.

    PubMed

    Vishnevskaya, E E

    1991-01-01

    The Author has examined the survival rates of 1543 cases of corpus uteri cancer, comparing the patients with and without pre-operative adjuvant treatment. Pre-operative treatment consisted of irradiation therapy and also in combined chemohormonal-radiotherapy. The results also referred to the type of radiotherapy and to the clinical background of patients (older age, severe general somatic diseases). The conclusions of this study underline the benefits of pre-operative irradiation therapy.

  15. Intraoperative radiation therapy in recurrent ovarian cancer

    SciTech Connect

    Yap, O.W. Stephanie . E-mail: stbeast@stanford.edu; Kapp, Daniel S.; Teng, Nelson N.H.; Husain, Amreen

    2005-11-15

    Purpose: To evaluate disease outcomes and complications in patients with recurrent ovarian cancer treated with cytoreductive surgery and intraoperative radiation therapy (IORT). Methods and Materials: A retrospective study of 24 consecutive patients with ovarian carcinoma who underwent secondary cytoreduction and intraoperative radiation therapy at our institution between 1994 and 2002 was conducted. After optimal cytoreductive surgery, IORT was delivered with orthovoltage X-rays (200 kVp) using individually sized and beveled cone applications. Outcomes measures were local control of disease, progression-free interval, overall survival, and treatment-related complications. Results: Of these 24 patients, 22 were available for follow-up analysis. Additional treatment at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and paracaval lymph node beds, inguinal region, or porta hepatitis. At a median follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients have recurred, of whom 4 are alive with disease and 13 died from disease. Five patients recurred within the radiation fields for a locoregional relapse rate of 32% and 12 patients recurred at distant sites with a median time to recurrence of 13.7 months. Five-year overall survival was 22% with a median survival of 26 months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from their treatments. Conclusion: In carefully selected patients with locally recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably tolerated and may contribute to achieving local control and disease palliation.

  16. Radiation recall dermatitis induced by tamoxifen during adjuvant breast cancer treatment

    PubMed Central

    Rhee, Jiyoung; Kim, Gwi Eon; Lee, Chang Hyun; Kwon, Jung-Mi; Han, Sang-Hoon; Kim, Young Suk

    2014-01-01

    Tamoxifen and radiotherapy are used in breast cancer treatment worldwide. Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman had a right quadrantectomy and an axillary lymph node dissection due to breast cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human epidermal growth factor receptor 2 negative. The patient received adjuvant chemotherapy followed by tamoxifen and radiotherapy. After 22 months of tamoxifen, the patient developed a localized heating sensation, tenderness, edema, and redness at the irradiated area of the right breast. The symptoms improved within 1 week without treatment. Three weeks later, however, the patient developed similar symptoms in the same area of the breast. She continued tamoxifen before and during dermatitis, and symptoms resolved within 1 week. PMID:25568855

  17. An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer.

    PubMed Central

    Munro, A. J.

    1995-01-01

    Meta-analysis of the published results from 54 randomised controlled trials of adjuvant chemotherapy in head and neck cancer suggests that chemotherapy might increase absolute survival by 6.5% (95% confidence interval 3.1-9.9%). The odds ratio in favour of chemotherapy is 1.37 (95% confidence interval 1.24-1.5). Single-agent chemotherapy given synchronously with radiotherapy increased survival by 12.1% (95% confidence interval 5-19%). The benefit from neoadjuvant chemotherapy was less: a rate difference of 3.7% (95% confidence interval 0.9-6.5%). The results suggest that the investigation of optimal agents and scheduling for synchronous radiotherapy and chemotherapy might still be important in clinical trials in head and neck cancer. PMID:7819055

  18. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    DTIC Science & Technology

    2012-09-01

    hepatic metabo- lism based on the ratio of total liver:intestinal CYP3A, the major cytochrome P450 enzyme sub-family responsible for lapatinib...combination with cyclosporin A. Alternatively, the increase in exposure was likely more resultant of competitive inhibition of cytochrome P450 enzymes by...sex on the clearance of cytochrome P450 3A substrates. Clin Pharmacokinet 44(1):33–60 27. Bischoff KB, Dedrick RL, Zaharko DS (1970) Preliminary

  19. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    DTIC Science & Technology

    2013-03-01

    transport studying docetaxel pharmacokinetics in wild-type FVB and Mdr1a/ b constitutive knockout (KO) mice. For all tissues in both the FVB and KO...16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b ...the role of PGP in drug PK. Dose mdr1a/ b knockout mice with LAPATINIB, DOCETAXEL, DOXORUBICIN, combination LAPATINIB and DOCETAXEL, and combination

  20. A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: Final results

    SciTech Connect

    Rouesse, Jacques . E-mail: j.rouesse@stcloud-huguenin.org; Lande, Brigitte de la; Bertheault-Cvitkovic, Frederique; Serin, Daniel; Graic, Yvon; Combe, Martin; Leduc, Bernard; Lucas, Virginie; Demange, Liliane; Tan Dat Nguyen; Castera, Daniel; Krzisch, Claude; Villet, Richard; Mouret-Fourme, Emmanuelle; Garbay, Jean-Remy; Nogues, Catherine

    2006-03-15

    Purpose: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. Methods and Materials: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m{sup 2} 5-fluorouracil, 12 mg/m{sup 2} mitoxantrone, and 500 mg/m{sup 2} cyclophosphamide, with concomitant radiotherapy (50 Gy {+-} 10-20-Gy boost). Patients in Arm B received 500 mg/m{sup 2} 5-fluorouracil, 60 mg/m{sup 2} epirubicin, and 500 mg/m{sup 2} cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. Results: Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). Conclusions: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.

  1. Longitudinal Assessments of Quality of Life in Endometrial Cancer Patients: Effect of Surgical Approach and Adjuvant Radiotherapy

    SciTech Connect

    Le, Tien; Menard, Chantal; Samant, Rajiv; Choan, E.; Hopkins, Laura; Faught, Wylam; Fung-Kee-Fung, Michael

    2009-11-01

    Purpose: Adjuvant radiotherapy (RT) is often considered for endometrial cancer. We studied the effect of RT and surgical treatment on patients' quality of life (QOL). Methods and Materials: All patients referred to the gynecologic oncology clinics with biopsy findings showing endometrial cancer were recruited. QOL assessments were performed using the European Organization for Research and Treatment of Cancer QOL questionnaire-C30, version 3. Assessments were obtained at study entry and at regular 3-month intervals for a maximum of 2 years. Open-ended telephone interviews were done every 6 months. Linear mixed regression models were built using QOL domain scores as dependent variables, with the predictors of surgical treatment and adjuvant RT type. Results: A total of 40 patients were recruited; 80% of the surgeries were performed by laparotomy. Significant improvements were seen in most QOL domains with increased time from treatment. Adjuvant RT resulted in significantly more severe bowel symptoms and improvement in insomnia compared with conservative follow-up. No significant adverse effect from adjuvant RT was seen on the overall QOL. Bowel symptoms were significantly increased in patients treated with laparotomy compared with laparoscopy in the patients treated with whole pelvic RT. Qualitatively, about one-half of the patients noted improvements in their overall QOL during follow-up, with easy fatigability the most prevalent. Conclusion: No significant adverse effect was seen on patients' overall QOL with adjuvant pelvic RT after the recovery period. The acute adverse effects on patients' QOL significantly improved with an increasing interval from diagnosis.

  2. Curative effect of the recent photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer

    PubMed Central

    SUN, BO; LI, WEI; LIU, NING

    2016-01-01

    Advanced colorectal cancer has a high mortality rate and conventional treatments have poor therapeutic effects. The aim of the present study was to analyze the recent curative effect and adverse reaction of photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer. A total of 23 patients with advanced colorectal cancer who had accepted semiconductor laser photodynamic adjuvant treatment were selected as the observation group. In addition, 30 patients who had accepted concurrent radiotherapy and chemotherapy during the same period served as the control group. The observation group received photofrin (2 mg/kg) intravenously in 100 ml of 5% glucose, followed by the introduction of the endoscopic optical fiber to deliver laser radiation with an intensity of 630 nm wavelength pulse power. After 2 days, necrotic tissues were removed and irradiation of the original or new tumor lesions was performed and necrotic tissues were removed. The total effective rate and survival time was higher and the length of hospital stay was shorter in the observation group in comparison with the control group. The differences were statistically significant (P<0.05). The number of patients in the control and observation groups with symptoms of hematochezia, change in bowel habit, intestinal stimulation and incomplete intestinal obstruction were reduced. Additionally, the reduced ratio of the observation group was significantly increased in comparison with the control group (P<0.05). The adverse reaction rate of the observation group was lower than that of the control group and this difference was also statistically significant (P<0.05). In conclusion, use of photodynamic treatment for young patients with advanced colorectal cancer can effectively improve the clinical symptoms and reduce complications. PMID:26998124

  3. Adjuvant chemotherapy with 5-fluorouracil in a patient with colorectal cancer and Familial Mediterranean Fever.

    PubMed

    Purim, Ofer; Sulkes, Aaron; Brenner, Baruch

    2007-07-01

    Colorectal cancer is a common malignancy often requiring adjuvant chemotherapy. Familial Mediterranean Fever is a chronic hereditary disease which is relatively prevalent in the Middle East and is associated with recurrent episodes of serosal, synovial or cutaneous inflammations. The aim of this paper was to describe a patient with Familial Mediterranean Fever who received fluorouracil-based adjuvant chemotherapy for colorectal cancer. A 56-year-old man with Familial Mediterranean Fever and amyloidosis was referred for evaluation and treatment following surgery for colorectal cancer. In light of his relatively young age, good general state of health and apparently well-controlled Familial Mediterranean Fever, he was treated with chemotherapy consisting of four cycles of 5-fluorouracil and leucovorin. The patient's clinical course during chemotherapy was unremarkable except for one minor attack of Familial Mediterranean Fever. The patient's follow-up was notable for periodic fluctuations in serum carcinoembryonic antigen levels, up to 4-fold of normal. The Familial Mediterranean Fever remained stable. Although our patient showed a good tolerability of treatment, the administration of chemotherapy to patients with Familial Mediterranean Fever raises several concerns. These include a potential deterioration in the Familial Mediterranean Fever status owing to chemotherapy-induced stress, the potential effect of Familial Mediterranean Fever or its treatment on the tolerability of chemotherapy and an overlapping toxicity of the drugs used to treat the two diseases. An increase in serum carcinoembryonic antigen in this setting may be related to the underlying pathophysiologic mechanism of Familial Mediterranean Fever but does not necessarily indicate disease recurrence. Clinicians should be aware of these issues considering the recent worldwide increase in colorectal cancer.

  4. Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging

    SciTech Connect

    Soper, J.T.; Berchuck, A.; Clarke-Pearson, D.L. )

    1991-08-15

    Forty-nine women with apparent Stage 1 and 2 ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as the first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.

  5. Cancer, unproven therapies, and magic.

    PubMed

    Wein, S

    2000-09-01

    Commonly used by cancer patients, unproven therapies are treatments that the practitioner claims can alter the disease process although there is no proof to support the claim. The reasons for the popularity of unproven therapies fall into two categories--practical considerations and fundamental mechanisms. Research has implicated the following practical factors: a pragmatic search for relief of symptoms, expression of a philosophical view, a need to reestablish a sense of control in life, and dissatisfaction with conventional medicine. Fundamental mechanisms include traditional magic, the heroic individual, and a delusional pattern of thinking. Underpinning and generating these factors is the fear of death. Particularly in patients with cancer, this is not only a fear of nonexistence, but of loneliness, the unknown, pain, loss of control, and emptiness. The popularity of unproven therapies poses a challenge to the medical system at large, and oncologists, psycho-oncologists, and palliative-care physicians, in particular. The essence of the challenge is to understand the reasons for the use of unproven therapies, to analyze our own behavior, and conclude what if anything our response should be. Unproven therapies (as with magic, a sense of heroism, and delusional thinking) fulfill the function of resolving the inexplicable and the psychologically painful--i.e., relieving the anxiety associated with cancer.

  6. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study)

    PubMed Central

    2011-01-01

    Background Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy. Methods/Design This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and

  7. Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

    SciTech Connect

    Beadle, Beth M.; Guadagnolo, B. Ashleigh Ballo, Matthew T.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Cormier, Janice N.; Mansfield, Paul F.; Ross, Merrick I.; Zagars, Gunar K.

    2009-04-01

    Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.

  8. Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study

    PubMed Central

    Le Roy, Bertrand; Tixier, Lucie; Pereira, Bruno; Sauvanet, Pierre; Buc, Emmanuel; Pétorin, Caroline; Déchelotte, Pierre; Pezet, Denis; Balayssac, David

    2016-01-01

    Background Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. Methods This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb–IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. Results Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis

  9. CATIONIC CERAMIDES AND ANALOGUES, LCL30 AND LCL85, AS ADJUVANTS TO PHOTODYNAMIC THERAPY OF TUMORS

    PubMed Central

    Korbelik, Mladen; Zhang, Wei; Saw, Kyi Min; Szulc, Zdzislaw M.; Bielawska, Alicja; Separovic, Duska

    2013-01-01

    Photodynamic therapy (PDT) is known to alter the expression of various genes in treated cells. This prompted us to examine the activity of genes encoding two important enzymes in sphingolipid (SL) metabolism, dihydroceramide desaturase (DES) and sphingosine kinase (SPHK), in mouse SCCVII tumor cells treated by PDT using either the porphyrin-based photosensitizer Photofrin or silicon phthalocyanine Pc4. The results revealed that PDT induced an upregulation in the expression of two major isoforms of both genes (DES1 and DES2 as well as SPHK1 and SPHK2). While the changes were generally moderate (2-3 fold gains), the increase in DES2 expression was more pronounced and it was much greater with Photofrin-PDT than with Pc4-PDT (over 23-fold vs. less than 5-fold). Combining either Photofrin-PDT or Pc4-PDT with the cationic C16-ceramide LCL30 (20 mg/kg i.p.) for treatment of subcutaneously growing SCCVII tumors rendered important differences in the therapy outcome. Photofrin-PDT, used at a dose that attained good initial response but no tumor cures, produced 50% cures when combined with a single LCL30 treatment. In contrast, the same LCL30 treatment combined with Pc4-PDT had no significant effect on tumor response. The optimal timing of LCL30 injection was immediately after Photofrin-PDT. The therapeutic benefit was lost when LCL30 was given in two 20 mg/kg injections encompassing intervals before and after PDT. LCL85, the cationic B13 ceramide analogue and SL-modulating agent, also increased cure rates of Photofrin-PDT treated tumors, but the therapeutic benefit was less pronounced than with LCL30. These results with LCL30 and LCL85, and our previous findings for LCL29 (another SL analogue), assert the potential of SLs for use as adjuvants to augment the efficacy of PDT-mediated tumor destruction. PMID:23911762

  10. Cationic ceramides and analogues, LCL30 and LCL85, as adjuvants to photodynamic therapy of tumors.

    PubMed

    Korbelik, Mladen; Zhang, Wei; Saw, Kyi Min; Szulc, Zdzislaw M; Bielawska, Alicja; Separovic, Duska

    2013-09-05

    Photodynamic therapy (PDT) is known to alter the expression of various genes in treated cells. This prompted us to examine the activity of genes encoding two important enzymes in sphingolipid (SL) metabolism, dihydroceramide desaturase (DES) and sphingosine kinase (SPHK), in mouse SCCVII tumor cells treated by PDT using either the porphyrin-based photosensitizer Photofrin or silicon phthalocyanine Pc4. The results revealed that PDT induced an upregulation in the expression of two major isoforms of both genes (DES1 and DES2 as well as SPHK1 and SPHK2). While the changes were generally moderate (2-3-fold gains), the increase in DES2 expression was more pronounced and it was much greater with Photofrin-PDT than with Pc4-PDT (over 23-fold vs. less than 5-fold). Combining either Photofrin-PDT or Pc4-PDT with the cationic C16-ceramide LCL30 (20mg/kg i.p.) for treatment of subcutaneously growing SCCVII tumors rendered important differences in the therapy outcome. Photofrin-PDT, used at a dose that attained good initial response but no tumor cures, produced 50% cures when combined with a single LCL30 treatment. In contrast, the same LCL30 treatment combined with Pc4-PDT had no significant effect on tumor response. The optimal timing of LCL30 injection was immediately after Photofrin-PDT. The therapeutic benefit was lost when LCL30 was given in two 20mg/kg injections encompassing intervals before and after PDT. LCL85, the cationic B13 ceramide analogue and SL-modulating agent, also increased cure rates of Photofrin-PDT treated tumors, but the therapeutic benefit was less pronounced than with LCL30. These results with LCL30 and LCL85, and our previous findings for LCL29 (another SL analogue), assert the potential of SLs for use as adjuvants to augment the efficacy of PDT-mediated tumor destruction.

  11. Gastric cancer and trastuzumab: first biologic therapy in gastric cancer

    PubMed Central

    Gunturu, Krishna S.; Woo, Yanghee; Beaubier, Nike; Remotti, Helen E.

    2013-01-01

    Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer. PMID:23450234

  12. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

    PubMed

    Aragon-Ching, Jeanny B; Trump, Donald L

    2016-09-01

    Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

  13. Antiangiogenic therapy for breast cancer

    PubMed Central

    2010-01-01

    Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria. PMID:21067536

  14. The effects of cancer and cancer therapies on wound healing

    SciTech Connect

    McCaw, D.L.

    1989-11-01

    Based on experimental evidence in rodents, most of the antineoplastic agents will affect wound healing. With most of the agents, this impairment is not sufficient to produce increased morbidity based on the clinical reports in humans. Radiation therapy appears to inhibit healing in both experimental animals and during clinical trials. In spite of this, it is reported that wounds in animals will heal when they are receiving radiation therapy after surgery. Based on the information presented here and experience at the University of Missouri, the decision to use adjuvant therapy should depend on the surgery performed. With a single incision that had no increased tension, there should be no hesitation to use adjuvant therapy. If removal of the tumor required reconstructive surgery, no radiation or chemotherapy should be used until the wound has healed. 30 references.

  15. Vectors for cancer gene therapy.

    PubMed

    Zhang,