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Sample records for advanced recurrent metastatic

  1. MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2016-06-03

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  2. Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond

    PubMed Central

    Mackay, Helen J.; Wenzel, Lari; Mileshkin, Linda

    2016-01-01

    Overview Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease. PMID:25993189

  3. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    ClinicalTrials.gov

    2016-07-10

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  4. Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

    PubMed Central

    Echarri, María José; Lopez-Martin, Ana; Hitt, Ricardo

    2016-01-01

    Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing. PMID:26927178

  5. Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma

    ClinicalTrials.gov

    2014-05-07

    Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Leiomyosarcoma; Adult Malignant Fibrous Histiocytoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma

  6. AZD0530 in Treating Patients With Recurrent Locally Advanced or Metastatic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2015-07-02

    Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Rhabdomyosarcoma; Dermatofibrosarcoma Protuberans; Endometrial Stromal Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma

  7. Sorafenib Tosylate in Treating Patients With Locally Advanced, Metastatic, or Locally Recurrent Thyroid Cancer

    ClinicalTrials.gov

    2014-01-15

    Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Recurrent Thyroid Cancer; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer

  8. Feasibility and Timing of Cytoreduction Surgery in Advanced (Metastatic or Recurrent) Gastrointestinal Stromal Tumors During the Era of Imatinib

    PubMed Central

    Chang, Shih-Chun; Liao, Chien-Hung; Wang, Shang-Yu; Tsai, Chun-Yi; Chiang, Kun-Chun; Cheng, Chi-Tung; Yeh, Ta-Sen; Chen, Yen-Yang; MA, Ming-Chun; Liu, Chien-Ting; Yeh, Chun-Nan

    2015-01-01

    Abstract The prognosis of advanced gastrointestinal stromal tumors (GISTs) was dramatically improved in the era of imatinib. Cytoreduction surgery was advocated as an additional treatment for advanced GISTs, especially when patients having poor response to imatinib or developing resistance to it. However, the efficacy and benefit of cytoreduction were still controversial. Likewise, the sequence between cytoreduction surgery and imatinib still need evaluation. In this study, we tried to assess the feasibility and efficiency of cytoreduction in advanced GISTs. Furthermore, we analyzed the impact of timing of the cytoreduction surgery on the prognosis of advanced GISTs. We conducted a prospective collecting retrospective review of patients with advanced GISTs (metastatic, unresectable, and recurrent GISTs) treated in Chang Gung memorial hospital (CGMH) since 2001 to 2013. We analyzed the impact of cytoreduction surgery to response to imatinib, progression-free survival (PFS), and overall survival (OS) in patients with advanced GISTs. Moreover, by the timing of cytoreduction to imatinib, we divided the surgical patients who had surgery before imatinib use into early group and those who had surgery after imatinib into late. We compared the clinical response to imatinib, PFS and OS between early and late cytoreduction surgical groups. Totally, 182 patients were enrolled into this study. Seventy-six patients underwent cytoreduction surgery. The demographic characteristics and tumor presentation were similar between surgical and non-surgical groups. The surgical group showed better complete response rate (P < 0.001) and partial response rate (P = 0.008) than non-surgical group. The 1-year, 3-year, and 5-year PFS were significantly superior in surgical group (P = 0.003). The 1-year, 3-year, and 5-year OS were superior in surgical group, but without statistical significance (P = 0.088). Dividing by cytoreduction surgical timing, the demographic

  9. Cetuximab for the treatment of locally advanced and recurrent/metastatic oral cancer: An investigation of distant metastasis

    PubMed Central

    Naruse, Tomofumi; Yanamoto, Souichi; Matsushita, Yuki; Sakamoto, Yuki; Morishita, Kota; Ohba, Seigo; Shiraishi, Takeshi; Yamada, Shin-Ichi; Asahina, Izumi; Umeda, Masahiro

    2016-01-01

    The aim of this retrospective study was to assess the efficacy and safety of cetuximab therapy for patients with locally advanced (LA) and recurrent/metastatic (R/M) oral squamous cell carcinoma (OSCC), with a specific focus on distant metastases (DMs). Data from 21 patients with unresectable LA and R/M OSCC treated with cetuximab therapy in our department between December, 2012 and July, 2015 were reviewed. The endpoint was the time-to-progression and the assessments made were tumor response rate, progression-free survival (PFS), overall survival (OS) and safety. The overall response rate was 57.1%, with a complete response (CR) rate of 33.3%. The overall median PFS and OS were 5.5 and 8.0 months, respectively. For patients with DMs, the overall response rate was 60.0%, with a CR rate of 40.0%. The median PFS and OS were 3.8 and 5.8 months, respectively. In addition, improved 1-year OS was observed following approval of cetuximab, although the differences between the group of patients treated after that time and historical controls were not statistically significantly (P=0.246). Grade 3–4 adverse events included infusion reaction (4 cases), neutropenia, hypophosphatemia, upper gastrointestinal hemorrhage, liver toxicity and mucositis (1 case each). There was one cetuximab-related death due to interstitial pneumonia. An acne-like rash was observed in all cases, but no grade 3 or 4 rash was reported. Hypomagnesemia was observed in 10 cases. Our results suggest that cetuximab may display significant therapeutic efficacy in patients with unresectable LA and R/M OSCC, including those with DMs. PMID:27446558

  10. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer

    PubMed Central

    Swiecicki, Paul L.; Bellile, Emily; Sacco, Assuntina G.; Pearson, Alexander T.; Taylor, Jeremy M. G.; Jackson, Trachette L.; Chepeha, Douglas B.; Spector, Matthew E.; Shuman, Andrew; Malloy, Kelly; Moyer, Jeffrey; McKean, Erin; McLean, Scott; Sukari, Ammar; Wolf, Gregory T.; Eisbruch, Avraham; Prince, Mark; Bradford, Carol; Carey, Thomas E.; Wang, Shaomeng; Nör, Jacques E.; Worden, Francis P.

    2016-01-01

    Background AT-101 is a BCL-2 Homolog domain 3 mimetic previously demonstrated to have tumoricidal effects in advanced solid organ malignancies. Given the evidence of activity in xenograft models, treatment with AT-101 in combination with docetaxel is a therapeutic doublet of interest in metastatic head and neck squamous cell carcinoma. Patients and Methods Patients included in this trial had unresectable, recurrent, or distantly metastatic head and neck squamous cell carcinoma (R/M HNSCC) not amenable to curative radiation or surgery. This was an open label randomized, phase II trial in which patients were administered AT-101 in addition to docetaxel. The three treatment arms were docetaxel, docetaxel plus pulse dose AT-101, and docetaxel plus metronomic dose AT-101. The primary endpoint of this trial was overall response rate. Results Thirty-five patients were registered and 32 were evaluable for treatment response. Doublet therapy with AT-101 and docetaxel was well tolerated with only 2 patients discontinuing therapy due to treatment related toxicities. The overall response rate was 11% (4 partial responses) with a clinical benefit rate of 74%. Median progression free survival was 4.3 months (range: 0.7–13.7) and overall survival was 5.5 months (range: 0.4–24). No significant differences were noted between dosing strategies. Conclusion Although met with a favorable toxicity profile, the addition of AT-101 to docetaxel in R/M HNSCC does not appear to demonstrate evidence of efficacy. PMID:27225873

  11. Suberoylanilide Hydroxamic Acid in Treating Patients With Metastatic and/or Locally Advanced or Locally Recurrent Thyroid Cancer

    ClinicalTrials.gov

    2014-07-23

    Insular Thyroid Cancer; Recurrent Thyroid Cancer; Stage II Follicular Thyroid Cancer; Stage II Papillary Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma

  12. TLR8 Agonist VTX-2337 and Cetuximab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Squamous Cell Cancer of Head and Neck

    ClinicalTrials.gov

    2015-03-03

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage

  13. Sapanisertib or Pazopanib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2016-10-31

    High Grade Sarcoma; Metastatic Leiomyosarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Recurrent Leiomyosarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Synovial Sarcoma; Recurrent Undifferentiated Pleomorphic Sarcoma; Uterine Corpus Leiomyosarcoma

  14. Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2015-08-29

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

  15. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  16. Indications for surgery in advanced/metastatic GIST.

    PubMed

    Ford, Samuel J; Gronchi, Alessandro

    2016-08-01

    Gastrointestinal stromal tumours (GISTs) are a relatively rare entity and often present as a locally advanced tumour or with metastatic disease. Complete surgical resection is the only means of cure in localised disease; however, imatinib therapy has greatly advanced the management of GIST and is established as both an adjunct to surgery in high-risk cases and as principle therapy in metastatic disease. Surgery in advanced GIST has undergone a renaissance in recent years with the potential for a combined treatment approach with either neoadjuvant imatinib in locally advanced primary disease or as an adjunct to imatinib in those with metastases or recurrent disease. Neoadjuvant imatinib can render a locally advanced primary GIST resectable, allow less invasive procedures or promote preservation of function, especially if the tumour is located in an anatomically difficult position. The role of surgery in metastatic or recurrent disease is more controversial and case selection is critical. The potential benefit is difficult to quantify, although surgery may have a limited favourable impact on progression-free survival and overall survival for those patients whose disease is responding to imatinib or those with limited focal progression. Patients with imatinib resistant disease should not be offered surgery unless as an emergency where palliative intervention may be justified. PMID:27318456

  17. Exemestane With or Without Entinostat in Treating Patients With Recurrent Hormone Receptor-Positive Breast Cancer That is Locally Advanced or Metastatic

    ClinicalTrials.gov

    2016-11-04

    Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  18. GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

    ClinicalTrials.gov

    2013-01-23

    Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  19. Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma (Cancer) of the Head and Neck

    ClinicalTrials.gov

    2013-01-23

    Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Salivary Gland Adenoid Cystic Carcinoma; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer

  20. Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer

    ClinicalTrials.gov

    2016-07-19

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  1. Cediranib Maleate in Treating Patients With Recurrent or Newly Diagnosed Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2015-04-14

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Laryngeal Squamous Cell Carcinoma; Stage IV Laryngeal Verrucous Carcinoma; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma; Stage IV Major Salivary Gland Carcinoma; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IV Oral Cavity Verrucous Carcinoma; Stage IV Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  2. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

    ClinicalTrials.gov

    2016-06-06

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  3. Lapatinib in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2014-01-06

    Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  4. Cabozantinib-S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

    ClinicalTrials.gov

    2016-10-10

    Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  5. The role of HPV status in recurrent/metastatic squamous cell carcinoma of the head and neck.

    PubMed

    Misiukiewicz, Krzysztof; Camille, Nadia; Gupta, Vishal; Bakst, Richard; Teng, Marita; Miles, Brett; Genden, Eric; Sikora, Andrew; Posner, Marshall

    2014-12-01

    Although the prognostic role of human papillomavirus (HPV) in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is well established, its prognostic and/or predictive role in recurrent/metastatic settings remains to be defined. Despite epidemic growth of HPV-positive oropharyngeal carcinoma, a low recurrence rate in HPV-positive patients results in a small number of patients entering clinical trials for recurrent and/or metastatic SCCHN. The consequent lack of statistical power and also significant data contamination by misclassification of HPV-positive patients leads to premature study conclusions. Even emerging data from the analysis of 2 randomized trials, SPECTRUM and EXTREME, do not provide enough evidence for any HPV-based therapeutic strategy. Many upcoming studies for locally advanced disease, including the ones with de-escalated strategies, will have an increasing number of patients with HPV. Optimal HPV testing strategies for reliable patient selection and HPV-driven therapeutic approaches will be essential. Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in recurrent/metastatic settings and discuss current promising studies and future directions that may help in the design of upcoming trials. PMID:25674839

  6. The role of HPV status in recurrent/metastatic squamous cell carcinoma of the head and neck.

    PubMed

    Misiukiewicz, Krzysztof; Camille, Nadia; Gupta, Vishal; Bakst, Richard; Teng, Marita; Miles, Brett; Genden, Eric; Sikora, Andrew; Posner, Marshall

    2014-12-01

    Although the prognostic role of human papillomavirus (HPV) in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is well established, its prognostic and/or predictive role in recurrent/metastatic settings remains to be defined. Despite epidemic growth of HPV-positive oropharyngeal carcinoma, a low recurrence rate in HPV-positive patients results in a small number of patients entering clinical trials for recurrent and/or metastatic SCCHN. The consequent lack of statistical power and also significant data contamination by misclassification of HPV-positive patients leads to premature study conclusions. Even emerging data from the analysis of 2 randomized trials, SPECTRUM and EXTREME, do not provide enough evidence for any HPV-based therapeutic strategy. Many upcoming studies for locally advanced disease, including the ones with de-escalated strategies, will have an increasing number of patients with HPV. Optimal HPV testing strategies for reliable patient selection and HPV-driven therapeutic approaches will be essential. Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in recurrent/metastatic settings and discuss current promising studies and future directions that may help in the design of upcoming trials.

  7. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma.

    PubMed

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-08-18

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. PMID:27621765

  8. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma

    PubMed Central

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-01-01

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.

  9. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma

    PubMed Central

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-01-01

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. PMID:27621765

  10. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma.

    PubMed

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-08-18

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.

  11. CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-07-26

    Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer

  12. Phase II Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-04-18

    Extensive Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Tumors Metastatic to Brain; Metastatic Breast Cancer

  13. Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2013-06-03

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Regional Gastrointestinal Carcinoid Tumor; Somatostatinoma

  14. Cetuximab and Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2013-07-26

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Tongue Cancer

  15. Sunitinib in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2014-07-21

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

  16. Treatment of Recurrent Metastatic Head and Neck Cancer: Focus on Cetuximab

    PubMed Central

    Patel, Akshar N.; Mehnert, Janice M.; Kim, Sung

    2012-01-01

    EGFR belongs to the ErbB family of receptor tyrosine kinases and is associated with worse prognosis in head and neck squamous cell carcinoma (HNSCC). Cetuximab is a monoclonal antibody to the extracellular domain of EGFR and inhibits its downstream actions via multiple mechanisms. Besides its proven efficacy in locally advanced and incurable HNSCC, cetuximab has the distinct advantage of having a relatively tolerable side effect profile and not potentiating radiation toxicity. Though therapies for advanced HNSCC are evolving, locoregional recurrence and/or distant metastases occur in a large percentage of patients. Though some patients can be salvaged with surgery or radiation therapy, the majority are incurable, and are treated palliatively with systemic therapy. In the setting of first line therapy for recurrent/metastatic HNSCC, the EXTREME trial provided level 1 evidence that cetuximab improves overall survival when combined with cisplatinum and 5 FU. Following progression on first line chemotherapy, several phase II trials suggest that cetuximab monotherapy is a reasonable choice in this setting. Future studies should concentrate on clinical and molecular markers that may allow more personalized approaches to treating HNSCC, and combining EGFR inhibitors with other agents in a synergistic approach. PMID:24179404

  17. TLR8 Agonist VTX-2337 and Cyclophosphamide in Treating Patients With Metastatic, Persistent, Recurrent, or Progressive Solid Tumors

    ClinicalTrials.gov

    2016-06-15

    Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Melanoma of the Skin; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer

  18. S0420, Sorafenib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2013-02-27

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  19. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-10-18

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

  20. A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-06-30

    Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC) Patients Who Are Resistant or Ineligible/Intolerant to Platinum-based Chemotherapy.; Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma

  1. Vorinostat in Treating Patients With Locally Recurrent or Metastatic Cancer of the Urothelium

    ClinicalTrials.gov

    2015-01-28

    Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Transitional Cell Carcinoma of the Bladder

  2. Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma

    PubMed Central

    Hedberg, Matthew L.; Goh, Gerald; Chiosea, Simion I.; Bauman, Julie E.; Freilino, Maria L.; Zeng, Yan; Wang, Lin; Diergaarde, Brenda B.; Gooding, William E.; Lui, Vivian W.Y.; Herbst, Roy S.; Lifton, Richard P.; Grandis, Jennifer R.

    2015-01-01

    BACKGROUND. Recurrence and/or metastasis occurs in more than half of patients with head and neck squamous cell carcinoma (HNSCC), and these events pose the greatest threats to long-term survival. We set out to identify genetic alterations that underlie recurrent/metastatic HNSCC. METHODS. Whole-exome sequencing (WES) was performed on genomic DNA extracted from fresh-frozen whole blood and patient-matched tumor pairs from 13 HNSCC patients with synchronous lymph node metastases and 10 patients with metachronous recurrent tumors. Mutational concordance within and between tumor pairs was used to analyze the spatiotemporal evolution of HNSCC in individual patients and to identify potential therapeutic targets for functional evaluation. RESULTS. Approximately 86% and 60% of single somatic nucleotide variants (SSNVs) identified in synchronous nodal metastases and metachronous recurrent tumors, respectively, were transmitted from the primary index tumor. Genes that were mutated in more than one metastatic or recurrent tumor, but not in the respective primary tumors, include C17orf104, inositol 1,4,5-trisphosphate receptor, type 3 (ITPR3), and discoidin domain receptor tyrosine kinase 2 (DDR2). Select DDR2 mutations have been shown to confer enhanced sensitivity to SRC-family kinase (SFK) inhibitors in other malignancies. Similarly, HNSCC cell lines harboring endogenous and engineered DDR2 mutations were more sensitive to the SFK inhibitor dasatinib than those with WT DDR2. CONCLUSION. In this WES study of patient-matched tumor pairs in HNSCC, we found synchronous lymph node metastases to be genetically more similar to their paired index primary tumors than metachronous recurrent tumors. This study outlines a compendium of somatic mutations in primary, metastatic, and/or recurrent HNSCC cancers, with potential implications for precision medicine approaches. FUNDING. National Cancer Institute, American Cancer Society, Agency for Science, Technology and Research of Singapore

  3. Cisplatin and Fluorouracil Compared With Carboplatin and Paclitaxel in Treating Patients With Inoperable Locally Recurrent or Metastatic Anal Cancer

    ClinicalTrials.gov

    2016-03-22

    Anal Basaloid Carcinoma; Anal Canal Cloacogenic Carcinoma; Anal Squamous Cell Carcinoma; Metastatic Anal Canal Carcinoma; Recurrent Anal Canal Carcinoma; Stage IIIB Anal Canal Cancer; Stage IV Anal Canal Cancer

  4. Anastomotic Recurrence of Colon Cancer-is it a Local Recurrence, a Second Primary, or a Metastatic Disease (Local Manifestation of Systemic Disease)?

    PubMed

    Gopalan, Sathiyavelavan; Bose, Jagadesh Chandra; Periasamy, S

    2015-06-01

    The aim of this study is to review the literature to find out the exact etiology of anastomotic cancers of colon post resection and differentiate them between a recurrence, second primary, and metastatic disease (local manifestation of systemic disease). Web-based literature search was done, and datas collected. We searched PubMed for papers using the keywords colon cancer recurrence, anastomotic recurrence, and recurrent colon carcinoma. We also searched for systematic review in the same topic. In addition, we used our personal referrence archive. Anastomotic recurrences of colon are postulated to arise due to inadequate margins, tumor implantation by exfoliated cells, altered biological properties of bowel anastomosis, and missed synchronous lesions. Some tumors are unique with repeated recurrence after repeated resection. Duration after primary surgery plays a major role in differentiating recurrent and second primary lesions. Repeated recurrences after repeated resections have to be considered a manifestation of systemic disease or metastatic disease due to the virulence of the disease. A detailed analysis and study of patients with colonic anastomotic lesion are required to differentiate it between a recurrent, a second primary lesion, and a metastatic disease (local manifestation of a systemic disease). The nomenclature is significant to study the survival of these patients, as a second primary lesion will have different survival compared to that of recurrent lesions.

  5. Carboplatin, Paclitaxel, Cetuximab, and Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Head and Neck Squamous Cell Cancer

    ClinicalTrials.gov

    2016-03-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  6. Advances in diagnosis and treatment of metastatic cervical cancer.

    PubMed

    Li, Haoran; Wu, Xiaohua; Cheng, Xi

    2016-07-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.

  7. Advances in diagnosis and treatment of metastatic cervical cancer

    PubMed Central

    2016-01-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

  8. Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-11-04

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Major Salivary Gland Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  9. Vorinostat in Combination With Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection

    ClinicalTrials.gov

    2016-10-11

    HIV Infection; Recurrent Anal Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Anal Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Unspecified Adult Solid Tumor, Protocol Specific

  10. Surgical salvage improves overall survival for HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer

    PubMed Central

    Guo, Theresa; Qualliotine, Jesse R.; Ha, Patrick K.; Califano, Joseph A.; Kim, Young; Saunders, John R.; Blanco, Ray; D'Souza, Gypsyamber; Zhang, Zhe; Chung, Christine H.; Kiess, Ana; Gourin, Christine G.; Koch, Wayne; Richmon, Jeremy D.; Agrawal, Nishant; Eisele, David W.; Fakhry, Carole

    2015-01-01

    Background Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for distant metastatic disease are limited. Methods A retrospective analysis of patients with recurrent OPSCC from two institutions between 2000-2012 was performed. P16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site and treatment modalities were compared by HPV tumor status. Overall survival was examined by Kaplan-Meier and Cox proportional hazards methods. Results The study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority were HPV-positive (n=80). HPV-positive tumor status was associated with longer time to recurrence (p<0.01). Anatomic site distribution of recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR] 0.23 (95%CI 0.09-0.58), p=0.002), longer time to recurrence (≥1 year; aHR 0.36 (0.18-0.74), p=0.006), and surgical salvage (aHR 0.26 (0.12-0.61), p=0.002) were independently associated with overall survival after recurrence. Surgical salvage was independently associated with improved overall survival compared to non-surgical treatment in both locoregional (aHR 0.15 (0.04-0.56), p=0.005) and distant metastatic recurrence (aHR 0.19 (0.05-0.75), p=0.018). Conclusions Surgical salvage is associated with improved overall survival for recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data is needed to confirm the role of surgical salvage for distant metastases. PMID:25782027

  11. PET in the management of locally advanced and metastatic NSCLC.

    PubMed

    Grootjans, Willem; de Geus-Oei, Lioe-Fee; Troost, Esther G C; Visser, Eric P; Oyen, Wim J G; Bussink, Johan

    2015-07-01

    Despite considerable improvements in the treatment options for advanced-stage non-small-cell lung cancer (NSCLC), disease-specific survival remains poor. With the aim of improving patient outcome, the treatment paradigm of locally advanced NSCLC has shifted from solely radiotherapy towards combined and intensified treatment approaches. Also, treatment for patients with stage IV (oligo)metastatic NSCLC has evolved rapidly, with therapeutic options that include a number of targeted agents, surgery, and stereotactic ablative radiotherapy. However, personalizing treatment to the individual patient remains difficult and requires monitoring of biological parameters responsible for treatment resistance to facilitate treatment selection, guidance, and adaptation. PET is a well-established molecular imaging platform that enables non-invasive quantification of many biological parameters that are relevant to both local and systemic therapy. With increasing clinical evidence, PET has gradually evolved from a purely diagnostic tool to a multifunctional imaging modality that can be utilized for treatment selection, adaptation, early response monitoring, and follow up in patients with NSCLC. Herein, we provide a comprehensive overview of the available clinical data on the use of this modality in this setting, and discuss future perspectives of PET imaging for the clinical management of patients with locally advanced and metastatic NSCLC.

  12. Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

    SciTech Connect

    Jereczek-Fossa, Barbara Alicja; Beltramo, Giancarlo; Fariselli, Laura; Fodor, Cristiana; Santoro, Luigi; Vavassori, Andrea; Zerini, Dario; Gherardi, Federica; Ascione, Carmen; Bossi-Zanetti, Isa; Mauro, Roberta; Bregantin, Achille; Bianchi, Livia Corinna; De Cobelli, Ottavio; Orecchia, Roberto

    2012-02-01

    Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [{sup 11}C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor

  13. Alisertib in Treating Patients With Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2016-02-02

    Myxofibrosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Leiomyosarcoma; Recurrent Liposarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Undifferentiated Pleomorphic Sarcoma; Stage III Soft Tissue Sarcoma; Stage IV Soft Tissue Sarcoma

  14. Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2016-07-27

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  15. Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2016-08-04

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

  16. Macrophage depletion reduces postsurgical tumor recurrence and metastatic growth in a spontaneous murine model of melanoma

    PubMed Central

    Tham, Muly; Khoo, Karen; Yeo, Kim Pin; Kato, Masashi; Prevost-Blondel, Amelle; Angeli, Veronique; Abastado, Jean-Pierre

    2015-01-01

    Surgical resection of tumors is often followed by regrowth at the primary site and metastases may emerge rapidly following removal of the primary tumor. Macrophages are important drivers of tumor growth, and here we investigated their involvement in postoperative relapse as well as explore macrophage depletion as an adjuvant to surgical resection. RETAAD mice develop spontaneous metastatic melanoma that begins in the eye. Removal of the eyes as early as 1 week of age did not prevent the development of metastases; rather, surgery led to increased proliferation of tumor cells locally and in distant metastases. Surgery-induced increase in tumor cell proliferation correlated with increased macrophage density within the tumor. Moreover, macrophages stimulate tumor sphere formation from tumor cells of post-surgical but not control mice. Macrophage depletion with a diet containing the CSF-1R specific kinase inhibitor Ki20227 following surgery significantly reduced postoperative tumor recurrence and abrogated enhanced metastatic outgrowth. Our results confirm that tumor cells disseminate early, and show that macrophages contribute both to post-surgical tumor relapse and growth of metastases, likely through stimulating a population of tumor-initiating cells. Thus macrophage depletion warrants exploration as an adjuvant to surgical resection. PMID:25762633

  17. Sorafenib in Treating Patients With Advanced or Metastatic Cancer of the Urinary Tract

    ClinicalTrials.gov

    2015-08-04

    Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder

  18. Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer.

    PubMed

    Khan, Tanweera S; Sundin, Anders; Juhlin, Claes; Wilander, Erik; Oberg, Kjell; Eriksson, Barbro

    2004-01-01

    The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial. PMID:15299189

  19. PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2016-01-06

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  20. Mifamurtide in Metastatic and Recurrent Osteosarcoma: A Patient Access Study with Pharmacokinetic, Pharmacodynamic, and Safety Assessments

    PubMed Central

    Anderson, P.M.; Meyers, P.; Kleinerman, E.; Venkatakrishnan, K.; Hughes, D.P.; Herzog, C.; Huh, W.; Sutphin, R.; Vyas, Y. M.; Shen, V.; Warwick, A.; Yeager, N.; Oliva, C.; Wang, B.; Liu, Y.; Chou, A.

    2015-01-01

    Purpose This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl –tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. Methods Patients received mifamurtide 2 mg/m2 intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24 hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. Results The study began therapy in January 2008; the last patient completed therapy in October 2012. 205 patients were enrolled; median age was 16.5 years and 143/204 (72%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30 minutes post-infusion, then in a loglinear manner 2–6 hours post-dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2 mg/m2 mifamurtide across the age range. Patients reported 3,415 IRAE after 7,122 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills+fever or headache+fatigue symptom clusters. One and two year OS was 70.6% and 41.4%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N=40) had similar 2-year OS (38.8%) as the entire cohort (41.4%) Conclusions Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 41.4%. A randomized clinical trial would be required to definitively determine impact on patient outcomes. PMID:23997016

  1. Management of muscle invasive, locally advanced and metastatic urothelial carcinoma of the bladder: a literature review with emphasis on the role of surgery

    PubMed Central

    Abufaraj, Mohammad; Gust, Kilian; Moschini, Marco; Foerster, Beat; Soria, Francesco; Mathieu, Romain

    2016-01-01

    Locally advanced (T3b, T4 and N1−N3) and metastatic urothelial bladder cancer (BCa) is a lethal disease with poor survival outcomes. Combination chemotherapy remains the treatment of choice in patients with metastatic disease and an important part of treatment in addition to radical cystectomy (RC) in patients with locally advanced tumour. Approximately half of patients who underwent RC for muscle invasive BCa relapse after surgery with either local recurrence or distant metastasis. This review focuses on the management of muscle invasive, locally advanced and metastatic BCa with emphasis on the role of surgery; to summarize the current knowledge in order to enhance clinical decision-making and counselling process. PMID:27785430

  2. Cetuximab and Everolimus in Treating Patients With Metastatic or Recurrent Colon Cancer or Head and Neck Cancer

    ClinicalTrials.gov

    2012-07-06

    Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Colon Cancer; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Colon

  3. Combined Aortic Resection and Stent Graft Insertion for Local Recurrence of Metastatic Lung Carcinoma Following Stereotactic Radiotherapy: A Case Report

    PubMed Central

    Matsutani, Noriyuki; Imazuru, Tomohiro; Morita, Shigeki; Takahashi, Yusuke; Shimokawa, Tomoki; Kawamura, Masafumi

    2015-01-01

    Stereotactic radiotherapy (SRT) is a useful treatment for malignant ling tumors. However, SRT is associated with complications such as high local recurrence rate and radiation-induced lung injury. Herein, we report a case of combined aortic resection for after SRT. An 82-year-old man underwent SRT for the metastatic lung carcinoma of rectal cancer at left lower lobe. Three years later, chest computed tomography showed local recurrence at the site of radiotherapy, with suspected invasion of the descending aorta. Thoracotomy was performed after metastatic lung carcinoma interpolation of a stent graft in the descending aorta. Because the tumor firmly adhered to the aorta, left lower lung lobe and aortic wall resection was performed. Pathological findings revealed fibrous hypertrophy and adhesion between the visceral pleura and aorta. As shown in our case, combined aortic resection and stent graft insertion is an effective minimally invasive and safe treatment for SRT-induced tissue damage. PMID:26256818

  4. Management of metastatic malignant thymoma with advanced radiation and chemotherapy techniques: report of a rare case.

    PubMed

    D'Andrea, Mark A; Reddy, G Kesava

    2015-02-25

    Malignant thymomas are rare epithelial neoplasms of the anterior superior mediastinum that are typically invasive in nature and have a higher risk of relapse that may ultimately lead to death. Here we report a case of an advanced malignant thymoma that was successfully treated with neoadjuvant chemotherapy followed by surgical resection and subsequently with advanced and novel radiation therapy techniques. A 65-year-old male was diagnosed with a stage IV malignant thymoma with multiple metastatic lesions involving the left peripheral lung and pericardium. Initial neoadjuvant chemotherapy with a cisplatin-based regimen resulted in a partial response allowing the inoperable tumor to become operable. Following surgical resection of the residual disease, the tumor recurred within a year. The patient then underwent a course of targeted three-dimensional intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). Five years after radiation therapy, the localized soft tissue thickening at the left upper lung anterior pleural space had resolved. Seven years after radiation therapy the tumor mass had completely resolved. No recurrences were seen and the patient is well even 8 years after IMRT/IGRT with a favorable outcome. Chemotherapy with targeted three-dimensional IMRT/IGRT should be considered the primary modality for the management of advanced malignant thymoma patients.

  5. Pharmacodynamic study of Disulfiram in Men with Non-metastatic Recurrent Prostate Cancer

    PubMed Central

    Schweizer, Michael T.; Lin, Jianqing; Blackford, Amanda; Bardia, Aditya; King, Serina; Armstrong, Andrew J.; Rudek, Michelle A.; Yegnasubramanian, Srinivasan; Carducci, Michael A.

    2013-01-01

    Background Preclinical drug screens identified disulfiram as a potent in vitro inhibitor of prostate cancer cell growth. Although many mechanisms for its anticancer activity have been proposed, tumor suppressor gene re-expression through promoter demethylation emerged as one of the more plausible. Methods We conducted an open-label, dose escalation trial of disulfiram in men with non-metastatic recurrent prostate cancer after local therapy. Dose escalation occurred if a demethylating “response” [i.e. ≥10% decrease in peripheral blood mononuclear cell (PBMC) global 5meC content] was observed in <3 patients in cohort 1. Cohort 1 and 2 received disulfiram 250 mg and 500 mg daily respectively. The primary endpoint was the proportion of subjects with a demethylation response. Secondary endpoints included rate of PSA progression at 6 months, changes in PSA doubling time and safety/tolerability. Results Changes in global 5meC content were observed in 2 of 9 patients (22.2%) in cohort 1 and 3 of 10 (30.0%) in cohort 2. Only 5 subjects were on trial for ≥6 months, all were in cohort 1 and all had PSA progression by 6 months. No changes in PSA kinetics were observed in either cohort. Disulfiram was poorly tolerated with 6 patients experiencing grade 3 AEs (3 per cohort). Three of the responders displayed pre-treatment instability in their 5meC content. Conclusions A minority of patients had transient global PBMC demethylation changes. Instability in 5meC may limit the reproducibility of these findings, limiting our ability to confirm our hypothesis. Given the toxicities and no clinical benefits, further development of disulfiram should not be pursued in this population. PMID:23958896

  6. Gefitinib (ZD1839, Iressa™) as palliative treatment in recurrent or metastatic head and neck cancer

    PubMed Central

    Kirby, A M; A'hern, R P; D'ambrosio, C; Tanay, M; Syrigos, K N; Rogers, S J; Box, C; Eccles, S A; Nutting, C M; Harrington, K J

    2006-01-01

    To assess the level of activity and toxicity of gefitinib (ZD1839, Iressa™) in a population of patients with locally recurrent and/or metastatic head and neck cancer. Patients were recruited into an expanded access programme through the multidisciplinary head and neck clinics at the Royal Marsden and St George's Hospitals. Patients were required to have received at least one course of standard systemic chemotherapy or radiation therapy, or be medically unfit for chemotherapy. Patients were commenced on single-agent gefitinib at a dose of 500 mg day−1. Clinical, symptomatic and radiological response, time to progression (TTP), survival and toxicity were recorded. A total of 47 patients were enrolled (35 male and 12 female) with a median age of 62 years (range 18–93 years). The observed clinical response rate was 8% with a disease control rate (complete response, partial response, stable disease) of 36%. In all, 34% of patients experienced an improvement in their symptoms. The median TTP and survival were 2.6 and 4.3 months, respectively. Acneiform folliculitis was the most frequent toxicity observed (76%) but the majority of cases were grade 1 or 2. Only four patients experienced grade 3 toxicity of any type (all cases of folliculitis). Gefitinib was well tolerated and yielded symptomatic improvement in one-third of patients. However, this agent appeared to possess limited antitumour activity in this group of patients with head and neck cancer in whom the objective response rate, median TTP and survival were all lower than has been reported in a previous study. PMID:16495923

  7. Bevacizumab and Erlotinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2014-02-11

    Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

  8. [FOLFIRINOX Combination Chemotherapy in Patients with Metastatic or Recurrent Pancreatic Cancer--A Single Institution Experience].

    PubMed

    Takeda, Yutaka; Katsura, Yoshiteru; Ohmura, Yoshiaki; Morimoto, Yoshihiro; Ishida, Tomo; Motoyama, Yurina; Ohneda, Yasuo; Sato, Yasufumi; Kuwahara, Ryuichi; Murakami, Kohei; Naito, Atsushi; Kagawa, Yoshinori; Okishiro, Masatsugu; Takeno, Atsushi; Egawa, Chiyomi; Kato, Takeshi; Tamura, Shigeyuki

    2015-11-01

    Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in Japan. oxaliplatin: L-OHP, irinotecan: CPT-11, fluorouracil: 5-FU, and Leucovorin: l-LV (FOLFIRINOX) combination chemotherapy provided significant improvements in overall and progression-free survival in a phase Ⅲ trial in France and in a phase Ⅱ trial in Japan. As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of FOLFIRINOX in metastatic or recurrent pancreatic cancer. Between October 2014 and July 2015, 10 patients received mFOLFIRINOX as follows: 2-hour infusion of LOHP at 85 mg/m2, 2-hour infusion of l-LV at 200 mg/m2 and infusion of CPT-11 over 90 min at 150 mg/m2, followed by continuous infusion of 5-FU over 46 hours at 2,400mg/m2. Prior to the treatment, a 5-hydroxytryptamine receptor antagonist, aprepitant, and dexamethasone were given. The treatment was repeated every 2 weeks until disease progression, unacceptable toxicity, discontinuation as decided by the investigators, or patient refusal. The mean age of the patients was 65.0 years (range, 59-75 years), and 4 out of 10 patients were men. Only 2 patients had no prior therapy. Nine patients had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0. Eight patients had metastasis and 2 had locally recurrent disease. The median number of treatment cycles was 5 (range, 1-14). The relative dose intensities of 5-FU, L-OHP and CPT-11 were 93.3% (range, 58.3-100%), 84.0% (range, 63.2-100%), and 76.0% (range, 44.4-83.3%), respectively. The major Grade 3 and 4 hematological toxicities were neutropenia (40%), leucopenia (30%), and thrombocytopenia(10%). The major Grade 2 and 3 non-hematological toxicities were diarrhea (30%), nausea (60%), and vomiting (10%). Serious adverse events occurred in 2 patients. Severe biliary tract infection causing sepsis was observed in 1 patient with a biliary stent. Overwhelming post-splenectomy infection was observed in 1 patient

  9. Selective Reoperation for Locally Recurrent or Metastatic Pancreatic Ductal Adenocarcinoma Following Primary Pancreatic Resection

    PubMed Central

    Thomas, Ryan M.; Truty, Mark J.; Nogueras-Gonzalez, Graciela M.; Fleming, Jason B.; Vauthey, Jean-Nicolas; Pisters, Peter W. T.; Lee, Jeffrey E.; Rice, David C.; Hofstetter, Wayne L.; Wolff, Robert A.; Varadhachary, Gauri R.; Wang, Huamin

    2013-01-01

    Background Resection of certain recurrent malignancies can prolong survival, but resection of recurrent pancreatic ductal adenocarcinoma is typically contraindicated because of poor outcomes. Methods All patients from 1992 to 2010 with recurrent pancreatic cancer after intended surgical cure were retrospectively evaluated. Clinicopathologic features were compared from patients who did and did not undergo subsequent reoperation with curative intent to identify factors associated with prolonged survival. Results Twenty-one of 426 patients (5 %) with recurrent pancreatic cancer underwent potentially curative reoperation for solitary local-regional (n=7) or distant (n=14) recurrence. The median disease-free interval after initial resection among reoperative patients was longer for those with lung or local-regional recurrence (52.4 and 41.1 months, respectively) than for those with liver recurrence (7.6 months, p=0.006). The median interval between reoperation and second recurrence was longer in patients with lung recurrence (median not reached) than with liver or local-regional recurrence (6 and 9 months, respectively, p=0.023). Reoperative patients with an initial disease-free interval >20 months had a longer median survival than those who did not (92.3 versus 31.3 months, respectively; p=0.033). Conclusion Patients with a solitary pulmonary recurrence of pancreatic cancer after a prolonged disease-free interval should be considered for reoperation, as they are more likely to benefit from resection versus other sites of solitary recurrence. PMID:22644446

  10. Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

    ClinicalTrials.gov

    2016-10-10

    BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Metastatic Pancreatic Adenocarcinoma; PALB2 Gene Mutation; Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  11. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-12-18

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  12. Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy

    ClinicalTrials.gov

    2015-12-22

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

  13. Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

    ClinicalTrials.gov

    2016-10-10

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  14. Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

    ClinicalTrials.gov

    2016-11-01

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  15. Capecitabine and Vorinostat in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer

    ClinicalTrials.gov

    2015-07-01

    Paranasal Sinus Squamous Cell Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  16. Vascular endothelial platelet endothelial cell adhesion molecule 1 (PECAM-1) regulates advanced metastatic progression

    PubMed Central

    DeLisser, Horace; Liu, Yong; Desprez, Pierre-Yves; Thor, Ann; Briasouli, Paraskevei; Handumrongkul, Chakrapong; Wilfong, Jonathon; Yount, Garret; Nosrati, Mehdi; Fong, Sylvia; Shtivelman, Emma; Fehrenbach, Melane; Cao, Gaoyuan; Moore, Dan H.; Nayak, Shruti; Liggitt, Denny; Kashani-Sabet, Mohammed; Debs, Robert

    2010-01-01

    Most patients who die from cancer succumb to treatment-refractory advanced metastatic progression. Although the early stages of tumor metastasis result in the formation of clinically silent micrometastatic foci, its later stages primarily reflect the progressive, organ-destructive growth of already advanced metastases. Early-stage metastasis is regulated by multiple factors within tumor cells as well as by the tumor microenvironment (TME). In contrast, the molecular determinants that control advanced metastatic progression remain essentially uncharacterized, precluding the development of therapies targeted against it. Here we show that the TME, functioning in part through platelet endothelial cell adhesion molecule 1 (PECAM-1), drives advanced metastatic progression and is essential for progression through its preterminal end stage. PECAM-1–KO and chimeric mice revealed that its metastasis-promoting effects are mediated specifically through vascular endothelial cell (VEC) PECAM-1. Anti–PECAM-1 mAb therapy suppresses both end-stage metastatic progression and tumor-induced cachexia in tumor-bearing mice. It reduces proliferation, but not angiogenesis or apoptosis, within advanced tumor metastases. Because its antimetastatic effects are mediated by binding to VEC rather than to tumor cells, anti–PECAM-1 mAb appears to act independently of tumor type. A modified 3D coculture assay showed that anti–PECAM-1 mAb inhibits the proliferation of PECAM-1–negative tumor cells by altering the concentrations of secreted factors. Our studies indicate that a complex interplay between elements of the TME and advanced tumor metastases directs end-stage metastatic progression. They also suggest that some therapeutic interventions may target late-stage metastases specifically. mAb-based targeting of PECAM-1 represents a TME-targeted therapeutic approach that suppresses the end stages of metastatic progression, until now a refractory clinical entity. PMID:20926749

  17. Metronomic cyclophosphamide therapy in hormone-naive patients with non-metastatic biochemical recurrent prostate cancer: a phase II trial.

    PubMed

    Calcagno, Fabien; Mouillet, Guillaume; Adotevi, Olivier; Maurina, Tristan; Nguyen, Thierry; Montcuquet, Philippe; Curtit, E; Kleinclauss, F; Pivot, Xavier; Borg, Christophe; Thiery-Vuillemin, Antoine

    2016-08-01

    After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non-metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials. PMID:27400698

  18. Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma

    ClinicalTrials.gov

    2016-06-14

    Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Oral Cavity Adenoid Cystic Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Oral Cavity Adenoid Cystic Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Oral Cavity Adenoid Cystic Carcinoma

  19. Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

    ClinicalTrials.gov

    2016-06-09

    Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

  20. Olaparib and Hsp90 Inhibitor AT13387 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2016-09-12

    Estrogen Receptor Negative; HER2/Neu Negative; High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Metastatic Solid Neoplasm; Primary Peritoneal High Grade Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

  1. Lapatinib Ditosylate in Treating Patients With Metastatic or Recurrent Head and Neck Cancer

    ClinicalTrials.gov

    2015-04-14

    Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  2. Application of a Drug-Induced Apoptosis Assay to Identify Treatment Strategies in Recurrent or Metastatic Breast Cancer

    PubMed Central

    Bosserman, Linda; Rogers, Karl; Willis, Carl; Davidson, Dirk; Whitworth, Pat; Karimi, Misagh; Upadhyaya, Gargi; Rutledge, James; Hallquist, Allan; Perree, Mathieu; Presant, Cary A.

    2015-01-01

    Background A drug-induced apoptosis assay has been developed to determine which chemotherapy drugs or regimens can produce higher cell killing in vitro. This study was done to determine if this assay could be performed in patients with recurrent or metastatic breast cancer patients, to characterize the patterns of drug-induced apoptosis, and to evaluate the clinical utility of the assay. A secondary goal was to correlate assay use with clinical outcomes. Methods In a prospective, non-blinded, multi institutional controlled trial, 30 evaluable patients with recurrent or metastatic breast cancer who were treated with chemotherapy had tumor samples submitted for the MiCK drug-induced apoptosis assay. After receiving results within 72 hours after biopsy, physicians could use the test to determine therapy (users), or elect to not use the test (non-users). Results The assay was able to characterize drug-induced apoptosis in tumor specimens from breast cancer patients and identified which drugs or combinations gave highest levels of apoptosis. Patterns of drug activity were also analyzed in triple negative breast cancer. Different drugs from a single class of agents often produced significantly different amounts of apoptosis. Physician frequently (73%) used the assay to help select chemotherapy treatments in patients, Patients whose physicians were users had a higher response (CR+PR) rate compared to non-users (38.1% vs 0%, p = 0.04) and a higher disease control (CR+PR+Stable) rate (81% vs 25%, p<0.01). Time to relapse was longer in users 7.4 mo compared to non-users 2.2 mo (p<0.01). Conclusions The MiCK assay can be performed in breast cancer specimens, and results are often used by physicians in breast cancer patients with recurrent or metastatic disease. These results from a good laboratory phase II study can be the basis for a future larger prospective multicenter study to more definitively establish the value of the assay. Trial Registration Clinicaltrials.gov NCT

  3. Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2016-05-16

    Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

  4. Trastuzumab in Treating Patients With Metastatic or Recurrent Salivary Gland Cancer

    ClinicalTrials.gov

    2013-02-27

    High-grade Salivary Gland Mucoepidermoid Carcinoma; Recurrent Salivary Gland Cancer; Salivary Gland Acinic Cell Tumor; Salivary Gland Adenocarcinoma; Salivary Gland Poorly Differentiated Carcinoma; Stage IVA Salivary Gland Cancer; Stage IVB Salivary Gland Cancer; Stage IVC Salivary Gland Cancer

  5. Sunitinib Malate in Treating Patients With Iodine-Refractory Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2015-09-28

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma

  6. Recurrent thrombotic occlusions of arteries and veins caused by intravascular metastatic adenocarcinoma.

    PubMed Central

    Levi, M; Bronkhorst, C; Noorduyn, L A; Vreeken, J

    1994-01-01

    The occurrence of unexplained, rapidly recurring occlusions of arteries and veins in a previously healthy young woman is described. Post mortem examination showed no macroscopic abnormalities but revealed microscopic metastatic adenocarcinoma with remarkable intravascular localisation of the malignant cells. Whereas highly sensitive markers for the existence of systemic activation of blood coagulation remained within the normal range, it is suggested that specific characteristics of the tumour cells may have been responsible for this particular clinical presentation. PMID:7962660

  7. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients.

  8. Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors

    ClinicalTrials.gov

    2016-05-26

    High-grade Salivary Gland Mucoepidermoid Carcinoma; Low-grade Salivary Gland Mucoepidermoid Carcinoma; Recurrent Salivary Gland Cancer; Salivary Gland Acinic Cell Tumor; Salivary Gland Adenocarcinoma; Salivary Gland Adenoid Cystic Carcinoma; Salivary Gland Anaplastic Carcinoma; Salivary Gland Malignant Mixed Cell Type Tumor; Salivary Gland Poorly Differentiated Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IV Salivary Gland Cancer

  9. Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2016-10-13

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  10. Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2016-10-05

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  11. Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-03-01

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Hereditary Breast/Ovarian Cancer - BRCA1; Hereditary Breast/Ovarian Cancer - BRCA2; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  12. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  13. Management of afferent loop obstruction from recurrent metastatic pancreatic cancer using a venting gastrojejunostomy

    PubMed Central

    Bakes, Debbie; Cain, Christian; King, Michael; Dong, Xiang Da (Eric)

    2013-01-01

    Pancreatic cancer is an aggressive malignancy potentially curable with surgical intervention. Following pancreaticoduodenectomy for suspected pancreatic head malignancy, patients have a high risk for both immediate and delayed problems due to surgical complications and recurrent disease. We report here a patient with pancreatic cancer treated with pancreaticoduodenectomy who developed recurrent disease resulting in obstruction of the afferent limb. The patient developed biliary obstruction and cholangitis at presentation. Her biliary tree failed to dilate which precluded safe percutaneous biliary decompression. During surgical exploration, she was found to have a dilated afferent limb at the level of the transverse mesocolon. The patient underwent decompression of the afferent limb as well as the biliary tree using a venting gastrojejunostomy to the blind loop. This represents a novel surgical approach for management of this complicated and difficult problem. PMID:24363832

  14. Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-02-18

    Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

  15. Systemic therapies for recurrent and/or metastatic salivary gland cancers.

    PubMed

    Vattemi, Emanuela; Graiff, Claudio; Sava, Teodoro; Pedersini, Rebecca; Caldara, Alessia; Mandarà, Marta

    2008-03-01

    Salivary gland carcinomas are rare cancers, comprising 1-5% of head and neck cancers. They represent a morphologically and clinically diverse group of tumors. The most commonly histopathologic types are mucoepidermoid cancer, adenoid cystic cancer and adenocarcinomas. Malignant salivary gland tumors generally present as painless, slow-growing tumors that are indistinguishable from benign tumors. Surgery is the principal treatment and is curative in early stage. Radiation therapy should be considered in most patients after surgical resection. Chemotherapy is reserved for palliative treatment of metastatic disease but results are disappointing. Recent studies have investigated the role of targeted therapies in a palliative setting. Multicentre cooperative group clinical trials are required to assess novel therapies to maximize patient resources in this uncommon tumor.

  16. [Molecular targeting agents for advanced or recurrent gastric cancer patients].

    PubMed

    Fuse, Nozomu

    2012-10-01

    The combination of fluoropyrimidine and platinum with or without epirubicin or docetaxel has been regarded as standard chemotherapy for advanced or recurrent gastric cancer patients. Recently, trastuzumab with conventional chemotherapy for human epidermal growth factor receptor(HER)2 positive gastric cancer patients was proved to be effective in terms of survival benefit and has become one of standard treatment options. Other molecular target agents, such as HER1, HER2, vascular endothelial growth factor, hepatocyte growth factor/c-Met, fibroblast growth factor and mammalian target of rapamycin inhibitors were and are being evaluated in clinical trials. However, no agents other than trastuzumab have shown clear survival benefit. The predictive biomarker seems to be necessary for developing new molecular targeting agents for gastric cancer with heterogeneity.

  17. Motility Related Actinin Alpha-4 Is Associated with Advanced and Metastatic Ovarian Carcinoma

    PubMed Central

    Barbolina, Maria V.; Adley, Brian P.; Kelly, David L.; Fought, Angela J.; Scholtens, Denise; Shea, Lonnie D.; Sharon Stack, M.

    2010-01-01

    Advanced and metastatic ovarian cancer is a leading cause of death from gynecologic malignancies. A more detailed understanding of the factors controlling invasion and metastasis may lead to novel anti-metastatic therapies. To model cellular interactions that occur during intraperitoneal metastasis, comparative cDNA microarray analysis and confirmatory real time RT-PCR were employed to uncover changes in gene expression that may occur in late stage ovarian cancer in response to microenvironmental cues, particularly native three-dimensional collagen I. Gene expression in human ovarian carcinoma tissues was evaluated on the RNA and protein level using real time RT-PCR and immunohistochemistry. Cell invasion and migration were evaluated in a collagen invasion assay and a scratch wound assay. Three-dimensional collagen I culture led to differential expression of several genes. The role of actinin alpha-4 (ACTN4), a cytosketeton-associated protein implicated in regulation of cell motility, was examined in detail. ACTN4 RNA and protein expression were associated with advanced and metastatic human ovarian carcinoma. This report demonstrates that a cytoskeletal-associated protein ACTN4 is upregulated by three-dimensional collagen culture conditions, leading to increased invasion and motility of ovarian cancer cells. Expression of ACTN4 in human ovarian tumors was found to be associated with advanced stage disease and peritoneal metastases. PMID:18362906

  18. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  19. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; Mello, Ramon Andrade de

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  20. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato

    2013-01-01

    Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. PMID:22886480

  1. FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast cancer.

    PubMed

    Siggelkow, Wulf; Rath, Werner; Buell, Udalrich; Zimny, Michael

    2004-06-01

    Breast cancer continues to be one of the most common cancers in North America and Western Europe. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG PET) represents a non-invasive functional imaging modality that is based on metabolic characteristics of malignant tumours. In breast cancer, FDG PET is more accurate than conventional methods for staging of distant metastases or local recurrences and enables early assessment of treatment response in patients undergoing primary chemotherapy. Recent data indicate a rationale for the use of FDG PET in cases of asymptomatically elevated tumour marker levels in the presence of uncertain results of conventional imaging. Despite the fact that PET cannot rule out microscopic disease, it does have particular value in providing, in a single examination, a reliable assessment of the true extent of the disease. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the assessment of asymptomatic patients with elevated tumour marker levels. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance. PMID:15146295

  2. [Advanced and Metastatic Lung Cancer – What is new in the Diagnosis and Therapy?].

    PubMed

    Rothschild, Sacha I

    2015-07-01

    Lung cancer is one of the most common types of malignancies worldwide. The majority of patients are diagnosed with an incurable advanced/metastatic stage disease. Palliative treatment approaches improve the survival and the quality of life of these patients. Lung cancer is subdivided according to histology and molecular biology. The most important classification separates small cell from non-small cell lung cancer. In the subgroup of non-small cell lung cancer novel treatment approaches coming along with an improved prognosis have been established during the last decade. The current manuscript provides an overview on current treatment options for metastatic lung cancer. Furthermore, an outlook on promising future treatment options is provided.

  3. Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder

    ClinicalTrials.gov

    2013-01-11

    Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Advanced Adult Primary Liver Cancer; Gastrointestinal Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  4. Phase II trial of 4'-epi-doxorubicin in locally advanced or metastatic gastric cancer.

    PubMed

    Cazap, E; Estevez, R; Bruno, M; Levy, D; Algamiz, C; Chacon, R; Badano, C; Romero, A; Desimone, G; Roca, E

    1988-06-30

    Patients with locally advanced or metastatic gastric adenocarcinoma received an i.v. bolus of 4'-epi-doxorubicin, 75/mg/m2/cycle, every 21 days. Partial responses were observed in 5 of 23 evaluable patients (21.7%). Treatment was generally well tolerated and toxicity was mild. The response rate to epirubicin appears to be very similar to that reported for doxorubicin. Larger doses of epirubicin could be safely used in future studies, and further evaluation of epirubicin in phase III trials is indicated.

  5. Molecular targeted therapies in advanced or metastatic chordoma patients: facts and hypotheses.

    PubMed

    Lebellec, Loïc; Aubert, Sébastien; Zaïri, Fahed; Ryckewaert, Thomas; Chauffert, Bruno; Penel, Nicolas

    2015-07-01

    Chordomas, derived from undifferentiated notochordal remnants, represent less than 4% of bone primary tumors. Despite surgery followed by radiotherapy, local and metastatic relapses are frequent. In case of locally advanced or metastatic chordomas, medical treatment is frequently discussed. While chemotherapy is ineffective, it would appear that some molecular targeted therapies, in particular imatinib, could slow down the tumor growth in case-reports, retrospective series, and phase I or II trials. Nineteen publications, between January 1990 and September 2014, have been found describing the activity of these targeted therapies. A systematic analysis of these publications shows that the best objective response with targeted therapies was stabilization in 52 to 69% of chordomas. Given the indolent course of advanced chordoma and because of the absence of randomized trial, the level of evidence to treat chordomas with molecular therapy is low (level III), whatever the drug. Furthermore, we could not draw firm conclusion on the activity of imatinib. Other putative targets have also been described. Therefore, further clinical trials are expected, especially with these targets. Nevertheless, it seems essential, in those future studies, to consider the naturally slow course of the disease.

  6. Subcutaneous nephrovesical bypass: Treatment for ureteral obstruction in advanced metastatic disease

    PubMed Central

    WANG, YUNYAN; WANG, GONGCHENG; HOU, PEIJIN; ZHUANG, HAIJUN; YANG, XIAOSONG; GU, SHUO; WANG, HENGBING; JI, LU; XU, ZONGYUAN; MENG, JUNSONG

    2015-01-01

    The aim of the present study was to explore the value of subcutaneous nephrovesical bypass (SNVB) for the treatment of ureteral obstruction due to pelvic metastatic disease. SNVB stents (n=30) were implanted in 24 patients with advanced metastatic disease between January 2008 and December 2012. Urinalysis, serum creatinine (SCr), glomerular filtration rate (GFR), quality of life (QoL) scores, and renal ultrasonography were evaluated at follow-up. The SNVB procedures were successful in all 24 patients. Patient follow-ups occurred at an average of 10.6 months. Preoperative hydronephrosis was eliminated in 16 cases (53.3%) and reduced in the remaining patients. Following surgery, SCr levels reduced significantly from 256±46 to 124±23 μmol/l (P<0.001). GFRs increased from 25±4.8 to 45±5.3 ml/min (P<0.01). The mean QoL scores were 3.4±1.4 preoperatively and 7.6±1.0 postoperatively (P<0.001). The results showed that SNVB is a minimally invasive, effective and safe procedure for patients with ureteral obstruction resulting from advanced malignant disease. As an alternative procedure to percutaneous nephrostomy, SNVB offers patients a better QoL. PMID:25435997

  7. Exceptional Response to Systemic Therapy in Advanced Metastatic Gastric Cancer: A Case Report

    PubMed Central

    Hartley, Marion; Manning, Maria A; Carroll, John E; Xiu, Joanne; Smaglo, Brandon G; Mikhail, Sameh; Salem, Mohamed E

    2016-01-01

    Gastroesophageal adenocarcinomas represent one of the top five most common types of cancer worldwide. Despite significant advancement, it is still not known which first-line chemotherapy option is best matched to an individual patient. The vast advances in molecular biology have led to the discovery of many potential predictive biomarkers, such as HER-2 neu, thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and topoisomerase-1 (TOPO1). These markers could allow us to select treatment based on an individual’s tumor profile, resulting in an improvement of outcome. Our report highlights two patients with metastatic gastric cancer that achieved an exceptional response with traditional therapy and provides insights into the future perspectives of molecular profile-directed chemotherapy. PMID:26918225

  8. Viral Therapy In Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-08-24

    Estrogen Receptor Negative; Estrogen Receptor Positive; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; HER2/Neu Positive; Invasive Breast Carcinoma; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Head and Neck Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  9. Case study of a chaplain's spiritual care for a patient with advanced metastatic breast cancer.

    PubMed

    Cooper, Rhonda S

    2011-01-01

    The case study seeks to describe an oncology chaplain's pastoral relationship with a 64-year-old woman with advanced metastatic breast cancer. The patient's distress was complicated by a history of anxiety and other chronic medical conditions. Approximately 16 pastoral encounters occurred during the last year of the patient's life. The patient, chaplain, and the pastoral conversations are presented as well as a retrospective assessment of them. The chaplain's interventions were appropriate for the patient's spiritual needs, particularly in regard to her fear of death, loneliness, grief that her life was "too short" and estrangement from her inherited faith tradition, with observable benefits for the patient. The oncology chaplain has a distinctive role in the healthcare team as one who can meet the patient at the point of their spiritual need, provide appropriate interventions and, thereby, ameliorate the distress, particularly in regard to death anxiety, peace of mind, and issues of meaning.

  10. The European Medicines Agency Review of Pertuzumab for the Treatment of Adult Patients With HER2-Positive Metastatic or Locally Recurrent Unresectable Breast Cancer: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use

    PubMed Central

    Borregaard, Jeanett; Jensen, Kristina Bech; Ersbøll, Jens; Galluzzo, Sara; Giuliani, Rosa; Ciceroni, Cinzia; Melchiorri, Daniela; Salmonson, Tomas; Bergh, Jonas; Schellens, Jan H.; Pignatti, Francesco

    2014-01-01

    Pertuzumab is a recombinant humanized monoclonal antibody that specifically targets the extracellular dimerization domain (subdomain II) of HER2. Based on the positive opinion from the European Medicines Agency (EMA) on March 4, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pertuzumab (Perjeta) for use in combination with trastuzumab and docetaxel for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease. The demonstration of clinical benefit for pertuzumab was based on a single, phase III, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel in previously untreated patients with locally advanced or metastatic HER2-positive breast cancer. In the primary analysis, median progression-free survival was 18.5 months in the pertuzumab group compared with 12.4 months in the placebo group (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.51–0.75; p < .0001). For the secondary endpoints, overall survival (HR: 0.66; 95% CI: 0.52–0.84; p = .0008) and objective response rate (80.2% vs. 69.3%) were also favored in the pertuzumab group. Toxicity was similar between groups except for higher incidence of diarrhea, rash, mucosal inflammation, dry skin, and neutropenia for pertuzumab compared with placebo. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu). PMID:24928613

  11. Prostate-specific antigen doubling time and survival in patients with advanced metastatic prostate cancer.

    PubMed

    Loberg, Robert D; Fielhauer, Jeffery R; Pienta, Brian A; Dresden, Scott; Christmas, Patty; Kalikin, Linda M; Olson, Karin B; Pienta, Kenneth J

    2003-12-29

    The relation between tumor kinetics and disease progression in patients with hormone-refractory prostate cancer (HRPC) has not been well described. Biochemical recurrence of prostate cancer is characterized by detectable prostate-specific antigen (PSA) levels after treatment and occurs in approximately 30% of patients after therapy for apparent localized disease. An increase in PSA almost always occurs before clinical evidence of disease. The ability to identify early biochemical failure in patients to assess disease aggressiveness and guide changes in treatment needs to be examined. We examined serial PSA data from 249 patients with metastatic disease to assess PSA doubling time (PSADT) in hormone-naive prostate cancer (HNPC) and HRPC states. In a subset of patients, the relation of PSADT to Gleason score and survival was studied. PSADT decreased from 37.5 +/- 4.5 weeks to 15.6 +/- 1.6 weeks (mean +/- SEM) in patients with HNPC versus HRPC. In this small study, PSADT did not correlate with Gleason score, survival from start of hormonal treatment, length of time receiving hormone therapy, or survival in the HRPC state. The decrease in PSADT with disease state may help provide insight into understanding the biology of late-stage disease.

  12. The Role of Irradiation in the Management of Locally Recurrent Non-Metastatic Soft Tissue Sarcoma of Extremity/Trunkal Locations

    PubMed Central

    Mott, Michael P.; Lucas, David R.; Miller, Peter R.; Kraut, Michael J.

    2004-01-01

    Background: Patients who have had initial curative intent therapy for non-metastatic soft tissue sarcoma, and who subsequently relapse at the initial site without evidence of metastatic disease, have various options regarding local treatment. The treatment options available will be determined by the extent of relapse, previous therapy rendered, and patient characteristics. We reported on a series of 31 patients treated initially with only surgery for extremity/trunkal high-grade soft tissue sarcoma and then seen for recurrence at our institution between 1980 and 1999. Local re-treatment consisted of combined modality therapy, most often aggressive surgical debulking/resection and irradiation, in an effort to reduce the need for amputation and, where anatomically allowable, to maintain a functional limb. We report our results in re-establishing local control, subsequent survival, and complication rates. Methods: Thirty-one patients with locally recurrent, non-metastatic high-grade soft tissue sarcoma, (excluding extraabdominal desmoid) were retrospectively reviewed to determine local control, survival, and complication rates associated with the relapsed disease. All patients had multimodality re-treatment most often utilizing aggressive surgical debulking and irradiation. The irradiation consisted of either external beam alone, brachytherapy alone, or a combination of external beam and brachytherapy. Nine patients also received multi-agent, multi-cycle chemotherapy using various regimens. In addition, the impact of surgical margin at the time of re-resection (gross versus microscopic disease), radiation treatment type, total radiation dose delivered, size of relapse, histological sub-type, sex and age, were evaluated to determine if they had any impact on the re-establishment of local control and subsequent survival. Results: Local control was re-established in 25 of 31 (80.6%) patients. Two additional patients with isolated local relapse after irradiation were

  13. ICON 2013: practical consensus recommendations for hormone receptor-positive Her2-negative advanced or metastatic breastcancer.

    PubMed

    Parikh, P M; Gupta, S; Dawood, S; Rugo, H; Bhattacharyya, G S; Agarwal, A; Chacko, R; Sahoo, T P; Babu, G; Agarwal, S; Munshi, A; Goswami, C; Smruti, B K; Bondarde, S; Desai, C; Rajappa, S; Somani, N; Singh, M; Nimmagadda, R; Pavitran, K; Mehta, A; Parmar, V; Desai, S; Nair, R; Doval, D

    2014-01-01

    The management of hormone receptor-positive Her2-negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

  14. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-06-20

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  15. Metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model is inhibited by neoadjuvant chemotherapy in combination with fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore.

    PubMed

    Hiroshima, Yukihiko; Maawy, Ali; Zhang, Yong; Murakami, Takashi; Momiyama, Masashi; Mori, Ryutaro; Matsuyama, Ryusei; Katz, Matthew H G; Fleming, Jason B; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Endo, Itaru; Hoffman, Robert M; Bouvet, Michael

    2014-01-01

    The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS+NAC; FGS only; and FGS+NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS had no benefit over BLS to prevent metastatic recurrence. NAC in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence.

  16. Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

    ClinicalTrials.gov

    2015-06-01

    Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

  17. Advances in Personalized Targeted Treatment of Metastatic Melanoma and Non-Invasive Tumor Monitoring

    PubMed Central

    Klinac, Dragana; Gray, Elin S.; Millward, Michael; Ziman, Mel

    2013-01-01

    Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved the way for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs) provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time. We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management. PMID:23515890

  18. Lapatinib in Treating Patients With Recurrent and/or Metastatic Adenoid Cystic Cancer or Other Salivary Gland Cancers

    ClinicalTrials.gov

    2013-10-10

    High-grade Salivary Gland Carcinoma; High-grade Salivary Gland Mucoepidermoid Carcinoma; Low-grade Salivary Gland Carcinoma; Low-grade Salivary Gland Mucoepidermoid Carcinoma; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Salivary Gland Acinic Cell Tumor; Salivary Gland Adenocarcinoma; Salivary Gland Adenoid Cystic Carcinoma; Salivary Gland Malignant Mixed Cell Type Tumor

  19. Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy

    PubMed Central

    Park, Inkeun; Choi, Seung Joon; Kim, Young Saing; Ahn, Hee Kyung; Hong, Junshik; Sym, Sun Jin; Park, Jinny; Cho, Eun Kyung; Lee, Jae Hoon; Shin, Yong Ju; Shin, Dong Bok

    2016-01-01

    Purpose The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. Materials and Methods Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed. Results A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. Conclusion Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials. PMID:27034148

  20. Risk of recurrence and conditional survival in complete responders treated with TKIs plus or less locoregional therapies for metastatic renal cell carcinoma

    PubMed Central

    Santini, Daniele; Santoni, Matteo; Conti, Alessandro; Procopio, Giuseppe; Verzoni, Elena; Galli, Luca; di Lorenzo, Giuseppe; De Giorgi, Ugo; De Lisi, Delia; Nicodemo, Maurizio; Maruzzo, Marco; Massari, Francesco; Buti, Sebastiano; Altobelli, Emanuela; Biasco, Elisa; Ricotta, Riccardo; Porta, Camillo; Vincenzi, Bruno; Papalia, Rocco; Marchetti, Paolo; Burattini, Luciano; Berardi, Rossana; Muto, Giovanni; Montironi, Rodolfo; Cascinu, Stefano; Tonini, Giuseppe

    2016-01-01

    PURPOSE We retrospectively analyzed the risk of recurrence and conditional Disease-Free Survival (cDFS) in 63 patients with complete remission during treatment with tirosin kinase inhibitor (TKI), alone or with local treatment in metastatic renal cell carcinoma. RESULTS 37% patients achieve CR with TKI alone, while 63% with additional loco-regional treatments. 49% patients recurred after CR, with a median Disease free survival of 28.2 months. Patients treated with multimodal approaches present lower rate of recurrence (40% vs 61%) and longer Disease free survival compared to patient treated with TKI alone (16.5 vs 41.9 months, p=0.039).Furthermore the rate of recurrence was higher in patients with brain (88%), pancreatic (71%) and bone metastasis (50%). Patients who continued TKI therapy after complete response had a longer disease free survival than patients who stopped therapy, although the difference was not significant (42.1 vs 25.1 months, p=0.254). 2y-cDFS was better in patients treated with multimodal treatment and who continued TKIs than the other patient arms. CONCLUSIONS The prognostic value of CR depends on the site where was obtained and how was obtained (with or without locoregional treatment). Cessation of TKI should be carefully considered in complete responder patients. PMID:27027342

  1. Once-Weekly, High-Dose Stereotactic Body Radiotherapy for Lung Cancer: 6-Year Analysis of 60 Early-Stage, 42 Locally Advanced, and 7 Metastatic Lung Cancers

    SciTech Connect

    Salazar, Omar M. Sandhu, Taljit S.; Lattin, Paul B.; Chang, Jung H.; Lee, Choon K.; Groshko, Gayle A.; Lattin, Cheryl J.

    2008-11-01

    Purpose: To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. Methods and Materials: A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy{sub 10}). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy{sub 10}. Respiration gating was used in 46%. Results: The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. Conclusions: SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older

  2. Propranolol Hydrochloride in Treating Patients With Locally Recurrent or Metastatic Solid Tumors That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-09-28

    Male Breast Cancer; Recurrent Melanoma; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Hepatocellular Carcinoma

  3. Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial

    PubMed Central

    Symonds, R Paul; Gourley, Charlie; Davidson, Susan; Carty, Karen; McCartney, Elaine; Rai, Debbie; Banerjee, Susana; Jackson, David; Lord, Rosemary; McCormack, Mary; Hudson, Emma; Reed, Nicholas; Flubacher, Maxine; Jankowska, Petra; Powell, Melanie; Dive, Caroline; West, Catharine M L; Paul, James

    2015-01-01

    Summary Background Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20–30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer. Methods In this randomised, double-blind, placebo-controlled phase 2 trial, which was done in 17 UK cancer treatment centres, patients aged 18 years or older initially diagnosed with metastatic carcinoma or who subsequently developed metastatic disease or local pelvic recurrence after radical treatment that was not amenable to exenterative surgery were recruited. Eligible patients received carboplatin AUC of 5 plus paclitaxel 175 mg/m2 by infusion every 3 weeks for a maximum of six cycles and were randomised centrally (1:1) through a minimisation approach to receive cediranib 20 mg or placebo orally once daily until disease progression. The stratification factors were disease site, disease-free survival after primary therapy or primary stage IVb disease, number of lines of previous treatment, Eastern Cooperative Oncology Group performance status, and investigational site. All patients, investigators, and trial personnel were masked to study drug allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat, and the safety analysis included all patients who received at least one dose of study drug. This trial is registered with the ISCRTN registry, number ISRCTN23516549, and has been completed. Findings Between Aug 19, 2010, and July 27, 2012, 69 patients were enrolled and randomly assigned to cediranib (n=34) or placebo (n=35). After a median

  4. Human monoclonal antibody 99mTc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment.

    PubMed

    Krause, B J; Baum, R P; Staib-Sebler, E; Lorenz, M; Niesen, A; Hör, G

    1997-01-01

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%.

  5. [Recurrence and survival rate of advanced gastric cancer after preoperative intraarterial EAP I injection therapy].

    PubMed

    Takeuchi, K; Taniguchi, H; Miyata, K; Koyama, H; Tanaka, H; Ueshima, Y; Okano, S; Oguro, A; Itoh, A; Sawai, K

    1993-08-01

    In our department, curative operations were performed for 32 patients with advanced gastric cancer from April 1989 to August 1990. Preoperative intra-arterial injection therapy with etoposide (100 mg), pirarubicin (20 mg) and cisplatin (20 mg) was given 18 patients. Recurrence and survival rate were investigated. The survival rate of patients with preoperative intra-arterial injection therapy 45 months after operation was 59.2%, while that of patients without preoperative intra-arterial injection therapy was 75.8%. There were no significant differences between these two groups. Three lymph node recurrences were seen in patients with preoperative intra-arterial injection therapy (recurrence rate, 16.7%). Four recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination 2, liver 1, local 1; recurrence rate, 28.6%). We earlier reported that preoperative intra-arterial cisplatin (40 or 60 mg) injection therapy may reduce the incidence of lymph node recurrence and liver metastasis but may not be effective to prevent postoperative peritoneal recurrence, while no peritoneal dissemination was observed in patients with preoperative intra-arterial EAP I injection therapy. Thus, it was concluded that further study of combination and dose of anti-cancer drug may improve effectiveness of preoperative intra-arterial injection therapy for gastric cancer.

  6. Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

    ClinicalTrials.gov

    2016-07-15

    Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Pancreatic Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Gallbladder Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer

  7. New strategies in metastatic melanoma: oncogene-defined taxonomy leads to therapeutic advances.

    PubMed

    Flaherty, Keith T; Fisher, David E

    2011-08-01

    The discovery of BRAF and KIT mutations provided the first basis for a molecular classification of cutaneous melanoma on therapeutic grounds. As BRAF-targeted therapy quickly moves toward regulatory approval and incorporation as standard therapy for patients with metastatic disease, proof of concept has also been established for targeting mutated KIT in melanoma. NRAS mutations have long been known to be present in a subset of melanomas and represent an elusive subgroup for targeted therapies. Matching patient subgroups defined by genetic aberrations in the phosphoinositide 3-kinase and p16/cyclin dependent kinase 4 (CDK4) pathways with appropriate targeted therapies has not yet been realized. And, an increasing understanding of lineage-specific transcriptional regulators, most notably MITF, and how they may play a role in melanoma pathophysiology, has provided another axis to approach with therapies. The foundation has been established for individual oncogene targeting, and current investigations seek to understand the intersection of these susceptibilities and other described potential targets and pathways. The melanoma field stands poised to take the lead among cancer subtypes in advancing combination therapy strategies that simultaneously target multiple biologic underpinnings of the disease. PMID:21670085

  8. Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-09-06

    Head and Neck Squamous Cell Carcinoma; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharynx Carcinoma; Recurrent Salivary Gland Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage III Major Salivary Gland Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage IV Nasopharyngeal Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma

  9. The combination of insulin-like growth factor receptor 1 (IGF1R) antibody cixutumumab and mitotane as a first-line therapy for patients with recurrent/metastatic adrenocortical carcinoma: a multi-institutional NCI-sponsored trial.

    PubMed

    Lerario, Antonio M; Worden, Francis P; Ramm, Carole A; Hesseltine, Elizabeth A; Hasseltine, Elizabeth A; Stadler, Walter M; Else, Tobias; Shah, Manisha H; Agamah, Edem; Rao, Krishna; Hammer, Gary D

    2014-08-01

    Adrenocortical carcinoma (ACC) is an aggressive malignancy, which lacks an effective systemic treatment. Abnormal activation of insulin-like growth factor receptor 1 (IGF1R) has been frequently observed. Preclinical studies demonstrated that pharmacological inhibition of IGF1R signaling in ACC has antiproliferative effects. A previous phase I trial with an IGF1R inhibitor has demonstrated biological activity against ACC. The objective of this study is to assess the efficacy of the combination of the IGF1R inhibitor cixutumumab (IMC-A12) in association with mitotane as a first-line treatment for advanced/metastatic ACC. We conducted a multicenter, randomized double-arm phase II trial in patients with irresectable recurrent/metastatic ACC. The original protocol included two treatment groups: IMC-A12 + mitotane and mitotane as a single agent, after an initial single-arm phase for safety evaluation with IMC-A12 + mitotane. IMC-A12 was dosed at 10 mg/kg intravenously every 2 weeks. The starting dose for mitotane was 2 g daily, subsequently adjusted according to serum levels/symptoms. The primary endpoint was progression-free survival (PFS) according to RECIST (Response Evaluation Criteria in Solid Tumors). This study was terminated before the randomization phase due to slow accrual and limited efficacy. Twenty patients (13 males, 7 females) with a median age of 50.2 years (range 21.9-79.6) were enrolled for the single-arm phase. Therapeutic effects were observed in 8/20 patients, including one partial response and seven stable diseases. The median PFS was 6 weeks (range 2.66-48). Toxic events included two grade 4 (hyperglycemia and hyponatremia) and one grade 5 (multiorgan failure). Although the regimen demonstrated activity in some patients, the relatively low therapeutic efficacy precluded further studies with this combination of drugs. PMID:24849545

  10. MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-01-23

    Adult Grade III Lymphomatoid Granulomatosis; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  11. Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2015-03-11

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  12. Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma

    ClinicalTrials.gov

    2015-12-03

    Fallopian Tube Cancer; Female Reproductive Cancer; Ovarian Carcinosarcoma; Ovarian Sarcoma; Recurrent Ovarian Epithelial Cancer; Recurrent Uterine Sarcoma; Stage III Ovarian Epithelial Cancer; Stage III Uterine Sarcoma; Stage IV Ovarian Epithelial Cancer; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma

  13. Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

    ClinicalTrials.gov

    2016-10-05

    Recurrent Colorectal Carcinoma; Recurrent Lung Carcinoma; Recurrent Pancreatic Carcinoma; Solid Neoplasm; Stage III Lung Cancer; Stage III Pancreatic Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Colorectal Cancer; Stage IV Lung Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

  14. Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-07-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  15. Advances of Targeted Therapy in Treatment of Unresectable Metastatic Colorectal Cancer

    PubMed Central

    Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    Despite being one of the most frequently diagnosed cancers worldwide, prognosis of metastatic colorectal cancer (CRC) was poor. Development and introduction of biologic agents in treatment of patients with metastatic CRC have brought improved outcomes. Monoclonal antibodies directing epidermal growth factor receptors and vascular endothelial growth factor are main biologic agents currently used in treatment of metastatic CRC. Encouraged by results from many clinical trials demonstrating efficacy of those monoclonal antibodies, the combination therapy with those targeted agents and conventional chemotherapeutic agents has been established as the standard therapy for patients with metastatic CRC. However, emergency of resistance to those target agents has limited the efficacy of treatment, and strategies to overcome the resistance are now being investigated by newly developed biological techniques clarifying how to acquire resistance. Here, we introduce mechanisms of action of the biologic agents currently used for treatment of metastatic CRC and several landmark historical clinical studies which have changed the main stream of treatment. The mechanism of resistance to those agents, one of serious problems in treatment metastatic CRC, and ongoing clinical trials to overcome the limitations and improve treatment outcomes will also be presented in this review. PMID:27127793

  16. Sequence of treatment in locally advanced and metastatic renal cell carcinoma

    PubMed Central

    Fischer, Stefanie; Gillessen, Silke

    2015-01-01

    The spectrum of drugs that have shown activity in advanced or metastatic renal cell carcinoma (RCC) has led to a debate on the optimal sequence of treatments. There is agreement on recommending targeted agents as the standard of care in this disease. Uncertainty, however, remains on the best first-line drug choice. Physicians and patients may select sunitinib, bevacizumab in combination with interferon-alpha (IFN-α), pazopanib, or—in poor risk patients—temsirolimus. There are also a variety of therapies with proven efficacy on hand in the second-line setting: sorafenib, pazopanib, axitinib, and everolimus. While most randomized RCC trials assessed progression free survival (PFS) as primary endpoint, some agents were shown to improve median overall survival (OS), and given in sequence they have extended the life expectancy of RCC patients from 13 months in the cytokine era to over 30 months. Despite the progress made, there are sobering aspects to the oncologic success story in RCC, as the new treatments do not obtain an objective response or disease stabilization (SD) in all patients. There are also as yet no predictors to select patients who might benefit and those who are primary resistant to specific drugs, and ultimately almost all patients will experience disease progression. Bearing inevitable treatment failure in mind, availability of further drugs and switching therapy while the patient is in a condition to continue pharmacotherapy is essential. Of note, depending on the setting, only 33-59% of patients receive second-line treatment. In this review we present data on first-, second-, and third-line treatment in RCC, and discuss the difficulties in their interpretation in the context of treatment sequence. We summarize biological aspects and discuss mechanisms of resistance to anti-angiogenic therapy and their implications for treatment selection. PMID:26816832

  17. FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre Cohort Study

    PubMed Central

    Rombouts, SJ; Mungroop, TH; Heilmann, MN; van Laarhoven, HW; Busch, OR; Molenaar, IQ; Besselink, MG; Wilmink, JW

    2016-01-01

    Introduction: FOLFIRINOX is emerging as new standard of care for fit patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to high toxicity rates reported in earlier studies. We reviewed our experience with FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy. Methods: We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our institution between April 2011 and December 2015. Unresectability (stage III and IV) was determined by the institution's multidisciplinary team for pancreatic cancer. Results: Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was given as first-line treatment in 82% of patients. Dose modifications were applied in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade 3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was 25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC, respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and 5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative therapy and 1 patient (6%) a resection, leading to a median survival of 21.8 months. Conclusion: FOLFIRINOX treatment with nearly routine dose modification was associated with acceptable toxicity rates, relatively high response rates and an encouraging overall survival.

  18. Self-perceived competence among medical residents in skills needed to care for patients with advanced dementia versus metastatic cancer.

    PubMed

    Manu, Erika; Marks, Adam; Berkman, Cathy S; Mullan, Patricia; Montagnini, Marcos; Vitale, Caroline A

    2012-06-01

    To examine medical residents' perceived competence in caring for patients with dementia we conducted an online survey of all 120 second, third and fourth-year residents in Internal Medicine, Medicine/Pediatrics, and Family Medicine at University of Michigan. A structured survey elicited residents' training, experience, confidence, and perceived career needs for skills in estimating prognosis, symptom management, and communication in caring for patients with dementia, compared to patients with metastatic cancer. Among the 61 (51 %) respondents, a majority report lower confidence in assessing prognosis and eliciting treatment wishes in patients with dementia (vs. metastatic cancer), and in performing skills integral to the care of patients with dementia, including the ability to assess caregiver needs, decisional capacity, advise on place of care, and manage agitation, despite viewing these skills as important to their future careers. These findings support the need for enhanced education on optimal care of patients with advanced dementia.

  19. Self-perceived competence among medical residents in skills needed to care for patients with advanced dementia versus metastatic cancer.

    PubMed

    Manu, Erika; Marks, Adam; Berkman, Cathy S; Mullan, Patricia; Montagnini, Marcos; Vitale, Caroline A

    2012-06-01

    To examine medical residents' perceived competence in caring for patients with dementia we conducted an online survey of all 120 second, third and fourth-year residents in Internal Medicine, Medicine/Pediatrics, and Family Medicine at University of Michigan. A structured survey elicited residents' training, experience, confidence, and perceived career needs for skills in estimating prognosis, symptom management, and communication in caring for patients with dementia, compared to patients with metastatic cancer. Among the 61 (51 %) respondents, a majority report lower confidence in assessing prognosis and eliciting treatment wishes in patients with dementia (vs. metastatic cancer), and in performing skills integral to the care of patients with dementia, including the ability to assess caregiver needs, decisional capacity, advise on place of care, and manage agitation, despite viewing these skills as important to their future careers. These findings support the need for enhanced education on optimal care of patients with advanced dementia. PMID:22477667

  20. Phase II trial of everolimus and erlotinib in patients with platinum-resistant recurrent and/or metastatic head and neck squamous cell carcinoma

    PubMed Central

    Massarelli, E.; Lin, H.; Ginsberg, L. E.; Tran, H. T.; Lee, J. J.; Canales, J. R.; Williams, M. D.; Blumenschein, G. R.; Lu, C.; Heymach, J. V.; Kies, M. S.; Papadimitrakopoulou, V.

    2015-01-01

    Background Enhanced phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key adaptive changes accounting for epidermal growth factor receptor (EGFR) inhibitor-resistant growth in head and neck squamous cell carcinoma (HNSCC). We designed a phase II clinical trial of EGFR tyrosine kinase inhibitor (TKI), erlotinib, in association with the mTOR inhibitor, everolimus, based on the hypothesis that the downstream effects of Akt through inhibition of mTOR may enhance the effectiveness of the EGFR-TKI in patients with recurrent/metastatic HNSCC. Patients and methods Patients with histologically or cytologically confirmed platinum-resistant HNSCC received everolimus 5 mg and erlotinib 150 mg daily orally until disease progression, intolerable toxicity, investigator or patient decision. Cytokines and angiogenic factors profile, limited mutation analysis and p16 immunohistochemistry status were included in the biomarker analysis. Results Of the 35 assessable patients, 3 (8%) achieved partial response at 4 weeks, 1 confirmed at 12 weeks; overall response rate at 12 weeks was 2.8%. Twenty-seven (77%) patients achieved disease stabilization at 4 weeks, 11 (31%) confirmed at 12 weeks. Twelve-week progression-free survival (PFS) was 49%, median PFS 11.9 weeks and median overall survival (OS) 10.25 months. High neutrophil gelatinase lipocalin (P = 0.01) and vascular endothelial growth factor (VEGF) (P = 0.04) plasma levels were significantly associated with worse OS. Conclusions The combination of erlotinib and everolimus did not show significant benefit in unselected patients with platinum-resistant metastatic HNSCC despite a manageable toxicity profile. Markers of tumor invasion and hypoxia identify a group of patients with particularly poor prognosis. Clinical trial number NCT00942734. PMID:26025965

  1. [Examination of the safety of docetaxel/cyclophosphamide combination therapy for advanced recurrent breast cancer].

    PubMed

    Yoneyama, Kimiyasu; Koshida, Yoshitomo; Toriumi, Fumiki; Murayama, Takaya; Toeda, Hiroyuki; Imazu, Yoshihiro; Motegi, Katsuhiko; Akamatsu, Hidetoshi; Ohyama, Renpei

    2006-10-01

    In the treatment of recurrent breast cancer in patients previously treated with anthracycline drugs, taxane drugs are generally used. This time, we retrospectively studied the safety of docetaxel/cyclophosphamide combination therapy (hereinafter referred to as TC therapy). Ten patients (mean age: 52.8 years old) were included in the study. Metastatic/recurrent sites included 3 skin, 2 each of contralateral breast, lung and bone, and 1 each of liver, carcinomatous pleurisy and supraclavicular lymph node. Seven patients had a history of anthracycline treatment. The patients received TC at doses of 60 mg/m(2) and 500 mg/m(2), respectively, every 3 weeks. With regard to adverse events, non-hematotoxic events included alopecia in all the patients, generalized malaise in 5, and abnormal nail in 1. Hematotoxic events were grades 2 and 3 decreased neutrophil count in 5 patients. One patient had grade 4 pyrexia associated with oral candida. The patient was admitted and treated with fluid replacement and granulocyte colony-stimulating factor (G-CSF). There were no other patients in whom the treatment was prolonged or dosage was reduced due to adverse reactions. TC therapy is considered to be a beneficial treatment method in terms of safety since it can be instituted on an outpatient basis. PMID:17033252

  2. Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

    ClinicalTrials.gov

    2013-06-03

    Childhood Chronic Myelogenous Leukemia; Childhood Desmoplastic Small Round Cell Tumor; Disseminated Neuroblastoma; Metastatic Childhood Soft Tissue Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  3. Interstitial high-dose-rate brachytherapy in locally advanced and recurrent vulvar cancer

    PubMed Central

    Białas, Brygida; Fijałkowski, Marek; Wojcieszek, Piotr; Szlag, Marta; Cholewka, Agnieszka; Ślęczka, Maciej; Kołosza, Zofia

    2016-01-01

    Purpose The aim of the study was to report our experience with high-dose-rate interstitial brachytherapy (HDR-ISBT) in locally advanced and recurrent vulvar cancer. Material and methods Between 2004 and 2014, fourteen women with locally advanced or recurrent vulvar cancer were treated using HDR-ISBT in our Centre. High-dose-rate interstitial brachytherapy was performed as a separate treatment or in combination with external beam radiotherapy (EBRT) (given prior to brachytherapy). Results Patients were divided into: group I (n = 6) with locally advanced tumors, stages III-IVA after an incisional biopsy only, and group II (n = 8) with recurrent vulvar cancer after previous radical surgery. In group I, median follow up was 12 months (range 7-18 months); 1-year overall survival (OS) was 83%. Transient arrest of cancer growth or tumor regression was noticed in all patients but 4/6 developed relapse. Median time to failure was 6.3 months (range 3-11 months). The 1-year progression-free survival (PFS) was 33%. In group II, median follow up was 28 months (range 13-90 months). The 1-year and 3-year OS was 100% and 80%, respectively. The arrest of cancer growth or tumor regression was achieved in all patients. In 4/8 patients neither clinical nor histological symptoms of relapse were observed but 4/8 women experienced relapse. Median time to failure was 31 months (range 13-76 months). The 1-year and 3-year PFS was 100% and 62.5%, respectively. Two patients (14.3%) in group II had severe late toxicity (G3). Conclusions High-dose-rate interstitial brachytherapy is a well-tolerated treatment option in selected patients with advanced or recurrent vulvar cancer. It is a safe and effective treatment modality for advanced and recurrent vulvar cancer, yielding good local control with acceptable late treatment related side effects. In our study, patients with recurrent vulvar cancer had better results in HDR-ISBT treatment, probably because of the smaller tumor volume. This

  4. Veliparib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-10-04

    Estrogen Receptor Negative; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  5. Saracatinib in Treating Patients With Locally Advanced or Metastatic Stomach or Gastroesophageal Junction Cancer

    ClinicalTrials.gov

    2014-06-19

    Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage III Gastric Cancer; Stage III Esophageal Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  6. Successful Resection of Isolated Para-Aortic Lymph Node Recurrence from Advanced Sigmoid Colon Cancer following 156 Courses of FOLFIRI Regimen

    PubMed Central

    Yamafuji, Kazuo; Asami, Atsunori; Baba, Hideo; Okamoto, Nobuhiko; Takahashi, Hidena; Takagi, Chisato; Kubochi, Kiyoshi

    2016-01-01

    Isolated para-aortic lymph node (PLN) recurrence from colorectal cancer (CRC) is rare, with no currently validated treatments. Few reports have described the successful resection of isolated PLN involvement from CRC following chemotherapy. We report the case of a 63-year-old man who underwent sigmoidectomy for sigmoid colon cancer at our hospital. Pathological examination demonstrated advanced sigmoid colon cancer with metastatic involvement in both of the tested PLNs. Palliative chemotherapy was initiated four weeks after surgical resection, with administration of the FOLFIRI regimen. Four years after the operation, computed tomography (CT) revealed an enlarged PLN below the left renal vein. As PLN enlarged to 15 mm in the minor axis on a CT scan in 2014 after receiving a total of 156 courses of the FOLFIRI regimen, we considered the enlarged PLN to represent an isolated metastasis. Accordingly, lymph node resection was performed with microscopically negative margins. The patient maintained a good quality of life without any side effects throughout the whole course of his treatment and remains disease-free at 24 months without chemotherapy after resection of the isolated PLN. Curative resection following chemotherapy may improve survival of carefully selected advanced CRC patients with locoregional recurrence, such as isolated PLN involvement. PMID:27648336

  7. Successful Resection of Isolated Para-Aortic Lymph Node Recurrence from Advanced Sigmoid Colon Cancer following 156 Courses of FOLFIRI Regimen.

    PubMed

    Takeshima, Kaoru; Yamafuji, Kazuo; Asami, Atsunori; Baba, Hideo; Okamoto, Nobuhiko; Takahashi, Hidena; Takagi, Chisato; Kubochi, Kiyoshi

    2016-01-01

    Isolated para-aortic lymph node (PLN) recurrence from colorectal cancer (CRC) is rare, with no currently validated treatments. Few reports have described the successful resection of isolated PLN involvement from CRC following chemotherapy. We report the case of a 63-year-old man who underwent sigmoidectomy for sigmoid colon cancer at our hospital. Pathological examination demonstrated advanced sigmoid colon cancer with metastatic involvement in both of the tested PLNs. Palliative chemotherapy was initiated four weeks after surgical resection, with administration of the FOLFIRI regimen. Four years after the operation, computed tomography (CT) revealed an enlarged PLN below the left renal vein. As PLN enlarged to 15 mm in the minor axis on a CT scan in 2014 after receiving a total of 156 courses of the FOLFIRI regimen, we considered the enlarged PLN to represent an isolated metastasis. Accordingly, lymph node resection was performed with microscopically negative margins. The patient maintained a good quality of life without any side effects throughout the whole course of his treatment and remains disease-free at 24 months without chemotherapy after resection of the isolated PLN. Curative resection following chemotherapy may improve survival of carefully selected advanced CRC patients with locoregional recurrence, such as isolated PLN involvement. PMID:27648336

  8. Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2014-11-14

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Neuroendocrine Tumor; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma; WDHA Syndrome

  9. Gefitinib in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2013-06-03

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma; WDHA Syndrome

  10. Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer

    PubMed Central

    Suzuki, Shuji; Shimazaki, Jiro; Morishita, Keiichi; Koike, Nobusada; Harada, Nobuhiko; Hayashi, Tsuneo; Suzuki, Mamoru

    2016-01-01

    The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m2) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1–14. The drug regimen was repeated every 4 weeks. SOX+bev treatment was associated with a response rate of 45.2%, a disease control rate of 71%, and a median progression-free survival (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients who received first-line chemotherapy benefited from treatment in terms of prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase level and skin rash. In conclusion, SOX+bev therapy was found to be feasible and safe for patients with advanced and recurrent colorectal cancer.

  11. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    PubMed Central

    Hao, Yanni; Wolfram, Verena; Cook, Jennifer

    2016-01-01

    Background Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Methods Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases), online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center), and web sites of health technology assessment (HTA) bodies. Publications were selected based on the search strategy and the overall study objectives. Results A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D). Other utility measures, such as the direct methods standard gamble (SG), time trade-off (TTO), and visual analog scale (VAS), were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL) instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer 23 (EORTC QLQ-BR23), Functional Assessment of Cancer Therapy – General questionnaire (FACT-G), and Utility-Based Questionnaire-Cancer (UBQ-C); most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex, income, and education, as well as disease progression, choice of utility elicitation method, and country settings, were identified

  12. Docetaxel plus cetuximab biweekly is an active regimen for the first-line treatment of patients with recurrent/metastatic head and neck cancer

    NASA Astrophysics Data System (ADS)

    Posch, Doris; Fuchs, Hannah; Kornek, Gabriela; Grah, Anja; Pammer, Johannes; Aretin, Marie-Bernadette; Fuereder, Thorsten

    2016-09-01

    For patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN) limited therapeutic options exist. Only a subset of patients is suitable for combination chemotherapy regimens. Biweekly docetaxel plus cetuximab might be an alternative option. Thus, we performed this retrospective analysis in unselected patients in order to investigate the efficacy and safety of this regimen. Thirty-one patients receiving off protocol docetaxel (50 mg/m2) plus cetuximab (500 mg/m2) biweekly were included. Data collection included baseline demographic, response rate (ORR), disease control rate (DCR), overall survival (OS), progression free survival (PFS) as well as toxicity. OS and PFS were 8.3 months (95% CI 4.8-11.8) and 4.0 months (95% CI 1.0-7.0), respectively. Three (9.7%) patients achieved a complete response and one patient (3.2%) a partial response. The DCR was 41.9% and we observed an ORR of 12.9%. The one-year survival rate was 25.8%. The therapy was well tolerated and the most common grade 3/4 adverse events were neutropenia (19.4%), hypomagnesaemia (12.9%) and acne-like rash (9.7%). Biweekly cetuximab/docetaxel is an effective regimen and well tolerated in R/M SCCHN patients not suitable for platinum doublet treatment. Further evaluation of this regimen in prospective clinical trials is warranted.

  13. Docetaxel plus cetuximab biweekly is an active regimen for the first-line treatment of patients with recurrent/metastatic head and neck cancer

    PubMed Central

    Posch, Doris; Fuchs, Hannah; Kornek, Gabriela; Grah, Anja; Pammer, Johannes; Aretin, Marie-Bernadette; Fuereder, Thorsten

    2016-01-01

    For patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN) limited therapeutic options exist. Only a subset of patients is suitable for combination chemotherapy regimens. Biweekly docetaxel plus cetuximab might be an alternative option. Thus, we performed this retrospective analysis in unselected patients in order to investigate the efficacy and safety of this regimen. Thirty-one patients receiving off protocol docetaxel (50 mg/m2) plus cetuximab (500 mg/m2) biweekly were included. Data collection included baseline demographic, response rate (ORR), disease control rate (DCR), overall survival (OS), progression free survival (PFS) as well as toxicity. OS and PFS were 8.3 months (95% CI 4.8–11.8) and 4.0 months (95% CI 1.0–7.0), respectively. Three (9.7%) patients achieved a complete response and one patient (3.2%) a partial response. The DCR was 41.9% and we observed an ORR of 12.9%. The one-year survival rate was 25.8%. The therapy was well tolerated and the most common grade 3/4 adverse events were neutropenia (19.4%), hypomagnesaemia (12.9%) and acne-like rash (9.7%). Biweekly cetuximab/docetaxel is an effective regimen and well tolerated in R/M SCCHN patients not suitable for platinum doublet treatment. Further evaluation of this regimen in prospective clinical trials is warranted. PMID:27597175

  14. Docetaxel plus cetuximab biweekly is an active regimen for the first-line treatment of patients with recurrent/metastatic head and neck cancer

    NASA Astrophysics Data System (ADS)

    Posch, Doris; Fuchs, Hannah; Kornek, Gabriela; Grah, Anja; Pammer, Johannes; Aretin, Marie-Bernadette; Fuereder, Thorsten

    2016-09-01

    For patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN) limited therapeutic options exist. Only a subset of patients is suitable for combination chemotherapy regimens. Biweekly docetaxel plus cetuximab might be an alternative option. Thus, we performed this retrospective analysis in unselected patients in order to investigate the efficacy and safety of this regimen. Thirty-one patients receiving off protocol docetaxel (50 mg/m2) plus cetuximab (500 mg/m2) biweekly were included. Data collection included baseline demographic, response rate (ORR), disease control rate (DCR), overall survival (OS), progression free survival (PFS) as well as toxicity. OS and PFS were 8.3 months (95% CI 4.8–11.8) and 4.0 months (95% CI 1.0–7.0), respectively. Three (9.7%) patients achieved a complete response and one patient (3.2%) a partial response. The DCR was 41.9% and we observed an ORR of 12.9%. The one-year survival rate was 25.8%. The therapy was well tolerated and the most common grade 3/4 adverse events were neutropenia (19.4%), hypomagnesaemia (12.9%) and acne-like rash (9.7%). Biweekly cetuximab/docetaxel is an effective regimen and well tolerated in R/M SCCHN patients not suitable for platinum doublet treatment. Further evaluation of this regimen in prospective clinical trials is warranted.

  15. Docetaxel plus cetuximab biweekly is an active regimen for the first-line treatment of patients with recurrent/metastatic head and neck cancer.

    PubMed

    Posch, Doris; Fuchs, Hannah; Kornek, Gabriela; Grah, Anja; Pammer, Johannes; Aretin, Marie-Bernadette; Fuereder, Thorsten

    2016-01-01

    For patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN) limited therapeutic options exist. Only a subset of patients is suitable for combination chemotherapy regimens. Biweekly docetaxel plus cetuximab might be an alternative option. Thus, we performed this retrospective analysis in unselected patients in order to investigate the efficacy and safety of this regimen. Thirty-one patients receiving off protocol docetaxel (50 mg/m(2)) plus cetuximab (500 mg/m(2)) biweekly were included. Data collection included baseline demographic, response rate (ORR), disease control rate (DCR), overall survival (OS), progression free survival (PFS) as well as toxicity. OS and PFS were 8.3 months (95% CI 4.8-11.8) and 4.0 months (95% CI 1.0-7.0), respectively. Three (9.7%) patients achieved a complete response and one patient (3.2%) a partial response. The DCR was 41.9% and we observed an ORR of 12.9%. The one-year survival rate was 25.8%. The therapy was well tolerated and the most common grade 3/4 adverse events were neutropenia (19.4%), hypomagnesaemia (12.9%) and acne-like rash (9.7%). Biweekly cetuximab/docetaxel is an effective regimen and well tolerated in R/M SCCHN patients not suitable for platinum doublet treatment. Further evaluation of this regimen in prospective clinical trials is warranted. PMID:27597175

  16. SB-715992 in Treating Patients With Advanced or Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2015-02-13

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  17. Metastatic Paraganglioma

    PubMed Central

    Fliedner, Stephanie M. J.; Lehnert, Hendrik; Pacak, Karel

    2010-01-01

    Paragangliomas (PGLs) are rare chromaffin cell tumors that can often be cured by resection. Although described for the first time in 1886 1, the diagnosis of PGL remains a challenge, because patients do not present with characteristic signs and symptoms. If untreated, PGL can have a devastating outcome due to myocardial infarction, severe hypertension, stroke and/or arrhytmia caused by catecholamine excess. Even after proper diagnosis, the risk of metastatic disease remains. In recent years the opinion that metastatic disease is rare in PGL had to be revised, particularly in patients presenting with extra-adrenal PGL, with a PGL exceeding a size of 5 cm and/or carrying an SDHB germline mutation (especially for children and adolescents). In up to 10 % of patients, metastases are already present at diagnosis of PGL. Measurement of plasma and urinary metanephrine levels has long been used effectively in the diagnosis of PGL. Recently, a dopaminergic phenotype (excess dopamine, L-3,4-dihydroxyphenylalanine and or methoxytyramine) was recognized as a good indicator for metastatic disease. Vast progress in targeted PET imaging (e.g. 18F-FDA, 18F-FDOPA, 18F-FDG) now allows for reliable early detection of metastatic disease. However, once metastatses are present, treatment options are limited. Survival of patients with metastatic PGL is variable. Depending on the study population the overall 5 year survival is 35–60 %, 2. Here we review recent advances involving findings about the genetic background, the molecular pathogenesis, new diagnostic indicators, pathologic markers and emerging treatment options for metastatic PGL. PMID:21167381

  18. Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications.

    PubMed

    Veeraraghavan, Jamunarani; Ma, Jiacheng; Hu, Yiheng; Wang, Xiao-Song

    2016-07-01

    Gene fusions have long been considered principally as the oncogenic events of hematologic malignancies, but have recently gained wide attention in solid tumors due to several milestone discoveries and the advancement of deep sequencing technologies. With the progress in deep sequencing studies of breast cancer transcriptomes and genomes, the discovery of recurrent and pathological gene fusions in breast cancer is on the focus. Recently, driven by new deep sequencing studies, several recurrent or pathological gene fusions have been identified in breast cancer, including ESR1-CCDC170, SEC16A-NOTCH1, SEC22B-NOTCH2, and ESR1-YAP1 etc. More important, most of these gene fusions are preferentially identified in the more aggressive breast cancers, such as luminal B, basal-like, or endocrine-resistant breast cancer, suggesting recurrent gene fusions as additional key driver events in these tumors other than the known drivers such as the estrogen receptor. In this paper, we have comprehensively summarized the newly identified recurrent or pathological gene fusion events in breast cancer, reviewed the contributions of new genomic and deep sequencing technologies to new fusion discovery and the integrative bioinformatics tools to analyze these data, highlighted the biological relevance and clinical implications of these fusion discoveries, and discussed future directions of gene fusion research in breast cancer. PMID:27372070

  19. Treatment of metastatic and recurrent cervix cancer with chemotherapy: a randomised trial comparing hydroxyurea with cisdiamminedichloro-platinum plus methotrexate.

    PubMed

    Bezwoda, W R; Nissenbaum, M; Derman, D P

    1986-01-01

    In a randomised trial comparing single-agent chemotherapy (hydroxyurea) to combination chemotherapy in advanced cervix cancer, response was seen in 57% (including 13% CR) of patients receiving the combination (DDP + MTX) regimen. Responding patients survived significantly longer (11 months) than either those receiving hydroxyurea or those not responding to combination chemotherapy (4 months). Two patients remain in complete remission for 14+ and 17+ months.

  20. Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer.

    PubMed

    Dang, Thu Oanh; Ogunniyi, Adebayo; Barbee, Meagan S; Drilon, Alexander

    2016-01-01

    The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.

  1. Carboplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-06-21

    High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  2. Development and validation of a risk score for advanced colorectal adenoma recurrence after endoscopic resection

    PubMed Central

    Facciorusso, Antonio; Di Maso, Marianna; Serviddio, Gaetano; Vendemiale, Gianluigi; Muscatiello, Nicola

    2016-01-01

    AIM: To develop and validate a risk score for advanced colorectal adenoma (ACA) recurrence after endoscopic polypectomy. METHODS: Out of 3360 patients who underwent colon polypectomy at University of Foggia between 2004 and 2008, data of 843 patients with 1155 ACAs was retrospectively reviewed. Surveillance intervals were scheduled by guidelines at 3 years and primary endpoint was considered 3-year ACA recurrence. Baseline clinical parameters and the main features of ACAs were entered into a Cox regression analysis and variables with P < 0.05 in the univariate analysis were then tested as candidate variables into a stepwise Cox regression model (conditional backward selection). The regression coefficients of the Cox regression model were multiplied by 2 and rounded in order to obtain easy to use point numbers facilitating the calculation of the score. To avoid overoptimistic results due to model fitting and evaluation in the same dataset, we performed an internal 10-fold cross-validation by means of bootstrap sampling. RESULTS: Median lesion size was 16 mm (12-23) while median number of adenomas was 2.5 (1-3), whereof the number of ACAs was 1.5 (1-2). At 3 years after polypectomy, recurrence was observed in 229 ACAs (19.8%), of which 157 (13.5%) were metachronous neoplasms and 72 (6.2%) local recurrences. Multivariate analysis, after exclusion of the variable “type of resection” due to its collinearity with other predictive factors, confirmed lesion size, number of ACAs and grade of dysplasia as significantly associated to the primary outcome. The score was then built by multiplying the regression coefficients times 2 and the cut-off point 5 was selected by means of a Receiver Operating Characteristic curve analysis. In particular, 248 patients with 365 ACAs fell in the higher-risk group (score ≥ 5) where 3-year recurrence was detected in 174 ACAs (47.6%) whereas the remaining 595 patients with 690 ACAs were included in the low-risk group (score < 5) where 3

  3. Analysis of Cancer Mutation Signatures in Blood by a Novel Ultra-Sensitive Assay: Monitoring of Therapy or Recurrence in Non-Metastatic Breast Cancer

    PubMed Central

    Chen, Zhenbin; Feng, Jinong; Buzin, Carolyn H.; Liu, Qiang; Weiss, Lawrence; Kernstine, Kemp; Somlo, George; Sommer, Steve S.

    2009-01-01

    Background Tumor DNA has been shown to be present both in circulating tumor cells in blood and as fragments in the plasma of metastatic cancer patients. The identification of ultra-rare tumor-specific mutations in blood would be the ultimate marker to measure efficacy of cancer therapy and/ or early recurrence. Herein we present a method for detecting microinsertions/deletions/indels (MIDIs) at ultra-high analytical selectivity. MIDIs comprise about 15% of mutations. Methods and Findings We describe MIDI-Activated Pyrophosphorolysis (MAP), a method of ultra-high analytical selectivity for detecting MIDIs. The high analytical selectivity of MAP is putatively due to serial coupling of two rare events: heteroduplex slippage and mis-pyrophosphorolysis. MAP generally has an analytical selectivity of one mutant molecule per >1 billion wild type molecules and an analytical sensitivity of one mutant molecule per reaction. The analytical selectivity of MAP is about 100,000-fold better than that of our previously described method of Pyrophosphorolysis Activated Polymerization-Allele specific amplification (PAP-A) for detecting MIDIs. The utility of this method is illustrated in two ways. 1) We demonstrate that two EGFR deletions commonly found in lung cancers are not present in tissue from four normal human lungs (107 copies of gDNA each) or in blood samples from 10 healthy individuals (107 copies of gDNA each). This is inconsistent, at least at an analytical sensitivity of 10−7, with the hypotheses of (a) hypermutation or (b) strong selection of these growth factor-mutated cells during normal lung development leads to accumulation of pre-neoplastic cells with these EGFR mutations, which sometimes can lead to lung cancer in late adulthood. Moreover, MAP was used for large scale, high throughput “gene pool” analysis. No germline or early embryonic somatic mosaic mutation was detected (at a frequency of >0.3%) for the 15/18 bp EGFR deletion mutations in 6,400 individuals

  4. A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma

    PubMed Central

    Gilbert, Jill; Schell, Michael J.; Zhao, Xiuhua; Murphy, Barbara; Tanvetyanon, Tawee; Leon, Marino E.; Hayes, D. Neil; Haigentz, Missak; Saba, Nabil; Nieva, Jorge; Bishop, Justin; Sidransky, David; Ravi, Rajani; Bedi, Atul; Chung, Christine H.

    2015-01-01

    Introduction A combination of cetuximab and sorafenib in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were assessed for potential benefit. Material and Methods In a randomized phase II study, R/M HNSCC patients were treated with cetuximab 400mg/m2 IV on day 1 followed by 250mg/m2 IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400mg PO twice-a-day (Arm B). Each cycle was 21 days. Tumor p16 and HPV status, and plasma immunomodulatory cytokine levels were assessed. Results Of 55 patients enrolled (Arm A-27, Arm B-28), 52 patients received assigned treatments and 43 were evaluable for response. Overall response rate was 8% for both arms. Median overall survival (OS) and progression-free survival (PFS) were 9.0 and 3.0 months in Arm A, and 5.7 and 3.2 months in Arm B, respectively. Forty-four patients had tumors available for p16 staining (35-negative, 9-positive). Three of nine p16-positive tumors were also HPV positive. The p16-negative patients had significantly better PFS compared to the p16-positive patients (3.7 vs. 1.6 months; p-value: 0.03), regardless of study arms. Twenty-four plasma samples were tested for 12 cytokine levels and patients with higher TGFβ1 levels had inferior PFS compared to lower levels (1.9 vs. 4.7 months; adjusted p-value: 0.015), regardless of study arms. Conclusions A subset of R/M patients with p16-negative tumors or lower plasma TGFβ1 levels had longer PFS given the cetuximab-based therapy. However, both arms showed only modest response and sorafenib given with cetuximab did not demonstrate clinical benefit. PMID:25593015

  5. Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study

    PubMed Central

    Chen, San-Chi; Chang, Peter Mu-Hsin

    2016-01-01

    Lessons Learned Cisplatin/tegafur/uracil/irinotecan triple combination therapy shows moderate response, especially in patients without previous chemoradiotherapy within the 6 months before this combination therapy. Toxicity is tolerable, and quality of life is improved in responders. Background. The prognosis is poor in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Triple combination therapy may increase tumor response. Methods. This phase I/II prospective trial first determined the dose-limiting toxicity and recommended dose of irinotecan with cisplatin and tegafur/uracil (UFUR) in phase I. Irinotecan was supplied at doses of 40, 50, 60, and 70 mg/m2 by using a standard 3+3 design. Doses of cisplatin and UFUR were held stable. In phase II, the recommended dose of irinotecan was administered intravenously (i.v.) over 90 min on day 1, with cisplatin 50 mg/m2 i.v. over 60 min also on day 1, and oral UFUR 200 mg twice a day for 5 days every 2 weeks a cycle. Results. In the phase I portion, 14 patients were enrolled, and the dose level of irinotecan at 60 mg/m2 was defined as the recommended dose for the phase II portion of the study. Among 43 patients enrolled in the phase II portion, complete response was seen in 2 patients (4.7%) and partial response in 10 patients (23.3%), and the disease control rate was 39.5%. In a subgroup analysis of patients whose prior chemoradiotherapy was more than 6 months earlier, a response rate of 40.7% and disease control rate of 59.3% were observed. Conclusion. Cisplatin/UFUR/irinotecan triple combination therapy is tolerated and effective for selected patients. Individualized choice of treatment will influence prognosis and quality of life in R/M HNSCC patients. PMID:27091418

  6. Phase II Study of Bevacizumab in Combination with Trastuzumab and Capecitabine as First-Line Treatment for HER-2-positive Locally Recurrent or Metastatic Breast Cancer

    PubMed Central

    Makhson, Anatoly; Gligorov, Joseph; Lichinitser, Mikhail; Lluch, Ana; Semiglazov, Vladimir; Scotto, Nana; Mitchell, Lada; Tjulandin, Sergei

    2012-01-01

    We report the first results from a phase II, open-label study designed to evaluate the efficacy and safety of bevacizumab in combination with trastuzumab and capecitabine as first-line therapy for human epidermal growth factor receptor (HER)-2-positive locally recurrent (LR) or metastatic breast cancer (MBC). Patients were aged ≥18 years with confirmed breast adenocarcinoma, measurable LR/MBC and documented HER-2-positive disease. Patients received bevacizumab (15 mg/kg on day 1) plus trastuzumab (8 mg/kg on day 1 of cycle 1, 6 mg/kg on day 1 of each subsequent cycle) plus capecitabine (1,000 mg/m2 twice daily, days 1–14) every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. Eighty-eight patients were enrolled; 40 (46%) are still on study treatment. The median follow-up was 8.8 months (range, 0.9–17.1 months). The overall response rate, the primary endpoint, was 73% (95% confidence interval [CI], 62%–82%), comprising 7% complete and 66% partial responses. The median progression-free survival interval was 14.4 months (95% CI, 10.4 months to not reached [NR]), with 35 events. The median time to progression was 14.5 months (95% CI, 10.5 months to NR), with 33 events. Treatment was well tolerated; main side effects were grade 3 hand–foot syndrome (22%), grade ≥3 diarrhea (9%), and grade ≥3 hypertension (7%). Overall, 44% of patients experienced grade ≥3 treatment-related adverse events and 13 patients discontinued capecitabine because of toxicity, but continued with bevacizumab and trastuzumab. Heart failure was seen in two patients. The combination of bevacizumab, trastuzumab, and capecitabine was clinically active as first-line therapy for patients with HER-2-positive MBC, with an acceptable safety profile and no unexpected toxicities. PMID:22467666

  7. Endobronchial valve placement as destination therapy for recurrent pneumothorax in the setting of advanced malignancy.

    PubMed

    Gilbert, Christopher R; Toth, Jennifer W; Osman, Umar; Reed, Michael F

    2015-03-01

    The development of a persistent air leak after pneumothorax can be encountered in patients with underlying structural lung disease. In those with advanced malignancy or other comorbidities, the ability to tolerate general anesthesia and thoracoscopic procedures may limit definitive management. We describe the case of a 68-y-old male with refractory acute myelogenous leukemia presenting with recurrent secondary spontaneous pneumothorax and persistent air leak related to an underlying fungal pneumonia. Endobronchial valve placement allowed for timely chest tube removal and discharge from the hospital, as well as avoidance of a thoracoscopic procedure and pleurodesis.

  8. Interstitial Photodynamic Therapy in Treating Patients With Recurrent Head and Neck Cancer

    ClinicalTrials.gov

    2016-10-20

    Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

  9. First-line cetuximab-based chemotherapies for patients with advanced or metastatic KRAS wild-type colorectal cancer

    PubMed Central

    Uemura, Mamoru; Kim, Ho Min; Hata, Tsuyoshi; Sakata, Kazuya; Okuyama, Masaki; Takemoto, Hiroyoshi; Fujii, Hitoshi; Fukuzaki, Takayuki; Morita, Tetsushi; Hata, Taishi; Takemasa, Ichiro; Satoh, Taroh; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Maski

    2016-01-01

    Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide. A burgeoning number of studies have demonstrated that the addition of cetuximab to another standard first-line regimen markedly improves the outcome of CRC treatment. However, at present, the efficacy and safety of cetuximab-based combination chemotherapy has not been well described in Japan. The aim of the present study was to evaluate the efficacy and safety of first-line chemotherapies that included cetuximab for patients with advanced or metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type CRC in Japan. This prospective multicenter observational study was conducted at 13 affiliated medical institutions. A total of 64 patients were enrolled between 2010 and 2013. The patients met the following criteria for eligibility: i) histologically confirmed, advanced or metastatic KRAS wild-type CRC; and ii) cetuximab-based chemotherapies administered as a first-line treatment. First-line cetuximab-based treatments were administered as follows: 29 patients (45.3%) received a combination of infusional fluorouracil, leucovorin and oxaliplatin; 14 patients (21.9%) received a combination of capecitabine and oxaliplatin; and 10 patients (15.6%) received a combination of infusional fluorouracil, leucovorin and irinotecan. The overall response rate (including complete plus partial responses) was 50% (32/64 patients). Initially, 48 lesions were diagnosed as unresectable. Among those, 13 lesions (27.1%) were converted to a resectable status following cetuximab-based combination chemotherapy treatments. The median overall survival time and the progression-free survival time were 1,189 and 359 days, respectively. The most frequent grade 3/4 adverse event was neutropenia, which occurred in 20.3% of the patients. The incidence of grade 3/4 skin toxicity was 17.2% (11/64 patients). Cetuximab-based therapies may represent a promising first-line regimen for patients with advanced or

  10. Prospects in cancer immunotherapy: treating advanced stage disease or preventing tumor recurrence?

    PubMed

    Manjili, Masoud H; Payne, Kyle K

    2015-06-01

    Human vaccines against infectious agents are often effective in a prophylactic setting. However, they are usually not effective when used post-exposure. Rabies vaccine is one of the exceptions, which can be used post-exposure, but is effective only when used in combination with other treatments. Similar results have been obtained with cancer vaccines and immunotherapies. Cancer immunotherapies generally prolong patients' survival when they are used during advanced stage disease. The potential of immunotherapy to cure cancer could be revealed when it is applied in a prophylactic setting. This article provides a brief overview of cancer immunotherapeutics and suggests that immunotherapy can cure cancer if used at the right time against the right target; we suggest that targeting cancer during dormancy in order to prevent tumor recurrence as advanced stage disease is potentially curative.

  11. Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review.

    PubMed

    Sherwood, James; Dearden, Simon; Ratcliffe, Marianne; Walker, Jill

    2015-01-01

    Increased understanding of the genetic aetiology of advanced non-small-cell lung cancer (aNSCLC) has facilitated personalised therapies that target specific molecular aberrations associated with the disease. Biopsy samples for mutation testing may be taken from primary or metastatic sites, depending on which sample is most accessible, and upon differing diagnostic practices between territories. However, the mutation status concordance between primary tumours and corresponding metastases is the subject of debate. This review aims to ascertain whether molecular diagnostic testing of either the primary or metastatic tumours is equally suitable to determine patient eligibility for targeted therapies. A literature search was performed to identify articles reporting studies of mutations in matched primary and metastatic aNSCLC tumour samples. Clinical results of mutation status concordance between matched primary and metastatic tumour samples from patients with aNSCLC were collated. Articles included in this review (N =26) all reported mutation status data from matched primary and metastatic tumour samples obtained from adult patients with aNSCLC. Generally, substantial concordance was observed between primary and metastatic tumours in terms of EGFR, KRAS, BRAF, p16 and p53 mutations. However, some level of discordance was seen in most studies; mutation testing methodologies appeared to play a key role in this, along with underlying tumour heterogeneity. Substantial concordance in mutation status observed between primary and metastatic tumour sites suggests that diagnostic testing of either tumour type may be suitable to determine a patient's eligibility for personalised therapies. As with all diagnostic testing, highly sensitive and appropriately validated mutation analysis methodologies are desirable to ensure accuracy. Additional work is also required to define how much discordance is clinically significant given natural tumour heterogeneity. The ability of both

  12. [Recurrence and survival rate of advanced gastric cancer after preoperative EAP-II intra-arterial infusion therapy].

    PubMed

    Masuyama, M; Taniguchi, H; Takeuchi, K; Miyata, K; Koyama, H; Tanaka, H; Higashida, T; Koishi, Y; Mugitani, T; Yamaguchi, T

    1994-09-01

    Ninety-eight patients with advanced gastric cancers underwent gastrectomy from Jan. 1989 to Dec. 1991. For these patients, preoperative intra-arterial injection therapy using EAP-II (etoposide 100 mg, epirubicin 20 mg, carboplatin 100 mg) was given to 24 patients. In this report, the recurrence and survival rate of these patients were investigated. After curative resection, the survival rate of patients with EAP-II 36 months after operation was 76.9%, while that of patients without EAP-II was 78.6%. There were no significant differences between these two groups. Two peritoneal carcinomatoses and two liver metastases were seen in patients with EAP-II (recurrence rate, 30.7%). Eight recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination, 4; local recurrence, 3; lymph node recurrence, 1). Previously, we reported that drugs were remarkably accumulated in gastric cancer tissue and regional lymph nodes after EAP-II intra-arterial injection therapy. This high accumulation might cause no local or lymph node recurrence was seen in patient with EAP-II. Thus, it was concluded that preoperative EAP-II intra-arterial injection may prevent local and lymph node recurrences, and that further study of the combination and dose of anti-cancer drug needed to improve the postoperative survival rate in advanced gastric cancer patients.

  13. Treatment of advanced or recurrent endometrial carcinoma with combination of etoposide, cisplatin, and 5-fluorouracil: a phase II study.

    PubMed

    Pierga, J Y; Dieras, V; Paraiso, D; Dorval, T; Palangie, T; Beuzeboc, P; Jouve, M; Scholl, S M; Garcia-Giralt, E; Pouillart, P

    1996-01-01

    Forty-nine consecutive patients with metastatic or recurrent endometrial carcinoma were treated with a monthly combination chemotherapy consisting of VP 16-213 80 mg/m2 i.v. Days 1-3, 5-fluorouracil (5-FU) 600 mg/m2 i.v. Days 1-3, and cisplatin 35 mg/m2 i.v. Days 1-3. The objective response rate was 41% (95% CI, 27-54%) with 14.3% complete responses. The median survival duration was 14 months. The median response duration was 12 months. The estimated median survival for responders was 20 months. Three patients are still free of disease 5 years after treatment. The major toxic effects were myelosuppression (less than 25% of grade III and IV leucopenia, and 14% grade III and IV thrombocytopenia). Grade III peripheral neuropathy was observed in five patients. Cisplatin administration had to be stopped due to renal toxicity in six patients. No treatment-related deaths occurred. The combination of etoposide, 5 fluorouracil, and cisplatin is an effective regimen with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.

  14. Oncolytic Reovirus in Combination With Chemotherapy in Metastatic or Recurrent Non–Small Cell Lung Cancer Patients With KRAS-Activated Tumors

    PubMed Central

    Villalona-Calero, Miguel A.; Lam, Elaine; Otterson, Gregory A.; Zhao, Weiqiang; Timmons, Matthew; Subramaniam, Deepa; Hade, Erinn M.; Gill, George M.; Coffey, Matthew; Selvaggi, Giovanni; Bertino, Erin; Chao, Bo; Knopp, Michael V.

    2016-01-01

    BACKGROUND The type 3 Dearing reovirus (Reolysin) is a naturally occurring virus that preferentially infects and causes oncolysis in tumor cells with a Ras-activated pathway. It induces host immunity and cell cycle arrest and acts synergistically with cytotoxic agents. METHODS This study evaluated Reolysin combined with paclitaxel and carboplatin in patients with metastatic/recurrent KRAS-mutated or epidermal growth factor receptor (EGFR)–mutated/amplified non–small cell lung cancer. RESULTS Thirty-seven patients were treated. Molecular alterations included 20 KRAS mutations, 10 EGFR amplifications, 3 EGFR mutations, and 4 BRAF-V600E mutations. In total, 242 cycles (median, 4; range, 1-47) were completed. The initial doses were area under the curve (AUC) 6 mg/mL/min for carboplatin, 200 mg/m2 for paclitaxel on day 1, and 3×1010 50% tissue culture infective dose for Reolysin on days 1 to 5 of each 21-day cycle. Because of diarrhea and febrile neutropenia (in the first 2 patients), subsequent doses were reduced to 175 mg/m2 for paclitaxel and AUC 5 mg/mL/min for carboplatin. Toxicities included fatigue, diarrhea, nausea/vomiting, neutropenia, arthralgia/myalgia, anorexia, and electrolyte abnormalities. Response Evaluation Criteria in Solid Tumors 1.0 responses included the following: partial response for 11 patients, stable disease (SD) for 20 patients, progressive disease for 4 patients, and not evaluable for 2 patients (objective response rate, 31%; 90% 1-sided lower confidence interval, 21%). Four SD patients had >40% positron emission tomography standardized uptake value reductions. The median progression-free survival, median overall survival, and 12-month overall survival rate were 4 months, 13.1 months, and 57%, respectively. Seven patients were alive after a median follow-up of 34.2 months; they included 2 patients without disease progression at 37 and 50 months. CONCLUSIONS Reolysin in combination with paclitaxel and carboplatin was well tolerated. The

  15. Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma

    ClinicalTrials.gov

    2016-09-26

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Nasopharyngeal Undifferentiated Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IV Nasopharyngeal Undifferentiated Carcinoma

  16. Is the Blood-Brain Barrier Relevant in Metastatic Germ Cell Tumor?

    SciTech Connect

    Azar, Jose M. Schneider, Bryan P.; Einhorn, Lawrence H.

    2007-09-01

    Purpose: Germ cell tumors are uniquely chemosensitive and curable, even with advanced metastatic disease. Central nervous system recurrence can terminate a complete remission in other chemosensitive tumors, such as small cell lung cancer, because of the blood-brain barrier (BBB). We propose to document that the BBB is also relevant in germ cell tumors despite their dramatic chemosensitivity. Methods and Materials: We present five cases illustrating the concept of the BBB in patients with metastatic testicular cancer treated with chemotherapy. Results: In our large series of patients with metastatic testicular cancer treated with chemotherapy, we identified 5 unique patients. These patients were rendered free of disease only to experience relapse in the brain alone. This included 1 patient who initially had good-risk metastatic disease by means of the International Germ Cell Collaborative Group staging system at the onset of chemotherapy. Conclusions: The BBB is relevant in patients with metastatic testicular cancer.

  17. Advances in First-Line Treatment for Patients with HER-2+ Metastatic Breast Cancer

    PubMed Central

    De Mattos-Arruda, Leticia

    2012-01-01

    Background. The prognosis for breast cancer patients overexpressing human epidermal growth factor receptor (HER)-2 has changed with anti–HER-2–targeted therapy. Although anti–HER-2 therapy with trastuzumab and chemotherapy is the standard first-line treatment, the best therapeutic regimen has yet to be defined, and new strategies are evolving. Methods. A literature review of well-established and recently published trials, reviews, and ongoing clinical trials addressing first-line treatment for HER-2+ metastatic breast cancer patients was performed. Results. Taxanes are the agents most commonly used in combination with trastuzumab, but other chemotherapy drugs, such as anthracyclines, vinorelbine, and gemcitabine and triple-combination therapies including platinum compounds, capecitabine, and taxanes have been studied. The combination of aromatase inhibitors with anti–HER-2 therapies is a new therapeutic option for some patients who coexpress HER-2 and hormone receptors, although its activity observed in randomized clinical trials seems to be inferior to that of chemotherapy plus anti–HER-2 therapies. In addition, new anti–HER-2 therapies have shown activity in HER-2+ tumors, both alone and in combination with trastuzumab. Conclusions. Trastuzumab plus chemotherapy is the current standard of care for the upfront treatment of HER-2+ breast cancer patients, though other anti–HER-2–targeting agents may appear as new standards in the upcoming years. PMID:22523199

  18. Advances and new perspectives in the treatment of metastatic colon cancer

    PubMed Central

    Recondo, Gonzalo Jr; Díaz-Cantón, Enrique; de la Vega, Máximo; Greco, Martin; Recondo, Gonzalo Sr; Valsecchi, Matias E

    2014-01-01

    During the last decade we have witnessed an unprecedented outburst of new treatment approaches for the management of metastatic colon cancer. Anti-angiogenic drugs, epidermal growth factor receptor blockers and multi-kinase inhibitors have all resulted in small but consistent improvement in clinical outcomes. However, this progress has paradoxically leaded us into new challenges. In many cases the clinical development was done in parallel and the lack of head-to-head comparison evolved into circumstances where several valid new “standards of care” are available. Even though desirable in essence, the availability of many options as well as different possible combinations frequently leaves the busy clinician in the difficult situation of having to choose between one or the other, sometimes without solid evidence to support each decision. In addition, progress never stops and new agents are continuously tested. For these reason this review will try to summarize all the clinical trials that constitute the theoretical framework that support our daily practice but will also procure the reader with rational answers to common clinical dilemmas by critically appraising the current literature. Lastly, we will provide with a compilation of promising new agents that may soon become our next line of defense against this deadly disease. PMID:25024813

  19. Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-10-25

    Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

  20. Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.

    PubMed

    Ohno, Shinji

    2016-08-01

    For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia. PMID:27151773

  1. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer.

    PubMed

    Yuan, Ying; Li, Xiao-Fen; Chen, Jia-Qi; Dong, Cai-Xia; Weng, Shan-Shan; Huang, Jian-Jin

    2014-01-01

    Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa(®)), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood-brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

  2. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    ClinicalTrials.gov

    2016-06-22

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  3. Pertuzumab in combination with trastuzumab and docetaxel for the treatment of HER2-positive metastatic or locally recurrent unresectable breast cancer.

    PubMed

    Fleeman, Nigel; Bagust, Adrian; Beale, Sophie; Dwan, Kerry; Dickson, Rumona; Proudlove, Chris; Dundar, Yenal

    2015-01-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of pertuzumab (Roche) to submit evidence for the clinical and cost effectiveness of pertuzumab + trastuzumab + docetaxel for the treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic or locally recurrent unresectable breast cancer in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarises the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) initial decision. At the time of writing, final guidance had not been published by NICE. The clinical evidence was mainly derived from an ongoing phase III randomised double-blind placebo-controlled international multicentre clinical trial (CLEOPATRA), designed to evaluate efficacy and safety in 808 patients, which compared pertuzumab + trastuzumab + docetaxel (pertuzumab arm) with placebo + trastuzumab + docetaxel (control arm). Both progression-free survival (PFS) and overall survival (OS) were analysed at two data cut-off points-May 2011 (median follow-up of 18 months) and May 2012 (median follow-up of 30 months). At both time points, PFS was significantly longer in the pertuzumab arm (18.5 months compared with 12.4 months in the control arm at the first data cut-off point and 18.7 versus 12.4 months at the second data cut-off point). Assessment of OS benefit suggested an improvement for patients in the pertuzumab arm with a strong trend towards an OS benefit at the second data cut-off point; however, due to the immaturity of the OS data, the magnitude of the OS benefit was uncertain. Importantly, cardiotoxicity was not increased in patients treated with a combination of pertuzumab + trastuzumab + docetaxel. The ERG's main concern with the

  4. Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial†

    PubMed Central

    Clement, P. M.; Gauler, T.; Machiels, J. P.; Haddad, R. I.; Fayette, J.; Licitra, L. F.; Tahara, M.; Cohen, E. E. W.; Cupissol, D.; Grau, J. J.; Guigay, J.; Caponigro, F.; de Castro, G.; de Souza Viana, L.; Keilholz, U.; del Campo, J. M.; Cong, X. J.; Ehrnrooth, E.; Vermorken, J. B.

    2016-01-01

    Background In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years. Patients and methods Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m2/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. Results Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45–1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62–1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54–1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76–1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%–77%) and diarrhea (70%–80%) with afatinib, and stomatitis (43%) and fatigue (31%–34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in

  5. Metastatic sebaceous cell carcinoma, review of the literature and use of electrochemotherapy as possible new treatment modality

    PubMed Central

    Baduel, Eugenio Sportoletti; Brizio, Matteo; Picciotto, Franco; Dika, Emi; Fierro, Maria Teresa; Macripò, Giuseppe; Quaglino, Pietro

    2016-01-01

    Abstract Background Metastatic extraorbital sebaceous carcinoma is a rare event that could involve the head and neck. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial. Material and methods Extensive literature search was done, and the treatment options are discussed. Results Results. The literature search found several treatment modalities in use for the treatment of metastatic extraorbital sebaceous carcinoma. Electrochemotherapy was not included in the reported treatments. We used this technique for a man of 85 years old with a recurrent and locally metastatic extraorbital sebaceous carcinoma of the scalp. During the period of 8 months, two sessions of electrochemotherapy were employed, which resulted in an objective response of the tumour and good quality of life. Conclusions Electrochemotherapy has shown to be a interesting tools for treatment of metastatic extraorbital sebaceous carcinoma when other radical options are not available or convenient. PMID:27679547

  6. Metastatic sebaceous cell carcinoma, review of the literature and use of electrochemotherapy as possible new treatment modality

    PubMed Central

    Baduel, Eugenio Sportoletti; Brizio, Matteo; Picciotto, Franco; Dika, Emi; Fierro, Maria Teresa; Macripò, Giuseppe; Quaglino, Pietro

    2016-01-01

    Abstract Background Metastatic extraorbital sebaceous carcinoma is a rare event that could involve the head and neck. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial. Material and methods Extensive literature search was done, and the treatment options are discussed. Results Results. The literature search found several treatment modalities in use for the treatment of metastatic extraorbital sebaceous carcinoma. Electrochemotherapy was not included in the reported treatments. We used this technique for a man of 85 years old with a recurrent and locally metastatic extraorbital sebaceous carcinoma of the scalp. During the period of 8 months, two sessions of electrochemotherapy were employed, which resulted in an objective response of the tumour and good quality of life. Conclusions Electrochemotherapy has shown to be a interesting tools for treatment of metastatic extraorbital sebaceous carcinoma when other radical options are not available or convenient.

  7. A Case of Metastatic Melanoma in the Ureter

    PubMed Central

    Hossack, Tania

    2016-01-01

    Advances in the treatment of melanoma are resulting in patients living for extended periods after being diagnosed with metastatic disease. Metastases to the ureter are rare, but they have been described in the literature on a number of occasions. In this case report, we describe a patient with established metastatic melanoma who, whilst taking and responding to immunomodulatory therapy, was found to have an obstructive mass in the middle of his left ureter. Rather than performing either a nephroureterectomy or partial resection of the ureter, we opted to perform an endoscopic resection of the melanoma. Follow-up imaging at 12 months shows no evidence of local disease recurrence. We submit that primary endoscopic management of metastatic melanoma in the ureter is a viable alternative to a radical approach.

  8. Bortezomib With or Without Irinotecan in Treating Patients With Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2014-05-07

    Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  9. Advance Directives and Do-Not-Resuscitate Orders in Patients with Cancer with Metastatic Spinal Cord Compression: Advanced Care Planning Implications

    PubMed Central

    Palmer, J. Lynn; Bianty, Josephine; Konzen, Benedict; Shin, Ki; Bruera, Eduardo

    2010-01-01

    Abstract Objectives Communication about end-of-life decisions is crucial. Although patients with metastatic spinal cord compression (MSCC) have a median survival time of 3 to 6 months, few data are available concerning the presence of advance directives and do-not-resuscitate (DNR) orders in this population. The objective of this study was to determine presence of advance directives and DNR order among patients with MSCC. Methods We retrospectively reviewed data concerning advance directives for 88 consecutive patients with cancer who had MSCC and required rehabilitation consultation at The University of Texas M. D. Anderson Cancer Center from September 20, 2005 to August 29, 2008. We characterized the data using univariate descriptive statistics and used the Fisher exact test to find correlations. Results The mean age of this patient population was 55 years (range, 24–81). Thirty patients (33%) were female. Twenty patients (23%) had a living will, 27 patients (31%) had health care proxies, and 10 patients (11%) had either out-of-hospital DNR order and/or dictated DNR note. The median survival time for these patients was 4.3 months. Conclusion Despite strong evidence showing short survival times for MSCC patients, it seems many of these patients are not aware of the urgency to have an advance directive. This may be an indicator of delayed end-of-life palliative care and suboptimal doctor–patient communication. Using the catastrophic event of a diagnosis of MSCC to trigger communication and initiate palliative care may be beneficial to patients and their families. PMID:20192843

  10. Sequence-dependence of cisplatin and 5-fluorouracil in advanced and recurrent gastric cancer.

    PubMed

    Koizumi, Wasaburo; Kurihara, Minoru; Hasegawa, Koichi; Chonan, Akimichi; Kubo, Yasuhiko; Maekawa, Ryuichiro; Iwasaki, Ryozo; Sasai, Tadashi; Fukuyama, Yoshio; Ishikawa, Kunitsugu; Miyoshi, Kazuo; Yasutake, Koichi; Hayakawa, Makoto

    2004-09-01

    This randomized controlled clinical trial was designed to compare the safety and effectiveness of different sequences of treatment with cisplatin (CDDP) and 5-fluorouracil (5-FU) in patients with unresectable advanced and post-operative recurrent gastric cancer. Patients with unresectable advanced or post-operative recurrent gastric cancer were randomly assigned by a registration center to group A or B. Group A received CDDP (80 mg/m(2)) as a continuous 2-h intravenous infusion on day 1 and 5-FU (700 mg/m(2)) as a continuous intravenous infusion on days 2-5. Group B was given 5-FU (700 mg/m(2)) as a continuous intravenous infusion on days 1-4, followed by CDDP (80 mg/m(2)) as a continuous 2-h intravenous infusion on day 5. Each course of chemotherapy was repeated every 28 days. A total of 74 patients were enrolled. One patient died accidentally, and 5 could not be evaluated. Response was assessable in 68 patients. The response rate was 31.3% (10/32) in group A as compared with 13.9% (5/36) in group B. Although the response rate was higher in Group A, the difference was not significant (p=0.085). The response rate in patients with diffuse type tumors was significantly lower in group B. There was no difference between the groups in response among patients with intestinal type tumors. The median overall survival was 239 and 174 days and time to progression was 175 and 140 days in group A and group B, respectively. Although there were trends toward longer survival and time to progression in group A, the differences between the groups were not statistically significant. There was also no difference in the type or incidence of adverse reactions. The results of this controlled study indicate that the overall response rate was slightly but not significantly higher in patients who received CDDP before 5-FU. Among patients with diffuse type tumors, the response rate was significantly lower when 5-FU was administered before CDDP. Our results suggest that CDDP should be given

  11. Subgroup Analyses from a Phase 3, Open-Label, Randomized Study of Eribulin Mesylate Versus Capecitabine in Pretreated Patients with Advanced or Metastatic Breast Cancer

    PubMed Central

    Twelves, Chris; Awada, Ahmad; Cortes, Javier; Yelle, Louise; Velikova, Galina; Olivo, Martin S.; Song, James; Dutcus, Corina E.; Kaufman, Peter A.

    2016-01-01

    PURPOSE AND METHODS Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged ≥18 years with advanced/metastatic breast cancer and ≤3 prior chemotherapies (≤2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m2 on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m2 on days 1–14 (21-day cycles). RESULTS In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms. CONCLUSIONS Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies. TRIAL REGISTRATION (PRIMARY STUDY) This study reports the subgroup analyses of eribulin versus capecitabine from a phase 3, open-label, randomized study (www.clinicaltrials.gov; ClinicalTrials.gov identifier: NCT00337103). PMID:27398025

  12. Results of chest wall resection for recurrent or locally advanced breast malignancies.

    PubMed

    Veronesi, Giulia; Scanagatta, Paolo; Goldhirsch, Aron; Rietjens, Mario; Colleoni, Marco; Pelosi, Giuseppe; Spaggiari, Lorenzo

    2007-06-01

    Between 1998 and 2003 we observed 15 women who underwent full thickness chest wall resection (FTCWR) followed by plastic reconstruction for locally recurrent or primary breast cancer. Preoperative symptoms were: pain (5 patients), malodorous ulceration (3 patients), presence of tumour mass (4 patients) and thoracic deformity (2 patients). One patient was asymptomatic. Surgery was partial sternectomy with rib resection in 9 patients, rib resection alone in 5, and total sternectomy in one. No perioperative mortality or major morbidity occurred; minor complications occurred in 3 patients (20%). Five of the six surviving patients reported a positive overall outcome in a telephonic interview. Median overall and disease-free survival were 23.4 and 17.5 months, respectively. In conclusion, FTCWR is a safe procedure with low morbidity and mortality that can provide good symptoms palliation in patients with locally advanced breast malignancies, so it should be considered more often by interdisciplinary care providers in those patients who fail to respond to classic multimodality treatment.

  13. Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer.

    PubMed

    Riemsma, Rob; Forbes, C A; Kessels, A; Lykopoulos, K; Amonkar, M M; Rea, D W; Kleijnen, J

    2010-08-01

    To undertake a systematic review of three first-line treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR+, i.e. ER+ and/or PgR+) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-to-progression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (Q-Twist difference = 1.5; P < 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5

  14. GTI-2040, Oxaliplatin, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer or Other Solid Tumors

    ClinicalTrials.gov

    2013-03-26

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  15. Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer or Cholangiocarcinoma

    ClinicalTrials.gov

    2015-06-03

    Extrahepatic Bile Duct Adenocarcinoma; Gallbladder Adenocarcinoma; Gallbladder Adenocarcinoma With Squamous Metaplasia; Hilar Cholangiocarcinoma; Recurrent Extrahepatic Bile Duct Carcinoma; Recurrent Gallbladder Carcinoma; Undifferentiated Gallbladder Carcinoma; Unresectable Extrahepatic Bile Duct Carcinoma; Unresectable Gallbladder Carcinoma

  16. Treatment for metastatic nasopharyngeal carcinoma.

    PubMed

    Bensouda, Y; Kaikani, W; Ahbeddou, N; Rahhali, R; Jabri, M; Mrabti, H; Boussen, H; Errihani, H

    2011-04-01

    Nasopharyngeal carcinoma (NPC) is a specific entity different from head and neck carcinoma. Incidence is higher in South-East Asia and North Africa. Prognosis, especially for locally advanced stages (IIB - IVB) and metastasis, remains poor: more than third of cases will present local and/or metastatic recurrence. Overall 5-year survival for all NPC stages ranges from 50% to 70%. The role of chemotherapy in metastasis is well established, and remains an important palliative treatment, although no randomized trial has been reported comparing the different chemotherapy regimens. As 1(st)-line treatment, platin-based regimens seems optimal; in 2(nd) line and after progression under platins, there is no consensus: monotherapy with drugs such as gemcitabine, capecitabine or taxanes has been the most widely tested, with acceptable results. Future trials should integrate targeted therapy, in the light of overexpression of EGFR1 and C-kit in NPC. The present study presents a review of the literature concerning the various studies of metastatic NPC. PMID:21177151

  17. Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye

    ClinicalTrials.gov

    2015-06-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  18. Dabrafenib for Treating Unresectable, Advanced or Metastatic BRAF V600 Mutation-Positive Melanoma: An Evidence Review Group Perspective.

    PubMed

    Fleeman, Nigel; Bagust, Adrian; Beale, Sophie; Boland, Angela; Dickson, Rumona; Dwan, Kerry; Richardson, Marty; Dundar, Yenal; Davis, Helen; Banks, Lindsay

    2015-09-01

    The National Institute for Health and Care Excellence (NICE) invited GlaxoSmithKline, the manufacturer of dabrafenib, to submit evidence for the clinical and cost effectiveness of dabrafenib for the treatment of unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision in October 2014. The clinical evidence for dabrafenib was derived from an ongoing phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BREAK-3) involving 230 patients randomized 2:1 to receive either dabrafenib or dacarbazine. A significant improvement in median progression-free survival (PFS) but not overall survival (OS) was reported in the dabrafenib arm compared with dacarbazine. Vemurafenib is considered a more appropriate comparator than is dacarbazine. The clinical evidence for vemurafenib was derived from a completed phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BRIM-3) involving 675 patients randomized 1:1 to receive either vemurafenib or dacarbazine. A significant improvement in median PFS and OS was reported in the vemurafenib arm compared with dacarbazine. As there is no direct evidence comparing dabrafenib versus vemurafenib, the company presented an indirect treatment comparison (ITC) that demonstrated no statistical differences between dabrafenib and vemurafenib for PFS or OS. The ERG expressed concerns with the ITC, mainly in relation to the validity of the assumptions underpinning the methodology; the ERG concluded this resulted in findings that are unlikely to be robust or reliable. Dabrafenib and

  19. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours

    PubMed Central

    Soo, Ross Andrew; Syn, Nicholas; Lee, Soo-Chin; Wang, Lingzhi; Lim, Xn-Yii; Loh, Marie; Tan, Sing-Huang; Zee, Ying-Kiat; Wong, Andrea Li-Ann; Chuah, Benjamin; Chan, Daniel; Lim, Siew-Eng; Goh, Boon-Cher; Soong, Richie; Yong, Wei-Peng

    2016-01-01

    The FDA-approved starting dosage of capecitabine is 1,250 mg/m2, and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m2. Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m2 b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m2 and 1,500 mg/m2. At 1,500 mg/m2, one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m2 b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment. PMID:27296624

  20. Systematic Review and Meta-Analysis on the Role of Chemotherapy in Advanced and Metastatic Neuroendocrine Tumor (NET)

    PubMed Central

    Wong, Matthew H.; Lee, Adrian; Li, Bob T.; Lumba, Sumit; Clarke, Stephen J.; Samra, Jaswinder; Pavlakis, Nick

    2016-01-01

    Background/Objectives In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect of chemotherapy on response rates (RR), progression-free survival (PFS), overall survival (OS) and toxicity compared to other chemotherapies/systemic therapies or best supportive care in patients with advanced or metastatic NET. Methods Randomised controlled trials (RCTs) from 1946 to 2015 were identified from MEDLINE, EMBASE, other databases and conference proceedings. Review of abstracts, quality assessment and data abstraction were performed independently by two investigators. Meta-analyses were conducted using Mantel-Haenszel analysis with random-effects modelling. Results Six RCTs comparing standard streptozotocin plus 5-fluorouacil (STZ/5FU) chemotherapy to other chemotherapy regimens, and 2 comparing this to interferon (IFN) were included. Only 1 study was considered at low risk of bias. STZ/5-FU was no different to other chemotherapies in response rate [RR 0.96; 95% confidence interval (CI) 0.72–1.27], PFS (RR 0.95; CI 0.81–1.13), or OS (RR 1.03; CI 0.77–1.39). IFN may produce higher response than STZ/5FU (RR 0.20; CI 0.04–1.13), but event rates were small and survival was no different. Interferon was associated with higher overall haematological (RR 0.47; CI 0.27–0.82) and lower overall renal toxicity (RR 3.61; CI 1.24–10.51). Conclusion Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors. There is currently no evidence that one chemotherapeutic regimen is significantly better than the other, nor is interferon better than chemotherapy. There is an urgent need to design RCTs comparing modern chemotherapy to other agents in NET. PMID:27362760

  1. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours.

    PubMed

    Soo, Ross Andrew; Syn, Nicholas; Lee, Soo-Chin; Wang, Lingzhi; Lim, Xn-Yii; Loh, Marie; Tan, Sing-Huang; Zee, Ying-Kiat; Wong, Andrea Li-Ann; Chuah, Benjamin; Chan, Daniel; Lim, Siew-Eng; Goh, Boon-Cher; Soong, Richie; Yong, Wei-Peng

    2016-01-01

    The FDA-approved starting dosage of capecitabine is 1,250 mg/m(2), and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m(2). Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m(2) b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m(2) and 1,500 mg/m(2). At 1,500 mg/m(2), one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m(2) b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment. PMID:27296624

  2. Pembrolizumab and Ziv-aflibercept in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-09-09

    Adult Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Colorectal Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Ovarian Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

  3. Iodine-125 seed implantation as an adjunct to surgery in advanced recurrent squamous cell cancer of the head and neck

    SciTech Connect

    Park, R.I.; Liberman, F.Z.; Lee, D.J.; Goldsmith, M.M.; Price, J.C. )

    1991-04-01

    Survival for extensive recurrent squamous cell carcinomas of the head and neck remains poor, with the major cause of death being local recurrence. Surgical implantation of iodine-125 interstitial seeds allows tumoricidal doses of radiation to be delivered to residual tumor while minimizing radiation doses to the surrounding tissues. From 1978 to 1988, 39 implantations were performed on 35 patients for extensive recurrent squamous cell carcinoma of the head and neck. The decision for implantation was based on positive margins or close to resection margins from frozen sections after salvage resection. The determinate 5-year disease-free survival was 41%, with both the overall and no evidence of disease 5-year survivals being 29%. Significant complications occurred in 36% of all cases. This figure increased to 56% when flap reconstruction was required. Possible reasons for this seemingly high complication rate are discussed. Considering the advanced nature of these recurrent carcinomas, surgical resection with iodine-125 seed implantation appears to be an effective method of managing disease that might otherwise be judged unresectable and treated for palliation only.

  4. Phase II Study of Intraventricular Methotrexate in Children With Recurrent or Progressive Malignant Brain Tumors

    ClinicalTrials.gov

    2016-06-30

    Recurrent Childhood Medulloblastoma; Recurrent Childhood Ependymoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Embryonal Tumor With Abundant Neuropil and True Rosettes; Metastatic Malignant Neoplasm to the Leptomeninges

  5. Long-Term Outcomes With Intraoperative Radiotherapy as a Component of Treatment for Locally Advanced or Recurrent Uterine Sarcoma

    SciTech Connect

    Barney, Brandon M.; Petersen, Ivy A.; Dowdy, Sean C.; Bakkum-Gamez, Jamie N.; Haddock, Michael G.

    2012-05-01

    Purpose: To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. Methods and Materials: From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORT dose was 12.5 Gy (range, 10-20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20-62.5 Gy), and 6 patients also received perioperative systemic therapy. Results: Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11-203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. Conclusions: A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence.

  6. 6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

    NASA Astrophysics Data System (ADS)

    Velikaya, V. V.; Musabaeva, L. I.; Lisin, V. A.; Startseva, Zh. A.

    2016-08-01

    The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

  7. Sorafenib for Metastatic Thyroid Cancer

    Cancer.gov

    A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

  8. Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer

    PubMed Central

    NAMIKAWA, TSUTOMU; MUNEKAGE, ERI; MUNEKAGE, MASAYA; MAEDA, HIROMICHI; YATABE, TOMOAKI; KITAGAWA, HIROYUKI; SAKAMOTO, KOUICHI; OBATAKE, MASAYUKI; KOBAYASHI, MICHIYA; HANAZAKI, KAZUHIRO

    2016-01-01

    The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P=0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3–4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically. PMID:27330770

  9. Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post‐liver transplantation recurrence

    PubMed Central

    Schiff, Eugene R.; Vierling, John M.; Landis, Charles; Fontana, Robert J.; Yang, Rong; McPhee, Fiona; Hughes, Eric A.; Noviello, Stephanie; Swenson, Eugene S.

    2016-01-01

    Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post‐liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open‐label ALLY‐1 study assessed the safety and efficacy of a 60‐mg once‐daily dosage of daclatasvir (pan‐genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24‐week follow‐up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on‐treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child‐Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%‐92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child‐Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%‐99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment‐related serious adverse events. Conclusion: The pan‐genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with

  10. Veliparib in Combination With Carboplatin and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors

    ClinicalTrials.gov

    2015-05-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  11. Metastatic Colonization

    PubMed Central

    Massagué, Joan; Obenauf, Anna C.

    2016-01-01

    Metastasis is the main cause of death from cancer. To colonize distant organs, circulating cancer cells must overcome many obstacles through mechanisms that we are starting to understand. Infiltrating distant tissue, evading immune defences, adapting to supportive niches, surviving as latent tumour-initiating seeds, and eventually breaking out to replace the host tissue, are key steps for metastatic colonization. These obstacles make metastasis a highly inefficient process, but once metastases are established current treatments frequently fail to provide durable responses. A better understanding of the mechanistic determinants of metastatic colonization is needed to better prevent and treat metastatic cancer. PMID:26791720

  12. [Effectiveness of chemoradiotherapy for a patient with local recurrence of advanced gastric cancer followed by curable gastrectomy].

    PubMed

    Natsume, Soichiro; Iwasaki, Yoshiaki; Yajima, Kazuhito; Yuu, Ken; Oohinata, Ryouki; Ishiyama, Satoshi; Takahashi, Keiichi; Maeda, Yoshiharu

    2014-11-01

    We report here the effectiveness of chemoradiotherapy for a patient with local recurrence followed by curable gastrectomy. A 57-year-old man presented with a history of total gastrectomy with distal pancreatectomy and splenectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for advanced gastric cancer arising from the cardia. Esophageal intramural metastasis and lymph node metastasis around the right recurrent nerve were detected by chest-abdominal computed tomography and gastrointestinal endoscopy 27 months after the initial gastrectomy. Stable disease was achieved following 7 courses of chemotherapy using S-1 plus CDDP. Concurrent chemoradiotherapy including administration of S-1 and radiation of total 50 Gy (2 Gy/25 Fr) was selected for local tumor control. The patient was not able to eat solid food because of esophageal stenosis from regrowth of intramural metastasis of the esophagus 60 months after the chemotherapy. A WallFlex™ Duodenal Stent was placed to improve the dysphagia 67 months after chemotherapy. The patient died from recurrence of gastric cancer 69 months after completion of the initial chemotherapy and 2 months after the stent insertion.

  13. Is radiotherapy an effective treatment option for recurrent metastatic malignant melanoma? A case report of short-course, large-fraction radiation and a literature review

    PubMed Central

    Hallock, Abhirami; Vujovic, Olga; Yu, Edward

    2011-01-01

    BACKGROUND Malignant melanoma is regarded to be radiation resistant. A case of recurrent malignant melanoma with in-transit metastasis treated with short-course, high-fraction palliative radiation is presented to illustrate the effectiveness of radiotherapy. METHOD An 80-year-old woman initially treated surgically for a primary malignant melanoma of the left lower leg presented with multiple in-transit metastases. Palliative radiation was offered to treat two fungating in-transit masses that were resistant to treatments of isolated limb infusion and intralesional interleukin-2. RESULTS Treatment consisted of short-course, high-fraction radiation with 800 cGy fractions given over three weeks on days 0, 7 and 21, for a total dose of 2400 cGy. She experienced a complete response that was maintained for six months. CONCLUSIONS Radiation is an effective treatment option for palliation of recurrent malignant melanoma. Complete response is possible even with short-course, high-fraction radiation. PMID:23204890

  14. Target Definition in Salvage Radiotherapy for Recurrent Prostate Cancer: The Role of Advanced Molecular Imaging

    PubMed Central

    Amzalag, Gaël; Rager, Olivier; Tabouret-Viaud, Claire; Wissmeyer, Michael; Sfakianaki, Electra; de Perrot, Thomas; Ratib, Osman; Miralbell, Raymond; Giovacchini, Giampiero; Garibotto, Valentina; Zilli, Thomas

    2016-01-01

    Salvage radiotherapy (SRT) represents the main treatment option for relapsing prostate cancer in patients after radical prostatectomy. Several open questions remain unanswered in terms of target volumes definition and delivered doses for SRT: the effective dose necessary to achieve biochemical control in the SRT setting may be different if the tumor recurrence is micro- or macroscopic. At the same time, irradiation of only the prostatic bed or of the whole pelvis will depend on the localization of the recurrence, local or locoregional. In the “theragnostic imaging” era, molecular imaging using positron emission tomography (PET) constitutes a useful tool for clinicians to define the site of the recurrence, the extent of disease, and individualize salvage treatments. The best option currently available in clinical routine is the combination of radiolabeled choline PET imaging and multiparametric magnetic resonance imaging (MRI), associating the nodal and distant metastases identification based on PET with the local assessment by MRI. A new generation of targeted tracers, namely, prostate-specific membrane antigen, show promising results, with a contrast superior to choline imaging and a higher detection rate even for low prostate-specific antigen levels; validation studies are ongoing. Finally, imaging targeting bone remodeling, using whole-body SPECT–CT, is a relevant complement to molecular/metabolic PET imaging when bone involvement is suspected. PMID:27065024

  15. 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    PubMed Central

    O’Donoghue, Joseph A.; Beylergil, Volkan; Lyashchenko, Serge; Ruan, Shutian; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Gonen, Mithat; Lewis, Jason S.; Holland, Jason P.; Cheal, Sarah M.; Reuter, Victor E.; Osborne, Joseph R.; Loda, Massimo F.; Smith-Jones, Peter M.; Weber, Wolfgang A.; Bander, Neil H.; Scher, Howard I.; Morris, Michael J.; Larson, Steven M.

    2015-01-01

    Purpose Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. 89Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection. Methods Ten patients with metastatic prostate cancer received 5 mCi of 89Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by 89Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of 89Zr-huJ591 was done. Optimal time for imaging post-injection was determined. Results The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of 89Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1–14 h) and 62 ± 13 h (range 51–89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153–317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on 89Zr-huJ591, while the remaining 11 lesions were 89Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on 89Zr-huJ591

  16. Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-10-14

    Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  17. VEGF Trap in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2015-02-02

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma

  18. Oncology nursing support for safe and effective use of eribulin in metastatic breast cancer.

    PubMed

    Donovan, Diana; Urquhart, Laura; Hopkins, Una; Knight, Sandra; Moore, Laura

    2014-01-01

    Nurse practitioners play important roles in breast cancer prevention, early detection, therapeutic efficacy, and surveillance. Assessment of a patient's health status is part of the nine nurse practitioner core competencies updated in 2012 by the National Organization of Nurse Practitioner Faculties. Although adverse events are common in treatment for metastatic breast cancer (MBC), proactive management strategies can limit the number and/or severity of adverse events. Additionally, knowledge of common metastatic sites and clinical signs/symptoms of recurrence provides one of the first-line strategies for successful treatment. We review five case studies of women with MBC who were managed successfully with eribulin mesylate in late lines of therapy after at least two chemotherapeutic regimens for advanced breast cancer that included both an anthracycline and a taxane in either the adjuvant or metastatic setting. PMID:24855406

  19. Tumor attributes predicting cutaneous metastatic destiny: a report of two interesting cases.

    PubMed

    Gurumurthi, Ravichandran; Thirumalai, Raja; Easow, Jose M; Mohan, Subhashini

    2014-07-01

    Cutaneous metastases are the result of complex interaction between the tumor cells ("seed") and the host environment ("soil"). Metastases to the skin can be an early sign of internal malignancy or represent recurrence of the primary tumor and portends a poorer prognosis. Invasion and metastasis are the hallmarks of on cogenesis. Skin is the largest organ in the body, but the incidence of metastases is low. With advances in molecular biology, factors responsible for the initiation and perpetuation of metastatic tumor cells at distant sites are being elucidated. The concept of "pre-metastatic niche" and interaction between various chemokines has given a new outlook in understanding the organ specificity of metastatic tumor cells. We present two cases of cutaneous metastases with interesting clinical findings correlating with its biologic subtypes.

  20. Rationale and design of LUX-Head & Neck 1: a randomised, Phase III trial of afatinib versus methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma who progressed after platinum-based therapy

    PubMed Central

    2014-01-01

    Background Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) receiving platinum-based chemotherapy as their first-line treatment have a dismal prognosis, with a median overall survival (OS) of ~7 months. Methotrexate is sometimes used following platinum failure or in patients not fit enough for platinum therapy, but this agent has not demonstrated any OS improvement. Targeted therapies are a novel approach, with the EGFR-targeting monoclonal antibody cetuximab (plus platinum-based chemotherapy) approved in the US and Europe in the first-line R/M setting, and as monotherapy following platinum failure in the US. However, there is still a high unmet medical need for new treatments that improve outcomes in the second-line R/M setting following failure on first-line platinum-containing regimens. Afatinib, an irreversible ErbB family blocker, was recently approved for the first-line treatment of EGFR mutation-positive metastatic non-small cell lung cancer. Afatinib has also shown clinical activity similar to cetuximab in a Phase II proof-of-concept HNSCC trial. Based on these observations, the Phase III, LUX-Head & Neck 1 study is evaluating afatinib versus methotrexate in R/M HNSCC patients following progression on platinum-based chemotherapy in the R/M setting. Methods/Design Patients with progressive disease after one first-line platinum-based chemotherapy are randomised 2:1 to oral afatinib (starting dose 40 mg once daily) or IV methotrexate (starting dose 40 mg/m2 once weekly) administered as monotherapy with best supportive care until progression or intolerable adverse events. Efficacy of afatinib versus methotrexate will be assessed in terms of progression-free survival (primary endpoint). Disease progression will be evaluated according to RECIST v1.1 by investigator and independent central review. Secondary endpoints include OS, tumour response and safety. Health-related quality of life and biomarker assessments will

  1. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established.

  2. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established. PMID:26805098

  3. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    PubMed

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity. PMID:17382431

  4. A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer

    PubMed Central

    Cetina, Lucely; Crombet, Tania; Jiménez-Lima, Roberto; Zapata, Sergio; Ramos, Mayra; Avila, Sandra; Coronel, Jaime; Charco, Eduardo; Bojalil, Rafael; Astudillo, Horacio; Bazán, Blanca; Dueñas-González, Alfonso

    2015-01-01

    Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m2 as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m2) or cisplatin (50 mg/m2) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5–96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer. PMID:25802932

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

    SciTech Connect

    Christiansen, Hans . E-mail: hchrist@gwdg.de; Hermann, Robert Michael; Martin, Alexios; Florez, Rodrigo; Kahler, Elke; Nitsche, Mirko; Hille, Andrea; Steiner, Wolfgang; Hess, Clemens F.; Pradier, Olivier

    2006-07-15

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

  6. Trastuzumab in Treating Patients With Locally Advanced or Metastatic Gallbladder Cancer or Bile Duct Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2014-05-15

    Adenocarcinoma of the Extrahepatic Bile Duct; Adenocarcinoma of the Gallbladder; Malignant Neoplasm; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  7. 7-Hydroxystaurosporine and Irinotecan Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)

    ClinicalTrials.gov

    2013-09-27

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Estrogen Receptor-negative Breast Cancer; Extensive Stage Small Cell Lung Cancer; Gastrointestinal Stromal Tumor; HER2-negative Breast Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Endometrial Carcinoma; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Cell Lung Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral

  8. Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas

    ClinicalTrials.gov

    2016-10-31

    Childhood Solid Neoplasm; Metastatic Melanoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hodgkin Lymphoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Rhabdomyosarcoma; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  9. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    ClinicalTrials.gov

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  10. Entinostat and Sorafenib Tosylate in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory or Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-18

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Unspecified Adult Solid Tumor, Protocol Specific

  11. Axitinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-05-31

    Extraocular Extension Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma

  12. [Palliative surgery for malignant bowel obstruction in patients with advanced and recurrent gastroenterological cancer].

    PubMed

    Kitani, Kotaro; Yukawa, Masao; Fujiwara, Yoshinori; Tsujie, Masanori; Hara, Joji; Ikeda, Mitsunori; Sato, Katsuaki; Isono, Sayuri; Kawai, Kenji; Miura, Ken; Watatani, Masahiro; Inoue, Masatoshi

    2013-11-01

    We report the outcomes of palliative surgery for the treatment of malignant bowel obstruction in patients with advanced gastroenterological cancer. We studied 20 patients who had undergone palliative surgery over 3 years. We analyzed the clinical findings, surgical procedure, postoperative clinical course, and prognosis. The origin of the patients was colorectal cancer( 9 cases), gastric cancer( 4 cases), uterine cancer( 3 cases), pancreatic cancer( 2 cases), bladder( 1 case), and anal cancer (1 case). Small bowel obstruction was noted in 8 cases and colorectal obstruction was noted in 14 cases. Colostomy was performed in 13 cases, resection and reconstruction were performed in 6 cases, and bypass was performed in 4 cases. Ninety percent of the patients were able to eat solid food following the surgery, but 20% of the patients were forced to have bowel obstruction. The median survival time after palliative surgery was 3 (range, 0-15) months, and 6 patients (30%) died within 2 months. We concluded that palliative surgery for the treatment of malignant bowel obstruction could improve the patients' quality of life. The decision for performing palliative surgery should be made while considering the patient's prognosis, wishes, and potential for symptom improvement. PMID:24393893

  13. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer

    PubMed Central

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo

    2015-01-01

    Objective To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Methods According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. Results In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Conclusions Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies. PMID:26157320

  14. Meta-analysis of chemotherapy with irinotecan or oxaliplatin-involved regimen for untreated metastatic advanced colorectal cancer.

    PubMed

    Zhuang, Luhong; Bai, Jianling; Huang, Huaying; Tang, Cuiju; Yang, Jinsong; Zhou, Baoning; Gong, Yongling; Duanmu, Zhong; Chen, Jinfei

    2010-01-01

    A large number of randomized controlled trials involving chemotherapy in the management of advanced colorectal cancer were conducted. 5-FU/LV in combination with irinotecan (IRI) or oxaliplatin (OXA) was used. The aim of the meta-analysis was to compare and evaluate the effectiveness and safety of the two therapeutic approaches for patients with advanced colorectal cancer. A literature search, study selection and assessment, data collection, and analysis were undertaken by two reviewers according to the Cochrane Handbook for Systematic Reviews of Interventions. Randomized controlled trials (RCTs) or quasi-RCTs comparing IRI versus OXA, in combination with 5-FU/LV in the treatment of advanced colorectal cancer were performed. Seven studies involving 2,107 patients met the inclusion criteria. The OXA + 5-FU/LV regimen showed a significant increase in survival by lower hazard ratios (HR) [HR 1.28; 95% CI (1.13-1.45)] and was associated with lower toxicities. The OXA + 5-FU/LV regimen was superior or equal to the IRI + 5-FU/LV regimen in prolonging time to progression and median survival. The IRI + 5-FU/LV regimen resulted in higher hazard ratios in nausea vomiting/emesis and diarrhea [HR 1.99, 95% CI (1.19-3.31); HR 1.83, 95% CI (1.38-2.44)] and lower hazard ratios in paresthesia, sensory neuropathy, and thrombocytopenia [HR 0.09, 95% CI (0.03-0.23); HR 0.04 95% CI (0.01-0.13); HR 0.19 95% CI (0.05-0.64)] than the OXA + 5-FU/LV regimen. Compared with IRI, OXA is more appropriate for the treatment of advanced colorectal cancer when combined with 5-FU/LV. OXA + 5-FU/LV should be considered as the first-line standard of care for advanced CRC patients.

  15. Radiosensitization of Chemotherapy-Refractory, Locally Advanced or Locally Recurrent Breast Cancer With Trastuzumab: A Phase II Trial

    SciTech Connect

    Horton, Janet K.; Halle, Jan; Ferraro, Madlyn; Carey, Lisa; Moore, Dominic T.; Ollila, David; Sartor, Carolyn I.

    2010-03-15

    Purpose: Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer. Methods and Materials: Eligible patients had measurable disease, normal cardiac function, and biopsy-confirmed residual HER2-positive disease. Patients received weekly trastuzumab (2 mg/kg intravenously), concurrent with radiotherapy (50 Gy) to the breast and regional lymph nodes for 5 weeks. If feasible, surgery followed radiotherapy. The primary endpoint was safety, and the secondary endpoint was efficacy (pathologic response and interval to symptomatic local progression). Results: Of the 19 patients enrolled, 7 were ineligible and received radiotherapy alone and 12 received therapy per protocol. Of these 12 patients, 11 had a Stage T4 diagnosis. Grade 3 toxicities included skin (n = 2) and lymphopenia (n = 1). One patient experienced delayed wound healing after surgery. No patients developed symptomatic cardiac dysfunction. Of the 7 patients who had undergone mastectomy, 3 (43%) had a substantial pathologic response (complete response or microscopic residual disease), significantly more than a comparison cohort (2 of 38 or 5%, p = .02). The median interval to symptomatic local progression was not reached. The median overall survival was 39 months. Conclusion: This is the first prospective trial providing evidence for a radiosensitizing effect of trastuzumab in breast cancer. The combination of trastuzumab and radiotherapy was well tolerated.

  16. Metastatic malignant chondroblastoma.

    PubMed

    Rodgers, W B; Mankin, H J

    1996-12-01

    A case of malignant chondroblastoma with metastases is reported. The patient initially presented with a lytic lesion in his left pubic ramus. He was treated with curettage, but the lesion recurred 3 years later. After repeated curettage, radiation therapy, and the late development of multiple bone and soft-tissue metastases, he succumbed to his disease 13 years after diagnosis. The surgical pathology from each of his several procedures was reviewed. Although no definite malignant transformation was apparent, a metastatic deposit curetted 3 months prior to death showed some increase in mitotic activity. Flow cytometry of specimens from the patient's first local recurrence and a late distant metastasis was performed and revealed the interval development of a minor aneuploid peak between the two samples. This fatal chondroblastoma is the only one in our series of 80 patients treated over the past 25 years. PMID:9001683

  17. Telaprevir- and Boceprevir-Based Triple Therapy for Hepatitis C in Liver Transplant Recipients with Advanced Recurrent Disease: A Multicenter Study

    PubMed Central

    Verna, Elizabeth C.; Saxena, Varun; Burton, James R.; O’Leary, Jacqueline G.; Dodge, Jennifer L.; Stravitz, Richard T.; Levitsky, Joshua; Trotter, James F.; Everson, Gregory T.; Brown, Robert S.; Terrault, Norah A.

    2016-01-01

    Background Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor (PI)-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis. Methods LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and safety. Results 45 patients with advanced fibrosis and 9 with cholestatic hepatitis (74% male, 57% with genotype 1a, and 63% prior non-responders) were included. SVR12 occurred in 51% of those with advanced fibrosis and 44% with cholestatic hepatitis, and eRVR was highly predictive of SVR12. Previous null/partial response (OR 0.09, p=0.003), low platelet count (OR 1.02, p=0.004), and steroid use (OR 0.16, p=0.03) were negatively associated with SVR12 in multivariable models. Six (11%) patients died during or after treatment, and hepatic decompensation during treatment occurred in 22% of patients with advanced fibrosis and 33% of patients with cholestatic hepatitis. Hispanic ethnicity (OR 9.37, p=0.03) and low albumin at treatment start (OR 0.01, p=0.001) were predictive of death or decompensation in multivariable models. Conclusions For LT recipients with recurrent advanced HCV and at highest need of effective treatment, PI-based triple therapy achieved sustained viral clearance in ~50% of patients. However, there is significant risk of serious adverse events including hepatic decompensation, arguing for earlier therapeutic intervention. The availability of antiviral drug combinations with higher efficacy and improved safety are of particular importance for post-transplant patients with advanced disease

  18. TORC1/2 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors

    ClinicalTrials.gov

    2016-06-17

    Adult Glioblastoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Solid Neoplasm; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  19. Gemcitabine Hydrochloride and Docetaxel With or Without Bevacizumab in Treating Patients With Advanced or Recurrent Uterine Leiomyosarcoma

    ClinicalTrials.gov

    2015-11-11

    Recurrent Uterine Corpus Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Corpus Leiomyosarcoma

  20. Malignant Pleural Effusion Supernatants Are Substitutes for Metastatic Pleural Tumor Tissues in EGFR Mutation Test in Patients with Advanced Lung Adenocarcinoma

    PubMed Central

    Wu, Ning; Nie, Xiaomeng; Xia, Yang; Han, Yiping; Li, Qiang; Zhu, Guanshan; Bai, Chong

    2014-01-01

    Background Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. Methods EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). Results EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). Conclusions The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test. PMID:24587142

  1. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    SciTech Connect

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses

  2. QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    ClinicalTrials.gov

    2016-10-26

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  3. Entinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer

    ClinicalTrials.gov

    2016-09-26

    Breast Adenocarcinoma; HER2/Neu Negative; Invasive Breast Carcinoma; Recurrent Breast Carcinoma; Solid Neoplasm; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  4. Young women with locally advanced breast cancer who achieve breast conservation after neoadjuvant chemotherapy have a low local recurrence rate.

    PubMed

    Sweeting, Raeshell S; Klauber-Demore, Nancy; Meyers, Michael O; Deal, Allison M; Burrows, Emily M; Drobish, Amy A; Anders, Carey K; Carey, Lisa A

    2011-07-01

    Women with locally advanced breast cancer (LABC) who are breast conservation (BCT) candidates after neoadjuvant chemotherapy have the best long-term outcome and low local-regional recurrence (LRR) rates. However, young women are thought to have a higher risk of LRR based on historical data. This study sought to evaluate LRR rates in young women who undergo BCT after neoadjuvant chemotherapy. We identified 122 women aged 45 years or younger with American Joint Committee on Cancer (AJCC) Stage II to III breast cancer, excluding T4d, treated with neoadjuvant chemotherapy from 1991 to 2007 from a prospective, Institutional Review Board-approved, single-institution database. Data were analyzed using Fisher eExact test, Wilcoxon tests, and the Kaplan-Meier method. Median follow-up was 6.4 years. Fifty-four (44%) patients had BCT and 68 (56%) mastectomy. Forty-six per cent were estrogen receptor-positivity and 28 per cent overexpressed Her2. Mean pretreatment T size was 5.6 cm in the BCT group and 6.7 cm in the mastectomy group (P = 0.04). LRR rates were no different after BCT compared with mastectomy (13 vs 18%, P = 0.6). Higher posttreatment N stage (P < 0.001) and AJCC stage (P = 0.008) were associated with LRR but not pretreatment staging. Disease-free survival was better for patients achieving BCT, with 5-year disease-free survival rates of 82 per cent (95% CI, 69 to 90%) compared with 58 per cent (95% CI, 45 to 69%) for mastectomy (P = 0.03). Young women with LABC who undergo BCT after neoadjuvant chemotherapy appear to have similar LRR rates compared with those with mastectomy. This suggests that neoadjuvant chemotherapy may identify young women for whom BCT may have an acceptable risk of LRR.

  5. Intraarterial Chemotherapy or Chemoembolization for Locally Advanced and/or Recurrent Hepatic Tumors: Evaluation of the Feeding Artery with an Interventional CT System

    SciTech Connect

    Hirai, Toshinori; Korogi, Yukunori; Ono, Ken; Maruoka, Kousei; Harada, Kazunori; Aridomi, Satoshi; Takahashi, Mutsumasa

    2001-05-15

    Purpose: To evaluate the utility of an interventional CT system for intraarterial chemotherapy or chemoembolization for locally advanced and/or recurrent hepatic tumors.Methods: Thirty-eight patients with locally advanced or recurrent hepatic tumors underwent 73 intraarterial contrast-enhanced CT (IA-CECT) examinations immediately before chemotherapy or chemoembolization. The degree of tumor vascularity on angiography and enhancement on IA-CECT was classified into three grades: no, mild, or marked vascularity. The IA-CECT grades were compared with the angiographic grades.Results: Twenty-nine (69%) of 42 examinations that were interpreted as having no or mild vascularity on angiography were classified as marked enhancement on IA-CECT. Based on IA-CECT findings, the position of the catheter was changed in 14 (19%) of 73 CT examinations. The reasons for the reposition were as follows: weak or no enhancement of the tumor (n = 11) or strong enhancement of the gallbladder wall (n = 3). The treatment strategy was changed in three patients (8%). No major complications relating to the interventional procedures were observed.Conclusions: IA-CECT is a reliable method when evaluating the perfusion of the tumor and adjacent normal tissues. The interventional CT system is useful for performing safe and effective intraarterial chemotherapy or chemoembolization in patients with locally advanced and/or recurrent hepatic tumors.

  6. Intratumoral PV701 in Treating Patients With Advanced or Recurrent Unresectable Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-23

    Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

  7. Outcomes in a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma

    SciTech Connect

    Paly, Jonathan J.; Hallemeier, Christopher L.; Biggs, Peter J.; Niemierko, Andrzej; Roeder, Falk; Martínez-Monge, Rafael; Whitson, Jared; Calvo, Felipe A.; Fastner, Gerd; Sedlmayer, Felix; Wong, William W.; Ellis, Rodney J.; Haddock, Michael G.; Choo, Richard; Shipley, William U.; Zietman, Anthony L.; Efstathiou, Jason A.

    2014-03-01

    Purpose/Objective(s): This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT). Methods and Materials: Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance. Results: IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P<.01), presence of sarcomatoid features (HR 3.7-6.9, P<.05), and higher IORT dose (HR 1.3, P<.001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P=.03). For locally recurrent tumors, positive margin status (HR 2.6, P=.01) was associated with decreased OS. Conclusions: We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to

  8. Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

    PubMed

    Inal, A; Kos, F T; Algin, E; Yildiz, R; Dikiltas, M; Unek, I T; Colak, D; Elkiran, E T; Helvaci, K; Geredeli, C; Dane, F; Balakan, O; Kaplan, M A; Durnali, A G; Harputoglu, H; Goksel, G; Ozdemir, N; Buyukberber, S; Gumus, M; Kucukoner, M; Ozkan, M; Uncu, D; Benekli, M; Isikdogan, A

    2012-01-01

    The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

  9. Metastatic Chordoma: Report of the Two Cases and Review of the Literature

    PubMed Central

    Rohatgi, Saurabh; Ramaiya, Nikhil H; Jagannathan, Jyothi P.; Howard, Stephanie A.; Shinagare, Atul B.; Krajewski, Katherine M.

    2015-01-01

    Chordomas are rare malignant bone tumours with a predilection for the axial skeleton, especially the sacrum and skull base. Median survival in patients with metastatic disease is usually dismal. Treatment is challenging due to the propensity for local recurrence, metastatic disease as well as lack of clear consensus regarding the optimal management. Our case report highlights two cases of sacral chordoma with locally recurrent and widespread metastatic disease, stable on molecular targeted therapy. PMID:26180502

  10. Everolimus, Erlotinib Hydrochloride, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer Previously Treated With Radiation Therapy

    ClinicalTrials.gov

    2016-03-01

    Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Tongue Cancer

  11. Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-04-18

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

  12. Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-09-26

    Endometrial Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC1 Uterine Corpus Cancer; Stage IIIC2 Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  13. Efficacy and safety of adding an agent to bevacizumab/taxane regimens for the first-line treatment of Her2-negative patients with locally recurrent or metastatic breast cancer: results from seven randomized controlled trials

    PubMed Central

    Liu, Xiaoqun; Liu, Xiangdong; Qiao, Tiankui; Chen, Wei; Yuan, Sujuan

    2016-01-01

    Background The combined therapy of bevacizumab (BEV) with taxane (paclitaxel or docetaxel) has shown an improvement on progression-free survival (PFS) and objective remission in Her2-negative patients with locally recurrent or metastatic breast cancer (LR/MBC). However, there was no benefit in overall survival (OS). The aim of this study was to evaluate the efficacy and safety of adding an agent to the BEV/taxane regimens for the treatment of Her2-negative patients with LR/MBC in a first-line setting. Materials and methods We searched PubMed, Web of Science, EMBASE, EBSCO, and the Cochrane Library databases for eligible trials. A meta-analysis was performed using Review Manager 5.0 freeware package. We calculated the hazard ratio (HR) for PFS and OS. The odds ratio (OR) was used to calculate objective response rate (ORR) and grade 3/4 drug-related adverse events. The heterogeneity of study outcomes was calculated by the χ2 test or I2 statistics. Results A total of 1,124 patients from seven randomized controlled trials were analyzed. Our meta-analysis showed that the ORR was significantly improved in the BEV/taxane-based triplet group when compared with the BEV/taxane-based doublet group (OR =1.31, 95% confidence interval [CI]: 1.03–1.67, P=0.03). A subset analysis showed that a similar result was achieved in the triplet group in which a cytotoxic agent was added (OR =1.46, 95% CI: 1.09–1.95, P=0.01). However, the PFS and OS had no statistically significant differences between the two groups (HR =0.87, 95% CI: 0.68–1.13, P=0.31; HR =0.98, 95% CI: 0.82–1.16, P=0.78, respectively). Regarding safety, thromboembolic events, fatigue, and diarrhea (all $grade 3) were more frequently observed in the BEV/taxane-based triplet group (OR =3.8, 95% CI: 1.86–7.79, P=0.0003; OR =1.55, 95% CI: 1.05–2.27, P=0.03; OR =2.1, 95% CI: 1.29–3.41, P=0.003, respectively). Other toxic effects had no statistically significant differences between the two groups. Conclusion Our

  14. Canadian Cancer Trials Group IND197: a phase II study of foretinib in patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-negative recurrent or metastatic breast cancer.

    PubMed

    Rayson, Daniel; Lupichuk, Sasha; Potvin, Kylea; Dent, Susan; Shenkier, Tamara; Dhesy-Thind, Sukhbinder; Ellard, Susan L; Prady, Catherine; Salim, Muhammad; Farmer, Patricia; Allo, Ghasson; Tsao, Ming-Sound; Allan, Alison; Ludkovski, Olga; Bonomi, Maria; Tu, Dongsheng; Hagerman, Linda; Goodwin, Rachel; Eisenhauer, Elizabeth; Bradbury, Penelope

    2016-05-01

    In murine models, overexpression of the MET receptor transgene induces tumors with human basal gene expression characteristics supporting MET inhibition as a treatment strategy for triple-negative breast cancer (TNBC). Foretinib is an oral multi-kinase inhibitor of MET, RON, AXL, TIE-2, and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Patients with centrally reviewed primary TNBC and 0-1 prior regimens for metastatic disease received daily foretinib 60 mg po in a 2-stage single-arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. In stage 2, correlative studies of MET, PTEN, EGFR, and p53 on archival and fresh tumor specimens were performed along with enumeration of CTCs. 45 patients were enrolled with 37 patients having response evaluable and centrally confirmed primary TNBC (cTNBC). There were 2 partial responses (ITT 4.7 % response evaluable cTNBC 5.4 %) with a median duration of 4.4 months (range 3.7-5 m) and 15 patients had stable disease (ITT 33 %, response evaluable cTNBC 40.5 %) with a median duration of 5.4 months (range 2.3-9.7 m). The most common toxicities (all grades/grade 3) were nausea (64/4 %), fatigue (60/4 %), hypertension (58/49 %), and diarrhea (40/7 %). Six serious adverse events were considered possibly related to foretinib and 4 patients went off study due to adverse events. There was no correlation between MET positivity and response nor between response and PTEN, EGFR, p53, or MET expression in CTCs. Although CCTG IND 197 did not meet its primary endpoint, the observation of a clinical benefit rate of 46 % in this cTNBC population suggests that foretinib may have clinical activity as a single, non-cytotoxic agent in TNBC (ClinicalTrials.gov number, NCT01147484). PMID:27116183

  15. Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-10-28

    Male Breast Cancer; Recurrent Breast Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  16. Genomic Sequencing in Determining Treatment in Patients With Metastatic Cancer or Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-07-26

    Metastatic Neoplasm; Recurrent Neoplasm; Recurrent Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Unresectable Malignant Neoplasm

  17. Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy to Treat Advanced/Recurrent Epithelial Ovarian Cancer: Results from a Retrospective Study on Prospectively Established Database1

    PubMed Central

    Sun, Jian-Hua; Ji, Zhong-He; Yu, Yang; Wu, Hai-Tao; Huang, Chao-Qun; Zhang, Qian; Yang, Xiao-Jun; Yonemura, Yutaka; Li, Yan

    2016-01-01

    BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS) and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC) remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed to treat peritoneal carcinomatosis (PC). This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A) or recurrent EOC (group B) were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI) 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2) for group B (P = .68). The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5) for group B (P = .034). Better median OS correlated with peritoneal cancer index (PCI) < 20 (76.6 months for PCI ≤ 20 group vs 38.5 months for PCI > 20 group, P = .01), complete cyroreduction (residual disease ≤ 2.5 mm) [79.5 months for completeness of cytoreduction (CC) score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05). Serious adverse events occurred in five patients (10.0%). Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety. PMID:27084429

  18. mTOR inhibition as an adjuvant therapy in a metastatic model of HPV+ HNSCC

    PubMed Central

    Coppock, Joseph D.; Vermeer, Paola D.; Vermeer, Daniel W.; Lee, Kimberly M.; Miskimins, W. Keith; Spanos, William C.; Lee, John H.

    2016-01-01

    Effective treatments for recurrent/metastatic human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) are limited. To aid treatment development, we characterized a novel murine model of recurrent/metastatic HPV+ HNSCC. Further analysis of the parental tumor cell line and its four recurrent/metastatic derivatives led to preclinical testing of an effective treatment option for this otherwise fatal disease. Reverse phase protein arrays identified key signaling cascades in the parental and recurrent/metastatic cell lines. While protein expression profiles differed among the recurrent/metastatic cell lines, activated proteins associated with the mTOR signaling cascade were a commonality. Based on these data, mTOR inhibition was evaluated as an adjuvant treatment for recurrent/metastatic disease. mTOR activity and treatment response were assessed in vitro by western blot, Seahorse, proliferation, clonogenic, and migration assays. Standard-of-care cisplatin/radiation therapy (CRT) versus CRT/rapamycin were compared in vivo. Low-dose rapamycin inhibited mTOR signaling, decreasing proliferation (43%) and migration (62%) while it enhanced CRT-induced cytotoxicity (3.3 fold) in clonogenic assays. Furthermore, rapamycin re-sensitized CRT-resistant, metastatic tumors to treatment in vivo, improving long-term cures (0–30% improved to 78–100%, depending on the recurrent/metastatic cell line) and limiting lymph node metastasis (32%) and lung metastatic burden (30 fold). Studies using immune compromised mice suggested rapamycin's effect on metastasis is independent of the adaptive immune response. These data suggest a role of mTOR activation in HPV+ HNSCC recurrent/metastatic disease and that adjuvant mTOR inhibition may enhance treatment of resistant, metastatic cell populations at the primary site and limit distant metastasis. PMID:27015118

  19. An Unusual Course of Metastatic Gastroesophageal Cancer

    PubMed Central

    Smith, William H.; Pintova, Sofya; DiMaio, Christopher J.; Manolas, Panagiotis; Lee, Dong-Seok; Hiotis, Spiros P.; Kartsonis, Maria; Holcombe, Randall F.; Dharmarajan, Kavita V.

    2015-01-01

    We are reporting on a case of a 41-year-old woman who presented with metastatic gastroesophageal junction cancer and who achieved prolonged survival with a multimodal treatment approach. After initially experiencing robust response to chemotherapy, she was treated for distant recurrence with palliative radiation to the gastrohepatic and supraclavicular lymph nodes and subsequently, given her unusual near-complete response, with reirradiation to the abdomen with curative intent for residual disease. The case presented is unique due to the patient's atypical treatment course, including technically difficult reirradiation to the abdomen, and the resulting prolonged survival despite metastatic presentation. PMID:26770853

  20. Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-11-04

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

  1. Mucoadhesive Oral Wound Rinse in Preventing and Treating Stomatitis in Patients With ER- or PR-Positive Metastatic or Locally Recurrent Breast Cancer That Cannot be Removed by Surgery Receiving Everolimus

    ClinicalTrials.gov

    2016-09-07

    Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Oral Complications; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  2. Pilot Trial of CRLX101 in Treatment of Patients With Advanced or Metastatic Stomach, Gastroesophageal, or Esophageal Cancer That Cannot be Removed by Surgery

    ClinicalTrials.gov

    2015-06-03

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  3. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-06-10

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  4. Selumetinib and Akt Inhibitor MK-2206 in Treating Patients With Refractory or Advanced Gallbladder or Bile Duct Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-09-08

    Adenocarcinoma of the Gallbladder; Adenocarcinoma With Squamous Metaplasia of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage II Gallbladder Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer

  5. TRIO-012: a multicenter, multinational, randomized, double-blind phase III study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer.

    PubMed

    Mackey, John; Gelmon, Karen; Martin, Miguel; McCarthy, Nicole; Pinter, Tamas; Rupin, Mathieu; Youssoufian, Hagop

    2009-11-01

    In this multinational, placebo-controlled, randomized phase III trial, Translational Research In Oncology (TRIO) will define the efficacy and safety of adding a novel antiangiogenic agent, IMC-1121B (ramucirumab), to standard first-line docetaxel chemotherapy for women with HER2-negative metastatic breast cancer. We will evaluate whether the addition of IMC-1121B prolongs progression-free survival and whether its use improves overall survival. Accrual is under way.

  6. Combined therapy: surgery and intraoperative HDR brachytherapy for locally advanced and recurrent rectal cancer. Practical experience of Brachytherapy Department in Warsaw

    PubMed Central

    Radziszewski, Jakub; Lyczek, Jaroslaw; Kawczynska, Maria; Kulik, Anna

    2009-01-01

    Purpose Patients with locally advanced and recurrent rectal cancer have a dismal prognosis. The aim of proposed combined therapy – surgery and intraoperative brachytherapy, is to improve results of already applied methods and to define optimal group of patients for this treatment. We introduce practical experience of Brachytherapy Department in Cancer Centre – Institute in Warsaw. Material and methods Patients with primary T4NxM0 rectal cancer and isolated local pelvic recurrence were qualified for therapy. Between January 2005 and September 2008, 13 patients were included: 4 with primary cancer and 9 with recurrence, median age of 56. After surgical resection intraoperative radiotherapy was delivered with boost of high dose rate brachytherapy of 20Gy dose to the tumor bed. Results Primary point of the study is to evaluate impact of applied therapy on local control (LC), overall survival (OS) and disease free survival (DFS). Median follow-up is 16 months. Four of the patients died and 3 survivors are disease-free. There was no case of perioperative mortality. Conclusions A multimodality approach, using surgical resection with intra operative brachytherapy improves local control as well as patients survival in comparison with historical treatment group. Combined therapy is related to high morbidity, but low mortality. The preliminary observations seem to correspond with other authors data.

  7. Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma : a NICE single technology appraisal.

    PubMed

    Kilonzo, Mary; Hislop, Jenni; Elders, Andrew; Fraser, Cynthia; Bissett, Donald; McClinton, Samuel; Mowatt, Graham; Vale, Luke

    2013-01-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute's single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE's subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies

  8. Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas.

    PubMed

    Cho, Eun Yoon; Park, Kyeongmee; Do, Ingu; Cho, Junhun; Kim, Jiyun; Lee, Jeeyun; Kim, Seonwoo; Kim, Kyoung-Mee; Sohn, Tae Sung; Kang, Won Ki; Kim, Sung

    2013-05-01

    Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be

  9. The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.

    PubMed

    Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B; Galante, Pedro A F; Perez, Rodrigo O; Camargo, Anamaria A

    2015-11-10

    Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.

  10. Intraoperative Radiation Therapy Reduces Local Recurrence Rates in Patients With Microscopically Involved Circumferential Resection Margins After Resection of Locally Advanced Rectal Cancer

    SciTech Connect

    Alberda, Wijnand J.; Verhoef, Cornelis; Nuyttens, Joost J.; Meerten, Esther van; Rothbarth, Joost; Wilt, Johannes H.W. de; Burger, Jacobus W.A.

    2014-04-01

    Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.

  11. The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

    PubMed Central

    Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B.; Galante, Pedro A.F.; Perez, Rodrigo O.; Camargo, Anamaria A.

    2015-01-01

    Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice. PMID:26451609

  12. Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function

    ClinicalTrials.gov

    2015-06-19

    Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

  13. Surgical Outcomes of Hemorrhagic Metastatic Brain Tumors

    PubMed Central

    Yoo, Heon; Jung, Eugene; Gwak, Ho Shin; Shin, Sang Hoon

    2011-01-01

    Purpose Hemorrhagic metastatic brain tumors are not rare, but little is known about the surgical outcome following treatment. We conducted this study to determine the result of the surgical outcome of hemorrhagic metastatic brain tumors. Materials and Methods From July 2001 to December 2008, 21 patients underwent surgery for hemorrhagic metastatic brain tumors at our institution. 15 patients had lung cancer, 3 had hepatocellular carcinoma, and the rest had rectal cancer, renal cell carcinoma, and sarcoma. 20 patients had macroscopic hemorrhage in the tumors, and one patient had intracerebral hemorrhage surrounding the tumor. A retrospective clinical review was conducted focusing on the patterns of presenting symptoms and signs, as well as local recurrence following surgery. Results Among 21 hemorrhagic brain metastases, local recurrence developed in two patients. The 12 month progression free survival rate was 86.1%. Mean time to progression was 20.8 months and median survival time after surgery was 11.7 months. Conclusion The results of our study showed that hemorrhagic metastatic brain tumors rarely recurred after surgery. Surgery should be considered as a good treatment option for hemorrhagic brain metastasis, especially in cases with increased intracranial pressure or severe neurologic deficits. PMID:21811426

  14. New developments in metastatic prostate cancer therapy.

    PubMed

    Manickavasagar, Thubeena; Gilson, Clare; Chowdhury, Simon; Kirby, Roger

    2015-04-01

    Metastatic prostate cancer is still commonly a lethal condition. The concept that 'men with prostate cancer die with rather than of their cancer' has been shown to be false. It is estimated that 10-20% of men in the UK present with locally advanced disease. Median overall survival remains only 3.5 years for men presenting with metastatic disease. The use of LHRH analogues to achieve medical castration has become the gold standard for both locally advanced prostate cancer, combined with radiotherapy, and metastatic disease. Androgen deprivation therapy (ADT) is the standard first-line treatment for advanced disease resulting in improvements in symptoms, radiological findings and PSA levels. Ultimately the majority of men with advanced prostate cancer will develop resistance to ADT Docetaxel is the standard first-line therapy recommended by international guidelines for patients with symptomatic metastatic castrate refractory prostate cancer who are suitable candidates for chemotherapy. More than 90% of patients with castrate refractory prostate cancer have bone metastases. Radium-223 dichloride is a novel alpha-emitting radiopharmaceutical agent, which mimics calcium and therefore targets bone metastases. It is indicated in patients with metastatic castrate refractory prostate cancer who have symptomatic bone metastases without visceral metastases.

  15. The European medicines agency review of eribulin for the treatment of patients with locally advanced or metastatic breast cancer: summary of the scientific assessment of the committee for medicinal products for human use.

    PubMed

    Pean, Elias; Klaar, Sigrid; Berglund, Eva Gil; Salmonson, Tomas; Borregaard, Jeanett; Hofland, Kenneth F; Ersbøll, Jens; Abadie, Eric; Giuliani, Rosa; Pignatti, Francesco

    2012-09-01

    The European Commission issued on March 17, 2011, a marketing authorization valid throughout the European Union (EU) for eribulin (Halaven; Eisai Limited). The decision was based on the favorable opinion of the Committee for Medicinal Products for Human Use recommending a marketing authorization for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least 2 chemotherapeutic regimens for advanced disease. Eribulin mesylate is a structurally simplified synthetic analogue of halichondrin B, which is a natural product isolated from the marine sponge Halichondria okadai (ATC code L01XX41). Eribulin is a nontaxane, microtubule dynamics inhibitor belonging to the halichondrin class of antineoplastic agents. Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates leading to G(2)-M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. The recommended dose of eribulin is 1.23 mg/m(2) (equivalent to 1.4 mg/m(2) eribulin mesylate) to be administered intravenously over 2 to 5 min on days 1 and 8 of a 3-week cycle. In the pivotal trial, eribulin was associated with increased overall survival in patients with locally advanced or metastatic breast cancer who received at least 2 prior chemotherapy lines for advanced disease (median overall survival was 13.2 months in the eribulin arm vs. 10.6 months in the control arm; HR = 0.805; 95% confidence interval, 0.677-0.958; P = 0.014). The most common side effects are asthenia or fatigue and neutropenia. The objective of this article is to summarize the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary report and product information, including product characteristics, are available on the European Medicines Agency website.

  16. Role of External Beam Radiotherapy in Patients With Advanced or Recurrent Nonanaplastic Thyroid Cancer: Memorial Sloan-Kettering Cancer Center Experience

    SciTech Connect

    Terezakis, Stephanie A. Lee, Kyungmouk S.; Ghossein, Ronald A.; Rivera, Michael; Tuttle, Robert M.; Wolden, Suzanne L.; Zelefsky, Michael J.; Wong, Richard J.; Patel, Snehal G.; Pfister, David G.; Shaha, Ashok R.; Lee, Nancy Y.

    2009-03-01

    Purpose: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. Methods and Materials: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT were identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). Results: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). Conclusion: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.

  17. [Condition of patients who require heart surgery during treatment for advanced digestive cancer and early recurrence after surgery- an assessment from the viewpoint of digestive surgeons].

    PubMed

    Fujisaki, Shigeru; Takashina, Motoi; Suzuki, Shuhei; Tomita, Ryouichi; Sakurai, Kenichi; Takayama, Tadatoshi; Takahashi, Hiroshi; Yamamoto, Tomonori

    2013-11-01

    The need for cardiac surgery among patients undergoing treatment for advanced digestive cancer is limited to the following situations:(i) heart diseases that can be life threatening if left untreated and that cannot be cured by medicinal treatment alone (e.g., cardiac tumors) and (ii) heart diseases (e.g., infectious endocarditis and pulmonary thromboembolism) occurring after digestive cancer surgery that need emergency treatment and that are resistant to medicinal treatment. We encountered 2 cases that required cardiac surgery.( Case 1) A 68-year-old woman with advanced gastric carcinoma accompanied by pyloric stenosis and left atrial myxoma underwent radical surgery for gastric cancer( Stage IIIA). Subsequently, the left atrial myxoma was resected before adjuvant chemotherapy for the treatment of gastric cancer was administered. One month after the surgery, multiple liver metastases appeared. However, they disappeared after chemotherapy was completed, and the patient survived for more than 3 years with complete response. (Case 2) A 67-year-old woman who underwent a Hartmann operation for obstructive rectal cancer (Stage II) experienced infectious endocarditis after the surgery. Because the endocarditis was resistant to medicinal treatment and acute heart failure was anticipated, cardiac surgery was performed. Approximately 2 months after the surgery, the bacilli( methicillin-resistant Staphylococcus aureus [MRSA]) were not found in blood culture. However, multiple liver metastases appeared immediately after the disappearance of the bacilli, and the patient died 3 months after the surgery. In both cases, cancer recurrence occurred early after cardiac surgery. Excessive surgical stress due to cardiac surgery may have promoted cancer recurrence. A decision pertaining to the timing of cardiac surgery is difficult in cases of patients with advanced digestive cancer and co-existing heart disease, which cannot be cured by medicinal treatment.

  18. HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial

    PubMed Central

    2013-01-01

    Background Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma. Methods Patients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFNγ-ELISPOT. Results No systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFNγ, TNFα, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient’s immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 ± 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease. Conclusions The HPV16-SLP vaccine was well tolerated and induced a broad IFNγ-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor

  19. Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas

    PubMed Central

    Balcerzak, S. P.; Kraft, A. S.; Edmonson, J. H.; Okuno, S. H.; Davey, M.; Mclaughlin, S.; Beard, M. T.; Rogatko, A.

    2004-01-01

    Patients:Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease. Dolastatin-10 (Dol-10) is a pentapeptide anti-microtubule agent that binds to tubulin sites distinct from vinca alkaloids. Based on the novel mechanism of action, limited activity of other anti-microtubular agents, and anti-neoplastic activity in pre-clinical screening of Dol-10, this multi-institutional phase II study was conducted to determine the objective response rate of Dol-10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of the adjuvant setting. Methods: Dol-10 was given intravenously at a dose of 400 μg/m2 and repeated every 21 days. Toxicities were assessed using the Common Toxicity Criteria (version 2.0). Radiographic studies and tumor measurements were repeated every two cycles to assess response [Miller AB, et al. Cancer 1981; 47(1): 207]. Results: Dol-10 was associated with hematological toxicity and with some vascular toxicities. There was no significant gastrointestinal, hepatic or renal toxicity. There was one death on study due to respiratory failure. There were no objective responses in 12 patients treated with Dol-10. Discussion: Based on this phase II trial, further study of Dol-10 on this schedule is not recommended in advanced or metastatic soft tissue sarcomas. PMID:18521404

  20. Recurrent varicocele

    PubMed Central

    Rotker, Katherine; Sigman, Mark

    2016-01-01

    Varicocele recurrence is one of the most common complications associated with varicocele repair. A systematic review was performed to evaluate varicocele recurrence rates, anatomic causes of recurrence, and methods of management of recurrent varicoceles. The PubMed database was evaluated using keywords “recurrent” and “varicocele” as well as MESH criteria “recurrent” and “varicocele.” Articles were not included that were not in English, represented single case reports, focused solely on subclinical varicocele, or focused solely on a pediatric population (age <18). Rates of recurrence vary with the technique of varicocele repair from 0% to 35%. Anatomy of recurrence can be defined by venography. Management of varicocele recurrence can be surgical or via embolization. PMID:26806078

  1. Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

    ClinicalTrials.gov

    2016-10-05

    Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Metastatic Pancreatic Adenocarcinoma; Progesterone Receptor Negative; Solid Neoplasm; Stage III Mesothelioma; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Small Cell Lung Carcinoma; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Small Cell Lung Carcinoma; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IV Mesothelioma; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Small Cell Lung Carcinoma; Triple-Negative Breast Carcinoma

  2. Cabozantinib-s-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors

    ClinicalTrials.gov

    2016-09-09

    Malignant Reproductive System Neoplasm; Malignant Urinary System Neoplasm; Metastatic Urethral Neoplasm; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Progressive Neoplastic Disease; Recurrent Bladder Carcinoma; Recurrent Urethra Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Solid Neoplasm; Stage III Bladder Urothelial Carcinoma; Stage III Urethral Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Urethral Cancer; Urethral Urothelial Carcinoma

  3. Metastatic Hepatocellular Carcinoma Responsive to Pembrolizumab.

    PubMed

    Truong, Phu; Rahal, Ahmad; Kallail, K James

    2016-06-04

    Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs with chronic liver disease. Surgical resection is the mainstay of therapy for localized disease whereas therapeutic options for advanced disease are limited. The innovative blockade of immune checkpoints with targeted immunotherapies, such as monoclonal antibodies against programmed death receptor 1 (PD-1), have shown promise in the treatment of solid malignancies. The PD-1 inhibiting antibodies, nivolumab and pembrolizumab prolonged overall survival in randomized trials in metastatic melanoma and advanced non-small cell lung cancer. This is a report of a 75-year-old male patient with metastatic HCC who was initially treated with the standard of therapy sorafenib. After failure of sorafenib therapy, pembrolizumab was started. There was a dramatic response to pembrolizumab with decrease in tumor size and drop in alfa fetoprotein. To the best of our knowledge, this is the first case report of metastatic HCC responsive to pembrolizumab after failure of sorafenib.

  4. Phase II trial of panitumumab with irinotecan as salvage therapy for patients with advanced or recurrent colorectal cancer (TOPIC study)

    PubMed Central

    NISHI, TOMOHIRO; HAMAMOTO, YASUO; NAGASE, MICHITAKA; DENDA, TADAMICHI; YAMAGUCHI, KENSEI; AMAGAI, KENJI; MIYATA, YOSHINORI; YAMANAKA, YASUHIRO; YANAI, KAI; ISHIKAWA, TSUTOMU; KUROKI, YOSHIFUMI; FUJII, HIROFUMI

    2016-01-01

    Little is known about the clinical impact of salvage panitumumab with irinotecan for metastatic colorectal cancer (mCRC) patients. The present study conducted a single-arm, multicenter phase II trial for mCRC with skin toxicity prevention program. The subjects were mCRC patients with wild-type KRAS, who showed resistance to fluoropyrimidine, oxaliplatin and irinotecan. Panitumumab was administered at a dose of 6 mg/kg every 2 weeks by intravenous infusion over 60 min, and irinotecan was administered at a dose of 100–180 mg/m2 every 2 weeks by intravenous infusion over 90 min, depending on the preceding treatment dose. To prevent skin toxicities, a moisturizer was applied and oral antibiotics (100 mg minocycline twice daily) were initiated for 6 weeks. The primary endpoint was the response rate (RR) determined by independent reviewers. Secondary endpoints were the disease control rate (DCR), progression-free survival (PFS) time, overall survival (OS) time and adverse events. A total of 35 patients were enrolled between October 2010 and March 2012. The median age was 61 years (range, 41–76 years), with 25 male and 10 female patients. The initial irinotecan dose was 150 mg/m2 in 19 patients and 180 mg/m2 in 1 patient. The remaining patients were treated with ≤120 mg/m2. A central review indicated a partial response in 8 patients (22.9%) and stable disease in 6 patients (17.1%), with an RR of 22.9% (95% confidence interval, 12.1–39.0) and a DCR of 40%. The RR of the patients with standard-dose irinotecan (150 or 180 mg/m2) was 30%, although that of low-dose irinotecan (100–120 mg/m2) was 13%. The median PFS time was 2.7 months, and the median OS time was 6.3 months. A grade 3 or above acne-like rash developed in 25.7% of patients. In conclusion, panitumumab and irinotecan as salvage therapy for mCRC KRAS wild-type patients with skin toxicity prevention exhibits limited efficacy. In particular, the effect of low-dose irinotecan with panitumumab appears to be

  5. The metastatic patterns of osteosarcoma.

    PubMed Central

    Jeffree, G. M.; Price, C. H.; Sissons, H. A.

    1975-01-01

    The paper presents a detailed comparison of the anatomical distribution and frequency of clinically evident metastases in 152 cases of osteosarcoma, and autopsy findings in 43 cases. The behaviour of long bone tumours is contrasted with those arising elsewhere, which tend to metastasize less widely because of early death from effects of the primary tumour. In both clinical and autopsy series long bone tumours produced lung metastases (LM) in over 90% of patients dying with metastases, but the terminal frequency of extra-pulmonary metastases (EPM) rises from a clinical level of 33% to 83% at autopsy. There was little difference between tumours of the major long bones in the frequency of either LM or EPM, but EPM from the humerus tended to be fewer and sited above the diaphragm and from the femur below it. EPM most often involved other bones, notably vertebrae and pelvis. Not more than 10% of tumours invaded regional lymph nodes but terminally a quarter of the long bone tumours had metastasized to heart and abdomen. The infrequency of metastases in muscle was confirmed. The median time for LM was 5-6 months after starting treatment, for EPM 9-10. months. First metastases after 24 months were infrequent, especially in children. With delay in the appearance of metastases, whether LM or EPM, post-metastatic survival lengthened. Neither age, sex nor mode of treatment of the primary notably affected metastatic frequency, although recurrences were much more numerous when radiotherapy, even with high dosage, was the definitive treatment. Local recurrence usually appeared within 6-8 months and was shown to lead to increased frequency of osseous metastases. It is suggested that terminal dissemination may often be tertiary but not always from a pulmonary secondary. PMID:1058038

  6. Metastatic pleural tumor

    MedlinePlus

    ... persons. Alternative Names Tumor - metastatic pleural Images Pleural space References Arenberg D, Pickens A. Metastatic malignant tumors. In: Mason RJ, Murray JF, Broaddus VC, et al., eds. Murray and Nadel's Textbook of Respiratory Medicine . 5th ed. Philadelphia, PA: Elsevier Saunders; 2010:chap ...

  7. An Open-Label, Single-Arm, Phase 2 Trial of the Polo-Like Kinase Inhibitor Volasertib (BI 6727) in Patients With Locally Advanced or Metastatic Urothelial Cancer

    PubMed Central

    Stadler, Walter M.; Vaughn, David J.; Sonpavde, Guru; Vogelzang, Nicholas J.; Tagawa, Scott T.; Petrylak, Daniel P.; Rosen, Peter; Lin, Chia-Chi; Mahoney, John; Modi, Sanjiv; Lee, Peter; Ernstoff, Marc S.; Su, Wu-Chou; Spira, Alexander; Pilz, Korinna; Vinisko, Richard; Schloss, Charles; Fritsch, Holger; Zhao, Charles; Carducci, Michael A.

    2015-01-01

    BACKGROUND Polo-like kinases (Plks) control multiple steps during the cell cycle, and Plk1 is overexpressed in urothelial cancer (UC). Volasertib (BI 6727), a Plk inhibitor, has demonstrated antitumor activity in several malignancies, including UC. In this phase 2 trial, the authors investigated volasertib as a second-line treatment in advanced/metastatic UC. METHODS Patients who progressed within 2 years of 1 prior chemotherapy regimen received 300 mg volasertib on day 1 every 3 weeks. The dose was escalated to 350 mg in cycle 2 if volasertib was tolerated in cycle 1. The primary endpoint was tumor response, which was assessed every 6 weeks; secondary endpoints were progression-free survival, overall survival, duration of response, safety, and pharmacokinetics. RESULTS Fifty patients were enrolled, and the median patient age was 68.5 years (range, 52-83 years). All patients had received prior platinum, 94% of patients had relapsed ≤2 years after prior therapy, 36% had liver metastases, and 54% had lung metastases. The median number of treatment cycles was 2 (range, 1-27 treatment cycles), and 23 patients were dose escalated at cycle 2. Seven patients (14%) had a partial response, 13 (26%) had stable disease, and 30 (60%) progressed within 6 weeks. The median response duration was 41 weeks (range, 29.1-77.3 weeks). The median progression-free survival was 1.4 months, and the median overall survival was 8.5 months. The most frequent grade 3 and 4 adverse events were neutropenia (28%), thrombocytopenia (20%), and anemia (16%). No cumulative toxicity was observed. CONCLUSIONS Volasertib as second-line treatment for advanced/metastatic UC had an acceptable safety profile but demonstrated insufficient antitumor activity for further evaluation as a monotherapy. PMID:24339028

  8. CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab.

    PubMed

    Petrioli, Roberto; Licchetta, Antonella; Roviello, Giandomenico; Pascucci, Alessandra; Francini, Edoardo; Bargagli, Gianluca; Conca, Raffaele; Miano, Salvatora Tindara; Marzocca, Giuseppe; Francini, Guido

    2012-01-01

    We evaluated the changes of the tumor markers CEA and CA19.9 as early predictors of progression in metastatic colorectal cancer (mCRC) patients participating in a clinical study and receiving chemotherapy and bevacizumab (Bev). Seventy-two patients had high baseline CEA or CA19.9 serum levels. By ROC analyses, the areas under the curves were 0.83 for variable CEA cutoff values for distinguishing progressive disease (PD) versus stable disease (SD)/partial remission (PR)/complete remission (CR), and 0.80 for variable CA19.9 cutoff values for distinguishing PD versus SD/PR/CR. Rises in CEA and CA19.9 may early signal the occurrence of progression in mCRC patients receiving chemotherapy and Bev. PMID:22236191

  9. Predictors of Recurrent AKI.

    PubMed

    Siew, Edward D; Parr, Sharidan K; Abdel-Kader, Khaled; Eden, Svetlana K; Peterson, Josh F; Bansal, Nisha; Hung, Adriana M; Fly, James; Speroff, Ted; Ikizler, T Alp; Matheny, Michael E

    2016-04-01

    Recurrent AKI is common among patients after hospitalized AKI and is associated with progressive CKD. In this study, we identified clinical risk factors for recurrent AKI present during index AKI hospitalizations that occurred between 2003 and 2010 using a regional Veterans Administration database in the United States. AKI was defined as a 0.3 mg/dl or 50% increase from a baseline creatinine measure. The primary outcome was hospitalization with recurrent AKI within 12 months of discharge from the index hospitalization. Time to recurrent AKI was examined using Cox regression analysis, and sensitivity analyses were performed using a competing risk approach. Among 11,683 qualifying AKI hospitalizations, 2954 patients (25%) were hospitalized with recurrent AKI within 12 months of discharge. Median time to recurrent AKI within 12 months was 64 (interquartile range 19-167) days. In addition to known demographic and comorbid risk factors for AKI, patients with longer AKI duration and those whose discharge diagnosis at index AKI hospitalization included congestive heart failure (primary diagnosis), decompensated advanced liver disease, cancer with or without chemotherapy, acute coronary syndrome, or volume depletion, were at highest risk for being hospitalized with recurrent AKI. Risk factors identified were similar when a competing risk model for death was applied. In conclusion, several inpatient conditions associated with AKI may increase the risk for recurrent AKI. These findings should facilitate risk stratification, guide appropriate patient referral after AKI, and help generate potential risk reduction strategies. Efforts to identify modifiable factors to prevent recurrent AKI in these patients are warranted.

  10. First-line therapy for treatment-naive patients with advanced/metastatic renal cell carcinoma: a systematic review of published randomized controlled trials.

    PubMed

    Takyar, Shweta; Diaz, Jose; Sehgal, Manu; Sapunar, Francisco; Pandha, Hardev

    2016-06-01

    In the recent years, a number of targeted therapies have been approved for first-line treatment of patients with metastatic renal cell carcinoma. A systematic review was conducted to assess the clinical efficacy, safety and effect of all first-line treatments evaluated to date on health-related quality of life (HRQoL). A systematic search of Embase, Cochrane and MEDLINE databases was performed to identify randomized controlled trials (1980-2015) evaluating any targeted therapy/immunotherapy against placebo or any other targeted intervention/immunotherapy in treatment-naive patients with metastatic renal cell carcinoma. Conference proceedings from major cancer congresses (2007-2015) were handsearched. Sixteen randomized controlled trials were identified, mostly phase III. Overall, targeted therapies were associated with either improved [sunitinib, bevacizumab+interferon α (IFNα) and temsirolimus] or comparable (sorafenib) progression-free survival (PFS) versus IFNα monotherapy. Sunitinib demonstrated comparable PFS and overall survival to pazopanib, comparable PFS to sorafenib and shorter PFS compared with bevacizumab+IFNα (although no conclusions were made with regard to superiority/inferiority). Compared with sorafenib, tivozanib demonstrated a significantly longer PFS, and both tivozanib and axitinib demonstrated higher response rates. Nintedanib demonstrated comparable PFS and overall survival to sunitinib in a phase II trial. Temsirolimus, sunitinib and sorafenib treatment led to better HRQoL versus IFNα; pazopanib was associated with better HRQoL versus sunitinib. No direct meta-analyses or indirect treatment comparison analysis were undertaken because of noncomparability of the trials. In general, targeted therapies demonstrated favourable clinical efficacy and improved HRQoL compared with IFNα monotherapy. The newer therapies, tivozanib and axitinib (but not nintedanib), appeared to exhibit greater clinical benefit (response rate) than older tyrosine

  11. Comparing nodal versus bony metastatic spread using tumour phylogenies

    PubMed Central

    Mangiola, Stefano; Hong, Matthew K. H.; Cmero, Marek; Kurganovs, Natalie; Ryan, Andrew; Costello, Anthony J.; Corcoran, Niall M.; Macintyre, Geoff; Hovens, Christopher M.

    2016-01-01

    The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extraprostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extraprostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage. PMID:27653089

  12. Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2013-12-10

    Bone Cancer; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma

  13. Curing Metastatic Breast Cancer.

    PubMed

    Sledge, George W

    2016-01-01

    Metastatic breast cancer is generally considered incurable, and this colors doctor-patient interactions for patients with metastatic disease. Although true for most patients, there appear to be important exceptions, instances where long-term disease-free survival occurs. Although these instances are few in number, they suggest the possibility of cure. How will we move toward cure for a much larger population of patients with metastatic disease? This article outlines a potential research agenda that might move us toward that distant goal. PMID:26759458

  14. Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors

    ClinicalTrials.gov

    2016-06-09

    Extensive Stage Small Cell Lung Cancer; Hereditary Paraganglioma; Male Breast Cancer; Malignant Paraganglioma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pheochromocytoma; Recurrent Prostate Cancer; Recurrent Renal Cell Cancer; Recurrent Small Cell Lung Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Regional Pheochromocytoma; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage III Uterine Sarcoma; Stage IIIA Breast Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Endometrial Carcinoma; Stage IV Neuroendocrine Carcinoma of the Skin; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Thyroid Gland Medullary Carcinoma

  15. Metastatic melanoma mimicking solitary fibrous tumor: report of two cases.

    PubMed

    Bekers, Elise M; van Engen-van Grunsven, Adriana C H; Groenen, Patricia J T A; Westdorp, Harm; Koornstra, Rutger H T; Bonenkamp, Johannes J; Flucke, Uta; Blokx, Willeke A M

    2014-02-01

    Malignant melanomas are known for their remarkable morphological variation and aberrant immunophenotype with loss of lineage-specific markers, especially in recurrences and metastases. Hot spot mutations in BRAF, NRAS, GNAQ, and GNA11 and mutations in KIT are oncogenic events in melanomas. Therefore, genotyping can be a useful ancillary diagnostic tool. We present one case each of recurrent and metastatic melanoma, both showing histological and immunohistochemical features of solitary fibrous tumor (SFT). Mutational analysis detected BRAF and NRAS mutations in the primary and secondary lesions, respectively. This result confirmed the diagnosis of recurrent/metastastic melanoma.

  16. Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

    PubMed Central

    Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

    2015-01-01

    Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

  17. Metastatic Bone Disease

    MedlinePlus

    ... Bone Disease cont. Page ( 4 ) MBD vs. Primary Bone Cancer The diagnosis of metastatic bone disease should not ... from an unknown primary carcinoma or a primary bone cancer (sarcoma). For example, if an area of bone ...

  18. Metastatic Crohn's disease.

    PubMed

    Sangüeza, O P; Davis, L S; Gourdin, F W

    1997-09-01

    Metastatic Crohn's disease is the term used for granulomatous lesions of Crohn's disease involving sites other than the gastrointestinal tract. Metastatic Crohn's disease has been considered uncommon, when in actuality it may simply be underdiagnosed or misdiagnosed since the clinical findings can be different. We report on three patients with this condition: one with generalized plaques, another with perineal and perianal ulcerations, and a third with a painless forearm nodule. PMID:9305298

  19. Pelvic Lymph Node Status Assessed by 18F-Fluorodeoxyglucose Positron Emission Tomography Predicts Low-Risk Group for Distant Recurrence in Locally Advanced Cervical Cancer: A Prospective Study

    SciTech Connect

    Kang, Sokbom; Park, Jung-Yeol; Lim, Myung-Chul; Song, Yong-Joong; Park, Se-Hyun; Kim, Seok-Ki; Chung, Dae-Chul; Seo, Sang-Soo; Kim, Joo-Young; Park, Sang-Yoon

    2011-03-01

    Purpose: To develop a prediction model to identify a low-risk group for distant recurrence in patients with locally advanced cervical cancer treated by concurrent chemoradiation. Methods and Materials: Prospectively, 62 patients with locally advanced cervical cancer were recruited as a training cohort. Clinical variables and parameters obtained from positron emission tomography (PET) and magnetic resonance imaging were analyzed by logistic regression. For the test set, 54 patients were recruited independently. To identify the low-risk group, negative likelihood ratio (LR) less than 0.2 was set to be a cutoff. Results: Among the training cohort, multivariate logistic analysis revealed that advanced International Federation of Gynecology and Obstetrics (FIGO) stage and a high serum squamous cancer cell (SCC) antigen level were significant risk factors (p = 0.015 and 0.025, respectively). Using the two parameters, criteria to determine a low-risk subset for distant recurrence were postulated: (1) FIGO Stage IIB or less and (2) pretreatment SCC < 2.4 (Model A). Positive pelvic node on PET completely predicted all cases with distant recurrence and thus was considered as another prediction model (Model B). In the test cohort, although Model A did not showed diagnostic performance, Model B completely predicted all cases with distant recurrence and showed a sensitivity of 100% with negative LR of 0. Across the training and test cohort (n = 116), the false negative rate was 0 (95% confidence interval 0%-7.6%). Conclusions: Positive pelvic node on PET is a useful marker in prediction of distant recurrence in patients with locally advanced cervical cancer who are treated with concurrent chemoradiation.

  20. The European Medicines Agency review of ipilimumab (Yervoy) for the treatment of advanced (unresectable or metastatic) melanoma in adults who have received prior therapy: summary of the scientific assessment of the Committee for Medicinal Products for Human Use.

    PubMed

    Hanaizi, Zahra; van Zwieten-Boot, Barbara; Calvo, Gonzalo; Lopez, Arantxa Sancho; van Dartel, Maaike; Camarero, Jorge; Abadie, Eric; Pignatti, Francesco

    2012-01-01

    On 13 July 2011 the European Commission issued a marketing authorisation valid throughout the European Union (EU) for ipilimumab for the treatment of advanced (unresectable or metastatic) melanoma in adults who have received prior therapy. Ipilimumab is a monoclonal antibody that specifically blocks the inhibitory signal of cytotoxic T lymphocyte antigen 4 (CTLA-4), resulting in T cell activation, proliferation and lymphocyte infiltration into tumours, leading to tumour cell death. The recommended induction regimen of ipilimumab is 3mg/kg administered intravenously over a 90 min period every 3 weeks for a total of four doses. In a phase 3 trial in patients with advanced melanoma, median overall survival for ipilimumab was 10 months versus 6 months for gp100, an experimental melanoma vaccine (Hazard ratio (HR) 0.66; 95% confidence interval (CI): 0.51, 0.87; p = 0.0026). Ipilimumab was most commonly associated with adverse reactions resulting from increased or excessive immune activity. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of ipilimumab. The most common side-effects (affecting more than 10% of patients) were diarrhoea, rash, pruritus, fatigue, nausea, vomiting, decreased appetite and abdominal pain. The objective of this paper is to summarise the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics (SmPC), are available on the European Medicines Agency (EMA) website (www.ema.europa.eu).

  1. Phase I dose-escalation study of cabazitaxel administered in combination with gemcitabine in patients with metastatic or unresectable advanced solid malignancies

    PubMed Central

    Puzanov, Igor; LoRusso, Patricia M.; Cohen, Roger B.; Morris, John C.; Olowokure, Olugbenga O.; Yin, Jian Y.; Doroumian, Séverine; Shen, Liji; Olszanski, Anthony J.

    2015-01-01

    Taxane–gemcitabine combinations have demonstrated antitumor activity. This phase I study (NCT01001221) aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus gemcitabine and to assess the preliminary efficacy of this combination. The patients included had metastatic or unresectable solid tumors and had exhausted standard treatment. Cohorts of three to six patients received cabazitaxel (15–20 mg/m2) before (part 1a) or after (part 1b) gemcitabine (700–1000 mg/m2) on Day 1 and gemcitabine alone on Day 8. Prophylactic growth factors were not allowed in cycle 1. In part 1a (n=12), five patients received 20 mg/m2 cabazitaxel plus 1000 mg/m2 gemcitabine (20/1000), five received 15/900, two received 15/700. In part 1b, all six patients received the lowest dose (700/15). At all doses, two or more patients experienced a DLT, regardless of administration sequence, including febrile neutropenia (n=4), grade 4 neutropenia (n=2), grade 4 thrombocytopenia (n=2), and grade 3 aspartate transaminase increase (n=1). The MTD was not established as all cohorts exceeded the MTD by definition. All patients experienced an adverse event; the most frequent all-grade nonhematologic events were fatigue (66.7%), decreased appetite (50.0%), and diarrhea (44.4%). The most frequent grade 3–4 hematologic abnormalities were neutropenia (83.3%), leukopenia (77.8%), and lymphopenia (72.2%). Toxicity was sequence-independent but appeared worse with gemcitabine followed by cabazitaxel. Durable partial responses were observed in three patients (prostate cancer, appendiceal cancer, and melanoma). The unacceptable DLTs with cabazitaxel plus gemcitabine, at doses reduced more than 25% from single-agent doses, preclude further investigation. PMID:26020806

  2. Palbociclib in Treating Patients With Metastatic HER-2 Positive or Triple-Negative Breast Cancer With Brain Metastasis

    ClinicalTrials.gov

    2016-05-26

    Breast Carcinoma Metastatic in the Brain; Estrogen Receptor Negative; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  3. Advances in Therapeutic Cancer Vaccines.

    PubMed

    Wong, Karrie K; Li, WeiWei Aileen; Mooney, David J; Dranoff, Glenn

    2016-01-01

    Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines. The clinical success of checkpoint blockade has underscored the role of peripheral tolerance mechanisms in limiting vaccine responses and highlighted the potential for combination therapies. Recent advances in transcriptome sequencing, computational modeling, and material engineering further suggest new opportunities to intensify cancer vaccines. This review will discuss the major approaches to therapeutic cancer vaccination and explore recent advances that inform the design of the next generation of cancer vaccines. PMID:26923002

  4. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    ClinicalTrials.gov

    2016-10-25

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  5. Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-08-25

    Extensive Stage Small Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  6. Recurrent novae

    NASA Technical Reports Server (NTRS)

    Hack, Margherita; Selvelli, Pierluigi

    1993-01-01

    Recurrent novae seem to be a rather inhomogeneous group: T CrB is a binary with a M III companion; U Sco probably has a late dwarf as companion. Three are fast novae; two are slow novae. Some of them appear to have normal chemical composition; others may present He and CNO excess. Some present a mass-loss that is lower by two orders of magnitude than classical novae. However, our sample is too small for saying whether there are several classes of recurrent novae, which may be related to the various classes of classical novae, or whether the low mass-loss is a general property of the class or just a peculiarity of one member of the larger class of classical novae and recurrent novae.

  7. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease. PMID:3587892

  8. A Phase II Clinical Study of mFOLFOX6 Plus Bevacizumab as First-line Therapy for Japanese Advanced/Recurrent Colorectal Cancer Patients

    PubMed Central

    Nishina, Tomohiro; Takano, Yoshinao; Denda, Tadamichi; Yasui, Hisateru; Takeda, Koji; Ura, Takashi; Esaki, Taito; Okuyama, Yusuke; Kondo, Ken; Takahashi, Yasuo; Sugiyama, Yasuyuki; Muro, Kei

    2013-01-01

    Objective In Japan, there had been no prospective clinical studies conducted in terms of modified FOLFOX6 + bevacizumab therapy. We performed a post-marketing Phase II multicenter clinical study to examine the efficacy and safety of this regimen as first-line therapy for Japanese patients with advanced/recurrent colorectal cancer. Methods Bevacizumab (5 mg/kg) was administered intravenously, and then oxaliplatin (85 mg/m2) and levofolinate calcium (200 mg/m2) were infused intravenously over 2 h. Subsequently, a bolus dose of 5-fluorouracil (400 mg/m2) was injected, followed by infusion of 5-fluorouracil (2400 mg/m2) for 46 h. This regimen was repeated every 2 weeks until 24 cycles unless there was disease progression, unacceptable toxicity or patient refusal. The primary end point was the response rate. Results Among the 70 patients enrolled, two patients withdrew the study before treatment, and 68 patients were eligible for analysis of efficacy and safety. The response rate was 51.5% (95% confidence interval: 39.0–63.8%). The median progression-free survival and median overall survival time were 12.6 months (95% confidence interval: 10.4–14.5 months) and 28.5 months [95% confidence interval: 23.1 months–(not applicable)], respectively. There were no treatment-related deaths observed. The most common Grade 3 and 4 adverse events included neutropenia in 35.3% of the patients, peripheral neuropathy in 16.2% and hypertension in 16.2%. All adverse events were manageable and tolerable. The exploratory analysis of polymorphisms of three genes, ERCC1, XPD and GSTP1, did not show any trends in terms of correlation with the efficacy or safety of modified FOLFOX6 + bevacizumab therapy. Conclusions Modified FOLFOX6 + bevacizumab therapy was manageable and tolerable in Japanese patients, achieving a high response rate. PMID:23999770

  9. Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58.

    PubMed

    Smith, Roy E; Anderson, Stewart J; Brown, Ann; Scholnik, Aaron P; Desai, Ajit M; Kardinal, Carl G; Lembersky, Barry C; Mamounas, Eleftherios P

    2002-12-01

    Based on the recommended phase II doses for doxorubicin (60 mg/m2) and docetaxel (60 mg/m2) and the National Surgical Adjuvant Breast and Bowel Project's (NSABP) experience with doxorubicin and cyclophosphamide (cyclophosphamide 600 mg/m2), we conducted a phase II trial at 18 institutions using doxorubicin/docetaxel/cyclophosphamide (ATC) given every 21 days, in preparation for a major adjuvant breast cancer study (NSABP B-30), in which ATC would be used. Eligibility requirements included measurable stage IIIB/IV breast cancer, performance status 0-2, normal left ventricular ejection fraction, and no prior chemotherapy for metastatic disease (nontaxane adjuvant chemotherapy was allowed if completed > 12 months before entry and if the cumulative dose of doxorubicin was =240 mg/m2). Eighty-nine patients were entered who ranged in age from 30-78 years (38.2% < 50 years; 61.8% =50 years). A total of 33.7% of patients had stage IIIB disease, and 66.3% had stage IV disease. Among the stage IV patients, 20.3% had received prior adjuvant chemotherapy. Dexamethasone premedication (8 mg p.o. b.i.d. for 3 days) and prophylactic ciprofloxacin (500 mg p.o. b.i.d. days 5-15) were used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in a prior cycle. After a cumulative dose of doxorubicin 480 mg/m2, patients could continue with docetaxel/cyclophosphamide alone. Eighty-nine patients and 577 courses were evaluable for toxicity. Median time on study as of May 2002 was 36.5 months (range, 28-47 months). Febrile neutropenia occurred in 34 patients (38%); 8 developed FN in the absence of prior prophylactic growth factor support; 26 developed FN despite prior growth factor support (for one patient this information was unavailable). There were no septic deaths. One patient died from pulmonary embolism. Other grade 3/4 adverse events included: nausea (9%), vomiting (7%), stomatitis (6

  10. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    ClinicalTrials.gov

    2013-03-18

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

  11. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence

    PubMed Central

    2013-01-01

    Background Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs). Results The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96). Conclusions The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required. PMID:23406686

  12. Systemic chemotherapy in inoperable or metastatic bladder cancer.

    PubMed

    Bamias, A; Tiliakos, I; Karali, M-D; Dimopoulos, M A

    2006-04-01

    Urothelial cancer is a common malignancy. The management of patients with recurrent disease after cystectomy or initially metastatic or unresectable disease represents a therapeutic challenge. Systemic chemotherapy prolongs survival but long-term survival remains infrequent. During recent years there has been improvement due to the use of novel chemotherapeutic agents, mainly gemcitabine and the taxanes. The long-considered-standard MVAC has been challenged by combinations showing more favourable toxicity profiles and equal (gemcitabine-cisplatin) or even improved (dose-dense, G-CSF-supported MVAC) efficacy. Specific interest has also been generated in specific groups of patients (elderly patients, patients with renal function impairment or comorbidities), who are not fit for the standard cisplatin-based chemotherapy but can derive significant benefit from carboplatin- or taxane-based treatment. Retrospective analyses have enabled the identification of groups of patients with different prognoses, who possibly require different therapeutic approaches. Modern chemotherapy offers a chance of long-term survival in patients without visceral metastases, possibly in combination with definitive local treatment. Finally, the progress of targeted therapies in other neoplasms seems to be reflected in advanced bladder cancer by recent studies indicating that biological agents can be combined with modern chemotherapy. The true role of such therapies is currently being evaluated. PMID:16303860

  13. Trifluridine/Tipiracil: A Review in Metastatic Colorectal Cancer.

    PubMed

    Burness, Celeste B; Duggan, Sean T

    2016-09-01

    Trifluridine/tipiracil (Lonsurf(®)) is a novel, orally active, antimetabolite agent comprised of trifluridine, a thymidine-based nucleoside analogue, and tipiracil, a potent thymidine phosphorylase inhibitor. Trifluridine is incorporated into DNA via phosphorylation, ultimately inhibiting cell proliferation. Tipiracil increases systemic exposure of trifluridine when coadministered. Trifluridine/tipiracil has recently been approved for the treatment of adult patients with metastatic colorectal cancer (mCRC) who are refractory to or are not considered candidates for, current standard chemotherapy and biological therapy in the EU and USA and in unresectable advanced or recurrent CRC in Japan. The approved regimen of oral twice-daily trifluridine/tipiracil (35 mg/m(2) twice daily on days 1-5 and 8-12 of each 28-day cycle) significantly improved overall survival and progression-free survival and was associated with a significantly higher disease control rate than placebo when added to best supportive care in the multinational, pivotal phase III trial (RECOURSE) and a phase II Japanese trial. Trifluridine/tipiracil was associated with an acceptable tolerability profile, with adverse events generally being managed with dose reductions, temporary interruptions in treatment or administration of granulocyte-colony stimulating factor. The most common grade 3-4 adverse events (≥10 %) were anaemia, neutropenia, thrombocytopenia and leukopenia. In conclusion, trifluridine/tipiracil is a useful additional treatment option for the management of mCRC in patients who are refractory to, or are not considered candidates for, currently available therapies. PMID:27568360

  14. SEOM clinical guidelines in metastatic breast cancer 2015.

    PubMed

    Gavilá, J; Lopez-Tarruella, S; Saura, C; Muñoz, M; Oliveira, M; De la Cruz-Merino, L; Morales, S; Alvarez, I; Virizuela, J A; Martin, M

    2015-12-01

    Metastatic breast cancer is essentially an incurable disease. However, recent advances have resulted in a significant improvement of overall survival. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with metastatic breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.

  15. Metastatic Crohn's disease.

    PubMed

    Lanka, Padmavathy; Lanka, Lakshmana Rao; Sylvester, N; Lakshmi, M Dhana; Ethirajan, N

    2014-01-01

    Crohn's disease, first described in 1922, is characterized by segmental granulomatous inflammation of the intestinal tract and frequently involves the cutaneous tissues as well. Cutaneous Crohn's disease (CCD) is synonymous with metastatic Crohn's disease (MSD). A case of CCD, without any gastrointestinal involvement is reported for its rarity.

  16. Surgical management of advanced gastric cancer: An evolving issue.

    PubMed

    Marano, L; Polom, K; Patriti, A; Roviello, G; Falco, G; Stracqualursi, A; De Luca, R; Petrioli, R; Martinotti, M; Generali, D; Marrelli, D; Di Martino, N; Roviello, F

    2016-01-01

    Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer. PMID:26632080

  17. The impact of epidermal growth factor receptor mutations on patterns of disease recurrence after chemoradiotherapy for locally advanced non–small cell lung cancer: a literature review and pooled analysis

    PubMed Central

    Ochiai, Satoru; Nomoto, Yoshihito; Watanabe, Yui; Yamashita, Yasufumi; Toyomasu, Yutaka; Kawamura, Tomoko; Takada, Akinori; Noriko; Sakuma, Hajime

    2016-01-01

    The purpose of this review was to evaluate the impact of epidermal growth factor receptor (EGFR) mutation status on disease recurrence in patients treated with chemoradiotherapy (CRT) for locally advanced non–small cell lung cancer (NSCLC). A literature search was conducted and a total of three studies were analyzed. There was no significant difference in the objective response rate between the EGFR mutation group and the EGFR wild-type group (odds ratios [OR] 1.46, 95% CI, 0.79–2.70, P = 0.228), and there was no significant difference in the incidence of disease recurrence (OR 1.37, 95% CI, 0.68–2.75, P = 0.379) between the two groups. There were significant difference in the incidence of local/locoregional progression (LP) (OR 0.35, 95% CI, 0.18–0.71, P = 0.003) and distant progression (DP) (OR 2.97, 95% CI, 1.59–5.54, P < 0.001). Brain metastasis (BM) was one of the main recurrence patterns of DP, and the incidence was significantly higher in the EGFR mutant group (OR 2.75, 95% CI, 1.43–5.31, P = 0.003). There were no statistically significant heterogeneities in these pooled analyses. The patterns of recurrence after CRT for locally advanced NSCLC were different according to EGFR mutation status. LP after CRT in patients with EGFR mutation was less frequent, but the high incidence of DP, especially BM, continued to be the major problem. On the other hand, LP continued to be the major problem in EGFR wild-type patients. In multimodality treatment for inoperable locally advanced NSCLC, we may need to consider different treatment strategies according to EGFR mutation status. PMID:27534790

  18. Health-related quality of life in locally advanced and metastatic breast cancer: methodological and clinical issues in randomised controlled trials.

    PubMed

    Ghislain, Irina; Zikos, Efstathios; Coens, Corneel; Quinten, Chantal; Balta, Vasiliki; Tryfonidis, Konstantinos; Piccart, Martine; Zardavas, Dimitrios; Nagele, Eva; Bjelic-Radisic, Vesna; Cardoso, Fatima; Sprangers, Mirjam A G; Velikova, Galina; Bottomley, Andrew

    2016-07-01

    Breast cancer is the leading cause of cancer death among women worldwide, and increasingly, randomised controlled trials of this disease are measuring the health-related quality of life of these patients. In this systematic Review, we assess the adequacy of methods used to report health-related quality of life (HRQOL) from 49 eligible randomised controlled trials of advanced breast cancer. We compare our findings with those from the literature to investigate whether the standard of HRQOL reporting in this field has changed. We conclude that the overall reporting of HRQOL has improved, but some crucial aspects remain problematic, such as the absence of HRQOL research hypotheses and the overemphasis on statistical rather than clinical significance. Additionally, new challenges are arising with the emergence of novel treatments and the advent of personalised medicine, and improved HRQOL tools are required to cover the range of side-effects of newer therapies. PMID:27396647

  19. Late breast recurrence after lumpectomy and irradiation

    SciTech Connect

    Kurtz, J.M.; Spitalier, J.M.; Amalric, R.

    1983-08-01

    For 276 patients with early breast cancer followed from 10 to 21 years after lumpectomy and radiotherapy, the recurrence rate in the treated breast was 15.6%, and 7.2% developed contralateral breast cancer. Only 63% of breast recurrences occurred within 5 years, and the remainder were late failures, with 5 of the 43 recurrences observed after 10 years. The proportion of failures occurring late was greater for T/sub 1/ than for T/sub 2/ tumors (53% vs 25%). Twenty-six percent of early recurrences were inoperable, and an adverse impact of early recurrence on 10-year survival was clearly demonstrable. Late recurrences were all operable and did not appear to be associated with decreased survival. Only 16 of the 36 patients (44%) with operable breast recurrence ever developed metastatic disease, and 5 year survival following salvage therapy was 62%. Although the treated breast remains at continuous cancer risk even beyond 5 years, the prognosis of late recurrence appears quite similar to that of contralateral breast cancer.

  20. Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver

    PubMed Central

    Said, Rabih; Kurzrock, Razelle; Naing, Aung; Hong, David S.; Fu, Siqing; Piha-Paul, Sarina; Wheler, Jennifer J; Janku, Filip; Kee, Bryan K; Bidyasar, Savita; Lim, Joann; Wallace, Michael; Tsimberidou, Apostolia M.

    2015-01-01

    BACKGROUND Liver metastases are associated with a poor prognosis. We investigated the use of hepatic arterial infusion (HAI) of irinotecan combination therapy in patients with liver metastases. PATIENTS AND METHODS Patients with histologically confirmed advanced cancer with liver metastases that was refractory to standard therapy were eligible. A standard “3+3” phase I study design was used to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Three cohorts were evaluated: HAI of irinotecan with systemic intravenous (IV) (a) bevacizumab, (b) oxaliplatin and bevacizumab, or (c) bevacizumab and cetuximab. RESULTS From October 2009 through December 2013, 98 patients with various tumor types were enrolled (median age, 62 years, range, 34–85; and median number of prior therapies, 4, range, 1–11). In cohorts A and C, dose escalation continued until the highest dose level—considered the MTD—was reached. In cohort B, dose escalation continued until dose level 3, and dose level 2 was considered the MTD. Rates of grade 3/4 adverse events were as follows: diarrhea, 8%; fatigue, 4%; neutropenia, 4%; thrombocytopenia, 2%; and skin rash, 2%. Seventy-seven patients were evaluable for response. Partial response was noted in 5 (6.5%) patients (neuroendocrine cancer, n=2; CRC, n=2; NSCLC, n=1); and stable disease ≥ 6 months in 17 (22.1%) patients (CRC, n=13; breast, n=1; neuroendocrine, n=1; NSCLC, n=1; pancreatic, n=1). CONCLUSIONS HAI irinotecan in combination with bevacizumab; oxaliplatin plus bevacizumab; or cetuximab plus bevacizumab was safe and may be a treatment option for selected patients with advanced cancer and liver involvement. PMID:25990659

  1. Recurrent malignant salivary gland neoplasms.

    PubMed

    Rodriguez-Bigas, M A; Sako, K; Razack, M S; Shedd, D P; Bakamjian, V Y; Castillo, N B; Rao, U

    1989-10-01

    Recurrent salivary gland malignancies present difficult therapeutic decisions and poor prognosis in many instances, and treatment becomes of a palliative nature only. As many of the salivary gland malignancies we see are of the recurrent type, the following study was done to determine the efficacy of a vigorous attempt at retreatment. During the period January 1, 1960, through December 31, 1984, 352 patients with major and minor salivary gland tumors were evaluated at our institution. There were 149 benign lesions and 203 patients with malignant tumors. Of these, 99 patients had recurrent and metastatic tumors that had been treated initially elsewhere. Thirty-three of these patients were able to be treated with curative intent: surgery, 21; surgery plus radiation, 9; radiation therapy alone, 2; and radiation plus chemotherapy, 1. The 5 year survival with no evidence of disease was achieved in three patients with surgery alone and two patients with surgery plus radiation therapy. The group of five patients was comprised of two patients with adenoid cystic carcinomas of the parotid, one with intermediate grade mucoepidermoid carcinoma of the parotid, one, sebaceous cell carcinoma of the parotid, and one, adenoid cystic carcinoma of an accessory salivary gland. The results of this study serve to re-emphasize the relative poor yield of attempts at retreatment of loco-regional recurrence of salivary gland tumors.

  2. Akt Inhibitor MK2206, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With Locally Advanced or Metastatic HER2-Positive Breast , Gastric, or Gastroesophageal Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2013-09-27

    Adenocarcinoma of the Gastroesophageal Junction; HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  3. Phase I Study of BIIB028, a selective heat shock protein 90 inhibitor, in patients with refractory metastatic or locally advanced solid tumors

    PubMed Central

    Hong, David; Said, Rabih; Falchook, Gerald; Naing, Aung; Moulder, Stacy; Tsimberidou, Apostolia-Maria; Galluppi, Gerald; Dakappagari, Naveen; Storgard, Chris; Kurzrock, Razelle; Rosen, Lee S.

    2014-01-01

    Purpose Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone involved in protein folding, activation, and assembly, including key mediators of signal transduction, cell cycle control, and transcriptional regulation. We conducted a phase I dose-finding and pharmacokinetic/pharmacodynamic study of BIIB028, a prodrug designed to inhibit Hsp90 activity. Patients and Methods Patients with advanced solid tumors were enrolled and received escalating doses of BIIB028 intravenously twice a week in 21-day cycles (3+3 design). Response was evaluated after 2 cycles. Results Forty-one patients received doses of 6 to 192 mg/m2. The maximum tolerated dose was 144 mg/m2. Dose-limiting toxicities were syncope (n=1) and fatigue (n=1). Common toxicities at least possibly related to drug were grade 1–2, including fatigue (46%), diarrhea (44%), nausea (44%), vomiting (29%), hot flushes (29%) and abnormal dreams (17%). The concentration-time curves for Day 1 and Day 18 for both prodrug and active metabolite (CF2772) showed a negligible difference. There was a dose-dependent increase in plasma exposure for BIIB028 (CF3647) and CF2772 with plasma half-life of 0.5 and 2.1 hours, respectively. Pharmacodynamic analyses demonstrated significant increases in Hsp70 in peripheral blood mononuclear cells and significantly decreased circulating human epidermal growth factor receptor 2- extracellular domain in all patients who received BIIB028 at dose levels ≥48mg/m2. Stable disease for at least 8 cycles (24 weeks) was achieved in 5 (12%) patients (6, 6, 8, 12.5 and 19 months). Conclusion BIIB028 is a well-tolerated molecule that demonstrated target impact and was associated with prolonged stable disease in 2 patients. PMID:23873691

  4. Metastatic chondroblastoma. Report of a fatal case with a review of the literature on atypical, aggressive, and malignant chondroblastoma.

    PubMed

    Kyriakos, M; Land, V J; Penning, H L; Parker, S G

    1985-04-15

    A boy with metastatic and fatal chondroblastoma is presented. Unlike previously published examples of metastatic chondroblastoma, these metastases developed before any operative manipulation of the primary tumor. The histologic characteristics of the primary, metastatic, and locally recurrent tumors were those of a conventional chondroblastoma. A review of published cases of atypical, aggressive, and malignant chondroblastoma is presented with current follow-up information. Although some metastatic chondroblastomas may result from operative manipulation of the primary tumor and are clinically benign, other histologically benign chondroblastomas exist that are capable of pursuing a malignant course. The authors designate these as malignant chondroblastomas. No histologic criteria exist for the separation of these tumors.

  5. Metastatic chondroblastoma. Report of a fatal case with a review of the literature on atypical, aggressive, and malignant chondroblastoma.

    PubMed

    Kyriakos, M; Land, V J; Penning, H L; Parker, S G

    1985-04-15

    A boy with metastatic and fatal chondroblastoma is presented. Unlike previously published examples of metastatic chondroblastoma, these metastases developed before any operative manipulation of the primary tumor. The histologic characteristics of the primary, metastatic, and locally recurrent tumors were those of a conventional chondroblastoma. A review of published cases of atypical, aggressive, and malignant chondroblastoma is presented with current follow-up information. Although some metastatic chondroblastomas may result from operative manipulation of the primary tumor and are clinically benign, other histologically benign chondroblastomas exist that are capable of pursuing a malignant course. The authors designate these as malignant chondroblastomas. No histologic criteria exist for the separation of these tumors. PMID:3978565

  6. [Metastatic Crohn's disease].

    PubMed

    Romero Gutiérrez, Marta; Alcántara Torres, Mariano; Muñoz Rosas, Concepción; Gómez Moreno, Ana Zaida; Guardiola Arévalo, Antonio; Rodríguez Merlo, Rufo; Carrobles Jiménez, José María

    2010-01-01

    Metastatic Crohn's disease is a granulomatous cutaneous lesion that appears in patients with Crohn's disease and is located in any skin area, separated from the lesions in the gastrointestinal tract. This entity is characterized by its heterogeneous behavior, both in its localization and clinical expression and in its effect on patients' quality of life. Histology is essential for diagnosis and shows non-caseating granulomas. There are no treatment guidelines and various therapeutic strategies have been employed, with variable response. In most patients, treatment with biological agents is highly effective. We describe three cases of metastatic Crohn's disease with the aim of analyzing the characteristics of this entity, which should always be included in the differential diagnosis of skin lesions in patients with Crohn's disease. A literature review is also provided.

  7. Characteristics and Patterns of Metastatic Disease from Chordoma

    PubMed Central

    Young, Victoria A.; Curtis, Kevin M.; Temple, H. Thomas; Eismont, Frank J.; DeLaney, Thomas F.; Hornicek, Francis J.

    2015-01-01

    Chordoma is a rare, slow-growing malignant tumor arising from notochordal remnants. A retrospective review of patient records at two major referral centers was undertaken to assess the incidence, location, and prognostic factors of metastatic disease from chordoma. 219 patients with chordoma (1962–2009) were identified. 39 patients (17.8%) developed metastatic disease, most frequently to lung (>50%). Median survival from the time of initial diagnosis was 130.4 months for patients who developed metastatic disease and 159.3 months for those who did not (P = 0.05). Metastatic disease was most common in the youngest patients (P = 0.07), and it was 2.5 times more frequent among patients with local recurrence (26.3%) than in those without (10.8%) (P = 0.003). Patient survival with metastatic disease was highly variable, and it was dependent on both the location of the tumor primary and the site of metastasis. Metastasis to distal bone was the most rapid to develop and had the worst prognosis. PMID:26843835

  8. Mechanosensitive pannexin-1 channels mediate microvascular metastatic cell survival.

    PubMed

    Furlow, Paul W; Zhang, Steven; Soong, T David; Halberg, Nils; Goodarzi, Hani; Mangrum, Creed; Wu, Y Gloria; Elemento, Olivier; Tavazoie, Sohail F

    2015-07-01

    During metastatic progression, circulating cancer cells become lodged within the microvasculature of end organs, where most die from mechanical deformation. Although this phenomenon was first described over a half-century ago, the mechanisms enabling certain cells to survive this metastasis-suppressive barrier remain unknown. By applying whole-transcriptome RNA-sequencing technology to isogenic cancer cells of differing metastatic capacities, we identified a mutation encoding a truncated form of the pannexin-1 (PANX1) channel, PANX1(1-89), as recurrently enriched in highly metastatic breast cancer cells. PANX1(1-89) functions to permit metastatic cell survival during traumatic deformation in the microvasculature by augmenting ATP release from mechanosensitive PANX1 channels activated by membrane stretch. PANX1-mediated ATP release acts as an autocrine suppressor of deformation-induced apoptosis through P2Y-purinergic receptors. Finally, small-molecule therapeutic inhibition of PANX1 channels is found to reduce the efficiency of breast cancer metastasis. These data suggest a molecular basis for metastatic cell survival on microvasculature-induced biomechanical trauma. PMID:26098574

  9. [Noticeable clinical response to S-1/CDDP combination therapy for Virchow node recurrence after surgery for advanced gastric carcinoma with marked involvement of the esophagus - report of a case].

    PubMed

    Sugawara, Hiromitsu; Ichiki, Masataka; Sai, Keijyou; Kamata, Keisuke; Ansai, Makoto; Nakano, Yoshiyuki; Kawamura, Masashi; Ichinose, Azusa; Miyazaki, Shukichi

    2009-05-01

    We have recently experienced a case in which S-1/CDDP combination therapy proved remarkably efficacious for a rapid, extensive lymph node recurrence with metastasis into a Virchow node that had developed after resection of advanced gastric carcinoma accompanied with a marked invasion of the esophagus. The patient, a woman aged 73, underwent a total gastrectomy upon left thoracolaparotomy for a gastric carcinoma at the cardia with a 5-cm involvement of the esophagus. On day 65 post-operation, a diagnosis of Virchow node and para-aortic lymph node recurrence was made on the basis of CT scan findings. Of tumor markers checked, CEA and CA19-9 were noted to be increased to as high as 37.55 ng/mL and 3,235 U/mL, respectively. The patient received three courses of S-1/CDDP combination therapy, with a consequent noticeable contraction of the Virchow node and enlarged para-aortic lymph node. Further, she was given two courses of S-1 therapy, which resulted in normalization of tumor markers. The patient has since been on continued chemotherapy without any sign of recurrence.

  10. Cancer-related multiple brain infarctions caused by Trousseau syndrome in a patient with metastatic colon cancer: a case report.

    PubMed

    Akiyama, Takahiko; Miyamoto, Yuji; Sakamoto, Yasuo; Tokunaga, Ryuma; Kosumi, Keisuke; Shigaki, Hironobu; Kurashige, Junji; Iwatsuki, Masaaki; Baba, Yoshifumi; Yoshida, Naoya; Baba, Hideo

    2016-12-01

    Thromboembolism that occurs in association with a malignant tumor is known as Trousseau syndrome. We herein present a case of Trousseau syndrome during systemic chemotherapy for metastatic colon cancer. A 65-year-old man with multiple liver metastases underwent primary tumor resection and systemic chemotherapy. Multiple brain infarctions were detected by magnetic resonance imaging immediately after first-line chemotherapy, which was deemed ineffective. There was no evidence of cardioembolic stroke or carotid atherosclerosis. Although the patient was initially asymptomatic, he subsequently developed paralysis. Despite anticoagulant treatment, he developed repeated recurrences of the infarction, and the area of the infarction spread as the liver metastases progressed. The patient's condition showed no response to an alternative treatment regimen for advanced colon carcinoma. He died approximately 11 months after tumor discovery. PMID:27595586

  11. Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

    ClinicalTrials.gov

    2016-07-05

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  12. Role of the neural niche in brain metastatic cancer.

    PubMed

    Termini, John; Neman, Josh; Jandial, Rahul

    2014-08-01

    Metastasis is the relentless pursuit of cancer to escape its primary site and colonize distant organs. This malignant evolutionary process is biologically heterogeneous, yet one unifying element is the critical role of the microenvironment for arriving metastatic cells. Historically, brain metastases were rarely investigated because patients with advanced cancer were considered terminal. Fortunately, advances in molecular therapies have led to patients living longer with metastatic cancer. However, one site remains recalcitrant to our treatment efforts, the brain. The central nervous system is the most complex biologic system, which poses unique obstacles but also harbors opportunities for discovery. Much of what we know about the brain microenvironment comes from neuroscience. We suggest that the interrelated cellular responses in traumatic brain injury may guide us toward new perspectives in understanding brain metastases. In this view, brain metastases may be conceptualized as progressive oncologic injury to the nervous system. This review discusses our evolving understanding of bidirectional interactions between the brain milieu and metastatic cancer.

  13. Health-related quality of life in patients with locally advanced or metastatic breast cancer treated with eribulin mesylate or capecitabine in an open-label randomized phase 3 trial.

    PubMed

    Cortes, Javier; Hudgens, Stacie; Twelves, Chris; Perez, Edith A; Awada, Ahmad; Yelle, Louise; McCutcheon, Susan; Kaufman, Peter A; Forsythe, Anna; Velikova, Galina

    2015-12-01

    The clinical benefit of eribulin versus capecitabine was evaluated using health-related quality of life (HRQoL) data from a phase 3 randomized trial in patients with pretreated advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT00337103). The study population has been described previously (Kaufman et al. in J Clin Oncol 33:594-601, 2015). Eligible patients received eribulin (1.4 mg/m(2) intravenously on days 1 and 8) or capecitabine (1.25 g/m(2) orally twice daily on days 1-14) per 21-day cycles. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire-Core 30 questions (QLQ-C30) and breast module-23 questions (QLQ-BR23), administered at baseline through 24 months, until disease progression or other antitumor treatment initiation. Minimally important difference (MID) and time to symptom worsening (TSW) were investigated. 1062 (96.4 %) Patients completed the EORTC questionnaire at baseline; overall, compliance was ≥80 %. Patients receiving capecitabine versus eribulin had significantly worse symptoms (higher scores) for nausea/vomiting (MID 8; P < 0.05) and diarrhea (MID 7; P < 0.05). Treatment with eribulin versus capecitabine, led to worse systemic therapy side-effects (dry mouth, different tastes, irritated eyes, feeling ill, hot flushes, headaches, and hair loss; MID 10; P < 0.01). Clinically meaningful worsening was observed for future perspective (MID 10; P < 0.05) with capecitabine and for systemic therapy side-effects scale (MID 10; P < 0.01) with eribulin. Patients receiving capecitabine experienced more-rapid deterioration in body image (by 2.9 months) and future perspective (by 1.4 months; P < 0.05) compared with those on eribulin; the opposite was observed for systemic side-effects where patients receiving eribulin experienced more-rapid deterioration than those receiving capecitabine (by 2 months; P < 0.05). Eribulin and capecitabine were found to have similar

  14. Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma

    ClinicalTrials.gov

    2016-09-12

    Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  15. Efficacy of goserelin plus anastrozole in premenopausal women with advanced or recurrent breast cancer refractory to an LH-RH analogue with tamoxifen: results of the JMTO BC08-01 phase II trial.

    PubMed

    Nishimura, Reiki; Anan, Keisei; Yamamoto, Yutaka; Higaki, Kenji; Tanaka, Maki; Shibuta, Kenji; Sagara, Yasuaki; Ohno, Shinji; Tsuyuki, Shigeru; Mase, Takahiro; Teramukai, Satoshi

    2013-05-01

    The aim of the present study was to assess the efficacy and tolerability of a luteinizing hormone-releasing hormone (LH-RH) analogue plus an aromatase inhibitor following failure to respond to standard LH-RH analogue plus tamoxifen (TAM) in premenopausal patients. Premenopausal women with estrogen receptor (ER)-positive and/or progesterone-receptor positive, advanced or recurrent breast cancer refractory to an LH-RH analogue plus TAM received goserelin (GOS) in conjunction with anastrozole (ANA). The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and safety. Between September 2008 and November 2010, 37 patients were enrolled. Thirty-five patients (94.6%) had ER-positive tumors, and 36 (97.3%) had human epidermal growth factor receptor (HER) 2-negative tumors. Thirty-six (97.3%) had measurable lesions and 1 (2.7%) had only bone metastasis. The ORR was 18.9% [95% confidence interval (CI), 8.0-35.2%], the CBR was 62.2% (95% CI, 44.8-77.5%) and the median PFS was 7.3 months. Eight patients had adverse drug reactions but none resulted in discontinuation of treatment. GOS plus ANA is a safe effective treatment for premenopausal women with hormone receptor-positive, recurrent or advanced breast cancer. The treatment may become viable treatment in the future, particularly when TAM is ineffective or contraindicated. Further studies and discussion are warranted.

  16. Autologous Immune Enhancement Therapy in Recurrent Ovarian Cancer with Metastases: A Case Report

    PubMed Central

    Manjunath, Sadananda Rao; Ramanan, Ganapathi; Dedeepiya, Vidyasagar Devaprasad; Terunuma, Hiroshi; Deng, Xuewen; Baskar, Subramani; Senthilkumar, Rajappa; Thamaraikannan, Paramasivam; Srinivasan, Thangavelu; Preethy, Senthilkumar; Abraham, Samuel J.K.

    2012-01-01

    Current therapeutic modalities for ovarian cancer such as chemotherapy, radiotherapy and surgery have been reported to yield only marginal success in improving survival rates of patients and have associated adverse effects. We report here a case of recurrent stage IV ovarian cancer, treated with cell-based autologous immune enhancement therapy (AIET) along with chemotherapy and followed up for 18 months. A 54-year-old female was diagnosed with a recurrence of ovarian carcinoma 1 year after initial surgical removal followed by chemotherapy for stage IIIC ovarian carcinoma. When diagnosed in 2010 with recurrence, she had liver and spleen metastases with a CA-125 level of 243 U/ml and a stage IV clinical status. Six infusions of AIET using autologous in vitro expanded and activated natural killer (NK) cells (CD3–CD56+) and activated T lymphocytes (CD3+CD56+) were administered in combination with 6 cycles of chemotherapy with carboplatin and doxorubicin. Following this treatment, CA-125 decreased to 4.7 U/ml along with regression of the metastatic lesions and an improved quality of life. No adverse reactions were reported after the AIET transfusions. Eighteen months of follow-up revealed a static nonprogressive disease. Combining AIET with chemotherapy and other conventional treatments has been found to be effective in our experience, as reported earlier, even in patients with advanced ovarian cancer, and we recommend this strategy be considered in treating similar cases. PMID:22666198

  17. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis.

    PubMed

    Karamurzin, Yevgeniy S; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R; Patel, Prusha; Pike, Malcolm C; Soslow, Robert A; Park, Kay J

    2015-11-01

    Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

  18. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells.

    PubMed

    Lawson, Devon A; Bhakta, Nirav R; Kessenbrock, Kai; Prummel, Karin D; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-10-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are initiated

  19. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells

    PubMed Central

    Lawson, Devon A.; Bhakta, Nirav R.; Kessenbrock, Kai; Prummel, Karin D.; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-01-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality1. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours2–5. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown2. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are

  20. Current and Emerging Systemic Therapy in Gastro-Esophageal Cancer "The Old and New Therapy for Metastatic Disease, The Role of Adjuvant and Neoadjuvant Therapy for Localized Disease".

    PubMed

    Lim, Bora; Jiang, Yixing

    2015-01-01

    Cancers of esophagus and stomach are common malignant diseases worldwide, and they are associated with serious morbidity and high mortality rates. When diagnosed at an early stage, gastro-esophageal cancers are potentially curable. Neo-adjuvant or adjuvant therapies using both chemotherapy and radiation therapy have been shown to reduce the risk of local recurrence and distant metastasis. For advanced or metastatic tumors, systemic chemotherapy offers symptomatic palliation and moderate benefits in survival. With recent advances in anti-cancer therapeutics, progress has been made to improve treatment response and life expectancy in patients with advanced gastro-esophageal cancers. Furthermore, the clinical use of molecularly targeted agents in combination with cytotoxic chemotherapeutics is being evaluated in a number of ongoing clinical trials. In this article, we review currently used standard systemic therapies including recently evolving targeted therapies for metastatic gastro-esophageal cancers, as well as the proven role and the regimens that are used as neoadjuvant and adjuvant treatment in localized gastro-esophageal cancers.

  1. TH-E-BRF-08: Subpopulations of Similarly-Responding Lesions in Metastatic Prostate Cancer

    SciTech Connect

    Lin, C; Harmon, S; Perk, T; Jeraj, R

    2014-06-15

    Purpose: In patients with multiple lesions, resistance to cancer treatments and subsequent disease recurrence may be due to heterogeneity of response across lesions. This study aims to identify subpopulations of similarly-responding metastatic prostate cancer lesions in bone using quantitative PET metrics. Methods: Seven metastatic prostate cancer patients treated with AR-directed therapy received pre-treatment and mid-treatment [F-18]NaF PET/CT scans. Images were registered using an articulated CT registration algorithm and transformations were applied to PET segmentations. Midtreatment response was calculated on PET-based texture features. Hierarchical agglomerative clustering was used to form groups of similarly-responding lesions, with the number of natural clusters (K) determined by the inconsistency coefficient. Lesion clustering was performed within each patient, and for the pooled population. The cophenetic coefficient (C) quantified how well the data was clustered. The Jaccard Index (JI) assessed similarity of cluster assignments from patient clustering and from population clustering. Results: 188 lesions in seven patients were identified for analysis (between 6 to 53 lesions per patient). Lesion response was defined as percent change relative to pre-treatment for 23 uncorrelated PET-based feature identifiers. . High response heterogeneity was found across all lesions (i.e. range ΔSUVmax =−95.98% to 775.00%). For intra-patient clustering, K ranged from 1–20. Population-based clustering resulted in 75 clusters, of 1-6 lesions each. Intra-patient clustering resulted in higher quality clusters than population clustering (mean C=0.95, range=0.89 to 1.00). For all patients, cluster assignments from population clustering showed good agreement to intra-patient clustering (mean JI=0.87, range=0.68 to 1.00). Conclusion: Subpopulations of similarly-responding lesions were identified in patients with multiple metastatic lesions. Good agreement was found between

  2. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    PubMed

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  3. Cancer Metastases: Early Dissemination and Late Recurrences

    PubMed Central

    Friberg, Sten; Nyström, Andreas

    2015-01-01

    BACKGROUND Metastatic cells from a primary tumor can occur before the primary cancer is detected. Metastatic cells can also remain in the patient for many years after removal of the primary tumor without proliferating. These dormant malignant cells can awaken and cause recurrent disease decades after the primary treatment. The purpose of this article is to review the clinical evidence for early dissemination and late recurrences in human malignant tumors. We used the following definitions: dormancy of cells may be defined as a nonproliferating state or an arrest in the cell cycle that results in a prolonged G0 phase. If one accepts the term “late metastases” to indicate a period exceeding 10 years from the removal of the primary tumor, then the two malignancies in which this occurs most frequently are cutaneous malignant melanoma (CMM) and renal cell carcinoma (RCC). METHODS PubMed, Web of Science, and Scopus were searched with the keywords “metastases,” “early dissemination,” “late recurrences,” “inadvertently transmitted cancer,” “tumor growth rate,” “dormancy,” “circulating tumor cells,” and “transplantation of cancer.” RESULTS Several case reports of early dissemination and late recurrences of various types of malignancies were found. Analyses of the growth rates of several malignant tumors in the original host indicated that the majority of cancers had metastasized years before they were detected. CMM, RCC, and malignant glioblastoma were the three most common malignancies resulting from an organ transplantation. CMM and RCC were also the two most common malignancies that showed dormancy. In several cases of transplanted CMM and RCC, the donor did not have any known malignancy or had had the malignancy removed so long ago that the donor was regarded as cured. CONCLUSION (1) Metastases can frequently exist prior to the detection of the primary tumor. (2) Metastatic cells may reside in organs in the original host that are not

  4. Management of an invasive and metastatic Sertoli cell tumor with associated myelotoxicosis in a dog

    PubMed Central

    Withers, Sita S.; Lawson, Corinne M.; Burton, Andrew G.; Rebhun, Robert B.; Steffey, Michele A.

    2016-01-01

    We describe the surgical and post-operative management of a large, invasive, and metastatic functional Sertoli cell tumor in a 9-year-old cryptorchid male Labrador retriever dog. Despite residual disease after surgery, bone marrow recovery occurred without administration of bone marrow stimulants and serum estradiol accurately predicted tumor recurrence. PMID:26933269

  5. Radiotherapy and brachytherapy for recurrent colorectal cancer

    SciTech Connect

    Nag, S. )

    1991-05-01

    Radical surgical excision of locoregional recurrence of colorectal carcinoma usually produces the best survival and should be attempted whenever possible. However, recurrences are often unresectable; hence palliative local therapy may be indicated. There are several options for the radiation therapy of local, unresectable, recurrent, or metastatic colorectal cancer. Whole pelvis irradiation of 4,000-5,000 cGy followed by a coned-down boost of 1,000-1,500 cGy generally provides good symptomatic palliation in 80-90% of patients, but long-term control or cure is rarely achieved. External beam irradiation of 2,000-3,000 cGy to the whole liver with or without concurrent chemotherapy may be used for palliation of metastatic disease to the liver. A combination of intraoperative radiation therapy applied directly to the tumor bed and external beam irradiation may improve local control and survival rates. Multiple options are available for the intraoperative use of brachytherapy which can deliver high radiation doses to the residual tumor, or tumor bed, sparing normal tissue.

  6. [Recurrence of upper aerodigestive tract tumors].

    PubMed

    Martin, Laurent; Zoubir, Mustapha; Le Tourneau, Christophe

    2014-05-01

    Recurrences of tumours of the upper aerodigestive tract are frequent despite the improvement of the primary treatment and they limit the rate of survival long-term. They occur in patients with multiple co-morbidities, often associated with sequelae or side effects of earlier treatments. The salvage treatment will add a cumulative toxicity and therapeutic options are limited. The choice will go from curator to palliative treatment. The report benefit-risk must be assessed in each case depending on the terrain and prognostic factors that have been identified, such as performance status, the time between initial disease and the recurrence, the site and the stratification of the recurrence. In operable non-metastatic recurrence surgery remains the treatment of choice. Multimodal treatment involving surgery, radiation therapy and chemotherapy in this context is being evaluated. Non-operable tumors have long been considered only in a palliative context. The evaluation of detailed irradiation as bifractionnated radiotherapy combined with chemotherapy helped establish protocols allowing long-term survivals and consider these treatments as potentially curators. However, the toxicity of these treatments is important. That is why the technical innovations of the radiation and the development of new chemotherapeutic agents today offer opportunities remaining to assess. The use of irradiation targeted by intensity-modulated radiation therapy (IMRT), and stereotactic radiotherapy by decreasing the irradiated volume should decrease the toxicity. Generally better tolerated than conventional chemotherapy agents, targeted therapies also took their places associated with radiotherapy in the treatment of these patients already treated. Cetuximab was the first agent obtaining an indication. Other agents are being evaluated in metastatic recurrent tumors, including exploring the possibilities of radiopotentialisation nanoparticles and the inhibitors of apoptosis proteins.

  7. Treatment of Metastatic Prostate Cancer in Older Adults.

    PubMed

    Loh, Kah Poh; Mohile, Supriya G; Kessler, Elizabeth; Fung, Chunkit

    2016-10-01

    The aging of the population, along with rising life expectancy, means that increasing numbers of older men will be diagnosed with prostate cancer, and a large proportion of these men will present with metastatic disease. In this paper, we discuss recent advances in prostate cancer treatment. In particular, we review management approaches for older patients with metastatic prostate cancer based on the decision tree developed by the International Society of Geriatric Oncology, which categorized older men as "fit," "vulnerable," and "frail" according to comprehensive geriatric assessment. PMID:27586377

  8. Improvement of survival and prospect of cure in patients with metastatic breast cancer.

    PubMed

    Cheng, Yee Chung; Ueno, Naoto T

    2012-07-01

    Patients with metastatic breast cancer have traditionally been considered incurable with conventional treatment. However, 5-10% of those patients survive more than 5 years, and 2-5% survive more than 10 years. Recent studies suggest that the survival of patients with metastatic breast cancer has been slowly improving. In this review, we examine the possible curative approach for a certain group of patients with metastatic breast cancer. We identify that patients most likely to benefit from such an aggressive approach are young and have good performance status, adequate body functional reserve, long disease-free interval before recurrence, oligometastatic disease, and low systemic tumor load. An aggressive multidisciplinary approach including both local treatment of macroscopic disease and systemic treatment of microscopic disease can result in prolonged disease control in certain patients with metastatic breast cancer. Whether patients with prolonged disease control are "cured" remains controversial.

  9. Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma

    PubMed Central

    Zhang, J.; Huang, J. Y.; Chen, Y. N.; Yuan, F.; Zhang, H.; Yan, F. H.; Wang, M. J.; Wang, G.; Su, M.; Lu, G; Huang, Y.; Dai, H.; Ji, J.; Zhang, J.; Zhang, J. N.; Jiang, Y. N.; Chen, S. J.; Zhu, Z. G.; Yu, Y. Y.

    2015-01-01

    Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control. We identified 27 mutated genes, of which 19 genes are reported in COSMIC database (ZNF208, CRNN, ATXN3, DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17, JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121, AKAP2, ACAN and ACADL), and eight genes have not previously been described in gastric cancer (CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2, DMBT1and DAB1).Additionally,GPX4 and MPND in 19q13.3-13.4 region, is characterized as a novel fusion-gene. This study disclosed novel biological markers and tumorigenic pathways that would predict gastric cancer occurring peritoneal metastasis. PMID:26330360

  10. A technetium-labeled monoclonal antibody for imaging metastatic melanoma

    SciTech Connect

    Frytak, S.; Creagan, E.T.; Brown, M.L.; Salk, D.; Nelp, W. )

    1991-04-01

    Twenty patients with histologically proven metastatic melanoma were scanned with a 99mtechnetium ({sup 99}mTc)-labeled melanoma antibody to determine the detection rate of known malignant lesions and to evaluate the antibody's ability to discover occult metastases. Isotope localization in different organs was as follows: liver 100%, bone 100%, subcutaneous lesions 80%, lymph nodes 54%, and lung 33%. Four unsuspected bone lesions and 16 occult subcutaneous lesions were found. False positive lesions were noted in two instances--one benign thyroid adenoma, and one arthritic bone lesion. One patient developed an atypical serum sickness reaction with a rash and arthralgias that responded rapidly to treatment. The {sup 99}mTc antimelanoma antibody is a safe and effective method to detect metastatic melanoma. It has potential use for screening newly diagnosed melanomas that carry an increased risk of recurrence.

  11. CTGF is a therapeutic target for metastatic melanoma.

    PubMed

    Finger, E C; Cheng, C-F; Williams, T R; Rankin, E B; Bedogni, B; Tachiki, L; Spong, S; Giaccia, A J; Powell, M B

    2014-02-27

    Metastatic melanoma remains a devastating disease with a 5-year survival rate of less than five percent. Despite recent advances in targeted therapies for melanoma, only a small percentage of melanoma patients experience durable remissions. Therefore, it is critical to identify new therapies for the treatment of advanced melanoma. Here, we define connective tissue growth factor (CTGF) as a therapeutic target for metastatic melanoma. Clinically, CTGF expression correlates with tumor progression and is strongly induced by hypoxia through HIF-1 and HIF-2-dependent mechanisms. Genetic inhibition of CTGF in human melanoma cells is sufficient to significantly reduce orthotopic tumor growth, as well as metastatic tumor growth in the lung of severe combined immunodeficient (SCID) mice. Mechanistically, inhibition of CTGF decreased invasion and migration associated with reduced matrix metalloproteinase-9 expression. Most importantly, the anti-CTGF antibody, FG-3019, had a profound inhibitory effect on the progression of established metastatic melanoma. These results offer the first preclinical validation of anti-CTGF therapy for the treatment of advanced melanoma and underscore the importance of tumor hypoxia in melanoma progression.

  12. A rare cause of recurrent cerebral emboli despite oral anticoagulation

    PubMed Central

    Dzialowski, Imanuel; Wolz, Martin; Meinhardt, Matthias; Waldow, Thomas

    2014-01-01

    We report on a patient with a history of colon carcinoma and clinical presentation of recurrent cardiac emboli despite oral anticoagulation for atrial fibrillation. On delayed transoesophageal echocardiography, finally a left atrial myxoma was suspected. Surgery, however, revealed a left atrial metastatic tumour with histopathological features of a colon adenocarcinoma. Metastases of colorectal adenocarcinoma invading cardiac structures are rare. Isolated literature reports describe metastatic masses detected in the right atrium reflecting natural haematogenous spreading of cancer, but none in the left heart. PMID:25246459

  13. Isolated humeral recurrence in endometrial carcinoma

    PubMed Central

    Devdas, Santosh Kumar; Digumarti, Leela; Digumarti, Raghunadharao; Patro, Kunha Charan; Nutakki, Ramakoteswararao

    2016-01-01

    Isolated skeletal metastasis in endometrial carcinoma at recurrence is very rare. We report a 52-year-old woman diagnosed to have FIGO Stage 1b, Grade 1 endometrioid adenocarcinoma, presenting with isolated distal humerus metastasis, 2 years after surgery and adjuvant radiotherapy for primary disease. Imaging, bone scintigraphy, and cytology confirmed the diagnosis of poorly differentiated metastatic adenocarcinoma. She was treated with local radiotherapy followed by six cycles of paclitaxel and carboplatin chemotherapy along with zoledronic acid, monthly. She is symptom-free after the treatment and at a first follow-up visit after 3 months.

  14. Isolated humeral recurrence in endometrial carcinoma.

    PubMed

    Devdas, Santosh Kumar; Digumarti, Leela; Digumarti, Raghunadharao; Patro, Kunha Charan; Nutakki, Ramakoteswararao

    2016-01-01

    Isolated skeletal metastasis in endometrial carcinoma at recurrence is very rare. We report a 52-year-old woman diagnosed to have FIGO Stage 1b, Grade 1 endometrioid adenocarcinoma, presenting with isolated distal humerus metastasis, 2 years after surgery and adjuvant radiotherapy for primary disease. Imaging, bone scintigraphy, and cytology confirmed the diagnosis of poorly differentiated metastatic adenocarcinoma. She was treated with local radiotherapy followed by six cycles of paclitaxel and carboplatin chemotherapy along with zoledronic acid, monthly. She is symptom-free after the treatment and at a first follow-up visit after 3 months. PMID:27688615

  15. Isolated humeral recurrence in endometrial carcinoma

    PubMed Central

    Devdas, Santosh Kumar; Digumarti, Leela; Digumarti, Raghunadharao; Patro, Kunha Charan; Nutakki, Ramakoteswararao

    2016-01-01

    Isolated skeletal metastasis in endometrial carcinoma at recurrence is very rare. We report a 52-year-old woman diagnosed to have FIGO Stage 1b, Grade 1 endometrioid adenocarcinoma, presenting with isolated distal humerus metastasis, 2 years after surgery and adjuvant radiotherapy for primary disease. Imaging, bone scintigraphy, and cytology confirmed the diagnosis of poorly differentiated metastatic adenocarcinoma. She was treated with local radiotherapy followed by six cycles of paclitaxel and carboplatin chemotherapy along with zoledronic acid, monthly. She is symptom-free after the treatment and at a first follow-up visit after 3 months. PMID:27688615

  16. Recurrent ovarian cancer.

    PubMed

    Pujade-Lauraine, E; Combe, P

    2016-04-01

    Recurrence still occurs in a majority of patients with advanced ovarian cancer. However, progress in the management has allowed a significant prolongation of survival for relapsing disease. These last years, the field of interest has moved from chemotherapy to targeted therapy which is dominated by anti-angiogenic and anti-PARP agents. It is assumed that platinum-free interval will not remain the main prognostic and predictive criterion in the future, and will be replaced by a multi-factorial approach. This trend for personalization of therapy has highlighted important neglected fields for clinical research such as multi-line (≥3) relapse, frail patients including elderly and symptomatic and supportive measures. PMID:27141075

  17. Recurrent Dislocation of the Patella

    PubMed Central

    Benítez, Gustavo

    2015-01-01

    Purpose: To evaluate results of medial patellofemoral ligament (MPFL) reconstruction associated with lateral release and advancement of vastus medialis in recurrent dislocation of the patella. Methods: We retrospectively evaluated 11 patients with a mean follow-up of 19 months. Mean age was 23, mainly women. We did MPFL reconstruction with semitendinosus or gracilis tendon depending on BMI, associated with advancement of vastus medialis and lateral release. Results: Mean Kujala score improved from 46,54 pts. preoperative to 88,36 postoperative. Our main complication was 1 patient with rigid knee, who required movilization under anesthesia and arthroscopic arthrolisis to improve her outcome. Conclusion: The combination of this techniques are a good alternative to treat patients with recurrent patella disclocation, with good short and mid-term results. Biomechanic intra and postop complications of MPFL reconstruction are related to patellar fixation, anatomic positioning of femoral tunnel and knee position of the graft fixation.

  18. Higher overall survival in metastatic pancreatic cancer: the impact of where and how treatment is delivered

    PubMed Central

    Usón, Pedro Luiz Serrano; França, Monique Sedlmaier; Rodrigues, Heloisa Veasey; Macedo, Antônio Luiz de Vasconcellos; Goldenberg, Alberto; Smaletz, Oren; Armentano, Daniela Pezzutti Domingues; Simon, Sergio Daniel; Gansl, Rene Claudio

    2015-01-01

    Objective To determine the overall survival of patients with advanced pancreatic cancer and evaluate factors that impact prognosis in a private cancer center. Methods Data from the Hospital Cancer Registry at Hospital Israelita Albert Einstein were retrospectively collected. The patients enrolled had metastatic cancer at diagnosis or earlier staging and subsequent recurrence. Cases of neuroendocrine tumors were excluded. Results A total of 65 patients were evaluated, including 63 with adenocarcinoma. The median overall survival for patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV cancer, there was no evidence of a statistically significant association between median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age (p=0.152). However, the number of lines of chemotherapy was significantly associated with survival (log-rank p=0.013), with an estimated median survival of 10.2 months for patients who received up to two lines of treatment and 23.5 months for those receiving more than two lines of chemotherapy. Conclusion The survival of patients treated was longer than that reported in the literature. The only statistically significant factor related to increased survival was higher number of lines of chemotherapy received. We believe that the higher socioeconomic status of patients surveyed in this study, as well as their greater access to treatment options, may have influenced their overall survival. PMID:26313433

  19. Icotinib plus gemcitabine for metastatic pancreatic cancer: A case report

    PubMed Central

    Zhao, Jing; Shen, Hong; Hu, Han-Guang; Huang, Jian-Jin

    2015-01-01

    A large majority of patients diagnosed with pancreatic cancer have advanced metastatic disease with unresectable malignancies. Despite treatment advances, the survival benefit from chemotherapeutic regimens and targeted drugs is limited. Moreover, their application is limited in China because of high toxicity and cost. Recently, inhibitors of epidermal growth factor receptor activity have shown promise for the treatment of solid cancers when used in combination with standard therapy. However, these drugs have not been evaluated extensively for the treatment of pancreatic cancer. Here, we report the treatment of a 64-year-old male with metastatic pancreatic cancer using a novel regimen of icotinib with gemcitabine. Marked shrinkage of the mass was observed after two treatment cycles, and partial remission was achieved. The abdominal pain was relieved. The adverse effects were tolerable and treatment cost was acceptable. This is the first reported case for the treatment of advanced pancreatic cancer with icotinib plus gemcitabine and demonstrates a promising therapeutic alternative. PMID:25805958

  20. TH-C-12A-07: Implementation of a Pulsed Low Dose Date Radiotherapy (PLRT) Protocol for Recurrent Cancers Using Advanced Beam Delivery

    SciTech Connect

    Ma, C; Lin, M; Chen, L; Price, R; Li, J; Kang, S; Wang, P; Lang, J

    2014-06-15

    Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategies were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.

  1. Metastatic Chordoma: A Diagnostic Challenge on Fine Needle Aspiration.

    PubMed

    Tranesh, Ghassan; Nassar, Aziza

    2016-01-01

    Chordomas are primary low grade malignant tumors of bone that usually arise within both ends of axial skeleton. The Notochord is a midline, ectoderm-derived structure that defines the phylum of chordates. Chordomas may pose difficult diagnostic challenges when encountered in secondary locations, such as lungs or other parenchymatous organs. We report the cytologic findings of a metastatic chordoma sampled through CT-scan guided fine needle aspiration (FNA) of lower lobe lung nodule in a 54-year-old man diagnosed with recurrent chordoma involving the lumber spine and paraspinal region.

  2. Metastatic Chordoma: A Diagnostic Challenge on Fine Needle Aspiration

    PubMed Central

    Tranesh, Ghassan; Nassar, Aziza

    2016-01-01

    Chordomas are primary low grade malignant tumors of bone that usually arise within both ends of axial skeleton. The Notochord is a midline, ectoderm-derived structure that defines the phylum of chordates. Chordomas may pose difficult diagnostic challenges when encountered in secondary locations, such as lungs or other parenchymatous organs. We report the cytologic findings of a metastatic chordoma sampled through CT-scan guided fine needle aspiration (FNA) of lower lobe lung nodule in a 54-year-old man diagnosed with recurrent chordoma involving the lumber spine and paraspinal region. PMID:26881166

  3. Glycoprotein non-metastatic b (GPNMB): A metastatic mediator and emerging therapeutic target in cancer

    PubMed Central

    Maric, Gordana; Rose, April AN; Annis, Matthew G; Siegel, Peter M

    2013-01-01

    Molecularly targeted therapies are rapidly growing with respect to their clinical development and impact on cancer treatment due to their highly selective anti-tumor action. However, many aggressive cancers such as triple-negative breast cancer (TNBC) currently lack well-defined therapeutic targets against which such agents can be developed. The identification of tumor-associated antigens and the generation of antibody drug-conjugates represent an emerging area of intense interest and growth in the field of cancer therapeutics. Glycoprotein non-metastatic b (GPNMB) has recently been identified as a gene that is over-expressed in numerous cancers, including TNBC, and often correlates with the metastatic phenotype. In breast cancer, GPNMB expression in the tumor epithelium is associated with a reduction in disease-free and overall survival. Based on these findings, glembatumumab vedotin (CDX-011), an antibody-drug conjugate that selectively targets GPNMB, is currently being investigated in clinical trials for patients with metastatic breast cancer and unresectable melanoma. This review discusses the physiological and potential pathological roles of GPNMB in normal and cancer tissues, respectively, and details the clinical advances and challenges in targeting GPNMB-expressing malignancies. PMID:23874106

  4. The AMORE Protocol for Advanced-Stage and Recurrent Nonorbital Rhabdomyosarcoma in the Head-and-Neck Region of Children: A Radiation Oncology View

    SciTech Connect

    Blank, Leo E.C.M.; Koedooder, Kees; Pieters, Bradley R.; Grient, Hans N.B. van der; Kar, Marlou van de; Buwalda, Joeri; Balm, Alfons J.M.; Merks, Johannes H.M.; Strackee, Simon D.; Freling, Nicole J.; Koning, Caro C.E.

    2009-08-01

    Purpose: A multidisciplinary approach, consisting of consecutive Ablative Surgery, MOld technique with afterloading brachytherapy and immediate surgical REconstruction (AMORE) applied after chemotherapy, was designed for children with rhabdomyosarcoma in the head-and-neck region. Analysis of the first 42 patients was performed. Methods and Materials: After macroscopically radical tumor resection, molds were constructed for each individual to fit into the surgical defect. The molds, made of 5-mm-thick layers of thermoplastic rubber, consisted of different parts. Flexible catheters were positioned between layers. After brachytherapy, the molds were removed. Surgical reconstruction was performed during the same procedure. Results: Dose to the clinical target volume varied from 40 to 50 Gy for the primary treatment (31 patients) and salvage treatment groups (11 patients). There were 18 females and 24 males treated from 1993 until 2007. Twenty-nine tumors were located in the parameningeal region, and 13 were located in the nonparameningeal region. Patient age at the time of AMORE was 1.2-16.9 years (average, 6.5 years). Follow-up was 0.2-14.5 years (average, >5.5 years). Eleven patients died, 3 with local recurrence only, 6 with local and distant disease, 1 died of distant metastases only, and 1 patient died of a second primary tumor. Overall 5-year survival rates were 70% for the primary treatment group and 82% for the salvage group. Treatment was well tolerated, and acute and late toxicity were mild. Conclusions: The AMORE protocol yields good local control and overall survival rates, and side effects are acceptable.

  5. Metastatic model of HPV+ oropharyngeal squamous cell carcinoma demonstrates heterogeneity in tumor metastasis.

    PubMed

    Vermeer, Daniel W; Coppock, Joseph D; Zeng, Erliang; Lee, Kimberly M; Spanos, William C; Onken, Michael D; Uppaluri, Ravindra; Lee, John H; Vermeer, Paola D

    2016-04-26

    Human papillomavirus induced (HPV+) cancer incidence is rapidly rising, comprising 60-80% of oropharyngeal squamous cell carcinomas (OPSCCs); while rare, recurrent/metastatic disease accounts for nearly all related deaths. An in vivo pre-clinical model for these invasive cancers is necessary for testing new therapies. We characterize an immune competent recurrent/metastatic HPV+ murine model of OPSSC which consists of four lung metastatic (MLM) cell lines isolated from an animal with HPV+ OPSCC that failed cisplatin/radiation treatment. These individual metastatic clonal cell lines were tested to verify their origin (parental transgene expression and define their physiological properties: proliferation, metastatic potential, heterogeneity and sensitivity/resistance to cisplatin and radiation. All MLMs retain expression of parental HPV16 E6 and E7 and degrade P53 yet are heterogeneous from one another and from the parental cell line as defined by Illumina expression microarray. Consistent with this, reverse phase protein array defines differences in protein expression/activation between MLMs as well as the parental line. While in vitro growth rates of MLMs are slower than the parental line, in vivo growth of MLM clones is greatly enhanced. Moreover, in vivo resistance to standard therapies is dramatically increased in 3 of the 4 MLMs. Lymphatic and/or lung metastasis occurs 100% of the time in one MLM line. This recurrent/metastatic model of HPV+ OPSCC retains the characteristics evident in refractory human disease (heterogeneity, resistance to therapy, metastasis in lymph nodes/lungs) thus serving as an ideal translational system to test novel therapeutics. Moreover, this system may provide insights into the molecular mechanisms of metastasis. PMID:27013584

  6. Metastatic model of HPV+ oropharyngeal squamous cell carcinoma demonstrates heterogeneity in tumor metastasis

    PubMed Central

    Vermeer, Daniel W.; Coppock, Joseph D.; Zeng, Erliang; Lee, Kimberly M.; Spanos, William C.; Onken, Michael D.; Uppaluri, Ravindra; Lee, John H.; Vermeer, Paola D.

    2016-01-01

    Human papillomavirus induced (HPV+) cancer incidence is rapidly rising, comprising 60–80% of oropharyngeal squamous cell carcinomas (OPSCCs); while rare, recurrent/metastatic disease accounts for nearly all related deaths. An in vivo pre-clinical model for these invasive cancers is necessary for testing new therapies. We characterize an immune competent recurrent/metastatic HPV+ murine model of OPSSC which consists of four lung metastatic (MLM) cell lines isolated from an animal with HPV+ OPSCC that failed cisplatin/radiation treatment. These individual metastatic clonal cell lines were tested to verify their origin (parental transgene expression and define their physiological properties: proliferation, metastatic potential, heterogeneity and sensitivity/resistance to cisplatin and radiation. All MLMs retain expression of parental HPV16 E6 and E7 and degrade P53 yet are heterogeneous from one another and from the parental cell line as defined by Illumina expression microarray. Consistent with this, reverse phase protein array defines differences in protein expression/activation between MLMs as well as the parental line. While in vitro growth rates of MLMs are slower than the parental line, in vivo growth of MLM clones is greatly enhanced. Moreover, in vivo resistance to standard therapies is dramatically increased in 3 of the 4 MLMs. Lymphatic and/or lung metastasis occurs 100% of the time in one MLM line. This recurrent/metastatic model of HPV+ OPSCC retains the characteristics evident in refractory human disease (heterogeneity, resistance to therapy, metastasis in lymph nodes/lungs) thus serving as an ideal translational system to test novel therapeutics. Moreover, this system may provide insights into the molecular mechanisms of metastasis. PMID:27013584

  7. Recurrent aphthous stomatitis

    PubMed Central

    Preeti, L; Magesh, KT; Rajkumar, K; Karthik, Raghavendhar

    2011-01-01

    Recurrent aphthous ulcers are common painful mucosal conditions affecting the oral cavity. Despite their high prevalence, etiopathogenesis remains unclear. This review article summarizes the clinical presentation, diagnostic criteria, and recent trends in the management of recurrent apthous stomatitis. PMID:22144824

  8. Treatment of advanced non-small cell lung cancer.

    PubMed

    De Petris, L; Crinò, L; Scagliotti, G V; Gridelli, C; Galetta, D; Metro, G; Novello, S; Maione, P; Colucci, G; de Marinis, F

    2006-03-01

    In the last decade the treatment of advanced-metastatic non-small cell lung cancer has substantially improved. If in the early 90s there was still concern about the real efficacy of chemotherapy over best suppotive care alone in the advanced setting, constant developments in clinical research have demonstrated the survival advantage of active anti-cancer drugs not only in the first-line setting, but, lately, even in patients with recurrent disease after failure of two previous chemotherapy lines. With the premises of high throughput technologies, translational research is aiming to characterize patients and tumors on a molecular basis. With pharmacogenomics it would then be possible to accurately predict patient outcome and tailor the treatment strategy according to the geno-phenotype of single patients.

  9. Subperiostial recurrence of chondroblastoma.

    PubMed

    Reddy, Sumanth; Deavers, Michael; Lin, Patrick; Haygood, Tamara Miner

    2009-01-01

    We present a case of subperiosteal recurrence of chondroblastoma adjacent to the greater trochanter that was initially thought to represent septic arthritis of the hip in a 10-year-old girl. Soft-tissue recurrence of chondroblastoma is very rare, with fewer than ten cases reported in the literature. We demonstrate the recurrence on both CT and MRI. The MRI clearly demonstrates the soft-tissue recurrence and the associated inflammatory changes, with signal characteristics not unlike the primary tumor. PMID:27307836

  10. [A Successful Case of Treatment of Colonic Metastasis and Peritoneal Recurrence of Type 4 Gastric Cancer by Using Colectomy and Chemotherapy].

    PubMed

    Tomita, Yasuto; Fujii, Yoritaka; Miura, Seiko; Fujita, Jun; Morioka, Emi; Kaida, Daisuke; Ohonishi, Toshio; Ohono, Yukako; Noguchi, Miki; Funaki, Hiroshi; Fujita, Hideto; Kinami, Shinichi; Nakano, Yasuharu; Ueda, Nobuhiko; Kosaka, Takeo; Sakata, Noriaki

    2015-11-01

    We present a successful case of treatment of colonic metastasis and peritoneal recurrence of type 4 gastric cancer by using colectomy and chemotherapy. A 70-year-old woman with a diagnosis of type 4 advanced gastric cancer underwent distal gastrectomy. The final pathological diagnosis was LM, circ, type 4, sig, pT4a (SE), ly1, v1, pN1, M0, P0, CY0, pStage Ⅲa. Adjuvant chemotherapy was conducted with oral administration of S-1, though regrettably the chemotherapy was interrupted because of diarrhea, an adverse effect of S-1. Metastatic recurrence occurred on the transverse colon, for which she underwent transverse colectomy 2.9 years after the initial surgery. Another colonic metastasis in the ascending colon along with peritoneal recurrence was diagnosed 3.11 years after the initial surgery, and the patient underwent a palliative colostomy and received chemotherapy with S-1 plus docetaxel. She was successfully treated up to a clinical CR with chemotherapy, and she died 5.10 years after the initial surgery. In this case, a good prognosis was obtained through the combination of resection of the recurrence sites, palliative surgery for avoiding obstruction, and chemotherapy using S-1 plus docetaxel for metachronous multiple metastases. PMID:26805106

  11. Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer: a systematic review and cost-effectiveness analysis.

    PubMed Central

    Westwood, Marie; Joore, Manuela; Whiting, Penny; van Asselt, Thea; Ramaekers, Bram; Armstrong, Nigel; Misso, Kate; Severens, Johan; Kleijnen, Jos

    2014-01-01

    BACKGROUND Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment with standard chemotherapy. Patients with NSCLC are therefore tested for EGFR-TK tumour gene mutations to inform treatment decisions. There are a variety of tests available to detect these mutations. The different tests vary in the specific mutations that they attempt to detect, the amount of tumour cells needed for the test to work, the time that it takes to give a result, the error rate of the test, and the cost of the test. OBJECTIVE To compare the performance and cost-effectiveness of EGFR-TK mutation tests used to identify previously untreated adults with locally advanced or metastatic NSCLC, who may benefit from first-line treatment with TKIs. DATA SOURCES Twelve databases to August 2012 [including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations and Daily Update (OvidSP), EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment database (HTA), Science Citation Index (SCI), Latin American and Caribbean Health Sciences Literature (LILACS), BIOSIS Previews, NIHR Health Technology Assessment programme, PROSPERO (International Prospective Register of Systematic Reviews)], research registers and conference proceedings. A web-based survey gathered data on technical performance of EGFR-TK mutation tests. METHODS Randomised controlled trials were assessed for methodological quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using QUADAS-2. There were insufficient data for meta-analysis. For accuracy studies, we calculated sensitivity and specificity together with 95% confidence intervals (CIs). Survival data were summarised

  12. Extraneural Metastases of Glioblastoma without Simultaneous Central Nervous System Recurrence

    PubMed Central

    Kim, Wonki; Yoo, Heon; Shin, Sang Hoon; Gwak, Ho Shin

    2014-01-01

    Glioblastoma multiforme (GBM) is well known as the most common malignant primary brain tumor. It could easily spread into the adjacent or distant brain tissue by infiltration, direct extension and cerebro-spinal fluid dissemination. The extranueural metastatic spread of GBM is relatively rare but it could have more progressive disease course. We report a 39-year-old man who had multiple bone metastases and malignant pleural effusion of the GBM without primary site recurrence. PMID:25408938

  13. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

    PubMed Central

    Hong, Matthew K.H.; Macintyre, Geoff; Wedge, David C.; Van Loo, Peter; Patel, Keval; Lunke, Sebastian; Alexandrov, Ludmil B.; Sloggett, Clare; Cmero, Marek; Marass, Francesco; Tsui, Dana; Mangiola, Stefano; Lonie, Andrew; Naeem, Haroon; Sapre, Nikhil; Phal, Pramit M.; Kurganovs, Natalie; Chin, Xiaowen; Kerger, Michael; Warren, Anne Y.; Neal, David; Gnanapragasam, Vincent; Rosenfeld, Nitzan; Pedersen, John S.; Ryan, Andrew; Haviv, Izhak; Costello, Anthony J.; Corcoran, Niall M.; Hovens, Christopher M.

    2015-01-01

    Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood. PMID:25827447

  14. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  15. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

    SciTech Connect

    Hong, Matthew K. H.; Macintyre, Geoff; Wedge, David C.; Van Loo, Peter; Patel, Keval; Lunke, Sebastian; Alexandrov, Ludmil B.; Sloggett, Clare; Cmero, Marek; Marass, Francesco; Tsui, Dana; Mangiola, Stefano; Lonie, Andrew; Naeem, Haroon; Sapre, Nikhil; Phal, Pramit M.; Kurganovs, Natalie; Chin, Xiaowen; Kerger, Michael; Warren, Anne Y.; Neal, David; Gnanapragasam, Vincent; Rosenfeld, Nitzan; Pedersen, John S.; Ryan, Andrew; Haviv, Izhak; Costello, Anthony J.; Corcoran, Niall M.; Hovens, Christopher M.

    2015-04-01

    Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. As a result, analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.

  16. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

    DOE PAGES

    Hong, Matthew K. H.; Macintyre, Geoff; Wedge, David C.; Van Loo, Peter; Patel, Keval; Lunke, Sebastian; Alexandrov, Ludmil B.; Sloggett, Clare; Cmero, Marek; Marass, Francesco; et al

    2015-04-01

    Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones,more » even years after removal of the prostate. As a result, analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.« less

  17. Yoga for women with metastatic breast cancer: results from a pilot study.

    PubMed

    Carson, James W; Carson, Kimberly M; Porter, Laura S; Keefe, Francis J; Shaw, Heather; Miller, Julie M

    2007-03-01

    Metastatic breast cancer (MBC) remains a terminal illness for which major treatment advances are slow to appear, and hence it is crucial that effective palliative interventions be developed to reduce the cancer-related symptoms of women with this condition during the remaining years of their lives. This pilot/feasibility study examined a novel, yoga-based palliative intervention, the Yoga of Awareness Program, in a sample of women with MBC. The eight-week protocol included gentle yoga postures, breathing exercises, meditation, didactic presentations, and group interchange. Outcome was assessed using daily measures of pain, fatigue, distress, invigoration, acceptance, and relaxation during two preintervention weeks and the final two weeks of the intervention. Thirteen women completed the intervention (mean age=59; mean time since diagnosis=7 years; two African American, 11 Caucasian). During the study, four participants had cancer recurrences, and the physical condition of several others deteriorated noticeably. Despite low statistical power, pre-to-post multilevel outcomes analyses showed significant increases in invigoration and acceptance. Lagged analyses of length of home yoga practice (controlling for individual mean practice time and outcome levels on the lagged days) showed that on the day after a day during which women practiced more, they experienced significantly lower levels of pain and fatigue, and higher levels of invigoration, acceptance, and relaxation. These findings support the need for further investigation of the effects of the Yoga of Awareness Program in women with MBC.

  18. A Proteogenomic Approach to Understanding MYC Function in Metastatic Medulloblastoma Tumors

    PubMed Central

    Staal, Jerome A.; Pei, Yanxin; Rood, Brian R.

    2016-01-01

    Brain tumors are the leading cause of cancer-related deaths in children, and medulloblastoma is the most prevalent malignant childhood/pediatric brain tumor. Providing effective treatment for these cancers, with minimal damage to the still-developing brain, remains one of the greatest challenges faced by clinicians. Understanding the diverse events driving tumor formation, maintenance, progression, and recurrence is necessary for identifying novel targeted therapeutics and improving survival of patients with this disease. Genomic copy number alteration data, together with clinical studies, identifies c-MYC amplification as an important risk factor associated with the most aggressive forms of medulloblastoma with marked metastatic potential. Yet despite this, very little is known regarding the impact of such genomic abnormalities upon the functional biology of the tumor cell. We discuss here how recent advances in quantitative proteomic techniques are now providing new insights into the functional biology of these aggressive tumors, as illustrated by the use of proteomics to bridge the gap between the genotype and phenotype in the case of c-MYC-amplified/associated medulloblastoma. These integrated proteogenomic approaches now provide a new platform for understanding cancer biology by providing a functional context to frame genomic abnormalities. PMID:27775567

  19. Androgen deprivation–induced NCoA2 promotes metastatic and castration-resistant prostate cancer

    PubMed Central

    Qin, Jun; Lee, Hui-Ju; Wu, San-Pin; Lin, Shih-Chieh; Lanz, Rainer B.; Creighton, Chad J.; DeMayo, Francesco J.; Tsai, Sophia Y.; Tsai, Ming-Jer

    2014-01-01

    A major clinical hurdle for the management of advanced prostate cancer (PCa) in patients is the resistance of tumors to androgen deprivation therapy (ADT) and their subsequent development into castration-resistant prostate cancer (CRPC). While recent studies have identified potential pathways involved in CRPC development, the drivers of CRPC remain largely undefined. Here we determined that nuclear receptor coactivator 2 (NCoA2, also known as SRC-2), which is frequently amplified or overexpressed in patients with metastatic PCa, mediates development of CRPC. In a murine model, overexpression of NCoA2 in the prostate epithelium resulted in neoplasia and, in combination with Pten deletion, promoted the development of metastasis-prone cancer. Moreover, depletion of NCoA2 in PTEN-deficient mice prevented the development of CRPC. In human androgen-sensitive prostate cancer cells, androgen signaling suppressed NCoA2 expression, and NCoA2 overexpression in murine prostate tumors resulted in hyperactivation of PI3K/AKT and MAPK signaling, promoting tumor malignance. Analysis of PCa patient samples revealed a strong correlation among NCoA2-mediated signaling, disease progression, and PCa recurrence. Taken together, our findings indicate that androgen deprivation induces NCoA2, which in turn mediates activation of PI3K signaling and promotes PCa metastasis and CRPC development. Moreover, these results suggest that the inhibition of NCoA2 has potential for PCa therapy. PMID:25295534

  20. Androgen deprivation-induced NCoA2 promotes metastatic and castration-resistant prostate cancer.

    PubMed

    Qin, Jun; Lee, Hui-Ju; Wu, San-Pin; Lin, Shih-Chieh; Lanz, Rainer B; Creighton, Chad J; DeMayo, Francesco J; Tsai, Sophia Y; Tsai, Ming-Jer

    2014-11-01

    A major clinical hurdle for the management of advanced prostate cancer (PCa) in patients is the resistance of tumors to androgen deprivation therapy (ADT) and their subsequent development into castration-resistant prostate cancer (CRPC). While recent studies have identified potential pathways involved in CRPC development, the drivers of CRPC remain largely undefined. Here we determined that nuclear receptor coactivator 2 (NCoA2, also known as SRC-2), which is frequently amplified or overexpressed in patients with metastatic PCa, mediates development of CRPC. In a murine model, overexpression of NCoA2 in the prostate epithelium resulted in neoplasia and, in combination with Pten deletion, promoted the development of metastasis-prone cancer. Moreover, depletion of NCoA2 in PTEN-deficient mice prevented the development of CRPC. In human androgen-sensitive prostate cancer cells, androgen signaling suppressed NCoA2 expression, and NCoA2 overexpression in murine prostate tumors resulted in hyperactivation of PI3K/AKT and MAPK signaling, promoting tumor malignance. Analysis of PCa patient samples revealed a strong correlation among NCoA2-mediated signaling, disease progression, and PCa recurrence. Taken together, our findings indicate that androgen deprivation induces NCoA2, which in turn mediates activation of PI3K signaling and promotes PCa metastasis and CRPC development. Moreover, these results suggest that the inhibition of NCoA2 has potential for PCa therapy.

  1. Combination therapy for metastatic renal cell carcinoma

    PubMed Central

    Buonerba, Carlo; Di Lorenzo, Giuseppe

    2016-01-01

    Current therapy for metastatic clear cell renal cell carcinoma (RCC) consists of the serial administration of single agents. Combinations of VEGF and mTOR inhibitors have been disappointing in previous randomized trials. However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. Moreover, the emergence of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors has spawned the investigation of combinations of these agents with VEGF inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. These ongoing phase III trials in conjunction with the development of predictive biomarkers and agents inhibiting novel therapeutic targets may provide much needed advances in this still largely incurable disease. PMID:27047959

  2. Alvespimycin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors

    ClinicalTrials.gov

    2013-04-09

    Male Breast Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Gastric Cancer; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Melanoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Ovarian Epithelial Cancer; Recurrent Prostate Cancer; Recurrent Renal Cell Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Colon Cancer; Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage III Gastric Cancer; Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Melanoma; Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Ovarian Epithelial Cancer; Stage III Renal Cell Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip

  3. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    ClinicalTrials.gov

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  4. Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma.

    PubMed

    Kramer, Kim; Kushner, Brian H; Modak, Shakeel; Pandit-Taskar, Neeta; Smith-Jones, Peter; Zanzonico, Pat; Humm, John L; Xu, Hong; Wolden, Suzanne L; Souweidane, Mark M; Larson, Steven M; Cheung, Nai-Kong V

    2010-05-01

    Innovation in the management of brain metastases is needed. We evaluated the addition of compartmental intrathecal antibody-based radioimmunotherapy (cRIT) in patients with recurrent metastatic central nervous system (CNS) neuroblastoma following surgery, craniospinal irradiation, and chemotherapy. Twenty one patients treated for recurrent neuroblastoma metastatic to the CNS, received a cRIT-containing salvage regimen incorporating intrathecal (131)I-monoclonal antibodies (MoAbs) targeting GD2 or B7H3 following surgery and radiation. Most patients also received outpatient craniospinal irradiation, 3F8/GMCSF immunotherapy, 13-cis-retinoic acid and oral temozolomide for systemic control. Seventeen of 21 cRIT-salvage patients are alive 7-74 months (median 33 months) since CNS relapse, with all 17 remaining free of CNS neuroblastoma. One patient died of infection at 22 months with no evidence of disease at autopsy, and one of lung and bone marrow metastases at 15 months, and one of progressive bone marrow disease at 30 months. The cRIT-salvage regimen was well tolerated, notable for myelosuppression minimized by stem cell support (n = 5), and biochemical hypothyroidism (n = 5). One patient with a 7-year history of metastatic neuroblastoma is in remission from MLL-associated secondary leukemia. This is significantly improved to published results with non-cRIT based where relapsed CNS NB has a median time to death of approximately 6 months. The cRIT-salvage regimen for CNS metastases was well tolerated by young patients, despite their prior history of intensive cytotoxic therapies. It has the potential to increase survival with better than expected quality of life.

  5. Radiofrequency Ablation of Unresectable Primary and Metastatic Hepatic Malignancies

    PubMed Central

    Curley, Steven A.; Izzo, Francesco; Delrio, Paolo; Ellis, Lee M.; Granchi, Jennifer; Vallone, Paolo; Fiore, Francesco; Pignata, Sandro; Daniele, Bruno; Cremona, Francesco

    1999-01-01

    Objective To describe the safety and efficacy of radiofrequency ablation (RFA) to treat unresectable malignant hepatic tumors in 123 patients. Background The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, or multifocality or inadequate functional hepatic reserve. Local application of heat is tumoricidal; therefore, the authors investigated a novel RFA system to treat patients with unresectable hepatic cancer. Patients and Methods Patients with hepatic malignancies were entered into a prospective, nonrandomized trial. The liver tumors were treated percutaneously or during surgery under ultrasound guidance using a novel LeVeen monopolar array needle electrode and an RF 2000 generator. All patients were followed to assess complications, treatment response, and recurrence of malignant disease. Results RFA was used to treat 169 tumors (median diameter 3.4 cm, range 0.5 to 12 cm) in 123 patients. Primary liver cancer was treated in 48 patients (39.1%), and metastatic liver tumors were treated in 75 patients (60.9%). Percutaneous and intraoperative RFA was performed in 31 patients (35.2%) and 92 patients (74.8%), respectively. There were no treatment-related deaths, and the complication rate after RFA was 2.4%. All treated tumors were completely necrotic on imaging studies after completion of RFA treatments. With a median follow-up of 15 months, tumor has recurred in 3 of 169 treated lesions (1.8%), but metastatic disease has developed at other sites in 34 patients (27.6%). Conclusions RFA is a safe, well-tolerated, and effective treatment to achieve tumor destruction in patients with unresectable hepatic malignancies. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA should be investigated. PMID:10400029

  6. Current treatment options for recurrent nasopharyngeal cancer

    PubMed Central

    Suárez, Carlos; Rodrigo, Juan P.; Rinaldo, Alessandra; Langendijk, Johannes A.; Shaha, Ashok R.

    2010-01-01

    Loco-regional control rate of nasopharyngeal carcinoma (NPC) has improved significantly in the past decade. However, local recurrence still represents a major cause of mortality and morbidity in advanced stages, and management of local failure remains a challenging issue in NPC. The best salvage treatment for local recurrent NPC remains to be determined. The options include brachytherapy, external radiotherapy, stereotactic radiosurgery, and nasopharyngectomy, either alone or in different combinations. In this article we will discuss the different options for salvage of locally recurrent NPC. Retreatment of locally recurrent NPC using radiotherapy, alone or in combination with other treatment modalities, as well as surgery, can result in long-term local control and survival in a substantial proportion of patients. For small-volume recurrent tumors (T1–T2) treated with external radiotherapy, brachytherapy or stereotactic radiosurgery, comparable results to those obtained with surgery have been reported. In contrast, treatment results of advanced-stage locally recurrent NPC are generally more satisfactory with surgery (with or without postoperative radiotherapy) than with reirradiation. PMID:20865269

  7. Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases

    PubMed Central

    2013-01-01

    Background More information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer. Methods From a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome. Results In the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion. Conclusions Our findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread. PMID:23497091

  8. In vivo capture and label-free detection of early metastatic cells

    PubMed Central

    Azarin, Samira M.; Yi, Ji; Gower, Robert M.; Aguado, Brian A.; Sullivan, Megan E.; Goodman, Ashley G.; Jiang, Eric J.; Rao, Shreyas S.; Ren, Yinying; Tucker, Susan L.; Backman, Vadim; Jeruss, Jacqueline S.; Shea, Lonnie D.

    2015-01-01

    Breast cancer is a leading cause of death for women, with mortality resulting from metastasis. Metastases are often detected once tumor cells affect the function of solid organs, with a high disease burden limiting effective treatment. Here we report a method for the early detection of metastasis using an implanted scaffold to recruit and capture metastatic cells in vivo, which achieves high cell densities and reduces the tumor burden within solid organs 10-fold. Recruitment is associated with infiltration of immune cells, which include Gr1hiCD11b+ cells. We identify metastatic cells in the scaffold through a label-free detection system using inverse-spectroscopic optical coherence tomography, which identifies changes to nanoscale tissue architecture associated with the presence of tumor cells. For patients at risk of recurrence, scaffold implantation following completion of primary therapy has the potential to identify metastatic disease at the earliest stage, enabling initiation of therapy while the disease burden is low. PMID:26348915

  9. Metastatic benign pleomorphic adenoma. Report of a case and review of the literature.

    PubMed

    Rodríguez-Fernández, Javier; Mateos-Micas, Mario; Martínez-Tello, Francisco J; Berjón, Jennifer; Montalvo, Juan Jose; Forteza-González, Gabriel; Galan-Hernández, Ramón

    2008-03-01

    Pleomorphic adenoma (PA), originally called mixed tumour, is the most common neoplasm of the salivary glands and is generally accepted as benign biologically. Occasionally PA may give rise to metastasis. The metastasis may develop in a PA in which a malignant transformation occurs, either arising a carcinoma in the PA (carcinoma ex-mixed tumour) or as a carcinosarcoma (so-called true malignant mixed tumour). However, very rare benign PA eventually metastasise, usually after having a previous recurrence, displaying benign histological features as well in the primary tumour as in the metastasis. These tumours have been termed metastatic PA or metastatic mixed tumours. The aim of this paper is to report one case of metastatic histological benign pleomorphic adenoma, and to consider the clinical, pathological and therapeutic consequences of these rare tumours as well as its possible causes and mechanisms for its behaviour.

  10. Management of recurrent miscarriage.

    PubMed

    Sugiura-Ogasawara, Mayumi; Ozaki, Yasuhiko; Suzumori, Nobuhiro

    2014-05-01

    Recurrent miscarriage is classically defined as three or more consecutive pregnancy losses. Many researchers have now revised this definition to two or more pregnancy losses because of the recent increase in the prevalence of childless couples. Established causes of recurrent miscarriage are antiphospholipid antibodies, uterine anomalies and abnormal chromosomes in either partner, particularly translocations. Antiphospholipid syndrome is the most important treatable cause of recurrent miscarriage. However, it is not yet established as to what kind of testing should be conducted in patients with recurrent pregnancy loss. Standardization of tests for antiphospholipid antibodies is needed. On the other hand, embryonic aneuploidy is the most frequent cause of recurrent miscarriage. Chromosome analysis of the embryo is important, because it has good predictive value for subsequent live birth. It is not necessary to give any medications for unexplained cases of recurrent miscarriage, and provision of psychological support may be the most important to encourage the couples to continue to conceive until a live birth results.

  11. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis

    PubMed Central

    Patel, Keval; Griffing, George T.; Hauptman, Paul J.

    2016-01-01

    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy. PMID:27127432

  12. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis.

    PubMed

    Patel, Keval; Griffing, George T; Hauptman, Paul J; Stolker, Joshua M

    2016-04-01

    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy. PMID:27127432

  13. Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors.

    PubMed

    Blumenthal, Deborah T; Yalon, Michal; Vainer, Gilad W; Lossos, Alexander; Yust, Shlomit; Tzach, Lior; Cagnano, Emanuela; Limon, Dror; Bokstein, Felix

    2016-09-01

    Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published.

  14. Evolving Pharmacotherapies for the Treatment of Metastatic Melanoma

    PubMed Central

    Salama, April K.S.

    2013-01-01

    Metastatic melanoma remains a difficult disease to treat, and long term survivors are rare. Over the past few years, however, breakthroughs in both immunotherapy as well as targeted agents have had a tremendous impact on patients diagnosed with this disease. This review summarizes recent advances in systemic therapies for melanoma, including immune modulators directed against cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), as well as a number of targeted agents. These approaches hold great promise as the landscape of therapeutic options for advanced melanoma continues to evolve. PMID:23843723

  15. Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer

    ClinicalTrials.gov

    2015-10-15

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Multiple Endocrine Neoplasia Type 1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor

  16. Actomyosin tension as a determinant of metastatic cancer mechanical tropism

    NASA Astrophysics Data System (ADS)

    McGrail, Daniel J.; Kieu, Quang Minh N.; Iandoli, Jason A.; Dawson, Michelle R.

    2015-04-01

    Despite major advances in the characterization of molecular regulators of cancer growth and metastasis, patient survival rates have largely stagnated. Recent studies have shown that mechanical cues from the extracellular matrix can drive the transition to a malignant phenotype. Moreover, it is also known that the metastatic process, which results in over 90% of cancer-related deaths, is governed by intracellular mechanical forces. To better understand these processes, we identified metastatic tumor cells originating from different locations which undergo inverse responses to altered matrix elasticity: MDA-MB-231 breast cancer cells that prefer rigid matrices and SKOV-3 ovarian cancer cells that prefer compliant matrices as characterized by parameters such as tumor cell proliferation, chemoresistance, and migration. Transcriptomic analysis revealed higher expression of genes associated with cytoskeletal tension and contractility in cells that prefer stiff environments, both when comparing MDA-MB-231 to SKOV-3 cells as well as when comparing bone-metastatic to lung-metastatic MDA-MB-231 subclones. Using small molecule inhibitors, we found that blocking the activity of these pathways mitigated rigidity-dependent behavior in both cell lines. Probing the physical forces exerted by cells on the underlying substrates revealed that though force magnitude may not directly correlate with functional outcomes, other parameters such as force polarization do correlate directly with cell motility. Finally, this biophysical analysis demonstrates that intrinsic levels of cell contractility determine the matrix rigidity for maximal cell function, possibly influencing tissue sites for metastatic cancer cell engraftment during dissemination. By increasing our understanding of the physical interactions of cancer cells with their microenvironment, these studies may help develop novel therapeutic strategies.

  17. Cutaneous metastatic pigmented breast carcinoma.

    PubMed

    Gaitan-Gaona, Francisco; Said, Mirra C; Valdes-Rodriguez, Rodrigo

    2016-01-01

    A 66-year-old woman presented with a 3 cm black, ulcerated nodule located on the skin of the upper abdomen, just below the breast. The lesion was painful to the touch, but the patient reported no other associated symptoms and was otherwise healthy. A 4-mm punch biopsy of the affected skin was obtained and the histological diagnosis was cutaneous metastatic pigmented breast carcinoma. PMID:27136637

  18. Microchimerism in recurrent miscarriage.

    PubMed

    Gammill, Hilary S; Stephenson, Mary D; Aydelotte, Tessa M; Nelson, J Lee

    2014-11-01

    Maternal-fetal cell exchange during pregnancy results in acquisition of microchimerism, which can durably persist in both recipients. Naturally acquired microchimerism may impact maternal-fetal interaction in pregnancy. We conducted studies to ask whether microchimerism that a woman acquired from her own mother is detectable before or during pregnancy in women with recurrent miscarriage. Fetal microchimerism was also assayed. Women with primary idiopathic recurrent miscarriage (n=23) and controls (n=31) were studied. Genotyping was conducted for probands, their mothers and the fetus, a non-shared polymorphism identified and quantitative polymerase chain reaction performed to measure microchimerismin peripheral blood mononuclear cells. Preconception comparisons were made between recurrent miscarriage subjects and controls, using logistic regression and Wilcoxon rank sum. Longitudinal microchimerism in subsequent pregnancies of recurrent miscarriage subjects was described. There was a trend toward lower preconception detection of microchimerism in recurrent miscarriage versus controls, 6% vs. 19% (1/16 vs. 6/31, P=0.2). During pregnancy, 3/11 (27%) of recurrent miscarriage subjects who went on to have a birth had detection of microchimerism from their own mother, whereas neither of two subjects who went on to miscarry had detection (0/2). This initial data suggest that microchimerism from a woman's own mother, while detectable in women with recurrent miscarriage, may differ from controls and according to subsequent pregnancy outcome. Further studies are needed to determine the cell types, quantities and any potential functional role of microchimerism in recurrent miscarriage.

  19. Recurrent mixed tumor.

    PubMed

    Batsakis, J G

    1986-01-01

    Recurrence of benign neoplasms can usually be attributed to incomplete excision. Such is the case with benign mixed tumors of salivary glands. Certain histopathologic features of mixed tumors, however, appear to facilitate recurrences. These are: a predominantly myxoid composition, and transcapsular extension by the tumor. Multicentric origin is possible, but it must be regarded as a much lower order of probability.

  20. High Grade Leiomyosarcoma Mimicking a Recurrent Angiomyxoma in the Perineum

    PubMed Central

    Sood, Neha; Swaika, Abhisek; Hanooshi, Bashar; Waldorf, James; Peterson, Jennifer; Wu, Kevin; Attia, Steven; Dinh, Tri A.

    2015-01-01

    Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six) reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma. PMID:26266017

  1. High Grade Leiomyosarcoma Mimicking a Recurrent Angiomyxoma in the Perineum.

    PubMed

    Sood, Neha; Swaika, Abhisek; Hanooshi, Bashar; Waldorf, James; Peterson, Jennifer; Wu, Kevin; Attia, Steven; Dinh, Tri A

    2015-05-01

    Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six) reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma.

  2. Metastatic pleomorphic adenoma to the supraspinatus muscle: a case report and review of a rare aggressive clinical entity

    PubMed Central

    McGarry, James G; Redmond, Maeve; Tuffy, John B; Wilson, Lorraine; Looby, Seamus

    2015-01-01

    We report a case of a 65-year-old female with a recurrent right parotid pleomorphic adenoma (PA) 24 years after initial surgical excision. Positron-emission tomography (PET) and computed tomography (CT) demonstrated an unusual suspicious FDG-avid erosive rim enhancing mass centered in the right supraspinatus muscle. Cytology from CT-guided aspiration of the mass was consistent with a histologically benign PA, and the patient was diagnosed with metastatic pleomorphic adenoma (MPA). The patient later developed diffuse pulmonary metastases and died within 3 months. MPA, although rare, is recognised as a potentially lethal malignant complication of recurrent or longstanding benign PA. As no biochemical or genetic parameters are predictive of malignant change, patients presenting with recurrent PA should be considered for screening for metastatic disease. PMID:26629288

  3. Aflibercept in the Treatment of Metastatic Colorectal Cancer

    PubMed Central

    Wang, Tzu-Fei; Lockhart, Albert Craig

    2012-01-01

    Colorectal cancer is the third most common cancer in the US. In recent decades, an improved understanding of the role of the angiogenesis pathway in colorectal cancer has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic colorectal cancer, and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. Here we review the role of angiogenesis in the tumorigenesis of colorectal cancer, strategies for targeting angiogenesis, and the clinical development of aflibercept. PMID:22253552

  4. Recurrent retroperitoneal extra-GIST with rhabdomyosarcomatous and chondrosarcomatous differentiations: a rare case and literature review

    PubMed Central

    Zhu, Pengcheng; Fei, Yan; Wang, Yue’e; Ao, Qilin; Wang, Guoping

    2015-01-01

    Selective tyrosine kinase inhibitor (TKI) targeting KIT and PDGFRA is the frontline therapy for metastatic and unresectable GIST patients. Some initially responsive patients experience tumor progress because of secondary drug resistance, and some cases can develop heterogeneous differentiation. Here we report a rare case of recurrent retroperitoneal extra-GIST with rhabdomyosarcomatous and chondrosarcomatous differentiation with TKI therapy after surgical tumorectomy. Histology, immunohistochemistry, and mutational analysis were performed on primary and recurrent samples. The current case represents the first report of a recurrent retroperitoneal extra-GIST harboring mixed morphologic phenotypes of rhabdomyosarcoma and chondrosarsoma after TKI treatment. The dual differentiation can represent diagnostic pitfall. PMID:26464733

  5. Advances in the management of basal cell carcinoma

    PubMed Central

    Carucci, John A.

    2015-01-01

    Basal cell carcinoma (BCC), a malignant neoplasm derived from non-keratinizing cells that originate in the basal layer of the epidermis, is the most common cancer in humans. Several factors such as anatomic location, histologic features, primary or recurrent tumors, and patient characteristics influence the choice of treatment modality for BCC. Mohs micrographic surgery (MMS) facilitates optimal margin control and conservation of normal tissue for the management of BCC; however, other treatment modalities may also be implemented in the correct clinical scenario. Other treatment modalities that will be reviewed include simple excision, electrodesiccation and curettage, cryotherapy, topical immunotherapy and chemotherapy, photodynamic therapy, and radiation therapy. In addition, targeted molecular therapeutic options for the treatment of advanced or metastatic BCC will be discussed in this informal review based on recent literature obtained by using PubMed with relevant search terms. PMID:26097726

  6. Metastatic Crohn's disease in a Chinese girl.

    PubMed

    Yu, J T H T; Chong, L Y; Lee, K C

    2006-12-01

    Metastatic Crohn's disease, in which non-caseating granulomatous infiltration of the skin occurs at sites separated from the gastro-intestinal tract by normal tissue, is the least common dermatologic manifestation of Crohn's disease. We report a 15-year-old girl with metastatic Crohn's disease presenting as granulomatous vulvar papules and nodules with typical histopathologic features. To the best of our knowledge, this is the first case of metastatic Crohn's disease in Chinese children reported in the English medical literature.

  7. Stereotactic Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Leung, T.-W.; Wong, Victy Y.W.; Tung, Stewart Y.

    2009-11-01

    Purpose: To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) who were treated with stereotactic radiotherapy (SRT). Methods and Materials: Thirty patients with non-metastatic, locally recurrent NPC who were treated with curative intent between 1998 and 2002 were retrospectively analyzed. The International Union Against Cancer T-stage distribution at recurrence (rT) was as follows: rT1-14, rT2-7, rT3-3, and rT4-6. All patients were treated with SRT with a daily fractional dose of 2.5-4.5 Gy (median, 3 Gy) in 8-22 fractions (median, 18 fractions). Total equivalent dose (TED) was calculated by the linear-quadratic formula without a time factor correction. Results: The 5-year actuarial overall survival rate, disease-specific survival rate, and local failure-free survival (LFFS) rate for the whole group were 40%, 41.4%, and 56.8%, respectively. The 3-year LFFS rates of rT1-2 and rT3-4 diseases were 65% and 66.7%, respectively. Seven of nine patients who received a TED <55 Gy recurred locally compared with 4 of 21 patients who received >=55 Gy. Their corresponding 5-year LFFS rates were 22.2% and 75.8% (p = 0.005). The TED was the only factor significant in affecting the local control on univariate analyses. Conclusion: SRT is an effective treatment for locally recurrent NPC. TED >=55 Gy should be given to secure a higher local control rate. The late complication rates were acceptable for patients with rT1-2 disease. For patients with rT3-4 disease, more works need to be done to further decrease the late complications.

  8. Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

    ClinicalTrials.gov

    2016-11-03

    Bladder Urothelial Carcinoma; Distal Urethral Carcinoma; Infiltrating Bladder Urothelial Carcinoma Associated With Urethral Carcinoma; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Proximal Urethral Carcinoma; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urethra Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Prostate Cancer; Stage IV Urethral Cancer; Ureter Carcinoma

  9. Risk of Recurrence in Laryngeal Cancer

    PubMed Central

    Sørum Falk, Ragnhild; Folkvard Evensen, Jan; Boysen, Morten; Brøndbo, Kjell

    2016-01-01

    A cohort study was undertaken to analyze the risk of recurrence among 1616 patients with primary squamous cell carcinoma of the larynx from 1983 to 2010 at a single, tertiary academic center in Oslo, Norway. The cohort was followed from the date of diagnosis to September 2011. Competing risk regression analysis assessed the association between various risk factors and the risk of recurrence, where death was considered a competing event. Recurrence was observed in 368 patients (23%) during the study period. The majority (71%) of recurrences involved the location of the primary tumor. The overall risk of recurrence during the first three years after initiating treatment was 20.5%. Increased risk of recurrence was observed in patients with supraglottic cancer, younger patients, those with T2–T3 tumors and in patients treated in the earlier part of the study period. Significant factors for recurrence in glottic carcinomas were age, treatment in the earlier part of the study and T-status, whereas age was a significant factor in supraglottic cancer. N-status appeared less significant. In conclusion, follow-up of laryngeal squamous cell carcinoma should place particular emphasis on the site of the primary tumor, younger patients, cases of supraglottic cancer and T2-T4 primary tumors, especially during the first three years after treatment. More studies are needed to assess the impact of surgical versus non-surgical treatment, and eventually the significance of recurrence, for disease-specific and overall survival in cases of advanced laryngeal squamous cell carcinoma. PMID:27716797

  10. Recurrent pregnancy loss.

    PubMed

    Rao, Kamini A; Pillai, Jyothi R

    2006-08-01

    Recurrent abortions are hisheartening to the couple and also to the treating clinicians. Miscarriage is the loss of pregnancy weighing 500 g or less. Recurrent miscarriage or habitual abortion is defined as three or more consective abortions. Important factors involved in recurrent early pregnancy loss are genetic factors, endocrine factors, anatomic factors, immunologic factors, infectious factors and environmental factors. The factors are described in a nutshell in the text. Any severe infection that leads to bacteraemia orviraemia can cause sporadic miscarriage. Congenital uterine abnormalities have been associated most often with second-trimestar pregnancy loss. As regarding management of recurrent pregnancy loss the clinician has limited options. The use of aspiration in low dose (75 mg) and heparin is beneficial in APS positive patients. Multivitamins and folic acid assume importance in thrombophilic disorders. Tender live care with regular antenatal check-ups go a great way in achieving live term pregnancy.

  11. [Successful Multimodal Treatment for Aggressive Extrahepatic Metastatic Hepatocellular Carcinoma - A Case Report].

    PubMed

    Gon, Hidetoshi; Kido, Masahiro; Fukumoto, Takumi; Takebe, Atsushi; Tanaka, Motofumi; Kuramitsu, Kaori; Kinoshita, Hisoka; Fukushima, Kenji; Urade, Takeshi; So, Shinichi; Shinzeki, Makoto; Matsumoto, Ippei; Ajiki, Tetsuo; Ku, Yonson

    2015-09-01

    A 38-year-old man underwent right hepatectomy for a huge hepatocellular carcinoma(HCC)in the right hepatic lobe. Four months later, recurrent and metastatic disease were observed in the remnant liver and right lung, respectively. We performed a hepatectomy for the recurrent lesion because transcatheter arterial chemoembolization (TACE) was not effective. After surgery, we initiated sorafenib treatment for the lung metastases. One year later, the lung metastases worsened and metastases were observed in the mediastinal lymph nodes, and both metastatic lesions were resected. Seven months later, para-aortic lymph nodal metastasis was observed and dissected. Three months later, metastasis to the supraclavicular lymph node was observed. We performed particle radiation therapy and a complete response was achieved. One year later, metastases in both lungs were observed and resected. Despite continued sorafenib administration throughout the clinical course, a metastasis to the left adrenal gland was observed. This lesion was extirpated because no other recurrent lesions were detected. At 4 years and 6 months after the first operation, no other recurrences have occurred. Currently, sorafenib is the initial drug of choice for HCC with extrahepatic metastases. It is possible to improve the prognosis of patients with HCC and extrahepatic metastases by applying surgical treatment during the course of sorafenib administration. PMID:26469171

  12. Intra-abdominal recurrence of colorectal cancer detected by radioimmunoguided surgery (RIGS system)

    SciTech Connect

    Sardi, A.; Workman, M.; Mojzisik, C.; Hinkle, G.; Nieroda, C.; Martin, E.W. Jr.

    1989-01-01

    Since 1986, 32 patients with metastatic colorectal cancer have undergone second-look radioimmunoguided surgery (RIGS system). The primary tumor was located in the right and transverse colon in 11 patients, left and sigmoid colon in 16, and rectum in five. The carcinoembryonic antigen level was elevated in 30 patients (94%); all patients underwent a computed tomographic scan of the abdomen and pelvis. The overall sensitivity of the computed tomographic scan was 41% (abdomen other than liver, 27%; liver, 58%; and pelvis, 22%). The RIGS system identified recurrent tumor in 81% of the patients. The most common site of metastasis was the liver (41%), independent of the primary location. Local/regional recurrences alone accounted for 40% of all recurrences. In six patients (18%), recurrent tumor was found only with the RIGS system. The RIGS system is more dependable in localizing clinically obscure metastases than other methods, and carcinoembryonic antigen testing remains the most accurate preoperative method to indicate suspected recurrences.

  13. Prognostic significance of nucleolar organizer regions in recurrent pleomorphic adenomas of salivary glands.

    PubMed

    Criscuolo, M; Migaldi, M; Collina, G; Cesinaro, A M; Galetti, R; Lo Bianco, F; Trentini, G P

    1994-12-01

    Pleomorphic adenoma (PA) is the commonest tumor of salivary glands. It is considered a benign tumor which may recur and rarely metastatize. There are no reliable histological criteria for predicting recurrences of PA. In this paper, Ag-NOR expression, evaluated by means a computer assisted image analysis system, has been tested on 11 cases of PA, their recurrences, 10 non recurrent PA and 5 cases of carcinoma ex PA. Mean AgNOR count, mean AgNOR area and mean AgNOR area/particle were determined in each group. AgNOR count and area did not show any significant differences between recurrent and non recurrent PA. On the contrary, AgNOR area/particle seems to be a useful tool in predicting the clinical behaviour of this lesion.

  14. Bone marrow-derived stem cell therapy for metastatic brain cancers.

    PubMed

    Kaneko, Yuji; Tajiri, Naoki; Staples, Meaghan; Reyes, Stephanny; Lozano, Diego; Sanberg, Paul R; Freeman, Thomas B; van Loveren, Harry; Kim, Seung U; Borlongan, Cesar V

    2015-01-01

    We propose that stem cell therapy may be a potent treatment for metastatic melanoma in the brain. Here we discuss the key role of a leaky blood-brain barrier (BBB) that accompanies the development of brain metastases. We review the need to characterize the immunological and inflammatory responses associated with tumor-derived BBB damage in order to reveal the contribution of this brain pathological alteration to the formation and growth of brain metastatic cancers. Next, we discuss the potential repair of the BBB and attenuation of brain metastasis through transplantation of bone marrow-derived mesenchymal stem cells with the endothelial progenitor cell phenotype. In particular, we review the need for evaluation of the efficacy of stem cell therapy in repairing a disrupted BBB in an effort to reduce neuroinflammation, eventually attenuating brain metastatic cancers. The demonstration of BBB repair through augmented angiogenesis and vasculogenesis will be critical to establishing the potential of stem cell therapy for the treatment/prevention of metastatic brain tumors. The overarching hypothesis we advanced here is that BBB breakdown is closely associated with brain metastatic cancers of melanoma, exacerbating the inflammatory response of the brain during metastasis, and ultimately worsening the outcome of metastatic brain cancers. Abrogating this leaky BBB-mediated inflammation via stem cell therapy represents a paradigm-shifting approach to treating brain cancer. This review article discusses the pros and cons of cell therapy for melanoma brain metastases.

  15. Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

    SciTech Connect

    Polishchuk, Alexei L.; Li, Richard; Little, Anthony; Hawkins, Randall A.; Hamilton, Jeffrey; Lau, Michael; Tran, Hung Chi; Lemons, Richard S.; Matthay, Katherine K.; DuBois, Steven G.; and others

    2014-07-15

    Purpose/Objectives: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. Methods and Materials: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with {sup 131}I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. Results: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. Conclusions: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore

  16. Metastatic thyroid carcinoma of the mandibule.

    PubMed

    Erdag, T; Bilgen, C; Ceryan, K

    1999-01-01

    A case of metastatic papillary carcinoma to the mandible is presented. Though relatively rare, metastatic tumours of the mandible should be included in the differential diagnosis of the tumours in the parotid region. For the primary site; being in the cervicofacial region, the thyroid gland must be considered by the head and neck surgeon.

  17. The motility-proliferation-metabolism interplay during metastatic invasion

    PubMed Central

    Hecht, Inbal; Natan, Sari; Zaritsky, Assaf; Levine, Herbert; Tsarfaty, Ilan; Ben-Jacob, Eshel

    2015-01-01

    Metastasis is the major cause for cancer patients’ death, and despite all the recent advances in cancer research it is still mostly incurable. Understanding the mechanisms that are involved in the migration of the cells in a complex environment is a key step towards successful anti-metastatic treatment. Using experimental data-based modeling, we focus on the fundamentals of metastatic invasion: motility, invasion, proliferation and metabolism, and study how they may be combined to maximize the cancer’s ability to metastasize. The modeled cells’ performance is measured by the number of cells that succeed in migration in a maze, which mimics the extracellular environment. We show that co-existence of different cell clones in the tumor, as often found in experiments, optimizes the invasive ability in a frequently-changing environment. We study the role of metabolism and stimulation by growth factors, and show that metabolism plays a crucial role in the metastatic process and should therefore be targeted for successful treatment. PMID:26337223

  18. The role of pharmacogenomics in metastatic renal cell carcinoma.

    PubMed

    Castellano, Daniel; Virizuela, Juan Antonio; Cruz, Josefina; Sepulveda, Juan Manuel; Sáez, María Isabel; Sáenz, Maribel; Paz-Ares, Luís

    2012-09-01

    Pharmacogenomics is the study of how variation in the genetic background affects an individual's response to a specific drug and/or its metabolism. Using knowledge about the genes which produce the enzymes that metabolize a specific drug, a physician may decide to raise or lower the dose, or even change to a different drug. Targeted therapy with tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors has led to a substantial improvement in the standard of care for patients with advanced or metastatic renal cell carcinoma (RCC). Although few studies have identified biomarkers that predict the response of targeted drugs in the treatment of metastatic RCC, some associations have been found. Several studies have identified genetic polymorphisms with implications in the pharmacokinetics and/or pharmacodynamics of TKIs and mTOR inhibitors and which are associated with a prolonged progression-free survival and/or overall survival in patients with metastatic RCC. Among the genes of interest, we should consider IL8, FGFR2, VEGFA, FLT4, and NR1I2. In this review, we discuss single nucleotide polymorphisms (SNPs) associated with outcome and toxicity following targeted therapies and provide recommendations for future trials to facilitate the use of SNPs in personalized therapy for this disease.

  19. The motility-proliferation-metabolism interplay during metastatic invasion.

    PubMed

    Hecht, Inbal; Natan, Sari; Zaritsky, Assaf; Levine, Herbert; Tsarfaty, Ilan; Ben-Jacob, Eshel

    2015-01-01

    Metastasis is the major cause for cancer patients' death, and despite all the recent advances in cancer research it is still mostly incurable. Understanding the mechanisms that are involved in the migration of the cells in a complex environment is a key step towards successful anti-metastatic treatment. Using experimental data-based modeling, we focus on the fundamentals of metastatic invasion: motility, invasion, proliferation and metabolism, and study how they may be combined to maximize the cancer's ability to metastasize. The modeled cells' performance is measured by the number of cells that succeed in migration in a maze, which mimics the extracellular environment. We show that co-existence of different cell clones in the tumor, as often found in experiments, optimizes the invasive ability in a frequently-changing environment. We study the role of metabolism and stimulation by growth factors, and show that metabolism plays a crucial role in the metastatic process and should therefore be targeted for successful treatment. PMID:26337223

  20. Vismodegib: A smoothened inhibitor for the treatment of advanced basal cell carcinoma.

    PubMed

    Aditya, Suruchi; Rattan, Aditya

    2013-10-01

    Incidence of basal cell carcinoma (BCC), the most common skin cancer in humans, is rising. Surgery is the mainstay of treatment but there is no standard of care for locally advanced or metastatic disease. Hedgehog signaling proteins are critical for cell growth and differentiation during embryogenesis; Hh pathway is silenced in adults. Dysregulated or aberrant Hh signaling has been implicated in the pathogenesis of BCC. This hyperactive pathway can be inhibited by use of smoothened inhibitors such as vismodegib. Food and drug administration approved this oral, once-daily medication in 2012 to treat adults with metastatic BCC or locally advanced, recurrent BCC after surgery and also for patients with locally advanced BCC who are not candidates for surgery or radiation treatment. Clinical studies have shown it to be highly efficacious and the most common adverse effects include, muscle spasms, alopecia and dysgeusia. Use of targeted biologic modifiers, exemplified by Hh directed therapeutics offer a new hope to patients with high-surgical morbidity or inoperable tumors.

  1. Metastatic breast cancer and its complications.

    PubMed

    Rubens, R D

    1992-12-01

    Tamoxifen is now established for use in premenopausal as well as postmenopausal patients. Recent reports have not shown its activity to be enhanced by the addition of either prednisolone, progestogens, or interferon. Reversible ocular toxicity from tamoxifen appears to be more common than had been previously realized. Different schedules giving the same dose intensity of doxorubicin give markedly different pharmacokinetic profiles. Although this does not lead to differences in responses or physical toxicity, it seems to have important implications for quality of life. Taxol is showing impressive activity in advanced breast cancer, and significant response rates have also been reported for carboplatin and podophyllotoxin derivatives. To achieve maximum effectiveness from the cyclophosphamide, methotrexate, and fluorouracil combination, attention to schedule and dose intensity has been shown to be important. No new effective cytotoxic combinations have been described. High-dose chemotherapy requiring bone marrow support remains experimental. Further progress has been made in monitoring the response of metastatic bone disease to treatment. The precise significance for patients of the results in many of the papers reviewed is often uncertain because they lack quality-of-life measures; the importance of this approach is emphasized. PMID:1457519

  2. Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma

    ClinicalTrials.gov

    2016-11-02

    Metastatic Ewing Sarcoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Bone Marrow; Metastatic Malignant Neoplasm in the Lung; Metastatic Peripheral Primitive Neuroectodermal Tumor of Bone; Peripheral Primitive Neuroectodermal Tumor of Soft Tissues

  3. Treatment of non-resectable and metastatic gastrointestinal stromal tumors: experience with the use of tyrosine kinase inhibitors in a third level hospital in Mexico

    PubMed Central

    Pimentel Renteria, Alberto; Pluma Jiménez, Miguel; Pérez Martínez, Mario; Martínez Martínez, Gloria; Rivera Rivera, Samuel; Grajales Álvarez, Rocío; Bautista Aragón, Yolanda; Quintana Quintana, Miguel; Alejandro Silva, Juan

    2016-01-01

    Background Stromal tumors of the digestive tract are uncommon malignant diseases, are subclassified as leiomyosarcomas and Gastrointestinal Stromal Tumors (GIST) depending on the molecular expression of tyrosine kinase receptor KIT (CD117). GISTs represent 1% of malignant tumors affecting this anatomical site. Localized tumours diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since tyrosine kinase inhibitors (TKIs) were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results We obtained information of 71 patients with metastatic, non-resectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%) with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%), most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 30.6 months and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400 mg per day. Treatment was well-tolerated in most cases. Conclusions Metastatic GIST evaluated in our center shows a different affection in gender and age, and our population shows a different response to TKIs

  4. Orthotopic non-metastatic and metastatic oral cancer mouse models.

    PubMed

    Bais, Manish V; Kukuruzinska, Maria; Trackman, Philip C

    2015-05-01

    Oral cancer is characterized by high morbidity and mortality with a predisposition to metastasize to different tissues, including lung, liver, and bone. Despite progress in the understanding of mutational profiles and deregulated pathways in oral cancer, patient survival has not significantly improved over the past decades. Therefore, there is a need to establish in vivo models that recapitulate human oral cancer metastasis to evaluate therapeutic potential of novel drugs. Here we report orthotopic tongue cancer nude mouse models to study oral cancer growth and metastasis using human metastatic (UMSCC2) and non-metastatic (CAL27) cell lines, respectively. Transduction of these cell lines with lentivirus expressing red fluorescent protein (DsRed) followed by injection into tongues of immunodeficient mice generated orthotopic tongue tumors that could be monitored for growth and metastasis by fluorescence measurement with an in vivo Imaging System (IVIS 200). The growth rates of CAL27-DsRed induced tumors were higher than UMSCC2-DsRed tumors after day 15, while UMSCC2-DsRed tumors revealed metastasis beginning on day 21. Importantly, UMSCC2 tumors metastasized to a number of tissues including the submandibular gland, lung, kidney, liver, and bone. Further, immunohistochemical analyses of tongue tumors induced by CAL27 and UMSCC2 cells revealed elevated expression of components of protumorigenic pathways deregulated in human cancers, including Cyclin D1, PCNA, Ki-67, LSD1, LOXL2, MT-MMP1, DPAGT1, E-cadherin, OCT4A, and H3K4me1/2. These orthotopic mouse models are likely to be useful tools for gaining insights into the activity and mechanisms of novel oral cancer drug candidates.

  5. Semaphorin 3D autocrine signaling mediates the metastatic role of annexin A2 in pancreatic cancer

    PubMed Central

    Foley, Kelly; Rucki, Agnieszka A.; Xiao, Qian; Zhou, Donger; Leubner, Ashley; Mo, Guanglan; Kleponis, Jennifer; Wu, Annie A.; Sharma, Rajni; Jiang, Qingguang; Anders, Robert A.; Iacobuzio-Donahue, Christine A.; Hajjar, Katherine A.; Maitra, Anirban; Jaffee, Elizabeth M.; Zheng, Lei

    2016-01-01

    Most patients with pancreatic ductal adenocarcinoma (PDA) present with metastatic disease at the time of diagnosis or will recur with metastases after surgical treatment. Semaphorin–plexin signaling mediates the migration of neuronal axons during development and of blood vessels during angiogenesis. The expression of the gene encoding semaphorin 3D (Sema3D) is increased in PDA tumors, and the presence of antibodies against the pleiotropic protein annexin A2 (AnxA2) in the sera of some patients after surgical resection of PDA is associated with longer recurrence-free survival. By knocking out AnxA2 in a transgenic mouse model of PDA (KPC) that recapitulates the progression of human PDA from premalignancy to metastatic disease, we found that AnxA2 promoted metastases in vivo. The expression of AnxA2 promoted the secretion of Sema3D from PDA cells, which coimmunoprecipitated with the co-receptor plexin D1 (PlxnD1) on PDA cells. Mouse PDA cells in which SEMA3D was knocked down or ANXA2-null PDA cells exhibited decreased invasive and metastatic potential in culture and in mice. However, restoring Sema3D in AnxA2-null cells did not entirely rescue metastatic behavior in culture and in vivo, suggesting that AnxA2 mediates additional prometastatic mechanisms. Patients with primary PDA tumors that have abundant Sema3D have widely metastatic disease and decreased survival compared to patients with tumors that have relatively low Sema3D abundance. Thus, AnxA2 and Sema3D may be new therapeutic targets and prognostic markers of metastatic PDA. PMID:26243191

  6. Metastatic growth from dormant cells induced by a col-I-enriched fibrotic environment.

    PubMed

    Barkan, Dalit; El Touny, Lara H; Michalowski, Aleksandra M; Smith, Jane Ann; Chu, Isabel; Davis, Anne Sally; Webster, Joshua D; Hoover, Shelley; Simpson, R Mark; Gauldie, Jack; Green, Jeffrey E

    2010-07-15

    Breast cancer that recurs as metastatic disease many years after primary tumor resection and adjuvant therapy seems to arise from tumor cells that disseminated early in the course of disease but did not develop into clinically apparent lesions. These long-term surviving, disseminated tumor cells maintain a state of dormancy, but may be triggered to proliferate through largely unknown factors. We now show that the induction of fibrosis, associated with deposition of type I collagen (Col-I) in the in vivo metastatic microenvironment, induces dormant D2.0R cells to form proliferative metastatic lesions through beta1-integrin signaling. In vitro studies using a three-dimensional culture system modeling dormancy showed that Col-I induces quiescent D2.0R cells to proliferate through beta1-integrin activation of SRC and focal adhesion kinase, leading to extracellular signal-regulated kinase (ERK)-dependent myosin light chain phosphorylation by myosin light chain kinase and actin stress fiber formation. Blocking beta1-integrin, Src, ERK, or myosin light chain kinase by short hairpin RNA or pharmacologic approaches inhibited Col-I-induced activation of this signaling cascade, cytoskeletal reorganization, and proliferation. These findings show that fibrosis with Col-I enrichment at the metastatic site may be a critical determinant of cytoskeletal reorganization in dormant tumor cells, leading to their transition from dormancy to metastatic growth. Thus, inhibiting Col-I production, its interaction with beta1-integrin, and downstream signaling of beta1-integrin may be important strategies for preventing or treating recurrent metastatic disease.

  7. Treatment options in patients with metastatic gastric cancer: Current status and future perspectives

    PubMed Central

    Bilici, Ahmet

    2014-01-01

    Despite advances in the treatment of gastric cancer, it remains the world’s second highest cause of cancer death. As gastric cancer is often diagnosed at an advanced stage, systemic chemotherapy is the mainstay of treatment for these patients. However, no standard palliative chemotherapy regimen has been accepted for patients with metastatic gastric cancer. Palliative chemotherapy including fluoropyrimidine, platin compounds, docetaxel and epirubicin prolongs survival, and improves a high quality of life to a greater extent than best supportive care. The number of clinical investigations associated with targeted agents has recently increased. Agents targeting the epidermal growth factor receptor 1 and human epidermal growth factor receptor 2 (HER2) have been widely tested. Trastuzumab was the first target drug developed, and pivotal phase III trials showed improved survival when trastuzumab was integrated into cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric cancer. Trastuzumab in combination with chemotherapy was thus approved to be a new standard of care for patients with HER2-positive advanced esophagogastric adenocarcinoma. Thus, the evaluation of HER2 status in all patients with metastatic gastroesophageal adenocarcinoma should be considered. Other agents targeting vascular endothelial growth factor, mammalian target of rapamycin, and other biological pathways have also been investigated in clinical trials, but showed little impact on the survival of patients. In this review, systemic chemotherapy and targeted therapies for metastatic gastric cancer in the first- and second-line setting are summarized in the light of recent advances. PMID:24744580

  8. Recurrent Fever in Children

    PubMed Central

    Torreggiani, Sofia; Filocamo, Giovanni; Esposito, Susanna

    2016-01-01

    Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time. PMID:27023528

  9. Intraoperative Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer.

    PubMed

    Oseledchyk, Anton; Zivanovic, Oliver

    2015-09-01

    Ovarian cancer, because it is largely confined to the peritoneal cavity, has a unique tumor biology and metastatic spread pattern. Its metastatic potential comes from detached tumor cells in the peritoneal cavity that re-attach to the mesothelial lining of the peritoneal surface. It is proposed that these micrometastases without neovasculature, as well as floating malignant cells, are drivers of early recurrence, since they can be neither resected nor adequately treated by systemic chemotherapy. This represents the major rationale for local treatment by means of postoperative intraperitoneal (IP) chemotherapy, which is the standard of care in the United States in patients with advanced-stage ovarian cancer who have minimal residual disease following cytoreductive surgery. An alternative loco-regional treatment strategy is the "HIPEC" procedure--hyperthermic IP chemoperfusion that is performed during the operation immediately following completion of gross tumor resection, and which provides improved tissue penetration and distribution of the chemotherapeutics. However, prospective data are limited and an outcomes benefit has yet to be shown. Here we discuss the advantages and pitfalls of HIPEC, as well as current data and ongoing prospective trials. PMID:26384807

  10. Gefitinib in Treating Patients With Metastatic or Unresectable Head and Neck Cancer or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-01-11

    Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Metastatic Parathyroid Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Parathyroid Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Larynx; Stage IIIB Non-small Cell Lung Cancer; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Follicular Thyroid Cancer; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus

  11. iTRAQ Quantitative Proteomic Comparison of Metastatic and Non-Metastatic Uveal Melanoma Tumors

    PubMed Central

    Crabb, John W.; Hu, Bo; Crabb, John S.; Triozzi, Pierre; Saunthararajah, Yogen; Singh, Arun D.

    2015-01-01

    Background Uveal melanoma is the most common malignancy of the adult eye. The overall mortality rate is high because this aggressive cancer often metastasizes before ophthalmic diagnosis. Quantitative proteomic analysis of primary metastasizing and non-metastasizing tumors was pursued for insights into mechanisms and biomarkers of uveal melanoma metastasis. Methods Eight metastatic and 7 non-metastatic human primary uveal melanoma tumors were analyzed by LC MS/MS iTRAQ technology with Bruch’s membrane/choroid complex from normal postmortem eyes as control tissue. Tryptic peptides from tumor and control proteins were labeled with iTRAQ tags, fractionated by cation exchange chromatography, and analyzed by LC MS/MS. Protein identification utilized the Mascot search engine and the human Uni-Prot/Swiss-Protein database with false discovery ≤ 1%; protein quantitation utilized the Mascot weighted average method. Proteins designated differentially expressed exhibited quantitative differences (p ≤ 0.05, t-test) in a training set of five metastatic and five non-metastatic tumors. Logistic regression models developed from the training set were used to classify the metastatic status of five independent tumors. Results Of 1644 proteins identified and quantified in 5 metastatic and 5 non-metastatic tumors, 12 proteins were found uniquely in ≥ 3 metastatic tumors, 28 were found significantly elevated and 30 significantly decreased only in metastatic tumors, and 31 were designated differentially expressed between metastatic and non-metastatic tumors. Logistic regression modeling of differentially expressed collagen alpha-3(VI) and heat shock protein beta-1 allowed correct prediction of metastasis status for each of five independent tumor specimens. Conclusions The present data provide new clues to molecular differences in metastatic and non-metastatic uveal melanoma tumors. While sample size is limited and validation required, the results support collagen alpha-3(VI) and

  12. [Treatment of recurrent furunculosis].

    PubMed

    Engelhard, Esther A N; Spanjaard, Lodewijk; Stijnis, C Kees

    2013-01-01

    The management of recurrent furunculosis is difficult, and often disappointing. We present the case of a 23-year-old female patient suffering from recurrent furunculosis. The furunculosis persisted after treatment with mupirocin nasal ointment, chlorhexidine soap and instructions for washing clothes, towels and bed sheets for a period of 7 days. Treatment with low-dose clindamycin for three months ultimately proved successful. We propose a structural approach for recurrent furunculosis in which extensive history-taking is followed by appropriate tests. Before prescribing an oral antibiotic (preferably low-dose clindamycin or a macrolide for 3 months), the patient should use an antimicrobial nasal ointment and soap and follow hygienic instructions as mentioned above. Members of the household who also have signs of the infection should be treated. Hygienic education is an essential component of treatment. We believe that this approach will lead to a treatment that is more effective and efficient.

  13. Recurrent wheezing in children

    PubMed Central

    Piazza, Michele; Piacentini, Giorgio

    2016-01-01

    Recurrent wheezing have a significant morbidity and it’s estimated that about one third of school-age children manifest the symptom during the first 5 years of life. Proper identification of children at risk of developing asthma at school age may predict long-term outcomes and improve treatment and preventive approach, but the possibility to identify these children at preschool age remains limited. For many years authors focused their studies to identify early children with recurrent wheezing at risk to develop asthma at school age. Different phenotypes have been proposed for a more precise characterization and a personalized plan of treatment. The main criticism concerns the inability to define stable phenotypes with the risk of overestimating or underestimating the characteristics of symptoms in these children. The aim of this review is to report the recent developments on the diagnosis and treatment of recurrent paediatric wheezing. PMID:26835404

  14. [Treatment of recurrent furunculosis].

    PubMed

    Engelhard, Esther A N; Spanjaard, Lodewijk; Stijnis, C Kees

    2013-01-01

    The management of recurrent furunculosis is difficult, and often disappointing. We present the case of a 23-year-old female patient suffering from recurrent furunculosis. The furunculosis persisted after treatment with mupirocin nasal ointment, chlorhexidine soap and instructions for washing clothes, towels and bed sheets for a period of 7 days. Treatment with low-dose clindamycin for three months ultimately proved successful. We propose a structural approach for recurrent furunculosis in which extensive history-taking is followed by appropriate tests. Before prescribing an oral antibiotic (preferably low-dose clindamycin or a macrolide for 3 months), the patient should use an antimicrobial nasal ointment and soap and follow hygienic instructions as mentioned above. Members of the household who also have signs of the infection should be treated. Hygienic education is an essential component of treatment. We believe that this approach will lead to a treatment that is more effective and efficient. PMID:23369819

  15. Treatment of metastatic breast cancer.

    PubMed

    Gradishar, William J

    2014-05-01

    Many newer agents in combination are being studied in the front-line treatment of women with HER2-positive metastatic breast cancer (MBC), but the story in the endocrine arena is more about the wise use of new strategies to overcome endocrine resistance, because no new antihormonal agents have been approved in the past decade. During his presentation at the NCCN 19th Annual Conference, Dr. William Gradishar explored what's new in the treatment of MBC, focusing primarily on enhancing the effect of endocrine therapy to overcome resistance with newer targeted agents such as everolimus, reevaluating the role of rebiopsy on disease progression and measuring circulating tumor cells as a surrogate of response to treatment, and reviewing the effective treatment regimens for HER2-positive disease.

  16. [Management of metastatic bladder cancer].

    PubMed

    Gauthier, Hélène; Serrate, Camille; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

    2014-12-01

    The management of patients with metastatic bladder cancer is mainly based on cytotoxic chemotherapy. The reference molecule is cisplatin. In 2014, first-line regimens include gemcitabine and cisplatin (GC protocol) or methotrexate, vinblastine, and cisplatin doxorubicin (MVAC protocol). When cisplatin is contra-indicated, another platinum Salt, carboplatin, is used in combination with gemcitabine. Vinflunine is the only molecule to have obtained a marketing approval for patients who failed first-line chemotherapy including a platinum salt. The overall prognosis of patients remains dismal, since the median overall survival is 12 to 14 months for patients being treated with cisplatin, whereas it is less than 1 year for patients receiving carboplatin. The identification of new effective drugs is a major challenge for the coming years. PMID:25668832

  17. Recurrent pregnancy loss.

    PubMed

    Hatasaka, H H; Varner, M W

    1994-12-01

    Recurrent pregnancy loss is a frustrating clinical dilemma for both patients and physicians because, in most cases, causes are nebulous and few treatments with proven benefit can be offered. Involved, expensive tests have frequently been proposed and their use has often filtered into clinical practice before their utility has been firmly demonstrated. Proposed causes of recurrent pregnancy loss include genetic and environmental etiologies, infectious agents, maternal congenital and acquired anatomic abnormalities, and immunologic and endocrinologic dysfunction. Appropriate management relies upon a realistic understanding of the often substantial limitations of currently available therapies.

  18. Tackling a Recurrent Pinealoblastoma

    PubMed Central

    Palled, Siddanna; Kalavagunta, Sruthi; Beerappa Gowda, Jaipal; Umesh, Kavita; Aal, Mahalaxmi; Abdul Razack, Tanvir pasha Chitraduraga; Gowda, Veerabhadre; Viswanath, Lokesh

    2014-01-01

    Pineoblastomas are rare, malignant, pineal region lesions that account for <0.1% of all intracranial tumors and can metastasize along the neuroaxis. Pineoblastomas are more common in children than in adults and adults account for <10% of patients. The management of pinealoblastoma is multimodality approach, surgery followed with radiation and chemotherapy. In view of aggressive nature few centres use high dose chemotherapy with autologus stem cell transplant in newly diagnosed cases but in recurrent setting the literature is very sparse. The present case represents the management of pinealoblastoma in the recurrent setting with reirradiation and adjuvant carmustine chemotherapy wherein the management guidelines are not definitive. PMID:25210636

  19. Recurrent Aphthous Stomatitis

    PubMed Central

    Akintoye, Sunday O.; Greenberg, Martin S.

    2014-01-01

    Recurrent Aphthous Stomatitis (RAS) is the most common ulcerative disease affecting the oral mucosa. It occurs mostly in healthy individuals and has atypical clinical presentation in immunocompromised individuals. The etiology of RAS is still unknown, but several local, systemic, immunologic, genetic, allergic, nutritional, and microbial factors, as well as immunosuppressive drugs, have been proposed as causative agents. Clinical management of RAS is based on severity of symptoms, frequency, size and number of lesions using topical and systemic therapies. The goals of therapy are to decrease pain and ulcer size, promote healing and decrease frequency of recurrence. PMID:24655523

  20. Discovery of a Metastatic Immune Escape Mechanism Initiated by the Loss of Expression of the Tumour Biomarker Interleukin-33.

    PubMed

    Saranchova, Iryna; Han, Jeffrey; Huang, Hui; Fenninger, Franz; Choi, Kyung Bok; Munro, Lonna; Pfeifer, Cheryl; Welch, Ian; Wyatt, Alexander W; Fazli, Ladan; Gleave, Martin E; Jefferies, Wilfred A

    2016-01-01

    A new paradigm for understanding immune-surveillance and immune escape in cancer is described here. Metastatic carcinomas express reduced levels of IL-33 and diminished levels of antigen processing machinery (APM), compared to syngeneic primary tumours. Complementation of IL-33 expression in metastatic tumours upregulates APM expression and functionality of major histocompatibility complex (MHC)-molecules, resulting in reduced tumour growth rates and a lower frequency of circulating tumour cells. Parallel studies in humans demonstrate that low tumour expression of IL-33 is an immune biomarker associated with recurrent prostate and kidney renal clear cell carcinomas. Thus, IL-33 has a significant role in cancer immune-surveillance against primary tumours, which is lost during the metastatic transition that actuates immune escape in cancer. PMID:27619158

  1. Discovery of a Metastatic Immune Escape Mechanism Initiated by the Loss of Expression of the Tumour Biomarker Interleukin-33

    PubMed Central

    Saranchova, Iryna; Han, Jeffrey; Huang, Hui; Fenninger, Franz; Choi, Kyung Bok; Munro, Lonna; Pfeifer, Cheryl; Welch, Ian; Wyatt, Alexander W.; Fazli, Ladan; Gleave, Martin E.; Jefferies, Wilfred A.

    2016-01-01

    A new paradigm for understanding immune-surveillance and immune escape in cancer is described here. Metastatic carcinomas express reduced levels of IL-33 and diminished levels of antigen processing machinery (APM), compared to syngeneic primary tumours. Complementation of IL-33 expression in metastatic tumours upregulates APM expression and functionality of major histocompatibility complex (MHC)-molecules, resulting in reduced tumour growth rates and a lower frequency of circulating tumour cells. Parallel studies in humans demonstrate that low tumour expression of IL-33 is an immune biomarker associated with recurrent prostate and kidney renal clear cell carcinomas. Thus, IL-33 has a significant role in cancer immune-surveillance against primary tumours, which is lost during the metastatic transition that actuates immune escape in cancer. PMID:27619158

  2. Negative correlation of ITCH E3 ubiquitin ligase and miRNA-106b dictates metastatic progression in pancreatic cancer.

    PubMed

    Luo, Zhu-Lin; Luo, Hui-Jun; Fang, Chen; Cheng, Long; Huang, Zhu; Dai, Ruiwu; Li, Kun; Tian, Fu-Zhou; Wang, Tao; Tang, Li-Jun

    2016-01-12

    Pancreatic cancer is one of the major malignancies and cause for mortality across the world, with recurrence and metastatic progression remaining the single largest cause of pancreatic cancer mortality. Hence it is imperative to develop novel biomarkers of pancreatic cancer prognosis. The E3 ubiquitin ligase ITCH has been previously reported to inhibit the tumor suppressive Hippo signaling by suppressing LATS1/2 in breast cancer and chronic lymphocytic leukemia. However, the role of ITCH in pancreatic cancer progression has not been described. Here we report that ITCH transcript and protein expression mimic metastatic trait in pancreatic cancer patients and cell lines. Loss-of-function studies of ITCH showed that the gene product is responsible for inducing metastasis in vivo. We furthermore show that hsa-miR-106b, which itself is down regulated in metastatic pancreatic cancer, directly interacts and inhibit ITCH expression. ITCH and hsa-miR-106b are thus potential biomarkers for pancreatic cancer prognosis.

  3. Cytoreductive nephrectomy for metastatic renal cell carcinoma.

    PubMed

    Chery, Lisly J; Karam, Jose A; Wood, Christopher G

    2016-09-01

    The incidence of renal cell carcinoma is increasing, with up to one-third of patients presenting with metastatic disease. Combination therapy is used to prolong survival in patients with metastatic renal cell carcinoma, which carries a poor prognosis. Although two pivotal phase 3 trials have demonstrated the efficacy of immunotherapy after cytoreductive nephrectomy for metastatic disease, for now, targeted therapy has replaced immunotherapy as the preferred systemic treatment in these patients. Two ongoing phase 3 trials are evaluating the role of cytoreductive nephrectomy prior to targeted therapy. Proper patient selection is paramount in achieving successful outcomes. PMID:27673288

  4. Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours

    PubMed Central

    Mahalingam, D; Wilding, G; Denmeade, S; Sarantopoulas, J; Cosgrove, D; Cetnar, J; Azad, N; Bruce, J; Kurman, M; Allgood, V E; Carducci, M

    2016-01-01

    Background: Mipsagargin (G-202; (8-O-(12-aminododecanoyl)-8-O-debutanoyl thapsigargin)-Asp-γ-Glu-γ-Glu-γ-GluGluOH)) is a novel thapsigargin-based targeted prodrug that is activated by PSMA-mediated cleavage of an inert masking peptide. The active moiety is an inhibitor of the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump protein that is necessary for cellular viability. We evaluated the safety of mipsagargin in patients with advanced solid tumours and established a recommended phase II dosing (RP2D) regimen. Methods: Patients with advanced solid tumours received mipsagargin by intravenous infusion on days 1, 2 and 3 of 28-day cycles and were allowed to continue participation in the absence of disease progression or unacceptable toxicity. The dosing began at 1.2 mg m−2 and was escalated using a modified Fibonacci schema to determine maximally tolerated dose (MTD) with an expansion cohort at the RP2D. Plasma was analysed for mipsagargin pharmacokinetics and response was assessed using RECIST criteria. Results: A total of 44 patients were treated at doses ranging from 1.2 to 88 mg m−2, including 28 patients in the dose escalation phase and 16 patients in an expansion cohort. One dose-limiting toxicity (DLT; Grade 3 rash) was observed in the dose escalation portion of the study. At 88 mg m−2, observations of Grade 2 infusion-related reaction (IRR, 2 patients) and Grade 2 creatinine elevation (1 patient) led to declaration of 66.8 mg m−2 as the recommended phase II dose (RP2D). Across the study, the most common treatment-related adverse events (AEs) were fatigue, rash, nausea, pyrexia and IRR. Two patients developed treatment-related Grade 3 acute renal failure that was reversible during the treatment-free portion of the cycle. To help ameliorate the IRR and creatinine elevations, a RP2D of 40 mg m−2 on day 1 and 66.8 mg m−2 on days 2 and 3 with prophylactic premedications and hydration on each

  5. Tumor Therapeutic Response and Vessel Tortuosity: Preliminary Report in Metastatic Breast Cancer

    PubMed Central

    Bullitt, Elizabeth; Lin, Nancy U.; Ewend, Matthew G.; Zeng, Donglin; Winer, Eric P.; Carey, Lisa A.; Smith, J. Keith

    2008-01-01

    No current non-invasive method is capable of assessing the efficacy of brain tumor therapy early during treatment. We outline an approach that evaluates tumor activity via statistical analysis of vessel shape using vessels segmented from MRA. This report is the first to describe the changes in vessel shape that occur during treatment of metastatic brain tumors as assessed by sequential MRA. In this preliminary study of 16 patients undergoing treatment for metastatic breast cancer we conclude that vessel shape may predict tumor response several months in advance of traditional methods. PMID:17354817

  6. Targeted therapy in her2-positive metastatic breast cancer: a review of the literature

    PubMed Central

    Zhu, X.; Verma, S.

    2015-01-01

    Breast tumours positive for her2 (human epidermal growth factor receptor 2) represent approximately 20% of all breast cancer cases and are associated with an aggressive natural history. The advent of targeted anti-her2 therapies has dramatically improved disease control and survival in patients with metastatic her2-positive breast cancer. Targeted agents are now considered the standard of care in the first-line setting and beyond. The present review summarizes the currently available data on targeted anti-her2 therapies from completed randomized phase iii clinical trials and briefly discusses emerging advances that will address unmet needs in metastatic her2-positive breast cancer. PMID:25848336

  7. Therapeutic Considerations in Treating HER2-Positive Metastatic Breast Cancer

    PubMed Central

    O’Sullivan, Ciara C.; Smith, Karen L.

    2014-01-01

    Despite advances in detection and treatment, metastatic breast cancer (MBC) remains the second highest cause of cancer-related death for women in the United States. Human epidermal growth factor receptor-2 (HER2) is amplified in 25–30% of breast cancers and is associated with aggressive disease and, historically, with poorer outcomes. The advent of trastuzumab, a monoclonal antibody to HER2, revolutionized the management of HER2-positive breast cancer (BC) in the metastatic and adjuvant settings. However, relapse despite adjuvant trastuzumab and resistance to trastuzumab in the metastatic setting remain substantial clinical problems for many patients with HER2-positive BC. As such, analyzing the mechanisms of trastuzumab resistance and developing new therapy to overcome trastuzumab resistance are research priorities. There has been progress, with the approval of three additional HER2-targeted agents in the last six years: lapatinib, pertuzumab, and ado-trastuzumab emtansine (T-DM1). Other HER2-targeted therapies, including neratinib and afatinib, are in clinical development, and trials of novel agents such as heat shock protein-90 (HSP90) inhibitors, phosphatidylinositol-3-kinase (PI3K) inhibitors, and HER2-targeted vaccines are ongoing. In addition to developing new therapy, research is addressing several unique challenges in the management of HER2-positive MBC. In this article, we discuss advances in the treatment of HER2-positive MBC, with a focus on novel HER2-targeted therapy and HER2-targeted agents recently approved by the United States Food and Drug Administration (FDA). Additionally, we also address the management of brain metastases (BM) and hormone receptor (HR) - positive, HER2-positive MBC. PMID:25285186

  8. Randomized Phase III Trial of Paclitaxel Once Per Week Compared With Nanoparticle Albumin-Bound Nab-Paclitaxel Once Per Week or Ixabepilone With Bevacizumab As First-Line Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance)

    PubMed Central

    Rugo, Hope S.; Barry, William T.; Moreno-Aspitia, Alvaro; Lyss, Alan P.; Cirrincione, Constance; Leung, Eleanor; Mayer, Erica L.; Naughton, Michael; Toppmeyer, Deborah; Carey, Lisa A.; Perez, Edith A.; Hudis, Clifford; Winer, Eric P.

    2015-01-01

    Purpose We compared nab-paclitaxel or ixabepilone once per week to paclitaxel with bevacizumab as first-line therapy for patients with advanced breast cancer (BC) to evaluate progression-free survival (PFS) for nab-paclitaxel or ixabepilone versus paclitaxel. Patients and Methods Eligible patients were age ≥ 18 years with chemotherapy-naive advanced BC. Patients were randomly assigned to bevacizumab with paclitaxel 90 mg/m2 (arm A), nab-paclitaxel 150 mg/m2 (arm B), or ixabepilone 16 mg/m2 (arm C), once per week for 3 of 4 weeks. Planned enrollment was 900 patients, which would give 88% power to detect a hazard ratio of 0.73. Results In all, 799 patients were enrolled, and 783 received treatment (97% received bevacizumab). Arm C was closed for futility at the first interim analysis (n = 241), and arm A (n = 267) and arm B (n = 275) were closed for futility at the second interim analysis. Median PFS for paclitaxel was 11 months, ixabepilone was inferior to paclitaxel (PFS, 7.4 months; hazard ratio, 1.59; 95% CI, 1.31 to 1.93; P < .001), and nab-paclitaxel was not superior to paclitaxel (PFS, 9.3 months; hazard ratio, 1.20; 95% CI, 1.00 to 1.45; P = .054). Results were concordant with overall survival; time to treatment failure was significantly shorter in both experimental arms v paclitaxel. Hematologic and nonhematologic toxicity, including peripheral neuropathy, was increased with nab-paclitaxel, with more frequent and earlier dose reductions. Conclusion In patients with chemotherapy-naive advanced BC, ixabepilone once per week was inferior to paclitaxel, and nab-paclitaxel was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms, particularly for nab-paclitaxel. Paclitaxel once per week remains the preferred palliative chemotherapy in this setting. PMID:26056183

  9. Recurrent infective endocarditis.

    PubMed Central

    Lossos, I. S.; Oren, R.

    1993-01-01

    Infective endocarditis is a serious disease associated with high mortality. Patients surviving recurrent bouts of infective endocarditis are reported infrequently. We report on a non-drug abuser patient who experienced seven episodes of infective endocarditis--the largest number reported to our knowledge in a single non-drug abuser patient. PMID:8290417

  10. Lung Cancer Indicators Recurrence

    Cancer.gov

    This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

  11. On Solving Linear Recurrences

    ERIC Educational Resources Information Center

    Dobbs, David E.

    2013-01-01

    A direct method is given for solving first-order linear recurrences with constant coefficients. The limiting value of that solution is studied as "n to infinity." This classroom note could serve as enrichment material for the typical introductory course on discrete mathematics that follows a calculus course.

  12. Recurrent Corneal Erosion

    MedlinePlus

    ... to apply a tight patch that restricts eye movement at night and upon waking so there is less likelihood of recurrence. If these rather simple procedures are not successful, the eye care professional may re-scrape the area to create a more irregular abrasion followed by ...

  13. Re-irradiation alternatives for recurrent high-grade glioma

    PubMed Central

    Dong, Yuanli; Fu, Chengrui; Guan, Hui; Zhang, Tianyi; Zhang, Zicheng; Zhou, Tao; Li, Baosheng

    2016-01-01

    Despite advances in the fields of surgery, chemotherapy and radiotherapy, the prognosis for high-grade glioma (HGG) remains unsatisfactory. The majority of HGG patients experience disease recurrence. To date, no standard treatments have been established for recurrent HGG. Repeat surgery and chemotherapy demonstrate moderate efficacy. As recurrent lesions are usually located within the previously irradiated field, a second course of irradiation was once considered controversial, as it was considered to exhibit unsatisfactory efficacy and radiation-related toxicities. However, an increasing number of studies have indicated that re-irradiation may present an efficacious treatment for recurrent HGG. Re-irradiation may be delivered via conventionally fractionated stereotactic radiotherapy, hypofractionated stereotactic radiation therapy, stereotactic radiosurgery and brachytherapy techniques. In the present review, the current literature regarding re-irradiation treatment for recurrent HGG is summarized with regard to survival outcome and side effects. PMID:27703519

  14. Bone metastatic disease: taking aim at new therapeutic targets.

    PubMed

    Coluzzi, F; Di Bussolo, E; Mandatori, I; Mattia, C

    2011-01-01

    Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.

  15. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  16. TAS-102 for Metastatic Colorectal Cancer

    Cancer.gov

    A summary of results from an international phase III trial that compared TAS-102 with placebo in patients with metastatic colorectal cancer whose disease progressed following prior treatments or who had health conditions that prevented the re-administrati

  17. Adenocarcinoma metastatic to the mandibular condyle.

    PubMed

    Webster, K

    1988-07-01

    Two cases of metastatic lesions presenting in the mandibular condyle as Temporo-Mandibular Joint Pain Dysfunction Syndrome are presented with a discussion on the mechanisms of tumour metastases to bone.

  18. Case for diagnosis. Metastatic Crohn's disease.

    PubMed

    Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; Sousa, Maria Silvia Laborne Alves de

    2016-01-01

    Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin. PMID:27579756

  19. Case for diagnosis. Metastatic Crohn's disease*

    PubMed Central

    Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; de Sousa, Maria Silvia Laborne Alves

    2016-01-01

    Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin. PMID:27579756

  20. Targeting bone metastatic cancer: Role of the mTOR pathway.

    PubMed

    Bertoldo, Francesco; Silvestris, Franco; Ibrahim, Toni; Cognetti, Francesco; Generali, Daniele; Ripamonti, Carla Ida; Amadori, Dino; Colleoni, Marco Angelo; Conte, Pierfranco; Del Mastro, Lucia; De Placido, Sabino; Ortega, Cinzia; Santini, Daniele

    2014-04-01

    One of the great challenges of cancer medicine is to develop effective treatments for bone metastatic cancer. Most patients with advanced solid tumors will develop bone metastasis and will suffer from skeletal related events associated with this disease. Although some therapies are available to manage symptoms derived from bone metastases, an effective treatment has not been developed yet. The mammalian target of rapamycin (mTOR) pathway regulates cell growth and survival. Alterations in mTOR signaling have been associated with pathological malignancies, including bone metastatic cancer. Inhibition of mTOR signaling might therefore be a promising alternative for bone metastatic cancer management. This review summarizes the current knowledge on mTOR pathway signaling in bone tissue and provides an overview on the known effects of mTOR inhibition in bone cancer, both in in vitro and in vivo models.

  1. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone.

    PubMed

    Arrigoni, Chiara; Bersini, Simone; Gilardi, Mara; Moretti, Matteo

    2016-01-01

    Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps. PMID:27571063

  2. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone

    PubMed Central

    Arrigoni, Chiara; Bersini, Simone; Gilardi, Mara; Moretti, Matteo

    2016-01-01

    Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps. PMID:27571063

  3. A case of non-specific interstitial pneumonia with recurrent gastric carcinoma and anti-Jo-1 antibody positive myositis.

    PubMed

    Ebisutani, Chikara; Ito, Isao; Kitaichi, Masanori; Tanabe, Naoya; Mishima, Michiaki; Kadowaki, Seizo

    2016-07-01

    We report the first case of non-specific interstitial pneumonia (NSIP) in a patient with cancer-associated myositis (CAM) that emerged along with the recurrence of the cancer. A 60-year-old woman, with a history of partial gastrectomy for gastric cancer 11 years ago, presented with exertional dyspnea with anti-Jo-1 antibody-positive myositis. Surgical lung biopsy showed NSIP with metastatic gastric cancer. Accordingly, her condition was diagnosed as CAM with cancer recurrence. In patients with a history of cancer, development of myositis may indicate cancer recurrence; therefore, careful observation would be necessary.

  4. Integrative analysis of 1q23.3 copy number gain in metastatic urothelial carcinoma

    PubMed Central

    Riester, Markus; Werner, Lillian; Bellmunt, Joaquim; Selvarajah, Shamini; Guancial, Elizabeth A.; Weir, Barbara A.; Stack, Edward C.; Park, Rachel S.; O’Brien, Robert; Schutz, Fabio A. B.; Choueiri, Toni K.; Signoretti, Sabina; Lloreta, Josep; Marchionni, Luigi; Gallardo, Enrique; Rojo, Federico; Garcia, Denise I.; Chekaluk, Yvonne; Kwiatkowski, David; Bochner, Bernard; Hahn, William C.; Ligon, Azra H.; Barletta, Justine A.; Loda, Massimo; Berman, David M.; Kantoff, Philip; Michor, Franziska; Rosenberg, Jonathan E.

    2014-01-01

    Purpose Metastatic urothelial carcinoma (UC) of the bladder is associated with multiple somatic copy number alterations (SCNAs). We evaluated SCNAs to identify predictors of poor survival in patients with metastatic UC treated with platinum-based chemotherapy. Experimental Design We obtained overall survival (OS) and array DNA copy number data from metastatic UC patients in two cohorts. Associations between recurrent SCNAs and OS were determined by a Cox proportional hazard model adjusting for performance status and visceral disease. mRNA expression was evaluated for potential candidate genes by Nanostring nCounter to identify transcripts from the region that are associated with copy number gain. In addition, expression data from an independent cohort was used to identify candidate genes. Results Multiple areas of recurrent significant gains and losses were identified. Gain of 1q23.3 was independently associated with a shortened OS in the both cohorts (adjusted HR 2.96; 95% CI, 1.35 to 6.48; P = 0.01 and adjusted HR 5.03; 95% CI 1.43-17.73; P < 0.001). The F11R, PFDN2, PPOX, USP21 and DEDD genes, all located on 1q23.3, were closely associated with poor outcome. Conclusions 1q23.3 copy number gain displayed association with poor survival in two cohorts of metastatic UC. The identification of the target of this copy number gain is ongoing, and exploration of this finding in other disease states may be useful for the early identification of poor risk UC patients. Prospective validation of the survival association is necessary to demonstrate clinical relevance. PMID:24486590

  5. Recurrent Infections May Signal Immunodeficiencies

    MedlinePlus

    ... Search AAAAI Breadcrumb navigation Home ▸ Conditions & Treatments ▸ Library ▸ Primary Immunodeficiency Disease Library ▸ Recurrent Infections May Signal Immunodeficiencies Share | Recurrent Infections May Signal Immunodeficiencies This article has been reviewed by Thanai Pongdee, MD, FAAAAI ...

  6. Innovative approaches to recurrent training

    NASA Technical Reports Server (NTRS)

    Noon, H.; Murphy, M.

    1984-01-01

    Innovative approaches to recurrent training for regional airline aircrews are explored. Guidelines for recurrent training programs which include in corporation of cockpit resource management are discussed. B.W.

  7. Impact of Diabetes and Hyperglycemia on Survival in Advanced Breast Cancer Patients

    PubMed Central

    Villarreal-Garza, Cynthia; Shaw-Dulin, Robin; Lara-Medina, Fernando; Bacon, Ludwing; Rivera, Daniel; Urzua, Lorena; Aguila, Christian; Ramirez-Morales, Rebeca; Santamaria, Julieta; Bargallo, Enrique; Mohar, Alejandro; Herrera, Luis A.

    2012-01-01

    Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC). Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS). A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels. PMID:22919369

  8. Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis.

    PubMed

    Safaee, Michael; Oh, Michael C; Bloch, Orin; Sun, Matthew Z; Kaur, Gurvinder; Auguste, Kurtis I; Tihan, Tarik; Parsa, Andrew T

    2013-03-01

    Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.

  9. Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review

    PubMed Central

    Tournigand, Christophe; Bonnetain, Franck; Richa, Hubert; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-01-01

    Systemic therapy is the standard care for patients with unresectable advanced colorectal cancer (CRC), but salvage surgery of metastatic disease should be considered in the case of adequate tumor shrinkage. Several drugs and combinations are now available for use in treating patients with advanced CRC, but the optimal sequence of therapy remains unknown. Moreover, the administration of antitumor therapy can be modulated by periods of maintenance or treatment breaks rather than delivered as full therapy until disease progression or unacceptable toxicity, followed by reintroduction of prior full therapy when required, before switching to other drugs. Consequently, randomized strategy trials are needed to define the optimal treatment sequences. Molecular testing for Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) is mandatory but not sufficient to select appropriate patients for epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. PMID:26673925

  10. State of the art management of metastatic gastroesophageal cancer

    PubMed Central

    Murphy, Adrian G.; Lynch, David

    2015-01-01

    The anatomical locations of upper gastrointestinal (GI) tumors have changed remarkably in the western world and reflect the increasing impact of obesity and gastroesophageal (GE) reflux rather than infectious etiologies. Incidence rates of GE tumors are rising rapidly and survival rates for patients with metastatic disease remain poor. Traditionally, cytotoxic chemotherapy has had some survival advantages but increasingly complex combination regimens are limited by toxicities. The advent of molecularly targeted therapy has provided additional options for patients with advanced disease including trastuzumab and ramucirumab. There has also been detailed molecular characterization of upper GI tumors which hopefully will result in improved tailoring of clinical trial design accounting for the heterogeneity inherent in GE tumors. While numerous targeted therapies are currently being studied in clinical trials, there is much excitement regarding the role of immunotherapy in GE cancers. Although further investigation is warranted, it represents a promising avenue for patients with advanced GE tumors. PMID:26539453

  11. Role of surgical consolidation in metastatic urothelial carcinoma

    PubMed Central

    Abe, Takashige; Matsumoto, Ryuji; Shinohara, Nobuo

    2016-01-01

    Purpose of review Since the development of systemic combination chemotherapy, postchemotherapy extirpation has been performed in selected patients mainly with locally advanced and/or initially unresectable bladder cancer, and, in very selected patients, surgical consolidation for visceral metastases has also been performed. The purpose of this article was to review and summarize the current evidence for the role of surgical consolidation in metastatic urothelial carcinoma. Recent findings The role of metastasectomy has not yet been examined in a randomized setting. In terms of locally advanced and/or node-positive bladder cancer, studies further support the benefit of surgical consolidation, especially after a favorable response to systemic chemotherapy. Regarding metastasectomy for visceral metastasis, recent evidence suggested that lung metastases (ideally small solitary lesions) are a good indication. Summary Patients with a good response to chemotherapy, limited nodal/pulmonary disease, and a favorable performance status are good candidates for surgical consolidation. Careful patient selection is mandatory. PMID:27471992

  12. Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review.

    PubMed

    Chibaudel, Benoist; Tournigand, Christophe; Bonnetain, Franck; Richa, Hubert; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-05-01

    Systemic therapy is the standard care for patients with unresectable advanced colorectal cancer (CRC), but salvage surgery of metastatic disease should be considered in the case of adequate tumor shrinkage. Several drugs and combinations are now available for use in treating patients with advanced CRC, but the optimal sequence of therapy remains unknown. Moreover, the administration of antitumor therapy can be modulated by periods of maintenance or treatment breaks rather than delivered as full therapy until disease progression or unacceptable toxicity, followed by reintroduction of prior full therapy when required, before switching to other drugs. Consequently, randomized strategy trials are needed to define the optimal treatment sequences. Molecular testing for Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) is mandatory but not sufficient to select appropriate patients for epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. PMID:26673925

  13. Tumor homogeneity between primary and metastatic sites for BRAF status in metastatic melanoma determined by immunohistochemical and molecular testing.

    PubMed

    Boursault, Lucile; Haddad, Véronique; Vergier, Béatrice; Cappellen, David; Verdon, Severine; Bellocq, Jean-Pierre; Jouary, Thomas; Merlio, Jean-Philippe

    2013-01-01

    BRAF inhibitors have demonstrated improvement of overall survival in patients with metastatic melanoma and BRAF(V600) mutations. In order to evaluate BRAF tumor heterogeneity between primary and metastatic site, we have evaluated the performance of immunohistochemistry (IHC) with an anti-BRAF(V600E) antibody in both localization by comparison with high resolution melting analysis followed by Sanger sequencing in a parallel blinded study. A total of 230 samples distributed as primary melanoma (n = 88) and different types of metastatic samples (n = 142) were studied in 99 patients with advanced or metastatic melanoma (stage III or IV). The prevalence of each BRAF mutation was c.1799T>A, BRAF(V600E) (45.2%), c.1799_1800TG>AA, BRAF(V600E2) (3.0%), c.1798_1799GT>AA, BRAF(V600K) (3.0%), c.1801 A>G, BRAF(K601E) (1.3%), c.1789_1790CT>TC, BRAF(L597S) (0.4%), c.1780G>A, BRAF(D594N) (0.9%) respectively. IHC was positive in 109/112 samples harboring BRAF(V600E/E2) mutations and negative in other cases. The cytoplasmic staining was either strongly positive in tumor cells of BRAF(V600E) mutated cases. It appeared strong brown, different from the vesicular grey cytoplasmic pigmentation of melanophages. Concordance between the two techniques was 96.4%. Sensitivity of IHC for detecting the BRAF(V600E/E2) mutations was 97.3%, while specificity was 100%. Both our IHC and molecular study demonstrated homogeneity between primary and metastatic sites for BRAF status in melanoma. This study also provides evidence that IHC may be a cost-effective first-line method for BRAF(V600E) detection. Thereafter, molecular techniques should be used in negative, ambiguous or non-contributive cases.

  14. Panitumumab: the evidence of its therapeutic potential in metastatic colorectal cancer care

    PubMed Central

    Martinelli, Erika; Morgillo, Floriana; Troiani, Teresa; Tortora, Giampaolo; Ciardiello, Fortunato

    2007-01-01

    Introduction: Colorectal cancer is the fourth most common malignant disease. Of newly diagnosed patients, 40% have metastatic disease at diagnosis, and approximately 25% of patients with localized disease at diagnosis will ultimately develop metastatic disease. The benefits of systemic chemotherapy in the treatment of metastatic colorectal cancer over best supportive care have been established. Panitumumab (ABX-EGF) is the first fully human monoclonal antibody developed for use in colorectal cancer that targets the extracellular domains of epidermal growth factor receptor. Aims: The goal of this article is to review the published evidence for the use of panitumumab in the treatment of metastatic colorectal cancer to define its therapeutic potential. Evidence review: The major evidence of panitumumab activity in colorectal cancer has appeared in meeting report abstracts. One phase II study in monotherapy, one in combination with chemotherapy, and one phase III study have included only patients with metastatic colorectal cancer. Clinical potential: To date, in phase II clinical studies panitumumab has demonstrated antitumor activity in advanced, refractory colorectal cancer. As monotherapy it resulted in a 10% response rate with 38% of patients having stable disease, and a 36% response rate with 46% stable disease when combined with chemotherapy. A phase III study indicates a clinically significant advantage of panitumumab as third-line monotherapy over best supportive care. Panitumumab appears to have a good tolerability profile, with no maximum tolerated dose yet defined. PMID:21221177

  15. Metastatic Crohn's disease: a review.

    PubMed

    Palamaras, I; El-Jabbour, J; Pietropaolo, N; Thomson, P; Mann, S; Robles, W; Stevens, H P

    2008-09-01

    Metastatic Crohn's disease (MCD) indicates the presence of non-caseating granuloma of the skin at sites separated from the gastrointestinal tract by normal tissue and is the least common dermatologic manifestation of CD. In adults, MCD usually appears after the initial diagnosis of CD in 70% of cases, whereas in children, it appears at the same time as CD in almost half of the cases. The most frequent skin lesions in adults are nodules, plaques with or without ulceration on the extremities and ulcers on the genitals. In children, genital swelling with or without erythema is the most frequent presentation of MCD. Simultaneous presence of perianal CD affects more females (60%) and particularly children. Associated gastrointestinal symptoms are present in one third of the cases in adults and in half of the cases in children. Treatment is often unsatisfactory. Randomised controlled trials are lacking. Various chemotherapeutic agents have been used such as oral metronidazole, topical and/or oral steroids, azathioprine, cyclosporine, sulfasalazine, tetracyclines, topical or systemic tacrolimus, infliximab alone or with methotrexate, and surgical treatment with oral zinc sulphate. MCD represents another 'great imitator'. This reviews the most relevant characteristics of this disease, in order to increase awareness and to avoid delay in diagnosis and improve management of the whole CD complex.

  16. Prolonged remission of recurrent cervical carcinoma following paclitaxel and carboplatin chemotherapy with paclitaxel maintenance chemotherapy.

    PubMed

    Micha, John P; Sassoon, Aaron F; Wong, Humberto; Goldstein, Bram H

    2015-08-01

    Cervical cancer recurs in ~30% of cases, for which a favorable prognosis is often unattainable. We describe a cervical cancer patient who developed metastatic disease ~5 years after her initial diagnosis. She was subsequently treated with six cycles of paclitaxel (175 mg/m) and carboplatin area under the curve (AUC) 5 chemotherapy every 21 days, and paclitaxel (135 mg/m) maintenance therapy every 21 days; the patient has remained in clinical remission after more than 5 years of follow-up. Chemotherapy has not historically been effective in managing recurrent, persistent, or metastatic cervical cancer. However, our case study involving paclitaxel and carboplatin chemotherapy with maintenance chemotherapy represents one of the longest documented remission rates in association with the management of recurrent cervical cancer.

  17. Recurrent Education: Trends and Issues.

    ERIC Educational Resources Information Center

    Organisation for Economic Cooperation and Development, Paris (France). Centre for Educational Research and Innovation.

    The document, consisting of three parts, focuses on recurrent education and the need for more effective deployment of educational resources within member countries of the Organization for Economic Cooperation and Development. The first section discusses the rationale for recurrent education. Recurrent education presents an educational opportunity…

  18. Glycogen synthase kinase-3β inhibition depletes the population of prostate cancer stem/progenitor-like cells and attenuates metastatic growth

    PubMed Central

    Kroon, Jan; in 't Veld, Lars S.; Buijs, Jeroen T.; Cheung, Henry; van der Horst, Geertje; van der Pluijm, Gabri

    2014-01-01

    Cancer cells with stem or progenitor properties play a pivotal role in the initiation, recurrence and metastatic potential of solid tumors, including those of the human prostate. Cancer stem cells are generally more resistant to conventional therapies thus requiring the characterization of key pathways involved in the formation and/or maintenance of this malignant cellular subpopulation. To this end, we identified Glycogen Synthase Kinase-3β (GSK-3β) as a crucial kinase for the maintenance of prostate cancer stem/progenitor-like cells and pharmacologic inhibition of GSK-3β dramatically decreased the size of this cellular subpopulation. This was paralleled by impaired clonogenicity, decreased migratory potential and dramatic morphological changes. In line with our in vitro observations, treatment with a GSK-3β inhibitor leads to a complete loss of tumorigenicity and a decrease in metastatic potential in preclinical in vivo models. These observed anti-tumor effects appear to be largely Wnt-independent as simultaneous Wnt inhibition does not reverse the observed antitumor effects of GSK-3β blockage. We found that GSK-3β activity is linked to cytoskeletal protein F-actin and inhibition of GSK-3β leads to disturbance of F-actin polymerization. This may underlie the dramatic effects of GSK-3β inhibition on prostate cancer migration. Furthermore, GSK-3β inhibition led to strongly decreased expression of several integrin types including the cancer stem cell-associated α2β1 integrin. Taken together, our mechanistic observations highlight the importance of GSK-3β activity in prostate cancer stemness and may facilitate the development of novel therapy for advanced prostate cancer. PMID:25344861

  19. Systemic embolisation as presentation and recurrence of cardiac myxoma two years after surgery.

    PubMed

    Liesting, C; Ramjankhan, F Z; van Herwerden, L A; Kofflard, M J M

    2010-10-01

    Primary cardiac tumours are rare when compared with metastatic involvement. The majority of primary cardiac tumours are benign and in adults the majority of these masses are myxomas. The treatment is surgical removal because of the risk of embolisation and/or cardiovascular complications. We describe a female presenting with systemic embolisation and recurrence of cardiac myxoma after surgery. Recurrence of myxoma is rare after surgery in case of solitary tumours but more frequent in patients with familial myxomas in association with the Carney complex. Genetic analysis revealed a mutation in the PRKAR1A gene that has never been described before. (Neth Heart J 2010;18:499502.). PMID:20978595

  20. Prevention of recurrent nephrolithiasis.

    PubMed

    Goldfarb, D S; Coe, F L

    1999-11-15

    The first episode of nephrolithiasis provides an opportunity to advise patients about measures for preventing future stones. Low fluid intake and excessive intake of protein, salt and oxalate are important modifiable risk factors for kidney stones. Calcium restriction is not useful and may potentiate osteoporosis. Diseases such as hyperparathyroidism, sarcoidosis and renal tubular acidosis should be considered in patients with nephrolithiasis. A 24-hour urine collection with measurement of the important analytes is usually reserved for use in patients with recurrent stone formation. In these patients, the major urinary risk factors include hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Effective preventive and treatment measures include thiazide therapy to lower the urinary calcium level, citrate supplementation to increase the urinary citrate level and, sometimes, allopurinol therapy to lower uric acid excretion. Uric acid stones are most often treated with citrate supplementation. Data now support the cost-effectiveness of evaluation and treatment of patients with recurrent stones. PMID:10593318

  1. Total enbloc spondylectomy for metastatic high grade spinal tumors: Early results

    PubMed Central

    Patil, Sanganagouda S; Nene, Abhay M

    2016-01-01

    Background: High grade metastatic spinal tumors are most common and are invasive. These patients can succumb to disease progression if not treated timely. Although considered as invasive and morbid, total enbloc spondylectomy (TES) in selected cases has better survival rates. The authors describe the results of TES for high grade metastatic spinal tumors. Materials and Methods: Five patients (four females and one male) underwent TES for solitary metastatic vertebral lesion between November 2012 and January 2014. These patients presented to us with spinal instability, unrelenting severe spinal pain and/or with severe progressive radiculopathy. Average age was 46.2 years (range 39–62 years). After complete investigations, computed tomography scan, magnetic resonance imaging scan and positron emission tomography (PET) scan, it was confirmed that these patients had high grade solitary vertebral metastatic tumor. Results: Average duration of followup was 18 months (range 16–20 months). The average preoperative visual analog scale score of 9.4 (range 9–10) improved to 2 (range 1–4) at last followup. Average blood loss was 1440 mL (range 1000–2000 mL). Average duration of surgery was 198 min (range 180–240 min). Significant pain relief was noticed in each patient in the immediate postoperative period and during followups. These patients attained complete functional activities of daily living with in a month. The imaging showed implants in situ, no recurrence of tumor, and no activity on PET scan at the final followup. Conclusion: The present series shows favorable short term results of TES for solitary, metastatic, high grade vertebral body tumors by a team approach. PMID:27512215

  2. Non-Prostate-Specific Membrane Antigen-Avid Metastatic Lung Nodule From Primary Prostatic Adenocarcinoma.

    PubMed

    Shetty, Deepa; Loh, Han; Bui, Chuong; Mansberg, Robert; Hadjashrafi, Amirazin; Do, Viet

    2016-10-01

    Ga-prostate-specific membrane antigen (PSMA) PET/CT is increasingly used to evaluate recurrent prostatic malignancy due to its high specificity. A 56-year-old man with previous history of treated prostate cancer 4 years earlier presented with rising prostate-specific antigen level and underwent Ga-PSMA PET/CT, which demonstrated an enlarging pulmonary nodule without PSMA avidity. The pulmonary nodule, however, showed moderate uptake on a corresponding FDG PET/CT study, suspicious of primary lung malignancy. Cytological and histopathological examination of the pulmonary nodule confirmed a metastatic deposit from ductal prostatic adenocarcinoma, an uncommon variant of prostatic malignancy.

  3. Estrogen Receptor Status Predicts Late-Onset Skeletal Recurrence in Breast Cancer Patients.

    PubMed

    Han, Hyun Ho; Lee, Sung Hwan; Kim, Baek Gil; Lee, Joo Hyun; Kang, Suki; Cho, Nam Hoon

    2016-02-01

    Estrogen receptor-positive (ER+) breast cancer (BCa) often recurs after long latency, and is known to favor bone as a metastatic site. We hypothesized that skeletal recurrence of ER+ BCa follows a different chronological pattern from that of nonskeletal recurrence.We retrospectively evaluated 434 matched pairs of ER+ and ER- female patients who underwent surgery for clinically localized BCa between 2005 and 2009. Patient age, tumor size, lymph node involvement, and adjuvant treatment biases were adjusted by the propensity score method. We conducted competing risk analysis to determine the prognostic significance of ER expression status on the risk of overall recurrence and late recurrence (after 3 years). We also compared chronological patterns of ER+ and ER- tumor recurrence, stratified by the first metastatic site (skeletal vs nonskeletal).After 3 postoperative years, ER+ tumor had a significantly higher risk of overall distant recurrence than ER- tumor (P = 0.02). When further stratified by first site of metastasis, only late skeletal recurrence was significantly associated with ER status (P = 0.029). In multivariate analysis, ER and lymph node involvement status were significant prognostic factors for late skeletal recurrence, with adjusted hazard ratios of 5.2 (95% CI = 1.2-22.4, P = 0.025) and 5.2 (1.7-16.3, P = 0.005), respectively. For nonskeletal distant recurrence, tumor size (>2 cm) was the only significant risk factor with adjusted hazard ratio of 2.8 (1.4-5.7, P = 0.005). Annual hazard of skeletal recurrence events of ER+ tumors continued to exist up to 10 years, while annual hazard of nonskeletal recurrences decreased after peaking at 5 years. ER- tumor recurrences exhibited similar annual hazard patterns across skeletal and nonskeletal sites.ER expression and lymph node involvement status were strong predictors of BCa late-onset (>3 years) recurrences, especially in skeletal sites. Therefore, skeletal system surveillance is

  4. Estrogen Receptor Status Predicts Late-Onset Skeletal Recurrence in Breast Cancer Patients

    PubMed Central

    Han, Hyun Ho; Lee, Sung Hwan; Kim, Baek Gil; Lee, Joo Hyun; Kang, Suki; Cho, Nam Hoon

    2016-01-01

    Abstract Estrogen receptor-positive (ER+) breast cancer (BCa) often recurs after long latency, and is known to favor bone as a metastatic site. We hypothesized that skeletal recurrence of ER+ BCa follows a different chronological pattern from that of nonskeletal recurrence. We retrospectively evaluated 434 matched pairs of ER+ and ER− female patients who underwent surgery for clinically localized BCa between 2005 and 2009. Patient age, tumor size, lymph node involvement, and adjuvant treatment biases were adjusted by the propensity score method. We conducted competing risk analysis to determine the prognostic significance of ER expression status on the risk of overall recurrence and late recurrence (after 3 years). We also compared chronological patterns of ER+ and ER− tumor recurrence, stratified by the first metastatic site (skeletal vs nonskeletal). After 3 postoperative years, ER+ tumor had a significantly higher risk of overall distant recurrence than ER− tumor (P = 0.02). When further stratified by first site of metastasis, only late skeletal recurrence was significantly associated with ER status (P = 0.029). In multivariate analysis, ER and lymph node involvement status were significant prognostic factors for late skeletal recurrence, with adjusted hazard ratios of 5.2 (95% CI = 1.2–22.4, P = 0.025) and 5.2 (1.7–16.3, P = 0.005), respectively. For nonskeletal distant recurrence, tumor size (>2 cm) was the only significant risk factor with adjusted hazard ratio of 2.8 (1.4–5.7, P = 0.005). Annual hazard of skeletal recurrence events of ER+ tumors continued to exist up to 10 years, while annual hazard of nonskeletal recurrences decreased after peaking at 5 years. ER− tumor recurrences exhibited similar annual hazard patterns across skeletal and nonskeletal sites. ER expression and lymph node involvement status were strong predictors of BCa late-onset (>3 years) recurrences, especially in skeletal sites. Therefore

  5. Recurrence and death in non-small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products.

    PubMed

    Fontanini, G; Vignati, S; Bigini, D; Mussi, A; Lucchi, M; Chiné, S; Angeletti, C A; Bevilacqua, G

    1996-06-01

    The 5-year survival rate of non-small cell lung carcinoma (NSCLC) has only marginally improved during the past two decades, despite advances in surgery and chemoradiotherapy. Major efforts are currently directed toward biological characterization of these tumors to define biomarkers able to add further prognostic information, thus improving new therapeutic protocols. We analyzed the predictive relevance of the microvessel count (MC), bcl-2 and p53 proteins, proliferative activity, and usual postsurgical parameters on recurrence and overall survival in a series of 70 patients with NSCLC. The expression of biological parameters (p53, bcl-2, proliferative activity, and MC) was detected using immunohistochemistry on paraffin-embedded and frozen sections from the tumors treated with surgical resection alone until relapse. In the univariate analysis, the histotype, tumor status, node status, p53, bcl-2, and MC have been shown to significantly affect progression and death. In the multiple logistic regression analysis, the MC (P < 0.000001), tumor status (P < 0.005), and node status (P < 0.0002) influenced the overall survival while prediction of relapse was strongly revealed by tumor status (P < 0.005), nodal metastatic involvement (P < 0.000001), and the assessment of the vascular count (P < 0.0004). These data have allowed the creation of a multivariate model which may add more information on risk of recurrence and death in patients with NSCLC and can form the basis for future randomized clinical trials.

  6. Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma.

    PubMed

    Khoja, Leila; Lorigan, Paul; Zhou, Cong; Lancashire, Matthew; Booth, Jessica; Cummings, Jeff; Califano, Raffaele; Clack, Glen; Hughes, Andrew; Dive, Caroline

    2013-06-01

    The incidence of melanoma is increasing worldwide. Advances in targeted agents and immunotherapy have improved outcomes in metastatic disease, but biomarkers are required to optimize treatment. We determined the prevalence of circulating tumor cells (CTCs) and explored their utility as prognostic and pharmacodynamic biomarkers. A total of 101 patients with metastatic cutaneous melanoma were recruited prospectively. CTC number was determined using the CellSearch platform and melanoma kits in samples taken at baseline and serially during treatment. CTC numbers ranged between 0 and 36 per 7.5 ml blood; 26% of patients had ≥ 2 CTCs. Baseline CTC number was prognostic for median overall survival (OS) in univariate analysis (2.6 vs. 7.2 months (P<0.011) for patients with ≥ 2 CTCs vs. <2 CTCs, respectively). In multivariate analysis, CTC number was an independent prognostic biomarker of OS (hazard ratio (HR) 2.403, 95% confidence interval (CI) 1.303-4.430, P=0.005). Patients receiving treatment in whom CTC number remained ≥ 2 CTCs during treatment had shorter median OS than those who maintained <2 CTCs (7 vs. 10 months, HR 0.34, 95% CI 0.14-0.81, log-rank test P=0.015). In conclusion, CTC number in metastatic cutaneous melanoma patients is prognostic for OS with a cutoff of 2 CTCs per 7.5 ml blood. CTC number measured before and throughout treatment provided additional prognostic information. Larger studies are warranted to confirm CTC biomarker utility in melanoma patients. PMID:23223143

  7. Minimizing metastatic risk in radiotherapy fractionation schedules

    NASA Astrophysics Data System (ADS)

    Badri, Hamidreza; Ramakrishnan, Jagdish; Leder, Kevin

    2015-11-01

    Metastasis is the process by which cells from a primary tumor disperse and form new tumors at distant anatomical locations. The treatment and prevention of metastatic cancer remains an extremely challenging problem. This work introduces a novel biologically motivated objective function to the radiation optimization community that takes into account metastatic risk instead of the status of the primary tumor. In this work, we consider the problem of developing fractionated irradiation schedules that minimize production of metastatic cancer cells while keeping normal tissue damage below an acceptable level. A dynamic programming framework is utilized to determine the optimal fractionation scheme. We evaluated our approach on a breast cancer case using the heart and the lung as organs-at-risk (OAR). For small tumor α /β values, hypo-fractionated schedules were optimal, which is consistent with standard models. However, for relatively larger α /β values, we found the type of schedule depended on various parameters such as the time when metastatic risk was evaluated, the α /β values of the OARs, and the normal tissue sparing factors. Interestingly, in contrast to standard models, hypo-fractionated and semi-hypo-fractionated schedules (large initial doses with doses tapering off with time) were suggested even with large tumor α/β values. Numerical results indicate the potential for significant reduction in metastatic risk.

  8. AR function in promoting metastatic prostate cancer

    PubMed Central

    Augello, Michael A.; Den, Robert B.

    2015-01-01

    Prostate cancer (PCa) remains a leading cause of cancer-related death in the USA. While localized lesions are effectively treated through radical prostatectomy and/or radiation therapy, treatment for metastatic disease leverages the addiction of these tumors on the androgen receptor (AR) signaling axis for growth and disease progression. Though initially effective, tumors resistant to AR-directed therapeutics ultimately arise (a stage of the disease known as castration-resistant prostate cancer) and are responsible for PCa-specific mortality. Importantly, an abundance of clinical and preclinical evidence strongly implicates AR signaling cascades in the development of metastatic disease in both early and late stages, and thus a concerted effort has been made to delineate the AR-specific programs that facilitate progression to metastatic PCa. A multitude of downstream AR targets as well as critical AR cofactors have been identified which impinge upon both the AR pathway as well as associated metastatic phenotypes. This review will highlight the functional significance of these pathways to disseminated disease and define the molecular underpinnings behind these unique, AR-driven, metastatic signatures. PMID:24425228

  9. Bone metastasis and the metastatic niche.

    PubMed

    Ren, Guangwen; Esposito, Mark; Kang, Yibin

    2015-11-01

    The bone marrow has been long known to host a unique environment amenable to colonization by metastasizing tumor cells. Yet, the underlying molecular interactions within this specialized microenvironment which give rise to the high incidence of bone metastasis in breast and prostate cancer patients have long remained uncharacterized. With the recent description of the bone metastatic "niche," considerable focus has been placed on understanding how the bone stroma contributes to each step of metastasis. Discoveries within this field have demonstrated that when cancer cells home to the niche in which hematopoietic and mesenchymal stem/progenitor cells normally reside, a bidirectional crosstalk emerges between the tumor cells and the bone metastatic stroma. This communication modulates every step of cancer cell metastasis to the bone, including the initial homing and seeding, formation of micrometastases, outgrowth of macrometastases, and the maintenance of long-term dormancy of disseminated tumor cells in the bone. In clinical practice, targeting the bone metastatic niche is evolving into a promising avenue for the prevention of bone metastatic relapse, therapeutic resistance, and other aspects of cancer progression. Here, we review the current knowledge concerning the role of the bone metastatic niche in bone metastasis.

  10. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

    PubMed Central

    Costa, Ricardo; Bacchi, Carlos E.; Almeida Filho, Paulo

    2013-01-01

    Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU). PMID:24455330

  11. A novel genome-wide in vivo screen for metastatic suppressors in human colon cancer identifies the positive WNT-TCF pathway modulators TMED3 and SOX12

    PubMed Central

    Duquet, Arnaud; Melotti, Alice; Mishra, Sonakshi; Malerba, Monica; Seth, Chandan; Conod, Arwen; Ruiz i Altaba, Ariel

    2014-01-01

    The progression of tumors to the metastatic state involves the loss of metastatic suppressor functions. Finding these, however, is difficult as in vitro assays do not fully predict metastatic behavior, and the majority of studies have used cloned cell lines, which do not reflect primary tumor heterogeneity. Here, we have designed a novel genome-wide screen to identify metastatic suppressors using primary human tumor cells in mice, which allows saturation screens. Using this unbiased approach, we have tested the hypothesis that endogenous colon cancer metastatic suppressors affect WNT-TCF signaling. Our screen has identified two novel metastatic suppressors: TMED3 and SOX12, the knockdown of which increases metastatic growth after direct seeding. Moreover, both modify the type of self-renewing spheroids, but only knockdown of TMED3 also induces spheroid cell spreading and lung metastases from a subcutaneous xenograft. Importantly, whereas TMED3 and SOX12 belong to different families involved in protein secretion and transcriptional regulation, both promote endogenous WNT-TCF activity. Treatments for advanced or metastatic colon cancer may thus not benefit from WNT blockers, and these may promote a worse outcome. PMID:24920608

  12. [Prognostic factors of localised, locally advanced or metastatic prostate cancer].

    PubMed

    Joly, Florence; Henry-Amar, Michel

    2007-07-01

    In prostate cancer, whatever the stage of the disease, the selection of a treatment strategy is based on prognostic factors. Clinical stage, serum PSA concentration and Gleason score are among the most recognised factors. A combination of these three parameters leads to a score used to define prognostic groups that are routinely used in daily practice. More recently, predictive statistical models have been developed that were associated with nomograms. The objective of nomograms is, for a given patient, to calculate his probability to develop disease extension or relapse based on clinical, biological, histological and therapeutic (radiotherapy, hormonotherapy) data. Such nomograms are not all validated and their application in daily practice is more difficult than that of classical prognostic classifications. Nowadays, the progress and accessibility to novel technologies applied to biology will make possible in the near future the assessment of new prognostic profiles based on genetic and/or proteomic tumour characteristics.

  13. Recurrent Miller Fisher syndrome.

    PubMed

    Madhavan, S; Geetha; Bhargavan, P V

    2004-07-01

    Miller Fisher syndrome (MFS) is a variant of Guillan Barre syndrome characterized by the triad of ophthalmoplegia, ataxia and areflexia. Recurrences are exceptional with Miller Fisher syndrome. We are reporting a case with two episodes of MFS within two years. Initially he presented with partial ophthalmoplegia, ataxia. Second episode was characterized by full-blown presentation characterized by ataxia, areflexia and ophthalmoplegia. CSF analysis was typical during both episodes. Nerve conduction velocity study was fairly within normal limits. MRI of brain was within normal limits. He responded to symptomatic measures initially, then to steroids in the second episode. We are reporting the case due to its rarity.

  14. Recurrent respiratory papillomatosis.

    PubMed

    Venkatesan, Naren N; Pine, Harold S; Underbrink, Michael P

    2012-06-01

    Recurrent respiratory papillomatosis (RRP) is a rare, benign disease with no known cure. RRP is caused by infection of the upper aerodigestive tract with the human papillomavirus (HPV). Passage through the birth canal is thought to be the initial transmission event, but infection may occur in utero. HPV vaccines have helped to provide protection from cervical cancer; however, their role in the prevention of RRP is undetermined. Clinical presentation of initial symptoms of RRP may be subtle. RRP course varies, and current management focuses on surgical debulking of papillomatous lesions with or without concurrent adjuvant therapy. PMID:22588043

  15. 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

    ClinicalTrials.gov

    2013-02-06

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small

  16. Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2014-06-10

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Colon Cancer; Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx

  17. [Successful treatment of locally advanced squamous cell carcinoma of the esophagus by combination chemotherapy with 5-fluorouracil plus nedaplatin following tracheal stent tube placement-a case report].

    PubMed

    Nishimura, Junya; Kubo, Naoshi; Lee, Tomohiro; Shinto, Osamu; Sakurai, Katsunobu; Toyokawa, Takahiro; Tanaka, Hiroaki; Muguruma, Kazuya; Shibutani, Masatsune; Yamazoe, Sadaaki; Nagahara, Hisashi; Kimura, Kenjiro; Amano, Ryosuke; Ohtani, Hiroshi; Yashiro, Masakazu; Maeda, Kiyoshi; Ohira, Masaichi; Hirakawa, Kosei

    2013-11-01

    The patient was a 68-year-old man who complained of hoarseness and dyspnea. Upper gastrointestinal endoscopy revealed a type 3 tumor located in the middle thoracic esophagus at 30 cm from the incisor tooth that involved one-fourth of the circumference of the esophagus. Histopathological examination revealed moderately differentiated squamous cell carcinoma. Chest computed tomography( CT) revealed severe tracheal stenosis due to compression by a metastatic lymph node along the left recurrent laryngeal nerve. The patient was diagnosed as having cT4( 106recL-trachea), N2( 101L, 106recL, 106recR), M0, Stage IVa unresectable esophageal carcinoma. After insertion of a tracheal stent tube( spiral Z stent: diameter, 18 mm; length, 80 mm) to improve dyspnea, combination chemotherapy with 5-fluorouracil( 5-FU) plus nedaplatin was administered. Subsequent CT and endoscopy showed that the main tumor and the metastatic lymph node had significantly reduced in size and that complete response (CR) had been achieved. Thirty months after the initial treatment, the patient showed no sign of disease recurrence, after completion of 19 cycles of chemotherapy. The patient did not experience any severe adverse events. We report a case of a patient with locally advanced squamous cell carcinoma of the esophagus successfully treated with 5-FU/nedaplatin combination chemotherapy following tracheal stent tube placement.

  18. Incidental radiologic findings at breast cancer diagnosis and likelihood of disease recurrence.

    PubMed

    Brothers, Joel M; Kidwell, Kelley M; Brown, Richard K J; Henry, N Lynn

    2016-01-01

    Despite guidelines recommending against its routine use, perioperative imaging for distant metastases is frequently performed in newly diagnosed breast cancer patients, uncovering incidental findings of uncertain significance. We assessed the clinical significance of incidental findings by determining if their presence is associated with disease recurrence. A retrospective review of staging imaging was performed in patients with stage II or III invasive breast cancer diagnosed during 2008-2009 at a large academic medical center. Data related to perioperative imaging and disease recurrence were abstracted from the medical record. Kaplan-Meier curves and Cox proportional hazards models were used to assess the association between incidental findings and time to disease recurrence. A total of 169 of 340 patients (49.7 %) underwent staging evaluation for distant metastases (CT chest, abdomen, pelvis, bone scan, and/or PET-CT). Of these, 146 (86.4 %) had at least one suspicious or indeterminate finding. Follow-up studies were performed in 73 (43.2 %) patients. Nineteen patients were diagnosed with metastatic disease at diagnosis, 18 of whom had stage III disease. In patients without metastatic disease at diagnosis, 32 later developed recurrence. Non-calcified pulmonary nodules were associated with shorter time to disease recurrence (hazard ratio 2.51, 95 % CI 1.13-5.57, p = 0.02). Imaging for distant metastases frequently reveals indeterminate findings, most of which are not associated with disease recurrence. The association between pulmonary nodules and recurrence warrants validation in an independent cohort. Overall, these findings support current guidelines recommending against routine extent of disease evaluation in patients with newly diagnosed stage II breast cancer. PMID:26797222

  19. Total En Bloc Spondylectomy for Primary and Metastatic Spine Tumors.

    PubMed

    Mesfin, Addisu; El Dafrawy, Mostafa H; Jain, Amit; Hassanzadeh, Hamid; Kebaish, Khaled M

    2015-11-01

    This study reports the surgical and clinical outcomes of spinal tumors managed with total en bloc spondylectomy. The authors searched their prospectively maintained database for patients undergoing total en bloc spondylectomy between 2001 and 2013. Ten patients (9 men, 1 woman; average age, 50.7 years; range, 42-68 years) were identified. The authors obtained demographic information, surgical outcomes (estimated blood loss, complications), and clinical outcomes (recurrence, survival). All patients had pain and were classified as American Spinal Injury Association grade E. The lesions were located in the thoracic (8 patients) and lumbar (2 patients) spine. Anterior column reconstruction was performed with strut allograft (7 patients), mesh cage (2 patients), and polymethyl methacrylate (1 patient). An average of 2.3 (range, 2-4) of 6 portions of the vertebrae were involved, according to the Kostuik classification. Mean estimated blood loss, operative time, and hospital stay were 3.5 L, 500 minutes, and 7.8 days, respectively. Perioperative complications included pleural tear (2 patients) and aortic tear, vena cava tear, retained sponge, pulmonary embolism, urinary tract infection, pneumothorax, anterior column support failure, and prominent instrumentation requiring removal (1 patient each). Postoperatively, all patients remained classified as American Spinal Injury Association grade E. Two patients had recurrence at distant spinal segments, and 1 had a new lesion in the thigh. Five patients had died (mean, 34.5 months after surgery), and 5 were alive a mean of 19.6 months after surgery (range, 6-48 months). Total en bloc spondylectomy is challenging, but in appropriately selected patients, it can be used to treat primary and metastatic spinal lesions.

  20. [Treatment of BRAF-mutated metastatic melanoma].

    PubMed

    Boyles, Tessa Bystrup; Svane, Inge Marie; Bastholt, Lars; Schmidt, Henrik

    2016-08-29

    Melanoma is an aggressive form of skin cancer which is the cause of a great number of skin cancer-related deaths worldwide and about 300 deaths in Denmark. After several years of failure of treatment of metastatic melanoma, the development of BRAF- and later MEK inhibitors was considered revolutionary. Treatment with BRAF inhibitors alone and especially in combination with a MEK inhibitor improves outcome for patients with BRAF V600-mutated metastatic melanoma. However, even when treated with the combination of the inhibitors, many patients develop acquired resistance within a year. PMID:27592869