Intensity-Modulated Radiotherapy for Cervical Node Squamous Cell Carcinoma Metastases From Unknown Head-and-Neck Primary Site: M. D. Anderson Cancer Center Outcomes and Patterns of Failure

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

Frank, Steven J., E-mail: sjfrank@mdanderson.or; Rosenthal, David I.; Petsuksiri, Janjira

2010-11-15

Purpose: Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. Methods and Materials: We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and themore » survival rates calculated using the Kaplan-Meier method. Results: Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. Conclusion: The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon.« less

Second primary cancers after cancer of unknown primary in Sweden and Germany: efficacy of the modern work-up.

PubMed

Liu, Hao; Hemminki, Kari; Sundquist, Jan; Holleczek, Bernd; Katalinic, Alexander; Emrich, Katharina; Brenner, Hermann

2013-05-01

In unsparing efforts to find the hidden primaries, second primary cancers (SPCs) unrelated to cancer of unknown primary (CUP) are found. The detection rates of SPCs after CUP can be considered as measures for the effectiveness of modern diagnostic techniques in finding tumors. We aimed to compare the rates of specific SPCs found after the work-up of CUP and the more sign/symptom-directed diagnostic approaches applied after any other cancer. The number of CUP patients identified in the nationwide Swedish database and nine German cancer registries was 24 641 from 1997 through 2006, and rate ratios (RRs) for SPCs were recorded in two follow-up periods. The detection rate of SPCs immediately after any other cancer was about two times higher in Germany than in Sweden, but the rate immediately after CUP was almost the same for the two datasets. In the joint analyses after CUP, the RRs of liver, lung, breast, and kidney cancers were higher than after any other cancer, whereas the RRs of prostate, urinary bladder, and connective tissue cancers as well as non-Hodgkin's lymphoma were not significantly different; the RR of cancers of upper aerodigestive tract was lower after CUP than after any other cancer. The joint data indicate that the work-up is efficient in detecting tumors in the thoracoabdominal organs that are screened by computed tomography. For some other organ sites, the more sign/symptom-directed diagnostic approaches may be equally efficient. However, none of the applied techniques could detect all tumors immediately after the first diagnosis.

Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-PP) for Patients With Advanced Cancer.

ClinicalTrials.gov

2010-08-02

Ovarian; Melanoma; Renal; Prostate; Colorectal; Endometrial Carcinoma; Cervical Carcinoma; Testicular Cancer; Thyroid Cancer; Small Cell Lung Carcinoma; Mesothelioma; Breast Carcinoma; Esophageal Carcinoma; Gastric Cancer; Pancreatic Carcinoma; Neuroendocrine Cancer; Liver Cancer; Gallbladder Cancer; Biliary Tract Cancer; Anal Carcinoma; Bone Sarcomas; Soft Tissue Sarcomas; Carcinoma of Unknown Origin, Primary

Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors

ClinicalTrials.gov

2017-11-22

Solid Neoplasm; Stage III Pancreatic Cancer; 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 Non-Small Cell Lung Cancer; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer; Sarcoma; Colorectal Cancer; Head and Neck Cancer; Cancer of Unknown Primary; Bladder Cancer; Ovarian Cancer

Cervical lymph node metastases from unknown primary cancer: a single-institution experience with intensity-modulated radiotherapy.

PubMed

Villeneuve, Hugo; Després, Philippe; Fortin, Bernard; Filion, Edith; Donath, David; Soulières, Denis; Guertin, Louis; Ayad, Tarek; Christopoulos, Apostolos; Nguyen-Tan, Phuc Felix

2012-04-01

To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer. Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method. With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up. In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities. Copyright © 2012 Elsevier Inc. All rights reserved.

Pretreatment costs of care and time to initial treatment for patients with cancer of unknown primary.

PubMed

Walker, Mark S; Weinstein, Laura; Luo, Roger; Marino, Ingrid

2018-06-01

Time to treatment and pretreatment costs may be affected by unknown primary tumor site. This retrospective study used electronic medical record data from patients in ten US community oncology practices. Eligible patients were ≥18 years, diagnosed with cancer of unknown primary (CUP) or known metastatic solid tumor, and presented between 1 January 2012 and 30 June 2014. Patients with CUP (n = 294) had a longer interval than non-CUP patients (n = 92) from presentation to treatment initiation (1.18 vs 0.49 months, p < 0.0001), and had higher pretreatment costs (US$27,882 vs US$20,449, p = 0.0075). When analyzed as monthly cost, the difference between groups in log-cost per month was nonsignificant. Higher pretreatment costs in CUP patients appeared attributable to significantly longer time to initiation of therapy.

Carcinoma of unknown primary: key radiological issues from the recent National Institute for Health and Clinical Excellence guidelines

PubMed Central

Taylor, M B; Bromham, N R; Arnold, S E

2012-01-01

Carcinoma of unknown primary origin (CUP) accounts for 3–5% of cancer cases and is the fourth most common cause of cancer death in the UK. CUP management is challenging, partly owing to the heterogeneity of the condition and its presentation, but also owing to the lack of dedicated clinical services for these patients. The recent National Institute for Health and Clinical Excellence (NICE) guidelines on metastatic malignancy of unknown primary origin were developed to improve the co-ordination of diagnostic and clinical services at hospitals treating cancer patients in England and Wales, in particular by the setting up of CUP teams to manage these patients. Radiologists have a vital role in the diagnosis of these patients and should work closely with the CUP team to streamline the diagnostic pathway. This article summarises areas of the NICE guidelines relevant to radiology and discusses the radiological management of patients with CUP, including initial investigation, the importance of biopsy, the management of specific presentations, special investigations and organisational issues. PMID:22374278

The current evidence for a biomarker-based approach in cancer of unknown primary.

PubMed

El Rassy, Elie; Pavlidis, Nicholas

2018-05-02

Cancer of unknown primary (CUP) accounts for the seventh to eighth most frequently diagnosed cancer yet its prognosis remains poor with conventional chemotherapy. The spectrum of therapeutic management includes both locoregional and systemic therapy and should intend to offer optimal benefit to favorable CUP patients and palliative care to unfavorable cases. The recent molecular advances have revolutionized the armamentarium of cancer treatments though a biomarker-based approach. Unfortunately, solid data in CUP is lacking in the absence of a CUP-specific driver molecular signature. This prompted us to screen the medical literature for clinical data that evaluates the efficacy and safety of the biomarker-based approach in CUP patients. In this review, we will summarize the available evidence for the applicability of targeted therapies in CUP. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bone metastases of unknown origin: epidemiology and principles of management.

PubMed

Piccioli, Andrea; Maccauro, Giulio; Spinelli, Maria Silvia; Biagini, Roberto; Rossi, Barbara

2015-06-01

Metastases are the most common malignancies involving bone; breast, prostate, lung and thyroid are the main sites of primary cancer. However, up to 30 % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and modern imaging technology (CT, MRI, PET). Sometimes only extensive histopathological investigations on bone specimens from biopsy can suggest the primary malignancy. At other times, a bone lesion can have such a highly undifferentiated histological appearance that a precise pathological classification on routine hematoxylin-eosin-stained section is not possible. The authors reviewed the relevant literature in an attempt to investigate the epidemiology of the histological primaries finally identified in patients with bone metastases from occult cancer, and a strategy of management and treatment of bone metastases from occult carcinomas is suggested. Lung, liver, pancreas and gastrointestinal tract are common sites for primary occult tumors. Adenocarcinoma is the main histological type, accounting for 70 % of all cases, while undifferentiated cancer accounts for 20 %. Over the past 30 years, lung cancer is the main causative occult primary for bone metastases and has a poor prognosis with an average survival of 4-8 months. Most relevant literature focuses on the need for standardized diagnostic workup, as surgery for bone lesions should be aggressive only when they are solitary and/or the occult primaries have a good prognosis; in these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Thus, orthopedic surgery has a mainly palliative role in preventing or stabilizing pathological fractures, relieving pain and facilitating the care of the patient in an attempt to provide the most appropriate therapy for the primary tumor as soon as possible. 5.

Epidemiology of neuroendocrine cancers in an Australian population.

PubMed

Luke, Colin; Price, Timothy; Townsend, Amanda; Karapetis, Christos; Kotasek, Dusan; Singhal, Nimit; Tracey, Elizabeth; Roder, David

2010-06-01

The aim was to explore incidence, mortality and case survivals for invasive neuroendocrine cancers in an Australian population and consider cancer control implications. Directly age-standardised incidence and mortality rates were investigated from 1980 to 2006, plus disease-specific survivals. Annual incidence per 100,000 increased from 1.7 in 1980-1989 to 3.3 in 2000-2006. A corresponding mortality increase was not observed, although numbers of deaths were low, reducing statistical power. Increases in incidence affected both sexes and were more evident for female lung, large bowel (excluding appendix), and unknown primary site. Common sites were lung (25.9%), large bowel (23.3%) (40.9% were appendix), small intestine (20.6%), unknown primary (15.0%), pancreas (6.5%), and stomach (3.7%). Site distribution did not vary by sex (p = 0.260). Younger ages at diagnosis applied for lung (p = 0.002) and appendix (p < 0.001) and older ages for small intestine (p < 0.001) and unknown primary site (p < 0.001). Five-year survival was 68.5% for all sites combined, with secular increases (p < 0.001). After adjusting for age and diagnostic period, survivals were higher for appendix and lower for unknown primary site, pancreas, and colon (excluding appendix). Incidence rates are increasing. Research is needed into possible aetiological factors for lung and large-bowel sites, including tobacco smoking, and excess body weight and lack of exercise, respectively; and Crohn's disease as a possible precursor condition.

Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: management and outcomes of a rare entity.

PubMed

Kotteas, E A; Pavlidis, N

2015-04-01

Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine tumour with distinct clinical and biological behaviour. We conducted a review of retrospective data extracted from 90 patients focusing on the management and outcome of this disease. We also compared life expectancy of these patients with the outcome of patients with known Merkel primaries and with neuroendocrine cancers of unidentifiable primary. There is a limited body of data for this type of malignancy, however, patients with Merkel cell nodal carcinoma of unknown primary site, seem to have better survival when treated aggressively than patients with cutaneous Merkel tumours of the same stage and equal survival with patients with low-grade neuroendocrine tumour of unknown origin. The lack of prospective trials, and the inadequate data, hamper the management of these tumours. Establishment of treatment guidelines is urgently needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Putting on the Brakes: Blocking the Growth of Metastases | Center for Cancer Research

Cancer.gov

Most of the suffering and death caused by cancer is due, not to the primary tumor, but to the ability of cancer cells to spread throughout the body and to form metastases in other organs. Breast and prostate cancers often have periods of dormancy, which can extend up to 30 years, between the identification and treatment of a primary tumor and the growth of overt metastases. What induces or inhibits metastatic dormancy is unknown, but prolonging this period may improve the survival of patients with these types of cancer.

Cytologic evaluation of cervical lymph node metastases from cancers of unknown primary origin.

PubMed

Pusztaszeri, Marc P; Faquin, William C

2015-01-01

Fine-needle aspiration biopsy (FNAB) is often the first diagnostic procedure performed in patients with head and neck (HN) masses. Metastatic squamous cell carcinoma (SCC) to cervical lymph nodes is by far the most common malignancy aspirated in the HN, but in approximately 3-10% of patients, a primary tumor will not be found even after complete clinico-radiological workup. Several HN cancers are associated with oncogenic viruses, including HPV-associated SCC and EBV-associated nasopharyngeal carcinoma (NPC). While the primary tumor is sometimes small or undetectable, patients often present initially with cervical lymph node metastases. HPV-associated SCC and EBV-associated NPC are typically non-keratinizing carcinomas that can mimic several other poorly differentiated HN cancers by FNAB but have a significantly better prognosis. Therefore, the precise classification of the metastatic disease in the FNAB material is very useful since it can facilitate the subsequent location of the primary tumor, and it can provide prognostic and therapeutic information as well. In this review, we discuss the major entities that can present as a metastatic cancer of unknown primary in cervical lymph node other than supraclavicular, including their cytologic features and the role of ancillary studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Metastasis to the pancreas and stomach from a breast cancer primary: a case report.

PubMed

Kliiger, Jason; Gorbaty, Mayer

2017-10-01

A 60-year-old female with an unknown family history initially presented with signs and symptoms concerning for gastrointestinal cancer. Regular breast cancer screening and subsequent work-up around this time demonstrated the presence of T2N1 stage II triple positive ductal adenocarcinoma of the left breast. Follow-up imaging for her gastrointestinal symptoms demonstrated a 3.5 cm solitary mass in the pancreas and diffuse thickening of the stomach wall. Biopsies of the gastrointestinal lesions were identified as metastatic foci of the breast cancer primary. Breast cancer metastases to the stomach and to the pancreas are both very rare events. Of the breast cancer primaries that do metastasize to the gastrointestinal system, it is unusual for the primary to be ductal adenocarcinoma. The rapid succession of diagnosing the primary source of breast cancer simultaneously with its metastases is also unusual. Timely identification and appropriate management of these rare metastases was made possible due to routine breast cancer screening.

FDG PET detection of unknown primary tumors.

PubMed

Bohuslavizki, K H; Klutmann, S; Kröger, S; Sonnemann, U; Buchert, R; Werner, J A; Mester, J; Clausen, M

2000-05-01

The management of patients presenting with metastases of unknown primary origin remains a clinical challenge despite a large variety of imaging modalities. The aim of this study was to evaluate FDG PET in detecting the sites of primary cancer in these patients. Fifty-three patients with metastatic cervical adenopathy (n = 44) or extracervical metastases (n = 9) of unknown primary origin were included after extensive but inconclusive conventional diagnostic work-up. Patients received 370 MBq FDG (10 mCi) intravenously, and whole-body images were acquired at 60 min after injection. Clinical, surgical, and histopathologic findings and complete correlative imaging were used to assess the results. In 27 of 53 patients FDG PET showed focal tracer accumulations corresponding to potential primary tumor sites located in the lungs (n = 12), the palatine tonsil (n = 5), the salivary glands (n = 2), the nasopharynx (n = 1), the oropharynx (n = 3), the maxillary sinus (n = 1), and the larynx (n = 1). Moreover, in 2 patients FDG PET revealed lesions suspected to be tumors in the breast and the ileocolonic area. In 20 (37.8%) of these 53 patients FDG PET was true-positive, identifying the primary tumor in the lungs (n = 10), the head and neck region (n = 8), the breast (n = 1), and the ileocolonic area (n = 1). In 6 of 27 patients FDG PET was false-positive, predominantly identifying suspicious areas in the palatine tonsil (n = 3). One patient denied further diagnostic work-up after PET; thus, positive PET could not be evaluated. In 26 of 53 patients PET did not reveal lesions suspected to be the primary. However, primary tumors were not found in these patients at clinical follow-up. FDG PET is a valuable diagnostic tool in patients with cancer of unknown primary because it imaged unknown primary tumors in about one third of all patients investigated. In addition, FDG PET assists in both guiding biopsies for histologic evaluation and selecting the appropriate treatment protocols for these patients.

Human Papillomavirus as a Diagnostic and Prognostic Tool in Cancer of Unknown Primary in the Head and Neck Region.

PubMed

Sivars, Lars; Tani, Edneia; Näsman, Anders; Ramqvist, Torbjörn; Munck-Wikland, Eva; Dalianis, Tina

2016-02-01

Human papillomavirus (HPV) is recognized as a risk factor for oropharyngeal squamous cell carcinomas (SCC), especially tonsillar and base of tongue cancer. Furthermore, HPV-positive tonsillar and base of tongue SCC have a significantly better prognosis than their HPV-negative counterparts and head and neck cancer (HNSCC) in general. HPV has recently also been implicated in cancer of unknown primary (CUP) in the head and neck region, where a primary tumour is not found despite extensive workup. Using fine-needle aspiration cytology to determine CUP HPV status in cervical lymph nodes could be of advantage, since it is minimally invasive and it is assumed that an HPV-positive lymph node metastasis likely has an HPV-positive otopharyngeal SCC origin. We review the current knowledge of HPV in HNSCC, with an emphasis on CUP of the head and neck region, its relation to oropharyngeal, tonsillar and base of tongue SCC and implications of HPV status for diagnosis, prognosis and treatment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Gastrointestinal tract metastasis as first presentation of breast cancer.

PubMed

Savanis, G; Simatos, G; Tzaida, O; Tsikkinis, C; Ammari, S; Mylonas, A; Kafasis, E; Nisiotis, A

2006-01-01

Gastrointestinal metastases of breast cancer are a rare occurrence. It is even rarer to be the first manifestation of an unknown breast cancer. We present 2 cases of metastatic breast cancer of the lobular type to the stomach and large bowel in 2 women, initially considered as primary disease. The establishment of diagnosis required experienced histopathologic and immunohistochemical examination. The management follows the principles of the primary disease. Surgery is spared for complications. Mean survival is one year. Prognosis is better for patients with positive hormonal receptors.

Spectrum of metastatic neoplasms of the brain: A clinicopathological study in a tertiary care cancer centre.

PubMed

Singh, Smrita; Amirtham, Usha; Premalata, Chennagiri S; Lakshmaiah, Kuntegowdanahalli C; Viswanath, Lokesh; Kumar, Rekha V

2018-01-01

While brain metastases (BM) are the most common causes of neurologic disorders in patients with known systemic malignancies, they can often be the initial manifestations of an undetected primary elsewhere. BM are major causes of morbidity and mortality in cancer patients. We describe a mixed population (data from both retrospective and prospective collection) having a BM from a solid tumor. We report the percentage distribution of the most frequent types of BM, confirming the data published in the literature. This paper may play a role in presenting the Southeast Asian reality compared with the Western countries. A tertiary-care cancer centre. Data for 4 years were retrieved from the records of the Department of Pathology of our institute. Hematolymphoid and meningeal tumors were excluded. Hematoxylin and eosin (H and E) stained slides were reviewed, and in cases with an unknown primary, immunohistochemistry (IHC) was advised. The panel of markers was chosen based on the histomorphology on H and E sections. IHC was done in cases with an unknown primary where paraffin blocks were available. Lung cancer was found to be the most common primary malignancy (n = 30; 48.4%) followed by breast cancer (n = 13; 21%), colorectal cancer (n = 6; 9.6%), and skin cancer (melanoma) [n = 3; 4.8%]. The incidence of BM from lung and breast cancer was similar to that seen in the Western studies. However, BM from colorectal cancer and melanoma show a higher and lower incidence, respectively, in comparison with the Western literature.

Integrated Cancer Repository for Cancer Research

ClinicalTrials.gov

2017-05-05

Pancreatic Cancer; Thyroid Cancer; Lung Cancer; Esophageal Cancer; Thymus Cancer; Colon Cancer; Rectal Cancer; GIST; Anal Cancer; Bile Duct Cancer; Duodenal Cancer; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Small Intestine Cancer; Peritoneal Surface Malignancies; Familial Adenomatous Polyposis; Lynch Syndrome; Bladder Cancer; Kidney Cancer; Penile Cancer; Prostate Cancer; Testicular Cancer; Ureter Cancer; Urethral Cancer; Hypopharyngeal Cancer; Laryngeal Cancer; Lip Cancer; Oral Cavity Cancer; Nasopharyngeal Cancer; Oropharyngeal Cancer; Paranasal Sinus Cancer; Nasal Cavity Cancer; Salivary Gland Cancer; Skin Cancer; CNS Tumor; CNS Cancer; Mesothelioma; Breastcancer; Leukemia; Melanoma; Sarcoma; Unknown Primary Tumor; Multiple Myeloma; Ovarian Cancer; Endometrial Cancer; Vaginal Cancer

Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary.

PubMed

Hannouf, M B; Winquist, E; Mahmud, S M; Brackstone, M; Sarma, S; Rodrigues, G; Rogan, P; Hoch, J S; Zaric, G S

2017-06-01

We aimed to investigate the cost-effectiveness of a 2000-gene-expression profiling (GEP) test to help identify the primary tumor site when clinicopathological diagnostic evaluation was inconclusive in patients with cancer of unknown primary (CUP). We built a decision-analytic-model to project the lifetime clinical and economic consequences of different clinical management strategies for CUP. The model was parameterized using follow-up data from the Manitoba Cancer Registry, cost data from Manitoba Health administrative databases and secondary sources. The 2000-GEP-based strategy compared to current clinical practice resulted in an incremental cost-effectiveness ratio (ICER) of $44,151 per quality-adjusted life years (QALY) gained. The total annual-budget impact was $36.2 million per year. A value-of-information analysis revealed that the expected value of perfect information about the test's clinical impact was $4.2 million per year. The 2000-GEP test should be considered for adoption in CUP. Field evaluations of the test are associated with a large societal benefit.

Malignant neoplasm in the axilla of a male: suspected primary carcinoma of an accessory mammary gland.

PubMed

Takeyama, Hiroshi; Takahashi, Hiroyuki; Tabei, Isao; Fukuchi, Osamu; Nogi, Hiroko; Kinoshita, Satoki; Uchida, Ken; Morikawa, Toshiaki

2010-04-01

A 58-year-old Japanese male patient visited our hospital for evaluation of an elastic hard mass, measuring 80 x 50 mm, in the right axillary area. Incisional biopsy for suspected malignancy was performed, and histopathologic examination by hematoxylin-eosin (H&E) staining yielded a diagnosis of poorly differentiated adenocarcinoma metastatic from an unknown primary. As the tumor was immunohistochemically positive for both ER and PgR, metastatic breast cancer was strongly suspected. Ultrasonography, CT, and MRI revealed no evidence of tumors in the bilateral mammary glands. Detailed examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. After chemotherapy, the patient underwent tumor resection with axillary lymph node dissection. On the basis of the histological features of H&E-stained specimens and immunohistochemistry of the resected tumor, this case was diagnosed as breast cancer of unknown origin in a male. The tumor could have been an axillary lymph node metastasis from an occult breast carcinoma, or primary cancer arising in an accessory mammary gland.

[Clinical diagnosis of primary unknown cancer-the present situation and problems].

PubMed

Mukai, Hirofumi

2009-06-01

The first step of diagnosis of primary unknown cancer(PUC)the detailed history intake and physical examination including breast, genitourinary system and rectum. Laboratory test, chest X-p and systemic computed tomography are allowed to be performed for all patients with PUC. Other tests should be performed according to the results of clinical and pathological evaluation. Utility of the tumor marker is limited, and this test is not recommended as a routine usage. There is not enough evidence on the utility of FDG-PTT or FDG-PET/CT for patients with PUC. Diagnosis of PUC should be made within one month from a patient's first visit to a hospital.

Long non-coding RNAs may serve as biomarkers in breast cancer combined with primary lung cancer

PubMed Central

Mao, Weimin; Chen, Bo; Yang, Shifeng; Ding, Xiaowen; Zou, Dehong; Mo, Wenju; He, Xiangming; Zhang, Xiping

2017-01-01

Long non-coding RNAs (lncRNAs) have been shown to play important regulatory role in certain type of cancers biology, including breast and lung cancers. However, the lncRNA expression in breast cancer combined with primary lung cancer remains unknown. In this study, databases of the Cancer Genome Atlas (TCGA) and the lncRNA profiler of contained candidate 192 lncRNAs were utilized. 11 lncRNAs were differentially expressed in breast cancer, 9 candidate lncRNAs were differentially expressed in lung cancer. In order to find the aberrant expression of lncRNAs in breast cancer combined with primary lung cancer, seven samples of primary breast cancer and lung cancer were studied for the expression of selected lncRNAs. The results showed that SNHG6 and NEAT1 were reversely expressed in breast cancer combined with primary lung cancer compared with primary breast or lung cancer. In addition, a significant correlation of lncRNAs was found in the patients whose age was above 56 in breast cancer. What's more, PVT1 expression was negatively correlated with the pathological stage, and the level of ER, PR, HER2, p53 in breast cancer. Furthermore, lncRNA expression did not have significant relationship with the 5-year survival of patients with breast cancer combined with primary lung cancer. The findings revealed that PVT1, SNHG6, NEAT1 may serve as a prognostic marker for breast cancer combined with primary lung cancer. Therefore, these lncRNAs are potential molecular indicators in the diagnosis and prognosis of cancer in the future. PMID:28938549

Patterns of care and survival after a cancer of unknown primary (CUP) diagnosis: A population-based nested cohort study in Australian Government Department of Veterans' Affairs clients.

PubMed

Schaffer, Andrea L; Pearson, Sallie-Anne; Dobbins, Timothy A; Er, Chuang C; Ward, Robyn L; Vajdic, Claire M

2015-08-01

Little is known about patterns of care after a cancer of unknown primary (CUP) diagnosis. We performed a retrospective cohort study to describe and compare the treatment, health service use and survival of patients with CUP and metastatic cancer of known primary among 143,956 Australian Government Department of Veterans' Affairs clients, 2004-2007. We randomly matched clients with CUP (C809; n=252) with clients with a first diagnosis of metastatic solid cancer of known primary (n=980). We ascertained health services from the month of diagnosis up to 2 months post-diagnosis for consultations, hospitalizations and emergency department visits, and up to 1 year for treatment. We compared cancer treatments using conditional logistic regression; consultation rates using negative binomial regression; and survival using stratified Cox regression. 30% of CUP patients and 70% of patients with known primary received cancer treatment and the median survival was 37 days and 310 days respectively. CUP patients received fewer cancer medicines (odds ratio (OR)=0.54, 95% confidence interval (CI) 0.33-0.89) and less cancer-related surgery (OR=0.25, 95% CI 0.15-0.41); males with CUP received more radiation therapy (OR=2.88, 95% CI 1.69-4.91). CUP patients had more primary care consultations (incidence rate ratio (IRR)=1.25, 95% CI 1.11-1.41), emergency department visits (IRR=1.86, 95% CI 1.50-2.31) and hospitalizations (IRR=1.18, 95% CI 1.03-1.35), and a higher risk of death within 30 days (hazard ratio=3.30, 95% CI 1.69-6.44). Patients with CUP receive less treatment but use more health services, which may reflect underlying patient and disease characteristics. Copyright © 2015 Commonwealth of Australia. Published by Elsevier Ltd.. All rights reserved.

Radiation therapy in the management of head-and-neck cancer of unknown primary origin: how does the addition of concurrent chemotherapy affect the therapeutic ratio?

PubMed

Chen, Allen M; Farwell, D Gregory; Lau, Derick H; Li, Bao-Qing; Luu, Quang; Donald, Paul J

2011-10-01

To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy. The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question. Copyright © 2011 Elsevier Inc. All rights reserved.

Primary peritoneal carcinoma metastasizing to breast: a single case report and literature review from clinic to biology

PubMed Central

Sun, Ji-Yuan; Gebre, Wondwossen; Dong, Yi-Min; Shaun, Xiao; Robbins, Rachel; Podrumar, Alida

2016-01-01

Primary peritoneal carcinoma (PPC) is a type of rare malignant epithelial tumor. Metastasis from PPC to breast has been rarely reported. PPC originates de novo from the peritoneal tissues rather than invasion or metastasis from adjacent or remote organs. PPCs have been implicated in many cases of carcinomas of unknown primary origin. It is similar to ovarian cancer (OvCa), because it shares the same common embryonic origin, the coelomic epithelium (mesodermal origin). The mechanism of oncogenesis remains elusive. In this article, we report a rare case of PPC in a patient 10 years after total abdominal hysterectomy and bilateral salpingooophorectomy for uterine leiomyoma, which was widely spread in the abdomen and metastasized to the colon, liver and distant organs including breast. The treatment is similar to that of primary ovarian cancer. We also reviewed the primary peritoneal cancer metastatic to breast and discuss the possible mechanisms and biology of primary peritoneal cancer, using experimental and animal model. PMID:27807506

One patient - three head and neck primaries: nasopharyngeal, tongue and thyroid cancers

PubMed Central

2013-01-01

Background We report a rare case of three head and neck malignancies in one patient. Squamous cell carcinoma of tongue and papillary thyroid carcinoma occurred as metachronous cancers in a patient with primary nasopharyngeal carcinoma. These three pathologically distinct malignancies of head and neck region in one patient is a rare phenomenon and is not reported so far. Case presentation A 60 year old Saudi female patient presented in March 2011 with locally advanced nasopharyngeal carcinoma. After completion of concurrent chemoradiation in June 2011, she developed two new primaries i-e thyroid cancer and tongue cancer in May 2012 along with recurrent nasopharyngeal carcinoma. We discuss histopathologic features, diagnostic tools and treatment modalities for this rarely existing case. Conclusion High index of suspicion and thorough work up is essential in follow up of patients with head and neck primary cancers. The effect of field cancerization and environmental factors need to be explored in greater depths in such selected cases. However, which patients are at increased risk of triplet primaries, is still unknown. PMID:24164964

Metastatic brain tumor

MedlinePlus

... the brain, the type of tissue involved, the original location of the tumor, and other factors. In rare cases, doctors do not know the original location. This is called cancer of unknown primary ( ...

Radiation Therapy in the Management of Head-and-Neck Cancer of Unknown Primary Origin: How Does the Addition of Concurrent Chemotherapy Affect the Therapeutic Ratio?

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

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Farwell, D. Gregory; Lau, Derick H.

2011-10-01

Purpose: To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patientsmore » (58%) were treated by intensity-modulated radiotherapy. Results: The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Conclusions: Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question.« less

Prognosis of Lung Cancer: Heredity or Environment

DTIC Science & Technology

2015-06-01

former/never smoker), the primary lung cancer risk factor (Table 1). More blacks smoked menthol cigarettes compared with whites. More whites self...Unknown 5 Smoking status at cohort entry Current 253 (72.5) 102 (68.9) Former 75 (21.5) 40 (27.0) Never 21 (6.0) 6 (4.1) Smokes (or smoked) menthol

The role of human papilloma virus and p16 in occult primary of the head and neck: a comprehensive review of the literature.

PubMed

Fotopoulos, George; Pavlidis, Nicholas

2015-02-01

Cancer of unknown primary of the head and neck is a challenging entity for the oncologist. The role of human papilloma virus/p16 in carcinogenesis and in prognosis is well established in certain HNSCC especially in that of the oropharynx. In the case of occult primary of the head and neck the role of HPV/p16 positivity is not well defined regarding prognosis and localization of the primary. An independent review of PubMed and ScienceDirect database was performed up to May 2014 using combinations of terms such as "occult primary of the head and neck", "CUP of the head and neck" "metastatic cervical squamous cell carcinoma of unknown primary", "HPV" and "HPV and head and neck cancer". Literature review shows a strong association between HPV/p16 positivity and primary location in the oropharynx in patients with CUP of the head and neck as well as a better clinical outcome. HPV positivity and p16 overexpression could be used as surrogate markers in the search of the primary site of patients with CUP of the head and neck therefore maybe guiding treatment decisions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bone tumor

MedlinePlus

Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

ClinicalTrials.gov

2018-06-25

Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

Targeting PRMT5 as a Novel Radiosensitization Approach for Primary and Recurrent Prostate Cancer Treatment

DTIC Science & Technology

2015-08-01

6], breast cancer [7], melanoma [8], leukemia and lymphoma [9,10], and glioblastoma [11]. The overexpression of PRMT5 correlatesse 5;NF-Y, Nuclear...multiple human cancers [3 11], though it is unknown how PRMT5 expression is regulated by cancer signaling. In leukemia and lymphoma cells, down...family of tumor suppressors in leukemia and lymphoma cells, Mol. Cell. Biol. 28 (2008) 6262–6277. [10] S. Pal, R.A. Baiocchi, J.C. Byrd, M.R. Grever, S.T

Improved Dosimetric and Clinical Outcomes With Intensity-Modulated Radiotherapy for Head-and-Neck Cancer of Unknown Primary Origin

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

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.ed; Li Baoqing; Farwell, D. Gregory

2011-03-01

Purpose: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively. Results: The 2-year estimates of overall survival, local-regional control,more » and disease-specific survival for the entire patient population were 86%, 89%, and84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p > 0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p < 0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p < 0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p < 0.001). Conclusions: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin.« less

Squamous cell carcinoma presenting with trigeminal anesthesia: An uncommon presentation of head & neck cancer with unknown primary.

PubMed

Shah, Ameer T; Dagher, Walid I; O'Leary, Miriam A; Wein, Richard O

The differential diagnosis of facial anesthesia is vast. This may be secondary to trauma, neoplasm, both intracranial and extracranial, infection, and neurologic disease. When evaluating a patient with isolated facial anesthesia, the head and neck surgeon often thinks of adenoid cystic carcinoma, which has a propensity for perineural invasion and spread. When one thinks of head and neck squamous cell carcinoma with or without unknown primary, the typical presentation involves dysphagia, odynophagia, weight loss, hoarseness, or more commonly, a neck mass. Squamous cell carcinoma presenting as facial anesthesia and perineural spread, with no primary site is quite rare. Case presentations and review of the literature. Trigeminal anesthesia is an uncommon presentation of head and neck squamous cell carcinoma with unknown primary. We present two interesting cases of invasive squamous cell carcinoma of the trigeminal nerve, with no primary site identified. We will also review the literature of head and neck malignancies with perineural spread and the management techniques for the two different cases presented. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of virus in N3 node dissection for head and neck cancer.

PubMed

Armas, Gian Luca; Su, Chih-Ying; Huang, Chao-Cheng; Fang, Fu-Min; Chen, Ching-Mei; Chien, Chih-Yen

2008-11-01

This study is to determine the impact of virus in surgical outcomes among patients of head and neck cancer with N3 lymph node metastasis. A retrospective analysis was conducted for 32 patients with operable N3 neck metastasis undergoing surgical treatment between January 1987 and October 2006. The nuclei of the tumor cells were investigated for the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNAs and were taken into account as the variable for survival analysis. The primary sites were oropharynx in 11 patients, tongue in 3, buccal mucosa in 1, hypopharynx in 8 and unknown primary in 9. The five-year cumulative overall survival rate was 40.7% and 5-year cumulative regional control rate was 55.8%. The 5-year cumulative overall survival rate of patients with unknown primary site (72.9%) and HPV or EBV positive in the tumor (77.8%) were significantly higher than those patients with known primary site (31.3%) and HPV or EBV negative in the tumor (27.4%), respectively (P = 0.0335 and P = 0.0348, log rank test). In conclusion, surgery with adjuvant therapy offers reasonable outcomes for operable N3 node in head and neck cancer in our cohort. In addition, patients with HPV or EBV positive in the tumor have a better survival.

Lung Adenocarcinoma with Anaplastic Lymphoma Kinase (ALK) Rearrangement Presenting as Carcinoma of Unknown Primary Site: Recognition and Treatment Implications.

PubMed

Hainsworth, John D; Anthony Greco, F

Molecular cancer classifier assays are being used with increasing frequency to predict tissue of origin and direct site-specific therapy for patients with carcinoma of unknown primary site (CUP). We postulated some CUP patients predicted to have non-small-cell lung cancer (NSCLC) by molecular cancer classifier assay may have anaplastic lymphoma kinase (ALK) rearranged tumors, and benefit from treatment with ALK inhibitors. We retrospectively reviewed CUP patients who had the 92-gene molecular cancer classifier assay (CancerTYPE ID; bioTheranostics, Inc.) performed on tumor biopsies to identify patients predicted to have NSCLC. Beginning in 2011, we have tested these patients for ALK rearrangements and epidermal growth factor receptor (EGFR) activating mutations, based on the proven therapeutic value of these targets in NSCLC. We identified CUP patients with predicted NSCLC who were subsequently found to have ALK rearrangements. NSCLC was predicted by the molecular cancer classifier assay in 37 of 310 CUP patients. Twenty-one of these patients were tested for ALK rearrangements, and four had an EML4-ALK fusion gene detected. The diagnosis of lung cancer was strongly suggested in only one patient prior to molecular testing. One patient received ALK inhibitor treatment and has had prolonged benefit. We report on patients with lung adenocarcinoma and ALK rearrangements originally diagnosed as CUP who were identified using a molecular cancer classifier assay. Although ALK inhibitors treatment experience is limited, this newly identifiable group of lung cancer patients should be considered for therapy according to guidelines for stage IV ALK-positive NSCLC.

Lung Adenocarcinoma with Anaplastic Lymphoma Kinase (ALK) Rearrangement Presenting as Carcinoma of Unknown Primary Site: Recognition and Treatment Implications.

PubMed

Hainsworth, John D; Anthony Greco, F

2016-03-01

Molecular cancer classifier assays are being used with increasing frequency to predict tissue of origin and direct site-specific therapy for patients with carcinoma of unknown primary site (CUP). We postulated some CUP patients predicted to have non-small-cell lung cancer (NSCLC) by molecular cancer classifier assay may have anaplastic lymphoma kinase (ALK) rearranged tumors, and benefit from treatment with ALK inhibitors. We retrospectively reviewed CUP patients who had the 92-gene molecular cancer classifier assay (CancerTYPE ID; bioTheranostics, Inc.) performed on tumor biopsies to identify patients predicted to have NSCLC. Beginning in 2011, we have tested these patients for ALK rearrangements and epidermal growth factor receptor (EGFR) activating mutations, based on the proven therapeutic value of these targets in NSCLC. We identified CUP patients with predicted NSCLC who were subsequently found to have ALK rearrangements. NSCLC was predicted by the molecular cancer classifier assay in 37 of 310 CUP patients. Twenty-one of these patients were tested for ALK rearrangements, and four had an EML4-ALK fusion gene detected. The diagnosis of lung cancer was strongly suggested in only one patient prior to molecular testing. One patient received ALK inhibitor treatment and has had prolonged benefit. We report on patients with lung adenocarcinoma and ALK rearrangements originally diagnosed as CUP who were identified using a molecular cancer classifier assay. Although ALK inhibitors treatment experience is limited, this newly identifiable group of lung cancer patients should be considered for therapy according to guidelines for stage IV ALK-positive NSCLC.

Switching benchmarks in cancer of unknown primary: from autopsy to microarray.

PubMed

Pentheroudakis, George; Golfinopoulos, Vassilios; Pavlidis, Nicholas

2007-09-01

Cancer of unknown primary (CUP) is associated with unknown biology and dismal prognosis. Information on the primary site of origin is scant and has never been analysed. We systematically reviewed all published evidence on the CUP primary site identified by two different approaches, either autopsy or microarray gene expression profiling. Published reports on identification of CUP primary site by autopsy or microarray-based multigene expression platforms were retrieved and analysed for year of publication, primary site, patient age, gender, histology, rate of primary identification, manifestations and metastatic deposits, microarray chip technology, training and validation sets, mathematical modelling, classification accuracy and number of classifying genes. From 1944 to 2000, a total of 884 CUP patients (66% males) underwent autopsy in 12 studies after presenting with metastatic or systemic symptoms and succumbing to their disease. A primary was identified in 644 (73%) of them, mostly in the lung (27%), pancreas (24%), hepatobiliary tree (8%), kidneys (8%), bowel, genital system and stomach, as a small focus of adenocarcinoma or poorly differentiated carcinoma. An unpredictable systemic dissemination was evident with high frequency of lung (46%), nodal (35%), bone (17%), brain (16%) and uncommon (18%) deposits. Between the 1944-1980 and the 1980-2000 series, female representation increased, 'undetermined neoplasm' diagnosis became rarer, pancreatic primaries were found less often while colonic ones were identified more frequently. Four studies using microarray technology profiled more than 500 CUP cases using classifier set of genes (ranging from 10 to 495) and reported strikingly dissimilar frequencies of assigned primary sites (lung 11.5%, pancreas 12.5%, bowel 12%, breast 15%, hepatobiliary tree 8%, kidneys 6%, genital system 9%, bladder 5%) in 75-90% of the cases. Evolution in medical imaging technology, diet and lifestyle habits probably account for changing epidemiology of CUP primaries in autopsies. Discrepant assignment of primary sites by microarrays may be due to the presence of 'sanctuary sites' in autopsies, molecular misclassification and the postulated presence of a pro-metastatic genetic signature. In view of the absence of patient therapeutic or prognostic benefit with primary identification, gene expression profiling should be re-orientated towards unraveling the complex pathophysiology of metastases.

Post-operative therapy following transoral robotic surgery for unknown primary cancers of the head and neck.

PubMed

Patel, Sapna A; Parvathaneni, Aarthi; Parvathaneni, Upendra; Houlton, Jeffrey J; Karni, Ron J; Liao, Jay J; Futran, Neal D; Méndez, Eduardo

2017-09-01

Our primary objective is to describe the post- operative management in patients with an unknown primary squamous cell carcinoma of the head and neck (HNSCC) treated with trans-oral robotic surgery (TORS). We conducted a retrospective multi-institutional case series including all patients diagnosed with an unknown primary HNSCC who underwent TORS to identify the primary site from January 1, 2010 to June 30, 2016. We excluded those with recurrent disease, ≤6months of follow up from TORS, previous history of radiation therapy (RT) to the head and neck, or evidence of primary tumor site based on previous biopsies. Our main outcome measure was receipt of post-operative therapy. The tumor was identified in 26/35 (74.3%) subjects. Post-TORS, 2 subjects did not receive adjuvant therapy due to favorable pathology. Volume reduction of RT mucosal site coverage was achieved in 12/26 (46.1%) subjects who had lateralizing tumors, ie. those confined to the palatine tonsil or glossotonsillar sulcus. In addition, for 8/26 (30.1%), the contralateral neck RT was also avoided. In 9 subjects, no primary was identified (pT0); four of these received RT to the involved ipsilateral neck nodal basin only without pharyngeal mucosal irradiation. Surgical management of an unknown primary with TORS can lead to deintensification of adjuvant therapy including avoidance of chemotherapy and reduction in RT doses and volume. There was no increase in short term treatment failures. Treatment after TORS can vary significantly, thus we advocate adherence to NCCN guideline therapy post-TORS to avoid treatment-associated variability. Published by Elsevier Ltd.

Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of HER2/Neu

ClinicalTrials.gov

2013-02-27

Advanced Adult Primary Liver Cancer; Anaplastic Thyroid Cancer; Bone Metastases; Carcinoma of the Appendix; Distal Urethral Cancer; Fallopian Tube Cancer; Gastrinoma; Glucagonoma; Inflammatory Breast Cancer; Insulinoma; Liver Metastases; Localized Unresectable Adult Primary Liver Cancer; Lung Metastases; Male Breast Cancer; Malignant Pericardial Effusion; Malignant Pleural Effusion; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Parathyroid Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Newly Diagnosed Carcinoma of Unknown Primary; Occult Non-small Cell Lung Cancer; Pancreatic Polypeptide Tumor; Primary Peritoneal Cavity Cancer; Proximal Urethral Cancer; Pulmonary Carcinoid Tumor; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adrenocortical Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Carcinoma of Unknown Primary; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Endometrial Carcinoma; Recurrent Esophageal Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Pancreatic Cancer; Recurrent Parathyroid Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; 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 Thyroid Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer; Skin Metastases; Small Intestine Adenocarcinoma; Somatostatinoma; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Adrenocortical Carcinoma; Stage III Bladder Cancer; Stage III Cervical Cancer; Stage III Colon Cancer; Stage III Endometrial Carcinoma; Stage III Esophageal Cancer; Stage III Follicular Thyroid Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Ovarian Epithelial Cancer; Stage III Pancreatic Cancer; Stage III Papillary Thyroid Cancer; Stage III Prostate Cancer; Stage III Rectal Cancer; Stage III Renal Cell Cancer; Stage III Salivary Gland Cancer; 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 Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Anal Cancer; Stage IIIA Breast Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Anal Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Adrenocortical Carcinoma; Stage IV Anal Cancer; Stage IV Bladder Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Endometrial Carcinoma; Stage IV Esophageal Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Gastric Cancer; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Pancreatic Cancer; Stage IV Papillary Thyroid Cancer; Stage IV Prostate Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Salivary Gland Cancer; 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 IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Stage IVB Vulvar Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer; Urethral Cancer Associated With Invasive Bladder Cancer; WDHA Syndrome

Quality of Life of Patients with Spinal Metastasis from Cancer of Unknown Primary Origin: A Longitudinal Study of Surgical Management Combined with Postoperative Radiation Therapy.

PubMed

Ma, Yifei; He, Shaohui; Liu, Tielong; Yang, Xinghai; Zhao, Jian; Yu, Hongyu; Feng, Jiaojiao; Xu, Wei; Xiao, Jianru

2017-10-04

Patients with spinal metastasis from cancer of unknown primary origin have limited life expectancy and poor quality of life. Surgery and radiation therapy remain the main treatment options, but, to our knowledge, there are limited data concerning quality-of-life improvement after surgery and radiation therapy and even fewer data on whether surgical intervention would affect quality of life. Patients were enrolled between January 2009 and January 2014 at the Changzheng Hospital, Shanghai, People's Republic of China. The quality of life of 2 patient groups (one group that underwent surgery followed by postoperative radiation therapy and one group that underwent radiation therapy only) was assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire during a 6-month period. A subgroup analysis of quality of life was performed to compare different surgical strategies in the surgical group. A total of 287 patients, including 191 patients in the group that underwent surgery and 96 patients in the group that underwent radiation therapy only, were enrolled in the prospective study; 177 patients completed all 5 checkpoints and 110 patients had died by the final checkpoint. The surgery group had significantly higher adjusted quality-of-life scores than the radiation therapy group in each domain of the FACT-G questionnaire (all p < 0.05). Subgroup analysis showed that adjusted functional and physical well-being scores were higher in the circumferential surgical decompression group. Surgery followed by postoperative radiation therapy improved and maintained quality of life in patients with spinal metastasis from cancer of unknown primary origin in the 6-month assessment. In terms of surgical strategies, circumferential decompression seems better than laminectomy alone in quality-of-life improvement. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Precision medicine based on epigenomics: the paradigm of carcinoma of unknown primary.

PubMed

Moran, Sebastián; Martinez-Cardús, Anna; Boussios, Stergios; Esteller, Manel

2017-11-01

Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings, addressing an unmet need in the diagnostic and clinical management of these patients. Despite the great diagnostic advances made in the past decade, the use of traditional diagnostic procedures only enables the tissue of origin to be determined in ∼30% of patients with CUP. Thus, development of molecularly guided diagnostic strategies has emerged to complement traditional procedures, thereby improving the clinical management of patients with CUP. In this Review, we present the latest data on strategies using epigenetics and other molecular biomarkers to guide therapeutic decisions involving patients with CUP, and we highlight areas warranting further research to engage the medical community in this unmet need.

Socioeconomic environment and cancer incidence: a French population-based study in Normandy

PubMed Central

2014-01-01

Background The struggle against social inequalities is a priority for many international organizations. The objective of the study was to quantify the cancer burden related to social deprivation by identifying the cancer sites linked to socioeconomic status and measuring the proportion of cases associated with social deprivation. Methods The study population comprised 68 967 cases of cancer diagnosed between 1997 and 2009 in Normandy and collected by the local registries. The social environment was assessed at an aggregated level using the European Deprivation Index (EDI). The association between incidence and socioeconomic status was assessed by a Bayesian Poisson model and the excess of cases was calculated with the Population Attributable Fraction (PAF). Results For lung, lips-mouth-pharynx and unknown primary sites, a higher incidence in deprived was observed for both sexes. The same trend was observed in males for bladder, liver, esophagus, larynx, central nervous system and gall-bladder and in females for cervix uteri. The largest part of the incidence associated with deprivation was found for cancer of gall-bladder (30.1%), lips-mouth-pharynx (26.0%), larynx (23.2%) and esophagus (19.6%) in males and for unknown primary sites (18.0%) and lips-mouth-pharynx (12.7%) in females. For prostate cancer and melanoma in males, the sites where incidence increased with affluence, the part associated with affluence was respectively 9.6% and 14.0%. Conclusions Beyond identifying cancer sites the most associated with social deprivation, this kind of study points to health care policies that could be undertaken to reduce social inequalities. PMID:24524213

An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis.

PubMed

Paschall, Amy V; Liu, Kebin

2016-08-14

Metastasis is the primary cause of mortality of breast cancer patients. The mechanism underlying cancer cell metastasis, including breast cancer metastasis, is largely unknown and is a focus in cancer research. Various breast cancer spontaneous metastasis mouse models have been established. Here, we report a simplified procedure to establish orthotopic transplanted breast cancer primary tumor and resultant spontaneous metastasis that mimic human breast cancer metastasis. Combined with the bioluminescence live tumor imaging, this mouse model allows tumor growth and progression kinetics to be monitored and quantified. In this model, a low dose (1 x 10(4) cells) of 4T1-Luc breast cancer cells was injected into BALB/c mouse mammary fat pad using a tuberculin syringe. Mice were injected with luciferin and imaged at various time points using a bioluminescent imaging system. When the primary tumors grew to the size limit as in the IACUC-approved protocol (approximately 30 days), mice were anesthetized under constant flow of 2% isoflurane and oxygen. The tumor area was sterilized with 70% ethanol. The mouse skin around the tumor was excised to expose the tumor which was removed with a pair of sterile scissors. Removal of the primary tumor extends the survival of the 4T-1 tumor-bearing mice for one month. The mice were then repeatedly imaged for metastatic tumor spreading to distant organs. Therapeutic agents can be administered to suppress tumor metastasis at this point. This model is simple and yet sensitive in quantifying breast cancer cell growth in the primary site and progression kinetics to distant organs, and thus is an excellent model for studying breast cancer growth and progression, and for testing anti-metastasis therapeutic and immunotherapeutic agents in vivo.

Impact of investigations in general practice on timeliness of referral for patients subsequently diagnosed with cancer: analysis of national primary care audit data.

PubMed

Rubin, G P; Saunders, C L; Abel, G A; McPhail, S; Lyratzopoulos, G; Neal, R D

2015-02-17

For patients with symptoms of possible cancer who do not fulfil the criteria for urgent referral, initial investigation in primary care has been advocated in the United Kingdom and supported by additional resources. The consequence of this strategy for the timeliness of diagnosis is unknown. We analysed data from the English National Audit of Cancer Diagnosis in Primary Care on patients with lung (1494), colorectal (2111), stomach (246), oesophagus (513), pancreas (327), and ovarian (345) cancer relating to the ordering of investigations by the General Practitioner and their nature. Presenting symptoms were categorised according to National Institute for Health and Care Excellence (NICE) guidance on referral for suspected cancer. We used linear regression to estimate the mean difference in primary-care interval by cancer, after adjustment for age, gender, and the symptomatic presentation category. Primary-care investigations were undertaken in 3198/5036 (64%) of cases. The median primary-care interval was 16 days (IQR 5-45) for patients undergoing investigation and 0 days (IQR 0-10) for those not investigated. Among patients whose symptoms mandated urgent referral to secondary care according to NICE guidelines, between 37% (oesophagus) and 75% (pancreas) were first investigated in primary care. In multivariable linear regression analyses stratified by cancer site, adjustment for age, sex, and NICE referral category explained little of the observed prolongation associated with investigation. For six specified cancers, investigation in primary care was associated with later referral for specialist assessment. This effect was independent of the nature of symptoms. Some patients for whom urgent referral is mandated by NICE guidance are nevertheless investigated before referral. Reducing the intervals between test order, test performance, and reporting can help reduce the prolongation of primary-care intervals associated with investigation use. Alternative models of assessment should be considered.

Impact of investigations in general practice on timeliness of referral for patients subsequently diagnosed with cancer: analysis of national primary care audit data

PubMed Central

Rubin, G P; Saunders, C L; Abel, G A; McPhail, S; Lyratzopoulos, G; Neal, R D

2015-01-01

Background: For patients with symptoms of possible cancer who do not fulfil the criteria for urgent referral, initial investigation in primary care has been advocated in the United Kingdom and supported by additional resources. The consequence of this strategy for the timeliness of diagnosis is unknown. Methods: We analysed data from the English National Audit of Cancer Diagnosis in Primary Care on patients with lung (1494), colorectal (2111), stomach (246), oesophagus (513), pancreas (327), and ovarian (345) cancer relating to the ordering of investigations by the General Practitioner and their nature. Presenting symptoms were categorised according to National Institute for Health and Care Excellence (NICE) guidance on referral for suspected cancer. We used linear regression to estimate the mean difference in primary-care interval by cancer, after adjustment for age, gender, and the symptomatic presentation category. Results: Primary-care investigations were undertaken in 3198/5036 (64%) of cases. The median primary-care interval was 16 days (IQR 5–45) for patients undergoing investigation and 0 days (IQR 0–10) for those not investigated. Among patients whose symptoms mandated urgent referral to secondary care according to NICE guidelines, between 37% (oesophagus) and 75% (pancreas) were first investigated in primary care. In multivariable linear regression analyses stratified by cancer site, adjustment for age, sex, and NICE referral category explained little of the observed prolongation associated with investigation. Interpretation: For six specified cancers, investigation in primary care was associated with later referral for specialist assessment. This effect was independent of the nature of symptoms. Some patients for whom urgent referral is mandated by NICE guidance are nevertheless investigated before referral. Reducing the intervals between test order, test performance, and reporting can help reduce the prolongation of primary-care intervals associated with investigation use. Alternative models of assessment should be considered. PMID:25602963

Cervical lymph node metastases of squamous cell carcinoma of unknown origin: the diagnostic value of FDG PET/CT and clinical outcome.

PubMed

Dale, Einar; Moan, Jon M; Osnes, Terje A; Bogsrud, Trond V

2017-02-01

FDG PET/CT is perceived as a valuable diagnostic tool in addition to the standard diagnostic workup for patients with isolated neck lymph nodes of squamous cell carcinoma of unknown primary (SCCUP). For patients with SCCUP intended for primary radiotherapy, we hypothesize that the previously reported FDG PET/CT detection rates are too high. From 2008 to 2015, 30 SCCUP patients were examined with FDG PET/CT. The objective of the FDG PET/CT examination was twofold: (1) improve the radiotherapy target definition, and (2) identify the primary cancer. Before the FDG PET/CT, the patients had been through a standard workup consisting of CT of the neck and chest, examination with flexible endoscopy with patient awake, panendoscopy and examination under general anesthesia, tonsillectomy and sometimes blind sampling biopsies, and MRI (floor of the mouth). All FDG PET/CTs were performed applying a flat table, head support and fixation mask as part of the radiotherapy treatment planning. Diagnostic CT with contrast was an integrated part of the PET/CT examination. Only 1/30 patients (cancer of the vallecula) had their primary cancer detected by FDG PET/CT. In addition, a non-biopsied patient with high uptake in the ipsilateral palatine tonsil was included, giving a detection rate of ≤7 % (95 % CI 2-21 %). In this retrospective study, we found that the FDG PET/CT detection rate of the primary for SCCUP patients is lower than previously reported. It is questionable whether FDG PET/CT is necessary for these patients when improved, advanced workup is available.

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases.

PubMed

Qian, Yun; Sang, Yiwen; Wang, Frederick X C; Hong, Bo; Wang, Qi; Zhou, Xinhui; Weng, Tianhao; Wu, Zhigang; Zheng, Min; Zhang, Hong; Yao, Hangping

2016-11-01

Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer.

Synchronous diagnosis of metastatic cancer to the thyroid is associated with poor prognosis.

PubMed

Chen, Jeng-Yeou; Chen, I-Wen; Hsueh, Chuen; Chao, Tzu-Chieh; Gao, Bing-Ru; Lin, Jen-Der

2015-03-01

The incidence and histopathological characteristics of metastatic cancers to the thyroid (MCT) are different in various geographic areas. The aim of this study was to elucidate the clinical features of MCT, including histocytological diagnosis and therapeutic outcomes. A retrospective analysis of patients with thyroid cancer treated and followed up at the Chang Gung Medical Center in Linkou was performed. Among 3957 patients with thyroid cancer, a total of 56 patients with MCT were evaluated. Of them, 47 patients (83.9 %) were diagnosed with malignancy or suspected malignancy via fine needle aspiration cytology of the thyroid. Synchronous primary cancers were diagnosed in 44 of the patients with MCT. Of the MCT, metastasis of lung cancer to the thyroid was the leading category. Other primary sites of MCT were the head and neck, gastrointestinal tract, kidneys, breast, cervix, and unknown primary site. The mean 5-, 10-, 20-, and 60-month survival rates were 46.4, 32.1, 21.4, and 7.9 % for the patients. Patients with metachronous thyroid carcinoma had significantly better survival than patients with synchronous cancer. In conclusions, the incidence of MCT in patients with thyroid cancer is low; however, the prognosis of patients with MCT is poor, especially in patients diagnosed with synchronous primary tumors. In this study, MCT commonly originated in organs located near the thyroid, such as the lungs, head, and neck. Close monitoring of these malignancies may improve the prognosis of patients with MCT in the future.

Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers | Office of Cancer Genomics

Cancer.gov

Human tumors show a high level of genetic heterogeneity, but the processes that influence the timing and route of metastatic dissemination of the subclones are unknown. Here we have used whole-exome sequencing of 103 matched benign, malignant and metastatic skin tumors from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumor, supporting parallel rather than linear evolution as the predominant model of metastasis.

Differences in experiences of care between patients diagnosed with metastatic cancer of known and unknown primaries: mixed-method findings from the 2013 cancer patient experience survey in England

PubMed Central

Bracher, Mike; Drosdowsky, Allison; Richardson, Alison; Symons, John; Mileshkin, Linda; Schofield, Penny

2017-01-01

Objectives To explore differences in experiences of care reported in the Cancer Patient Experience Survey (CPES) between patients with cancer of unknown primary (CUP) and those with metastatic disease of known primary (non-CUP); to determine insights pertaining to the experiences of care for CUP respondents from free-text comments. Design Two separate, but related, studies, involving secondary analysis of existing data. Using frequency matching of CUP and non-CUP patients, statistical comparisons of responses to CPES questions were conducted. Free-text comments from CUP respondents were analysed thematically. Setting and participants The CPES questionnaire comprises 63 closed questions measuring 8 areas that relate to experience of care and 3 free-text questions. Questionnaires were mailed to all adult patients (aged ≥16 years) in England with cancer admitted to hospital between 1 September 2013 and 30 November 2013. Results Matched analysis of closed response items from 2992 patients found significant differences between CUP (n=1496) and non-CUP patients (n=1496): CUP patients were more likely to want more written information about their type of cancer and tests received, to receive their diagnosis from a general practitioner (GP) and have seen allied health professionals, but less likely to have understood explanations of their condition or had surgery. Freetext responses (n=3055) were coded into 17 categories and provided deeper insight regarding patient information and interactions with GPs. CPES data may include a preponderance of patients with favourable CUP subtypes and patients initially identified as CUP but whose primary was subsequently identified. Conclusions These are the first large-scale studies to explore the experiences of care of CUP patients. The significant differences identified between the experiences of CUP and non-CUP patients suggest CUP patients require more psychosocial support and specific interventions to manage diagnostic uncertainty and the multiple investigations many CUP patients face. Substantial limitations were identified with the CPES data, emphasising the need for prospective studies. PMID:28963312

S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells

PubMed Central

Wang, Yan; Sun, ZhongSheng; Szyf, Moshe

2017-01-01

S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent. PMID:29340097

S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells.

PubMed

Wang, Yan; Sun, ZhongSheng; Szyf, Moshe

2017-12-19

S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent.

Severe Unresponsive Hypoglycemia Associated with Neuroendocrine Tumor of Unknown Primary Site - 18 Years after Rectal Cancer Surgery. Case Report.

PubMed

Rusu, Octavia Cristina; Costea, Radu Virgil; Popa, Cristian Constantin; Iliesiu, Andreea; Dumitru, Adrian; Becheanu, Gabriel; Neagu, Stefan Ilie

2015-09-01

Neuroendocrine tumors are derived from cells that have the unique ability to synthesize, store and secrete a variety of metabolically active substances, peptides and amines, characteristic of the tissue of origin, which can cause distinct clinical syndromes. We present the case of a 58-year-old patient diagnosed and surgically treated in January 1996 for stage III inferior rectal cancer, who was readmitted after 18 years presenting persistent diarrheic syndrome and asthenia. Investigations performed (abdominal CT) showed multiple liver metastases, initially suspected as being related to the rectal cancer. Biopsy of liver metastases and pathological and immunohistochemical analysis demonstrated the neuroendocrine origin (moderately differentiated neuroendocrine tumor). Seven months after the identification of liver metastases and after initiation of oncological therapy with Interferon and Somatostatin, the patient presented severe hypoglycemia (serum glucose 13-70 mg/dl) proved to be due to insulin-like factors (serum insulin level 64.9 ìU/ml) secreted by metastases. Due to the aggressive evolution of neuroendocrine tumor, with multiple episodes of severe hypoglycemia, resistant to treatment, the patient died approximately one month after the occurrence of hypoglycemic episodes. Despite comprehensive tests (abdominal CT scan, colonoscopy, bone scintigraphy and PET/CT), the primary site of the neuroendocrine tumors remained unknown.

Patient-derived orthotopic xenograft models for cancer of unknown primary precisely distinguish chemotherapy, and tumor-targeting S. typhimurium A1-R is superior to first-line chemotherapy.

PubMed

Miyake, Kentaro; Kiyuna, Tasuku; Miyake, Masuyo; Kawaguchi, Kei; Yoon, Sang Nam; Zhang, Zhiying; Igarashi, Kentaro; Razmjooei, Sahar; Wangsiricharoen, Sintawat; Murakami, Takashi; Li, Yunfeng; Nelson, Scott D; Russell, Tara A; Singh, Arun S; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Singh, Shree Ram; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

2018-01-01

Cancer of unknown primary (CUP) is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy. CUP consists of diverse malignancy groups, making personalized precision therapy essential. The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft (PDOX) model. This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S. typhimurium A1-R with first-line chemotherapy using the CUP PDOX model. The present study is the first to use a CUP PDOX model, which was able to precisely distinguish the chemotherapeutic course. We found that a carboplatinum (CAR)-based regimen was effective for this CUP patient. We also demonstrated that S. typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy. Our results indicate that S. typhimurium A1-R has clinical potential for CUP, a resistant disease that requires effective therapy.

Diagnostic value of 18F-fluordesoxyglucose positron emission tomography for patients with brain metastasis from unknown primary site.

PubMed

Wolpert, Fabian; Weller, Michael; Berghoff, Anna Sophie; Rushing, Elisabeth; Füreder, Lisa Michaela; Petyt, Gregory; Leske, Henning; Andratschke, Nicolaus; Regli, Luca; Neidert, Marian Christoph; Stupp, Roger; Stahel, Rolf; Dummer, Reinhard; Frauenfelder, Thomas; Roth, Patrick; Reyns, Nicolas; Kaufmann, Philipp Antonio; Preusser, Matthias; Le Rhun, Emilie

2018-04-17

In 30% of patients with brain metastasis (BM), neurological symptoms are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). Here, we define the diagnostic value of 18 F-fluordesoxyglucose positron emission tomography (FDG-PET/CT) in the workup of BM-CUPS. We screened 565 patients operated for BM at the University Hospital Zurich and identified 64 patients with BM-CUPS with data on both FDG-PET/CT and contrast-enhanced chest/abdomen computed tomography (CT) available at BM diagnosis. A cohort of 125 patients with BM-CUPS from Lille and Vienna was used for validation. FDG-PET/CT was not superior to chest/abdomen CT in localising the primary lesion in the discovery cohort, presumably because most primary tumours were lung cancers. However, FDG-PET/CT identified additional lesions suspicious of extracranial metastases in 27 of 64 patients (42%). The inclusion of FDG-PET/CT findings shifted the graded prognostic assessment (GPA) score from 3 with CT alone to 2.5 for PET/CT (p = 3.8 × 10 -5 , Wilcoxon's test), resulting in a predicted survival of 5.3 versus 3.8 months (p = 6.1 × 10 -5 ; Wilcoxon's test). All observations were confirmed in the validation cohort. Lung cancers are the most common primary tumour in BM-CUPS; accordingly, CT alone shows similar overall sensitivity for detecting the primary tumour as FDG-PET/CT. Yet, FDG-PET/CT improves the accuracy of staging by detecting more metastases, reflected by decreased GPA scores and decreased predicted survival. Therefore, randomised trials on patients with BM should standardise methods of staging, notably when stratifying for GPA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intensity-Modulated Radiotherapy for Cervical Lymph Node Metastases From Unknown Primary Cancer

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

Madani, Indira; Vakaet, Luc; Bonte, Katrien

2008-07-15

Purpose: To compare the effectiveness of intensity-modulated radiotherapy (IMRT) and conventional (two-dimensional) radiotherapy in the treatment of cervical lymph node metastases from unknown primary cancer (UPC). Methods and Materials: Between February 2003 and September 2006, 23 patients with UPC of squamous cell carcinoma were treated with IMRT. Extended putative mucosal and bilateral nodal sites were irradiated to a median dose of 66 Gy. In 19 patients, IMRT was performed after lymph node dissection, and in 4 patients primary radiotherapy was given. The conventional radiotherapy group (historical control group) comprised 18 patients treated to a median dose of 66 Gy betweenmore » August 1994 and October 2003. Results: Twenty patients completed treatment. As compared with conventional radiotherapy, the incidence of Grade 3 acute dysphagia was significantly lower in the IMRT group (4.5% vs. 50%, p = 0.003). By 6 months, Grade 3 xerostomia was detected in 11.8% patients in the IMRT group vs. 53.4% in the historical control group (p = 0.03). No Grade 3 dysphagia or skin fibrosis was observed after IMRT but these were noted after conventional radiotherapy (26.7%, p = 0.01) and 26.7%, p = 0.03) respectively). With median follow-up of living patients of 17 months, there was no emergence of primary cancer. One patient had persistent nodal disease and another had nodal relapse at 5 months. Distant metastases were detected in 4 patients. The 2-year overall survival and distant disease-free probability after IMRT did not differ significantly from those for conventional radiotherapy (74.8% vs. 61.1% and 76.3% vs. 68.4%, respectively). Conclusions: Use of IMRT for UPC resulted in lower toxicity than conventional radiotherapy, and was similar in efficacy.« less

CUP Syndrome-Metastatic Malignancy with Unknown Primary Tumor.

PubMed

Zaun, Gregor; Schuler, Martin; Herrmann, Ken; Tannapfel, Andrea

2018-03-09

2-4% of newly diagnosed cases of malignant disease involve cancer of unknown primary (CUP). This mixed entity is one of the 6 most common types of malignant disease in Germany. Highly refined treatment strategies can now be offered to patients with CUP. This review is based on pertinent publications retrieved by a selective search in PubMed with an emphasis on articles from the past decade. The current guidelines and recommendations of specialty societies were also considered in the evaluation. CUP most commonly manifests itself as metastases to the lymph nodes, lungs, liver, or bones. With the aid of imaging studies, including functional hybrid imaging and further medical examination, a primary tumor can be discovered in up to 40% of patients initially diagnosed with CUP. Immunohistochemistry guided by histomorphology often enables precise characterization of the lesion and can be supplemented, in selected cases, by molecular-genetic diagnostic evaluation. The most commonly detected types of primary tumor are cancers of the lung, pancreas, liver, and biliary system. For patients with local metastases, surgical resection or radiotherapy with curative intent is usually indicated, sometimes in the framework of a multimodal treatment concept. The median 2-year survival of patients with disseminated CUP is only 20%. For such patients, specific types of systemic therapy are recommended on the basis of the diagnostic characterization of the disease. Immune-modulatory antibodies can be effective, particularly in the treatment of CUP that has been characterized with biomarkers, but should still be considered experimental at present. A combination of conventional and innovative diagnostic methods enables the provision of highly refined therapeutic strategies to patients with CUP who are undergoing treatment in interdisciplinary cancer centers.

High-Dose Chemotherapy With Autologous Stem-Cell Support As Adjuvant Therapy in Breast Cancer: Overview of 15 Randomized Trials

PubMed Central

Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Rodenhuis, Sjoerd; Peters, William P.; Leonard, Robert C.; Barlow, William E.; Tallman, Martin S.; Bergh, Jonas; Nitz, Ulrike A.; Gianni, Alessandro M.; Basser, Russell L.; Zander, Axel R.; Coombes, R. Charles; Roché, Henri; Tokuda, Yutaka; de Vries, Elisabeth G.E.; Hortobagyi, Gabriel N.; Crown, John P.; Pedrazzoli, Paolo; Bregni, Marco; Demirer, Taner

2011-01-01

Purpose Adjuvant high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation (AHST) for high-risk primary breast cancer has not been shown to prolong survival. Individual trials have had limited power to show overall benefit or benefits within subsets. Methods We assembled individual patient data from 15 randomized trials that compared HDC versus control therapy without stem-cell support. Prospectively defined primary end points were relapse-free survival (RFS) and overall survival (OS). We compared the effect of HDC versus control by using log-rank tests and proportional hazards regression, and we adjusted for clinically relevant covariates. Subset analyses were by age, number of positive lymph nodes, tumor size, histology, hormone receptor (HmR) status, and human epidermal growth factor receptor 2 (HER2) status. Results Of 6,210 total patients (n = 3,118, HDC; n = 3,092 control), the median age was 46 years; 69% were premenopausal, 29% were postmenopausal, and 2% were unknown menopausal status; 49.5% were HmR positive; 33.5% were HmR negative, and 17% were unknown HmR status. The median follow-up was 6 years. After analysis was adjusted for covariates, HDC was found to prolong relapse-free survival (RFS; hazard ratio [HR], 0.87; 95% CI, 0.81 to 0.93; P < .001) but not overall survival (OS; HR, 0.94; 95% CI, 0.87 to 1.02; P = .13). For OS, no covariates had statistically significant interactions with treatment effect, and no subsets evinced a significant effect of HDC. Younger patients had a significantly better RFS on HDC than did older patients. Conclusion Adjuvant HDC with AHST prolonged RFS in high-risk primary breast cancer compared with control, but this did not translate into a significant OS benefit. Whether HDC benefits patients in the context of targeted therapies is unknown. PMID:21768471

Inactivation of LLC1 gene in nonsmall cell lung cancer

PubMed Central

Hong, Kyeong-Man; Yang, Sei-Hoon; Chowdhuri, Sinchita R.; Player, Audrey; Hames, Megan; Fukuoka, Junya; Meerzaman, Daoud; Dracheva, Tatiana; Sun, Zhifu; Yang, Ping; Jen, Jin

2007-01-01

Serial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium, but absent or downregulated in most primary non-small cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells, but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5-aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis. PMID:17304513

Paraneoplastic Hypocalcemia Developed in Gastric Cancer Accompanied by Osteoblastic Metastasis.

PubMed

Okazaki, Jun; Muguruma, Naoki; Kitamura, Shinji; Kimura, Tetsuo; Okamoto, Koichi; Miyamoto, Hiroshi; Kishi, Kazuhiro; Bando, Yoshimi; Kondo, Takeshi; Endo, Itsuro; Abe, Masahiro; Takayama, Tetsuji

2017-01-01

Paraneoplastic syndromes are generally defined as clinical disorders associated with malignant diseases, and hypocalcemia associated with cancer is a rare condition. A woman in her 60s was referred to our hospital for the further examination of massive ascites due to carcinoma of unknown primary origin. She complained of numbness around her lips, and marked hypocalcemia of 5.0 mg/dL was noted. After two courses of chemotherapy, computed tomography showed a decrease in the ascites, and her serum calcium level increased. Although hypocalcemia is a very rare condition in patients with gastric cancer, serum calcium values should be evaluated when neurological symptoms are observed.

[Clinical significance of four quadrant localization in the diagnosis and treatment of metastatic carcinoma of the neck with unknown primary].

PubMed

Gao, Y Y; Chen, X H

2017-06-05

Objective: The aim of this study is to investigate the clinical significance of four quadrant localization in the diagnosis and treatment of unknown primary cervical metastases. Method: The clinical data with unknown primary cervical metastases, were analyzed retrospectively. All the patients have not been found the original site in the initial treatment. There are four quadrants in the neck, the neck line as the longitudinal axis, and edge of cricoid cartilage as the horizontal axis. When cervical metastasis occurred in the left and right upper quadrant, the primary tumor site and radiotherapy from the skull base to the root of the neck; when appear in left and right lower quadrant, the primary investigation site and radiotherapy from neck to thoracic mediastinum, left lower abdomen also includes following primary search. At the same time, bilateral cervical metastasis cancers, focusing on the central line near the primary focus. Specific treatment strategies include ipsilateral total neck dissection and radical radiotherapy of the above radiotherapy site. Result: Left upper neck in 4 cases, right upper neck in 5 cases, left lower neck in 7 cases, lower right neck in 8 cases and mixed area in 6 cases. Only 10 of 30 patients (33.3%) with primary sites were found in the follow up period. In accordance with the four quadrant localization, the median time was 6 months. Conclusion: Four quadrant localization to locate the primary site is accurate, and individualized comprehensive treatment is the key to improve the curative effect. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

PubMed

Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

2017-10-01

Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.

Lysosomal Degradation of CD44 Mediates Ceramide Nanoliposome-induced Anoikis and Diminished Extravasation in Metastatic Carcinoma Cells*

PubMed Central

Haakenson, Jeremy K.; Khokhlatchev, Andrei V.; Choi, Younhee J.; Linton, Samuel S.; Zhang, Pu; Zaki, Peter M.; Fu, Changliang; Cooper, Timothy K.; Manni, Andrea; Zhu, Junjia; Fox, Todd E.; Dong, Cheng; Kester, Mark

2015-01-01

The ceramide nanoliposome (CNL) has shown promise in being able to treat a variety of primary tumors. However, its potential for treating metastatic cancer remains unknown. In this study, we demonstrate that CNL increases anoikis while preventing cancer cell extravasation under both static and physiological fluid flow conditions. Mechanistically, CNL limits metastases by decreasing CD44 protein levels in human breast and pancreatic cancer cells via lysosomal degradation of CD44, independent of palmitoylation or proteasome targeting. siRNA down-regulation of CD44 mimics CNL-induced anoikis and diminished extravasation of cancer cells. Taken together, our data indicate that ceramide limits CD44-dependent cancer cell migration, suggesting that CNL could be used to prevent and treat solid tumor metastasis. PMID:25681441

Subjective ultrasound assessment, the ADNEX model and ultrasound-guided tru-cut biopsy to differentiate disseminated primary ovarian cancer from metastatic non-ovarian cancer.

PubMed

Epstein, E; Van Calster, B; Timmerman, D; Nikman, S

2016-01-01

To compare subjective ultrasound assessment and the ADNEX model with ultrasound-guided tru-cut biopsy to differentiate disseminated primary ovarian cancer from metastatic non-ovarian cancer. This was a prospective study including 143 consecutive women with disseminated malignancy of unknown primary origin, with a pelvic tumor/carcinosis. Women underwent either transvaginal or transrectal ultrasound as well as transabdominal ultrasound examination followed by tru-cut biopsy. The ultrasound examiner assessed tumor morphology, spread in the pelvis and abdomen, and predicted tumor origin as primary ovarian or metastatic using both subjective assessment and the ADNEX model. Histology from tru-cut biopsy served as the gold standard for assessment of diagnostic accuracy. Biopsy adequacy and the complication rate were assessed. Tru-cut biopsy was performed transvaginally in 131/143 (92%) women. Two women needed inpatient care (one had abdominal wall hematoma, and one infection). Biopsy resulted in a conclusive diagnosis in 126/143 (88%) women, amongst whom cytoreductive surgery was performed in 30/126 confirming the diagnosis in all cases. Non-ovarian metastatic cancer was found in 37/126 (29%) women and primary ovarian cancer in 89/126 (71%) women. Subjective ultrasound evaluation had a sensitivity of 82% (73/89) and a specificity of 70% (26/37) in predicting primary ovarian cancer. The ADNEX model had an area under the receiver-operating characteristics curve of 0.891 (95% CI, 0.794-0.946) (in women with an ovarian lesion, n = 104). Tumor origin was associated with age, CA 125, previous neoplasia, presence of omental cake and tumor mobility. Subjective ultrasound assessment and the ADNEX model can both be used to predict whether a pelvic tumor is metastatic and of non-ovarian origin, indicating the need for tru-cut biopsy, which is associated with very few complications and will provide a conclusive diagnosis in nine out of 10 women. Copyright © 2015 ISUOG. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases.

PubMed

Le Pennec, Soazig; Konopka, Tomasz; Gacquer, David; Fimereli, Danai; Tarabichi, Maxime; Tomás, Gil; Savagner, Frédérique; Decaussin-Petrucci, Myriam; Trésallet, Christophe; Andry, Guy; Larsimont, Denis; Detours, Vincent; Maenhaut, Carine

2015-04-01

The contribution of intratumor heterogeneity to thyroid metastatic cancers is still unknown. The clonal relationships between the primary thyroid tumors and lymph nodes (LN) or distant metastases are also poorly understood. The objective of this study was to determine the phylogenetic relationships between matched primary thyroid tumors and metastases. We searched for non-synonymous single-nucleotide variants (nsSNVs), gene fusions, alternative transcripts, and loss of heterozygosity (LOH) by paired-end massively parallel sequencing of cDNA (RNA-Seq) in a patient diagnosed with an aggressive papillary thyroid cancer (PTC). Seven tumor samples from a stage IVc PTC patient were analyzed by RNA-Seq: two areas from the primary tumor, four areas from two LN metastases, and one area from a pleural metastasis (PLM). A large panel of other thyroid tumors was used for Sanger sequencing screening. We identified seven new nsSNVs. Some of these were early events clonally present in both the primary PTC and the three matched metastases. Other nsSNVs were private to the primary tumor, the LN metastases and/or the PLM. Three new gene fusions were identified. A novel cancer-specific KAZN alternative transcript was detected in this aggressive PTC and in dozens of additional thyroid tumors. The PLM harbored an exclusive whole-chromosome 19 LOH. We have presented the first, to our knowledge, deep sequencing study comparing the mutational spectra in a PTC and both LN and distant metastases. This study has yielded novel findings concerning intra-tumor heterogeneity, clonal evolution and metastases dissemination in thyroid cancer. © 2015 Society for Endocrinology.

Primary Care Providers’ Experiences with Urine Toxicology Tests to Manage Prescription Opioid Misuse and Substance Use Among Chronic Non-Cancer Pain Patients in Safety Net Healthcare Settings

PubMed Central

Ceasar, Rachel; Chang, Jamie; Zamora, Kara; Hurstak, Emily; Kushel, Margot; Miaskowski, Christine; Knight, Kelly

2016-01-01

Background Guideline recommendations to reduce prescription opioid misuse among patients with chronic non-cancer pain include the routine use of urine toxicology tests for high-risk patients. Yet little is known about how the implementation of urine toxicology tests among patients with co-occurring chronic non-cancer pain and substance use impacts primary care providers’ management of misuse. In this paper, we present clinicians’ perspectives on the benefits and challenges of implementing urine toxicology tests in the monitoring of opioid misuse and substance use in safety net healthcare settings. Methods We interviewed 23 primary care providers from six safety net healthcare settings whose patients had a diagnosis of co-occurring chronic non-cancer pain and substance use. We transcribed, coded, and analyzed interviews using grounded theory methodology. Results The benefits of implementing urine toxicology tests for primary care providers included less reliance on intuition to assess for misuse and the ability to identify unknown opioid misuse and/or substance use. The challenges of implementing urine toxicology tests included insufficient education and training about how to interpret and implement tests, and a lack of clarity on how and when to act on tests that indicated misuse and/or substance use. Conclusions These data suggest that primary care clinicians’ lack of education and training to interpret and implement urine toxicology tests may impact their management of patient opioid misuse and/or substance use. Clinicians may benefit from additional education and training about the clinical implementation and use of urine toxicology tests. Additional research is needed on how primary care providers implementation and use of urine toxicology tests impacts chronic non-cancer pain management in primary care and safety net healthcare settings among patients with co-occurring chronic non-cancer pain and substance use. PMID:26682471

Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid

PubMed Central

Pentsova, Elena I.; Shah, Ronak H.; Tang, Jiabin; Boire, Adrienne; You, Daoqi; Briggs, Samuel; Omuro, Antonio; Lin, Xuling; Fleisher, Martin; Grommes, Christian; Panageas, Katherine S.; Meng, Fanli; Selcuklu, S. Duygu; Ogilvie, Shahiba; Distefano, Natalie; Shagabayeva, Larisa; Rosenblum, Marc; DeAngelis, Lisa M.; Viale, Agnes; Berger, Michael F.

2016-01-01

Purpose Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue. Materials and Methods We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer. Results We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations. Conclusion The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS. PMID:27161972

Reliability of rapid reporting of cancers in New Hampshire.

PubMed

Celaya, Maria O; Riddle, Bruce L; Cherala, Sai S; Armenti, Karla R; Rees, Judy R

2010-01-01

The New Hampshire State Cancer Registry (NHSCR) has a 2-phase reporting system. An abbreviated, "rapid" report of cancer diagnosis or treatment is due to the central registry within 45 days of diagnosis and a more detailed, definitive report is due within 180 days. Rapid reports are used for various research studies, but researchers who contact patients are warned that the rapid reports may contain inaccuracies. This study aimed to assess the reliability of rapid cancer reports. For diagnosis years 2000-2004, we compared the rapid and definitive reports submitted to NHSCR. We calculated the sensitivity and positive predictive value of rapid reports; the reliability of key data items overall and for major sites; and the time between diagnosis and submission of the report. Rapid reports identified incident cancer cases with a sensitivity of 88.5%. The overall accuracy of key data items was high. The accuracy of primary sites identified by rapid reports was high generally but lower for ovarian and unknown primaries. A subset analysis showed that 47% of cancers were reported within 90 days of diagnosis. Rapid reports submitted to NHSCR are generally of high quality and present a useful opportunity for research investigations in New Hampshire.

The desire to survive: the adaptation process of adult cancer patients undergoing radiotherapy.

PubMed

Chao, Yu Huan; Wang, Shou-Yu; Hsu, Tsui Hua; Wang, Kai Wei K

2015-01-01

Radiotherapy is one of the primary treatment strategies for cancer. However, patients not only deal with the side-effects of radiotherapy, but they must also endure the psychological distress caused by cancer. This study explores how cancer patients adapt to the treatment process when receiving radiotherapy. This study used a grounded theory approach, and eight in-depth interviews were conducted with newly diagnosed cancer patients who received radiotherapy as a primary treatment. The core category that emerged from this study was "the desire to survive". The categories and subcategories that emerged from the data include facing unknown situations (e.g. searching for relevant information and decision-making considerations, and listening to healthcare professionals' suggestions), experiencing the pain of treatment (e.g. tolerating side-effects, tolerating inconvenience during the treatment, accepting support during the treatment, and adjusting lifestyles), and chances to extend life (e.g. accepting fate, determination to undergo the treatment, and adjusting negative emotions). The study results provide a better understanding of the experiences of cancer patients undergoing radiotherapy. Healthcare professionals should provide effective medical management for side-effects and psychological support to cancer patients during the journey of radiotherapy. © 2014 The Authors. Japan Journal of Nursing Science © 2014 Japan Academy of Nursing Science.

Identification and survival outcomes of a cohort of patients with cancer of unknown primary in Ontario, Canada.

PubMed

Kim, Chong S; Hannouf, Malek B; Sarma, Sisira; Rodrigues, George B; Rogan, Peter K; Mahmud, Salaheddin M; Winquist, Eric; Brackstone, Muriel; Zaric, Gregory S

2015-11-01

Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS). We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. We cross-validated CUP diagnosis and obtained additional information about metastasis through data linkage with the SDS/DAD database. OS was assessed using Cox regression models adjusting for histology and sites of metastases. We identified 3564 patients diagnosed with CUP. Patients without histologically confirmed disease (n = 1821) had a one-year OS of 10.9%, whereas patients with confirmed histology (n = 1743) had a one-year OS of 15.6%. The most common metastatic sites were in the respiratory or digestive systems (n = 1603), and the most common histology was adenocarcinoma (n = 939). Three-year survival rates were 3.5%, 5.3%, 41.6% and 3.6% among adenocarcinoma, unspecified carcinoma, squamous cell carcinoma and undifferentiated histology, respectively. Three-year survival rates were 40%, 2.4%, 8.0% and 4.6% among patients with metastases localised to lymph nodes, the respiratory or digestive systems, other specified sites, and unspecified sites, respectively. CUP patients in Ontario have a poor prognosis. Some subgroups may have better survival rates, such as patients with metastases localised to lymph nodes and patients with squamous cell histology.

Lysosomal degradation of CD44 mediates ceramide nanoliposome-induced anoikis and diminished extravasation in metastatic carcinoma cells.

PubMed

Haakenson, Jeremy K; Khokhlatchev, Andrei V; Choi, Younhee J; Linton, Samuel S; Zhang, Pu; Zaki, Peter M; Fu, Changliang; Cooper, Timothy K; Manni, Andrea; Zhu, Junjia; Fox, Todd E; Dong, Cheng; Kester, Mark

2015-03-27

The ceramide nanoliposome (CNL) has shown promise in being able to treat a variety of primary tumors. However, its potential for treating metastatic cancer remains unknown. In this study, we demonstrate that CNL increases anoikis while preventing cancer cell extravasation under both static and physiological fluid flow conditions. Mechanistically, CNL limits metastases by decreasing CD44 protein levels in human breast and pancreatic cancer cells via lysosomal degradation of CD44, independent of palmitoylation or proteasome targeting. siRNA down-regulation of CD44 mimics CNL-induced anoikis and diminished extravasation of cancer cells. Taken together, our data indicate that ceramide limits CD44-dependent cancer cell migration, suggesting that CNL could be used to prevent and treat solid tumor metastasis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Orbital metastases in Italy

PubMed Central

Magliozzi, Patrizio; Strianese, Diego; Bonavolontà, Paola; Ferrara, Mariantonia; Ruggiero, Pasquale; Carandente, Raffaella; Bonavolontà, Giulio; Tranfa, Fausto

2015-01-01

AIM To describe a series of Italian patients with orbital metastasis focusing on the outcomes in relation to the different primary site of malignancy. METHODS Retrospective chart review of 93 patients with orbital metastasis collected in a tertiary referral centre in a period of 38y and review of literature. RESULTS Out of 93 patients, 52 were females and 41 were males. Median age at diagnosis was 51y (range 1 to 88y). The patients have been divided into four groups on the basis of the year of diagnosis. The frequency of recorded cases had decreased significantly (P<0.05) during the last 9.5y. Primary tumor site was breast in 36 cases (39%), kidney in 10 (11%), lung in 8 (9%), skin in 6 (6%); other sites were less frequent. In 16 case (17%) the primary tumor remained unknown. The most frequent clinical findings were proptosis (73%), limited ocular motility (55%), blepharoptosis (46%) and blurred vision (43%). The diagnosis were established by history, ocular and systemic evaluation, orbital imaging studies and open biopsy or fine needle aspiration biopsy (FNAB). Treatment included surgical excision, irradiation, chemotherapy, hormone therapy, or observation. Ninety-one percent of patients died of metastasis with an overall mean survival time (OMST) after the orbital diagnosis of 13.5mo. CONCLUSION Breast, kidney and lung are the most frequent primary sites of cancer leading to an orbital metastasis. When the primary site is unknown, gastrointestinal tract should be carefully investigated. In the last decade a decrease in the frequency of orbital metastasis has been observed. Surgery provides a local palliation. Prognosis remains poor with a OMST of 13.5mo ranging from the 3mo in the lung cancer to 24mo in the kidney tumor. PMID:26558220

Histogram Analysis of Apparent Diffusion Coefficients for Occult Tonsil Cancer in Patients with Cervical Nodal Metastasis from an Unknown Primary Site at Presentation.

PubMed

Choi, Young Jun; Lee, Jeong Hyun; Kim, Hye Ok; Kim, Dae Yoon; Yoon, Ra Gyoung; Cho, So Hyun; Koh, Myeong Ju; Kim, Namkug; Kim, Sang Yoon; Baek, Jung Hwan

2016-01-01

To explore the added value of histogram analysis of apparent diffusion coefficient (ADC) values over magnetic resonance (MR) imaging and fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for the detection of occult palatine tonsil squamous cell carcinoma (SCC) in patients with cervical nodal metastasis from a cancer of an unknown primary site. The institutional review board approved this retrospective study, and the requirement for informed consent was waived. Differences in the bimodal histogram parameters of the ADC values were assessed among occult palatine tonsil SCC (n = 19), overt palatine tonsil SCC (n = 20), and normal palatine tonsils (n = 20). One-way analysis of variance was used to analyze differences among the three groups. Receiver operating characteristic curve analysis was used to determine the best differentiating parameters. The increased sensitivity of histogram analysis over MR imaging and (18)F-FDG PET/CT for the detection of occult palatine tonsil SCC was evaluated as added value. Histogram analysis showed statistically significant differences in the mean, standard deviation, and 50th and 90th percentile ADC values among the three groups (P < .0045). Occult palatine tonsil SCC had a significantly higher standard deviation for the overall curves, mean and standard deviation of the higher curves, and 90th percentile ADC value, compared with normal palatine tonsils (P < .0167). Receiver operating characteristic curve analysis showed that the standard deviation of the overall curve best delineated occult palatine tonsil SCC from normal palatine tonsils, with a sensitivity of 78.9% (15 of 19 patients) and a specificity of 60% (12 of 20 patients). The added value of ADC histogram analysis was 52.6% over MR imaging alone and 15.8% over combined conventional MR imaging and (18)F-FDG PET/CT. Adding ADC histogram analysis to conventional MR imaging can improve the detection sensitivity for occult palatine tonsil SCC in patients with a cervical nodal metastasis originating from a cancer of an unknown primary site. © RSNA, 2015.

Incidence and risk factors of synchronous colorectal cancer in patients with esophageal cancer: an analysis of 480 consecutive colonoscopies before surgery.

PubMed

Yoshida, Naoya; Tamaoki, Yuka; Baba, Yoshifumi; Sakamoto, Yasuo; Miyamoto, Yuji; Iwatsuki, Masaaki; Shono, Takashi; Miyamoto, Hideaki; Imuta, Masanori; Kurashige, Junji; Sawayama, Hiroshi; Tokunaga, Ryuma; Watanabe, Masayuki; Sasaki, Yutaka; Yamashita, Yasuyuki; Baba, Hideo

2016-12-01

The precise incidence rates of multiple primary colorectal cancers in esophageal cancer patients are unknown. In total, 480 consecutive patients with esophageal cancers surgically resected in the Kumamoto University Hospital received preoperative total colonoscopy for the assessment of colorectal disease between April 2005 and February 2016. We retrospectively investigated the occurrence of synchronous colorectal cancer with esophageal cancer. In addition, we examined the risk factors for the incidence of multiple primary colorectal cancers. Of the 480 patients, 14 (2.9 %) had synchronous colorectal cancers, 13 had well-differentiated tubular adenocarcinomas, and 1 had papillary adenocarcinoma. Other 14 patients had metachronous colorectal cancer. The current incidence rates of synchronous and total (both synchronous and metachronous) colorectal cancers outnumbered those in normal healthy population and those in esophageal cancer patients which previously reported by The Japan Esophageal Society. The age ≥70 years (hazard ratio 4.82, 95 % confidence interval 1.473-15.78; p = 0.009) and Brinkman index ≥800 (hazard ratio 3.47, 95 % confidence interval 1.056-11.37; p = 0.040) were the independent risk factors for the incidence of synchronous colorectal cancer. They were also the independent risk factors for the incidence of total colorectal cancer. The results of the present study suggested that pretreatment screening with total colonoscopy is meaningful for patients with esophageal cancer, because the frequency of synchronous colorectal cancer was not negligible. Particularly, in patients >70 years and with history of heavy smoking, pretreatment colonoscopy might be necessary.

Comprehensive analysis of cancers of unknown primary for the biomarkers of response to immune checkpoint blockade therapy.

PubMed

Gatalica, Zoran; Xiu, Joanne; Swensen, Jeff; Vranic, Semir

2018-05-01

Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Avoiding immune destruction is a major cancer characteristic and therapies aimed at immune checkpoint blockade are in use for several specific cancer types. A comprehensive survey of predictive biomarkers to immune checkpoint blockade in CUP were explored in this study. About 389 cases of CUP were analysed for mutations in 592 genes and 52 gene fusions using a massively parallel DNA sequencing platform (next-generation sequencing [NGS]). Total mutational load (TML) and microsatellite instability (MSI) were calculated from NGS data. PD-L1 expression was explored using immunohistochemistry (with 5% cutoff value). High TML was seen in 11.8% (46/389) of tumours. MSI-high (MSI-H) was detected in 7/384 (1.8%) of tumours. Tumour PD-L1 expression was detected in 80/362 CUP (22%). A small proportion of CUP cases harboured genetic alterations of negative predictive biomarkers to immune checkpoint inhibitors (predictors to hyperprogression) including MDM2 gene amplification (2%) and loss of function JAK2 gene mutations (1%). Amplifications of CD274 (PD-L1) and PDCD1LG2 (PD-L2) genes were also rare (1.4% and 0.8%, respectively). The most frequently mutated genes were TP53 (54%), KRAS (22%), ARID1A (13%), PIK3CA (9%), CDKN2A (8%), SMARCA4 (7%) and PBRM1, STK11, APC, RB1 (5%, respectively). Using a multiplex testing approach, 28% of CUP carried one or more predictive biomarkers (MSI-H, PD-L1 and/or TML-H) to the immune checkpoint blockade, providing a novel option for treatment in patients with CUP. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Comparison of survival and clinicopathologic features in colorectal cancer among African American, Caucasian, and Chinese patients treated in the United States: Results from the surveillance epidemiology and end results (SEER) database.

PubMed

Lin, Junzhong; Qiu, Miaozhen; Xu, Ruihua; Dobs, Adrian Sandra

2015-10-20

African American patients of colorectal cancer (CRC) were found to have a worse prognosis than Caucasians, but it has not been fully understood about the survival difference among Chinese and these two races above. In this study, we used the Surveillance, Epidemiology and End Results database to analyze the survival difference among these three race/ethnicities in the United States. Adenocarcinoma patients of colorectal cancer with a race/ethnicity of Caucasian, Chinese and African American were enrolled for study. Patients were excluded if they had more than one primary cancer but the CRC was not the first one, had unknown cause of death or unknown survival months. The 5-year cause specific survival (CSS) was our primary endpoint. Totally, there were 585,670 eligible patients for analysis. Chinese patients had the best and African American patients had the worst 5-year CSS (66.7% vs 55.9%), P < 0.001. The 5-year CSS for Caucasian patients was 62.9%. Race/ethnicity was an independent prognostic factor in the multivariate analysis, P < 0.001. The comparison of clinicopathologic factors among these three race/ethnicities showed that the insurance coverage rate, income, percentage that completing high school and percentage of urban residence was lowest in the African American patients. Chinese patients had the highest percentage of married, while African American patients ranked lowest. More African American patients were diagnosed as stage IV and had high percentage of signet ring cell and mucinous adenocarcinoma. It is likely that biological differences as well as socioeconomic status both contribute to the survival disparity among the different race/ethnicities.

Comparison of survival and clinicopathologic features in colorectal cancer among African American, Caucasian, and Chinese patients treated in the United States: Results from the surveillance epidemiology and end results (SEER) database

PubMed Central

Dobs, Adrian Sandra

2015-01-01

African American patients of colorectal cancer (CRC) were found to have a worse prognosis than Caucasians, but it has not been fully understood about the survival difference among Chinese and these two races above. In this study, we used the Surveillance, Epidemiology and End Results database to analyze the survival difference among these three race/ethnicities in the United States. Adenocarcinoma patients of colorectal cancer with a race/ethnicity of Caucasian, Chinese and African American were enrolled for study. Patients were excluded if they had more than one primary cancer but the CRC was not the first one, had unknown cause of death or unknown survival months. The 5-year cause specific survival (CSS) was our primary endpoint. Totally, there were 585,670 eligible patients for analysis. Chinese patients had the best and African American patients had the worst 5-year CSS (66.7% vs 55.9%), P < 0.001. The 5-year CSS for Caucasian patients was 62.9%. Race/ethnicity was an independent prognostic factor in the multivariate analysis, P < 0.001. The comparison of clinicopathologic factors among these three race/ethnicities showed that the insurance coverage rate, income, percentage that completing high school and percentage of urban residence was lowest in the African American patients. Chinese patients had the highest percentage of married, while African American patients ranked lowest. More African American patients were diagnosed as stage IV and had high percentage of signet ring cell and mucinous adenocarcinoma. It is likely that biological differences as well as socioeconomic status both contribute to the survival disparity among the different race/ethnicities. PMID:26375551

Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing.

PubMed

Demeulemeester, Jonas; Kumar, Parveen; Møller, Elen K; Nord, Silje; Wedge, David C; Peterson, April; Mathiesen, Randi R; Fjelldal, Renathe; Zamani Esteki, Masoud; Theunis, Koen; Fernandez Gallardo, Elia; Grundstad, A Jason; Borgen, Elin; Baumbusch, Lars O; Børresen-Dale, Anne-Lise; White, Kevin P; Kristensen, Vessela N; Van Loo, Peter; Voet, Thierry; Naume, Bjørn

2016-12-09

Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer. We sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients. By comparing the cells' DNA copy number aberration (CNA) landscapes with those of the primary tumors and lymph node metastasis, we establish that 53% of the single cells morphologically classified as tumor cells are DTCs disseminating from the observed tumor. The remaining cells represent either non-aberrant "normal" cells or "aberrant cells of unknown origin" that have CNA landscapes discordant from the tumor. Further analyses suggest that the prevalence of aberrant cells of unknown origin is age-dependent and that at least a subset is hematopoietic in origin. Evolutionary reconstruction analysis of bulk tumor and DTC genomes enables ordering of CNA events in molecular pseudo-time and traced the origin of the DTCs to either the main tumor clone, primary tumor subclones, or subclones in an axillary lymph node metastasis. Single-cell sequencing of bone marrow epithelial-like cells, in parallel with intra-tumor genetic heterogeneity profiling from bulk DNA, is a powerful approach to identify and study DTCs, yielding insight into metastatic processes. A heterogeneous population of CNA-positive cells is present in the bone marrow of non-metastatic breast cancer patients, only part of which are derived from the observed tumor lineages.

Cytology and direct HPV testing on Fine-Needle aspirates from cervical lymph node metastases of patients with Oropharyngeal Squamous Cell Carcinoma or occult primary.

PubMed

Rollo, Francesca; Dona', Maria Gabriella; Pellini, Raul; Pichi, Barbara; Marandino, Ferdinando; Covello, Renato; Benevolo, Maria

2018-06-06

Cervical lymph node Fine Needle Aspirates (FNAs) may represent the only specimens available for an initial characterization of patients with lymphadenopathy. Morphology and HPV-DNA presence were evaluated in FNAs collected from patients with oropharyngeal cancer (OPSCC) or cancer of unknown primary (CUP). FNA HPV results were compared with those of the respective formalin-fixed paraffin-embedded (FFPE) primary cancer. Liquid-based cytology was performed on FNAs collected in PreservCyt. HPV-DNA was analyzed by the INNO-LiPA HPV genotyping Extra II on both cytological and FFPE samples. The CINtec ® Histology Kit was used to assess p16 expression in cancer tissues. Forty-seven FNAs were collected from OPSCC and 16 from CUP patients. Cancer cells were found in 35/47 cases (74.5%), while 11 (23.4%) showed only necrosis, and 1 (2.1%) was negative for malignancy. HPV-DNA was detected in 30/47 FNAs (63.8%), mostly harboring HPV16 (90.0%). An excellent agreement was observed between the FNA and corresponding FFPE HPV status (raw agreement: 97.5%; Cohen K: 0.94). The HPV test result on the necrotic FNAs completely matched that of the respective primary cancer. FNA HPV testing correctly identified 26/27 HPV-driven OPSCCs (96.3%). HPV was detected in 9/16 FNAs (56.2%) from CUP patients. HPV status of metastatic cervical lymph node FNAs reflects that of the corresponding primary OPSCCs even when cell integrity in the FNA is not preserved and only necrotic debris are present. In patients with initial CUP, HPV-positivity on the FNA may guide the diagnostic workup and therapeutic management, since it suggests an oropharyngeal origin. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Gene expression analysis of pancreatic cell lines reveals genes overexpressed in pancreatic cancer.

PubMed

Alldinger, Ingo; Dittert, Dag; Peiper, Matthias; Fusco, Alberto; Chiappetta, Gennaro; Staub, Eike; Lohr, Matthias; Jesnowski, Ralf; Baretton, Gustavo; Ockert, Detlef; Saeger, Hans-Detlev; Grützmann, Robert; Pilarsky, Christian

2005-01-01

Pancreatic cancer is one of the leading causes of cancer-related death. Using DNA gene expression analysis based on a custom made Affymetrix cancer array, we investigated the expression pattern of both primary and established pancreatic carcinoma cell lines. We analyzed the gene expression of 5 established pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-1, Capan-2 and HPAF II) and 5 primary isolates, 1 of them derived from benign pancreatic duct cells. Out of 1,540 genes which were expressed in at least 3 experiments, we found 122 genes upregulated and 18 downregulated in tumor cell lines compared to benign cells with a fold change >3. Several of the upregulated genes (like Prefoldin 5, ADAM9 and E-cadherin) have been associated with pancreatic cancer before. The other differentially regulated genes, however, play a so far unknown role in the course of human pancreatic carcinoma. By means of immunohistochemistry we could show that thymosin beta-10 (TMSB10), upregulated in tumor cell lines, is expressed in human pancreatic carcinoma, but not in non-neoplastic pancreatic tissue, suggesting a role for TMSB10 in the carcinogenesis of pancreatic carcinoma. Using gene expression profiling of pancreatic cell lines we were able to identify genes differentially expressed in pancreatic adenocarcinoma, which might contribute to pancreatic cancer development. Copyright 2005 S. Karger AG, Basel.

Pre-referral GP consultations in patients subsequently diagnosed with rarer cancers: a study of patient-reported data.

PubMed

Mendonca, Silvia C; Abel, Gary A; Lyratzopoulos, Georgios

2016-03-01

Some patients with cancer experience multiple pre-diagnostic consultations in primary care, leading to longer time intervals to specialist investigations and diagnosis. Patients with rarer cancers are thought to be at higher risk of such events, but concrete evidence of this is lacking. To examine the frequency and predictors of repeat consultations with GPs in patients with rarer cancers. Patient-reported data on pre-referral consultations from three English national surveys of patients with cancer (2010, 2013, and 2014), pooled to maximise the sample size of rarer cancers. The authors examined the frequency and crude and adjusted odds ratios for ≥3 (versus 1-2) pre-referral consultations by age, sex, ethnicity, level of deprivation, and cancer diagnosis (38 diagnosis groups, including 12 rarer cancers without prior relevant evidence). Among 7838 patients with 12 rarer cancers, crude proportions of patients with ≥3 pre-referral consultations ranged from >30.0% to 60.0% for patients with small intestine, bone sarcoma, liver, gallbladder, cancer of unknown primary, soft-tissue sarcoma, and ureteric cancer. The range was 15.0-30.0% for patients with oropharyngeal, anal, parotid, penile, and oral cancer. The overall proportion of responders with any cancer who had ≥3 consultations was 23.4%. Multivariable logistic regression indicated concordant patterns, with strong evidence for variation between rarer cancers (P <0.001). Patients with rarer cancers experience pre-referral consultations at frequencies suggestive of middle-to-high diagnostic difficulty. The findings can guide the development of new diagnostic interventions and 'safety-netting' approaches for symptomatic presentations encountered in patients with rarer cancers. © British Journal of General Practice 2016.

Pre-referral GP consultations in patients subsequently diagnosed with rarer cancers: a study of patient-reported data

PubMed Central

Mendonca, Silvia C; Abel, Gary A; Lyratzopoulos, Georgios

2016-01-01

Background Some patients with cancer experience multiple pre-diagnostic consultations in primary care, leading to longer time intervals to specialist investigations and diagnosis. Patients with rarer cancers are thought to be at higher risk of such events, but concrete evidence of this is lacking. Aim To examine the frequency and predictors of repeat consultations with GPs in patients with rarer cancers. Design and setting Patient-reported data on pre-referral consultations from three English national surveys of patients with cancer (2010, 2013, and 2014), pooled to maximise the sample size of rarer cancers. Method The authors examined the frequency and crude and adjusted odds ratios for ≥3 (versus 1–2) pre-referral consultations by age, sex, ethnicity, level of deprivation, and cancer diagnosis (38 diagnosis groups, including 12 rarer cancers without prior relevant evidence). Results Among 7838 patients with 12 rarer cancers, crude proportions of patients with ≥3 pre-referral consultations ranged from >30.0% to 60.0% for patients with small intestine, bone sarcoma, liver, gallbladder, cancer of unknown primary, soft-tissue sarcoma, and ureteric cancer. The range was 15.0–30.0% for patients with oropharyngeal, anal, parotid, penile, and oral cancer. The overall proportion of responders with any cancer who had ≥3 consultations was 23.4%. Multivariable logistic regression indicated concordant patterns, with strong evidence for variation between rarer cancers (P <0.001). Conclusion Patients with rarer cancers experience pre-referral consultations at frequencies suggestive of middle-to-high diagnostic difficulty. The findings can guide the development of new diagnostic interventions and ‘safety-netting’ approaches for symptomatic presentations encountered in patients with rarer cancers. PMID:26917657

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

PubMed

Pritchard, Antonia L; Johansson, Peter A; Nathan, Vaishnavi; Howlie, Madeleine; Symmons, Judith; Palmer, Jane M; Hayward, Nicholas K

2018-01-01

While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and higher overall burden of mutations in all cancer genes. We identified several pathogenic variants that likely predispose to at least one of the tumours in patients with multiple cancers. We additionally present evidence that there may be a higher burden of variants of unknown significance in 'cancer genes' in patients with multiple cancer types. Further screens of this nature need to be carried out to build evidence to show if the cancers observed in these patients form part of a cancer spectrum associated with single germline variants in these genes, whether multiple layers of susceptibility exist (oligogenic or polygenic), or if the occurrence of multiple different cancers is due to random chance.

Metastatic orbital tumors in southern China during an 18-year period.

PubMed

Yan, Jianhua; Gao, Shaohui

2011-09-01

To determine the primary sites, clinical features, treatment, and outcome of 46 patients with cancer metastatic to the orbits in southern China. Retrospective review of medical records at a tertiary center in southern China between Jan 1, 1991 and Dec 31, 2008. The study included 35 males and 11 females, with an age range of 3-78 years (average 47 years). All of the patients came from southern China. The left orbit was affected more frequently than the right orbit (3:2), and no cases were bilaterally involved. The most common primary cancer that metastasizes to the orbit is nasopharyngeal carcinoma (30.34%), followed by lung cancer (8.70%), liver cancer (6.52%), breast carcinoma (4.35%), renal cell cancer (4.35%), medullary thyroid carcinoma (2.17%), lacrimal gland carcinoma (2.17%), stomach carcinoma (2.17%), mediastinum carcinoma (2.17%), other forms (6.52%), and unknown carcinomas (30.34%). Orbital metastasis was the first sign of systemic cancer in 24 patients (52.17%). The five most common clinical findings at the initial examination were abnormal eye position (65.22%), proptosis (63.04%), increased orbital pressure (54.35%), diplopia (54.35%), and limited ocular motility (52.17%), followed by swollen eyelid (50%), visible mass or swelling (46%), blurred vision (41%), conjunctival hyperemia, and edema (35%), pain (28%), blepharoptosis (20%), papilledema (17%), and vasodilatation of the retina (7%). Primary treatment included surgical excision, radiotherapy, systemic chemotherapy, and observation. Among the patients (78% of 46) with sufficient follow-up time (mean 20.7 months), 30.56% of them died of disseminated metastasis. Twenty-five percent of them were in remission with no active metastases and 27.78% of them were living with active metastases. Overall, the mean survival time was 18 months (range, 5-38 months) after diagnosis of orbital metastasis. The most common primary cancer that metastasizes to the orbit is nasopharyngeal carcinoma (30.34%), followed by lung cancer (8.70%) and liver cancer (6.52%) in southern China. Orbital metastasis can display a variety of clinical features and should be considered in patients with known systemic cancer. The systemic prognosis is generally poor.

Does endoscopic ultrasound improve detection of locally recurrent anal squamous-cell cancer?

PubMed

Peterson, Carrie Y; Weiser, Martin R; Paty, Philip B; Guillem, Jose G; Nash, Garrett M; Garcia-Aguilar, Julio; Patil, Sujata; Temple, Larissa K

2015-02-01

Evaluating patients for recurrent anal cancer after primary treatment can be difficult owing to distorted anatomy and scarring. Many institutions incorporate endoscopic ultrasound to improve detection, but the effectiveness is unknown. The aim of this study is to compare the effectiveness of digital rectal examination and endoscopic ultrasound in detecting locally recurrent disease during routine follow-up of patients with anal cancer. This study is a retrospective, single-institution review. This study was conducted at an oncologic tertiary referral center. Included were 175 patients with nonmetastatic anal squamous-cell cancer, without persistent disease after primary chemoradiotherapy, who had at least 1 posttreatment ultrasound and examination by a colorectal surgeon. The primary outcomes measured were the first modality to detect local recurrence, concordance, crude cancer detection rate, sensitivity, specificity, and predictive value. Eight hundred fifty-five endoscopic ultrasounds and 873 digital rectal examinations were performed during 35 months median follow-up. Overall, ultrasound detected 7 (0.8%) mesorectal and 32 (3.7%) anal canal abnormalities; digital examination detected 69 (7.9%) anal canal abnormalities. Locally recurrent disease was found on biopsy in 8 patients, all detected first or only with digital examination. Four patients did not have an ultrasound at the time of diagnosis of recurrence. The concordance of ultrasound and digital examination in detecting recurrent disease was fair at 0.37 (SE, 0.08; 95% CI, 0.21-0.54), and there was no difference in crude cancer detection rate, sensitivity, specificity, and negative or positive predictive values. The heterogeneity of follow-up timing and examinations is not standardized in this study but is reflective of general practice. Endoscopic ultrasound did not provide any advantage over digital rectal examination in identifying locally recurrent anal cancer, and should not be recommended for routine surveillance.

Clonal evolution and heterogeneity in metastatic head and neck cancer-An analysis of the Austrian Study Group of Medical Tumour Therapy study group.

PubMed

Melchardt, Thomas; Magnes, Teresa; Hufnagl, Clemens; Thorner, Aaron R; Ducar, Matthew; Neureiter, Daniel; Tränkenschuh, Wolfgang; Klieser, Eckhard; Gaggl, Alexander; Rösch, Sebastian; Rasp, Gerd; Hartmann, Tanja N; Pleyer, Lisa; Rinnerthaler, Gabriel; Weiss, Lukas; Greil, Richard; Egle, Alexander

2018-04-01

Tumour heterogeneity and clonal evolution within a cancer patient are deemed responsible for relapse in malignancies and present challenges to the principles of targeted therapy, for which treatment modality is often decided based on the molecular pathology of the primary tumour. Nevertheless, the clonal architecture in distant relapse of head and neck cancer is fairly unknown. For this project, we analysed a cohort of 386 patients within the Austrian Registry of head and neck cancer. We identified 26 patients with material from the primary tumour, the distant metastasis after curative first-line treatment and a germline sample for analysis of clonal evolution. After pathological analyses, these samples were analysed using a targeted massively parallel sequencing (MPS) panel of 257 genes known to be recurrently mutated in head and neck cancer plus a genome-wide SNP-set. Despite histological diagnosis of distant metastasis, no corresponding mutation in the supposed metastases was found in two of 23 (8.6%) evaluable patients suggesting a primary tumour of the lung instead of a distant metastasis of head and neck cancer. We observed a branched pattern of evolution in 31.6% of the analysed patients. This pattern was associated with a shorter time to distant metastasis, compared with a pattern of punctuated evolution. Structural genomic changes over time were also present in 7 of 12 (60%) evaluable patients with metachronous metastases. Targeted MPS demonstrated substantial heterogeneity at the time of diagnosis and a complex pattern of evolution during disease progression in head and neck cancer. Copy number analyses revealed additional changes that were not detected by mutational analyses. Mutational and structural changes contribute to tumour heterogeneity at diagnosis and progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Feasibility of using negative ultrasonography results of axillary lymph nodes to predict sentinel lymph node metastasis in breast cancer patients.

PubMed

Chen, Xue; He, Yingjian; Wang, Jiwei; Huo, Ling; Fan, Zhaoqing; Li, Jinfeng; Xie, Yuntao; Wang, Tianfeng; Ouyang, Tao

2018-06-14

Knowledge of the pathology of axillary lymph nodes (ALN) in breast cancer patients is critical for determining their treatment. Ultrasound is the best noninvasive evaluation for the ALN status. However, the correlation between negative ultrasound results and the sentinel lymph nodes (SLN) pathology remains unknown. To test the hypothesis that negative ultrasound results of ALN predict the negative pathology results of SLN in breast cancer patients, we assessed the association between ALN ultrasonography-negative results and the SLN pathology in 3115 patients with breast cancer recruited between October 2010 and April 2016 from a single cancer center, prospective database. Of these patients who met the inclusion criteria, 2317 (74.4%) had no SLN pathological metastasis. In the univariate analysis, other 798 patient with positive SLN tended to be under age 40 and premenopausal, having large tumor sizes (>2 cm), higher histological grade of primary tumor, positive hormone receptors, and negative HER-2 status (P < .05 for all). In the multivariate analysis, menstrual status, tumor size, ER status and histological types of primary tumor remained to be independent predictors for SLN pathological metastasis. The area under curve (AUC) was 0.658 (95% CI = 0.637-0.679), P > .05. In conclusion, only a 74.4% consistency between ALN ultrasonography-negative results and negative pathological SLN results, although menstrual status, tumor size, histologic subtypes of primary tumor and ER status were found to be statistically independent predictors of positive SLN among patients negative for ALN ultrasonography. Therefore, the present study suggests that negative ultrasound results of ALN do not adequately predict the negative pathology results of SLN in breast cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

[A Case of Cystic Cervical Lymph Node Metastasis of HPV-positive Tonsil Cancer, Being Discriminated as the Branchiogenic Carcinoma].

PubMed

Kambara, Rumi; Tamai, Masamitsu; Horii, Arata

2016-02-01

In recent years, human papillomavirus (HPV)-positive oropharyngeal carcinomas have been increasing. The first manifestation of these tumors is frequently as cystic metastasis to cervical lymph nodes that may precede recognition of the primary tumor, so, they often result in misdiagnosis as branchial cleft cysts. We report a case of cystic cervical lymph node metastasis of HPV-positive tonsil cancer. The patient was a 70-years-old man who noticed a mass on his left neck. The tumor was large and soft, and it was diagnosed as benign in fine-needle aspiration cytology. We diagnosed the tumor as a branchial cleft cyst and undertook surgery. The histopathological diagnosis was squamous cell carcinoma arising from a branchiogenic cyst. However, because it did not satisfy the diagnostic criteria, we diagnosed the tumor as an unknown primary tumor. One year later, left tonsil cancer was suspected based on PET-CT imaging and a left tonsillectomy was undertaken, whereafter tonsil cancer was found. In p16 immunostaining, it was positive in both cystic mass and tonsil. The cervical mass was cystic lymph node metastasis of HPV-positive tonsil cancer. It is important to investigate the oropharynx, when we found cystic cervical mass, because HPV-positive oropharyngeal carcinoma frequently results in cystic neck metastasis.

Heat shock protein 27 regulates human prostate cancer cell motility and metastatic progression

PubMed Central

Voll, Eric A; Ogden, Irene M; Pavese, Janet M; Huang, XiaoKe; Xu, Li; Jovanovic, Borko D; Bergan, Raymond C

2014-01-01

Prostate cancer (PCa) is the most common form of cancer in American men. Mortality from PCa is caused by the movement of cancer cells from the primary organ to form metastatic tumors at distant sites. Heat shock protein 27 (HSP27) is known to increase human PCa cell invasion and its overexpression is associated with metastatic disease. The role of HSP27 in driving PCa cell movement from the prostate to distant metastatic sites is unknown. Increased HSP27 expression increased metastasis as well as primary tumor mass. In vitro studies further examined the mechanism of HSP27-induced metastatic behavior. HSP27 did not affect cell detachment, adhesion, or migration, but did increase cell invasion. Cell invasion was dependent upon matrix metalloproteinase 2 (MMP-2), whose expression was increased by HSP27. In vivo, HSP27 induced commensurate changes in MMP-2 expression in tumors. These findings demonstrate that HSP27 drives metastatic spread of cancer cells from the prostate to distant sites, does so across a continuum of expression levels, and identifies HSP27-driven increases in MMP-2 expression as functionally relevant. These findings add to prior studies demonstrating that HSP27 increases PCa cell motility, growth and survival. Together, they demonstrate that HSP27 plays an important role in PCa progression. PMID:24798191

Germline genetics of cancer of unknown primary (CUP) and its specific subtypes.

PubMed

Hemminki, Kari; Chen, Bowang; Kumar, Abhishek; Melander, Olle; Manjer, Jonas; Hallmans, Göran; Pettersson-Kymmer, Ulrika; Ohlsson, Claes; Folprecht, Gunnar; Löffler, Harald; Krämer, Alwin; Försti, Asta

2016-04-19

Cancer of unknown primary site (CUP) is a fatal cancer diagnosed through metastases at various organs. Little is known about germline genetics of CUP which appears worth of a search in view of reported familial associations in CUP. In the present study, samples from CUP patients were identified from 2 Swedish biobanks and a German clinical trial, totaling 578 CUP patients and 7628 regionally matched controls. Diagnostic data specified the organ where metastases were diagnosed. We carried out a genome-wide association study on CUP cases and controls. In the whole sample set, 6 loci reached an allelic p-value in the range of 10-7 and were supported by data from the three centers. Three associations were located next to non-coding RNA genes. rs2660852 flanked 5'UTR of LTA4H (leukotriene A4 hydrolase), rs477145 was intronic to TIAM1 (T-cell lymphoma invasion and metastases) and rs2835931 was intronic to KCNJ6 (potassium channel, inwardly rectifying subfamily J, member 6). In analysis of subgroups of CUP patients (smokers, non-smokers and CUP with liver metastases) genome-wide significant associations were noted. For patients with liver metastases associations on chromosome 6 and 11, the latter including a cluster of genes DHCR7 and NADSYN1, encoding key enzymes in cholesterol and NAD synthesis, and KRTAP5-7, encoding a keratin associated protein. This first GWAS on CUP provide preliminary evidence that germline genes relating to inflammation (LTA4H), metastatic promotion (TIAM1) in association with lipid metabolic disturbance (chromosome 11 cluster) may contribute to the risk of CUP.

A case of metastatic lobular breast carcinoma with detection of the primary tumor after ten years.

PubMed

Kobayashi, Tetsuro; Adachi, Shiro; Matsuda, Yasuki; Tominaga, Syusei

2007-01-01

Lobular carcinoma of the breast is known to metastasize to unusual sites such as the gastrointestinal tract, peritoneum, and gynecologic organs. We report a patient with intraperitoneal metastases from lobular carcinoma who was originally treated for an unknown primary cancer. Ten years later, a tumor was found in her left breast and the diagnosis was changed to peritoneal metastases from invasive lobular carcinoma. Immunohistochemistry revealed that the metastases were high molecular weight cytokeratin (CK34betaE12) and estrogen receptor-positive, but were E-cadherin-negative. These results assisted in diagnosis. Surgeons should be aware of the characteristics of metastasis lobular carcinoma.

Validity of self-reported fertility-threatening cancer treatments in female young adult cancer survivors.

PubMed

Roberts, Samantha C; Knight, Amber; Whitcomb, Brian W; Gorman, Jessica R; Dietz, Andrew C; Irene Su, H

2017-08-01

Detailed cancer treatment information is important to fertility and pregnancy care of female young adult cancer survivors. Accuracy of self-report of treatments that impact fertility and pregnancy is unknown. This study assessed agreement between self-report and medical records on receipt of fertility-threatening treatments. A national cohort study of female young adult cancer survivors reported cancer treatments via Web-based questionnaires. Primary cancer treatment records were abstracted. Self-reported exposure to fertility-threatening therapies (alkylating chemotherapy, stem cell transplant, pelvic radiation, hysterectomy, and/or oophorectomy) was compared to medical records. Logistic regression models estimated odds ratios (OR) for characteristics associated with inaccurate self-report of fertility-threatening therapies. The study included 101 survivors (mean age 28.2, SD 6.3). Lymphoma (33%), breast cancer (26%), and gynecologic cancers (10%) were the most common cancers. Accuracy of self-report was 68% for alkylating chemotherapy and 92-97% for radiation, surgery, and transplant. Significant proportions of survivors who were treated with transplant (8/13, 62%), alkylating chemotherapy (18/43, 42%), pelvic radiation (4/13, 31%), or hysterectomy and/or oophorectomy (3/13, 23%) did not report undergoing these therapies. In adjusted analysis, age ≤ 25 at diagnosis (OR 3.4, 95% CI 1.3-8.7) and recurrence (OR 6.0, 95% CI 1.5-24.4) were related to inaccurate self-report. Female young adult cancer survivors have limited recall of fertility-threatening cancer treatment exposures. Reproductive health providers and researchers who need this information may require primary medical records or treatment summaries. Additional patient education regarding treatment-related reproductive risks is needed to facilitate patient engagement in survivorship. Obtaining a cancer treatment summary will help survivors communicate their prior treatment exposures to reproductive healthcare providers.

Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status

PubMed Central

Fehm, Tanja; Becker, Sven; Duerr-Stoerzer, Silke; Sotlar, Karl; Mueller, Volkmar; Wallwiener, Diethelm; Lane, Nancy; Solomayer, Erich; Uhr, Jonathan

2007-01-01

Introduction At the time when metastatic disease is identified, assessment of human epidermal growth factor receptor (HER)2 status might help to optimize treatment decisions if HER2 status was not determined at first diagnosis and if HER2 positivity has been acquired during disease progression. Within this context, determination of serum HER2 or evaluation of HER2 status in circulating tumor cells (CTCs) may be of clinical relevance because metastatic tissue may be difficult to obtain for analysis as a result of its localization. The aim of this study was therefore to determine the HER2 status in serum and corresponding CTCs in patients with metastatic breast cancer whose primary tumors were HER2 negative or of unknown HER2 status. Methods Blood samples were obtained from 77 metastatic breast cancer patients with negative (n = 44) or unknown (n = 33) HER2 status. Serum HER2 was determined using a commercial HER2/neu ELISA kit. CTCs were detected by slide-based assay using immunomagnetic enrichment and characterized by phenotyping and genotyping. Alternatively, a commercial kit, based on RT-PCR, was used to detect and characterize CTCs. Results Twenty out of 77 patients with metastatic disease had elevated serum levels of HER2. Blood samples could be analyzed for the presence of CTCs in 67 patients. Eight out of 21 patients with detectable CTCs exhibited HER2 amplification. Twenty-three out of 77 patients were HER2 positive using at least one method. Concordance between HER2 status of CTCs and serum HER2 was observed in 15 of 21 patients (71%). In six patients conflicting results were obtained. Three patients with elevated serum HER2 status had HER2-negative CTCs, whereas three patients with HER2-positive CTCs had normal serum HER2 levels. Conclusion A subgroup of patients with initially negative or unknown HER2 status can have elevated serum HER2 levels and/or HER2-positive CTCs at the time of development of metastatic disease. Although only a small number of patients were studied, our observations are of clinical relevance because, currently, these patients do not have access to HER2-targeted therapy. PMID:17963511

Laparoscopic resection of synchronous colorectal cancers in separate specimens.

PubMed

Inada, Ryo; Yamamoto, Seiichiro; Takawa, Masashi; Fujita, Shin; Akasu, Takayuki

2014-08-01

Laparoscopic approaches are increasingly being used in patients with colorectal cancer, but the feasibility of laparoscopic resection of synchronous colorectal cancers in separate specimens remains unknown. In such cases, it is necessary to consider the site of port placement, sequence of dissection, choice of specimen extraction sites, specimen handling, and extracorporeal anastomosis sites. Moreover, the need for complete mesenteric dissection in two areas, removal of two separate specimens containing malignancies, and two anastomoses elicit unique questions related to technical considerations. The aim of this study was to determine the feasibility of laparoscopic resection of two separate specimens containing malignancies for multiple synchronous colorectal cancers. Between June 2001 and January 2013, 1341 patients with colorectal cancer underwent laparoscopic surgery at our institution. Of them, 11 patients underwent laparoscopy-assisted combined resection of two separate colorectal specimens for multiple synchronous primary colorectal cancers. We retrospectively reviewed their surgical outcomes. All procedures were completed laparoscopically without perioperative mortality. Patients underwent right-sided colon resection for right-sided cancer and left-sided or rectal resection for left-sided colon or rectal cancer. The median duration of surgery was 296 min, and the median blood loss was 65 mL. Median time to first postoperative liquid and solid intake was 1 day and 3 days, respectively. Most patients were discharged on postoperative day 8. With regard to postoperative complications, two patients had a surgical-site infection. Laparoscopic resection of two separate colorectal specimens for multiple synchronous primary colorectal cancers is a feasible and safe procedure. © 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

Gene expression profiles help identify the tissue of origin for metastatic brain cancers.

PubMed

Wu, Alan H B; Drees, Julia C; Wang, Hangpin; VandenBerg, Scott R; Lal, Anita; Henner, William D; Pillai, Raji

2010-04-26

Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

PubMed Central

2010-01-01

Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers. PMID:20420692

Preoperative tumour staging with multidisciplinary team assessment improves the outcome in locally advanced primary rectal cancer.

PubMed

Palmer, G; Martling, A; Cedermark, B; Holm, T

2011-12-01

Multidisciplinary team meetings have been introduced as a result of developments in preoperative radiological tumour staging and neoadjuvant treatment. Multidisciplinary team recommendations will influence treatment decisions but their effect on patient outcome is unknown. The aim of this study was to assess outcome in relation to preoperative local and distant staging, with or without multidisciplinary team assessment. A population-based registry of all patients with rectal cancer, treated in the Stockholm region from 1995 to 2004, identified 303 patients with locally advanced primary rectal cancer. The patients were classified into three groups: group 1, preoperative local and distant radiological tumour staging with discussion at a multidisciplinary team meeting; group 2, preoperative staging but no multidisciplinary team assessment; and group 3, no proper preoperative radiological staging. Neoadjuvant treatment was more prevalent in groups 1 and 2 than in group 3. The incidence of R0 resection differed significantly between the groups (52% in group 1, 43% in group 2 and 21% in group 3; P < 0.001). Local tumour control was achieved in 57%, 36%, and 19% of patients in groups 1, 2 and 3, respectively (P < 0.001). The estimated overall 5-year survival of patients was 30%, 28% and 12% in groups 1, 2 and 3, respectively. Preoperative radiological tumour staging in patients with locally advanced primary rectal cancer and discussion at a multidisciplinary team meeting increases the proportion of patients receiving neoadjuvant treatment and cancer-specific end-points. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Malignant Transformation and Stromal Invasion from Normal or Hyperplastic Tissues: True or False?

PubMed Central

Man, Yan-gao; Grinkemeyer, Michael; Izadjoo, Mina; Stojadinovic, Alexander

2011-01-01

Carcinogenesis is believed to be a multi-step process, progressing sequentially from normal to hyperplastic, to in situ, and to invasive stages. A number of studies, however, have detected malignancy-associated alterations in normal or hyperplastic tissues. As the molecular profile and clinical features of these tissues have not been defined, the authors invited several well-recognized pathologist, oncologists, biologist, surgeons, and molecular biologist to offer their opinion on: (1) whether these tissues belong to a previously unrevealed malignant entity or focal alterations with no significant consequence? (2) whether these alterations are linked to early onset of cancer or cancer of unknown primary site, and (3) how to further define these lesions? PMID:21811519

Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies.

PubMed

Lakatos, Peter-Laszlo; Lakatos, Laszlo

2008-07-07

The risk of colorectal cancer for any patient with ulcerative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer include extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflammation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epidemiological trends and causes for the observed changes. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this change is unknown; it may partly be explained by the more widespread use of maintenance therapy and surveillance colonoscopy.

The role of cytokeratins 20 and 7 and estrogen receptor analysis in separation of metastatic lobular carcinoma of the breast and metastatic signet ring cell carcinoma of the gastrointestinal tract.

PubMed

Tot, T

2000-06-01

Metastatic signet ring cell carcinomas of unknown primary site can represent a clinical problem. Gastrointestinal signet ring cell carcinomas and invasive lobular carcinomas of the breast are the most common sources of these metastases. Immunohistochemical algorithms have been successfully used in the search for the unknown primary adenocarcinomas. In the present study a series of primary invasive lobular breast carcinomas (79 cases) and their metastases and a series of gastrointestinal signet ring cell carcinomas (22 primary and 13 metastases) were stained with monoclonal antibodies for cytokeratin (CK) 20 and CK7 and for estrogen receptors (ER). The staining was evaluated as negative (no staining), focally (less than 10% of the tumor cells stained) or diffusely positive. All the primary and metastatic gastrointestinal signet ring cell carcinomas proved to be CK20 positive, while only 2/79 (3%) of the primary and 1/21 metastatic lobular carcinomas (5%) stained positively for this CK. None of the gastrointestinal carcinomas and the majority of the lobular carcinomas expressed ER. The majority of the tumors were CK7+. Using CK20 alone, 33 of 34 metastases could be properly classified as gastrointestinal (CK20+) or mammary (CK20-). ER identified 31/34 of breast cancer metastases. By combining the results of CK20 and ER staining all the metastases could be properly classified as the CK20+/ER- pattern identified all the gastrointestinal tumors.

Combined p16 and p53 expression in cervical cancer of unknown primary and other prognostic parameters : A single-center analysis.

PubMed

Yildirim, Müjdat; Müller von der Grün, Jens; Winkelmann, Ria; Fokas, Emmanouil; Rödel, Franz; Ackermann, Hanns; Rödel, Claus; Balermpas, Panagiotis

2017-04-01

Cervical cancer of unknown primary (CUP) represents an uncommon and heterogeneous subentity of head and neck cancer. However, both optimal diagnostics and therapy remain unclear. An improved understanding of the underlying pathology is essential to enable future tailored therapies and optimized outcomes. We retrospectively analyzed 53 patients with head and neck CUP and 48 available cervical lymph node specimens. All patients have received radiotherapy between 2007 and 2015. Preradiotherapy involved lymph node specimens were analyzed for p16 and p53 immunoreactivity. The prognostic relevance of the combined p16 and p53 status and other clinical parameters were examined by univariate and multivariate analyses. Median patient age was 61.5 years and median irradiation dose to the involved nodal levels was 66 Gy. Of the 48 evaluated specimens, 13 (27%) were p16-positive and 31 (64.6%) p53-positive. After a median follow up of 32.9 months, patients with p16-negative and simultaneously p53-positive tumors showed a significantly inferior tumor-specific survival (TSS) compared to those with either p16+/p53-, p16+/p53+, or p16-/p53- (univariate: p = 0.055, multivariate: p = 0.038). Other factors with an adverse impact on TSS in the univariate analysis were smoking history (p = 0.032) and nodal stage (p = 0.038). The combined p16- and p53-expression status in cervical metastases of CUP may represent a simple method for risk stratification. Further validation of these biomarkers in large prospective trials is essential to design rational trials for CUP treatment optimization.

[Safe and effective administration of carboplatin-based chemotherapy in a patient undergoing hemodialysis with cancer of unknown primary by monitoring observed AUC of carboplatin-a case report].

PubMed

Kondo, Masahiro; Kuroda, Junko; Ikai, Yoshitomo; Hayashi, Rumiko; Uegaki, Shiori; Yoshida, Tatsuya; Yoshida, Atsuhiro; Komatsu, Hirokazu; Kimura, Kazunori

2012-11-01

Here we report a case of successful treatment with combination chemotherapy of carboplatin(CBDCA)and paclitaxel for a patient undergoing hemodialysis(HD)with cancer of unknown primary, conducted by monitoring the observed AUC of ultrafilterable CBDCA. CBDCA was administered at a dose of 125 mg on day 1 in each course, an amount which had been calculated by the Calvert formula(GFR: 0, target AUC: 5). HD was started at a point in time one hour after the completion of each CBDCA administration, and performed for 5 hours in each course. Blood samples were collected during the first 3 courses of chemotherapy to measure the plasma concentration of free-platinum. The observed AUCs(o-AUC)of CBDCA in the first, second and third courses were 3. 03, 3. 44 and 3. 50mg·min/mL, respectively. The o-AUC in the first course was lower than that in the second course. The o-AUC in the second course was nearly equal to that in the third course, while each o-AUC was below the target AUC(t-AUC). Partial response was achieved after two courses of the CBDCA and paclitaxel combination chemotherapy, with adverse events of Grade 3 neutropenia and Grade 3 peripheral neuropathy observed in each course after the second course of chemotherapy. o-AUC of CBDCA administered to HD patients can not only be below t-AUC, as in this case, but also oppositely above t-AUC in cases with different doses of CBDCA or HD settings. Our results suggest that the monitoring of o-AUC of CBDCA is useful when practicing CBDCA-based chemotherapy safely and effectively in cancer patients undergoing HD.

Cervical lymph node metastases of squamous cell carcinoma from an unknown primary: outcomes and patterns of failure.

PubMed

Mistry, R C; Qureshi, S S; Talole, S D; Deshmukh, S

2008-01-01

Management of cervical lymph nodes metastases of squamous cell carcinoma (SCC) from primary of unknown origin (PUO) is contentious and there is insignificant data from India on this subject. To present experience of management of these patients treated with curative intent at a single institution. Retrospective study of patients treated between 1989-1994 in a tertiary referral cancer centre. Eighty-nine patients were evaluated in the study period and their survival compared with patients with common sites of primary in the head and neck with comparable node stage. Kaplan-Meier method. The clinical stage of the neck nodes at presentation was N1 in 11%, N2a in 28.5%, N2b in 22.5%, N3 in 35% and Nx in 3.4% patients. All patients underwent surgery and 70 patients received more than 40Gy postoperative radiotherapy. Twenty-nine (32.6%) patients had relapse of which 19 (21%) were in the neck. Postoperative radiotherapy did not influence the neck relapse (p=0.72). Primary was detected in 13 patients (14.6%) on subsequent follow up. The overall five and eight-years survival was 55% and 51% respectively. The overall five-year survival was better compared to patients with known primary with comparable node stage. Patients with cervical lymph nodes metastases of SCC from PUO have reasonable survival and low rate of development of subsequent primary when treated with surgery and radiotherapy. The overall survival is comparable to that of patients with known primary and hence an attempt at cure should always be made.

Clinical factors impacting on late dysphagia following radiotherapy in patients with head and neck cancer.

PubMed

Deschuymer, Sarah; Nevens, Daan; Duprez, Fréderic; Laenen, Annouschka; Dejaeger, Eddy; De Neve, Wilfried; Goeleven, Ann; Nuyts, Sandra

2018-05-23

Patient and treatment characteristics of patients with head and neck cancer (HNSCC) were correlated with dysphagia scored on swallowing-videofluoroscopy (VFS) and with patient- and physician-scored dysphagia. 63 HNSCC patients treated with radiotherapy (RT) were evaluated at baseline, and 6 and 12 months post-RT. VFS was scored with Penetration Aspiration Scale (PAS) and Swallowing Performance Scale (SPS). Physician- and patient-scored dysphagia were prospectively recorded according to Common Terminology Criteria for Adverse Events scoring system, Radiation Therapy Oncology Group/EORTC scoring system and European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ H&N35). Univariable analysis revealed a significant association between tumour-subsite and higher SPS (p = 0.02) and patient-scored dysphagia (p = 0.02) at baseline. At 12 months, tumour-subsite was significantly associated with higher PAS and SPS. Multivariable analysis and pairwise comparison showed that hypopharyngeal cancer and carcinoma of unknown primary  were associated with higher SPS at baseline and at 12 months, respectively (p = 0.03 and p = 0.01). Upfront neck dissection (UFND) was significantly associated with higher SPS and physician-scored dysphagia in univariable analysis at all timepoints. At 12 months, there was also a significant association with higher PAS (p < 0.01) and patient-scored dysphagia (p < 0.01). After multivariable analysis, the association between UFND and higher PAS (p < 0.01) and SPS (p < 0.01) remained significant at 12 months. Hypopharyngeal tumours and carcinoma of unknown primary were related to more dysphagia at baseline and at 12 months, respectively. Furthermore, UFND was associated with more severe dysphagia scored by physicians and patients and on VFS at 12 months. Advances in knowledge: This is the first paper reporting a significant link between UFND and late dysphagia scored with VFS. We advocate abandoning UFND and preserving neck dissection as a salvage option post-RT.

Identification of Occupational Cancer Risks in British Columbia, Canada: A Population-Based Case—Control Study of 1,155 Cases of Colon Cancer

PubMed Central

Fang, Raymond; Le, Nhu; Band, Pierre

2011-01-01

Objective Cancer has been recognized to have environmental origin, but occupational cancer risk studies have not been fully documented. The objective of this paper was to identify occupations and industries with elevated colon cancer risk based on lifetime occupational histories collected from 15,463 incident cancer cases. Method A group matched case-control design was used. All cases were diagnosed with histologically proven colon cancers, with cancer controls being all other cancer sites, excluding rectum, lung and unknown primary, diagnosed at the same period of time from the British Columbia Cancer Registry. Data analyses were done on all 597 Canadian standard occupation titles and 1,104 standard industry titles using conditional logistic regression for matched data sets and the likelihood ratio test. Results Excess colon cancer risks was observed in a number of occupations and industries, particularly those with low physical activity and those involving exposure to asbestos, wood dusts, engine exhaust and diesel engine emissions, and ammonia. Discussion The results of our study are in line with those from the literature and further suggest that exposure to wood dusts and to ammonia may carry an increased occupational risk of colon cancer. PMID:22073015

p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary.

PubMed

McDowell, Lachlan J; Young, Richard J; Johnston, Meredith L; Tan, Tze-Jian; Kleid, Stephen; Liu, Chen S; Bressel, Mathias; Estall, Vanessa; Rischin, Danny; Solomon, Benjamin; Corry, June

2016-04-15

The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site. © 2016 American Cancer Society.

Efficacy and Toxicity of Chemoradiotherapy Using Intensity-Modulated Radiotherapy for Unknown Primary of Head and Neck

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

Sher, David J., E-mail: dsher@lroc.harvard.edu; Balboni, Tracy A.; Haddad, Robert I.

2011-08-01

Purpose: No single standard treatment paradigm is available for head-and-neck squamous cell carcinoma of an unknown primary (HNCUP). Bilateral neck radiotherapy with mucosal axis irradiation is widely used, with or without chemotherapy and/or surgical resection. Intensity-modulated radiotherapy (IMRT) is a highly conformal method for delivering radiation that is becoming the standard of care and might reduce the long-term treatment-related sequelae. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for HNCUP. Patients and Materials: A retrospective study of all patients treated at the Dana-Farber Cancer Institute for HNCUP with IMRT between August 2004 and January 2009. The primary endpointmore » was overall survival; the secondary endpoints were locoregional and distant control, and acute and chronic toxicity. Results: A total of 24 patients with HNCUP were included. Of these patients, 22 had Stage N2 disease or greater. All patients underwent neck computed tomography, positron emission tomography-computed tomography, and examination under anesthesia with directed biopsies. Of the 24 patients, 22 received concurrent chemotherapy, and 7 (29%) also underwent induction chemotherapy. The median involved nodal dose was 70 Gy, and the median mucosal dose was 60 Gy. With a median follow-up of 2.1 years, the 2-year actuarial overall survival and locoregional control rate was 92% and 100%, respectively. Only 25% of the patients had Grade 2 xerostomia, although 11 patients (46%) required esophageal dilation for stricture. Conclusion: In a single-institution series, IMRT-based chemoradiotherapy for HNCUP was associated with superb overall survival and locoregional control. The xerostomia rates were promising, but the aggressive therapy was associated with significant rates of esophageal stenosis.« less

CD22 antigen is broadly expressed on lung cancer cells and is a target for antibody-based therapy.

PubMed

Tuscano, Joseph M; Kato, Jason; Pearson, David; Xiong, Chengyi; Newell, Laura; Ma, Yunpeng; Gandara, David R; O'Donnell, Robert T

2012-11-01

Most patients with lung cancer still die from their disease, necessitating additional options to improve treatment. Here, we provide evidence for targeting CD22, a cell adhesion protein known to influence B-cell survival that we found is also widely expressed in lung cancer cells. In characterizing the antitumor activity of an established anti-CD22 monoclonal antibody (mAb), HB22.7, we showed CD22 expression by multiple approaches in various lung cancer subtypes, including 7 of 8 cell lines and a panel of primary patient specimens. HB22.7 displayed in vitro and in vivo cytotoxicity against CD22-positive human lung cancer cells and tumor xenografts. In a model of metastatic lung cancer, HB22.7 inhibited the development of pulmonary metastasis and extended overall survival. The finding that CD22 is expressed on lung cancer cells is significant in revealing a heretofore unknown mechanism of tumorigenesis and metastasis. Our work suggests that anti-CD22 mAbs may be useful for targeted therapy of lung cancer, a malignancy that has few tumor-specific targets. ©2012 AACR.

The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

PubMed

Birnbaum, Jeanette; Gadi, Vijayakrishna K; Markowitz, Elan; Etzioni, Ruth

2016-02-16

Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. U.S. women aged 50 to 74 years. 10 and 25 years. Population. Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Disease models simplify reality and cannot capture all breast cancer subtypes. Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. University of Washington and National Cancer Institute.

New oral anticoagulants in patients with cancer: current state of evidence.

PubMed

Sardar, Partha; Chatterjee, Saurav; Herzog, Eyal; Pekler, Gerald; Mushiyev, Savi; Pastori, Luciano J; Visco, Ferdinand; Aronow, Wilbert S

2015-01-01

Effectiveness of new oral anticoagulants (NOAC) in patients with cancer is not clearly defined. There remain concerns of doubtful benefit and chances of potential harm with newer agents. In this meta-analysis, we evaluated the efficacy and safety of NOAC in patients with cancer. PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched from January 01, 2001 through February 28, 2013. Randomized controlled trials reporting efficacy and safety data of NOACs (rivaroxaban, dabigatran, and apixaban) with control (low-molecular-weight heparin/vitamin K antagonists/placebo) for patients with cancer were included. Primary efficacy outcome was venous thromboembolism (VTE) or VTE-related death, and primary safety outcome was clinically relevant bleeding. We used random-effects models. Six trials randomized 19,832 patients, and 1197 patients had cancer. Risk of VTE or VTE-related death was not significantly different with NOAC versus control [odds ratio (OR), 0.80; 95% confidence interval (CI), 0.39-1.65] in patients with cancer. Separate analysis for individual effects showed similar results for rivaroxaban (OR, 1.08; 95% CI, 0.60-1.94) and dabigatran (OR, 0.91; 95% CI, 0.21-3.91). Clinically relevant bleeding was not higher with NOAC compared with control (OR, 1.49; 95% CI, 0.82-2.71); individual effect of rivaroxaban showed similar results. No statistically significant difference of efficacy and safety with NOAC was found between patients with and without cancer. Rivaroxaban might be equally effective and safe as vitamin K antagonist in patients with cancer. Dabigatran is as effective as comparator; however, safety profile of dabigatran is unknown. Randomized trials of new anticoagulants specific to the cancer population are necessary, and NOAC also need to be evaluated against low-molecular-weight heparin.

Patterns of Cancer in Kurdistan - Results of Eight Years Cancer Registration in Sulaymaniyah Province-Kurdistan-Iraq.

PubMed

Khoshnaw, Najmaddin; Mohammed, Hazha A; Abdullah, Dana A

2015-01-01

Cancer has become a major health problem associated with high mortality worldwide, especially in developing countries. The aim of our study was to evaluate the incidence rates of different types of cancer in Sulaymaniyah from January-2006 to January-2014. The data were compared with those reported for other middle east countries. This retrospective study depended on data collected from Hiwa hospital cancer registry unit, death records and histopathology reports in all Sulaymaniyah teaching hospitals, using international classification of diseases. A total of 8,031 cases were registered during the eight year period, the annual incidence rate in all age groups rose from 38 to 61.7 cases/100,000 population/year, with averages over 50 in males and 50.7 in females. The male to female ratio in all age groups were 0.98, while in the pediatric age group it was 1.33. The hematological malignancies in all age groups accounted for 20% but in the pediatric group around half of all cancer cases. Pediatric cancers were occluding 7% of total cancers with rates of 10.3 in boys and 8.7 in girls. The commonest malignancies by primary site were leukemia, lymphoma, brain, kidney and bone. In males in all age groups they were lung, leukaemia, lymphoma, colorectal, prostate, bladder, brain, stomach, carcinoma of unknown primary (CUP) and skin, while in females they were breast, leukaemia, lymphoma, colorectal, ovary, lung, brain, CUP, and stomach. Most cancers were increased with increasing age except breast cancer where decrease was noted in older ages. High mortality rates were found with leukemia, lung, lymphoma, colorectal, breast and stomach cancers. We here found an increase in annual cancer incidence rates across the period of study, because of increase of cancer with age and higher rates of hematological malignancies. Our study is valuable for Kurdistan and Iraq because it provides more accurate data about the exact patterns of cancer and mortality in our region.

Tissue-specific mutation accumulation in human adult stem cells during life

NASA Astrophysics Data System (ADS)

Blokzijl, Francis; de Ligt, Joep; Jager, Myrthe; Sasselli, Valentina; Roerink, Sophie; Sasaki, Nobuo; Huch, Meritxell; Boymans, Sander; Kuijk, Ewart; Prins, Pjotr; Nijman, Isaac J.; Martincorena, Inigo; Mokry, Michal; Wiegerinck, Caroline L.; Middendorp, Sabine; Sato, Toshiro; Schwank, Gerald; Nieuwenhuis, Edward E. S.; Verstegen, Monique M. A.; van der Laan, Luc J. W.; de Jonge, Jeroen; Ijzermans, Jan N. M.; Vries, Robert G.; van de Wetering, Marc; Stratton, Michael R.; Clevers, Hans; Cuppen, Edwin; van Boxtel, Ruben

2016-10-01

The gradual accumulation of genetic mutations in human adult stem cells (ASCs) during life is associated with various age-related diseases, including cancer. Extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of ASC divisions, owing to unavoidable random mutations that arise during DNA replication. However, the rates and patterns of mutations in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. Liver ASCs, however, have different mutation spectra compared to those of the colon and small intestine. Mutational signature analysis reveals that this difference can be attributed to spontaneous deamination of methylated cytosine residues in the colon and small intestine, probably reflecting their high ASC division rate. In liver, a signature with an as-yet-unknown underlying mechanism is predominant. Mutation spectra of driver genes in cancer show high similarity to the tissue-specific ASC mutation spectra, suggesting that intrinsic mutational processes in ASCs can initiate tumorigenesis. Notably, the inter-individual variation in mutation rate and spectra are low, suggesting tissue-specific activity of common mutational processes throughout life.

Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets

PubMed Central

Santagata, Sandro; Cahill, Daniel P.; Taylor-Weiner, Amaro; Jones, Robert T.; Van Allen, Eliezer M.; Lawrence, Michael S.; Horowitz, Peleg M.; Cibulskis, Kristian; Ligon, Keith L.; Tabernero, Josep; Seoane, Joan; Martinez-Saez, Elena; Curry, William T.; Dunn, Ian F.; Paek, Sun Ha; Park, Sung-Hye; McKenna, Aaron; Chevalier, Aaron; Rosenberg, Mara; Barker, Frederick G.; Gill, Corey M.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Hoang, Mai P.; Choueiri, Toni K.; Signoretti, Sabina; Sougnez, Carrie; Rabin, Michael S.; Lin, Nancy U.; Winer, Eric P.; Stemmer-Rachamimov, Anat; Meyerson, Matthew; Garraway, Levi; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Batchelor, Tracy T.; Baselga, Jose; Louis, David N.

2016-01-01

Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. PMID:26410082

Cell membrane softening in human breast and cervical cancer cells

NASA Astrophysics Data System (ADS)

Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

2015-08-01

Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-06-01

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

Male breast cancer arising in ectopic axillary breast tissue: A diagnostic dilemma.

PubMed

Xie, Yangchun; Huang, Jin; Xiao, Desheng; Zhong, Meizuo

2013-06-01

Male breast cancer arising in ectopic axillary breast tissue is a rare occurrence and few cases have been reported in the literature. Due to its rarity, male axillary breast cancer is easy to misdiagnose. As for adenocarcinoma in the axilla, it is difficult to identify whether the origin is the mammary tissue or the skin appendages, particularly in cases where there is a poor differentiation. The present study reports the case of a male patient with a right axillary lesion that had been present for 6 months. A histological evaluation revealed the features of a poorly-differentiated adenocarcinoma with regards to the pathological report. The patient was diagnosed with a metastatic adenocarcinoma with unknown primary origin. However, following 4 cycles of intensive chemotherapy, the patient experienced bone metastasis while the local lesion was in partial remission. Further immunohistochemistry confirmed its mammary origin. There is limited literature relating to male ectopic axillary breast cancer, and a high probability of misdiagnosis of this disease.

Male breast cancer arising in ectopic axillary breast tissue: A diagnostic dilemma

PubMed Central

XIE, YANGCHUN; HUANG, JIN; XIAO, DESHENG; ZHONG, MEIZUO

2013-01-01

Male breast cancer arising in ectopic axillary breast tissue is a rare occurrence and few cases have been reported in the literature. Due to its rarity, male axillary breast cancer is easy to misdiagnose. As for adenocarcinoma in the axilla, it is difficult to identify whether the origin is the mammary tissue or the skin appendages, particularly in cases where there is a poor differentiation. The present study reports the case of a male patient with a right axillary lesion that had been present for 6 months. A histological evaluation revealed the features of a poorly-differentiated adenocarcinoma with regards to the pathological report. The patient was diagnosed with a metastatic adenocarcinoma with unknown primary origin. However, following 4 cycles of intensive chemotherapy, the patient experienced bone metastasis while the local lesion was in partial remission. Further immunohistochemistry confirmed its mammary origin. There is limited literature relating to male ectopic axillary breast cancer, and a high probability of misdiagnosis of this disease. PMID:23833669

Late esophageal toxicity after radiation therapy for head and neck cancer.

PubMed

Chen, Allen M; Li, Bao-Qing; Jennelle, Richard L S; Lau, Derick H; Yang, Claus C; Courquin, Jean; Vijayakumar, Srinivasan; Purdy, James A

2010-02-01

The aim of this study was to determine the incidence of esophageal toxicity after radiation therapy for head and neck cancer. The records of 211 patients treated by radiation therapy for head and neck cancer were reviewed to identify those with dysphagia lasting more than 90 days after therapy. Late toxicity criteria established by the Radiation Therapy Oncology Group were used to score the symptoms. The incidence of grade 3+ esophageal toxicity at 3 and 6 months was 30% and 19%, respectively. The rate of gastrotomy-tube dependence at 3 and 6 months was 20% and 11%, respectively. Hypopharyngeal and unknown primary site (p = .01, for both), T4 disease (p = .01), and the use of concurrent chemotherapy (p = .001) were associated with grade 3+ esophageal toxicity and stricture formation. A significant proportion of patients exhibit symptoms of esophageal toxicity after radiation therapy for head and neck cancer. Therefore, preventive strategies need further investigation. Copyright 2009 Wiley Periodicals, Inc.

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

PubMed Central

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-01-01

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity. PMID:27279498

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer.

PubMed

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-06-09

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

The Genetics of Osteosarcoma

PubMed Central

Martin, Jeff W.; Squire, Jeremy A.; Zielenska, Maria

2012-01-01

Osteosarcoma is a primary bone malignancy with a particularly high incidence rate in children and adolescents relative to other age groups. The etiology of this often aggressive cancer is currently unknown, because complicated structural and numeric genomic rearrangements in cancer cells preclude understanding of tumour development. In addition, few consistent genetic changes that may indicate effective molecular therapeutic targets have been reported. However, high-resolution techniques continue to improve knowledge of distinct areas of the genome that are more commonly associated with osteosarcomas. Copy number gains at chromosomes 1p, 1q, 6p, 8q, and 17p as well as copy number losses at chromosomes 3q, 6q, 9, 10, 13, 17p, and 18q have been detected by numerous groups, but definitive oncogenes or tumour suppressor genes remain elusive with respect to many loci. In this paper, we examine studies of the genetics of osteosarcoma to comprehensively describe the heterogeneity and complexity of this cancer. PMID:22685381

APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma

PubMed Central

Leonard, Brandon; Hart, Steven N.; Burns, Michael B.; Carpenter, Michael A.; Temiz, Nuri A.; Rathore, Anurag; Vogel, Rachel Isaksson; Nikas, Jason B.; Law, Emily K.; Brown, William L.; Li, Ying; Zhang, Yuji; Maurer, Matthew J.; Oberg, Ann L.; Cunningham, Julie M.; Shridhar, Viji; Bell, Debra A.; April, Craig; Bentley, David; Bibikova, Marina; Cheetham, R. Keira; Fan, Jian-Bing; Grocock, Russell; Humphray, Sean; Kingsbury, Zoya; Peden, John; Chien, Jeremy; Swisher, Elizabeth M.; Hartmann, Lynn C.; Kalli, Kimberly R.; Goode, Ellen L.; Sicotte, Hugues; Kaufmann, Scott H.; Harris, Reuben S.

2013-01-01

Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here we report wide variation in expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in a majority of ovarian cancer cell lines (3 standard deviations above the mean of normal ovarian surface epithelial cells) and high grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5′TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5′TC dinucleotide motifs in early-stage high grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA ‘repair’ enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. PMID:24154874

The Fragile X Protein binds mRNAs involved in cancer progression and modulates metastasis formation

PubMed Central

Lucá, Rossella; Averna, Michele; Zalfa, Francesca; Vecchi, Manuela; Bianchi, Fabrizio; Fata, Giorgio La; Del Nonno, Franca; Nardacci, Roberta; Bianchi, Marco; Nuciforo, Paolo; Munck, Sebastian; Parrella, Paola; Moura, Rute; Signori, Emanuela; Alston, Robert; Kuchnio, Anna; Farace, Maria Giulia; Fazio, Vito Michele; Piacentini, Mauro; De Strooper, Bart; Achsel, Tilmann; Neri, Giovanni; Neven, Patrick; Evans, D Gareth; Carmeliet, Peter; Mazzone, Massimiliano; Bagni, Claudia

2013-01-01

The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression. PMID:24092663

Unknown primary squamous cell carcinoma of the head and neck: retrospective analysis of 80 cases.

PubMed

Mizuta, Masanobu; Kitamura, Morimasa; Tateya, Ichiro; Tamaki, Hisanobu; Tanaka, Shinzo; Asato, Ryo; Shinohara, Shogo; Takebayashi, Shinji; Maetani, Toshiki; Kitani, Yoshiharu; Kumabe, Yohei; Kojima, Tsuyoshi; Ushiro, Koji; Ichimaru, Kazuyuki; Honda, Keigo; Yamada, Koichiro; Omori, Koichi

2018-06-01

The management of patients with cervical metastasis in head and neck cancer of unknown primary (HNCUP) remains controversial. This current multicenter retrospective study investigated the treatment outcomes of patients with HNCUP. The study included patients who were treated curatively at 12 institutions in Japan from January 2006 to December 2015. Eighty patients with HNCUP were included. The median follow-up period was 34 months. The three-year overall survival (OS), disease-specific survival (DSS), regional relapse-free survival (RRFS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS) rates were 72.5%, 80.3%, 74.0%, 89.7%, and 86.9%, respectively. Nodal status was a significant factor for OS, DSS, RRFS, and DMFS; and extracapsular extension (ECE) was significant for OS and DSS. There was a distinct difference between the survival rates of patients with N1-2a and N2b-3 disease. RT was a significant positive factor for LPFS (3-year LPFS, RT 93.0% vs. no RT 83.0%, p = .043). For N2a as well as N1 disease without ECE, a single treatment modality, including ND or RT alone is acceptable. When ND alone is performed, thorough monitoring should be continued during follow-up to identify the emergence of the primary lesion.

Proportion and characteristics of men with unknown risk category in the National Prostate Cancer Register of Sweden.

PubMed

Tomic, Katarina; Westerberg, Marcus; Robinson, David; Garmo, Hans; Stattin, Pär

2016-12-01

Knowledge on missing data in a clinical cancer register is important to assess the validity of research results. For analysis of prostate cancer (Pca), risk category, a composite variable based on serum levels of prostate specific antigen (PSA), stage, and Gleason score, is crucial for treatment decisions and a strong determinant of outcome. The aim of this study was to assess the proportion and characteristics of men in the National Prostate Cancer Register (NPCR) of Sweden with unknown risk category. Men diagnosed with Pca between 1998 and 2012 registered in NPCR with known or unknown risk category were compared with respect to age, socioeconomic factors, comorbidity, cancer characteristics, cancer treatment, and mortality from Pca and other causes. In total, 3315 of 129 391 (3%) men had unknown risk category. Compared to other men in NPCR, these men more often had a concomitant bladder cancer diagnosis, 19% versus 1%, diagnosis of benign prostatic hyperplasia 31% versus 5%, received unspecified Pca treatment 16% versus 3%, had higher comorbidity, Charlson Comorbidity Index 2 or higher, 34% versus 13%, and had lower Pca mortality 12% versus 30%, but similar mortality from other causes. Men with unknown risk category were rare in NPCR but distinctly different from other men in NPCR in many aspects including higher comorbidity and lower Pca mortality.

Search for familial clustering of multiple myeloma with any cancer.

PubMed

Frank, C; Fallah, M; Chen, T; Mai, E K; Sundquist, J; Försti, A; Hemminki, K

2016-03-01

Multiple myeloma (MM) is a disease of immunoglobulin-producing plasma cells, which reside mainly in the bone marrow. Family members of MM patients are at a risk of MM, but whether other malignancies are in excess in family members is not established and is the aim of this study. MM patients (24 137) were identified from the Swedish Cancer Registry from years 1958 to 2012. Relative risks (RRs) were calculated for MM defined by any cancer diagnosed in first-degree relatives and compared with individuals whose relatives had no cancer. MM was reliably associated with relative's colorectal, breast and prostate cancers, non-thyroid endocrine tumors, leukemia and cancer of unknown primary; in addition, MM was associated with subsites of bone and connective tissue tumors and of non-Hodgkin lymphoma, including lymphoplasmacytic lymphoma/Waldenström macroglobulinema (RR 3.47). MM showed a strong association (RR 1.91) in colorectal cancer families, possibly as part of an unidentified syndrome. All the associations of MM with discordant cancers are novel suggesting that MM shares genetic susceptibility with many cancers. The associations of MM bone and connective tissue tumors were supported by at least two independent results. Whether the results signal bone-related biology shared by MM and these tumors deserves further study.

Variation in promptness of presentation among 10,297 patients subsequently diagnosed with one of 18 cancers: Evidence from a National Audit of Cancer Diagnosis in Primary Care

PubMed Central

Keeble, Stuart; Abel, Gary A; Saunders, Catherine L; McPhail, Sean; Walter, Fiona M; Neal, Richard D; Rubin, Gregory P; Lyratzopoulos, Georgios

2014-01-01

Cancer awareness public campaigns aim to shorten the interval between symptom onset and presentation to a doctor (the ‘patient interval’). Appreciating variation in promptness of presentation can help to better target awareness campaigns. We explored variation in patient intervals recorded in consultations with general practitioners among 10,297 English patients subsequently diagnosed with one of 18 cancers (bladder, brain, breast, colorectal, endometrial, leukaemia, lung, lymphoma, melanoma, multiple myeloma, oesophageal, oro-pharyngeal, ovarian, pancreatic, prostate, renal, stomach, and unknown primary) using data from of the National Audit of Cancer Diagnosis in Primary Care (2009–2010). Proportions of patients with ‘prompt’/‘non-prompt’ presentation (0–14 or 15+ days from symptom onset, respectively) were described and respective odds ratios were calculated by multivariable logistic regression. The overall median recorded patient interval was 10 days (IQR 0–38). Of all patients, 56% presented promptly. Prompt presentation was more frequent among older or housebound patients (p < 0.001). Prompt presentation was most frequent for bladder and renal cancer (74% and 70%, respectively); and least frequent for oro-pharyngeal and oesophageal cancer (34% and 39%, respectively, p <.001). Using lung cancer as reference, the adjusted odds ratios of non-prompt presentation were 2.26 (95% confidence interval 1.57–3.25) and 0.42 (0.34–0.52) for oro-pharyngeal and bladder cancer, respectively. Sensitivity analyses produced similar findings. Routinely recorded patient interval data reveal considerable variation in the promptness of presentation. These findings can help to prioritise public awareness initiatives and research focusing on symptoms of cancers associated with greater risk of non-prompt presentation, such as oro-pharyngeal and oesophageal cancer. What's new? A critical aspect of cancer diagnosis is how promptly patients consult a doctor after they first notice initial symptoms. Here, the authors examine differences in this so-called patient interval in English patients subsequently diagnosed with one of 18 cancers. On average, patients with bladder and renal cancer as well as older and housebound patients consulted a doctor relatively promptly while patients with oro-pharyngeal and oesophageal cancer took the longest until first presenting to a general practitioner. The authors point out that cancer awareness campaigns should encompass symptoms of oro-pharyngeal and oesophageal cancer aiming to shorten the patient interval for these cancers. PMID:24515930

Genomic Testing and Resulting Medical Decisions

ClinicalTrials.gov

2017-10-03

Cancer of Unknown Origin; Cancer Refractory; Cancer of Stomach; Cancer Head Neck; Cancer of Skin; Cancer, Lung; Cancer Colorectal; Cancer of Esophagus; Cancer, Bladder; Cancer, Uterus; Cancer Cervix; Cancer Liver; Cancer, Kidney; Cancer, Breast; Hematologic Neoplasms

VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer.

PubMed

St Laurent, Georges; Shtokalo, Dmitry; Dong, Biao; Tackett, Michael R; Fan, Xiaoxuan; Lazorthes, Sandra; Nicolas, Estelle; Sang, Nianli; Triche, Timothy J; McCaffrey, Timothy A; Xiao, Weidong; Kapranov, Philipp

2013-07-22

The function of the non-coding portion of the human genome remains one of the most important questions of our time. Its vast complexity is exemplified by the recent identification of an unusual and notable component of the transcriptome - very long intergenic non-coding RNAs, termed vlincRNAs. Here we identify 2,147 vlincRNAs covering 10 percent of our genome. We show they are present not only in cancerous cells, but also in primary cells and normal human tissues, and are controlled by canonical promoters. Furthermore, vlincRNA promoters frequently originate from within endogenous retroviral sequences. Strikingly, the number of vlincRNAs expressed from endogenous retroviral promoters strongly correlates with pluripotency or the degree of malignant transformation. These results suggest a previously unknown connection between the pluripotent state and cancer via retroviral repeat-driven expression of vlincRNAs. Finally, we show that vlincRNAs can be syntenically conserved in humans and mouse and their depletion using RNAi can cause apoptosis in cancerous cells. These intriguing observations suggest that vlincRNAs could create a framework that combines many existing short ESTs and lincRNAs into a landscape of very long transcripts functioning in the regulation of gene expression in the nucleus. Certain types of vlincRNAs participate at specific stages of normal development and, based on analysis of a limited set of cancerous and primary cell lines, they appear to be co-opted by cancer-associated transcriptional programs. This provides additional understanding of transcriptome regulation during the malignant state, and could lead to additional targets and options for its reversal.

Hexavalent Chromium Induces Chromosome Instability in Human Urothelial Cells

PubMed Central

Wise, Sandra S.; Holmes, Amie L.; Liou, Louis; Adam, Rosalyn M.; Wise, John Pierce

2016-01-01

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of Cr(VI) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Hexavalent chromium (Cr(VI)) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer specifically and may be a mechanism for metal-induced bladder cancer in general. PMID:26908176

Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

ClinicalTrials.gov

2013-12-17

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Engagement of Patients With Advanced Cancer

ClinicalTrials.gov

2017-05-12

End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

Use of Inpatient Palliative Care by Type of Malignancy.

PubMed

Ruck, Jessica M; Canner, Joseph K; Smith, Thomas J; Johnston, Fabian M

2018-06-05

Although mounting evidence supports the use of palliative care (PC) to improve care experiences and quality of life for oncology patients, the frequency of and factors associated with PC use during oncology-related hospitalizations remain unknown. Using the National Inpatient Sample dataset, hospitalizations during 2012-2014 for a primary diagnosis of cancer with high risk of in-hospital mortality were identified. PC use was identified using the V66.7 ICD-9 code. Factors associated with the cost of hospitalization were identified using multivariable gamma regression. During the study period, 124,186 hospitalizations were identified with a primary diagnosis of malignancy (melanoma, breast, colon, gynecologic, prostate, male genitourinary, head/neck, urinary tract, noncolon gastrointestinal, lung, brain, bone/soft tissue, endocrine, or nonlung thoracic). Most patients were treated at a teaching hospital (51-77% by cancer type), and use of PC ranged from 10% for patients with endocrine cancers to 31% for patients with melanoma. Patients utilizing PC had a lower frequency of operative procedures (4-33% vs. 34-79% by cancer type, all p ≤ 0.001), a higher rate of in-hospital death (30-45% vs. 4-10% by cancer type, all p < 0.001), and a lower total hospitalization cost (median: $5076-17,151 vs. $10,918-29,287 by cancer type, p ≤ 0.01 except male genitourinary). In an adjusted analysis, the cost of hospitalization was significantly associated (all p < 0.001) with patient gender, race, age, operative, in-hospital death, extended length of stay, and PC. In summary, inpatient PC utilization varied by cancer type. PC was associated with lower utilization of surgical procedures, shorter length of stay, and lower hospitalization cost. Lower hospitalization cost was also seen for patients who were older, female, or African American.

Pregnancy-associated-cancer in the French West Indies (Martinique): maternal and neonatal outcomes.

PubMed

Melan, Kathleen; Volumenie, Jean-Luc; Wan-Ajouhu, Gaël; Ulric-Gervaise, Stephen; Veronique-Baudin, Jacqueline; Joachim, Clarisse

2017-10-02

The management of pregnancy-associated-cancer (PAC) requires epidemiological evaluation of the pathways of care. The aim of this study was to describe maternal and neonatal outcomes of PAC in Martinique. A retrospective study was conducted using data from medical records and the Martinique Cancer Registry for all PAC diagnosed between 1st January 2000 and 31st December 2014. Eighteen women were diagnosed with PAC: 17 during pregnancy and one during the postpartum period. Mean age at diagnosis was 35.7 ± 5.4 years. PAC were mainly gynecological cancers (12/18); the other sites were: lymphoma, brain, liver, colon, skin and unknown primary site. In most cases, PAC was detected in symptomatic individuals (72.2%). Nine women had nodal involvement or initial metastasis at diagnosis. No chemotherapy was administered in cases of preservation of pregnancy. Seven fetal losses caused by abortion and miscarriage were recorded, and 11 women conducted viable pregnancies. The main neonatal pathology observed was prematurity (58.3%). Cancer management during pregnancy is a challenge for French West-Indies territories. A Caribbean Observatory of rare cancers could help to ensure a coordinated approach to support and monitoring for these patients.

Head and neck squamous cell carcinoma of unknown primary: Outcomes of a pre-defined institutional treatment policy in a region with a high prevalence of skin cancer.

PubMed

Huo, Michael; Panizza, Benedict; Bernard, Anne; Porceddu, Sandro V

2018-02-01

To determine the rate of subsequent primary site failure in patients with head and neck squamous cell carcinoma of unknown primary (UKP HNSCC) in a region with a high prevalence of cutaneous squamous cell carcinoma, according to a pre-determined institutional policy. Secondary aims included regional and distant control, and overall survival. Patients presenting between April 2005 and June 2016 to the Princess Alexandra Hospital Head and Neck Multidisciplinary Meeting with UKP HNSCC from either presumed mucosal or cutaneous sites treated with curative intent were eligible. Patients with presumed mucosal origin were treated with radiation therapy (RT) with or without chemotherapy, while patients with presumed cutaneous SCC were treated with surgery and post-operative RT with or without chemotherapy. A total of 63 patients met the inclusion criteria. Median follow up duration was 3.9 years (IQR 2.07-5.14). There were no subsequent primary site failures. The rate of nodal failure among presumed mucosal patients was 11.5%, and 8.1% among presumed cutaneous patients. The rate of distant metastatic failure was 11.1% among all patients. The estimated 5 year overall survival was 71.2% (95% CI 59.2-85.7%). Treatment according to our pre-defined institutional policy for UKP HNSCC in a region with a high prevalence of cutaneous SCC appears to be safe and effective with low rates of mucosal primary emergence and nodal failure. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Prevalence and Survival Patterns of Patients with Bone Metastasis from Common Cancers in Thailand.

PubMed

Phanphaisarn, Areerak; Patumanond, Jayantorn; Settakorn, Jongkolnee; Chaiyawat, Parunya; Klangjorhor, Jeerawan; Pruksakorn, Dumnoensun

2016-01-01

Bone metastasis is a single condition but presents with various patterns and severities. Skeletal- related events (SREs) deteriorate overall performance status and reduce quality of life. However, guidelines for early detection and management are limited. This study includes a survey of the prevalence of bone metastasis in cases with common cancers in Thailand as well as a focus on survival patterns and SREs. A retrospective cohort analysis was conducted using a database of the Chiang Mai Cancer Registry and the Musculoskeletal Tumor Registry of the OLARN Center, Chiang Mai University. The prevalence of bone metastasis from each type of primary cancer was noted and time-to-event analysis was performed to estimate cancer survival rates after bone metastasis. There were 29,447 cases of the ten most common cancers in Thailand, accounting for 82.2% of the entire cancer registry entries during the study period. Among those cases, there were 2,263 with bone metastases, accounting for 7.68% of entries. Bone metastasis from lung, liver, breast, cervix and prostate are common in the Thai population, accounting for 83.4% of all positive cases. The median survival time of all was 6 months. Of the bone metastases, 48.9% required therapeutic intervention, including treatment of spinal cord and nerve root compression, pathological fractures, and bone pain. The frequency of the top five types of bone metastasis in Thailand were different from the frequencies in other countries, but corresponded to the relative prevalence of the cancers in Thailand and osteophilic properties of each cancer. The results of this study support the establishment of country specific guidelines for primary cancer identification with skeletal lesions of unknown origin. In addition, further clinical studies of the top five bone metastases should be performed to develop guidelines for optimal patient management during palliative care.

Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-03-28

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

28 CFR 79.21 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... lymphocytic leukemia, multiple myeloma, lymphomas, Hodgkin's disease, primary cancer of the thyroid, primary cancer of the male breast, primary cancer of the female breast, primary cancer of the esophagus, primary cancer of the stomach, primary cancer of the pharynx, primary cancer of the small intestine, primary...

Expression of SRSF3 is Correlated with Carcinogenesis and Progression of Oral Squamous Cell Carcinoma.

PubMed

Peiqi, Liu; Zhaozhong, Guo; Yaotian, Yin; Jun, Jia; Jihua, Guo; Rong, Jia

2016-01-01

Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck with high mortality rates. The mechanisms of initiation and development of OSCC remain largely unknown. Dysregulated alternative splicing of pre-mRNA has been associated with OSCC. Splicing factor SRSF3 is a proto-oncogene and overexpressed in multiple cancers. The aim of this study was to uncover the relationship between SRSF3 and carcinogenesis and progression of oral squamous cell carcinoma. The expression of SRSF3 in oral normal, dysplasia, or carcinoma tissues was analyzed by immunohistochemistry. The expression levels of EMT-related genes were quantified by real-time quantitative RT-PCR. The expression of SRSF3 in DMBA treated primary cultured oral epithelial cells were analyzed by western blot. SRSF3 is overexpressed in oral cancer and moderate or severe dysplasia tissues. Patients with high grade cancer or lymphatic metastasis showed up-regulated expression of SRSF3. Knockdown of SRSF3 repressed the expression of Snail and N-cadherin in vitro. Carcinogen DMBA treated primary cultured oral epithelial cells showed significantly increased SRSF3 level than in control cells. Our results suggested that SRSF3 is associated with the initiation and development of OSCC and may be a biomarker and therapeutic target of OSCC.

Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery.

PubMed

Keung, Emily Z; Hornick, Jason L; Bertagnolli, Monica M; Baldini, Elizabeth H; Raut, Chandrajit P

2014-02-01

Although sarcoma histology is recognized as a prognostic factor, most studies of retroperitoneal sarcomas report results combining multiple histologies and are inadequately powered to identify prognostic factors specific to a particular histology. We reviewed our experience with retroperitoneal dedifferentiated liposarcoma (RP DDLPS) to identify factors predictive of outcomes. All patients with RP DDLPS treated at our institution between 1998 and 2008 were reviewed. Multivariable Cox regression analyses were performed to identify factors predictive of progression-free survival (PFS), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and overall survival (OS). We identified 119 patients with primary DDLPS. Median tumor size was 20.5 cm; 21% were multifocal. French Federation of Cancer Centers Sarcoma Group tumor grades were intermediate in 53% of patients and high in 28% (unknown 19%). Resections were complete (R0/R1) in 80% of patients and incomplete (R2) in 11% (unknown 9%). Tumors were removed intact in 72% of patients and fragmented in 16% (unknown 12%). Median follow-up was 74.1 months. One hundred patients (84%) experienced recurrence or progression, with 92% occurring in the retroperitoneum. Median PFS, LRFS, DRFS, and OS were 21.1, 21.5, 45.8, and 59.0 months, respectively, and were significantly worse with R2 resection. On multivariate analysis, tumor integrity (intact vs fragmented) was predictive of PFS, multifocality predicted LRFS, and extent of resection (R0/R1 vs R2), grade, and tumor integrity predicted OS. In this cohort of primary RP DDLPS, factors under surgeon control (tumor integrity, extent of resection) and reflective of tumor biology (grade, multifocality) impact patient outcomes. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Is CDX2 immunostaining useful for delineating anorectal from penile/vulvar squamous cancer in the setting of squamous cell carcinoma with clinically unknown primary site presenting with histologically confirmed inguinal lymph node metastasis?

PubMed

Gunia, Sven; Koch, Stefan; May, Matthias

2013-02-01

Penile, vulvar and anal squamous cell carcinomas (SCCs) share histomorphological overlap and are prone to lymphatic dissemination into inguinal nodes. Anal SCCs might derive from the anorectal zone (ARZ), anal transitional zone, squamous zone or from perianal skin. These anatomically distinct zones differ in terms of their embryological development. We sought to investigate the role of caudal-related homeobox 2 (CDX2), a homeobox gene implicated in the development and anterior/posterior pattern specification from duodenum to rectum including the ARZ, in terms of narrowing the possible sites of origin to be considered in the setting of SCC with unknown primary presenting with histologically confirmed inguinal lymph node metastasis. By immunohistochemistry (IHC) employing a panel of antibodies directed against CK5/6, CK7, CK20, p63, p16, CEA and CDX2, we compared 89 penile, 11 vulvar and eight anal SCCs with respect to their staining profiles. Moreover, anal SCCs were subjected to in situ hybridisation (ISH) for high-risk human papillomavirus (HPV) subtypes. By IHC, CDX2 expression was observed in 2/8 anal SCCs (25%) while being absent from all penile and vulvar SCCs examined. High-risk HPV subtypes were detected by ISH in all anal SCCs examined, which were uniformly p16-positive by IHC. CDX2 might be valuable in terms of narrowing the possible sites of origin to be considered in the setting of SCC with unknown primary presenting with inguinal lymph node metastasis. However, despite its favourable specificity, the diagnostic benefit achieved by this observation is limited by the low sensitivity.

Descriptive statistical analysis of a real life cohort of 2419 patients with brain metastases of solid cancers.

PubMed

Berghoff, Anna S; Schur, Sophie; Füreder, Lisa M; Gatterbauer, Brigitte; Dieckmann, Karin; Widhalm, Georg; Hainfellner, Johannes; Zielinski, Christoph C; Birner, Peter; Bartsch, Rupert; Preusser, Matthias

2016-01-01

We provide a descriptive statistical analysis of baseline characteristics and the clinical course of a large real-life cohort of brain metastases (BM) patients. We performed a retrospective chart review for patients treated for BM of solid cancers at the Medical University of Vienna between 1990 and 2011. We identified a total of 2419 BM patients (50.5% male, 49.5% female, median age 59 years). The primary tumour was lung cancer in 43.2%, breast cancer in 15.7%, melanoma in 16.4%, renal cell carcinoma in 9.1%, colorectal cancer in 9.3% and unknown in 1.4% of cases. Rare tumour types associated with BM included genitourinary cancers (4.1%), sarcomas (0.7%). gastro-oesophageal cancer (0.6%) and head and neck cancers (0.2%). 48.7% of patients presented with a singular BM, 27.7% with 2-3 and 23.5% with >3 BM. Time from primary tumour to BM diagnosis was shortest in lung cancer (median 11 months; range 1-162) and longest in breast cancer (median 44 months; 1-443; p<0.001). Multiple BM were most frequent in breast cancer (30.6%) and least frequent in colorectal cancer (8.5%; p<0.001). Patients with breast cancer had the longest median overall survival times (8 months), followed by patients with lung cancer (7 months), renal cell carcinoma (7 months), melanoma (5 months) and colorectal cancer (4 months; p<0.001; log rank test). Recursive partitioning analysis and graded prognostic assessment scores showed significant correlation with overall survival (both p<0.001, log rank test). Evaluation of the disease status in the past 2 months prior to patient death showed intracranial progression in 35.9%, extracranial progression in 27.5% and combined extracranial and intracranial progression in 36.6% of patients. Our data highlight the heterogeneity in presentation and clinical course of BM patients in the everyday clinical setting and may be useful for rational planning of clinical studies.

Hexavalent chromium induces chromosome instability in human urothelial cells

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

Wise, Sandra S.; Holmes, Amie L.; Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damagemore » in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.« less

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status

PubMed Central

Mudali, Shiyama V.; Fu, Baojin; Lakkur, Sindhu S.; Luo, Mingde; Embuscado, Erlinda E.

2009-01-01

EphA2 is a transmembrane receptor tyrosine kinase that functions in the regulation of cell growth, survival, angiogenesis, and migration and EphA2 targeting has been proposed as a novel therapeutic strategy for neoplasms that overexpress this protein. EphA2 overexpression has been correlated with increased invasive and metastatic ability in pancreatic cancer cell lines. However, the patterns of EphA2 expression in human pancreatic cancers and associated metastases is unknown, as are the genetics of EphA2 in this tumor type. We collected clinicopathologic data and paraffin-embedded materials from 98 patients with primary and/or metastatic pancreatic cancer and performed immunohistochemical labeling for EphA2 protein. EphA2 protein immunolabeling was found in 207 of 219 samples (95%). The expression was predominantly cytoplasmic, although predominant membranous staining was observed in a minority of cases. When evaluated specifically for labeling intensity, primary and metastatic carcinomas were more strongly positive compared to benign ducts and PanIN lesions (P < 0.00001 and P < 0.01, respectively) and poorly differentiated carcinomas were more strongly positive for EphA2 than well and moderately differentiated tumors (P < 0.005). When primary carcinomas without metastatic disease were specifically compared to carcinomas with associated metastatic disease, the advanced carcinomas showed relatively less strong positive labeling for EphA2 (P < 0.008). Moreover, decreased EphA2 labeling was more commonly found in liver (P < 0.002), lung (P < 0.004) or peritoneal metastases (P < 0.01) as compared to distant lymph node metastases (P < 0.01). Genetic sequencing of the tyrosine kinase domain of EPHA2 in 22 samples of xenograft enriched pancreatic cancer did not reveal any inactivating mutations. However, EPHA2 amplification was found in 1 of 33 pancreatic cancers corresponding to a lymph node metastasis, indicating EPHA2 genomic amplification may underlie EphA2 overexpression in a minority of patients. Our data confirms that EphA2 is overexpressed in pancreatic cancer, but suggests a relative loss of EphA2 in co-existent pancreatic cancer metastases as well as a role for EPHA2 in organ specific metastasis. PMID:17146615

Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection.

PubMed

Axelsson, Lars; Nyman, Jan; Haugen-Cange, Hedda; Bove, Mogens; Johansson, Leif; De Lara, Shahin; Kovács, Anikó; Hammerlid, Eva

2017-06-10

Head and neck cancer of unknown primary (HNCUP) is rare and prospective studies are lacking. The impact of different prognostic factors such as age and N stage is not completely known, the optimal treatment is not yet established, and the reported survival rates vary. In the last decade, human papilloma virus (HPV) has been identified as a common cause of and important prognostic factor in oropharyngeal cancer, and there is now growing interest in the importance of HPV for HNCUP. The aim of the present study on curatively treated HNCUP was to investigate the prognostic importance of different factors, including HPV status, treatment, and overall survival. A search for HNCUP was performed in the Swedish Cancer Registry, Western health district, between the years 1992-2009. The medical records were reviewed, and only patients with squamous cell carcinoma or undifferentiated carcinoma treated with curative intent were included. The tumor specimens were retrospectively analyzed for HPV with p16 immunostaining. Sixty-eight patients were included. The mean age was 59 years. The majority were males, and had N2 tumors. Sixty-nine percent of the tumors were HPV positive using p16 staining. Patients who were older than 70 years, patients with N3-stage tumors, and patients with tumors that were p16 negative had a significantly worse prognosis. The overall 5-year survival rate for patients with p16-positive tumors was 88% vs 61% for p16-negative tumors. Treatment with neck dissection and postoperative radiation or (chemo) radiation had 81 and 88% 5-year survival rates, respectively. The overall and disease-free 5-year survival rates for all patients in the study were 82 and 74%. Curatively treated HNCUP had good survival. HPV infection was common. Independent prognostic factors for survival were age over 70 years, HPV status and N3 stage. We recommend that HPV analysis should be performed routinely for HNCUP. Treatment with neck dissection and postoperative radiation or (chemo) radiation showed similar survival rates.

Testicular cancer

MedlinePlus

Cancer - testes; Germ cell tumor; Seminoma testicular cancer; Nonseminoma testicular cancer; Testicular neoplasm ... The exact cause of testicular cancer is unknown. Factors that may ... Abnormal testicle development Exposure to certain chemicals ...

Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer

ClinicalTrials.gov

2014-05-06

Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

The fragile X protein binds mRNAs involved in cancer progression and modulates metastasis formation.

PubMed

Lucá, Rossella; Averna, Michele; Zalfa, Francesca; Vecchi, Manuela; Bianchi, Fabrizio; La Fata, Giorgio; Del Nonno, Franca; Nardacci, Roberta; Bianchi, Marco; Nuciforo, Paolo; Munck, Sebastian; Parrella, Paola; Moura, Rute; Signori, Emanuela; Alston, Robert; Kuchnio, Anna; Farace, Maria Giulia; Fazio, Vito Michele; Piacentini, Mauro; De Strooper, Bart; Achsel, Tilmann; Neri, Giovanni; Neven, Patrick; Evans, D Gareth; Carmeliet, Peter; Mazzone, Massimiliano; Bagni, Claudia

2013-10-01

The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

A model and nomogram to predict tumor site origin for squamous cell cancer confined to cervical lymph nodes.

PubMed

Ali, Arif N; Switchenko, Jeffrey M; Kim, Sungjin; Kowalski, Jeanne; El-Deiry, Mark W; Beitler, Jonathan J

2014-11-15

The current study was conducted to develop a multifactorial statistical model to predict the specific head and neck (H&N) tumor site origin in cases of squamous cell carcinoma confined to the cervical lymph nodes ("unknown primaries"). The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for patients with an H&N tumor site who were diagnosed between 2004 and 2011. The SEER patients were identified according to their H&N primary tumor site and clinically positive cervical lymph node levels at the time of presentation. The SEER patient data set was randomly divided into 2 data sets for the purposes of internal split-sample validation. The effects of cervical lymph node levels, age, race, and sex on H&N primary tumor site were examined using univariate and multivariate analyses. Multivariate logistic regression models and an associated set of nomograms were developed based on relevant factors to provide probabilities of tumor site origin. Analysis of the SEER database identified 20,011 patients with H&N disease with both site-level and lymph node-level data. Sex, race, age, and lymph node levels were associated with primary H&N tumor site (nasopharynx, hypopharynx, oropharynx, and larynx) in the multivariate models. Internal validation techniques affirmed the accuracy of these models on separate data. The incorporation of epidemiologic and lymph node data into a predictive model has the potential to provide valuable guidance to clinicians in the treatment of patients with squamous cell carcinoma confined to the cervical lymph nodes. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Bone morphogenetic protein and bone metastasis, implication and therapeutic potential.

PubMed

Ye, Lin; Mason, Malcolm D; Jiang, Wen G

2011-01-01

Bone metastasis is one of the most common and severe complications in advanced malignancies, particularly in the three leading cancers; breast cancer, prostate cancer and lung cancer. It is currently incurable and causes severe morbidities, including bone pain, hypercalcemia, pathological fracture, spinal cord compression and consequent paralysis. However, the mechanisms underlying the development of bone metastasis remain largely unknown. Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and are pluripotent factors involved in the regulation of embryonic development and postnatal homeostasis of various organs and tissues, by controlling cellular differentiation, proliferation and apoptosis. Since they are potent regulators for bone formation, there is an increasing interest to investigate BMPs and their roles in bone metastasis. BMPs have been implicated in various neoplasms, at both primary and secondary tumors, particularly skeletal metastasis. Recently studies have also suggested that BMP signaling and their antagonists play pivotal roles in bone metastasis. In this review, we discuss the current knowledge of aberrations of BMPs which have been indicated in tumor progression, and particularly in the development of bone metastasis.

IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery

ClinicalTrials.gov

2018-05-01

Stage III Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; 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

Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2015-01-15

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

HER2 expression identifies dynamic functional states within circulating breast cancer cells.

PubMed

Jordan, Nicole Vincent; Bardia, Aditya; Wittner, Ben S; Benes, Cyril; Ligorio, Matteo; Zheng, Yu; Yu, Min; Sundaresan, Tilak K; Licausi, Joseph A; Desai, Rushil; O'Keefe, Ryan M; Ebright, Richard Y; Boukhali, Myriam; Sil, Srinjoy; Onozato, Maristela L; Iafrate, Anthony J; Kapur, Ravi; Sgroi, Dennis; Ting, David T; Toner, Mehmet; Ramaswamy, Sridhar; Haas, Wilhelm; Maheswaran, Shyamala; Haber, Daniel A

2016-09-01

Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER + /HER2 - primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2 + and HER2 - subpopulations: HER2 + circulating tumour cells are more proliferative but not addicted to HER2, consistent with activation of multiple signalling pathways; HER2 - circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2 + and HER2 - circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2 + and HER2 - circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2 + state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2 - phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance.

A naive Bayes algorithm for tissue origin diagnosis (TOD-Bayes) of synchronous multifocal tumors in the hepatobiliary and pancreatic system.

PubMed

Jiang, Weiqin; Shen, Yifei; Ding, Yongfeng; Ye, Chuyu; Zheng, Yi; Zhao, Peng; Liu, Lulu; Tong, Zhou; Zhou, Linfu; Sun, Shuo; Zhang, Xingchen; Teng, Lisong; Timko, Michael P; Fan, Longjiang; Fang, Weijia

2018-01-15

Synchronous multifocal tumors are common in the hepatobiliary and pancreatic system but because of similarities in their histological features, oncologists have difficulty in identifying their precise tissue clonal origin through routine histopathological methods. To address this problem and assist in more precise diagnosis, we developed a computational approach for tissue origin diagnosis based on naive Bayes algorithm (TOD-Bayes) using ubiquitous RNA-Seq data. Massive tissue-specific RNA-Seq data sets were first obtained from The Cancer Genome Atlas (TCGA) and ∼1,000 feature genes were used to train and validate the TOD-Bayes algorithm. The accuracy of the model was >95% based on tenfold cross validation by the data from TCGA. A total of 18 clinical cancer samples (including six negative controls) with definitive tissue origin were subsequently used for external validation and 17 of the 18 samples were classified correctly in our study (94.4%). Furthermore, we included as cases studies seven tumor samples, taken from two individuals who suffered from synchronous multifocal tumors across tissues, where the efforts to make a definitive primary cancer diagnosis by traditional diagnostic methods had failed. Using our TOD-Bayes analysis, the two clinical test cases were successfully diagnosed as pancreatic cancer (PC) and cholangiocarcinoma (CC), respectively, in agreement with their clinical outcomes. Based on our findings, we believe that the TOD-Bayes algorithm is a powerful novel methodology to accurately identify the tissue origin of synchronous multifocal tumors of unknown primary cancers using RNA-Seq data and an important step toward more precision-based medicine in cancer diagnosis and treatment. © 2017 UICC.

BMS-247550 in Treating Patients With Liver or Gallbladder Cancer

ClinicalTrials.gov

2014-05-13

Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Resectable 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

Identification of Luminal Breast Cancers that Establish a Tumor Supportive Macroenvironment Defined by Pro-Angiogenic Platelets and Bone Marrow Derived Cells

PubMed Central

Kuznetsov, Hanna S.; Marsh, Timothy; Markens, Beth A.; Castaño, Zafira; Greene-Colozzi, April; Hay, Samantha A.; Brown, Victoria E.; Richardson, Andrea L.; Signoretti, Sabina; Battinelli, Elisabeth M.; McAllister, Sandra S.

2012-01-01

Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer cells and patient tumor specimens (LBC “instigators”) establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors (“responders”). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells (BMCs) enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGFR2+ tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. PMID:22896036

Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain

PubMed Central

2012-01-01

Background Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. The aim of this study was to determine whether enhanced excitability of primary sensory neurons contributed to peripheral sensitization and tumor-induced hyperalgesia during cancer condition. In this study, using techniques of whole-cell patch-clamp recording associated with immunofluorescent staining, single-cell reverse-transcriptase PCR and behavioral test, we investigated whether the intrinsic membrane properties and the excitability of small-sized dorsal root ganglion (DRG) neurons altered in a rat model of bone cancer pain, and whether suppression of DRG neurons activity inhibited the bone cancer-induced pain. Results Our present study showed that implantation of MRMT-1 tumor cells into the tibial canal in rats produced significant mechanical and thermal hyperalgesia in the ipsilateral hind paw. Moreover, implantation of tumor cells provoked spontaneous discharges and tonic excitatory discharges evoked by a depolarizing current pulse in small-sized DRG neurons. In line with these findings, alterations in intrinsic membrane properties that reflect the enhanced neuronal excitability were observed in small DRG neurons in bone cancer rats, of which including: 1) depolarized resting membrane potential (RMP); 2) decreased input resistance (Rin); 3) a marked reduction in current threshold (CT) and voltage threshold (TP) of action potential (AP); 4) a dramatic decrease in amplitude, overshot, and duration of evoked action potentials as well as in amplitude and duration of afterhyperpolarization (AHP); and 5) a significant increase in the firing frequency of evoked action potentials. Here, the decreased AP threshold and increased firing frequency of evoked action potentials implicate the occurrence of hyperexcitability in small-sized DRG neurons in bone cancer rats. In addiotion, immunofluorescent staining and single-cell reverse-transcriptase PCR revealed that in isolated small DRG neurons, most neurons were IB4-positive, or expressed TRPV1 or CGRP, indicating that most recorded small DRG neurons were nociceptive neurons. Finally, using in vivo behavioral test, we found that blockade of DRG neurons activity by TTX inhibited the tumor-evoked mechanical allodynia and thermal hyperalgesia in bone cancer rats, implicating that the enhanced excitability of primary sensory neurons underlied the development of bone cancer pain. Conclusions Our present results suggest that implantation of tumor cells into the tibial canal in rats induces an enhanced excitability of small-sized DRG neurons that is probably as results of alterations in intrinsic electrogenic properties of these neurons. Therefore, alterations in intrinsic membrane properties associated with the hyperexcitability of primary sensory neurons likely contribute to the peripheral sensitization and tumor-induced hyperalgesia under cancer condition. PMID:22472208

Digital Image Processing Technique for Breast Cancer Detection

NASA Astrophysics Data System (ADS)

Guzmán-Cabrera, R.; Guzmán-Sepúlveda, J. R.; Torres-Cisneros, M.; May-Arrioja, D. A.; Ruiz-Pinales, J.; Ibarra-Manzano, O. G.; Aviña-Cervantes, G.; Parada, A. González

2013-09-01

Breast cancer is the most common cause of death in women and the second leading cause of cancer deaths worldwide. Primary prevention in the early stages of the disease becomes complex as the causes remain almost unknown. However, some typical signatures of this disease, such as masses and microcalcifications appearing on mammograms, can be used to improve early diagnostic techniques, which is critical for women’s quality of life. X-ray mammography is the main test used for screening and early diagnosis, and its analysis and processing are the keys to improving breast cancer prognosis. As masses and benign glandular tissue typically appear with low contrast and often very blurred, several computer-aided diagnosis schemes have been developed to support radiologists and internists in their diagnosis. In this article, an approach is proposed to effectively analyze digital mammograms based on texture segmentation for the detection of early stage tumors. The proposed algorithm was tested over several images taken from the digital database for screening mammography for cancer research and diagnosis, and it was found to be absolutely suitable to distinguish masses and microcalcifications from the background tissue using morphological operators and then extract them through machine learning techniques and a clustering algorithm for intensity-based segmentation.

Relation between residential magnetic fields, light-at-night, and nocturnal urine melatonin levels in women: Volume 1 -- Background and purpose, methods, results, discussion. Final report

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

Kaune, W.; Davis, S.; Stevens, R.

Scientists have postulated a link between exposure to magnetic fields and reduced blood melatonin levels. This EPRI study was designed to supplement a National Cancer Institute study (NCI-BC) of magnetic fields, light-at-night, and the risk of breast cancer. By expanding the exposure assessment of the NCI-BC and collecting data on urine melatonin levels, this project provides new insight into a possible magnetic field-melatonin link. It has been proposed that exposure to 60-Hz (power frequency) magnetic fields may increase the risk of breast cancer by suppressing the normal nocturnal rise in melatonin production in the pineal gland. It remains unknown whethermore » the human pineal gland is reproducibly responsive or sensitive to magnetic field exposure, and whether such exposures could alter elements of the endogenous hormonal environment in women that might be important in the etiology of breast cancer. The objective of this research was to investigate whether exposure to power-frequency magnetic fields and/or light-at-night is associated with levels of the primary urinary melatonin metabolite in women without a history of breast cancer.« less

Relation between residential magnetic fields, light-at-night, and nocturnal urine melatonin levels in women: Volume 2 -- Magnetic field exposure analysis. Final report

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

Kaune, W.; Davis, S.; Stevens, R.

Scientists have postulated a link between exposure to magnetic fields and reduced blood melatonin levels. This EPRI study was designed to supplement a National Cancer Institute study (NCI-BC) of magnetic fields, light-at-night, and the risk of breast cancer. By expanding the exposure assessment of the NCI-BC and collecting data on urine melatonin levels, this project provides new insight into a possible magnetic field-melatonin link. It has been proposed that exposure to 60-Hz (power frequency) magnetic fields may increase the risk of breast cancer by suppressing the normal nocturnal rise in melatonin production in the pineal gland. It remains unknown whethermore » the human pineal gland is reproducibly responsive or sensitive to magnetic field exposure, and whether such exposures could alter elements of the endogenous hormonal environment in women that might be important in the etiology of breast cancer. The objective of this research was to investigate whether exposure to power-frequency magnetic fields and/or light-at-night is associated with levels of the primary urinary melatonin metabolite in women without a history of breast cancer.« less

Study of the Pan-ERBB Inhibitor Neratinib Given in Combination With Everolimus, Palbociclib or Trametinib in Advanced Cancer Subjects With EGFR Mutation/Amplification, HER2 Mutation/Amplification or HER3/4 Mutation

ClinicalTrials.gov

2018-03-26

Malignant Neoplasm of Breast; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Neoplasms of Uncertain or Unknown Behavior

Metabolic treatment of cancer: intermediate results of a prospective case series.

PubMed

Schwartz, Laurent; Buhler, Ludivine; Icard, Philippe; Lincet, Hubert; Steyaert, Jean-Marc

2014-02-01

The combination of hydroxycitrate and lipoic acid has been demonstrated by several laboratories to be effective in reducing murine cancer growth. All patients had failed standard chemotherapy and were offered only palliative care by their referring oncologist. Karnofsky status was between 50 and 80. Life expectancy was estimated to be between 2 and 6 months. Ten consecutive patients with chemoresistant advanced metastatic cancer were offered compassionate metabolic treatment. They were treated with a combination of lipoic acid at 600 mg i.v. (Thioctacid), hydroxycitrate at 500 mg t.i.d. (Solgar) and low-dose naltrexone at 5 mg (Revia) at bedtime. Primary sites were lung carcinoma (n=2), colonic carcinoma (n=2), ovarian carcinoma (n=1), esophageal carcinoma (n=1), uterine sarcoma (n=1), cholangiocarcinoma (n=1), parotid carcinoma (n=1) and unknown primary (n=1). The patients had been heavily pre-treated. One patient had received four lines of chemotherapy, four patients three lines, four patients two lines and one patient had received radiation therapy and chemotherapy. An eleventh patient with advanced prostate cancer resistant to hormonotherapy treated with hydroxycitrate, lipoic acid and anti-androgen is also reported. One patient was unable to receive i.v. lipoic acid and was switched to oral lipoic acid (Tiobec). Toxicity was limited to transient nausea and vomiting. Two patients died of progressive disease within two months. Two other patients had to be switched to conventional chemotherapy combined with metabolic treatment, one of when had a subsequent dramatic tumor response. Disease in the other patients was either stable or very slowly progressive. The patient with hormone-resistant prostate cancer had a dramatic fall in Prostate-Specific Antigen (90%), which is still decreasing. These very primary results suggest the lack of toxicity and the probable efficacy of metabolic treatment in chemoresistant advanced carcinoma. It is also probable that metabolic treatment enhances the efficacy of cytotoxic chemotherapy. These results are in line with published animal data. A randomized clinical trial is warranted.

3-Tesla MRI Response to TACE in HCC (Liver Cancer)

ClinicalTrials.gov

2016-08-22

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

Amyopathic Dermatomyositis: A Concise Review of Clinical Manifestations and Associated Malignancies.

PubMed

Udkoff, Jeremy; Cohen, Philip R

2016-10-01

Amyopathic dermatomyositis is a rare, idiopathic, connective tissue disease that presents with dermatologic lesions of classic dermatomyositis but lacks the myopathy of this disease. Cutaneous manifestations may include Gottron's sign, heliotrope rash, and characteristic patterns of poikiloderma. There is a substantial risk for developing interstitial lung disease or malignancy in patients with amyopathic dermatomyositis. A literature review of amyopathic dermatomyositis was performed using the PubMed medical database. The key features of amyopathic dermatomyositis, including autoantibodies, clinical presentation and dermatologic manifestations, epidemiology, history, associated malignancies, management, and pathogenesis, are summarized in this review. Cancer (solid tumor) (73/79, 89 %) and hematologic malignancies (9/79, 11 %) were reported in 79 patients, with three patients having more than one malignancy. In addition, there were six patients with amyopathic dermatomyositis who had tumor of unknown primary, and eight patients with cancer-associated amyopathic dermatomyositis for whom no additional details were provided. From the group of 73 tumors for whom primary origin and sex were available, malignancy of the genitourinary organs (24/73, 33 %), aerorespiratory organs (15/73, 21 %), and breast (14/73, 19 %) were the most commonly observed solid organ tumors. Tumors of the genitourinary organs (15/48, 31 %) and breast (14/48, 29 %) were the most frequent neoplasms in women, accounting for 29 of 48 (60 %) cancers, with the most common sites being breast (14/48, 29 %), ovary (8/48, 17 %), and cervix or uterus (5/48, 10 %). In men, tumors of the aerorespiratory (9/25, 36 %) and genitourinary (9/25, 36 %) tracts were the most common neoplasms, accounting for 72 % (18/25) of cancers; the most common sites of primary malignancy were nasopharyngeal (6/25, 24 %), bladder (4/25, 16 %), and either colorectal, lung or prostate cancer (three cancers each, 12 %). In summary, the search for an undiagnosed associated malignancy in patients with amyopathic dermatomyositis should focus towards the organs most frequently affected. Similar to classic dermatomyositis, ovarian and nasopharyngeal cancers are also common in amyopathic dermatomyositis. However, in contrast to lung cancer, which is the most frequent malignancy associated with classic dermatomyositis, breast cancer was the most common type of malignancy reported in patients with amyopathic dermatomyosotis.

Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-04-27

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; 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

Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-01-05

Chemotherapeutic Agent Toxicity; Neuropathy; Neurotoxicity Syndrome; Pain; 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

Impact of prior cancer history on the overall survival of patients newly diagnosed with cancer: A pan-cancer analysis of the SEER database.

PubMed

Zhou, Huaqiang; Huang, Yan; Qiu, Zeting; Zhao, Hongyun; Fang, Wenfeng; Yang, Yunpeng; Zhao, Yuanyuan; Hou, Xue; Ma, Yuxiang; Hong, Shaodong; Zhou, Ting; Zhang, Yaxiong; Zhang, Li

2018-04-18

The population of cancer survivors with prior cancer is rapidly growing. Whether a prior cancer diagnosis interferes with outcome is unknown. We conducted a pan-cancer analysis to determine the impact of prior cancer history for patients newly diagnosed with cancer. We identified 20 types of primary solid tumors between 2004 and 2008 in the Surveillance, Epidemiology, and End Results database. Demographic and clinicopathologic variables were compared by χ 2 test and t-test as appropriate. The propensity score-adjusted Kaplan-Meier method and Cox proportional hazards models were used to evaluate the impact of prior cancer on overall survival (OS). Among 1,557,663 eligible patients, 261,474 (16.79%) had a history of prior cancer. More than 65% of prior cancers were diagnosed within 5 years. We classified 20 cancer sites into two groups (PCI and PCS) according to the different impacts of prior cancer on OS. PCI patients with a prior cancer history, which involved the colon and rectum, bone and soft tissues, melanoma, breast, cervix uteri, corpus and uterus, prostate, urinary bladder, kidney and renal pelvis, eye and orbits, thyroid, had inferior OS. The PCS patients (nasopharynx, esophagus, stomach, liver, gallbladder, pancreas, lung, ovary and brain) with a prior cancer history showed similar OS to that of patients without prior cancer. Our pan-cancer study presents the landscape for the survival impact of prior cancer across 20 cancer types. Compared to the patients without prior cancer, the PCI group had inferior OS, while the PCS group had similar OS. Further studies are still needed. © 2018 UICC.

Preoperative cancer cachexia and short-term outcomes following surgery.

PubMed

Mason, Meredith C; Garcia, Jose M; Sansgiry, Shubhada; Walder, Annette; Berger, David H; Anaya, Daniel A

2016-10-01

Cancer cachexia is an important measure of physiologic reserve associated with worse survival and represents an actionable factor for the cancer population. However, the incidence of cachexia in surgical cancer patients and its impact on postoperative outcomes are currently unknown. A prospective cohort study enrolling patients having elective cancer surgery (2012-2014) at a Veterans Affairs tertiary referral center. Preoperative cancer cachexia (weight loss ≥5% over 6-mo period before surgery) was the predictor of interest. The primary outcome was 60-d postoperative complications (VA Surgical Quality Improvement Program). Patients were grouped by body mass index (BMI) category (<25, 25-29.9, ≥30), and interaction between cachexia and BMI was tested for the primary outcome. Multivariate logistic regression was used to examine the association between preoperative cachexia and postoperative complications. Of 253 patients, 16.6% had preoperative cachexia, and 51.8% developed ≥ 1 postoperative complications. Complications were more common in cachectic patients (64.3% versus 49.3%, P = 0.07). This association varied by BMI category, and interaction analysis was significant for those with normal or underweight BMI (BMI < 25, P = 0.03). After multivariate modeling, in patients with normal or underweight BMI, preoperative cachexia was associated with higher odds of postoperative complications (odds ratios, 5.08 [95% confidence intervals, 1.18-21.88]; P = 0.029). Additional predictors of complications included major surgery (3.19 [1.24-8.21], P = 0.01), ostomy (4.43 [1.68-11.72], P = 0.003), and poor baseline performance status (2.31 [1.05-5.08], P = 0.03). Cancer cachexia is common in surgical patients, and is an important predictor of postoperative complications, though its effect varies by BMI. As a modifiable predictor of worse outcomes, future studies should examine the role of cachexia treatment before cancer surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of Breast Cancer Interstitial Fluids by TmT Labeling, LTQ-Orbitrap Velos Mass Spectrometry and Pathway Analysis

PubMed Central

Cinzia, Raso; Carlo, Cosentino; Marco, Gaspari; Natalia, Malara; Xuemei, Han; Daniel, McClatchy; Kyu, Park Sung; Maria, Renne; Nuria, Vadalà; Ubaldo, Prati; Giovanni, Cuda; Vincenzo, Mollace; Francesco, Amato; Yates, John R.

2012-01-01

Cancer is currently considered as the end point of numerous genomic and epigenomic mutations and as the result of the interaction of transformed cells within the stromal microenvironment. The present work focuses on breast cancer, one of the most common malignancies affecting the female population in industrialized countries. In this study we perform a proteomic analysis of bioptic samples from human breast cancer, namely interstitial fluids and primary cells, normal vs disease tissues, using Tandem mass Tags (TmT) quantitative mass spectrometry combined with the MudPIT technique. To the best of our knowledge this work, with over 1700 proteins identified, represents the most comprehensive characterization of the breast cancer interstitial fluid proteome to date. Network analysis was used to identify functionally active networks in the breast cancer associated samples. From the list of differentially expressed genes we have retrieved the associated functional interaction networks. Many different signaling pathways were found activated, strongly linked to invasion, metastasis development, proliferation and with a significant cross-talking rate. This pilot study presents evidence that the proposed quantitative proteomic approach can be applied to discriminate between normal and tumoral samples and for the discovery of yet unknown carcinogenesis mechanisms and therapeutic strategies. PMID:22563702

Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts.

PubMed

Comito, Giuseppina; Pons Segura, Coral; Taddei, Maria Letizia; Lanciotti, Michele; Serni, Sergio; Morandi, Andrea; Chiarugi, Paola; Giannoni, Elisa

2017-01-03

Zoledronic acid (ZA) is a biphosphonate used for osteoporosis treatment and also proved to be effective to reduce the pain induced by bone metastases when used as adjuvant therapy in solid cancers. However, it has been recently proposed that ZA could have direct anti-tumour effects, although the molecular mechanism is unknown. We herein unravel a novel anti-tumour activity of ZA in prostate cancer (PCa), by targeting the pro-tumorigenic properties of both stromal and immune cells. Particularly, we demonstrate that ZA impairs PCa-induced M2-macrophages polarization, reducing their pro-invasive effect on tumour cells and their pro-angiogenic features. Crucially, ZA administration reverts cancer associated fibroblasts (CAFs) activation by targeting the mevalonate pathway and RhoA geranyl-geranylation, thereby impairing smooth muscle actin-α fibers organization, a prerequisite of fibroblast activation. Moreover, ZA prevents the M2 macrophages-mediated activation of normal fibroblast, highlighting the broad efficacy of this drug on tumour microenvironment. These results are confirmed in a metastatic xenograft PCa mouse model in which ZA-induced stromal normalization impairs cancer-stromal cells crosstalk, resulting in a significant reduction of primary tumour growth and metastases. Overall these findings reinforce the efficacy of ZA as a potential therapeutic approach to reduce cancer aggressiveness, by abrogating the supportive role of tumour microenvironment.

Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-08-28

Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast 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

Carcinoma of Unknown Primary Treatment (PDQ®)—Health Professional Version

Cancer.gov

Carcinoma of unknown primary (CUP) treatment depends on the best determination of the primary site, if possible. Treatment options may include surgery, radiation therapy, and systemic treatment. Get detailed information about diagnosis and treatment of CUP in this summary for clinicians.

Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer

ClinicalTrials.gov

2013-06-03

Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; 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

Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

ClinicalTrials.gov

2016-02-15

Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; 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

Correlation between adenoma detection rate in colonoscopy- and fecal immunochemical testing-based colorectal cancer screening programs.

PubMed

Cubiella, Joaquín; Castells, Antoni; Andreu, Montserrat; Bujanda, Luis; Carballo, Fernando; Jover, Rodrigo; Lanas, Ángel; Morillas, Juan Diego; Salas, Dolores; Quintero, Enrique

2017-03-01

The adenoma detection rate (ADR) is the main quality indicator of colonoscopy. The ADR recommended in fecal immunochemical testing (FIT)-based colorectal cancer screening programs is unknown. Using the COLONPREV (NCT00906997) study dataset, we performed a post-hoc analysis to determine if there was a correlation between the ADR in primary and work-up colonoscopy, and the equivalent figure to the minimal 20% ADR recommended. Colonoscopy was performed in 5722 individuals: 5059 as primary strategy and 663 after a positive FIT result (OC-Sensor™; cut-off level 15 µg/g of feces). We developed a predictive model based on a multivariable lineal regression analysis including confounding variables. The median ADR was 31% (range, 14%-51%) in the colonoscopy group and 55% (range, 21%-83%) in the FIT group. There was a positive correlation in the ADR between primary and work-up colonoscopy (Pearson's coefficient 0.716; p  < 0.001). ADR in the FIT group was independently related to ADR in the colonoscopy group: regression coefficient for colonoscopy ADR, 0.71 ( p  = 0.009); sex, 0.09 ( p  = 0.09); age, 0.3 ( p  = 0.5); and region 0.00 ( p  = 0.9). The equivalent figure to the 20% ADR was 45% (95% confidence interval, 35%-56%). ADR in primary and work-up colonoscopy of a FIT-positive result are positively and significantly correlated.

Correlation between adenoma detection rate in colonoscopy- and fecal immunochemical testing-based colorectal cancer screening programs

PubMed Central

Castells, Antoni; Andreu, Montserrat; Bujanda, Luis; Carballo, Fernando; Jover, Rodrigo; Lanas, Ángel; Morillas, Juan Diego; Salas, Dolores; Quintero, Enrique

2016-01-01

Background The adenoma detection rate (ADR) is the main quality indicator of colonoscopy. The ADR recommended in fecal immunochemical testing (FIT)-based colorectal cancer screening programs is unknown. Methods Using the COLONPREV (NCT00906997) study dataset, we performed a post-hoc analysis to determine if there was a correlation between the ADR in primary and work-up colonoscopy, and the equivalent figure to the minimal 20% ADR recommended. Colonoscopy was performed in 5722 individuals: 5059 as primary strategy and 663 after a positive FIT result (OC-Sensor™; cut-off level 15 µg/g of feces). We developed a predictive model based on a multivariable lineal regression analysis including confounding variables. Results The median ADR was 31% (range, 14%–51%) in the colonoscopy group and 55% (range, 21%–83%) in the FIT group. There was a positive correlation in the ADR between primary and work-up colonoscopy (Pearson’s coefficient 0.716; p < 0.001). ADR in the FIT group was independently related to ADR in the colonoscopy group: regression coefficient for colonoscopy ADR, 0.71 (p = 0.009); sex, 0.09 (p = 0.09); age, 0.3 (p = 0.5); and region 0.00 (p = 0.9). The equivalent figure to the 20% ADR was 45% (95% confidence interval, 35%–56%). Conclusions ADR in primary and work-up colonoscopy of a FIT-positive result are positively and significantly correlated. PMID:28344793

Role of Definitive Radiation Therapy in Carcinoma of Unknown Primary in the Abdomen and Pelvis

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

Kelly, Patrick; Das, Prajnan; Varadhachary, Gauri R.

2012-04-01

Objectives: Carcinoma of unknown primary (CUP) in the abdomen and pelvis is a heterogeneous group of cancers with no standard treatment. Considered by many to be incurable, these patients are often treated with chemotherapy alone. In this study, we determined the effectiveness of radiation therapy in combination with chemotherapy in patients with CUP in the abdomen and pelvis. Patients and Methods: Medical records were reviewed for 37 patients with CUP treated with radiation therapy for disease located in the soft tissues and/or nodal basins of the abdomen and pelvis at University of Texas M.D. Anderson Cancer between 2002 and 2009.more » All patients underwent chemotherapy, either before or concurrent with radiation therapy. Patients were selected for radiation therapy on the basis of histologic type, disease extent, and prior therapy response. Twenty patients underwent definitive radiation therapy (defined as radiation therapy targeting all known disease sites with at least 45 Gy) and 17 patients underwent palliative radiation therapy. Only 6 patients had surgical resection of their disease. Patient and treatment characteristics were extracted and the endpoints of local disease control, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity incidence were analyzed. Results: The 2-year PFS and OS rates for the entire cohort were 32% and 57%, respectively. However, in patients treated with definitive radiation therapy, the rates were 48% and 76%, and 7 patients lived more than 3 years after treatment with no evidence of disease progression. Nevertheless, radiation-associated toxicity was significant in this cohort, as 40% experienced Grade 2 or higher late toxicities. Conclusions: The use of definitive radiation therapy should be considered in selected patients with CUP in the soft tissues or nodal basins of the abdomen and pelvis.« less

Patterns of care analysis for head & neck cancer of unknown primary site: a survey inside the German society of radiation oncology (DEGRO).

PubMed

Müller von der Grün, Jens; Bon, Dimitra; Rödel, Claus; Balermpas, Panagiotis

2018-05-14

Due to the absence of randomized trials, the optimal management for squamous cell cancer of unknown primary in the head and neck region (SCCHN CUP) remains controversial. Current strategies are based on retrospective studies, clinical experience, and institutional policies. An anonymous questionnaire with a total of 24 questions was created and distributed by the use of an online version (Google Forms®, Google, Mountain View, CA, USA) as well as a printout version as equivalent option. An email with a link to the survey and the questionnaire as attachment was sent to 361 DEGRO(German Society of Radiation Oncology)-associated departments. Frequency distributions of responses for each question were calculated. The data were also analyzed by type of practice. Representativity of the sample size for the DEGRO was also evaluated. 66 responses were received including answers from 20 (30%) university departments, 16 (24%) non-university institutions, and 30 (46%) radiation oncology practices. 95% of the participants routinely present these cases in an interdisciplinary tumor board and use intensity modulated radiotherapy (IMRT) techniques for SCCHN CUP treatment. Surgery includes neck dissection in 83% and tonsillectomy in 73% of the cases. Human papilloma virus (HPV) status is routinely determined in 82% of the departments. Statistically significant differences between universities and institutions and clinics and practices could be found with respect to positron emission tomography-computed tomography (PET-CT) utilization, indications for chemotherapy, radiotherapy volumes, and cumulative doses. Diagnostics and treatment for SCCHN CUP within the DEGRO remain heterogeneous. A prospective register trial with standard operation procedures is warranted to homogenize and possibly improve management.

PET Imaging of Ovarian Carcinoma With 18F-FSPG

ClinicalTrials.gov

2018-06-04

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

PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

ClinicalTrials.gov

2018-02-08

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

Differential proteomic profiling of primary and recurrent chordomas.

PubMed

Chen, Su; Xu, Wei; Jiao, Jian; Jiang, Dongjie; Liu, Jian; Chen, Tenghui; Wan, Zongmiao; Xu, Leqin; Zhou, Zhenhua; Xiao, Jianru

2015-05-01

Chordomas are locally destructive tumors with high rates of recurrence and a poor prognosis. The mechanisms involved in chordoma recurrence remain largely unknown. In the present study, we examined the proteomic profile of a chordoma primary tumor (CSO) and a recurrent tumor (CSR) through mass spectrum in a chordoma patient who underwent surgery. Bioinformatic analysis of the profile showed that 359 proteins had a significant expression difference and 21 pathways had a striking alteration between the CSO and the CSR. The CSR showed a significant increase in carbohydrate metabolism. Immunohistochemistry (IHC) confirmed that the cancer stem cell marker activated leukocyte cell adhesion molecule (ALCAM or CD166) expression level was higher in the recurrent than that in the primary tumor. The present study analyzed the proteomic profile change between CSO and CSR and identified a new biomarker ALCAM in recurrent chordomas. This finding sheds light on unraveling the pathophysiology of chordoma recurrence and on exploring more effective prognostic biomarkers and targeted therapies against this devastating disease.

Safety and Tolerability of TAR-200 and Nivolumab in Subjects With Muscle-Invasive Bladder Cancer

ClinicalTrials.gov

2018-05-04

Bladder Cancer TNM Staging Primary Tumor (T) T2; Bladder Cancer TNM Staging Primary Tumor (T) T2A; Bladder Cancer TNM Staging Primary Tumor (T) T2B; Bladder Cancer TNM Staging Primary Tumor (T) T3; Bladder Cancer TNM Staging Primary Tumor (T) T3A; Bladder Cancer TNM Staging Primary Tumor (T) T3B; Bladder Cancer TNM Staging Regional Lymph Node (N) N0; Bladder Cancer TNM Staging Regional Lymph Node (N) N1; Bladder Cancer TNM Staging Distant Metastasis (M) M0

Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer

ClinicalTrials.gov

2018-04-26

Recurrent Uterine Corpus Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Cancer; Recurrent Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cavity Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast cancer through AKT and NF-κB signaling.

PubMed

Xu, Hongying; Xiao, Qian; Fan, Yu; Xiang, Tingxiu; Li, Chen; Li, Chunhong; Li, Shuman; Hui, Tianli; Zhang, Lu; Li, Hongzhong; Li, Lili; Ren, Guosheng

2017-06-01

ADAMTS18 dysregulation plays an important role in many disease processes including cancer. We previously found ADAMTS18 as frequently methylated tumor suppressor gene (TSG) for multiple carcinomas, however, its biological functions and underlying molecular mechanisms in breast carcinogenesis remain unknown. Here, we found that ADAMTS18 was silenced or downregulated in breast cancer cell lines. ADAMTS18 was reduced in primary breast tumor tissues as compared with their adjacent noncancer tissues. ADAMTS18 promoter methylation was detected in 70.8% of tumor tissues by methylation-specific PCR, but none of the normal tissues. Demethylation treatment restored ADAMTS18 expression in silenced breast cell lines. Ectopic expression of ADAMTS18 in breast tumor cells resulted in inhibition of cell migration and invasion. Nude mouse model further confirmed that ADAMTS18 suppressed breast cancer metastasis in vivo. Further mechanistic studies showed that ADAMTS18 suppressed epithelial-mesenchymal transition (EMT), further inhibited migration and invasion of breast cancer cells. ADAMT18 deregulated AKT and NF-κB signaling, through inhibiting phosphorylation levels of AKT and p65. Thus, ADAMTS18 as an antimetastatic tumor suppressor antagonizes AKT and NF-κB signaling in breast tumorigenesis. Its methylation could be a potential tumor biomarker for breast cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Poor prognostic role of the pretreatment platelet counts in colorectal cancer: A meta-analysis.

PubMed

Rao, Xu-Dong; Zhang, Hua; Xu, Zheng-Shui; Cheng, Hua; Shen, Wei; Wang, Xin-Ping

2018-06-01

Recently, a wide variety of studies have suggested that elevated platelet counts are associated with survival in patients with colorectal cancer. On one hand several studies suggest a negative connection in colorectal cancer patients with pre-operative thrombocytosis, on the other hand other studies contradicts this. However, it remains unknown whether elevated platelet counts are associated with survival in colorectal cancer patients. We therefore conducted this meta-analysis to evaluate the prognostic role of platelet counts in colorectal cancer. PubMed, Embase, and the Cochrane Library databases were searched from their inception to October 15, 2016 to identify relevant studies that have explored the prognostic role of platelet counts in colorectal cancer. Studies that examined the association between platelet counts and prognoses in colorectal cancer and that provided a hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) and/or disease-free survival (DFS) were included. This meta-analysis included 9 retrospective cohort studies involving 3413 patients with colorectal cancer. OS was shorter in patients with elevated platelet counts than in patients with normal counts (HR 2.11, 95% CI: 1.68-2.65). For DFS, an elevated platelet count was also a poor predictor (HR 2.51, 95% CI: 1.84-3.43). In this meta-analysis, we suggest that an elevated platelet count is a negative predictor of survival in both primary colorectal cancer and resectable colorectal liver metastases.

TMPRSS4 regulates levels of integrin α5 in NSCLC through miR-205 activity to promote metastasis.

PubMed

Larzabal, L; de Aberasturi, A L; Redrado, M; Rueda, P; Rodriguez, M J; Bodegas, M E; Montuenga, L M; Calvo, A

2014-02-04

TMPRSS4 is a membrane-anchored protease involved in cell migration and invasion in different cancer types including lung cancer. TMPRSS4 expression is increased in NSCLC and its inhibition through shRNA reduces lung metastasis. However, molecular mechanisms leading to the protumorigenic regulation of TMPRSS4 in lung cancer are unknown. miR-205 was identified as an overexpressed gene upon TMPRSS4 downregulation through microarray analysis. Cell migration and invasion assays and in vivo lung primary tumour and metastasis models were used for functional analysis of miR-205 overexpression in H2170 and H441 cell lines. Luciferase assays were used to identify a new miR-205 direct target in NSCLC. miR-205 overexpression promoted an epithelial phenotype with increased E-cadherin and reduced fibronectin. Furthermore, miR-205 expression caused a G0/G1 cell cycle arrest and inhibition of cell growth, migration, attachment to fibronectin, primary tumour growth and metastasis formation in vivo. Integrin α5 (a proinvasive protein) was identified as a new miR-205 direct target in NSCLC. Integrin α5 downregulation in lung cancer cells resulted in complete abrogation of cell migration, a decreased capacity to adhere to fibronectin and reduced in vivo tumour growth, compared with control cells. TMPRSS4 silencing resulted in a concomitant reduction of integrin α5 levels. We have demonstrated for the first time a new molecular pathway that connects TMPRSS4 and integrin α5 through miR-205 to regulate cancer cell invasion and metastasis. Our results will help designing new therapeutic strategies to inhibit this novel pathway in NSCLC.

Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

ClinicalTrials.gov

2018-05-25

Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Breast Cancer

Cost of Cancer-Related Neutropenia or Fever Hospitalizations, United States, 2012.

PubMed

Tai, Eric; Guy, Gery P; Dunbar, Angela; Richardson, Lisa C

2017-06-01

Neutropenia and subsequent infections are life-threatening treatment-related toxicities of chemotherapy. Among patients with cancer, hospitalizations related to neutropenic complications result in substantial medical costs, morbidity, and mortality. Previous estimates for the cost of cancer-related neutropenia hospitalizations are based on older and limited data. This study provides nationally representative estimates of the cost of cancer-related neutropenia hospitalizations. We examined data from the 2012 National Inpatient Sample and Kids' Inpatient Database. Hospitalizations for cancer-related neutropenia were defined as those with a primary or secondary diagnosis of cancer and a diagnosis of neutropenia or a fever of unknown origin. We examined characteristics of cancer-related neutropenia hospitalizations among children (age < 18 years) and adults (age ≥ 18 years). Adjusted predicted margins were used to estimate length of stay and cost per stay. There were 91,560 and 16,859 cancer-related neutropenia hospitalizations among adults and children, respectively. Total cost of cancer-related neutropenia hospitalizations was $2.3 billion for adults and $439 million for children. Cancer-related neutropenia hospitalizations accounted for 5.2% of all cancer-related hospitalizations and 8.3% of all cancer-related hospitalization costs. For adults, the mean length of stay for cancer-related neutropenia hospitalizations was 9.6 days, with a mean hospital cost of $24,770 per stay. For children, the mean length of stay for cancer-related neutropenia hospitalizations was 8.5 days, with a mean hospital cost of $26,000 per stay. We found the costs of cancer-related neutropenia hospitalizations to be substantially high. Efforts to prevent and minimize neutropenia-related complications among patients with cancer may decrease hospitalizations and associated costs.

Cost of Cancer-Related Neutropenia or Fever Hospitalizations, United States, 2012

PubMed Central

Guy, Gery P.; Dunbar, Angela; Richardson, Lisa C.

2017-01-01

Purpose: Neutropenia and subsequent infections are life-threatening treatment-related toxicities of chemotherapy. Among patients with cancer, hospitalizations related to neutropenic complications result in substantial medical costs, morbidity, and mortality. Previous estimates for the cost of cancer-related neutropenia hospitalizations are based on older and limited data. This study provides nationally representative estimates of the cost of cancer-related neutropenia hospitalizations. Methods: We examined data from the 2012 National Inpatient Sample and Kids’ Inpatient Database. Hospitalizations for cancer-related neutropenia were defined as those with a primary or secondary diagnosis of cancer and a diagnosis of neutropenia or a fever of unknown origin. We examined characteristics of cancer-related neutropenia hospitalizations among children (age < 18 years) and adults (age ≥ 18 years). Adjusted predicted margins were used to estimate length of stay and cost per stay. Results: There were 91,560 and 16,859 cancer-related neutropenia hospitalizations among adults and children, respectively. Total cost of cancer-related neutropenia hospitalizations was $2.3 billion for adults and $439 million for children. Cancer-related neutropenia hospitalizations accounted for 5.2% of all cancer-related hospitalizations and 8.3% of all cancer-related hospitalization costs. For adults, the mean length of stay for cancer-related neutropenia hospitalizations was 9.6 days, with a mean hospital cost of $24,770 per stay. For children, the mean length of stay for cancer-related neutropenia hospitalizations was 8.5 days, with a mean hospital cost of $26,000 per stay. Conclusion: We found the costs of cancer-related neutropenia hospitalizations to be substantially high. Efforts to prevent and minimize neutropenia-related complications among patients with cancer may decrease hospitalizations and associated costs. PMID:28437150

Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma.

PubMed

Cao, Yueyu; Qiao, Jing; Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

2017-02-28

Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides "killing" PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors.

Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-12-28

Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; 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; Undifferentiated Ovarian Carcinoma

Associations between residual disease and survival in epithelial ovarian cancer by histologic type.

PubMed

Melamed, Alexander; Manning-Geist, Beryl; Bregar, Amy J; Diver, Elisabeth J; Goodman, Annekathryn; Del Carmen, Marcela G; Schorge, John O; Rauh-Hain, J Alejandro

2017-11-01

Surgical cytoreduction has been postulated to affect survival by increasing the efficacy of chemotherapy in ovarian cancer. We hypothesized that women with high-grade serous ovarian cancer, which usually responds to chemotherapy, would derive greater benefit from complete cytoreduction than those with histologic subtypes that are less responsive to chemotherapy, such as mucinous and clear cell carcinoma. We conducted a retrospective cohort study of patients who underwent primary cytoreductive surgery and adjuvant chemotherapy for stage IIIC or IV epithelial ovarian cancer from 2011 to 2013 using data from the National Cancer Database. We constructed multivariable models to quantify the magnitude of associations between residual disease status (no residual disease, ≤1cm, or >1cm) and all-cause mortality by histologic type among women with clear cell, mucinous, and high-grade serous ovarian cancer. Because 26% of the sample had unknown residual disease status, we used multiple imputations in the primary analysis. We identified 6,013 women with stage IIIC and IV high-grade serous, 307 with clear cell, and 140 with mucinous histology. The association between residual disease status and mortality hazard did not differ significantly among histologic subtypes of ovarian cancer (p for interaction=0.32). In covariate adjusted models, compared to suboptimal cytoreduction, cytoreduction to no gross disease was associated with a hazard reduction of 42% in high-grade serous carcinoma (hazard ratio [HR]=0.58, 95% confidence interval [CI]=0.49-0.68), 61% in clear cell carcinoma (HR=0.39, 95% CI=0.22-0.69), and 54% in mucinous carcinoma (HR=0.46, 95% CI=0.22-0.99). We found no evidence that surgical cytoreduction was of greater prognostic importance in high-grade serous carcinomas than in histologies that are less responsive to chemotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

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

ClinicalTrials.gov

2018-03-22

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

Carcinoma of Unknown Primary Treatment (PDQ®)—Patient Version

Cancer.gov

Carcinoma of unknown primary (CUP), treatment can include surgery, radiation therapy, chemotherapy, or hormone therapy. Get detailed information about the diagnosis and treatment of CUP in this expert-reviewed summary.

Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The Role and Timing of Radiosurgery

PubMed Central

Han, Hyun Jin; Chang, Won Seok; Jung, Hyun Ho; Park, Yong Gou

2016-01-01

Background Up to 15% of all patients with brain metastases have no clearly detected primary site despite intensive evaluation, and this incidence has decreased with the use of improved imaging technology. Radiosurgery has been evaluated as one of the treatment modality for patients with limited brain metastases. In this study, we evaluated the effectiveness of radiosurgery for brain metastases from unknown primary tumors. Methods We retrospectively evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain metastases radiologically diagnosed between August 1992 and September 2007 in our institution. First, the brain metastases were grouped into metachronous, synchronous, and precocious presentations according to the timing of diagnosis of the brain metastases. Then, synchronous and precocious brain metastases were further grouped into 1) unknown primary; 2) delayed known primary; and 3) synchronous metastases according to the timing of diagnosis of the primary origin. We analyzed the survival time and time to new brain metastasis in each group. Results Of the 540 patients, 29 (5.4%) presented precocious or synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor was not found even after intensive and repeated systemic evaluation in 10 patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed known primary, 1.2%); and diagnosed at the same time as the brain metastases in 16 patients (synchronous metastasis, 55.2%). No statistically significant differences in survival time and time to new brain metastasis were found among the three groups. Conclusion Identification of a primary tumor before GKRS did not affect the patient outcomes. If other possible differential diagnoses were completely excluded, early GKRS can be an effective treatment option for brain metastases from unknown primary tumor. PMID:27867920

Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers

ClinicalTrials.gov

2017-02-10

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; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Quantitative modeling of clinical, cellular, and extracellular matrix variables suggest prognostic indicators in cancer: a model in neuroblastoma.

PubMed

Tadeo, Irene; Piqueras, Marta; Montaner, David; Villamón, Eva; Berbegall, Ana P; Cañete, Adela; Navarro, Samuel; Noguera, Rosa

2014-02-01

Risk classification and treatment stratification for cancer patients is restricted by our incomplete picture of the complex and unknown interactions between the patient's organism and tumor tissues (transformed cells supported by tumor stroma). Moreover, all clinical factors and laboratory studies used to indicate treatment effectiveness and outcomes are by their nature a simplification of the biological system of cancer, and cannot yet incorporate all possible prognostic indicators. A multiparametric analysis on 184 tumor cylinders was performed. To highlight the benefit of integrating digitized medical imaging into this field, we present the results of computational studies carried out on quantitative measurements, taken from stromal and cancer cells and various extracellular matrix fibers interpenetrated by glycosaminoglycans, and eight current approaches to risk stratification systems in patients with primary and nonprimary neuroblastoma. New tumor tissue indicators from both fields, the cellular and the extracellular elements, emerge as reliable prognostic markers for risk stratification and could be used as molecular targets of specific therapies. The key to dealing with personalized therapy lies in the mathematical modeling. The use of bioinformatics in patient-tumor-microenvironment data management allows a predictive model in neuroblastoma.

Study to Evaluate the Safety and Tolerability of Avelumab in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies

ClinicalTrials.gov

2018-04-27

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Neoplasms of Uncertain or Unknown Behavior

Metformin and Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-04-17

Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

Associations between structural capabilities of primary care practices and performance on selected quality measures.

PubMed

Friedberg, Mark W; Coltin, Kathryn L; Safran, Dana Gelb; Dresser, Marguerite; Zaslavsky, Alan M; Schneider, Eric C

2009-10-06

Recent proposals to reform primary care have encouraged physician practices to adopt such structural capabilities as performance feedback and electronic health records. Whether practices with these capabilities have higher performance on measures of primary care quality is unknown. To measure associations between structural capabilities of primary care practices and performance on commonly used quality measures. Cross-sectional analysis. Massachusetts. 412 primary care practices. During 2007, 1 physician from each participating primary care practice (median size, 4 physicians) was surveyed about structural capabilities of the practice (responses representing 308 practices were obtained). Data on practice structural capabilities were linked to multipayer performance data on 13 Healthcare Effectiveness Data and Information Set (HEDIS) process measures in 4 clinical areas: screening, diabetes, depression, and overuse. Frequently used multifunctional electronic health records were associated with higher performance on 5 HEDIS measures (3 in screening and 2 in diabetes), with statistically significant differences in performance ranging from 3.1 to 7.6 percentage points. Frequent meetings to discuss quality were associated with higher performance on 3 measures of diabetes care (differences ranging from 2.3 to 3.1 percentage points). Physician awareness of patient experience ratings was associated with higher performance on screening for breast cancer and cervical cancer (1.9 and 2.2 percentage points, respectively). No other structural capabilities were associated with performance on more than 1 measure. No capabilities were associated with performance on depression care or overuse. Structural capabilities of primary care practices were assessed by physician survey. Among the investigated structural capabilities of primary care practices, electronic health records were associated with higher performance across multiple HEDIS measures. Overall, the modest magnitude and limited number of associations between structural capabilities and clinical performance suggest the importance of continuing to measure the processes and outcomes of care for patients. The Commonwealth Fund.

Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-02-14

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Neoplasm; High Grade Ovarian Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage III Fallopian Tube Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Primary Peritoneal Cancer AJCC v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism.

PubMed

Louzada, Martha L; Carrier, Marc; Lazo-Langner, Alejandro; Dao, Vi; Kovacs, Michael J; Ramsay, Timothy O; Rodger, Marc A; Zhang, Jerry; Lee, Agnes Y Y; Meyer, Guy; Wells, Philip S

2012-07-24

Long-term low-molecular-weight heparin (LMWH) is the current standard for treatment of venous thromboembolism (VTE) in cancer patients. Whether treatment strategies should vary according to individual risk of VTE recurrence remains unknown. We performed a retrospective cohort study and a validation study in patients with cancer-associated VTE to derive a clinical prediction rule that stratifies VTE recurrence risk. The cohort study of 543 patients determined the model with the best classification performance included 4 independent predictors (sex, primary tumor site, stage, and prior VTE) with 100% sensitivity, a wide separation of recurrence rates, 98.1% negative predictive value, and a negative likelihood ratio of 0.16. In this model, the score sum ranged between -3 and 3 score points. Patients with a score ≤ 0 had low risk (≤ 4.5%) for recurrence and patients with a score >1 had a high risk (≥ 19%) for VTE recurrence. Subsequently, we applied and validated the rule in an independent set of 819 patients from 2 randomized, controlled trials comparing low-molecular-weight heparin to coumarin treatment in cancer patients. By identifying VTE recurrence risk in cancer patients with VTE, we may be able to tailor treatment, improving clinical outcomes while minimizing costs.

Assessing the Racial and Ethnic Disparities in Breast Cancer Mortality in the United States

PubMed Central

Yedjou, Clement G.; Tchounwou, Paul B.; Payton, Marinelle; Miele, Lucio; Fonseca, Duber D.; Lowe, Leroy; Alo, Richard A.

2017-01-01

Breast cancer is the second leading cause of cancer related deaths among women aged 40–55 in the United States and currently affects more than one in ten women worldwide. It is also one of the most diagnosed cancers in women both in wealthy and poor countries. Fortunately, the mortality rate from breast cancer has decreased in recent years due to increased emphasis on early detection and more effective treatments in White population. Although the mortality rates have declined in some ethnic populations, the overall cancer incidence among African American and Hispanic populations has continued to grow. The goal of the present review article was to highlight similarities and differences in breast cancer morbidity and mortality rates primarily among African American women compared to White women in the United States. To reach our goal, we conducted a search of articles in journals with a primary focus on minority health, and authors who had published articles on racial/ethnic disparity related to breast cancer patients. A systematic search of original research was conducted using MEDLINE, PUBMED and Google Scholar databases. We found that racial/ethnic disparities in breast cancer may be attributed to a large number of clinical and non-clinical risk factors including lack of medical coverage, barriers to early detection and screening, more advanced stage of disease at diagnosis among minorities, and unequal access to improvements in cancer treatment. Many African American women have frequent unknown or unstaged breast cancers than White women. These risk factors may explain the differences in breast cancer treatment and survival rate between African American women and White women. New strategies and approaches are needed to promote breast cancer prevention, improve survival rate, reduce breast cancer mortality, and ultimately improve the health outcomes of racial/ethnic minorities. PMID:28475137

Assessing the Racial and Ethnic Disparities in Breast Cancer Mortality in the United States.

PubMed

Yedjou, Clement G; Tchounwou, Paul B; Payton, Marinelle; Miele, Lucio; Fonseca, Duber D; Lowe, Leroy; Alo, Richard A

2017-05-05

Breast cancer is the second leading cause of cancer related deaths among women aged 40-55 in the United States and currently affects more than one in ten women worldwide. It is also one of the most diagnosed cancers in women both in wealthy and poor countries. Fortunately, the mortality rate from breast cancer has decreased in recent years due to increased emphasis on early detection and more effective treatments in White population. Although the mortality rates have declined in some ethnic populations, the overall cancer incidence among African American and Hispanic populations has continued to grow. The goal of the present review article was to highlight similarities and differences in breast cancer morbidity and mortality rates primarily among African American women compared to White women in the United States. To reach our goal, we conducted a search of articles in journals with a primary focus on minority health, and authors who had published articles on racial/ethnic disparity related to breast cancer patients. A systematic search of original research was conducted using MEDLINE, PUBMED and Google Scholar databases. We found that racial/ethnic disparities in breast cancer may be attributed to a large number of clinical and non-clinical risk factors including lack of medical coverage, barriers to early detection and screening, more advanced stage of disease at diagnosis among minorities, and unequal access to improvements in cancer treatment. Many African American women have frequent unknown or unstaged breast cancers than White women. These risk factors may explain the differences in breast cancer treatment and survival rate between African American women and White women. New strategies and approaches are needed to promote breast cancer prevention, improve survival rate, reduce breast cancer mortality, and ultimately improve the health outcomes of racial/ethnic minorities.

Expression of phosphodiesterase 6 (PDE6) in human breast cancer cells.

PubMed

Dong, Hongli; Claffey, Kevin P; Brocke, Stefan; Epstein, Paul M

2013-01-01

Considerable epidemiological evidence demonstrates a positive association between artificial light at night (LAN) levels and incidence rates of breast cancer, suggesting that exposure to LAN is a risk factor for breast cancer. There is a 30-50% higher risk of breast cancer in the highest LAN exposed countries compared to the lowest LAN countries, and studies showing higher incidence of breast cancer among shift workers exposed to more LAN have led the International Agency for Research on Cancer to classify shift work as a probable human carcinogen. Nevertheless, the means by which light can affect breast cancer is still unknown. In this study we examined established human breast cancer cell lines and patients' primary breast cancer tissues for expression of genetic components of phosphodiesterase 6 (PDE6), a cGMP-specific PDE involved in transduction of the light signal, and previously thought to be selectively expressed in photoreceptors. By microarray analysis we find highly significant expression of mRNA for the PDE6B, PDE6C, and PDE6D genes in both the cell lines and patients' tissues, minimal expression of PDE6A and PDE6G and no expression of PDE6H. Using antibody specific for PDE6β, we find expression of PDE6B protein in a wide range of patients' tissues by immunohistochemistry, and in MCF-7 breast cancer cells by immunofluorescence and Western blot analysis. Considerable expression of key circadian genes, PERIOD 2, CLOCK, TIMELESS, CRYPTOCHROME 1, and CRYPTOCHROME 2 was also seen in all breast cancer cell lines and all patients' breast cancer tissues. These studies indicate that genes for PDE6 and control of circadian rhythm are expressed in human breast cancer cells and tissues and may play a role in transducing the effects of light on breast cancer.

Vascular endothelial growth factor C promotes cervical cancer cell invasiveness via regulation of microRNA-326/cortactin expression.

PubMed

Cheng, Yang; Jiang, Shuyi; Yuan, Jin; Liu, Junxiu; Simoncini, Tommaso

2018-04-16

Vascular endothelial growth factor C (VEGF-C) accelerates cervical cancer metastasis, while the detailed mechanism remains largely unknown. Recent evidence indicates that microRNA play a crucial role in controlling cancer cell invasiveness. In the present study, we investigated the role of miR-326 in VEGF-C-induced cervical cancer cell invasion. VEGF-C expression was higher and miR-326 was much lower in primary cervical cancer specimens than that in non-cancerous specimens, and a negative correlation between VEGF-C and miR-326 was found. On cervical carcinoma cell line SiHa cells, treatment with VEGF-C downregulated miR-326 level and increased cortactin protein expression. Transfection with miR-326 mimic reversed cortactin expression induced by VEGF-C, suggesting that VEGF-C increased cortactin via downregulation of miR-326. VEGF-C activated c-Src and c-Src inhibitor PP2 abolished VEGF-C effect on miR-326 and cortactin expression, implying that VEGF-C regulated miR-326/cortactin via c-Src signaling. VEGF-C promoted SiHa cell invasion index, which was largely inhibited by transfection with miR-326 antagonist or by siRNA against cortactin. In conclusion, our findings implied that VEGF-C reduced miR-326 expression and increased cortactin expression through c-Src signaling, leading to enhanced cervical cancer invasiveness. This may shed light on potential therapeutic strategies for cervical cancer therapy.

Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-10-23

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; 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; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

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

ClinicalTrials.gov

2018-05-22

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

Overview of the 8th Edition TNM Classification for Head and Neck Cancer.

PubMed

Huang, Shao Hui; O'Sullivan, Brian

2017-07-01

The main purpose of the TNM system is to provide an anatomic-based classification to adequately depict cancer prognosis. Accurate cancer staging is important for treatment selection and outcome prediction, research design, and cancer control activities. To maintain clinical relevance, periodical updates to TNM are necessary. The recently published 8th edition TNM classification institutes the following changes to the staging of head and neck (excluding thyroid cancer): new stage classifications [HPV-related oropharyngeal cancer (HPV+ OPC) and soft tissue sarcoma of the head and neck (HN-STS)] and modification of T and N categories [T and N categories for nasopharyngeal cancer (NPC), T categories for oral cavity squamous cell carcinomas (OSCC), N categories for non-viral related head and neck cancer and unknown primary (CUP), and T categories for head and neck cutaneous carcinoma]. These changes reflect better understanding tumor biology and clinical behavior (e.g., HPV+ OPC and HN-STS), improved outcomes associated with technical advances in diagnosis and treatment (e.g., NPC), evolving knowledge about additional prognostic factors and risk stratification from research and observation (e.g., inclusion of depth of invasion variable for OSCC, inclusion of extranodal extension variable for all non-viral head and neck cancer, and reintroduction of size criteria for non-Merkel cell cutaneous carcinoma of the head and neck). This review summarizes the changes and potential advantages and limitations/caveats associated with them. Further evidence is needed to evaluate whether these changes would result in improvement in TNM stage performance to better serve the needs for clinical care, research, and cancer control.

Human Breast Cancer Cells Are Redirected to Mammary Epithelial Cells upon Interaction with the Regenerating Mammary Gland Microenvironment In-Vivo

PubMed Central

Bussard, Karen M.; Smith, Gilbert H.

2012-01-01

Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display ‘normal’ behavior when placed into ‘normal’ ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for ‘normal’ gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo. PMID:23155468

Pit-1 inhibits BRCA1 and sensitizes human breast tumors to cisplatin and vitamin D treatment

PubMed Central

Seoane, Samuel; Arias, Efigenia; Sigueiro, Rita; Sendon-Lago, Juan; Martinez-Ordoñez, Anxo; Castelao, Esteban; Eiró, Noemí; Garcia-Caballero, Tomás; Macia, Manuel; Lopez-Lopez, Rafael; Maestro, Miguel; Vizoso, Francisco; Mouriño, Antonio; Perez-Fernandez, Roman

2015-01-01

The POU class 1 homeobox 1 (POU1F1, also known as Pit-1), pertaining to the Pit-Oct-Unc (POU) family of transcription factors, has been related to tumor growth and metastasis in breast. However, its role in response to breast cancer therapy is unknown. We found that Pit-1 down-regulated DNA-damage and repair genes, and specifically inhibited BRCA1 gene expression, sensitizing breast cancer cells to DNA-damage agents. Administration of 1α, 25-dihydroxy-3-epi-vitamin D3 (3-Epi, an endogenous low calcemic vitamin D metabolite) reduced Pit-1 expression, and synergized with cisplatin, thus, decreasing cell proliferation and apoptosis in vitro, and reducing tumor growth in vivo. In addition, fifteen primary cultures of human breast tumors showed significantly decreased proliferation when treated with 3-Epi+cisplatin, compared to cisplatin alone. This response positively correlated with Pit-1 levels. Our findings demonstrate that high levels of Pit-1 and reduced BRCA1 levels increase breast cancer cell susceptibility to 3-Epi+cisplatin therapy. PMID:25992773

Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: a prospective study.

PubMed

Paleri, Vinidh; Carding, Paul; Chatterjee, Sanjoy; Kelly, Charles; Wilson, Janet Ann; Welch, Andrew; Drinnan, Michael

2012-12-01

The voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown. We conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time-points. Of 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time-point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures. To the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self-reported voice quality, even in the long term. Copyright © 2012 Wiley Periodicals, Inc.

CRISPR-Cas9-based target validation for p53-reactivating model compounds

PubMed Central

Wanzel, Michael; Vischedyk, Jonas B; Gittler, Miriam P; Gremke, Niklas; Seiz, Julia R; Hefter, Mirjam; Noack, Magdalena; Savai, Rajkumar; Mernberger, Marco; Charles, Joël P; Schneikert, Jean; Bretz, Anne Catherine; Nist, Andrea; Stiewe, Thorsten

2015-01-01

Inactivation of the p53 tumor suppressor by Mdm2 is one of the most frequent events in cancer, so compounds targeting the p53-Mdm2 interaction are promising for cancer therapy. Mechanisms conferring resistance to p53-reactivating compounds are largely unknown. Here we show using CRISPR-Cas9–based target validation in lung and colorectal cancer that the activity of nutlin, which blocks the p53-binding pocket of Mdm2, strictly depends on functional p53. In contrast, sensitivity to the drug RITA, which binds the Mdm2-interacting N terminus of p53, correlates with induction of DNA damage. Cells with primary or acquired RITA resistance display cross-resistance to DNA crosslinking compounds such as cisplatin and show increased DNA cross-link repair. Inhibition of FancD2 by RNA interference or pharmacological mTOR inhibitors restores RITA sensitivity. The therapeutic response to p53-reactivating compounds is therefore limited by compound-specific resistance mechanisms that can be resolved by CRISPR-Cas9-based target validation and should be considered when allocating patients to p53-reactivating treatments. PMID:26595461

Respiratory status determines the effect of emodin on cell viability.

PubMed

Dumit, Verónica I; Zerbes, Ralf M; Kaeser-Pebernard, Stephanie; Rackiewicz, Michal; Wall, Mona T; Gretzmeier, Christine; Küttner, Victoria; van der Laan, Martin; Braun, Ralf J; Dengjel, Jörn

2017-06-06

The anthraquinone emodin has been shown to have antineoplastic properties and a wealth of unconnected effects have been linked to its use, most of which are likely secondary outcomes of the drug treatment. The primary activity of emodin on cells has remained unknown. In the present study we demonstrate dramatic and extensive effects of emodin on the redox state of cells and on mitochondrial homeostasis, irrespectively of the cell type and organism, ranging from the yeast Saccharomyces cerevisiae to human cell lines and primary cells. Emodin binds to redox-active enzymes and its effectiveness depends on the oxidative and respiratory status of cells. We show that cells with efficient respiratory metabolism are less susceptible to emodin, whereas cells under glycolytic metabolism are more vulnerable to the compound. Our findings indicate that emodin acts in a similar way as known uncouplers of the mitochondrial electron transport chain and causes oxidative stress that particularly disturbs cancer cells.

Respiratory status determines the effect of emodin on cell viability

PubMed Central

Dumit, Verónica I; Zerbes, Ralf M; Kaeser-Pebernard, Stephanie; Rackiewicz, Michal; Wall, Mona T; Gretzmeier, Christine; Küttner, Victoria; van der Laan, Martin; Braun, Ralf J; Dengjel, Jörn

2017-01-01

The anthraquinone emodin has been shown to have antineoplastic properties and a wealth of unconnected effects have been linked to its use, most of which are likely secondary outcomes of the drug treatment. The primary activity of emodin on cells has remained unknown. In the present study we demonstrate dramatic and extensive effects of emodin on the redox state of cells and on mitochondrial homeostasis, irrespectively of the cell type and organism, ranging from the yeast Saccharomyces cerevisiae to human cell lines and primary cells. Emodin binds to redox-active enzymes and its effectiveness depends on the oxidative and respiratory status of cells. We show that cells with efficient respiratory metabolism are less susceptible to emodin, whereas cells under glycolytic metabolism are more vulnerable to the compound. Our findings indicate that emodin acts in a similar way as known uncouplers of the mitochondrial electron transport chain and causes oxidative stress that particularly disturbs cancer cells. PMID:28415582

Financial outcomes of transoral robotic surgery: A narrative review.

PubMed

Othman, Sammy; McKinnon, Brian J

2018-04-03

To determine the current cost impact and financial outcomes of transoral robotic surgery in Otolaryngology. A narrative review of the literature with a defined search strategy using Pubmed, MEDLINE, CINAHL, and Web of Science. Using keywords ENT or otolaryngology, cost or economic, transoral robotic surgery or TORs, searches were performed in Pubmed, MEDLINE, CINAHL, and Web of Science and reviewed by the authors for inclusion and analysis. Six total papers were deemed appropriate for analysis. All addressed cost impact of transoral robotic surgery (TORs) as compared to open surgical methods in treating oropharyngeal cancer and/or the identification of the primary tumor within unknown primary squamous cell carcinoma. Results showed TORs to be cost-effective. Transoral robotic surgery is currently largely cost effective for both treatment and diagnostic procedures. However, further studies are needed to qualify long-term data. Copyright © 2018. Published by Elsevier Inc.

Obesity and Peritoneal Surface Disease: Outcomes after Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Appendiceal and Colon Primary Tumors

PubMed Central

Votanopoulos, Konstantinos I.; Swords, Douglas S.; Swett, Katrina R.; Randle, Reese W.; Shen, Perry; Stewart, John H.; Levine, Edward A.

2014-01-01

Background It is estimated that 37 % of the U.S. population is obese. It is unknown how obesity influences the operative and survival outcomes of cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) procedures. Methods A retrospective analysis of a prospective database of 1,000 procedures was performed. Type of malignancy, performance status, resection status, hospital and intensive care unit stay, comorbidities, morbidity, mortality, and survival were reviewed. Results A total of 246 patients with body mass index (BMI) of >30 kg/m2 underwent 272 CRS/HIPEC procedures. Ninety-five (38.6 %) were severely obese (BMI > 35 kg/m2). A total of 135 (49.6 %) procedures were performed for appendiceal and 60 (22.1 %) for colon cancer. Median follow-up was 52 months. Both major and minor morbidity were similar for obese and non-obese patients. The 30-day mortality rates for obese and nonobese patients were 1.5 and 2.5 %, respectively. Median intensive care unit and hospital stay were 1 and 9 days, regardless of BMI. The 30-day readmission rate was similar between obese and non-obese patients (24.8 vs. 19.4 %, p = 0.11). Median survival for low-grade appendiceal cancer (LGA) was 76 months for obese patients and 107 months for non-obese patients (p = 0.32). Survival was worse for severely obese patients (median survival 54 months) versus non-obese patients with LGA (p = 0.04). Survival was similar for obese and non-obese patients with peritoneal surface disease (PSD) from colon cancer or high-grade appendiceal cancer. Conclusions Obesity does not influence postoperative morbidity or mortality of patients with PSD, regardless of primary tumor. Severe obesity is associated with decreased long-term survival only in patients with LGA primary disease; however, application of CRS/HIPEC still offers meaningful prolongation of life. Obesity should not be considered a contraindication for CRS/HIPEC procedures. PMID:23800899

Unknown primary Merkel cell carcinoma: 23 new cases and a review.

PubMed

Tarantola, Tina I; Vallow, Laura A; Halyard, Michele Y; Weenig, Roger H; Warschaw, Karen E; Weaver, Amy L; Roenigk, Randall K; Brewer, Jerry D; Otley, Clark C

2013-03-01

Knowledge is limited regarding unknown primary Merkel cell carcinoma (UPMCC). We sought to document the characteristics and behavior of UPMCC, and determine the most appropriate treatment. A multicenter, retrospective, consecutive study reviewing patients given a diagnosis of UPMCC between 1981 and 2008 was completed. In addition, a literature review of cases of UPMCC was performed. In all, 23 patients with UPMCC are described and 34 cases from previous reports are compiled. Among the 23 new cases of UPMCC, the average age at diagnosis was 66.0 years; the majority of patients were male (87%) and Caucasian (100% of those reported). One patient was immunosuppressed, and 39% had a history of other cancer. After the initial biopsy, 16 patients had further evaluation of the involved lymph node basin. Half of these had additional positive nodes (8 of 16). The majority of patients had lymph node basin involvement only (78%), whereas 22% had lymph node basin and distant metastasis. The most common lymph node basin involved was inguinal. The median size of the involved lymph node at diagnosis was 5.0 cm. At 2 years, the overall survival of stage IIIB UPMCC was significantly improved versus stage IIIB known primary Merkel cell carcinoma (MCC): 76.9% to 36.4%. Limited number of cases and retrospective review are limitations. Our data demonstrate improved overall survival in patients with stage IIIB UPMCC versus those with stage IIIB known primary MCC. Because of the unpredictable natural history of UPMCC, we recommend individualization of care based on the details of each patient's clinical presentation. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Secondary malignant neoplasms in testicular cancer survivors.

PubMed

Curreri, Stephanie A; Fung, Chunkit; Beard, Clair J

2015-09-01

Testicular cancer is the most common cancer among men aged 15 to 40 years, and the incidence of testicular cancer is steadily increasing. Despite successful treatment outcomes and the rate of survival at 5 to 10 years being 95%, survivors can experience late effects of both their cancer and the treatment they received, including secondary malignant neoplasms (SMNs). We discuss the development of non-germ cell SMNs that develop after diagnosis and treatment of testicular cancer and their effect on mortality. Patients diagnosed with testicular cancer frequently choose postoperative surveillance if they are diagnosed with clinical stage I disease. These patients may experience an increased risk for developing SMNs following radiation exposure from diagnostic imaging. Similarly, radiotherapy for testicular cancer is associated with increased risks of developing both solid tumors and leukemia. Studies have reported that patients exposed to higher doses of radiation have an increased risk of developing SMNs when compared with patients who received lower doses of radiation. Patients treated with chemotherapy also experience an increased risk of developing SMNs following testicular cancer, though the risk following chemotherapy and radiation therapy combined is not well described. A large population-based study concluded that the rate ratios for both cancer-specific and all-cause mortality for SMNs among testicular cancer survivors were not significantly different from those of matched first cancers. Although it is known that patients who receive adjuvant chemotherapy or radiotherapy or who undergo routine diagnostic or follow-up imaging for a primary testicular cancer are at an increased risk for developing SMNs, the extent of this risk is largely unknown. It is critically important that research be conducted to determine this risk and its contributing factors as accurately as possible. Copyright © 2015 Elsevier Inc. All rights reserved.

Family history of cancer and risk of sporadic differentiated thyroid carcinoma.

PubMed

Xu, Li; Li, Guojun; Wei, Qingyi; El-Naggar, Adel K; Sturgis, Erich M

2012-03-01

Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since the 1980s. Although the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid carcinoma (DTC). Therefore, the authors explored the association between sporadic DTC and family history of cancer. In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer. The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR, 4.1; 95% CI, 1.7-9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR, 4.6; 95% CI, 1.9-11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR, 7.4; 95% CI, 1.8-30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs 35.5%, P = .01). The study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. Copyright © 2011 American Cancer Society.

Family History of Cancer and Risk of Sporadic Differentiated Thyroid Carcinoma

PubMed Central

Xu, Li; Li, Guojun; Wei, Qingyi; El-Naggar, Adel K.; Sturgis, Erich M.

2011-01-01

BACKGROUND Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since 1980s. While the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid cancer (DTC). Therefore, we explored the association between sporadic DTC and family history of cancer. METHODS In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer. RESULTS The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR = 4.1, 95% CI: 1.7–9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR = 4.6, 95 CI%: 1.9–11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR = 7.4, 95% CI: 1.8–30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs. 35.5%, p = 0.01). CONCLUSIONS Our study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. PMID:21800288

Malignancies in Primary Sclerosing Cholangitis – A Continuing Threat

PubMed Central

Bonato, Giulia; Cristoferi, Laura; Strazzabosco, Mario; Fabris, Luca

2016-01-01

Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease of unknown etiology, primarily targeting cholangiocytes at any portion of the biliary tree. No effective medical treatments are currently available. A unique feature of PSC is its close association (about 80%) with inflammatory bowel disease (IBD), mainly ulcerative colitis (UC). As in many chronic inflammatory conditions, cancer development can complicate PSC, accounting for >40% of deaths. Cholangiocarcinoma (CCA), gallbladder carcinoma (GBC) and colorectal carcinoma (CRC) have been variably associated to PSC, with a prevalence up to 13–14%. The risk of cancer is one of the most challenging issues in the management of PSC; it raises several questions about cancer surveillance, early diagnosis, prevention and treatment. Key Messages Among the different cancers complicating PSC, CCA is the most relevant, because it is more frequent (incidence of 0.5–1.5%) and because the prognosis is poor (5-year survival <10%). Early diagnosis of CCA in PSC can be difficult because lesions may not be evident in radiological studies. Surgical resection provides disappointing results; liver transplantation combined with neoadjuvant chemoradiotherapy is being proposed, but this approach is limited to a highly selected group of patients and is available only in a few specialized centers. Similar to CCA, GBC carries a dismal prognosis. Since it is difficult to discriminate GBC from other gallbladder abnormalities, cholecystectomy has been proposed in all gallbladder lesions detected in PSC, regardless of their size. CRC is a frequent complication of PSC associated to UC; its incidence steadily increases with time of colitis, reaching up to 20–30% of the patients after 20 years. Colonoscopy with extensive histologic sampling at an annual/biannual interval is an effective surveillance strategy. However, when dysplastic lesions are detected, preemptive proctocolectomy should be considered. Conclusions PSC may be regarded as paradigmatic of the sequence leading from chronic inflammatory epithelial damage to neoplastic transformation. Understanding the molecular mechanisms regulating this patho-genetic sequence, may improve strategies of disease surveillance and cancer prevention and treatment. PSC is a chronic inflammatory cholangiopathy of unknown etiology but likely immune-mediated, characterized by peribiliary inflammation and fibrosis leading to strictures in any portion (intra-and/or extrahepatic) of the bile duct system. No effective medical treatments are currently available. A unique feature of PSC is the close association (about 80%) with IBD, mainly UC, often diagnosed before PSC (PSC/UC). As in other chronic inflammatory diseases, development of malignancies is a feared complication of PSC. PMID:26641079

Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts

PubMed Central

Comito, Giuseppina; Segura, Coral Pons; Taddei, Maria Letizia; Lanciotti, Michele; Serni, Sergio; Morandi, Andrea; Chiarugi, Paola; Giannoni, Elisa

2017-01-01

Zoledronic acid (ZA) is a biphosphonate used for osteoporosis treatment and also proved to be effective to reduce the pain induced by bone metastases when used as adjuvant therapy in solid cancers. However, it has been recently proposed that ZA could have direct anti-tumour effects, although the molecular mechanism is unknown. We herein unravel a novel anti-tumour activity of ZA in prostate cancer (PCa), by targeting the pro-tumorigenic properties of both stromal and immune cells. Particularly, we demonstrate that ZA impairs PCa-induced M2-macrophages polarization, reducing their pro-invasive effect on tumour cells and their pro-angiogenic features. Crucially, ZA administration reverts cancer associated fibroblasts (CAFs) activation by targeting the mevalonate pathway and RhoA geranyl-geranylation, thereby impairing smooth muscle actin-α fibers organization, a prerequisite of fibroblast activation. Moreover, ZA prevents the M2 macrophages-mediated activation of normal fibroblast, highlighting the broad efficacy of this drug on tumour microenvironment. These results are confirmed in a metastatic xenograft PCa mouse model in which ZA-induced stromal normalization impairs cancer-stromal cells crosstalk, resulting in a significant reduction of primary tumour growth and metastases. Overall these findings reinforce the efficacy of ZA as a potential therapeutic approach to reduce cancer aggressiveness, by abrogating the supportive role of tumour microenvironment. PMID:27223431

Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer: a systematic review.

PubMed

Fernandes, Ricardo; Mazzarello, Sasha; Stober, Carol; Vandermeer, Lisa; Dudani, Shaan; Ibrahim, Mohamed F K; Majeed, Habeeb; Perdrizet, Kirstin; Shorr, Risa; Hutton, Brian; Fergusson, Dean; Clemons, Mark

2017-01-01

Due to the high rate of febrile neutropenia (FN) with docetaxel-cyclophosphamide (DC) chemotherapy, primary FN prophylaxis is recommended. However, the optimal choice of prophylaxis [i.e., granulocyte-colony stimulating factors (G-CSF) or antibiotics] is unknown. A systematic review was performed to address this knowledge gap. Embase, Ovid Medline, Pubmed, the Cochrane database of systematic reviews, and Cochrane register of controlled trials were searched from 1946 to April 2016 for studies evaluating primary prophylactic FN treatments in breast cancer patients receiving DC chemotherapy. Outcome measures evaluated included: incidence of FN and treatment-related hospitalizations, chemotherapy dose reduction/delays/discontinuations, and adverse events. Screening and data collection were performed by two independent reviewers. Of 2105 identified records, 7 studies (n = 2535) met the pre-specified eligibility criteria. Seven additional studies (n = 621) were identified from prior systematic reviews. There were 3 randomized controlled trials (RCTs) (n = 2256) and 11 retrospective studies (n = 900). Study sample sizes ranged from 30 to 982 patients (median 99.5), evaluating pegfilgrastim (n = 1274), filgrastim (n = 1758), and oral ciprofloxacin (n = 108). Given the heterogeneity of patients and study design, a narrative synthesis of results was performed. Median FN rates with and without primary prophylaxis were 6.6 % (IQR 3.9-10.6 %) and 31.3 % (IQR 25-33 %), respectively. No FN-related deaths were reported. No RCT directly compared G-CSF with antibiotic interventions. Primary FN prophylaxis reduces the incidence of FN. Despite considerable cost and toxicity differences between G-CSF and antibiotics, there is insufficient data to make a recommendation of one strategy over another.

A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin

PubMed Central

Seaman, Vincent; Dearwent, Steve M; Gable, Debra; Lewis, Brian; Metcalf, Susan; Orloff, Ken; Tierney, Bruce; Zhu, Jane; Logue, James; Marchetto, David; Ostroff, Stephen; Hoffman, Ronald; Xu, Mingjiang; Carey, David; Erlich, Porat; Gerhard, Glenn; Roda, Paul; Iannuzzo, Joseph; Lewis, Robert; Mellow, John; Mulvihill, Linda; Myles, Zachary; Wu, Manxia; Frank, Arthur; Gross-Davis, Carol Ann; Klotz, Judith; Lynch, Adam; Weissfeld, Joel; Weinberg, Rona; Cole, Henry

2010-01-01

Cancer cluster investigations rarely receive significant public health resource allocations due to numerous inherent challenges and the limited success of past efforts. In 2008, a cluster of polycythemia vera, a rare blood cancer with unknown etiology, was identified in northeast Pennsylvania. A multidisciplinary group of federal and state agencies, academic institutions, and local healthcare providers subsequently developed a multifaceted research portfolio designed to better understand the cause of the cluster. This research agenda represents a unique and important opportunity to demonstrate that cancer cluster investigations can produce desirable public health and scientific outcomes when necessary resources are available. PMID:20617023

Importance of residual primary cancer after induction therapy for esophageal adenocarcinoma.

PubMed

Raja, Siva; Rice, Thomas W; Ehrlinger, John; Goldblum, John R; Rybicki, Lisa A; Murthy, Sudish C; Adelstein, David; Videtic, Gregory; McNamara, Michael P; Blackstone, Eugene H

2016-09-01

To (1) assess the continuous distribution of the percentage of residual primary cancer in resection specimens after induction therapy for locally advanced esophageal adenocarcinoma, (2) determine the effects of residual primary cancer on survival after esophagectomy, (3) ascertain interplay between residual primary cancer and classical classifications of response to induction therapy (ypTNM), and (4) identify predictors of residual primary cancer. From January 2006 to November 2012, 188 patients (78%) underwent accelerated chemoradiotherapy, and 52 patients (22%) underwent chemotherapy alone followed by esophagectomy for adenocarcinoma. Mean age was 61 ± 9.2 years, and 89% were male. Residual primary cancer, assessed as the percentage of residual primary cancer cells in resection specimens, was quantified histologically by a gastrointestinal pathologist. Random Forest technology was used for data analysis. Twenty-five specimens (10%) had no residual primary cancer (ypT0), 79 (33%) had 1% to 25% residual cancer, 91 (38%) had 26% to 75%, and 45 (19%) had >75%. Survival was worse with increasing residual primary cancer, plateauing at 75%. Greater residual primary cancer was associated with worse survival across the spectrum of higher ypTN. Higher ypT, larger number of positive nodes, and use of induction chemotherapy rather than induction chemoradiotherapy were associated with greater residual primary cancer. Less residual primary cancer in response to preoperative therapy is associated with a linear increase in survival after esophagectomy for locally advanced esophageal adenocarcinoma; however, survival is poorer than for resected early-stage cancers. Therefore, for patients with poor prognostic indicators, including higher percentage of residual primary cancer, the role of adjuvant therapy needs to be further examined in an attempt to improve survival. Copyright © 2016. Published by Elsevier Inc.

Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-05-25

Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; 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; Undifferentiated Ovarian Carcinoma

Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-05-03

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; 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; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

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

Primary Care Physicians' Support of Shared Decision Making for Different Cancer Screening Decisions.

PubMed

Elston Lafata, Jennifer; Brown, Richard F; Pignone, Michael P; Ratliff, Scott; Shay, L Aubree

2017-01-01

Despite its widespread advocacy, shared decision making (SDM) is not routinely used for cancer screening. To better understand the implementation barriers, we describe primary care physicians' (PCPs') support for SDM across diverse cancer screening contexts. Surveys were mailed to a random sample of USA-based PCPs. Using multivariable logistic regression analyses, we tested for associations of PCPs' support of SDM with the US Preventive Service Task Force (USPSTF) assigned recommendation grade, assessed whether the decision pertained to not screening older patients, and the PCPs' autonomous v. controlled motivation-orientation for using SDM. PCPs (n = 278) were, on average, aged 52 years, 38% female, and 69% white. Of these, 79% endorsed discussing screening benefits as very important to SDM; 64% for discussing risks; and 31% for agreeing with patient's opinion. PCPs were most likely to rate SDM as very important for colorectal cancer screening in adults aged 50-75 years (69%), and least likely for colorectal cancer screening in adults aged >85 years (34%). Regression results indicated the importance of PCPs' having autonomous or self-determined reasons for engaging in SDM (e.g., believing in the benefits of SDM) (OR = 2.29, 95% CI, 1.87 to 2.79). PCPs' support for SDM varied by USPSTF recommendation grade (overall contrast, X 2 = 14.7; P = 0.0054), with support greatest for A-Grade recommendations. Support for SDM was lower in contexts where decisions pertained to not screening older patients (OR = 0.45, 95% CI, 0.35 to 0.56). It is unknown whether PCPs' perceptions of the importance of SDM behaviors differs with specific screening decisions or the potential limited ability to generalize findings. Our results highlight the need to document SDM benefits and consider the specific contextual challenges, such as the level of uncertainty or whether evidence supports recommending/not recommending screening, when implementing SDM across an array of cancer screening contexts. © The Author(s) 2016.

The Society of Thoracic Surgeons General Thoracic Surgery Database: establishing generalizability to national lung cancer resection outcomes.

PubMed

LaPar, Damien J; Bhamidipati, Castigliano M; Lau, Christine L; Jones, David R; Kozower, Benjamin D

2012-07-01

The Society of Thoracic Surgeons General Thoracic Surgery Database (GTDB) has demonstrated outstanding results for lung cancer resection. However, whether the GTDB results are generalizable nationwide is unknown. The purpose of this study was to establish the generalizability of the GTDB by comparing lung cancer resection results with those of the Nationwide Inpatient Sample (NIS), the largest all-payer inpatient database in the United States. From 2002 to 2008, primary lung cancer resection outcomes were compared between the GTDB (n = 19,903) and the NIS (n = 246,469). Primary outcomes were the proportion of procedures performed nationally that were captured in the GTDB and differences in mortality rates and hospital length of stay. Observed differences in patient characteristics, operative procedures, and postoperative events were also analyzed. Annual GTDB lung cancer resection volume has increased over time but only captures an estimated 8% of resections performed nationally. The GTDB and NIS databases had similar median patient age (67 vs 68 years) and female sex (50% vs 49%), lobectomy was the most common procedure (64.7% vs 79.7%; p < 0.001), and pneumonectomies were uncommon (6.3% vs 7.2%; p < 0.001). Compared with NIS, the GTDB had significantly lower unadjusted discharge mortality rates (1.8% vs 3.0%), median length of stay (5.0 vs 7.0 days; p < 0.001), and postoperative pulmonary complication rates (18.5% vs 23.6%, p < 0.001). The GTDB represents a small percentage of the lung cancer resections performed nationally and reports significantly lower mortality rates and shorter hospital length of stay than national results. The GTDB is not broadly generalizable. These results establish a benchmark for future GTDB comparisons and highlight the importance of increasing participation in the database. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy

ClinicalTrials.gov

2018-05-21

Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Mixed Epithelial Tumor; Malignant Ovarian Mucinous Tumor; Malignant Ovarian Neoplasm; Malignant Ovarian Serous Tumor; Malignant Ovarian Transitional Cell Tumor; Ovarian Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; 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; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis.

PubMed

Kuk, Deborah; Shoushtari, Alexander N; Barker, Christopher A; Panageas, Katherine S; Munhoz, Rodrigo R; Momtaz, Parisa; Ariyan, Charlotte E; Brady, Mary Sue; Coit, Daniel G; Bogatch, Kita; Callahan, Margaret K; Wolchok, Jedd D; Carvajal, Richard D; Postow, Michael A

2016-07-01

Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006-2010 and 2011-2013 had better overall survival than patients diagnosed in 2000-2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the overall survival of patients with these melanoma subtypes starting at the time of distant metastatic disease. The present study found that patients with uveal, acral, nonacral cutaneous, and unknown primary melanoma have similar overall survival after distant metastases have been diagnosed. These findings provide information for oncologists to reconsider previously held assumptions and appropriately counsel patients. Patients with mucosal melanoma have worse overall survival and are thus a group in need of specific research and advocacy. ©AlphaMed Press.

Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis

PubMed Central

Kuk, Deborah; Shoushtari, Alexander N.; Barker, Christopher A.; Panageas, Katherine S.; Munhoz, Rodrigo R.; Momtaz, Parisa; Ariyan, Charlotte E.; Brady, Mary Sue; Coit, Daniel G.; Bogatch, Kita; Callahan, Margaret K.; Wolchok, Jedd D.; Carvajal, Richard D.

2016-01-01

Background. Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. Materials and Methods. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Results. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006–2010 and 2011–2013 had better overall survival than patients diagnosed in 2000–2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Conclusion. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Implications for Practice: Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the overall survival of patients with these melanoma subtypes starting at the time of distant metastatic disease. The present study found that patients with uveal, acral, nonacral cutaneous, and unknown primary melanoma have similar overall survival after distant metastases have been diagnosed. These findings provide information for oncologists to reconsider previously held assumptions and appropriately counsel patients. Patients with mucosal melanoma have worse overall survival and are thus a group in need of specific research and advocacy. PMID:27286787

Clinical outcome of endoscopic mucosal resection for esophageal squamous cell cancer invading muscularis mucosa and submucosal layer.

PubMed

Yoshii, T; Ohkawa, S; Tamai, S; Kameda, Y

2013-07-01

When a tumor invades the muscularis mucosa and submucosal layer (T1a-MM and T1b in Japan), esophageal squamous cell cancer poses 10-50% risk of lymph node metastasis. By this stage of esophageal cancer, surgery, although very invasive, is the standard radical therapy for the patients. Endoscopic mucosal resection (EMR) is the absolutely curable treatment for cancer in the superficial mucosal layer. Because of its minimal invasiveness, the indications of EMR may be expanded to include the treatment of T1a-MM and T1b esophageal carcinoma. To date, the clinical outcomes of EMR for T1a-MM and T1b patients have not been fully elucidated. Here, the retrospective analysis of the clinical outcomes is reported. Between January 1994 and December 2007, 247 patients underwent EMR at Kanagawa Cancer Center. Of these individuals, 44 patients with 44 lesions fulfilled the following criteria: (i) extended EMR treatment for clinical T1a-MM and T1b tumor; (ii) diagnosis of clinical N0M0; and (iii) follow up for at least 1 year, and negative vertical margin. These patients were reviewed for their clinical features and outcomes. Statistical analyses were performed by the Kaplan-Meier methods, the Chi-square test, and the Cox proportional hazard model. P-value of <0.05 was considered statistically significant. The data were analyzed in February 2009. Based on the informed consent and their general health conditions, 44 patients decided the following treatments immediately after the EMR: 2 underwent surgery, 1 underwent adjuvant chemotherapy, and 41 selected follow up without any additional therapy. Of the 41 patients, 20 selected this course by choice, 12 because of severe concurrent diseases, 2 because of poor performance status, and 7 because of other multiple primary cancers. Twelve patients died; two were cause specific (4.5%), eight from multiple primary cancers, one from severe concurrent diseases, and one from unknown causes. No critical complications were noted. Median follow-up time was 51 months (12-126). Five patients ultimately developed lymph node metastasis. One patient with adjuvant chemotherapy required surgery, and another was treated with chemotherapy whose subsequent death was cause specific. The other three patients received chemoradiotherapy and have not shown cause-specific death. Overall and cause-specific survival rates at 5 years were 67.3% and 91.8%, respectively. Among 41 patients treated by EMR alone, only one died from primary esophageal cancer (2.4%), and overall and cause-specific survival rates at 5 years were 75.6% and 97.6%, respectively. Multivariate analysis revealed that severe concurrent diseases including multiple primary cancers and the administration of 5-fluorouracil-based chemotherapy for multiple primary cancers significantly influenced survival (P= 0.025, hazard ratio [HR] 13.1 [95% confidence interval 1.5-114]) and (P= 0.037, HR 0.213 [95% confidence interval 0.05-0.914]), respectively. Eight and six patients developed metachronous esophageal squamous cell cancer and local recurrence, respectively. With the exception of one patient, they could be retreated endoscopically. EMR is a reasonable option for the patients with T1a-MM and T1b esophageal carcinoma without clinical metastasis, especially for the individuals with severe concurrent diseases. The prognostic factors for the benefit of EMR in such cases should be further examined. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

OPT-821 With or Without Vaccine Therapy in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer in Second or Third Complete Remission

ClinicalTrials.gov

2017-09-12

Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; 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

Area-level variations in cancer care and outcomes.

PubMed

Keating, Nancy L; Landrum, Mary Beth; Lamont, Elizabeth B; Bozeman, Samuel R; McNeil, Barbara J

2012-05-01

: Substantial regional variations in health-care spending exist across the United States; yet, care and outcomes are not better in higher-spending areas. Most studies have focused on care in fee-for-service Medicare; whether spillover effects exist in settings without financial incentives for more care is unknown. : We studied care for cancer patients in fee-for-service Medicare and the Veterans Health Administration (VA) to understand whether processes and outcomes of care vary with area-level Medicare spending. : An observational study using logistic regression to assess care by area-level measures of Medicare spending. : Patients with lung, colorectal, or prostate cancers diagnosed during 2001-2004 in Surveillance, Epidemiology, and End Results (SEER) areas or the VA. The SEER cohort included fee-for-service Medicare patients aged older than 65 years. : Recommended and preference-sensitive cancer care and mortality. : In fee-for-service Medicare, higher-spending areas had higher rates of recommended care (curative surgery and adjuvant chemotherapy for early-stage non-small-cell lung cancer and chemotherapy for stage III colon cancer) and preference-sensitive care (chemotherapy for stage IV lung and colon cancer and primary treatment of local/regional prostate cancer) and had lower lung cancer mortality. In the VA, we observed minimal variation in care by area-level Medicare spending. : Our findings suggest that intensity of care for Medicare beneficiaries is not driving variations in VA care, despite some overlap in physician networks. Although the Dartmouth Atlas work has been of unprecedented importance in demonstrating variations in Medicare spending, new measures may be needed to better understand variations in other populations.

Genetic Diagnosis before Surgery has an Impact on Surgical Decision in BRCA Mutation Carriers with Breast Cancer.

PubMed

Park, Sungmin; Lee, Jeong Eon; Ryu, Jai Min; Kim, Issac; Bae, Soo Youn; Lee, Se Kyung; Yu, Jonghan; Kim, Seok Won; Nam, Seok Jin

2018-05-01

The first aim of our study was to evaluate surgical decision-making by BRCA mutation carriers with breast cancer based on the timing of knowledge of their BRCA mutation status. The second aim was to evaluate breast cancer outcome following surgical treatment. This was a retrospective study of 164 patients diagnosed with invasive breast cancer, tested for BRCA mutation, and treated with primary surgery between 2004 and 2015 at Samsung Medical Center in Seoul, Korea. We reviewed types of surgery and timing of the BRCA test result. We compared surgical decision- making of BRCA carriers with breast cancer based on the timing of knowledge of their BRCA mutation status. Only 15 (9.1%) patients knew their BRCA test results before their surgery, and 149 (90.9%) knew the results after surgery. In patients with unilateral cancer, there was a significant difference between groups whose BRCA mutation status known before surgery and groups whose BRCA status unknown before surgery regarding the choice of surgery (p = 0.017). No significant difference was observed across surgery types of risk of ipsilateral breast tumor recurrence (p = 0.765) and contralateral breast cancer (p = 0.69). Genetic diagnosis before surgery has an impact on surgical decision choosing unilateral mastectomy or bilateral mastectomy in BRCA mutation carriers with breast cancer. Knowledge about BRCA mutation status after initial surgery led to additional surgeries for patients with BCS. Thus, providing genetic counseling and genetic testing before surgical choice and developing treatment strategies for patients with a high risk of breast cancer are important.

[Acute kidney injury in cancer patients].

PubMed

Rosa, Józef; Sydor, Antoni; Pelczar, Anna

2011-01-01

Acute kidney injury is a common and serious complication of cancer. We analyzed medical records of 335 cancer patients who were treated in Internal Diseases and Nephrology Department with Dialysis Center at St. Lucas Hospital in Tarnow in years 2009 and 2010. AKI was diagnosed according to the RIFLE classification in 91 cases (43 woman and 48 men). The average age was 68.7 years (from 18 to 93 years). 54 patients were classified as category F, 23 as category I and 14 as category R of the RIFLE classification. 60.4% of the patients were diagnosed with metastatic cancer, 12.1% with a regionally developed disease, 18.7% with cancer limited to one organ and in 8.8% the stage of the disease could not be established. The highest incidence of AKI was observed in patients with cancer of the cervix, ovary, prostate, breast, stomach and of unknown primary site. The most common risk factor of AKI was hypovolemia diagnosed in 35% of cases. Obstruction of the urinary tract, the second most frequent risk factor was observed in 26% of cases. 14.5% of the patients required hemodialysis. In the group of dialysed patients 38.5% of them died, 61.5% were discharged from hospital after improvement of renal function. In the group of non-dialysed patients mortality rate was 25.6%; survivors in that group presented improvement in renal function. Evaluation of the renal function in patients with cancer is essential.

Epstein–Barr Virus in Gliomas: Cause, Association, or Artifact?

PubMed Central

Akhtar, Saghir; Vranic, Semir; Cyprian, Farhan Sachal; Al Moustafa, Ala-Eddin

2018-01-01

Gliomas are the most common malignant brain tumors and account for around 60% of all primary central nervous system cancers. Glioblastoma multiforme (GBM) is a grade IV glioma associated with a poor outcome despite recent advances in chemotherapy. The etiology of gliomas is unknown, but neurotropic viruses including the Epstein–Barr virus (EBV) that is transmitted via salivary and genital fluids have been implicated recently. EBV is a member of the gamma herpes simplex family of DNA viruses that is known to cause infectious mononucleosis (glandular fever) and is strongly linked with the oncogenesis of several cancers, including B-cell lymphomas, nasopharyngeal, and gastric carcinomas. The fact that EBV is thought to be the causative agent for primary central nervous system (CNS) lymphomas in immune-deficient patients has led to its investigations in other brain tumors including gliomas. Here, we provide a review of the clinical literature pertaining to EBV in gliomas and discuss the possibilities of this virus being simply associative, causative, or even an experimental artifact. We searched the PubMed/MEDLINE databases using the following key words such as: glioma(s), glioblastoma multiforme, brain tumors/cancers, EBV, and neurotropic viruses. Our literature analysis indicates conflicting results on the presence and role of EBV in gliomas. Further comprehensive studies are needed to fully implicate EBV in gliomagenesis and oncomodulation. Understanding the role of EBV and other oncoviruses in the etiology of gliomas, would likely open up new avenues for the treatment and management of these, often fatal, CNS tumors. PMID:29732319

Second Primary Head and Neck Cancers After Non-Head and Neck Primary Cancers.

PubMed

Schlieve, Thomas; Heidel, R Eric; Carlson, Eric R

2016-12-01

The purpose of the present study was to determine the rate of second primary head and neck cancer development among patients with a primary cancer diagnosed outside the head and neck region, to present the clinical characteristics of this population, and to determine whether any variables are associated with survival. We designed a case series based on a sample of patients diagnosed with head and neck cancer who had previously been diagnosed with cancer located outside the head and neck region. The primary predictor variable was a diagnosis of cancer outside the head and neck region. The primary outcome variable was the diagnosis of a second cancer in the head and neck region. χ 2  Goodness-of-fit tests were used to test for differences between the observed and expected rates. A total of 19,406 cancers were diagnosed at the University of Tennessee Cancer Institute during the study period from July 1, 2004 to June 30, 2014. The rate of second primary head and neck cancer among patients with a non-head and neck primary cancer was 0.2%. These 40 cancers occurred among a total of 849 head and neck squamous cell carcinoma (HNSCC) cases (5%) diagnosed during the study period. The most common location for a second primary HNSCC was the gingiva (27.5%), followed by the oral tongue (17.5%). Significantly more gingival cancers were diagnosed than expected (P < .001) and significantly fewer tongue cancers than expected (P = .01). The most common primary cancer was prostate (27.5%), followed by breast (25%). The median survival was 28.5 months after the second primary diagnosis. A nonsignificant effect was found for age (P = .30), tobacco use (P = .12), gender (P = .60), TNM stage (P = .29), and treatment protocol (P = .96) on survival. The development of a second primary HNSCC in a population of patients with non-head and neck primary cancers is associated with decreased overall survival. The most common presentation of a second primary HNSCC in our study was in the gingiva and the most common primary cancer was in the prostate. Clinicians should consider the increased proportion of gingival cancers in this population when examining patients and be aware of the decrease in overall survival. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Development of Multiple Primary Cancers in Lung Cancer Patients: Appalachian Versus Non-Appalachian Populations of Kentucky.

PubMed

Pravosud, Vira; Huang, Bin; Tucker, Thomas; Vanderford, Nathan L

2017-12-01

The aim of this study was to investigate whether patients with lung cancer in Appalachian Kentucky are more likely to develop multiple primary cancers than patients in non-Appalachian Kentucky. Additional analyses were conducted to identify other factors that may be associated with an increased hazard of developing multiple primary cancers in patients with lung cancer. The data for this retrospective, population-based cohort study of 26,456 primary lung cancer patients were drawn from the Kentucky Cancer Registry. For inclusion in the study, patients must have been diagnosed between January 1, 2000 and December 31, 2013 and they must either have continually resided in Appalachian Kentucky or continually resided in non-Appalachian Kentucky. Cases were excluded if the patient was diagnosed as having additional primary cancers within 3 months of the initial diagnosis of primary lung cancer. The medical records for each case were examined to determine whether the patient was subsequently diagnosed as having additional primary cancers. The Cox proportional hazards model was then used to assess whether there was an association between the region in which the patients live and the likelihood of developing multiple primary cancers. Time to event was considered as the time from diagnosis to either death or development of a second primary cancer. The results presented here indicate that the risk of developing multiple primary cancers is the same for patients with lung cancer throughout Kentucky (hazard ratio [HR] 1.002, P = 0.9713). We found no evidence for a greater hazard in patients from Appalachia; however, additional analyses revealed several high-risk groups. Male patients and older patients had a significantly greater hazard of developing multiple primary cancers (HR 1.169, P = 0.012 and 1.015, P = 0.0001, respectively). In addition, patients who underwent surgery and those who were diagnosed initially as having an earlier stage of cancer also were more likely to develop multiple primary cancers (HR 1.446, P = 0.0003 and 0.684, P = 0.0015, respectively). This is a negative study. Patients with primary lung cancer living in Appalachian Kentucky are not at a greater risk of developing multiple primary cancers than those residing in non-Appalachian Kentucky. High-risk groups identified in this study are male patients and older patients. The increased hazard seen in patients who underwent surgery or those who were diagnosed as having earlier stages of lung cancer are likely an artifact of these patients living longer and, therefore, having more time to develop additional primary cancers.

Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

ClinicalTrials.gov

2018-04-24

Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; 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; Undifferentiated Ovarian Carcinoma

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

Triple synchronous primary lung cancer: a case report and review of the literature.

PubMed

Kashif, Muhammad; Ayyadurai, Puvanalingam; Thanha, Luong; Khaja, Misbahuddin

2017-09-01

Multiple primary lung cancer may present in synchronous or metachronous form. Synchronous multiple primary lung cancer is defined as multiple lung lesions that develop at the same time, whereas metachronous multiple primary lung cancer describes multiple lung lesions that develop at different times, typically following treatment of the primary lung cancer. Patients with previously treated lung cancer are at risk for developing metachronous lung cancer, but with the success of computed tomography and positron emission tomography, the ability to detect both synchronous and metachronous lung cancer has increased. We present a case of a 63-year-old Hispanic man who came to our hospital for evaluation of chest pain, dry cough, and weight loss. He had recently been diagnosed with adenocarcinoma in the right upper lobe, with a poorly differentiated carcinoma favoring squamous cell cancer based on bronchoalveolar lavage of the right lower lobe for which treatment was started. Later, bronchoscopy incidentally revealed the patient to have an endobronchial lesion that turned out to be mixed small and large cell neuroendocrine lung cancer. Our patient had triple synchronous primary lung cancers that histologically were variant primary cancers. Triple synchronous primary lung cancer management continues to be a challenge. Our patient's case suggests that multiple primary lung cancers may still occur at a greater rate than can be detected by high-resolution computed tomography.

Hypermethylation of the breast cancer-associated gene 1 promoter does not predict cytologic atypia or correlate with surrogate end points of breast cancer risk.

PubMed

Bean, Gregory R; Ibarra Drendall, Catherine; Goldenberg, Vanessa K; Baker, Joseph C; Troch, Michelle M; Paisie, Carolyn; Wilke, Lee G; Yee, Lisa; Marcom, Paul K; Kimler, Bruce F; Fabian, Carol J; Zalles, Carola M; Broadwater, Gloria; Scott, Victoria; Seewaldt, Victoria L

2007-01-01

Mutation of the breast cancer-associated gene 1 (BRCA1) plays an important role in familial breast cancer. Although hypermethylation of the BRCA1 promoter has been observed in sporadic breast cancer, its exact role in breast cancer initiation and association with breast cancer risk is unknown. The frequency of BRCA1 promoter hypermethylation was tested in (a) 14 primary breast cancer biopsies and (b) the initial random periareolar fine-needle aspiration (RPFNA) cytologic samples obtained from 61 asymptomatic women who were at increased risk for breast cancer. BRCA1 promoter hypermethylation was assessed from nucleotide -150 to nucleotide +32 relative to the transcription start site. RPFNA specimens were stratified for cytologic atypia using the Masood cytology index. BRCA1 promoter hypermethylation was observed at similar frequency in nonproliferative (normal; Masood

A protocol for a discrete choice experiment: understanding preferences of patients with cancer towards their cancer care across metropolitan and rural regions in Australia.

PubMed

Wong, Shu Fen; Norman, Richard; Dunning, Trisha L; Ashley, David M; Lorgelly, Paula K

2014-10-24

Medical decision-making in oncology is a complicated process and to date there are few studies examining how patients with cancer make choices with respect to different features of their care. It is also unknown whether patient choices vary by geographical location and how location could account for observed rural and metropolitan cancer differences. This paper describes an ongoing study that aims to (1) examine patient and healthcare-related factors that influence choices of patients with cancer; (2) measure and quantify preferences of patients with cancer towards cancer care using a discrete choice experiment (DCE) and (3) explore preference heterogeneity between metropolitan and rural locations. A DCE is being conducted to understand how patients with cancer choose between two clinical scenarios accounting for different patient and healthcare-related factors (and levels). Preliminary qualitative research was undertaken to guide the development of an appropriate DCE design including characteristics that are important and relevant to patients with cancer. A fractional factorial design using the D-efficiency criteria was used to estimate interactions among attributes. Multinomial logistic regression will be used for the primary DCE analysis and to control for sociodemographic and clinical characteristics. The Barwon Health Human Research Ethics Committee approved the study. Findings from the study will be presented in national/international conferences and peer-reviewed journals. Our results will form the basis of a feasibility study to inform the development of a larger scale study into preferences of patients with cancer and their association with cancer outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

Samarzija, Ivana; Beard, Peter, E-mail: peter.beard@epfl.ch

Highlights: Black-Right-Pointing-Pointer Unknown cellular mutations complement papillomavirus-induced carcinogenesis. Black-Right-Pointing-Pointer Hedgehog pathway components are expressed by cervical cancer cells. Black-Right-Pointing-Pointer Hedgehog pathway activators and inhibitors regulate cervical cancer cell biology. Black-Right-Pointing-Pointer Cell immortalization by papillomavirus and activation of Hedgehog are independent. -- Abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of themore » Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer.« less

Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2.

PubMed

Wang, Min; Ren, Dong; Guo, Wei; Wang, Zeyu; Huang, Shuai; Du, Hong; Song, Libing; Peng, Xinsheng

2014-07-01

Evidence in literature has demonstrated that some microRNAs (miRNAs) play a pivotal role in most solid tumor metastasis. Previous studies have showed that miR-100 is downregulated in human prostate cancer tissue compared to normal prostate and also significantly decreased in bone metastatic prostate cancer samples compared with primary prostate cancer. Argonaute 2 (AGO2) is the core effector protein of the miRNA-induced silencing complex and overexpression of AGO2 might enhance tumor metastasis. However, it is unknown whether and how miR-100 and AGO2 regulates metastasis of prostate cancer. Here, we report that miR-100 negatively regulated migration, invasion, epithelial-mesenchymal transition (EMT), colony formation, spheroid formation and expression of the stemness factors c-Myc, Oct4 and Klf4 in PC-3 and DU145 cells. Furthermore, miR-100 expression was negatively correlated with bone metastasis of prostate cancer patients. Notably, luciferase assay showed that AGO2 was a direct target of miR-100. Downregulation of AGO2 repressed migration, invasion, EMT and stemness of prostate cancer cells, and reversed the effects seen with miR-100 downregulation. Downregulation of AGO2 enhanced expression of miR-34a and miR-125b which can suppress migration, invasion, EMT and stemness of cancer cells. Taken together, our findings indicate that loss of miR-100 promotes the metastatic ability of prostate cancer cells at least partially by upregulating AGO2 expression through modulating migration, invasion, EMT and stemness of cancer cells, and suggest that miR-100/AGO2 may play an important role in regulating the metastasis of prostate cancer and is a potential target of prevention and therapy.

Completeness of T, N, M and stage grouping for all cancers in the Mallorca Cancer Registry.

PubMed

Ramos, M; Franch, P; Zaforteza, M; Artero, J; Durán, M

2015-11-04

TNM staging of cancer is used to establish the treatment and prognosis for cancer patients, and also allows the assessment of screening programmes and hospital performance. Collection of staging data is becoming a cornerstone for cancer registries. The objective of the study was to assess the completeness of T, N, M and stage grouping registration for all cancers in the Mallorca Cancer Registry in 2006-2008 and to explore differences in T, N, M and stage grouping completeness by site, gender, age and type of hospital. All invasive cancer cases during the period 2006-2008 were selected. DCO, as well as children's cancers, CNS, unknown primary tumours and some haematological cases were excluded. T, N, M and stage grouping were collected separately and followed UICC (International Union Against Cancer) 7th edition guidelines. For T and N, we registered whether they were pathological or clinical. Ten thousand two hundred fifty-seven cases were registered. After exclusions, the study was performed with 9283 cases; 39.4 % of whom were women and 60.6 % were men. T was obtained in 48.6 % cases, N in 36.5 %, M in 40 % and stage in 37.9 %. T and N were pathological in 71 % of cases. Stage completeness exceeded 50 % in lung, colon, ovary and oesophagus, although T also exceeded 50 % at other sites, including rectum, larynx, colon, breast, bladder and melanoma. No differences were found in TNM or stage completeness by gender. Completeness was lower in younger and older patients, and in cases diagnosed in private clinics. T, N, M and stage grouping data collection in population-based cancer registries is feasible and desirable.

[Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

PubMed

Lyu, J M; Xiong, H C; Wu, B; Zhou, X Q; Hu, J

2018-02-23

Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P <0.05). Conclusions: The second primary cancers of MPC cases initially diagnosed of digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

28 CFR 79.56 - Proof of primary renal cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary renal cancer. 79.56... cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... conclusion that a claimant developed primary renal cancer must be supported by medical documentation. In all...

28 CFR 79.66 - Proof of primary renal cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... claimant. A conclusion that a claimant developed primary renal cancer must be supported by medical...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.66 - Proof of primary renal cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... claimant. A conclusion that a claimant developed primary renal cancer must be supported by medical...

28 CFR 79.56 - Proof of primary renal cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary renal cancer. 79.56... cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... conclusion that a claimant developed primary renal cancer must be supported by medical documentation. In all...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.56 - Proof of primary renal cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary renal cancer. 79.56... cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... conclusion that a claimant developed primary renal cancer must be supported by medical documentation. In all...

28 CFR 79.66 - Proof of primary renal cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... claimant. A conclusion that a claimant developed primary renal cancer must be supported by medical...

28 CFR 79.66 - Proof of primary renal cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... claimant. A conclusion that a claimant developed primary renal cancer must be supported by medical...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.66 - Proof of primary renal cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... claimant. A conclusion that a claimant developed primary renal cancer must be supported by medical...

28 CFR 79.56 - Proof of primary renal cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary renal cancer. 79.56... cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... conclusion that a claimant developed primary renal cancer must be supported by medical documentation. In all...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.56 - Proof of primary renal cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary renal cancer. 79.56... cancer. (a) In determining whether a claimant developed primary renal cancer following pertinent... conclusion that a claimant developed primary renal cancer must be supported by medical documentation. In all...

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

ClinicalTrials.gov

2017-06-13

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

Intraoperative 3D Navigation for Single or Multiple 125I-Seed Localization in Breast-Preserving Cancer Surgery.

PubMed

Pouw, Bas; de Wit-van der Veen, Linda J; van Duijnhoven, Frederieke; Rutgers, Emiel J Th; Stokkel, Marcel P M; Valdés Olmos, Renato A; Vrancken Peeters, Marie-Jeanne T F D

2016-05-01

Mammographic screening has led to the identification of more women with nonpalpable breast cancer, many of them to be treated with breast-preserving surgery. To accomplish radical tumor excision, adequate localization techniques such as radioactive seed localization (RSL) are required. For RSL, a radioactive I-seed is implanted central in the tumor to enable intraoperative localization using a γ-probe. In case of extensive tumor or multifocal carcinoma, multiple I-seeds can be used to delineate the involved area. Preoperative imaging is performed different from surgical positioning; therefore, exact I-seed depth remains unknown during surgery. Twenty patients (mean age, 56.8 years) with 25 implanted I-seeds scheduled for RSL were included. Sixteen patients had 1 I-seed implanted in the primary lesion, 3 patients had 2 I-seeds, and 1 patient had 3 I-seeds. Freehand SPECT localized I-seeds by measuring γ-counts from different directions, all registered by an optical tracking system. A reconstruction and visualization algorithm enabled 3-dimensional (3D) navigation toward the I-seeds. Freehand SPECT visualized all I-seeds in primary tumors and provided preincision depth information. The deviation, mean (SD), between the freehand SPECT depth and the surgical depth estimation was 1.9 (2.1) mm (range, 0-7 mm). Three-dimensional freehand SPECT was especially useful identifying multiple implanted I-seeds because the conventional γ-probe has more difficulty discriminating I-seeds transcutaneous. Freehand SPECT with 3D navigation is a valuable tool in RSL for both single and multiple implanted I-seeds in breast-preserving cancer surgery. Freehand SPECT provides continuous updating 3D imaging with information about depth and location of the I-seeds contributing to adequate excision of nonpalpable breast cancer.

Childhood Cancer Survivor Study participants' perceptions and understanding of the Affordable Care Act.

PubMed

Park, Elyse R; Kirchhoff, Anne C; Perez, Giselle K; Leisenring, Wendy; Weissman, Joel S; Donelan, Karen; Mertens, Ann C; Reschovsky, James D; Armstrong, Gregory T; Robison, Leslie L; Franklin, Mariel; Hyland, Kelly A; Diller, Lisa R; Recklitis, Christopher J; Kuhlthau, Karen A

2015-03-01

The Patient Protection and Affordable Care Act (ACA) established provisions intended to increase access to affordable health insurance and thus increase access to medical care and long-term surveillance for populations with pre-existing conditions. However, childhood cancer survivors' coverage priorities and familiarity with the ACA are unknown. Between May 2011 and April 2012, we surveyed a randomly selected, age-stratified sample of 698 survivors and 210 siblings from the Childhood Cancer Survivor Study. Overall, 89.8% of survivors and 92.1% of siblings were insured. Many features of insurance coverage that survivors considered "very important" are addressed by the ACA, including increased availability of primary care (94.6%), no waiting period before coverage initiation (79.0%), and affordable premiums (88.1%). Survivors were more likely than siblings to deem primary care physician coverage and choice, protections from costs due to pre-existing conditions, and no start-up period as "very important" (P < .05 for all). Only 27.3% of survivors and 26.2% of siblings reported familiarity with the ACA (12.1% of uninsured v 29.0% of insured survivors; odds ratio, 2.86; 95% CI, 1.28 to 6.36). Only 21.3% of survivors and 18.9% of siblings believed the ACA would make it more likely that they would get quality coverage. Survivors' and siblings' concerns about the ACA included increased costs, decreased access to and quality of care, and negative impact on employers and employees. Although survivors' coverage preferences match many ACA provisions, survivors, particularly uninsured survivors, were not familiar with the ACA. Education and assistance, perhaps through cancer survivor navigation, are critically needed to ensure that survivors access coverage and benefits. © 2015 by American Society of Clinical Oncology.

Childhood Cancer Survivor Study Participants' Perceptions and Understanding of the Affordable Care Act

PubMed Central

Park, Elyse R.; Kirchhoff, Anne C.; Perez, Giselle K.; Leisenring, Wendy; Weissman, Joel S.; Donelan, Karen; Mertens, Ann C.; Reschovsky, James D.; Armstrong, Gregory T.; Robison, Leslie L.; Franklin, Mariel; Hyland, Kelly A.; Diller, Lisa R.; Recklitis, Christopher J.; Kuhlthau, Karen A.

2015-01-01

Purpose The Patient Protection and Affordable Care Act (ACA) established provisions intended to increase access to affordable health insurance and thus increase access to medical care and long-term surveillance for populations with pre-existing conditions. However, childhood cancer survivors' coverage priorities and familiarity with the ACA are unknown. Methods Between May 2011 and April 2012, we surveyed a randomly selected, age-stratified sample of 698 survivors and 210 siblings from the Childhood Cancer Survivor Study. Results Overall, 89.8% of survivors and 92.1% of siblings were insured. Many features of insurance coverage that survivors considered “very important” are addressed by the ACA, including increased availability of primary care (94.6%), no waiting period before coverage initiation (79.0%), and affordable premiums (88.1%). Survivors were more likely than siblings to deem primary care physician coverage and choice, protections from costs due to pre-existing conditions, and no start-up period as “very important” (P < .05 for all). Only 27.3% of survivors and 26.2% of siblings reported familiarity with the ACA (12.1% of uninsured v 29.0% of insured survivors; odds ratio, 2.86; 95% CI, 1.28 to 6.36). Only 21.3% of survivors and 18.9% of siblings believed the ACA would make it more likely that they would get quality coverage. Survivors' and siblings' concerns about the ACA included increased costs, decreased access to and quality of care, and negative impact on employers and employees. Conclusion Although survivors' coverage preferences match many ACA provisions, survivors, particularly uninsured survivors, were not familiar with the ACA. Education and assistance, perhaps through cancer survivor navigation, are critically needed to ensure that survivors access coverage and benefits. PMID:25646189

Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma

PubMed Central

Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

2017-01-01

Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides “killing” PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors. PMID:28146424

Survival in patients with metachronous second primary lung cancer.

PubMed

Ha, Duc; Choi, Humberto; Chevalier, Cory; Zell, Katrina; Wang, Xiao-Feng; Mazzone, Peter J

2015-01-01

Four to 10% of patients with non-small cell lung cancer subsequently develop a metachronous second primary lung cancer. The decision to perform surveillance or screening imaging for patients with potentially cured lung cancer must take into account the outcomes expected when detecting metachronous second primaries. To assess potential survival differences between patients with metachronous second primary lung cancer compared to matched patients with first primary lung cancer. We retrospectively reviewed patients diagnosed with lung cancer at the Cleveland Clinic (2006-2010). Metachronous second primary lung cancer was defined as lung cancer diagnosed after a 4-year, disease-free interval from the first lung cancer, or if there were two different histologic subtypes diagnosed at different times. Patients with first primary lung cancer diagnosed in the same time period served as control subjects. Propensity score matching was performed using age, sex, smoking history, histologic subtype, and collaborative stage, with a 1:3 case-control ratio. Survival analyses were performed by Cox proportional hazards modeling and Kaplan-Meier estimates. Forty-four patients met criteria for having a metachronous second primary lung cancer. There were no statistically significant differences between case subjects and control subjects in prognostic variables. The median survival time and 2-year overall survival rate for the metachronous second primary group, compared with control subjects, were as follows: 11.8 versus 18.4 months (P = 0.18) and 31.0 versus 40.9% (P = 0.28). The survival difference was largest in those with stage I metachronous second primaries (median survival time, 26.8 vs. 60.4 mo, P = 0.09; 2-year overall survival, 56.3 vs. 71.2%, P = 0.28). Patients with stage I metachronous second primary lung cancer may have worse survival than those who present with a first primary lung cancer. This could influence the benefit-risk balance of screening the high-risk cohort with a previously treated lung cancer.

Lack of active follow-up of cancer patients in Chennai, India: implications for population-based survival estimates

PubMed Central

Rama, Ranganathan; Shanta, Viswanathan

2008-01-01

Abstract Objective To measure the bias in absolute cancer survival estimates in the absence of active follow-up of cancer patients in developing countries. Methods Included in the study were all incident cases of the 10 most common cancers and corresponding subtypes plus all tobacco-related cancers not ranked among the top 10 that were registered in the population-based cancer registry in Chennai, India, during 1990–1999 and followed through 2001. Registered incident cases were first matched with those in the all-cause mortality database from the vital statistics division of the Corporation of Chennai. Unmatched incident cancer cases were then actively followed up to determine their survival status. Absolute survival was estimated by using an actuarial method and applying different assumptions regarding the survival status (alive/dead) of cases under passive and active follow-up. Findings Before active follow-up, matches between cases ranged from 20% to 66%, depending on the site of the primary tumour. Active follow-up of unmatched incident cases revealed that 15% to 43% had died by the end of the follow-up period, while the survival status of 4% to 38% remained unknown. Before active follow-up of cancer patients, 5-year absolute survival was estimated to be between 22% and 47% higher, than when conventional actuarial assumption methods were applied to cases that were lost to follow-up. The smallest survival estimates were obtained when cases lost to follow-up were excluded from the analysis. Conclusion Under the conditions that prevail in India and other developing countries, active follow-up of cancer patients yields the most reliable estimates of cancer survival rates. Passive case follow-up alone or applying standard methods to estimate survival is likely to result in an upward bias. PMID:18670662

Radiotherapy for ductal carcinoma in situ and risk of second non-breast cancers.

PubMed

Withrow, Diana R; Morton, Lindsay M; Curtis, Rochelle E; Schonfeld, Sara J; Berrington de González, Amy

2017-11-01

Radiotherapy for ductal carcinoma (DCIS) is increasing, but the risks and benefits of the treatment remain uncertain. We aimed to investigate the relationship between radiotherapy for DCIS and risk of second non-breast cancers in a large US cohort. We conducted a retrospective cohort study of 52,556 women in 12 U.S. population-based cancer registries diagnosed with first primary DCIS during 1992-2008 at age 25-79 years. We estimated relative risks (RRs), attributable risks (AR), and excess absolute risks (EAR) of second non-breast cancers associated with radiotherapy using Poisson regression adjusted for age at year of diagnosis, grade, hormonal therapy (yes/no or unknown), and time since diagnosis. Approximately half of the women (46.3%) received radiotherapy. Radiotherapy was associated with an increased risk of all second non-breast cancers combined [RR 1.17, 95% confidence interval (CI) 1.08-1.28] and all in-field, radiation-related second cancers combined (RR 1.37, 95% CI 1.15-1.63), driven by second lung cancers (RR 1.33, 95% CI 1.10-1.60) and non-CLL leukemia (RR 1.71, 95% CI 1.02-2.86). The estimated cumulative excess risk of all second non-breast cancers was 0.8% by 15 years after DCIS diagnosis. Radiotherapy was associated with an increased risk of second non-breast cancers. The specific excess of cancers at sites likely in/near the radiotherapy field suggests the findings are unlikely due exclusively to confounding, but further research into factors related to receipt of radiotherapy is needed. Our risk estimates can be used to help assess the balance of the risks and benefits of radiotherapy for DCIS and to inform clinical practice.

The role of BRCA1 in homologous recombination repair in response to replication stress: significance in tumorigenesis and cancer therapy

PubMed Central

2013-01-01

Germ line mutations in breast cancer gene 1 (BRCA1) predispose women to breast and ovarian cancers. Although BRCA1 is involved in many important biological processes, the function of BRCA1 in homologous recombination (HR) mediated repair is considered one of the major mechanisms contributing to its tumor suppression activity, and the cause of hypersensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors when BRCA1 is defective. Mounting evidence suggests that the mechanism of repairing DNA double strand breaks (DSBs) by HR is different than the mechanism operating when DNA replication is blocked. Although BRCA1 has been recognized as a central component in HR, the precise role of BRCA1 in HR, particularly under replication stress, has remained largely unknown. Given the fact that DNA lesions caused by replication blockages are the primary substrates for HR in mitotic cells, functional analysis of BRCA1 in HR repair in the context of replication stress should benefit our understanding of the molecular mechanisms underlying tumorigenesis associated with BRCA1 deficiencies, as well as the development of therapeutic approaches for cancer patients carrying BRCA1 mutations or reduced BRCA1 expression. This review focuses on the current advances in this setting and also discusses the significance in tumorigenesis and cancer therapy. PMID:23388117

Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

PubMed

Hartog, H; Boezen, H M; de Jong, M M; Schaapveld, M; Wesseling, J; van der Graaf, W T A

2013-12-01

High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood levels and of it's main binding protein, IGFBP-3, on overall survival and occurrence of second primary breast tumors in breast cancer patients, as well as reproductive and lifestyle factors that could modify this risk. Patients were accrued from six hospitals in the Netherlands between 1998 and 2003. Total IGF-1 and IGFBP-3 were measured in 582 plasma samples. No significant association between IGF-1 and IGFBP-3 plasma levels and overall survival was found. However, in a multivariate Cox regression model including standard prognostic variables high IGF-1 levels were related to worse overall survival in patients receiving endocrine therapy (HR = 1.37, 95% CI: 1.11, 1.69, P 0.004). These data at least indicate that higher IGF-1 levels, and as a consequence most likely IGF-1-induced signaling, are related to a less favorable overall survival in breast cancer patients treated with endocrine therapy. Interventions aimed at reducing circulating levels of IGF-1 in hormone receptor positive breast cancer may improve survival. Copyright © 2013 Elsevier Ltd. All rights reserved.

Specific cellular accumulation of photofrin-II in EC cells promotes photodynamic treatment efficacy in esophageal cancer.

PubMed

Gao, Shegan; Liang, Shuo; Ding, Kaili; Qu, Zhifeng; Wang, Ying; Feng, Xiaoshan

2016-06-01

Photodynamic therapy (PDT), which uses a light-sensitive compound and laser irradiation, is a light-based oncological treatment modality. PDT offers an alternative, less invasive treatment for various malignant tumors, such as esophageal cancer (EC), through a photochemical reaction induced by photofrin-II or other oncotropic photosensitizers without severe complications. Previous studies has shown that cancerous tissues accumulated more photosensitizers than paired normal tissues, however, whether it is cellular or vascular mechanisms remains unknown. Herein, in vivo and in vitro examinations were performed to study the mechanisms by which photofrin-II effectively and specifically killed EC cells. In this study, EC tissue of patients treated with photofrin-II, human ESCC cellline SHEEC and parental normal cellline SHEE, primary culture cells of EC tissue were used. The concentration of photofrin-II in cells were evaluated by high-performance liquid chromatography (HPLC). The results exhibited that accumulation of photofrin-II in cancerous cells were significantly higher than that in non-cancerous cells (p<0.05) under certain dose and time period of incubation of photofrin-II. In summary, our study showed that, photofrin-II specifically accumulated in EC cells in vivo and in vitro after controlling for vascular factors, which provided strong evidence that maybe the cellular factor is the main mechanism by which photofrin-II-mediated PDT selectively caused EC cells death. Copyright © 2016 Elsevier B.V. All rights reserved.

Use of PET and Other Functional Imaging to Guide Target Delineation in Radiation Oncology.

PubMed

Verma, Vivek; Choi, J Isabelle; Sawant, Amit; Gullapalli, Rao P; Chen, Wengen; Alavi, Abass; Simone, Charles B

2018-06-01

Molecular and functional imaging is increasingly being used to guide radiotherapy (RT) management and target delineation. This review summarizes existing data in several disease sites of various functional imaging modalities, chiefly positron emission tomography/computed tomography (PET/CT), with respect to RT target definition and management. For gliomas, differentiation between postoperative changes and viable tumor is discussed, as well as focal dose escalation and reirradiation. Head and neck neoplasms may also benefit from precise PET/CT-based target delineation, especially for cancers of unknown primary; focal dose escalation is also described. In lung cancer, PET/CT can influence coverage of tumor volumes, dose escalation, and adaptive management. For cervical cancer, PET/CT as an adjunct to magnetic resonance imaging planning is discussed, as are dose escalation and delineation of avoidance targets such as the bone marrow. The emerging role of choline-based PET for prostate cancer and its impact on dose escalation is also described. Lastly, given the essential role of PET/CT for target definition in lymphoma, phase III trials of PET-directed management are reviewed, along with novel imaging modalities. Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic care going forward. Copyright © 2018 Elsevier Inc. All rights reserved.

Oral nutritional support can shorten the duration of parenteral hydration in end-of-life cancer patients: a randomized controlled trial.

PubMed

Ishiki, Hiroto; Iwase, Satoru; Gyoda, Yasuaki; Kanai, Yoshiaki; Ariyoshi, Keisuke; Miyaji, Tempei; Tahara, Yukiko; Kawaguchi, Takashi; Chinzei, Mieko; Yamaguchi, Takuhiro

2015-01-01

Tube feeding or hydration is often considered for end-of-life cancer patients despite the negative effects on quality of life. The efficacy of oral nutritional support in this setting is unknown. We conducted a randomized trial to compare the efficacies of an amino acid jelly, Inner Power® (IP), and a liquid enteral product, Ensure Liquid® (EL), in terminally ill cancer patients. We randomly assigned patients to 3 arms: EL, IP, and EL+IP. The primary endpoint was drip infusion in vein (DIV)-free survival, which was defined as the duration from nutritional support initiation to administration of parenteral hydration. Twenty-seven patients were enrolled in the study, of whom 21 were included in the intention-to-treat analysis. The median age of the subjects was 69 yr. There were significant differences between the arms with regard to the median DIV-free survival (0.5, 6.0, and 4.5 days in the EL, IP, and EL + IP arms, respectively; P = 0.05). The median overall survival was 7, 9, and 8 days in the EL, IP, and EL + IP arms, respectively. IP may shorten the duration of parenteral hydration in terminally ill cancer patients and does not affect their survival.

Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow-derived cells.

PubMed

Kuznetsov, Hanna S; Marsh, Timothy; Markens, Beth A; Castaño, Zafira; Greene-Colozzi, April; Hay, Samantha A; Brown, Victoria E; Richardson, Andrea L; Signoretti, Sabina; Battinelli, Elisabeth M; McAllister, Sandra S

2012-12-01

Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer (LBC) cells and patient tumor specimens (LBC "instigators") establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors ("responders"). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGF receptor 2(+) tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which cancer patients are likely to relapse. Our findings highlight the macroenvironment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from adjuvant therapy. ©2012 AACR.

Value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules.

PubMed

Schwarz, Carsten; Schönfeld, Nicolas; Bittner, Roland C; Mairinger, Thomas; Rüssmann, Holger; Bauer, Torsten T; Kaiser, Dirk; Loddenkemper, Robert

2013-01-01

The diagnostic value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules (SPN) is still under debate among pneumologists, radiologists and thoracic surgeons. In a prospective observational manner, flexible bronchoscopy was routinely performed in 225 patients with SPN of unknown origin. Of the 225 patients, 80.5% had lung cancer, 7.6% had metastasis of an extrapulmonary primary tumour and 12% had benign aetiology. Unsuspected endobronchial involvement was found in 4.4% of all 225 patients (or in 5.5% of patients with lung cancer). In addition, flexible bronchoscopy clarified the underlying aetiology in 41% of the cases. The bronchoscopic biopsy results from the SPN were positive in 84 (46.5%) patients with lung cancer. Surgery was cancelled due to the results of flexible bronchoscopy in four cases (involvement of the right main bronchus (impaired pulmonary function did not allow pneumonectomy) n=1, small cell lung cancer n=1, bacterial pneumonia n=2), and the surgical strategy had to be modified to bilobectomy in one patient. Flexible bronchoscopy changed the planned surgical approach in five cases substantially. These results suggest that routine flexible bronchoscopy should be included in the regular pre-operative work-up of patients with SPN.

Localized morphea after breast implant for breast cancer: A case report.

PubMed

Moretti, A; Bianchi, F; Abbate, I V; Gherardi, G; Bonavita, M; Passoni, E; Nazzaro, G; Bramati, A; Dazzani, M C; Piva, S; Paternò, E; Frungillo, N; Farina, G; La Verde, N

2018-03-01

Early breast cancer follow-up guidelines for patients who underwent surgery suggest a regular and accurate clinical examination of the breast area, for an early identification of cutaneous or subcutaneous breast cancer relapse. Nonetheless, breast skin lesions arising in patients treated with mastectomy for breast cancer can be caused by several diseases. A series of diagnostic hypotheses should be considered, not only focusing on cutaneous metastasis, but also on dermatologic and systemic diseases. In February 2015, a 37-year-old patient underwent a right subcutaneous mastectomy for stage IIA breast cancer. Five months after beginning adjuvant chemotherapy, she noted hyperpigmentation and thickening of the skin on the right breast. Differential diagnosis included local relapse, skin infection, lymphoma, or primary cutaneous disease, and a skin biopsy was performed. The histopathologic specimen showed full-thickness sclerosis, with features of localized morphea. Therapy with clobetasol was prescribed, with progressive resolution of the thickness. The collaboration between many professionals in a multidisciplinary team (oncologist, dermatologist, plastic surgeon, and pathologist) was crucial to achieving the diagnosis. In the literature, some articles describe correlation between connective tissue diseases and silicone breast implants, but the pathogenetic mechanisms are unknown. We report a rare case of breast morphea after positioning a silicone implant in a patient who had undergone mastectomy. This clinical report represents an interesting model of multidisciplinary management of a patient with breast cancer who developed an uncommon dermatologic disease. Further studies are needed to clarify the association between silicone implants and breast morphea.

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

ClinicalTrials.gov

2018-05-14

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 AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

The Incidence of Other Primary Cancers in Patients with Cutaneous Lymphoma.

PubMed

Kim, Young Jae; Shin, Ho Jeong; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Lee, Woo Jin

2018-06-01

Skin cancer is the most common other primary cancer in patients with lymphoma. However, an intriguing association between cutaneous lymphoma and other primary cancers has been suggested in a few studies. This study investigated other primary cancers in patients with cutaneous lymphoma to evaluate the risk for occurrence of each type of cancer. We screened for other primary cancers in 428 patients with cutaneous lymphoma. Clinical features were analyzed according to the lineage and origin of the lymphomas. We calculated the standardized incidence ratio with statistical analysis for each group according to age. Among 330 patients with cutaneous T cell lymphoma and 98 with cutaneous B cell lymphoma, a total of 43 cancers in 38 patients were finally included. Other primary cancers were prevalent in patients with cutaneous B cell lymphoma and patients with secondary cutaneous lymphoma. However, those differences were not significant when the age was calibrated by multiple logistic regression. Metachronously higher standardized incidence ratios were observed for primary lung (standardized incidence ratio [SIR], 14.81; 95% confidence interval [CI], 3.05~39.54), skin (SIR, 68.05; 95% CI, 14.03~181.62), and breast (SIR, 12.91; 95% CI, 1.56~41.41) cancers with statistical significance. Other primary cancers more preferentially occurred in patients with cutaneous lymphoma. Clinicians should carefully examine patients with cutaneous lymphoma for other cancers, especially lung, skin, and breast cancers.

The Incidence of Other Primary Cancers in Patients with Cutaneous Lymphoma

PubMed Central

Kim, Young Jae; Shin, Ho Jeong; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho

2018-01-01

Background Skin cancer is the most common other primary cancer in patients with lymphoma. However, an intriguing association between cutaneous lymphoma and other primary cancers has been suggested in a few studies. Objective This study investigated other primary cancers in patients with cutaneous lymphoma to evaluate the risk for occurrence of each type of cancer. Methods We screened for other primary cancers in 428 patients with cutaneous lymphoma. Clinical features were analyzed according to the lineage and origin of the lymphomas. We calculated the standardized incidence ratio with statistical analysis for each group according to age. Results Among 330 patients with cutaneous T cell lymphoma and 98 with cutaneous B cell lymphoma, a total of 43 cancers in 38 patients were finally included. Other primary cancers were prevalent in patients with cutaneous B cell lymphoma and patients with secondary cutaneous lymphoma. However, those differences were not significant when the age was calibrated by multiple logistic regression. Metachronously higher standardized incidence ratios were observed for primary lung (standardized incidence ratio [SIR], 14.81; 95% confidence interval [CI], 3.05~39.54), skin (SIR, 68.05; 95% CI, 14.03~181.62), and breast (SIR, 12.91; 95% CI, 1.56~41.41) cancers with statistical significance. Conclusion Other primary cancers more preferentially occurred in patients with cutaneous lymphoma. Clinicians should carefully examine patients with cutaneous lymphoma for other cancers, especially lung, skin, and breast cancers. PMID:29853749

Molecular dynamics simulation analysis of Focal Adhesive Kinase (FAK) docked with solanesol as an anti-cancer agent

PubMed Central

Daneial, Betty; Joseph, Jacob Paul Vazhappilly; Ramakrishna, Guruprasad

2017-01-01

Focal adhesion kinase (FAK) plays a primary role in regulating the activity of many signaling molecules. Increased FAK expression has been associated in a series of cellular processes like cell migration and survival. FAK inhibition by an anti cancer agent is critical. Therefore, it is of interest to identify, modify, design, improve and develop molecules to inhibit FAK. Solanesol is known to have inhibitory activity towards FAK. However, the molecular principles of its binding with FAK is unknown. Solanesol is a highly flexible ligand (25 rotatable bonds). Hence, ligand-protein docking was completed using AutoDock with a modified contact based scoring function. The FAK-solanesol complex model was further energy minimized and simulated in GROMOS96 (53a6) force field followed by post simulation analysis such as Root mean square deviation (RMSD), root mean square fluctuations (RMSF) and solvent accessible surface area (SASA) calculations to explain solanesol-FAK binding. PMID:29081606

REAL-TIME INTRAVITAL IMAGING ESTABLISHES TUMOUR-ASSOCIATED MACROPHAGES AS THE EXTRASKELETAL TARGET OF BISPHOSPHONATE ACTION IN CANCER

PubMed Central

Junankar, Simon; Shay, Gemma; Jurczyluk, Julie; Ali, Naveid; Down, Jenny; Pocock, Nicholas; Parker, Andrew; Nguyen, Akira; Sun, Shuting; Kashemirov, Boris; McKenna, Charles E.; Croucher, Peter I.; Swarbrick, Alexander; Weilbaecher, Katherine; Phan, Tri Giang; Rogers, Michael J.

2014-01-01

Recent clinical trials have shown that bisphosphonate drugs improve breast cancer patient survival independent of their anti-resorptive effects on the skeleton. However, since bisphosphonates bind rapidly to bone mineral, the exact mechanisms of their anti-tumour action, particularly on cells outside of bone, remain unknown. Here we used real-time intravital two-photon microscopy to show extensive leakage of fluorescent bisphosphonate from the vasculature in 4T1 mouse mammary tumours, where it initially binds to areas of small, granular microcalcifications that are engulfed by tumour-associated macrophages (TAMs), but not tumour cells. Importantly, we also observed uptake of radiolabeled bisphosphonate in the primary breast tumour of a patient and showed the resected tumour to be infiltrated with TAMs and to contain similar granular microcalcifications. These data represent the first compelling in vivo evidence that bisphosphonates can target cells in tumours outside the skeleton and that their anti-tumour activity is likely to be mediated via TAMs. PMID:25312016

Molecular dynamics simulation analysis of Focal Adhesive Kinase (FAK) docked with solanesol as an anti-cancer agent.

PubMed

Daneial, Betty; Joseph, Jacob Paul Vazhappilly; Ramakrishna, Guruprasad

2017-01-01

Focal adhesion kinase (FAK) plays a primary role in regulating the activity of many signaling molecules. Increased FAK expression has been associated in a series of cellular processes like cell migration and survival. FAK inhibition by an anti cancer agent is critical. Therefore, it is of interest to identify, modify, design, improve and develop molecules to inhibit FAK. Solanesol is known to have inhibitory activity towards FAK. However, the molecular principles of its binding with FAK is unknown. Solanesol is a highly flexible ligand (25 rotatable bonds). Hence, ligand-protein docking was completed using AutoDock with a modified contact based scoring function. The FAK-solanesol complex model was further energy minimized and simulated in GROMOS96 (53a6) force field followed by post simulation analysis such as Root mean square deviation (RMSD), root mean square fluctuations (RMSF) and solvent accessible surface area (SASA) calculations to explain solanesol-FAK binding.

Genome Study Yields Clues to Head and Neck Cancers

Cancer.gov

Researchers have surveyed the genetic changes in nearly 300 head and neck cancers, revealing some previously unknown alterations that may play a role in the disease, including in patients whose cancer is associated with the human papillomavirus (HPV).

Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-05-03

Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Molecular effects of soy phytoalexin glyceollins in human prostate cancer cells LNCaP

USDA-ARS?s Scientific Manuscript database

Glyceollins are soy–derived phytoalexins that have been proposed to be candidate cancer preventive compounds. The effect of the glyceollins on prostate cancer is unknown. The present study examined the molecular effects of soy phytoalexins, glyceollins, on the human prostate cancer cell line LNCaP t...

Women with peritoneal carcinomatosis of unknown origin: Efficacy of image-guided biopsy to determine site-specific diagnosis.

PubMed

Hewitt, M J; Anderson, K; Hall, G D; Weston, M; Hutson, R; Wilkinson, N; Perren, T J; Lane, G; Spencer, J A

2007-01-01

To evaluate the use of image-guided biopsy (IGB) in routine clinical practice to obtain site-specific diagnoses in women presenting with peritoneal carcinomatosis (PC). Retrospective case study. Tertiary referral centre. A total of 149 consecutive women with PC who underwent IGB. Biopsy was performed in women considered unsuitable for primary surgery because of poor performance status or disease unlikely to be optimally debulked, with a prior history of malignancy or where there was clinicoradiological uncertainty about primary tumour site. Standard haematoxylin-eosin histological analysis was supplemented with immunohistochemistry. The rate of site-specific diagnosis. A total of 149 women underwent IGB using computed tomography or ultrasound over a 6-year period. The only complication was one rectus sheath haematoma. In 138 (93%) women, a site-specific cancer diagnosis was made on the IGB (including 111 müllerian tract, 8 gastrointestinal tract, 4 breast and 3 lymphoma); in ten women, a repeat biopsy was necessary, giving an overall failure rate of 7%. In a further six women, malignancy was confirmed but a site-specific diagnosis could not be made, and in four women, biopsy showed benign tissue. A site-specific diagnosis was obtained in 29 of the 32 women (94%) with previous malignancy, of which 18/32 (56%) showed a new primary cancer. IGB is a safe and accurate technique for providing site-specific diagnoses in women with PC in routine clinical practice, including those with a previous relevant malignancy. IGB can replace laparoscopic or open biopsy in defining primary therapeutic options. The data would suggest that the biopsy should be performed with ultrasound where feasible.

Vaccine Therapy in Treating Patients With Stage IIIC-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer Following Surgery and Chemotherapy

ClinicalTrials.gov

2017-10-12

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Tumor; Fallopian Tube Mucinous Neoplasm; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; 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; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-01-09

Mixed Mesodermal (Mullerian) Tumor; Ovarian Carcinosarcoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Sarcoma AJCC v7; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Sarcoma AJCC v7; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Uterine Sarcoma AJCC v7; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Uterine Sarcoma AJCC v7; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Uterine Sarcoma AJCC v7; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Sarcoma AJCC v7; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Sarcoma AJCC v7; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Sarcoma AJCC v7; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Sarcoma AJCC v7; Stage IVB Uterine Sarcoma AJCC v7; Uterine Carcinosarcoma

Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: Intrahepatic Disease on the Rise.

PubMed

Saha, Supriya K; Zhu, Andrew X; Fuchs, Charles S; Brooks, Gabriel A

2016-05-01

Challenges in the diagnosis and classification of cholangiocarcinoma have made it difficult to quantify the true incidence of this highly aggressive malignancy. We analyzed the Surveillance, Epidemiology, and End Results data to assess long-term trends in the age-standardized incidence of intrahepatic and extrahepatic cholangiocarcinoma between 1973 and 2012, correcting for systematic coding errors. Because intrahepatic cholangiocarcinoma (ICC) may frequently be misdiagnosed as cancer of unknown primary (CUP), we also analyzed trends in the incidence of CUP. Between 1973 and 2012, the reported U.S. incidence of ICC increased from 0.44 to 1.18 cases per 100,000, representing an annual percentage change (APC) of 2.30%; this trend has accelerated during the past decade to an APC of 4.36%. The incidence of extrahepatic cholangiocarcinoma increased modestly from 0.95 to 1.02 per 100,000 during the 40-year period (APC, 0.14%). The incidence of CUP with histologic features potentially consistent with cholangiocarcinoma decreased by 51% between 1973 and 2012 (APC, -1.87%), whereas the incidence of CUP with squamous or nonepithelial histologic features increased modestly (APC, 0.42%). The recognized incidence of ICC in the U.S. continues to rise, whereas the incidence of ECC is stable. The incidence of CUP has fallen dramatically during the same time period. Clinical distinctions between cholangiocarcinoma (particularly intrahepatic cholangiocarcinoma [ICC]) and cancer of unknown primary (CUP) can be challenging. Recent discoveries have identified recurrent and potentially targetable genomic abnormalities in ICC, highlighting the importance of improving diagnosis. This study demonstrates that the incidence of ICC is increasing in the U.S., whereas the incidence of extrahepatic cholangiocarcinoma is stable. Concomitantly, the incidence of CUP has declined dramatically, suggesting that improved distinction between ICC and CUP may be a major driver of the increasing recognized incidence of ICC. The increasing incidence of ICC warrants further study of prevention and treatment approaches. ©AlphaMed Press.

Randomized open-label non-comparative multicenter phase II trial of sequential erlotinib and docetaxel versus docetaxel alone in patients with non-small-cell lung cancer after failure of first-line chemotherapy: GFPC 10.02 study.

PubMed

Auliac, J B; Chouaid, C; Greillier, L; Greiller, L; Monnet, I; Le Caer, H; Falchero, L; Corre, R; Descourt, R; Bota, S; Berard, H; Schott, R; Bizieux, A; Fournel, P; Labrunie, A; Marin, B; Vergnenegre, A

2014-09-01

Concomitant administration of erlotinib with standard chemotherapy does not appear to improve survival among patients with non-small-cell lung cancer (NSCLC), but preliminary studies suggest that sequential administration might be effective. To assess the efficacy and tolerability of second-line sequential administration of erlotinib and docetaxel in advanced NSCLC. In an open-label phase II trial, patients with advanced NSCLC, EGFR wild-type or unknown, PS 0-2, in whom initial cisplatin-based chemotherapy had failed were randomized to sequential erlotinib 150 mg/d (day 2-16)+docetaxel (75 mg/m(2) d1) (arm ED) or docetaxel (75 mg/m(2) d1) alone (arm D) (21-day cycle). The primary endpoint was the progression-free survival rate at 15 weeks (PFS 15). Secondary endpoints included PFS, overall survival (OS), the overall response rate (ORR) and tolerability. Based on a Simon optimal two-stage design, the ED strategy was rejected if the primary endpoint was below 33/66 patients at the end of the two Simon stages. 147 patients were randomized (median age: 60±8 years, PS 0/1/2: 44/83/20 patients; males: 78%). The ED strategy was rejected, with only 18 of 73 patients achieving PFS15 in arm ED at the end of stage 2 and 17 of 74 patients in arm D. In arms ED and D, respectively, median PFS was 2.2 and 2.5 months and median OS was 6.5 and 8.3 months. Sequential erlotinib and docetaxel was not more effective than docetaxel alone as second-line treatment for advanced NSCLC with wild-type or unknown EGFR status. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Gastric cancer and Helicobacter pylori infection in the eastern Libya: a descriptive epidemiological study.

PubMed

Elzouki, Abdel-Naser Y; Buhjab, Soad I; Alkialani, Akram; Habel, Salah; Sasco, Annie J

2012-06-01

The aim of this study was to determine the pattern of histologically-proven gastric cancer in Eastern Libya and explore its association with Helicobacter pylori infection. The registries of the Departments of Histopathology, Faculty of Medicine, Benghazi University and Oncology, Al-Jomhoria Hospital, Benghazi, were reviewed for cases with primary gastrointestinal cancer from January 2000 to December 2002 (sole Histopathology and Oncology Departments in Eastern Libya). Slides of hematoxylin and eosin stain of gastric cancer patients were re-stained to detect H. pylori. The American Joint Committee on Cancer Tumor, Node, Metastasis staging was used for clinical and pathologic staging. Gastric cancer biopsy materials were classified into intestinal or diffuse type according to Lauren criteria. One hundred and fourteen cases of gastric cancer were diagnosed. Tumor stages were: 2 (14%), 3 (21%), 4 (57%) and unknown (8%). Most common site of involvement was the antrum (48%). Diffuse adenocarcinoma occurred in 56 patients (49.1%), intestinal adenocarcinoma in 46 (40.4%) and malignant gastric lymphoma in 12 (10.5%). The overall frequency of H. pylori infection was 63.2% (72/114), more frequent in intestinal adenocarcinoma (71.7%) and malignant lymphoma (66.6%) than diffuse adenocarcinoma (55.3%). The frequency of gastric cancer increased throughout the three years of study. The majority of the patients were diagnosed in locally advanced or metastatic stage. Clearly more efforts need to be given to early detection. We showed a stronger association of H. pylori infection with intestinal type gastric adenocarcinoma and malignant lymphoma than diffuse adenocarcinoma suggesting that H. pylori infection is the most probable causal factor of gastric cancer in this part of Libya. Copyright © 2012 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

Chemoradiotherapy response in recurrent rectal cancer.

PubMed

Yu, Stanley K T; Bhangu, Aneel; Tait, Diana M; Tekkis, Paris; Wotherspoon, Andrew; Brown, Gina

2014-02-01

The efficacy of response to preoperative chemoradiotherapy (CRT) in recurrent versus primary rectal cancer has not been investigated. We compared radiological downsizing between primary and recurrent rectal cancers following CRT and determined the optimal size reduction threshold for response validated by survival outcomes. The proportional change in tumor length for primary and recurrent rectal cancers following CRT was compared using the independent sample t-test. Overall survival (OS) was calculated using the Kaplan-Meier product limit method and differences between survival for tumor size reduction thresholds of 30% (response evaluation criteria in solid tumors [RECIST]), 40%, and 50% after CRT in primary and recurrent rectal cancer groups. A total of 385 patients undergoing CRT were analyzed, 99 with recurrent rectal cancer and 286 with primary rectal cancer. The mean proportional reduction in maximum craniocaudal length was significantly higher for primary rectal tumors (33%) compared with recurrent rectal cancer (11%) (P < 0.01). There was no difference in OS for either primary or recurrent rectal cancer when ≤30% or ≤40% definitions were used. However, for both primary and recurrent tumors, significant differences in median 3-year OS were observed when a RECIST cut-off of 50% was used. OS was 99% versus 77% in primary and 100% versus 42% in recurrent rectal cancer (P = 0.002 and P = 0.03, respectively). Only patients that demonstrated >50% size reduction showed a survival benefit. Recurrent rectal cancer appears radioresistant compared with primary tumors for tumor size after CRT. Further investigation into improving/intensifying chemotherapy and radiotherapy for locally recurrent rectal cancer is justified. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Quality of Life and Care Needs of Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

ClinicalTrials.gov

2017-05-03

Anxiety; Fatigue; Nausea and Vomiting; Neurotoxicity Syndrome; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer

PubMed Central

Roussos, Evanthia T.; Balsamo, Michele; Alford, Shannon K.; Wyckoff, Jeffrey B.; Gligorijevic, Bojana; Wang, Yarong; Pozzuto, Maria; Stobezki, Robert; Goswami, Sumanta; Segall, Jeffrey E.; Lauffenburger, Douglas A.; Bresnick, Anne R.; Gertler, Frank B.; Condeelis, John S.

2011-01-01

We have shown previously that distinct Mena isoforms are expressed in invasive and migratory tumor cells in vivo and that the invasion isoform (MenaINV) potentiates carcinoma cell metastasis in murine models of breast cancer. However, the specific step of metastatic progression affected by this isoform and the effects on metastasis of the Mena11a isoform, expressed in primary tumor cells, are largely unknown. Here, we provide evidence that elevated MenaINV increases coordinated streaming motility, and enhances transendothelial migration and intravasation of tumor cells. We demonstrate that promotion of these early stages of metastasis by MenaINV is dependent on a macrophage–tumor cell paracrine loop. Our studies also show that increased Mena11a expression correlates with decreased expression of colony-stimulating factor 1 and a dramatically decreased ability to participate in paracrine-mediated invasion and intravasation. Our results illustrate the importance of paracrine-mediated cell streaming and intravasation on tumor cell dissemination, and demonstrate that the relative abundance of MenaINV and Mena11a helps to regulate these key stages of metastatic progression in breast cancer cells. PMID:21670198

Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer.

PubMed

Roussos, Evanthia T; Balsamo, Michele; Alford, Shannon K; Wyckoff, Jeffrey B; Gligorijevic, Bojana; Wang, Yarong; Pozzuto, Maria; Stobezki, Robert; Goswami, Sumanta; Segall, Jeffrey E; Lauffenburger, Douglas A; Bresnick, Anne R; Gertler, Frank B; Condeelis, John S

2011-07-01

We have shown previously that distinct Mena isoforms are expressed in invasive and migratory tumor cells in vivo and that the invasion isoform (Mena(INV)) potentiates carcinoma cell metastasis in murine models of breast cancer. However, the specific step of metastatic progression affected by this isoform and the effects on metastasis of the Mena11a isoform, expressed in primary tumor cells, are largely unknown. Here, we provide evidence that elevated Mena(INV) increases coordinated streaming motility, and enhances transendothelial migration and intravasation of tumor cells. We demonstrate that promotion of these early stages of metastasis by Mena(INV) is dependent on a macrophage-tumor cell paracrine loop. Our studies also show that increased Mena11a expression correlates with decreased expression of colony-stimulating factor 1 and a dramatically decreased ability to participate in paracrine-mediated invasion and intravasation. Our results illustrate the importance of paracrine-mediated cell streaming and intravasation on tumor cell dissemination, and demonstrate that the relative abundance of Mena(INV) and Mena11a helps to regulate these key stages of metastatic progression in breast cancer cells.

Role of ERRF, a Novel ER-Related Nuclear Factor, in the Growth Control of ER-Positive Human Breast Cancer Cells

PubMed Central

Su, Dan; Fu, Xiaoying; Fan, Songqing; Wu, Xiao; Wang, Xin-Xin; Fu, Liya; Dong, Xue-Yuan; Ni, Jianping Jenny; Fu, Li; Zhu, Zhengmao; Dong, Jin-Tang

2012-01-01

Whereas estrogen–estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)–negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER–mediated growth of breast cancer cells and could, thus, be a potential therapeutic target. PMID:22341523

Comments on "Radiofrequency electromagnetic fields and some cancers of unknown etiology: An ecological study".

PubMed

Mortazavi, S A R; Mortazavi, Ghazal; Mortazavi, S M J

2017-12-31

This correspondence refers to the Science of the Total Environment article by Gonzalez-Rubio et al. entitled "Radiofrequency electromagnetic fields and some cancers of unknown etiology: An ecological study". Authors of this paper have presented the findings of their preliminary epidemiological study which combined epidemiology, statistics and geographical information systems (GIS). Gonzalez-Rubio et al. have analyzed the possible link between exposure to Radiofrequency Electromagnetic Fields (RF-EMF) in the city of Albacete, Spain and the incidence of cancers such as lymphomas, and brain tumors. The shortcomings of this study are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

ClinicalTrials.gov

2017-07-10

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

Long Non-coding RNAs (LncRNA) Regulated by Transforming Growth Factor (TGF) β

PubMed Central

Richards, Edward J.; Zhang, Gu; Li, Zhu-Peng; Permuth-Wey, Jennifer; Challa, Sridevi; Li, Yajuan; Kong, William; Dan, Su; Bui, Marilyn M.; Coppola, Domenico; Mao, Wei-Min; Sellers, Thomas A.; Cheng, Jin Q.

2015-01-01

Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes. Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by tumor cells to depart from the primary tumor site, invade surrounding tissue, and establish distant metastases. Transforming growth factor β (TGFβ) signaling has been shown to be a major inducer of EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here we report a genome-wide lncRNA profile in mouse mammary epithelial NMuMG cells upon TGFβ induction of EMT. Among 10,802 lncRNAs profiled, over 600 were up-regulated and down-regulated during the EMT, respectively. Furthermore, we identify that lncRNA-HIT (HOXA transcript induced by TGFβ) mediates TGFβ function, i.e. depletion of lncRNA-HIT inhibits TGFβ-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is also significantly elevated in the highly metastatic 4T1 cells. Knockdown of lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth, and metastasis. E-cadherin was identified as a major target of lncRNA-HIT. Moreover, lncRNA-HIT is conserved in humans and elevated expression associates with more invasive human primary breast carcinoma. Collectively, these data suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in regulation of EMT and breast cancer invasion and metastasis, and could be potential therapeutic targets in breast cancers. PMID:25605728

Who do you prefer? A study of public preferences for health care provider type in performing cutaneous surgery and cosmetic procedures in the United States.

PubMed

Bangash, Haider K; Ibrahimi, Omar A; Green, Lawrence J; Alam, Murad; Eisen, Daniel B; Armstrong, April W

2014-06-01

The public preference for provider type in performing cutaneous surgery and cosmetic procedures is unknown in the United States. An internet-based survey was administered to the lay public. Respondents were asked to select the health care provider (dermatologist, plastic surgeon, primary care physician, general surgeon, and nurse practitioner/physician's assistant) they mostly prefer to perform different cutaneous cosmetic and surgical procedures. Three hundred fifty-four respondents undertook the survey. Dermatologists were identified as the most preferable health care provider to evaluate and biopsy worrisome lesions on the face (69.8%), perform skin cancer surgery on the back (73.4%), perform skin cancer surgery on the face (62.7%), and perform laser procedures (56.3%) by most of the respondents. For filler injections, the responders similarly identified plastic surgeons and dermatologists (47.3% vs 44.6%, respectively) as the most preferred health care provider. For botulinum toxin injections, there was a slight preference for plastic surgeons followed by dermatologists (50.6% vs 38.4%). Plastic surgeons were the preferred health care provider for procedures such as liposuction (74.4%) and face-lift surgery (96.1%) by most of the respondents. Dermatologists are recognized as the preferred health care providers over plastic surgeons, primary care physicians, general surgeons, and nurse practitioners/physician's assistants to perform a variety of cutaneous cosmetic and surgical procedures including skin cancer surgery, on the face and body, and laser procedures. The general public expressed similar preferences for dermatologists and plastic surgeons regarding filler injections.

DNA Misfolding Found to Cause Cancer in IDH-mutant Gliomas

Cancer.gov

Researchers studying IDH-mutant brain tumors have identified a previously unknown genetic mechanism that may contribute to cancer. A change in how DNA is arranged, or packaged, in the cell nucleus may inappropriately activate a gene associated with brain cancer.

Elevated red blood cell distribution width is associated with liver function tests in patients with primary hepatocellular carcinoma.

PubMed

Wei, Ting-Ting; Tang, Qing-Qin; Qin, Bao-Dong; Ma, Ning; Wang, Li-Li; Zhou, Lin; Zhong, Ren-Qian

2016-11-25

Red blood cell distribution width (RDW), a routinely tested parameter of the complete blood count (CBC), has been reported to be increased in various cancers and correlated with the patients' clinical characteristics. However, the significance of RDW in primary hepatocellular carcinoma (pHCC) is largely unknown. The aim of this study was to evaluate the associations between RDW and the clinical characteristics of pHCC patients. Medical records of 110 treatment-naive pHCC patients were retrospectively reviewed. Their clinical characteristics on admission, including RDW, liver function tests and tumor stage, were extracted, and their relationships were analyzed using Spearman correlation and Kruskal-Wallis test. Sixty-eight healthy individuals were set as controls. RDW was significantly increased in pHCC patients and correlated with the liver function tests. However, no correlation between RDW and tumor stage was found. RDW may be used to assess the liver function, but not the tumor stage in pHCC patients.

[A case of pulmonary malignant melanoma mimicking lung abscess].

PubMed

Mochizuki, Hideaki; Chikui, Emiko; Tokumaru, Aya; Kato, Takayuki; Arai, Tomio; Takahashi, Hideki

2011-06-01

An 84-year-old man was admitted with paresis of the right lower limb. Hemorrhagic lesions were demonstrated in the left frontoparietal lobe and cerebellum by cranial computed tomography (CT) and magnetic resonance imaging (MRI). Chest CT revealed an ill-defined mass measuring 4 x 6 cm in the left lower lobe of the lung, although bronchoscopic examination failed to obtain pathological diagnosis. Clinical diagnosis of primary lung cancer with multiple brain metastases was made, and he underwent whole brain radiotherapy. The pulmonary and cerebral lesions mimicked abscesses during his clinical course, and he died of respiratory failure due to bilateral pneumonia three months after admission. Autopsy revealed that both the pulmonary and brain lesions were malignant melanomas, but no other melanoma lesions could be identified despite meticulous investigation. Although malignant melanoma with an unknown primary site is rare in Japan, careful evaluation of the CT and MRI findings might be the key to correct diagnosis in this case.

Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-02-14

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-03-22

Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Tumor; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Profiling for primary-care presentation, investigation and referral for liver cancers: evidence from a national audit.

PubMed

Hughes, Daniel L; Neal, Richard D; Lyratzopoulos, Georgios; Rubin, Greg

2016-04-01

The incidence of liver cancer across Europe is increasing. There is a lack of evidence within the current literature on the identification and investigation of liver cancer within primary care. We aimed to profile liver cancer recognition and assessment as well as the timeliness of liver cancer diagnosis from within the primary-care setting in the UK. Data were obtained from the National Audit of Cancer Diagnosis in Primary Care 2009-2010 and analysed. We calculated the patient interval, the primary-care interval and the number of prereferral consultations for liver cancer. We then compared these data with prior data on the respective indicators for other common cancers. The median patient interval was 9 days (interquartile range 0-31 days), and the median primary-care interval for liver cancer was 11 days (interquartile range 0-40 days). Of the 90 patients, 21 (23.3%) had three or more consultations with their general practitioner before specialist referral. For the three metrics (patient interval, primary-care interval and number of prereferral consultations), liver cancer has average or longer intervals when compared with other cancers. The most common symptomatic presentation of liver cancer within the primary-care setting was right upper quadrant pain (11%), followed by decompensated liver failure (9%). Of the patients, 12% were diagnosed with liver cancer on the basis of an incidental finding of an abnormal liver function test. This study provides a detailed and thorough overview of the recognition of liver cancer and the promptness of liver cancer identification in an English context, and should inform strategies for improving the timeliness of diagnosis.

HPV status in patients with head and neck of carcinoma of unknown primary site: HPV, tobacco smoking, and outcome.

PubMed

Tribius, Silke; Hoffmann, Anna S; Bastrop, Sophie; Görögh, Tibor; Haag, Jochen; Röcken, Christoph; Clauditz, Till; Grob, Tobias; Wilczak, Waldemar; Tennstedt, Pierre; Borcherding, Aileen; Petersen, Cordula; Hoffmann, Markus

2012-11-01

Infection with human papillomavirus (HPV) is linked to oropharyngeal cancer. This analysis investigated possible associations between HPV status, smoking history and survival outcome in patients with neck metastasis and carcinoma of unknown primary (CUP). Registries at the Universities of Hamburg and Kiel were searched for patients with CUP diagnosed from 2002 to 2011 who had formalin-fixed and paraffin-embedded metastatic lymph node samples available. All patients underwent routine diagnostic procedures to establish the primary site and received radiotherapy (60Gy using conventional fractionation) with or without concurrent cisplatin-based chemotherapy depending on disease extent. Genotyping was performed using polymerase chain reaction; p16([INK4a]) expression was assessed using immunohistochemistry. Sixty-three patients were included; 23 (37%) had HPV DNA/p16+ samples and 40 (63%) were negative for either/both markers. A high proportion of patients had a history of tobacco smoking; significantly fewer patients with HPV+/p16+ samples were smokers than those who were negative for either/both markers (61% vs. 90%, respectively; p = 0.0067). There were no statistically significant differences between overall or recurrence-free survival in HPV+/p16+ patients vs. those negative for either/both markers. Overall survival appeared to be superior in patients with <10 pack-years smoking history and HPV+/p16+ disease. This study, the largest to date investigating HPV status in head and neck CUP, identified HPV and p16 overexpression in over one-third of patients. Tobacco smoking history appeared to affect survival in HPV+/p16+ patients. Smoking status should be considered as a prognostic factor in patients with CUP, along with HPV DNA status. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mutational analysis of multiple lung cancers: Discrimination between primary and metastatic lung cancers by genomic profile.

PubMed

Goto, Taichiro; Hirotsu, Yosuke; Mochizuki, Hitoshi; Nakagomi, Takahiro; Shikata, Daichi; Yokoyama, Yujiro; Oyama, Toshio; Amemiya, Kenji; Okimoto, Kenichiro; Omata, Masao

2017-05-09

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.

Physical and mental health status of survivors of multiple cancer diagnoses: findings from the National Health Interview Survey.

PubMed

Andrykowski, Michael A

2012-07-15

Little research has identified the physical and mental health status of survivors of multiple primary cancer diagnoses. By using data from the population-based 2009 National Health Information Survey, 154 survivors of multiple primary cancer diagnoses, 1427 survivors of a single cancer diagnosis, and 25,004 individuals without a history of cancer diagnosis were identified. The multiple cancer group was compared with the single cancer and no cancer groups with regard to physical and mental health status using analysis of covariance and binary logistic regression. Relative to the no cancer group, the multiple cancer group reported significantly poorer mental health status, greater lifetime, recent, and current prevalence of a variety of medical conditions and comorbidities, and more health-related disability. Although observed group differences between the multiple cancer and single cancer groups were less pronounced than those between the multiple cancer and no cancer groups, a consistent pattern was also evident; the multiple cancer group reported significantly poorer status relative to the single cancer group across a range of mental and physical health and illness-related disability indices. Diagnosis of 2 or more primary cancers (excluding nonmelanoma skin cancers) is associated with increased risk for poorer physical and mental health status over and above that associated with diagnosis of a single primary cancer. Survivors of multiple and single primary cancer diagnoses should be considered as distinct subgroups, and increased attention should be devoted to the unique status and needs of survivors of multiple primary cancer diagnoses. Copyright © 2011 American Cancer Society.

Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.

PubMed

Saunus, Jodi M; Quinn, Michael C J; Patch, Ann-Marie; Pearson, John V; Bailey, Peter J; Nones, Katia; McCart Reed, Amy E; Miller, David; Wilson, Peter J; Al-Ejeh, Fares; Mariasegaram, Mythily; Lau, Queenie; Withers, Teresa; Jeffree, Rosalind L; Reid, Lynne E; Da Silva, Leonard; Matsika, Admire; Niland, Colleen M; Cummings, Margaret C; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Kassahn, Karin S; Narayanan, Vairavan; Taib, Nur Aishah; Teo, Soo-Hwang; Chow, Yock Ping; kConFab; Jat, Parmjit S; Brandner, Sebastian; Flanagan, Adrienne M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Grimmond, Sean M; Simpson, Peter T; Waddell, Nicola; Lakhani, Sunil R

2015-11-01

Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting HER3, which is broadly over-expressed and activated in BMs, independent of primary site and systemic therapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Clonal haemopoiesis and therapy-related myeloid malignancies in elderly patients: a proof-of-concept, case-control study.

PubMed

Gillis, Nancy K; Ball, Markus; Zhang, Qing; Ma, Zhenjun; Zhao, YuLong; Yoder, Sean J; Balasis, Maria E; Mesa, Tania E; Sallman, David A; Lancet, Jeffrey E; Komrokji, Rami S; List, Alan F; McLeod, Howard L; Alsina, Melissa; Baz, Rachid; Shain, Kenneth H; Rollison, Dana E; Padron, Eric

2017-01-01

Clonal haemopoiesis of indeterminate potential (CHIP) is an age-associated genetic event linked to increased risk of primary haematological malignancies and increased all-cause mortality, but the prevalence of CHIP in patients who develop therapy-related myeloid neoplasms is unknown. We did this study to investigate whether chemotherapy-treated patients with cancer who have CHIP are at increased risk of developing therapy-related myeloid neoplasms. We did a nested, case-control, proof-of-concept study to compare the prevalence of CHIP between patients with cancer who later developed therapy-related myeloid neoplasms (cases) and patients who did not develop these neoplasms (controls). We identified cases from our internal biorepository of 123 357 patients who consented to participate in the Total Cancer Care biobanking protocol at Moffitt Cancer Center (Tampa, FL, USA) between Jan 1, 2006, and June 1, 2016. We included all individuals who were diagnosed with a primary malignancy, were treated with chemotherapy, subsequently developed a therapy-related myeloid neoplasm, and were 70 years or older at either diagnosis. For inclusion in this study, individuals must have had a peripheral blood or mononuclear cell sample collected before the diagnosis of therapy-related myeloid neoplasm. Controls were individuals who were diagnosed with a primary malignancy at age 70 years or older and were treated with chemotherapy but did not develop therapy-related myeloid neoplasms. Controls were matched to cases in at least a 4:1 ratio on the basis of sex, primary tumour type, age at diagnosis, smoking status, chemotherapy drug class, and duration of follow-up. We used sequential targeted and whole-exome sequencing and described clonal evolution in cases for whom paired CHIP and therapy-related myeloid neoplasm samples were available. The primary endpoint of this study was the development of therapy-related myeloid neoplasm and the primary exposure was CHIP. We identified 13 cases and 56 case-matched controls. The prevalence of CHIP in all patients (23 [33%] of 69 patients) was higher than has previously been reported in elderly individuals without cancer (about 10%). Cases had a significantly higher prevalence of CHIP than did matched controls (eight [62%] of 13 cases vs 15 [27%] of 56 controls, p=0·024; odds ratio 5·75, 95% CI 1·52-25·09, p=0·013). The most commonly mutated genes in cases with CHIP were TET2 (three [38%] of eight patients) and TP53(three [38%] of eight patients), whereas controls most often had TET2 mutations (six [40%] of 15 patients). In most (four [67%] of six patients) cases for whom paired CHIP and therapy-related myeloid neoplasm samples were available, the mean allele frequency of CHIP mutations had expanded by the time of the therapy-related myeloid neoplasm diagnosis. However, a subset of paired samples (two [33%] of six patients) had CHIP mutations that decreased in allele frequency, giving way to expansion of a distinct mutant clone. Patients with cancer who have CHIP are at increased risk of developing therapy-related myeloid neoplasms. The distribution of CHIP-related gene mutations differs between individuals with therapy-related myeloid neoplasm and those without, suggesting that mutation-specific differences might exist in therapy-related myeloid neoplasm risk. Moffitt Cancer Center. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetics and Molecular Diagnostics in Retinoblastoma--An Update.

PubMed

Soliman, Sameh E; Racher, Hilary; Zhang, Chengyue; MacDonald, Heather; Gallie, Brenda L

2017-01-01

Retinoblastoma is the prototype genetic cancer: in one or both eyes of young children, most retinoblastomas are initiated by biallelic mutation of the retinoblastoma tumor suppressor gene, RB1, in a developing retinal cell. All those with bilateral retinoblastoma have heritable cancer, although 95% have not inherited the RB1 mutation. Non-heritable retinoblastoma is always unilateral, with 98% caused by loss of both RB1 alleles from the tumor, whereas 2% have normal RB1 in tumors initiated by amplification of the MYCN oncogene. Good understanding of retinoblastoma genetics supports optimal care for retinoblastoma children and their families. Retinoblastoma is the first cancer to officially acknowledge the seminal role of genetics in cancer, by incorporating "H" into the eighth edition of cancer staging (2017): those who carry the RB1 cancer-predisposing gene are H1; those proven to not carry the familial RB1 mutation are H0; and those at unknown risk are HX. We suggest H0* be used for those with residual <1% risk to carry a RB1 mutation due to undetectable mosaicism. Loss of RB1 from a susceptible developing retinal cell initiates the benign precursor, retinoma. Progressive genomic changes result in retinoblastoma, and cancer progression ensues with increasing genomic disarray. Looking forward, novel therapies are anticipated from studies of retinoblastoma and metastatic tumor cells and the second primary cancers that the carriers of RB1 mutations are at high risk to develop. Here, we summarize the concepts of retinoblastoma genetics for ophthalmologists in a question/answer format to assist in the care of patients and their families. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Major Histocompatibilty Complex-Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera.

PubMed

Lee, K W; Choi, B; Kim, Y M; Cho, C W; Park, H; Moon, J I; Choi, G-S; Park, J B; Kim, S J

2017-06-01

Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 10 5 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2L d -restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4 + and CD8 + T cells at various time points. We found that immunocompetence against tumors depends heavily on cancer-specific CD8 + T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4 + T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62L hi CCR7 + ) as well as effector memory cells (CD62L lo CCR7 - ). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of pulmonary nodules in head and neck cancer patients - Our experience and interpretation of the British Thoracic Society Guidelines.

PubMed

Green, Richard; King, Matthew; Reid, Helen; Murchison, John T; Evans, Andrew; Nixon, Iain J

2017-08-01

and purpose of the study: The frequency of lung nodules in the head and neck cancer population is unknown, currently the only guidance available recommends following local policy. The aim of this study was to determine the incidence of pulmonary nodules in our head and neck cancer group and interpret the recently updated British Thoracic Society (BTS) Lung Nodule Guidelines in a head and neck cancer setting. 100 patients were diagnosed with head and neck cancer between July 2013-March 2014, clinico-pathological, demographic and radiological data was extracted from the electronic records. Images with lung findings were re-reviewed by a single consultant radiologist for patients with lung pathology on the initial staging CT report. Twenty patients (20%) had discreet pulmonary findings on CT. Eleven (11%) had lung nodules, 6 (6%) had lesions suspicious for metastasis and 3 (3%) had co-incidental bronchogenic primary cancers. These patients were re-imaged between 6 and 18 months and in 1 patient the previously identified 7 mm nodule had progressed to 16 mm at 1 year. There was no set follow up imaging protocol used. The MDT in NHS Lothian has reviewed the BTS guidance and now has a local policy for the management of lung nodules in head and neck cancer patients. Lung Nodules in the head and neck cancer population are common >10%. Higher risk patients with larger nodules should be risk assessed with validated assessment tools. PET-CT has a place in the assessment of lung nodules when risk of malignancy is high. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

ClinicalTrials.gov

2018-04-11

Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

Relationship between variant forms of estrogen receptor RNA and an apoptosis-related RNA, TRPM-2, with survival in patients with breast cancer.

PubMed

Rennie, P S; Mawji, N R; Coldman, A J; Godolphin, W; Jones, E C; Vielkind, J R; Bruchovsky, N

1993-12-15

Although smaller variant forms of estrogen receptor (ER) messenger RNA (mRNA) have been detected in breast tumors, neither their prevalence nor their prognostic significance have been evaluated. Similarly, TRPM-2 mRNA, the product of a gene induced principally during the onset of apoptosis, is present in mouse and human breast cancer cell lines, but whether it also occurs in primary breast tumors and is related to disease outcome is unknown. The relative expression and transcript size of ER mRNA and TRPM-2 mRNA in 126 primary breast tumors were measured by Northern analysis and compared with tumor grade, hormone receptor status, extent of tumor necrosis, and survival. In ER-positive tumors, 64% of the tumors had only the normal 6.5 kb ER mRNA, an additional 9% had the normal plus smaller ER mRNA, and 2% had variant forms. Only 8% of ER-negative tumors had ER mRNA transcripts. There were significant relationships between the occurrence of ER mRNA and low tumor grade, ER-positive receptor status, and better survival. In contrast, TRPM-2 mRNA was found in only 17% of breast tumors, none of which could be grouped with respect to grade, hormone receptor status, or survival. The presence of smaller variant forms of ER mRNA either alone or in association with the normal ER transcript is not indicative of an unfavorable prognosis, whereas TRPM-2 mRNA occurs in many primary breast tumors, but has no apparent relationship to survival.

Second primary cancers of the breast: incidence and risk factors.

PubMed Central

Hislop, T. G.; Elwood, J. M.; Coldman, A. J.; Spinelli, J. J.; Worth, A. J.; Ellison, L. G.

1984-01-01

Between 1946 and 1976 over 9,000 women with breast cancer were seen within one year of diagnosis at the A. Maxwell Evans Clinic (AMEC) in Vancouver, British Columbia. By 1978, 275 had a subsequent diagnosis of a second primary in the contralateral breast: 100 were diagnosed within 1 year, and 175 after 1 year of the first primary. Two separate comparison groups of AMEC patients with unilateral breast cancer were selected to identify risk factors for bilateral breast cancer and to determine the incidence. The average annual incidence rates for a second primary in the contralateral breast were 5.0, 4.1 and 3.0 per 1,000 women for women less than 45 years, 45-54 years, and over 55 years of age at diagnosis of first primary breast cancer, respectively. These rates remained stable for at least 15 years after the diagnosis of the first primary. Two risk factors were found for bilateral cancer within 1 year of the first primary, histologic diagnosis of lobular carcinoma and absence of pathologic involvement of axillary nodes; one risk factor was found for bilateral breast cancer after 1 year of the first primary, family history of breast cancer. PMID:6691900

Second primary cancers following borderline ovarian tumors.

PubMed

Sanci, Muzaffer; Gultekin, Emre; Cingillioglu, Basak; Gultekin, Ozge Elmastas; Ozvural, Seyfettin; Emirdar, Volkan; Yildirim, Yusuf

2011-06-01

Several studies have reported an increased risk of second primary cancers subsequent to invasive epithelial ovarian cancer. However, there is no adequate data regarding such risk in borderline ovarian tumors (BOTs). The aim of this study was to evaluate the risk of subsequent second primary cancers among women with BOTs. BOT patients treated in our center between December 1985 and April 2009 were retrospectively screened for developing second primary cancer during follow-up period. There were 96 women diagnosed with BOT. Mean age at the time of diagnosis was 47 ± 14.3, ranging from 19 to 79. Eighty-eight (91.6%) patients had stage I disease, two patients (2.1%) had stage II and six (6.2%) had stage III. Twenty-five (26.0%) patients received platinum-based adjuvant chemotherapy. Mean follow-up time was 96.5 ± 442 months (range: 9-280 months). There were ten (10.4%) recurrences. Only one patient developed second primary cancer. Second primary cancer observed in this case was basal cell carsinoma of the eyelid, which was diagnosed 2 years after primary disease. There were no patients with common women's cancers such as breast and colorectal cancers. These findings do not suggest increased risk of subsequent cancers in patients with BOT. However, population-based studies are needed for evaluating exact risk of developing second primary malignancies in women with BOTs.

Cancer-associated fibroblasts in a human HEp-2 established laryngeal xenografted tumor are not derived from cancer cells through epithelial-mesenchymal transition, phenotypically activated but karyotypically normal.

PubMed

Wang, Mei; Wu, Chun-Ping; Pan, Jun-Yan; Zheng, Wen-Wei; Cao, Xiao-Juan; Fan, Guo-Kang

2015-01-01

Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression and even initiation. However, the origins of CAFs in various cancer types remain controversial, and one of the important hypothesized origins is through epithelial-mesenchymal transition (EMT) from cancer cells. In this study, we investigated whether the HEp-2 laryngeal cancer cells are able to generate CAFs via EMT during tumor formation, which is now still unknown. The laryngeal xenografted tumor model was established by inoculating the HEp-2 laryngeal cancer cell line in nude mice. Primary cultured CAFs from the tumor nodules and matched normal fibroblasts (NFs) from the adjacent connective tissues were subcultured, purified, and verified by immunofluorescence. Migration, invasion, and proliferation potentials were compared between the CAFs and NFs. A co-culture of CAFs with HEp-2 cells and a co-injection of CAFs with HEp-2 cells in nude mice were performed to examine the cancer-promoting potential of CAFs to further verify their identity. Karyotypic analyses of the CAFs, NFs, and HEp-2 cells were conducted. A co-culture of NFs with HEp-2 cells was also performed to examine the expression of activated markers of CAFs. A pathological examination confirmed that the laryngeal xenografted tumor model was successfully established, containing abundant CAFs. Immunocytochemical staining verified the purities and identities of the CAFs and NFs. Although the CAFs manifested higher migration, invasion, proliferation, and cancer-promoting capacities compared with the NFs, an analysis of chromosomes revealed that both the CAFs and NFs showed typical normal mouse karyotypes. In addition, the NFs co-cultured with HEp-2 cells did not show induced expressions of activated markers of CAFs. Our findings reveal that the CAFs in the HEp-2 established laryngeal xenografted tumor are not of laryngeal cancer origin but of mouse origin, indicating that the HEp-2 laryngeal cancer cells cannot generate their own CAFs via EMT in this model.

TERT promoter mutation in adult granulosa cell tumor of the ovary.

PubMed

Pilsworth, Jessica A; Cochrane, Dawn R; Xia, Zhouchunyang; Aubert, Geraldine; Färkkilä, Anniina E M; Horlings, Hugo M; Yanagida, Satoshi; Yang, Winnie; Lim, Jamie L P; Wang, Yi Kan; Bashashati, Ali; Keul, Jacqueline; Wong, Adele; Norris, Kevin; Brucker, Sara Y; Taran, Florin-Andrei; Krämer, Bernhard; Staebler, Annette; Oliva, Esther; Shah, Sohrab P; Kommoss, Stefan; Kommoss, Friedrich; Gilks, C Blake; Baird, Duncan M; Huntsman, David G

2018-02-15

The telomerase reverse transcriptase (TERT) gene is highly expressed in stem cells and silenced upon differentiation. Cancer cells can attain immortality by activating TERT to maintain telomere length and telomerase activity, which is a crucial step of tumorigenesis. Two somatic mutations in the TERT promoter (C228T; C250T) have been identified as gain-of-function mutations that promote transcriptional activation of TERT in multiple cancers, such as melanoma and glioblastoma. A recent study investigating TERT promoter mutations in ovarian carcinomas found C228T and C250T mutations in 15.9% of clear cell carcinomas. However, it is unknown whether these mutations are frequent in other ovarian cancer subtypes, in particular, sex cord-stromal tumors including adult granulosa cell tumors. We performed whole-genome sequencing on ten adult granulosa cell tumors with matched normal blood and identified a TERT C228T promoter mutation in 50% of tumors. We found that adult granulosa cell tumors with mutated TERT promoter have increased expression of TERT mRNA and exhibited significantly longer telomeres compared to those with wild-type TERT promoter. Extension cohort analysis using allelic discrimination revealed the TERT C228T mutation in 51 of 229 primary adult granulosa cell tumors (22%), 24 of 58 recurrent adult granulosa cell tumors (41%), and 1 of 22 other sex cord-stromal tumors (5%). There was a significant difference in overall survival between patients with TERT C228T promoter mutation in the primary tumors and those without it (p = 0.00253, log-rank test). In seven adult granulosa cell tumors, we found the TERT C228T mutation present in recurrent tumors and absent in the corresponding primary tumor. Our data suggest that TERT C228T promoter mutations may have an important role in progression of adult granulosa cell tumors.

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial.

PubMed

Ali, H R; Dariush, A; Thomas, J; Provenzano, E; Dunn, J; Hiller, L; Vallier, A-L; Abraham, J; Piper, T; Bartlett, J M S; Cameron, D A; Hayward, L; Brenton, J D; Pharoah, P D P; Irwin, M J; Walton, N A; Earl, H M; Caldas, C

2017-08-01

We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown. The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed. Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78-4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24-3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033-0.31; P < 0.001). Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients. NCT01093235. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer.

PubMed

Wong, Kah Keng; Hussain, Faezahtul Arbaeyah; Loo, Suet Kee; López, José I

2017-12-01

Spermatogenesis-associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non-malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non-malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non-malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty-nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H-score) was not associated with overall survival or disease-specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Integrating Primary Care Providers in the Care of Cancer Survivors: Gaps in Evidence and Future Opportunities

PubMed Central

Nekhlyudov, Larissa; O’Malley, Denalee M.; Hudson, Shawna V.

2017-01-01

For over a decade since the release of the Institute of Medicine report, From Cancer Patient to Cancer Survivor: Lost in Transition, there has been a focus on providing coordinated, comprehensive care for cancer survivors that emphasized the role of primary care. Several models of care have been described which primarily focused on primary care providers (PCPs) as receivers of cancer survivors and specific types of information (e.g. survivorship care plans) from oncology based care, and not as active members of the cancer survivorship team. In this paper, we reviewed survivorship models that have been described in the literature, and specifically focused on strategies aiming to integrate primary care providers in caring for cancer survivors across different settings. We offer insights differentiating primary care providers’ level of expertise in cancer survivorship and how such expertise may be utilized. We provide recommendations for education, clinical practice, research and policy initiatives that may advance the integration of primary care providers in the care of cancer survivors in diverse clinical settings. PMID:28049575

Intravital Microscopy in Evaluating Patients With Primary Peritoneal, Fallopian Tube, or Stage IA-IV Ovarian Cancer

ClinicalTrials.gov

2018-06-20

Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Ovarian Cancer; Stage IB Ovarian Cancer; Stage IC Ovarian Cancer; Stage II Ovarian Cancer; Stage IIA Ovarian Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage III Ovarian Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Ovarian Cancer

Toward the human cellular microRNAome.

PubMed

McCall, Matthew N; Kim, Min-Sik; Adil, Mohammed; Patil, Arun H; Lu, Yin; Mitchell, Christopher J; Leal-Rojas, Pamela; Xu, Jinchong; Kumar, Manoj; Dawson, Valina L; Dawson, Ted M; Baras, Alexander S; Rosenberg, Avi Z; Arking, Dan E; Burns, Kathleen H; Pandey, Akhilesh; Halushka, Marc K

2017-10-01

MicroRNAs are short RNAs that serve as regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell-autonomously, and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data have caused considerable confusion, and comprehensive cell-level data do not yet exist. Here, we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues. It identified both specific and ubiquitous patterns of expression that strongly correlate with adjacent superenhancer activity. Analysis of unaligned RNA reads uncovered 207 unknown minor strand (passenger) microRNAs of known microRNA loci and 495 novel putative microRNA loci. Although cancer cell lines generally recapitulated the expression patterns of matched primary cells, their isomiR sequence families exhibited increased disorder, suggesting DROSHA- and DICER1-dependent microRNA processing variability. Cell-specific patterns of microRNA expression were used to de-convolute variable cellular composition of colon and adipose tissue samples, highlighting one use of these cell-specific microRNA expression data. Characterization of cellular microRNA expression across a wide variety of cell types provides a new understanding of this critical regulatory RNA species. © 2017 McCall et al.; Published by Cold Spring Harbor Laboratory Press.

Stimulation of the ovaries in women with breast cancer undergoing fertility preservation: Alternative versus standard stimulation protocols; the study protocol of the STIM-trial.

PubMed

Dahhan, T; Balkenende, E M E; Beerendonk, C C M; Fleischer, K; Stoop, D; Bos, A M E; Lambalk, C B; Schats, R; van Golde, R J T; Schipper, I; Louwé, L A; Cantineau, A E P; Smeenk, J M J; de Bruin, J P; Reddy, N; Kopeika, Y; van der Veen, F; van Wely, M; Linn, S C; Goddijn, M

2017-10-01

Chemotherapy for breast cancer may have a negative impact on reproductive function due to gonadotoxicity. Fertility preservation via banking of oocytes or embryos after ovarian stimulation with FSH can increase the likelihood of a future live birth. It has been hypothesized that elevated serum estrogen levels during ovarian stimulation may induce breast tumour growth. This has led to the use of alternative stimulation protocols with addition of tamoxifen or letrozole. The effectiveness of these stimulation protocols in terms of oocyte yield is unknown. Randomized open-label trial comparing ovarian stimulation plus tamoxifen and ovarian stimulation plus letrozole with standard ovarian stimulation in the course of fertility preservation. The study population consists of women with breast cancer who opt for banking of oocytes or embryos, aged 18-43years at randomisation. Primary outcome is the number of oocytes retrieved at follicle aspiration. Secondary outcomes are number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation. Concerning the lack of evidence on which stimulation protocol should be used in women with breast cancer and the growing demand for fertility preservation, there is an urgent need to undertake this study. By performing this study, we will be able to closely monitor the effects of various stimulation protocols in women with breast cancer and pave the way for long term follow up on the safety of this procedure in terms of breast cancer prognosis. NTR4108. Copyright © 2017 Elsevier Inc. All rights reserved.

JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia.

PubMed

Bonetto, Andrea; Aydogdu, Tufan; Jin, Xiaoling; Zhang, Zongxiu; Zhan, Rui; Puzis, Leopold; Koniaris, Leonidas G; Zimmers, Teresa A

2012-08-01

Cachexia, the metabolic dysregulation leading to sustained loss of muscle and adipose tissue, is a devastating complication of cancer and other chronic diseases. Interleukin-6 and related cytokines are associated with muscle wasting in clinical and experimental cachexia, although the mechanisms by which they might induce muscle wasting are unknown. One pathway activated strongly by IL-6 family ligands is the JAK/STAT3 pathway, the function of which has not been evaluated in regulation of skeletal muscle mass. Recently, we showed that skeletal muscle STAT3 phosphorylation, nuclear localization, and target gene expression are activated in C26 cancer cachexia, a model with high IL-6 family ligands. Here, we report that STAT3 activation is a common feature of muscle wasting, activated in muscle by IL-6 in vivo and in vitro and by different types of cancer and sterile sepsis. Moreover, STAT3 activation proved both necessary and sufficient for muscle wasting. In C(2)C(12) myotubes and in mouse muscle, mutant constitutively activated STAT3-induced muscle fiber atrophy and exacerbated wasting in cachexia. Conversely, inhibiting STAT3 pharmacologically with JAK or STAT3 inhibitors or genetically with dominant negative STAT3 and short hairpin STAT3 reduced muscle atrophy downstream of IL-6 or cancer. These results indicate that STAT3 is a primary mediator of muscle wasting in cancer cachexia and other conditions of high IL-6 family signaling. Thus STAT3 could represent a novel therapeutic target for the preservation of skeletal muscle in cachexia.

JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia

PubMed Central

Bonetto, Andrea; Aydogdu, Tufan; Jin, Xiaoling; Zhang, Zongxiu; Zhan, Rui; Puzis, Leopold; Koniaris, Leonidas G.

2012-01-01

Cachexia, the metabolic dysregulation leading to sustained loss of muscle and adipose tissue, is a devastating complication of cancer and other chronic diseases. Interleukin-6 and related cytokines are associated with muscle wasting in clinical and experimental cachexia, although the mechanisms by which they might induce muscle wasting are unknown. One pathway activated strongly by IL-6 family ligands is the JAK/STAT3 pathway, the function of which has not been evaluated in regulation of skeletal muscle mass. Recently, we showed that skeletal muscle STAT3 phosphorylation, nuclear localization, and target gene expression are activated in C26 cancer cachexia, a model with high IL-6 family ligands. Here, we report that STAT3 activation is a common feature of muscle wasting, activated in muscle by IL-6 in vivo and in vitro and by different types of cancer and sterile sepsis. Moreover, STAT3 activation proved both necessary and sufficient for muscle wasting. In C2C12 myotubes and in mouse muscle, mutant constitutively activated STAT3-induced muscle fiber atrophy and exacerbated wasting in cachexia. Conversely, inhibiting STAT3 pharmacologically with JAK or STAT3 inhibitors or genetically with dominant negative STAT3 and short hairpin STAT3 reduced muscle atrophy downstream of IL-6 or cancer. These results indicate that STAT3 is a primary mediator of muscle wasting in cancer cachexia and other conditions of high IL-6 family signaling. Thus STAT3 could represent a novel therapeutic target for the preservation of skeletal muscle in cachexia. PMID:22669242

AFP464 in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery

ClinicalTrials.gov

2014-02-21

Male Breast Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Renal Cell Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

PubMed Central

Workel, Hagma H.; Tijans, Aline M.; Terwindt, Anouk L.J.; Brunekreeft, Kim L.; Plat, Annechien; Klip, Harry G.; Eggink, Florine A.; Leffers, Ninke; Helfrich, Wijnand; Samplonius, Douwe F.; Bremer, Edwin; Wisman, G. Bea A.; Daemen, Toos; Duiker, Evelien W.; Hollema, Harry; Nijman, Hans W.; de Bruyn, Marco

2016-01-01

CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis. We further demonstrate that CD103+ TIL were almost exclusively CD3+ TCRαβ+ CD8αβ+ CD4- T cells, but heterogeneously expressed T cell memory and differentiation markers. Activation of peripheral T cells in the presence of HGSC was sufficient to trigger induction of CD103 in over 90% of all CD8+ cells in a T cell receptor (TCR)- and TGFβR1-dependent manner. Finally, CD103+ TIL isolated from primary HGSC showed signs of recent activation and dominantly co-expressed key immunotherapeutic targets PD-1 and CD27. Taken together, our data indicate CD103+ TIL in HGSC are formed as the result of an adaptive anti-tumor immune response that might be reactivated by (dual) checkpoint inhibition. PMID:27650547

Aspirin use and head and neck cancer survival: an observational study of 11,623 person-years follow-up.

PubMed

Kim, Shin-Ae; Roh, Jong-Lyel; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2018-02-01

Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risks for certain human cancers. However, the effects of aspirin and NSAIDs on head and neck squamous cell carcinoma (HNSCC) remain controversial, and the prognostic effects of these drugs in patients with HNSCC are largely unknown. This study examined the clinical impact of aspirin and NSAIDs on disease recurrence and survival in patients with HNSCC. This study analysed a cohort of 1392 consecutive patients who received definitive treatment for previously untreated HNSCC at our tertiary referral center. Aspirin or NSAID use was considered positive if the patients were receiving aspirin or NSAID medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilised to determine the association of aspirin and/or NSAID use with recurrence, survival, and second primary cancer occurrence. Of 1392 patients, 81 (5.8%) and 89 (6.4%) received post-diagnosis treatment with aspirin and NSAIDs, respectively. After controlling for clinical factors, aspirin and NSAIDs were not significantly associated with recurrence, survival, or second cancer occurrence (P > 0.05). The cumulative dose of aspirin or NSAIDs did not alter survival outcomes (P > 0.05). Our data illustrated that the use of aspirin or NSAIDs has no effect on survival or recurrence in patients with HNSCC.

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer.

PubMed

Fujisawa, Rina; Shibuya, Hitoshi; Harata, Naoki; Yuasa-Nakagawa, Keiko; Toda, Kazuma; Hayashi, Keiji

2014-02-01

Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers. The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed. Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years. Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5-10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.

Investigating Barriers in HIV-Testing Oncology Patients: The IBITOP Study, Phase I.

PubMed

Merz, Laurent; Zimmermann, Stefan; Peters, Solange; Cavassini, Matthias; Darling, Katharine E A

2016-10-01

Although the prevalence of non-AIDS-defining cancers (non-ADCs) among people living with HIV is rising, we observed HIV testing rates below 5% at our oncology center, against a regional HIV prevalence of 0.2%-0.4%. We performed the Investigating Barriers in HIV-Testing Oncology Patients (IBITOP) study among oncology physicians and patients. Between July 1 and October 31, 2013, patients of unknown HIV status newly diagnosed with solid-organ non-ADCs referred to Lausanne University Hospital Oncology Service, Switzerland, were offered free HIV testing as part of their oncology work-up. The primary endpoints were (a) physician willingness to offer and patient acceptance of HIV testing and (b) physicians' reasons for not offering testing. Of 239 patients of unknown HIV status with a new non-ADC diagnosis, 43 (18%) were offered HIV testing, of whom 4 declined (acceptance rate: 39 of 43; 91%). Except for 21 patients tested prior to oncology consultation, 175 patients (of 239; 73%) were not offered testing. Testing rate declined among patients who were >70 years old (12% versus 30%; p = .04); no non-European patients were tested. Physicians gave reasons for not testing in 16% of cases, the main reason being patient follow-up elsewhere (10 patients; 5.7%). HIV testing during the IBITOP study increased the HIV testing rate to 18%. Although the IBITOP study increased HIV testing rates, most patients were not tested. Testing was low or nonexistent among individuals at risk of late HIV presentation (older patients and migrants). Barriers to testing appear to be physician-led, because patient acceptance of testing offered was very high (91%). In November 2013, the Swiss HIV testing recommendations were updated to propose testing in cancer patients. Phase II of the IBITOP study is examining the effect of these recommendations on HIV testing rates and focusing on physician-led testing barriers. Patients of unknown HIV status newly diagnosed with solid-organ non-AIDS-defining cancers were offered free HIV testing. Physician and patient barriers to HIV testing were examined. Most patients (82%) were not offered testing, and testing of individuals at risk of late HIV presentation (older patients and migrants) was low or nonexistent. Conversely, patient acceptance of testing offered was very high (91%), suggesting that testing barriers in this setting are physician-led. Since this study, the Swiss HIV testing recommendations now advise testing cancer patients before chemotherapy. Phase II of the Investigating Barriers in HIV-Testing Oncology Patients study is examining the effect of these recommendations on testing rates and physician barriers. ©AlphaMed Press.

Survival and surgical outcomes of cardiac cancer of the remnant stomach in comparison with primary cardiac cancer

PubMed Central

2014-01-01

Background Although cardiac cancer of the remnant stomach and primary cardiac cancer both occur in the same position, their clinical characteristics and outcomes have not been compared previously. The objective of this study was designed to evaluate the prognosis of cardiac cancer of the remnant stomach in comparison with primary cardiac cancer. Methods In this retrospective comparative study, clinical data and prognosis were compared in 48 patients with cardiac cancer of the remnant stomach and 96 patients with primary cardiac cancer who underwent radical resection from January 1995 to June 2007. Clinicopathologic characteristics, survival times, mortality, and complications were analyzed. Results The 5-year survival rate was significantly higher in patients with primary cardiac cancer than in those with cardiac cancer of the remnant stomach (28.4% vs. 16.7%, P = 0.035). Serosal invasion, lymph node metastasis and tumor location were independent prognostic factors for survival. Subgroup analysis, however, showed similar survival rates in patients with primary cardiac cancer and cardiac cancer of the remnant stomach without serosal invasion (25.0% vs. 43.8%, P = 0.214) and without lymph node metastasis (25.0% vs. 38.8%, P = 0.255), as well as similar complication rates (20.8% vs. 11.5%, P = 0.138). Conclusion Although the survival rates after radical resection in patients with cardiac cancer of the remnant stomach were poorer than in those with primary cardiac cancer, they were similar in survival rates when patients without serosal invasion or lymph node metastasis. Therefore, early detection is an important way to improve overall survival in cardiac cancer of the remnant stomach. PMID:24468299

Malignant Melanoma Presenting as a Mediastinal Malignant Melanoma Presenting as a Mediastinal Unknown Primary Origin?

PubMed

Pujani, Mukta; Hassan, Mohd Jaseem; Jetley, Sujata; Raina, Prabhat Kumar; Kumar, Mukesh

2017-01-01

The most common site of primary malignant melanoma is the skin, however, virtually any organ system may be involved. Metastatic melanoma of unknown primary origin accounts for approximately 2-6% of all melanoma cases. The mediastinum as the site for malignant melanoma is extremely rare, both as a primary or metastatic lesion. Primary malignant melanoma of mediastinum is very rare with only a handful of reports in the literature. We hereby report a rare case of malignant melanoma of mediastinum in a 31 year old male who was initially misdiagnosed on fine needle aspiration cytology as adenocarcinoma for which he received chemotherapy with clinical deterioration. Even on extensive meticulous search, no primary was discovered.

Prediagnostic plasma vitamin B6 (pyridoxal 50-phosphate) and survival in patients with colorectal cancer

USDA-ARS?s Scientific Manuscript database

Higher plasma pyridoxal 5'-phosphate (PLP) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma PLP on survival of patients with colorectal cancer is unknown. We prospectively examined whether prediagnostic plasma PLP levels are associated with mortality...

77 FR 55091 - National Childhood Cancer Awareness Month, 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... Proclamation Every year, thousands of children across America are diagnosed with cancer--an often life-threatening illness that remains the leading cause of death by disease for children under the age of 15. The causes of pediatric cancer are still largely unknown, and though new discoveries are resulting in new...

Trimethoxy-resveratrol and piceatannol administered orally suppress and inhibit tumor formation and growth in prostate cancer xenografts

USDA-ARS?s Scientific Manuscript database

Resveratrol (Res) is recognized as a promising cancer chemoprevention dietary polyphenol with antioxidative, anti-inflammatory and anticancer properties. However, the role of its analogues in prostate cancer (PCa) chemoprevention is still unknown. METHODS. We synthesized natural and synthetic anal...

Using radioactive drugs could lead to better imaging of prostate cancer | Center for Cancer Research

Cancer.gov

Medical imaging (x-ray, ultrasound, MRI, CT, PET scan) is a noninvasive way to view the internal structures of the body. However, these tools are not ideal for detecting cancer that has spread, or metastasized, because the precise location of these cancer cells is unknown. Researchers are now testing an experimental radiotracer called 18F-DCFPyL to help find sites of cancer in

A Novel Yeast Genomics Method for Identifying New Breast Cancer Susceptibility Genes

DTIC Science & Technology

2007-05-01

find new candidate genes for breast cancer susceptibility in women and identifying these human genes can further improve monitoring and treatment...breast cancer susceptibility genes in humans that are currently unknown and not deducible from current methodologies. It is a fundamental...template to faithfully repair the broken strand. In human cancer it is loss of HR, rather than NHEJ, that is more important in increasing cancer

Transitioning to routine breast cancer risk assessment and management in primary care: what can we learn from cardiovascular disease?

PubMed

Phillips, Kelly-Anne; Steel, Emma J; Collins, Ian; Emery, Jon; Pirotta, Marie; Mann, G Bruce; Butow, Phyllis; Hopper, John L; Trainer, Alison; Moreton, Jane; Antoniou, Antonis C; Cuzick, Jack; Keogh, Louise

2016-01-01

To capitalise on advances in breast cancer prevention, all women would need to have their breast cancer risk formally assessed. With ~85% of Australians attending primary care clinics at least once a year, primary care is an opportune location for formal breast cancer risk assessment and management. This study assessed the current practice and needs of primary care clinicians regarding assessment and management of breast cancer risk. Two facilitated focus group discussions were held with 17 primary care clinicians (12 GPs and 5 practice nurses (PNs)) as part of a larger needs assessment. Primary care clinicians viewed assessment and management of cardiovascular risk as an intrinsic, expected part of their role, often triggered by practice software prompts and facilitated by use of an online tool. Conversely, assessment of breast cancer risk was not routine and was generally patient- (not clinician-) initiated, and risk management (apart from routine screening) was considered outside the primary care domain. Clinicians suggested that routine assessment and management of breast cancer risk might be achieved if it were widely endorsed as within the remit of primary care and supported by an online risk-assessment and decision aid tool that was integrated into primary care software. This study identified several key issues that would need to be addressed to facilitate the transition to routine assessment and management of breast cancer risk in primary care, based largely on the model used for cardiovascular disease.

Inherited Disorders as a Risk Factor and Predictor of Neurodevelopmental Outcome in Pediatric Cancer

ERIC Educational Resources Information Center

Ullrich, Nicole J.

2008-01-01

Each year in the United States, an average of one to two children per 10,000 develop cancer. The etiology of most childhood cancer remains largely unknown but is likely attributable to random or induced genetic aberrations in somatic tissue. However, a subset of children develops cancer in the setting of an underlying inheritable condition…

Genome-scale analysis identifies GJB2 and ERO1LB as prognosis markers in patients with pancreatic cancer.

PubMed

Zhu, Tao; Gao, Yuan-Feng; Chen, Yi-Xin; Wang, Zhi-Bin; Yin, Ji-Ye; Mao, Xiao-Yuan; Li, Xi; Zhang, Wei; Zhou, Hong-Hao; Liu, Zhao-Qian

2017-03-28

Pancreatic cancer is a complex and heterogeneous disease with the etiology largely unknown. The deadly nature of pancreatic cancer, with an extremely low 5-year survival rate, renders urgent a better understanding of the molecular events underlying it. The aim of this study is to investigate the gene expression module of pancreatic adenocarcinoma and to identify differentially expressed genes (DEGs) with prognostic potentials. Transcriptome microarray data of five GEO datasets (GSE15471, GSE16515, GSE18670, GSE32676, GSE71989), including 117 primary tumor samples and 73 normal pancreatic tissue samples, were utilized to identify DEGs. The five sets of DEGs had an overlapping subset consisting of 98 genes (90 up-regulated and 8 down-regulated), which were probably common to pancreatic cancer. Gene ontology (GO) analysis of the 98 DEGs showed that cell cycle and cell adhesion were the major enriched processes, and extracellular matrix (ECM)-receptor interaction and p53 signaling pathway were the most enriched pathways according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Elevated expression of gap junction protein beta 2 (GJB2) and reduced endoplasmic reticulum oxidoreductase 1-like beta (ERO1LB) expression were validated in an independent cohort. Kaplan-Meier survival analysis revealed that GJB2 and ERO1LB levels were significantly associated with the overall survival of pancreatic cancer patients. GJB2 and ERO1LB are implicated in pancreatic cancer progression and can be used to predict patient survival. Therapeutic strategies targeting GJB2 and facilitating ERO1LB expression may deserve evaluation to improve prognosis of pancreatic cancer patients.

Fast track multi-discipline treatment (FTMDT trial) versus conventional treatment in colorectal cancer--the design of a prospective randomized controlled study

PubMed Central

2011-01-01

Background Laparoscopy-assisted surgery, fast-track perioperative treatment are both increasingly used in colorectal cancer treatment, for their short-time benefits of enhanced recovery and short hospital stays. However, the benefits of the integration of the Laparoscopy-assisted surgery, fast-track perioperative treatment, and even with the Xelox chemotherapy, are still unknown. In this study, the three treatments integration is defined as "Fast Track Multi-Discipline Treatment Model" for colorectal cancer and this model extends the benefits to the whole treatment process of colorectal cancer. The main purpose of the study is to explore the feasibility of "Fast Track Multi-Discipline Treatment" model in treatment of colorectal cancer. Methods The trial is a prospective randomized controlled study with 2 × 2 balanced factorial design. Patients eligible for the study will be randomized to 4 groups: (I) Laparoscopic surgery with fast track perioperative treatment and Xelox chemotherapy; (II) Open surgery with fast track perioperative treatment and Xelox chemotherapy; (III) Laparoscopic surgery with conventional perioperative treatment and mFolfox6 chemotherapy; (IV) Open surgery with conventional perioperative treatment and mFolfox6 chemotherapy. The primary endpoint of this study is the hospital stays. The secondary endpoints are the quality of life, chemotherapy related adverse events, surgical complications and hospitalization costs. Totally, 340 patients will be enrolled with 85 patients in each group. Conclusions The study initiates a new treatment model "Fast Track Multi-Discipline Treatment" for colorectal cancer, and will provide feasibility evidence on the new model "Fast Track Multi-Discipline Treatment" for patients with colorectal cancer. Trial registration ClinicalTrials.gov: NCT01080547 PMID:22111914

Impact of physical activity in group versus individual physical activity on fatigue in patients with breast cancer: A pilot study.

PubMed

Desbiens, Christine; Filion, Myriam; Brien, Marie-Chantale; Hogue, Jean-Charles; Laflamme, Christian; Lemieux, Julie

2017-10-01

Physical activity improves the quality of life of cancer survivors, but whether there is a difference between individual vs. group physical activity is unknown. To compare fatigue at 12 weeks in breast cancer survivors after participation in a program of group vs. individual video-assisted physical activity. This was a randomized phase II pilot study carried out in breast cancer survivors at a tertiary breast cancer center. Eligible patients were randomized to individual or group 12-week physical activity program. The primary outcome was fatigue (FACT-F). Aerobic capacity (6-min walk test), muscular strength, and quality-of-life (FACT-G and FACT-B) were assessed. Because of poor accrual, 200 consecutive breast cancer patients were surveyed about their physical activity habits to assess reasons for low recruitment. For all participants (n = 26; n = 12 for group vs. n = 14 for individual), there were some improvement in FACT-F, FACT-G, FACT-B, physical activity level, aerobic capacity, and shoulder strength. Among the 200 patients surveyed, 58% were interested to increase their physical activity level, 15% declared that they were already exercising enough, 9% declared being unable to, 3% declared having no time, and 2% declared having no interest, and other reasons (13%). Among the 200 patients surveyed, 25% preferred in group, 57% preferred alone, and 18% had no preference. Low recruitment precluded conclusions about the efficacy of physical activity practiced in group vs. individually, but both groups derived a benefit. Low willingness to change exercising habits could be the biggest barrier to physical activity in breast cancer survivors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perceptions of Active Surveillance and Treatment Recommendations for Low-risk Prostate Cancer: Results from a National Survey of Radiation Oncologists and Urologists.

PubMed

Kim, Simon P; Gross, Cary P; Nguyen, Paul L; Smaldone, Marc C; Shah, Nilay D; Karnes, R Jeffrey; Thompson, R Houston; Han, Leona C; Yu, James B; Trinh, Quoc D; Ziegenfuss, Jeanette Y; Sun, Maxine; Tilburt, Jon C

2014-07-01

With the growing concerns about overtreatment in prostate cancer, the extent to which radiation oncologists and urologists perceive active surveillance (AS) as effective and recommend it to patients are unknown. To assess opinions of radiation oncologists and urologists about their perceptions of AS and treatment recommendations for low-risk prostate cancer. National survey of specialists. Radiation oncologists and urologists practicing in the United States. A total of 1366 respondents were asked whether AS was effective and whether it was underused nationally, whether their patients were interested in AS, and treatment recommendations for low-risk prostate cancer. Pearson's χ test and multivariate logistic regression were used to test for differences in physician perceptions on AS and treatment recommendations. Overall, 717 (52.5%) of physicians completed the survey with minimal differences between specialties (P=0.92). Although most physicians reported that AS is effective (71.9%) and underused in the United States (80.0%), 71.0% stated that their patients were not interested in AS. For low-risk prostate cancer, more physicians recommended radical prostatectomy (44.9%) or brachytherapy (35.4%); fewer endorsed AS (22.1%). On multivariable analysis, urologists were more likely to recommend surgery [odds ratio (OR): 4.19; P<0.001] and AS (OR: 2.55; P<0.001), but less likely to recommend brachytherapy (OR: 0.13; P<0.001) and external beam radiation therapy (OR: 0.11; P<0.001) compared with radiation oncologists. Most prostate cancer specialists in the United States believe AS effective and underused for low-risk prostate cancer, yet continue to recommend the primary treatments their specialties deliver.

DHA-mediated regulation of lung cancer cell migration is not directly associated with Gelsolin or Vimentin expression.

PubMed

Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K

2016-06-15

Deaths associated with cancer metastasis have steadily increased making the need for newer, anti-metastatic therapeutics imparative. Gelsolin and vimentin, actin binding proteins expressed in metastatic tumors, participate in actin remodelling and regulate cell migration. Docosahexaenoic acid (DHA) limits cancer cell proliferation and adhesion but the mechanisms involved in reducing metastatic phenotypes are unknown. We aimed to investigate the effects of DHA on gelsolin and vimentin expression, and ultimately cell migration and proliferation, in this context. Non-invasive lung epithelial cells (MLE12) and invasive lung cancer cells (A549) were treated with DHA (30μmol/ml) or/and 8 bromo-cyclic adenosine monophosphate (8 Br-cAMP) (300μmol/ml) for 6 or 24h either before (pre-treatment) or after (post-treatment) plating in transwells. Migration was assessed by the number of cells that progressed through the transwell. Gelsolin and vimentin expression were measured by Western blot and confocal microscopy in cells, and by immunohistochemistry in human lung cancer biopsy samples. A significant decrease in cell migration was detected for A549 cells treated with DHA verses control but this same decrease was not seen in MLE12 cells. DHA and 8 Br-cAMP altered gelsolin and vimentin expression but no clear pattern of change was observed. Immunofluorescence staining indicated slightly higher vimentin expression in human lung tissue that was malignant compared to control. Collectively, our data indicate that DHA inhibits cancer cell migration and further suggests that vimentin and gelsolin may play secondary roles in cancer cell migration and proliferation, but are not the primary regulators. Copyright © 2016 Elsevier Inc. All rights reserved.

DHA-Mediated Regulation of Lung Cancer Cell Migration Is Not Directly Associated with Gelsolin or Vimentin Expression

PubMed Central

Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K.

2016-01-01

AIMS Deaths associated with cancer metastasis have steadily increased making the need for newer, anti-metastatic therapeutics imparative. Gelsolin and vimentin, actin binding proteins expressed in metastatic tumors, participate in actin remodelling and regulate cell migration. Docosahexaenoic acid (DHA) limits cancer cell proliferation and adhesion but the mechanisms involved in reducing metastatic phenotypes are unknown. We aimed to investigate the effects of DHA on gelsolin and vimentin expression, and ultimately cell migration and proliferation, in this context. MAIN METHODS Non-invasive lung epithelial cells (MLE12) and invasive lung cancer cells (A549) were treated with DHA (30 μmol/ml) or/and 8 bromo-cyclic adenosine monophosphate (8 Br-cAMP) (300 μmol/ml) for 6 or 24 h either before (pre-treatment) or after (post-treatment) plating in transwells. Migration was assessed by the number of cells that progressed through the transwell. Gelsolin and vimentin expression were measured by western blot and confocal microscopy in cells, and by immunohistochemistry in human lung cancer biospy samples. KEY FINDINGS A significant decrease in cell migration was detected for A549 cells treated with DHA verses control but this same decrease was not seen in MLE12 cells. DHA and 8 Br-cAMP altered gelsolin and vimentin expression but no clear pattern of change was observed. Immunoflorescence staining indicated slightly higher vimentin expression in human lung tissue that was malignant compared to control. SIGNIFICANCE Collectively, our data indicate that DHA inhibits cancer cell migration and further suggests that vimentin and gelsolin may play secondary roles in cancer cell migration and proliferation, but are not the primary regulators. PMID:27157519

Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy for Patients with Resectable Synchronous Colon Cancer and Liver-confined Metastases: A Nationwide Database Study.

PubMed

Liang, Yi-Hsin; Shao, Yu-Yun; Chen, Ho-Min; Cheng, Ann-Lii; Lai, Mei-Shu; Yeh, Kun-Huei

2017-12-01

Although irinotecan and oxaliplatin are both standard treatments for advanced colon cancer, it remains unknown whether either is effective for patients with resectable synchronous colon cancer and liver-confined metastasis (SCCLM) after curative surgery. A population-based cohort of patients diagnosed with de novo SCCLM between 2004 and 2009 was established by searching the database of the Taiwan Cancer Registry and the National Health Insurance Research Database of Taiwan. Patients who underwent curative surgery as their first therapy followed by chemotherapy doublets were classified into the irinotecan group or oxaliplatin group accordingly. Patients who received radiotherapy or did not receive chemotherapy doublets were excluded. We included 6,533 patients with de novo stage IV colon cancer. Three hundred and nine of them received chemotherapy doublets after surgery; 77 patients received irinotecan and 232 patients received oxaliplatin as adjuvant chemotherapy. The patients in both groups exhibited similar overall survival (median: not reached vs. 40.8 months, p=0.151) and time to the next line of treatment (median: 16.5 vs. 14.3 months, p=0.349) in both univariate and multivariate analyses. Additionally, patients with resectable SCCLM had significantly shorter median overall survival than patients with stage III colon cancer who underwent curative surgery and subsequent adjuvant chemotherapy, but longer median overall survival than patients with de novo stage IV colon cancer who underwent surgery only at the primary site followed by standard systemic chemotherapy (p<0.001). Irinotecan and oxaliplatin exhibited similar efficacy in patients who underwent curative surgery for resectable SCCLM. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

A multicenter study of primary brain tumor incidence in Australia (2000–2008)

PubMed Central

Dobes, Martin; Shadbolt, Bruce; Khurana, Vini G.; Jain, Sanjiv; Smith, Sarah F.; Smee, Robert; Dexter, Mark; Cook, Raymond

2011-01-01

There are conflicting reports from Europe and North America regarding trends in the incidence of primary brain tumor, whereas the incidence of primary brain tumors in Australia is currently unknown. We aimed to determine the incidence in Australia with age-, sex-, and benign-versus-malignant histology-specific analyses. A multicenter study was performed in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), which has a combined population of >7 million with >97% rate of population retention for medical care. We retrospectively mined pathology databases servicing neurosurgical centers in NSW and ACT for histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008. Data were weighted for patient outflow and data completeness. Incidence rates were age standardized and trends analyzed using joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed. The overall US-standardized incidence of primary brain tumors was 11.3 cases 100 000 person-years (±0.13; 95% confidence interval, 9.8–12.3) during the study period with no significant linear increase. A significant increase in primary malignant brain tumors from 2000 to 2008 was observed; this appears to be largely due to an increase in malignant tumor incidence in the ≥65-year age group. This collection represents the most contemporary data on primary brain tumor incidence in Australia. Whether the observed increase in malignant primary brain tumors, particularly in persons aged ≥65 years, is due to improved detection, diagnosis, and care delivery or a true change in incidence remains undetermined. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence that can be independent of multiple interstate cancer registries. PMID:21727214

Risk of second primary malignancies among cancer survivors in the United States, 1992 through 2008.

PubMed

Donin, Nicholas; Filson, Christopher; Drakaki, Alexandra; Tan, Hung-Jui; Castillo, Alex; Kwan, Lorna; Litwin, Mark; Chamie, Karim

2016-10-01

In the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers. The authors identified patients aged ≥18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined. A cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and 2.88, respectively, for men and women) and bladder cancer (hazard ratios of 1.88 and 1.66, respectively, for men and women) predicted the highest risk of developing a second cancer. For patients with 2 incident cancers, 13% died of their initial cancer, but greater than one-half (55%) died of their second primary malignancy. Lung cancer was the cause of death in 12% of patients with 2 incident cancers. Nearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer. Greater than one-half of patients with 2 incident cancers died of their secondary malignancy. The findings from the current study may inform care strategies among cancer survivors. Cancer 2016;122:3075-3086. © 2016 American Cancer Society. © 2016 American Cancer Society.

EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-01-15

Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Uterine Sarcoma; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Learning the landscape: implementation challenges of primary care innovators around cancer survivorship care.

PubMed

O'Malley, Denalee; Hudson, Shawna V; Nekhlyudov, Larissa; Howard, Jenna; Rubinstein, Ellen; Lee, Heather S; Overholser, Linda S; Shaw, Amy; Givens, Sarah; Burton, Jay S; Grunfeld, Eva; Parry, Carly; Crabtree, Benjamin F

2017-02-01

This study describes the experiences of early implementers of primary care-focused cancer survivorship delivery models. Snowball sampling was used to identify innovators. Twelve participants (five cancer survivorship primary care innovators and seven content experts) attended a working conference focused on cancer survivorship population strategies and primary care transformation. Data included meeting discussion transcripts/field notes, transcribed in-depth innovator interviews, and innovators' summaries of care models. We used a multistep immersion/crystallization analytic approach, guided by a primary care organizational change model. Innovative practice models included: (1) a consultative model in a primary care setting; (2) a primary care physician (PCP)-led, blended consultative/panel-based model in an oncology setting; (3) an oncology nurse navigator in a primary care practice; and (4) two subspecialty models where PCPs in a general medical practice dedicated part of their patient panel to cancer survivors. Implementation challenges included (1) lack of key stakeholder buy-in; (2) practice resources allocated to competing (non-survivorship) change efforts; and (3) competition with higher priority initiatives incentivized by payers. Cancer survivorship delivery models are potentially feasible in primary care; however, significant barriers to widespread implementation exist. Implementation efforts would benefit from increasing the awareness and potential value-add of primary care-focused strategies to address survivors' needs. Current models of primary care-based cancer survivorship care may not be sustainable. Innovative strategies to provide quality care to this growing population of survivors need to be developed and integrated into primary care settings.

Effects of the length of central cancer registry operations on identification of subsequent cancers and on survival estimates.

PubMed

Qiao, Baozhen; Schymura, Maria J; Kahn, Amy R

2016-10-01

Population-based cancer survival analyses have traditionally been based on the first primary cancer. Recent studies have brought this practice into question, arguing that varying registry reference dates affect the ability to identify earlier cancers, resulting in selection bias. We used a theoretical approach to evaluate the extent to which the length of registry operations affects the classification of first versus subsequent cancers and consequently survival estimates. Sequence number central was used to classify tumors from the New York State Cancer Registry, diagnosed 2001-2010, as either first primaries (value=0 or 1) or subsequent primaries (≥2). A set of three sequence numbers, each based on an assumed reference year (1976, 1986 or 1996), was assigned to each tumor. Percent of subsequent cancers was evaluated by reference year, cancer site and age. 5-year relative survival estimates were compared under four different selection scenarios. The percent of cancer cases classified as subsequent primaries was 15.3%, 14.3% and 11.2% for reference years 1976, 1986 and 1996, respectively; and varied by cancer site and age. When only the first primary was included, shorter registry operation time was associated with slightly lower 5-year survival estimates. When all primary cancers were included, survival estimates decreased, with the largest decreases seen for the earliest reference year. Registry operation length affected the identification of subsequent cancers, but the overall effect of this misclassification on survival estimates was small. Survival estimates based on all primary cancers were slightly lower, but might be more comparable across registries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bridging the gap between primary care and the cancer system

PubMed Central

Sisler, Jeffrey; McCormack-Speak, Pat

2009-01-01

ABSTRACT PROBLEM BEING ADDRESSED Patient care is poorly coordinated between family physicians and the cancer system and the working relationships are not strong. OBJECTIVE OF PROGRAM To improve integration of patient care and communication between FPs and cancer specialists; enhance FPs’ knowledge of cancer and the cancer system; and promote the role of primary care within the cancer care system. PROGRAM DESCRIPTION The Uniting Primary Care and Oncology (UPCON) Network of CancerCare Manitoba has created partnerships with 12 primary care clinics in Winnipeg, Man, by providing the following: access to the provincial electronic medical record for cancer; small group continuing professional development for a “lead physician” from each clinic to make him or her the local cancer resource; educational outreach to all clinic staff; and changes within CancerCare Manitoba to highlight the role of FPs. CONCLUSION Lead physicians are appreciated by their clinic colleagues, and these FPs are the main users of the cancer electronic medical record. A strong cancer continuing professional development program has been implemented and a voice for primary care has been created within the agency. The UPCON Network is now expanding throughout Manitoba. PMID:19282538

Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center.

PubMed

Suki, Dima; Khoury Abdulla, Rami; Ding, Minming; Khatua, Soumen; Sawaya, Raymond

2014-10-01

Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990-2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2-77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24-34 months) and 9 months (95% CI 6-11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3-1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6-11 months). The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

Descriptive characteristics of prostate cancer in patients with a history of primary male breast cancer - a SEER analysis.

PubMed

Abhyankar, Nikita; Hoskins, Kent F; Abern, Michael R; Calip, Gregory S

2017-09-25

Current evidence on risk of prostate cancer following a diagnosis of male breast cancer is limited and guidance for screening in this potentially higher-risk population remainsunclear. Our objective was to quantify prostate cancer risk in men diagnosed with breast cancer. We identified men diagnosed with first primary breast cancer between 1988 and 2012 using the Surveillance, Epidemiology and End Results Program registry databases. Men were followed for occurrence of a second primary prostate cancer and secondary outcomes of cancer-specific and overall survival. Stratified analyses were performed by age, breast cancer stage, race, and breast cancer hormone receptor status. Excess risk per 10,000 person-years and standardized incidence ratios (SIR) with 95% confidence intervals (95% CI) were calculated. We used multivaraible Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for characteristics associated with secondary prostate cancer and survival. From a cohort of 5753 men with breast cancer with median follow up of 4.3 years, we identified 250 cases of second primary prostate cancer. Overall, the incidence of second primary prostate cancer was modestly greater than expected (SIR = 1.12, 95% CI 0.93-1.33), although not statistically significant. Stratified analyses demonstrated associations for men ages 65-74 at the time of breast cancer diagnosis (SIR = 1.34, 95%CI 1.01-1.73), hormone receptor-positive breast cancer (SIR = 1.23, 95%CI 1.11-1.39) or AJCC stage I breast cancer (SIR = 1.36, 95%CI 1.04-1.75) and second primary prostate cancer diagnosis. The incidence of prostate cancer in men with history of breast cancer is similar to the general population. Men with favorable characteristics of their breast cancer were more likely to develop prostate cancer, possibly due to a lower competing risk of breast cancer mortality.

42 CFR 81.25 - Guidelines for claims including two or more primary cancers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... cancers. 81.25 Section 81.25 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Estimate Probability of Causation § 81.25 Guidelines for claims including two or more primary cancers. For claims including two or more primary cancers, DOL will use NIOSH-IREP to calculate the estimated...

42 CFR 81.25 - Guidelines for claims including two or more primary cancers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... cancers. 81.25 Section 81.25 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Estimate Probability of Causation § 81.25 Guidelines for claims including two or more primary cancers. For claims including two or more primary cancers, DOL will use NIOSH-IREP to calculate the estimated...

42 CFR 81.25 - Guidelines for claims including two or more primary cancers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... cancers. 81.25 Section 81.25 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Estimate Probability of Causation § 81.25 Guidelines for claims including two or more primary cancers. For claims including two or more primary cancers, DOL will use NIOSH-IREP to calculate the estimated...

42 CFR 81.25 - Guidelines for claims including two or more primary cancers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... cancers. 81.25 Section 81.25 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Estimate Probability of Causation § 81.25 Guidelines for claims including two or more primary cancers. For claims including two or more primary cancers, DOL will use NIOSH-IREP to calculate the estimated...

42 CFR 81.25 - Guidelines for claims including two or more primary cancers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... cancers. 81.25 Section 81.25 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Estimate Probability of Causation § 81.25 Guidelines for claims including two or more primary cancers. For claims including two or more primary cancers, DOL will use NIOSH-IREP to calculate the estimated...

Temporal relationship between cancer and myositis identifies two distinctive subgroups of cancers: impact on cancer risk and survival in patients with myositis.

PubMed

Kang, Eun Ha; Lee, Sang Jin; Ascherman, Dana P; Lee, Yun Jong; Lee, Eun Young; Lee, Eun Bong; Song, Yeong Wook

2016-09-01

The aim was to compare standardized incidence ratios (SIRs) of cancers temporally related and unrelated to active myositis in patients with myositis. Fifty-two cancer cases were identified in 281 myositis patients. SIRs of cancers having temporal overlap with the active phase of myositis [cancers concurrent with active myositis (CAM), n = 30] and cancers not having such temporal overlap [cancers non-concurrent with active myositis (CNM), n = 22] were compared in 281 patients. Patients with CAM were older at diagnosis of myositis, had a greater tendency to be male, more frequent dysphagia and less frequent interstitial lung disease than patients with CNM. CAM SIR (95% CI) was 1.78 (1.19, 2.56) and CNM SIR 1.23 (0.75, 1.90). The peak SIR was observed in the seventh decade of life for CAM and in the third decade for CNM. When stratified by myositis-cancer intervals, CAM SIR was 9.94 (6.43, 14.67) within 1 year of myositis diagnosis, whereas no temporal relationship was found for CNM. Elevated SIRs were observed for oesophageal cancer [57.77 (11.91, 168.82)], non-Hodgkin's lymphoma [41.43 (13.45, 96.69)], adenocarcinoma of unknown primary origin [67.6 (18.42, 173.07]), lung cancer [7.27 (1.98, 18.61)] and ovarian cancer [19.15 (2.32, 69.17)] within 3 years of CAM diagnosis. The cancer stage at the time of diagnosis was more advanced in CAM than CNM (P < 0.001), with a correspondingly increased hazard ratio of mortality [4.3 (1.5, 12.7)] in patients with CAM vs CNM. A significantly elevated SIR was found for CAM, whereas there was a comparable SIR for CNM relative to the general population. Multiple types of cancers showed elevated SIRs among CAM, but none among CNM. Given that cancer stages in CAM were far advanced at diagnosis, mortality risk was greater in patients with CAM. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive familial breast cancer cases.

PubMed

Adank, Muriel A; Verhoef, Senno; Oldenburg, Rogier A; Schmidt, Marjanka K; Hooning, Maartje J; Martens, John W M; Broeks, Annegien; Rookus, Matti; Waisfisz, Quinten; Witte, Birgit I; Jonker, Marianne A; Meijers-Heijboer, Hanne

2013-05-01

The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting. Cancer incidences were compared between first degree relatives of 107 familial breast cancer patients positive for the CHEK2∗1100delC mutation (CHEK2 positive families) and first degree relatives of 314 familial breast cancer patients without the CHEK2∗1100delC mutation (CHEK2 negative families). All families were derived from the same pool of familial non-BRCA1/2 breast cancer families (n=2554). Medical information of 2188 first degree relatives of these families was analysed for cancer risk. CHEK2∗1100delC status of relatives was unknown. Increased breast cancer risk (hazard ratio (HR) 2.0 (95% confidence interval (CI): 1.4-2.7), p<0.001) was observed in sisters of CHEK2∗1100delC positive index cases compared to sisters of CHEK2∗1100delC negative index cases. HR was 1.6 (95% CI: 1.0-2.4) for mothers of CHEK2 positive versus negative index cases (p=0.041). For second primary breast cancers HR was increased in CHEK2∗1100delC positive index cases (HR 2.1, 95% CI: 1.3-3.3, p=0.003) and their sisters (HR 2.6, 95% CI: 1.1-6.1, p=0.025). There is an excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive non-BRCA1/2 familial breast cancer patients compared to non-CHEK2∗1100delC familial breast cancer relatives. Genotyping for the CHEK2∗1100delC mutation in a familial breast cancer setting contributes to optimal clinical surveillance in countries in which this mutation is prevalent. Carriers and female relatives are eligible for stringent breast surveillance programs. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Value of Continuity between Primary Care and Surgical Care in Colon Cancer.

PubMed

Hussain, Tanvir; Chang, Hsien-Yen; Luu, Ngoc-Phuong; Pollack, Craig Evan

2016-01-01

Improving continuity between primary care and cancer care is critical for improving cancer outcomes and curbing cancer costs. A dimension of continuity, we investigated how regularly patients receive their primary care and surgical care for colon cancer from the same hospital and whether this affects mortality and costs. Using Surveillance, Epidemiology, and End Results Program Registry (SEER)-Medicare data, we performed a retrospective cohort study of stage I-III colon cancer patients diagnosed between 2000 and 2009. There were 23,305 stage I-III colon cancer patients who received primary care in the year prior to diagnosis and underwent operative care for colon cancer. Patients were assigned to the hospital where they had their surgery and to their primary care provider's main hospital, and then classified according to whether these two hospitals were same or different. Outcomes examined were hazards for all-cause mortality, subhazard for colon cancer specific mortality, and generalized linear estimate for costs at 12 months, from propensity score matched models. Fifty-two percent of stage I-III colon patients received primary care and surgical care from the same hospital. Primary care and surgical care from the same hospital was not associated with reduced all-cause or colon cancer specific mortality, but was associated with lower inpatient, outpatient, and total costs of care. Total cost difference was $8,836 (95% CI $2,746-$14,577), a 20% reduction in total median cost of care at 12 months. Receiving primary care and surgical care at the same hospital, compared to different hospitals, was associated with lower costs but still similar survival among stage I-III colon cancer patients. Nonetheless, health care policy which encourages further integration between primary care and cancer care in order to improve outcomes and decrease costs will need to address the significant proportion of patients receiving health care across more than one hospital.

Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods.

PubMed

Dieli-Conwright, Christina M; Mortimer, Joanne E; Schroeder, E Todd; Courneya, Kerry; Demark-Wahnefried, Wendy; Buchanan, Thomas A; Tripathy, Debu; Bernstein, Leslie

2014-04-03

Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments. This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation. This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and aerobic exercise training and inform intervention programs that will optimally improve physiological and psychosocial health during cancer survivorship, and that are ultimately aimed at improving prognosis. NCT01140282; June 10, 2010.

Hypermethylation of the TSLC1 Gene Promoter in Primary Gastric Cancers and Gastric Cancer Cell Lines

PubMed Central

Honda, Teiichiro; Waki, Takayoshi; Jin, Zhe; Sato, Kiyoshi; Motoyama, Teiichi; Kawata, Sumio; Kimura, Wataru; Nishizuka, Satoshi; Murakami, Yoshinori

2002-01-01

The TSLC1 (tumor suppressor in lung cancer–1) gene is a novel tumor suppressor gene on chromosomal region 11q23.2, and is frequently inactivated by concordant promoter hypermethylation and loss of heterozygosity (LOH) in non‐small cell lung cancer (NSCLC). Because LOH on 11q has also been observed frequently in other human neoplasms including gastric cancer, we investigated the promoter methylation status of TSLC1 in 10 gastric cancer cell lines and 97 primary gastric cancers, as well as the corresponding non‐cancerous gastric tissues, by bisulfite‐SSCP analysis followed by direct sequencing. Allelic status of the TSLC1 gene was also investigated in these cell lines and primary gastric cancers. The TSLC1 promoter was methylated in two gastric cancer cell lines, KATO‐III and ECC10, and in 15 out of 97 (16%) primary gastric cancers. It was not methylated in non‐cancerous gastric tissues, suggesting that this hypermethylation is a cancer‐specific alteration. KATO‐III and ECC10 cells retained two alleles of TSLC1, both of which showed hypermethylation, associated with complete loss of gene expression. Most of the primary gastric cancers with promoter methylation also retained heterozygosity at the TSLC1 locus on 11q23.2. These data indicate that bi‐allelic hypermethylation of the TSLC1 promoter and resulting gene silencing occur in a subset of primary gastric cancers. PMID:12716461

Environmental and occupational interventions for primary prevention of cancer: a cross-sectorial policy framework.

PubMed

Espina, Carolina; Porta, Miquel; Schüz, Joachim; Aguado, Ildefonso Hernández; Percival, Robert V; Dora, Carlos; Slevin, Terry; Guzman, Julietta Rodriguez; Meredith, Tim; Landrigan, Philip J; Neira, Maria

2013-04-01

Nearly 13 million new cancer cases and 7.6 million cancer deaths occur worldwide each year; 63% of cancer deaths occur in low- and middle-income countries. A substantial proportion of all cancers are attributable to carcinogenic exposures in the environment and the workplace. We aimed to develop an evidence-based global vision and strategy for the primary prevention of environmental and occupational cancer. We identified relevant studies through PubMed by using combinations of the search terms "environmental," "occupational," "exposure," "cancer," "primary prevention," and "interventions." To supplement the literature review, we convened an international conference titled "Environmental and Occupational Determinants of Cancer: Interventions for Primary Prevention" under the auspices of the World Health Organization, in Asturias, Spain, on 17-18 March 2011. Many cancers of environmental and occupational origin could be prevented. Prevention is most effectively achieved through primary prevention policies that reduce or eliminate involuntary exposures to proven and probable carcinogens. Such strategies can be implemented in a straightforward and cost-effective way based on current knowledge, and they have the added benefit of synergistically reducing risks for other noncommunicable diseases by reducing exposures to shared risk factors. Opportunities exist to revitalize comprehensive global cancer control policies by incorporating primary interventions against environmental and occupational carcinogens.

The relationship of TMPRSS2-ERG gene fusion between primary and metastatic prostate cancers.

PubMed

Guo, Charles C; Wang, Yan; Xiao, Li; Troncoso, Patricia; Czerniak, Bogdan A

2012-05-01

Recent studies have revealed the presence of TMPRSS2-ERG gene fusion in both primary and metastatic prostate cancers. However, the relationship between primary and corresponding metastatic prostate cancers with respect to the status of this gene fusion remains unclear. Using fluorescence in situ hybridization, we evaluated the rearrangement of the ERG gene in the radical prostatectomy specimens and corresponding lymph node metastases from 19 patients with prostate cancer. The mean age of the patients was 61 years, and the median Gleason score in the radical prostatectomy specimens was 7 (4 + 3). Prostate cancer was unifocal in 6 cases and multifocal in 13 cases, including 10 with 2 foci and 3 with 3 foci. In the primary prostate cancers, rearrangement of the ERG gene was observed in 13 cases and associated with deletion of the 5' ERG gene in 8 cases. In the metastases, the ERG rearrangement was present in 10 cases and associated with deletion of the 5' ERG gene in 6 cases. In unifocal prostate cancers, the status of the ERG rearrangement was concordant between the primary prostate cancer and metastasis in 5 of 6 cases. In multifocal prostate cancer, despite a significant interfocal discordance, the status of the ERG rearrangement was concordant between the index (largest) primary tumor focus and metastasis in all 13 cases. Our study demonstrates a close relationship of the TMPRSS2-ERG gene fusion status between primary and metastatic prostate cancer. The concordance of the ERG gene rearrangement status between the index primary tumor focus and metastasis suggests that metastasis most likely arises from the index tumor focus in multifocal prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Long-term Outcomes of One Stage Surgery Using Transanal Colorectal Tube for Acute Colorectal Obstruction of Stage II/III Distal Colon Cancer.

PubMed

Okuda, Yusuke; Yamada, Tomonori; Hirata, Yoshikazu; Shimura, Takaya; Yamaguchi, Ryuzo; Sakamoto, Eiji; Sobue, Satoshi; Nakazawa, Takahiro; Kataoka, Hiromi; Joh, Takashi

2018-06-06

Since oncological outcomes of transanal colorectal tube (TCT) placement, an endoscopic treatment for colorectal cancer (CRC) with acute colorectal obstruction (ACO), remain unknown, this study analyzed long-term outcomes of TCT placement for stage II/III CRC with ACO. Data were retrospectively reviewed from consecutive patients with distal stage II/III CRC who underwent surgery between January 2007 and December 2011 at two Japanese hospitals. One hospital conducted emergency surgery and the other performed TCT placement as the standard treatment for all CRCs with ACO. Propensity score (PS) matching was used to adjust baseline characteristics between two groups. Among 754 patients with distal stage II/III CRC, 680 did not have ACO (non-ACO group) and 74 had ACO (ACO group). The PS matching between both hospitals identified 234 pairs in the non-ACO group and 23 pairs in the ACO group. In the non-ACO group, the surgical quality was equivalent between the two institutions, with no significant differences in overall survival (OS) and disease-free survival (DFS). In the ACO group, the rate of primary resection/anastomosis was higher in the TCT group than in the surgery group (87.0% vs. 26.1%; p < 0.001). No significant differences were noted between the surgery and the TCT groups in OS (5-year OS, 61.9% vs. 51.5%; p=0.490) and DFS (5-year DFS, 45.9% vs. 38.3%; p=0.658). TCT placement can achieve similar long-term outcomes to emergency surgery, with a high rate of primary resection/anastomosis for distal stage II/III colon cancer with ACO.

Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) β: LncRNA-hit-mediated TGFβ-induced epithelial to mesenchymal transition in mammary epithelia.

PubMed

Richards, Edward J; Zhang, Gu; Li, Zhu-Peng; Permuth-Wey, Jennifer; Challa, Sridevi; Li, Yajuan; Kong, William; Dan, Su; Bui, Marilyn M; Coppola, Domenico; Mao, Wei-Min; Sellers, Thomas A; Cheng, Jin Q

2015-03-13

Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes. Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by tumor cells to depart from the primary tumor site, invade surrounding tissue, and establish distant metastases. Transforming growth factor β (TGFβ) signaling has been shown to be a major inducer of EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here we report a genome-wide lncRNA profile in mouse mammary epithelial NMuMG cells upon TGFβ induction of EMT. Among 10,802 lncRNAs profiled, over 600 were up-regulated and down-regulated during the EMT, respectively. Furthermore, we identify that lncRNA-HIT (HOXA transcript induced by TGFβ) mediates TGFβ function, i.e. depletion of lncRNA-HIT inhibits TGFβ-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is also significantly elevated in the highly metastatic 4T1 cells. Knockdown of lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth, and metastasis. E-cadherin was identified as a major target of lncRNA-HIT. Moreover, lncRNA-HIT is conserved in humans and elevated expression associates with more invasive human primary breast carcinoma. Collectively, these data suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in regulation of EMT and breast cancer invasion and metastasis, and could be potential therapeutic targets in breast cancers. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Down-regulation of TCF21 by hypermethylation induces cell proliferation, migration and invasion in colorectal cancer

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

Dai, Youyi; Duan, Huaxin; The First Affiliated Hospital of Hunan Normal University

Epigenetic alteration induced loss function of the transcription factor 21 (TCF21) has been associated with different types of human cancers. However, the epigenetic regulation and molecular functions of TCF21 in colorectal cancer (CRC) remain unknown. In this study, TCF21 expression levels and methylation status of its promoter region in CRC cell lines (n = 5) and CRC tissues (n = 151) as well as normal colorectal mucosa (n = 30) were assessed by RTq-PCR and methylation analysis (methylation specific PCR, MSP and bisulfite sequencing PCR, BSP), respectively. The cellular functions of TCF21 on CRC cell proliferation, apoptosis, invasion and migration were investigated in vitro. Our data revealedmore » that TCF21 was frequently silenced by promoter hypermethylation in both tested CRC cell lines and primary CRC, and correlation analysis between methylation status and clinicopathologic parameters found that TCF21 methylation was significantly correlated with lymph node invasion (P = 0.013), while no significant correlation was found in other parameters. In addition, demethylation treatment resulted in re-expression of TCF21 in CRC cell lines, and cellular function experiments revealed that restoration of TCF21 inhibited CRC cell proliferation, promoted apoptosis and suppressed cell invasion and migration, suggesting that TCF21 may function as a tumor suppressor gene, which is downregulated through promoter hypermethylation in CRC development. - Highlights: • TCF21 was frequently silenced by promoter DNA methylation in CRC cells. • TCF21 was frequently methylated in primary CRC and significantly correlated with metastasis. • Restoration of TCF21 promotes cell apoptosis of CRC cells. • Restoration of TCF21 inhibits cell invasion and migration of CRC cells.« less

Stereotactic body radiotherapy for second primary lung cancer and intra-parenchymal lung metastasis in patients previously treated with surgery: evaluation of indications and predictors of decreased respiratory function.

PubMed

Ishihara, Takeaki; Yamada, Kazunari; Harada, Aya; Yukiue, Haruhiro; Tanahashi, Masayuki; Niwa, Hiroshi; Matsui, Takashi; Yokomura, Koshi; Ejima, Yasuo; Sasaki, Ryohei

2018-05-03

The adaptation criteria for administration of stereotactic body radiotherapy (SBRT) to patients with lung cancer who previously underwent surgery and subsequently developed a second primary lung cancer (SPLC) or intra-parenchymal lung metastasis (IPLM) are controversial, unlike the criteria for repeat surgery. We aimed to evaluate the feasibility of SBRT for these patients. Factors associated with decreased respiratory function were also evaluated. Sixty-nine patients with 89 lesions who underwent SBRT between 2008 and 2017 were analyzed. Of these, 29 were diagnosed with SPLC while the remaining 40 had IPLM. The distribution of histological types was as follows: squamous cell carcinoma (n = 13 lesions); adenocarcinoma (n = 25); non-small cell carcinoma (n = 1); unknown histological type (n = 49). The prescribed doses to the planning target volume (PTV) were 50 Gy in five fractions for 85 lesions and 60 Gy in 10 fractions for four lesions at PTV mean. Over a median follow-up period of 55 months, the 4-year overall survival and local control rates were 50.3% and 87.6%, respectively. Six patients experienced grade 2 radiation pneumonitis and one experienced grade 3. Two patients experienced grade 5 pulmonary fibrosis. Decreased respiratory function was observed in 10 patients (15.1%). On multivariate analysis, the presence of pulmonary disease before SBRT was the only statistically significant factor associated with decreased respiratory function. SBRT is safe and feasible in patients with SPLC or IPLM previously treated surgically. Pre-existing pulmonary disease was a predictive factor for decreased respiratory function.

Patterns of failure in patients with early onset (synchronous) resectable liver metastases from rectal cancer.

PubMed

Butte, Jean M; Gonen, Mithat; Ding, Peirong; Goodman, Karyn A; Allen, Peter J; Nash, Garrett M; Guillem, Jose; Paty, Philip B; Saltz, Leonard B; Kemeny, Nancy E; Dematteo, Ronald P; Fong, Yuman; Jarnagin, William R; Weiser, Martin R; D'Angelica, Michael I

2012-11-01

The optimal combination of available therapies for patients with resectable synchronous liver metastases from rectal cancer (SLMRC) is unknown, and the pattern of recurrence after resection has been poorly investigated. In this study, the authors examined recurrence patterns and survival after resection of SLMRC. Consecutive patients with SLMRC (disease-free interval, ≤12 months) who underwent complete resection of the rectal primary and liver metastases between 1990 and 2008 were identified from a prospective database. Demographics, tumor-related variables, and treatment-related variables were correlated with recurrence patterns. Competing risk analysis was used to determine the risk of pelvic and extrapelvic recurrence. In total, 185 patients underwent complete resection of rectal primary and liver metastases. One hundred eighty patients (97%) received chemotherapy during their treatment course, and 91 patients (49%) received pelvic radiation therapy either before (N = 65; 71.4%), or after (N = 26; 28.6%) rectal resection. The 5-year disease-specific survival rate was 51% for the entire cohort with a median follow-up of 44 months for survivors. One hundred thirty patients (70%) developed a recurrence: Eighteen patients (10%) had recurrences in the pelvis in combination with other sites, and 7 of these (4%) had an isolated pelvic recurrence. Recurrence pattern did not correlate with survival. Competing risk analysis demonstrated that the likelihood of a pelvic recurrence was significantly lower than that of an extrapelvic recurrence (P < .001). Of the patients with SLMRC who developed recurrent disease, systemic sites were overwhelmingly more common than pelvic recurrences. The current results indicated that the selective exclusion of radiotherapy may be considered in patients who are diagnosed with simultaneous disease. Copyright © 2012 American Cancer Society.

Second cancers in patients with male breast cancer: a literature review.

PubMed

Grenader, Tal; Goldberg, Anthony; Shavit, Linda

2008-06-01

The risk of second malignancies among female breast cancer patients has been studied for decades. In contrast, very little is known about second primary tumors in men. Risk factors for breast cancer in men, including genetic, hormonal and environmental factors, provide parallels to the etiology of breast cancer in women. This review considers the literature related to the risk of developing a second cancer in patients with male breast cancer. A systematic review of the literature between 1966 and 2007 was conducted and acceptable articles used for analysis. All retrieved articles were screened to identify any papers that had been missed. Studies were included if they discussed the risk of subsequent malignancy in patients with male breast cancer. Patients with history of male breast cancer have an increased risk of a second ipsilateral, or contralateral breast cancer (standardized incidence ratio 30-110). The risk of subsequent contralateral breast cancer was highest in men under 50 years of age at the time of the diagnosis of the initial cancer. The data on non-breast second primary cancers is diverse. One study has suggested an increased incidence of cancers of the small intestine, prostate, rectum and pancreas, and of non-melanoma skin cancer and myeloid leukaemia. Other investigators did not find an increase in the overall risk of subsequent cancer development in men diagnosed initially with primary breast cancer. Although sarcoma, lung and esophageal cancers are well recognized complications of radiation therapy for female breast cancer, there is no evidence for the association of these cancers following radiation therapy in male breast cancer. Although the incidence of second primary cancer in patients with primary male breast cancer requires further study, male breast cancer survivors should probably undergo periodic screening for the early detection of second breast cancers and other adverse health effects.

Receipt of Cancer Screening Services: Surprising Results for Some Rural Minorities

ERIC Educational Resources Information Center

Bennett, Kevin J.; Probst, Janice C.; Bellinger, Jessica D.

2012-01-01

Background: Evidence suggests that rural minority populations experience disparities in cancer screening, treatment, and outcomes. It is unknown how race/ethnicity and rurality intersect in these disparities. The purpose of this analysis is to examine the cancer screening rates among minorities in rural areas. Methods: We utilized the 2008…

Colorectal cancer screening practices of primary care providers: results of a national survey in Malaysia.

PubMed

Norwati, Daud; Harmy, Mohamed Yusoff; Norhayati, Mohd Noor; Amry, Abdul Rahim

2014-01-01

The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics.

Cryptogenic organizing pneumonia masquerading as lung carcinoma: A case report and review of the literature

PubMed Central

Huo, Ji-Ping; Liu, Cui; Jin, Bei-Bei; Duan, Feng-Xia; Mei, Sheng-Hui; Li, Xin-Gang; Zhao, Zhi-Gang

2018-01-01

Cryptogenic organizing pneumonia (COP) is a rare pulmonary disorder of unknown etiology. COP with hemoptysis as the primary presenting symptom has rarely been reported. The present study reported a case of COP that resembled lung carcinoma with hemoptysis as the only clinical symptom. The patient recovered well following thoracoscope surgery. A literature review of 119 COP cases between 1995 and 2015 was presented. Cough, fever and dyspnea were the most common clinical manifestations. The most common imaging manifestations were multiple or single consolidation, lung nodules, migratory sign, reversed halo sign, and multiple ground-glass opacity. A total of 3 cases exhibited COP accompanied by lung cancer. Glucocorticoids were effective for the majority of cases and invasive surgeries were implemented in most cases. The majority of cases recovered or relieved, and the prognosis of COP was relatively good. COP was easily confused with lung tumor and it is necessary to make differential diagnosis between COP and lung cancer. Invasive surgery should be avoided when possible to avoid or reduce patient trauma. PMID:29399056

MRI to delineate the gross tumor volume of nasopharyngeal cancers: which sequences and planes should be used?

PubMed

Popovtzer, Aron; Ibrahim, Mohannad; Tatro, Daniel; Feng, Felix Y; Ten Haken, Randall K; Eisbruch, Avraham

2014-09-01

Magnetic resonance imaging (MRI) has been found to be better than computed tomography for defining the extent of primary gross tumor volume (GTV) in advanced nasopharyngeal cancer. It is routinely applied for target delineation in planning radiotherapy. However, the specific MRI sequences/planes that should be used are unknown. Twelve patients with nasopharyngeal cancer underwent primary GTV evaluation with gadolinium-enhanced axial T1 weighted image (T1) and T2 weighted image (T2), coronal T1, and sagittal T1 sequences. Each sequence was registered with the planning computed tomography scans. Planning target volumes (PTVs) were derived by uniform expansions of the GTVs. The volumes encompassed by the various sequences/planes, and the volumes common to all sequences/planes, were compared quantitatively and anatomically to the volume delineated by the commonly used axial T1-based dataset. Addition of the axial T2 sequence increased the axial T1-based GTV by 12% on average (p = 0.004), and composite evaluations that included the coronal T1 and sagittal T1 planes increased the axial T1-based GTVs by 30% on average (p = 0.003). The axial T1-based PTVs were increased by 20% by the additional sequences (p = 0.04). Each sequence/plane added unique volume extensions. The GTVs common to all the T1 planes accounted for 38% of the total volumes of all the T1 planes. Anatomically, addition of the coronal and sagittal-based GTVs extended the axial T1-based GTV caudally and cranially, notably to the base of the skull. Adding MRI planes and sequences to the traditional axial T1 sequence yields significant quantitative and anatomically important extensions of the GTVs and PTVs. For accurate target delineation in nasopharyngeal cancer, we recommend that GTVs be outlined in all MRI sequences/planes and registered with the planning computed tomography scans.

Quantitative HER2 and p95HER2 levels in primary breast cancers and matched brain metastases.

PubMed

Duchnowska, Renata; Sperinde, Jeff; Chenna, Ahmed; Huang, Weidong; Weidler, Jodi M; Winslow, John; Haddad, Mojgan; Paquet, Agnes; Lie, Yolanda; Trojanowski, Tomasz; Mandat, Tomasz; Kowalczyk, Anna; Czartoryska-Arłukowicz, Bogumiła; Radecka, Barbara; Jarosz, Bożena; Staszkiewicz, Rafal; Kalinka-Warzocha, Ewa; Chudzik, Małgorzata; Biernat, Wojciech; Jassem, Jacek

2015-09-01

Patients with advanced breast cancer positive for human epidermal growth factor receptor 2 (HER2) are at high risk for brain metastasis (BM). The prevalence and significance of expression of HER2 and its truncated form p95HER2 (p95) in BM is unknown. Seventy-five pairs of formalin-fixed paraffin-embedded samples from matched primary breast cancers (PBCs) and BM were assayed for quantitative p95 and HER2-total (H2T) protein expression using the p95 VeraTag and HERmark assays, respectively. There was a net increase in p95 and H2T expression in BM relative to the matched PBC (median 1.5-fold, P = .0007 and 2.1-fold, P < .0001, respectively). Cases with H2T-positive tumors were more likely to have the largest (≥5-fold) increase in p95 (odds ratio = 6.3, P = .018). P95 positivity in PBC correlated with progression-free survival (hazard ratio [HR] = 2.2, P = .013), trended with shorter time to BM (HR = 1.8, P = .070), and correlated with overall survival (HR = 2.1, P = .042). P95 positivity in BM correlated with time to BM (HR = 2.0, P = .016) but did not correlate with overall survival from the time of BM diagnosis (HR = 1.2, P = .61). This is the first study of quantitative p95 and HER2 expression in matched PBC and BM. BM of breast cancer shows significant increases in expression of both biomarkers compared with matched PBC. These data provide a rationale for future correlative studies on p95 and HER2 levels in BM. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2017-03-09

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

Assessment of the influence of one's education on early diagnosis of multiple primary cancer in patients with uveal melanoma.

PubMed

Mierzwa-Dobranowska, Marzena; Romanowska-Dixon, Bozena

2012-01-01

This study will show a comparison of two groups of patients with uveal melanoma; one group with multiple primary cancer, and a second group with no identifiable second cancer, in terms of education and occupation. Study concerns 240 patients, who were isolated from patients being treated with uveal melanoma at the Department of Ophthalmology and Ocular Oncology Jagiellonian University Medical College in the period from 1998 to 2007. On the basis of medical history and medical records 97 patients were diagnosed with the one or more independent primary cancers. These patients were subjected to comparative analysis with a group of 143 patients with uveal melanoma as a control group. Analyzing the impact of education on the recognition of multiple primary cancer, there were significantly more frequent diagnoses of second primary cancers among patients with secondary and higher education than among those who had primary and vocational education. Among the obtained data on patients in the study group, the largest occupational group (according to the ISCO-88 (COM)) constituted "professionals". In the control group prevailed "craft and related trades workers". The results suggest the great importance of knowledge about risk factors for the development of cancer among patients with uveal melanoma and the ensuing more scrupulous search for succesive primary neoplasm and indicate the neccesity of organizing broad prophylactic actions. uveal melanoma, multiple primary cancer.

Other primary systemic cancers in patients with melanoma: Analysis of balanced acral and nonacral melanomas.

PubMed

Bae, Soo Hyeon; Seon, Hyun Ju; Choi, Yoo Duk; Shim, Hyun-Jeong; Lee, Jee-Bum; Yun, Sook Jung

2016-02-01

Although other primary systemic cancers in patients with melanoma have been studied, there have been few focusing on acral melanomas. We assessed other primary systemic cancers in patients with acral and nonacral melanomas. We analyzed other primary cancers in 452 patients with melanoma from 1994 to 2013. Metachronous cancers were defined as those given a diagnosis more than 2 months after diagnosis of melanoma. The others were considered prechronous or synchronous cancers. Among 51 cases of other primary cancers, gastrointestinal cancer (35.3%, n = 18/51) was the most common, followed by thyroid (17.6%), lung (11.8%), and breast (5.9%). Those were more prevalent in the acral melanoma group (12.8%, n = 31/243) compared with the nonacral melanoma group (9.6%, n = 20/209). Of 23 cases of metachronous cancer, the risk was the highest in bone marrow, followed by oral cavity, bladder, colon, lung, and thyroid. Among 28 cases of prechronous or synchronous cancers, gastrointestinal tract (35.7%, n = 10/28) was the most common site, followed by thyroid (17.9%), breast (10.7%), and lung (7.1%). The study is limited by a small number of patients. Careful follow-up and imaging studies are necessary for early detection of other primary cancers and metastatic lesions in patients with melanoma. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Are biomechanical changes necessary for tumor progression?

NASA Astrophysics Data System (ADS)

Kas, Josef A.

2014-03-01

Already the Roman Celsus recognized rigid tissue as characteristic for solid tumors. Conversely, changes towards a weaker cytoskeleton have been described as a feature of cancer cells since the early days of tumor biology. It remains unclear if a carcinoma's rigid signature stems from more inflexible cells or is caused by the stroma. Despite that the importance of cell biomechanics for tumor progression becomes more and more evident the chicken-and-egg problem to what extent cancer cells already change their mechanical properties within the solid tumor in order to transgress its boundary or mechanical changes are induced by the microenvironment when the cell has left the tumor has been discussed highly controversial. Comprehensive clinical biomechanical measurements only exist from tumor tissue without the possibility to identify individual cells or from individual cancer cells from pleural effusions. Since the biomechanical properties of cells in carcinomas remain unknown measurements on individual cells that directly stem out of primary tumor samples are required, which we have conducted. We found in cervix and mammary carcinomas a distinctive increase of softer cells as well as contractile cells. A soft and contractile cell is like a strong elastic rope. The cell can generate a strong tensile tension to pull its self along and is soft against compression to avoid jamming.

Differential proteomic analysis of a human breast tumor and its matched bone metastasis identifies cell membrane and extracellular proteins associated with bone metastasis.

PubMed

Dumont, Bruno; Castronovo, Vincent; Peulen, Olivier; Blétard, Noëlla; Clézardin, Philippe; Delvenne, Philippe; De Pauw, Edwin A; Turtoi, Andrei; Bellahcène, Akeila

2012-04-06

The classical fate of metastasizing breast cancer cells is to seed and form secondary colonies in bones. The molecules closely associated with these processes are predominantly present at the cell surface and in the extracellular space, establishing the first contacts with the target tissue. In this study, we had the rare opportunity to analyze a bone metastatic lesion and its corresponding breast primary tumor obtained simultaneously from the same patient. Using mass spectrometry, we undertook a proteomic study on cell surface and extracellular protein-enriched material. We provide a repertoire of significantly modulated proteins, some with yet unknown roles in the bone metastatic process as well as proteins notably involved in cancer cell invasiveness and in bone metabolism. The comparison of these clinical data with those previously obtained using a human osteotropic breast cancer cell line highlighted an overlapping group of proteins. Certain differentially expressed proteins are validated in the present study using immunohistochemistry on a retrospective collection of breast tumors and matched bone metastases. Our exclusive set of selected proteins supports the setup of further investigations on both clinical samples and experimental bone metastasis models that will help to reveal the finely coordinated expression of proteins that favor the development of metastases in the bone microenvironment.

Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin.

PubMed

Wang, Yupeng; Gao, Wenqing; Shi, Xuyan; Ding, Jingjin; Liu, Wang; He, Huabin; Wang, Kun; Shao, Feng

2017-07-06

Pyroptosis is a form of cell death that is critical for immunity. It can be induced by the canonical caspase-1 inflammasomes or by activation of caspase-4, -5 and -11 by cytosolic lipopolysaccharide. The caspases cleave gasdermin D (GSDMD) in its middle linker to release autoinhibition on its gasdermin-N domain, which executes pyroptosis via its pore-forming activity. GSDMD belongs to a gasdermin family that shares the pore-forming domain. The functions and mechanisms of activation of other gasdermins are unknown. Here we show that GSDME, which was originally identified as DFNA5 (deafness, autosomal dominant 5), can switch caspase-3-mediated apoptosis induced by TNF or chemotherapy drugs to pyroptosis. GSDME was specifically cleaved by caspase-3 in its linker, generating a GSDME-N fragment that perforates membranes and thereby induces pyroptosis. After chemotherapy, cleavage of GSDME by caspase-3 induced pyroptosis in certain GSDME-expressing cancer cells. GSDME was silenced in most cancer cells but expressed in many normal tissues. Human primary cells exhibited GSDME-dependent pyroptosis upon activation of caspase-3 by chemotherapy drugs. Gsdme -/- (also known as Dfna5 -/- ) mice were protected from chemotherapy-induced tissue damage and weight loss. These findings suggest that caspase-3 activation can trigger necrosis by cleaving GSDME and offer new insights into cancer chemotherapy.

Extracellular Hsp90 and TGFβ regulate adhesion, migration and anchorage independent growth in a paired colon cancer cell line model.

PubMed

de la Mare, Jo-Anne; Jurgens, Tamarin; Edkins, Adrienne L

2017-03-16

Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-β pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-β pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown. The paired SW480 and SW620 colon cancer cell lines, derived from a primary tumour and its lymph node metastasis, respectively, were used as an in vitro model to study key cellular processes required for metastasis. The status of the TGF-β pathway was examined in these cells using ELISA, flow cytometry, western blot analysis and confocal microscopy. Furthermore, the effect of addition or inhibition of the TGF-β pathway and Hsp90 on adhesion, migration and anchorage-independent growth, was determined in the cell lines. When comparing the canonical TGF-β1 pathway in the genetically paired cell lines our data suggests that this pathway may be constitutively active in the SW620 metastasis-derived cell line and not the SW480 primary tumour-derived line. In addition, we report that, when present in combination, TGF-β1 and Hsp90β stimulate anchorage-independent growth, reduce adhesion and stimulate migration. This effect is potentiated by inhibition of the TGF-β1 receptor and occurs via an alternate TGF-β1 pathway, mediated by αvβ6 integrin. Interestingly, in the SW620 cells, activation of this alternate TGF-β1 signalling machinery does not appear to require inhibition of the canonical TGF-β1 receptor, which would allow them to respond more effectively to the pro-metastasis stimulus of a combination of Hsp90β and TGF-β1 and this could account for the increased migratory capacity of these cells. In this study we report an apparent synergy between TGF-β1 and Hsp90β in stimulating migratory behaviour of colon cancer cells when signalling occurs via αvβ6 integrin as opposed to the canonical TGF-β1 pathway.

Evaluation and management of head and neck squamous cell carcinoma of unknown primary.

PubMed

Martin, Jeffrey M; Galloway, Thomas J

2015-07-01

The diagnostic evaluation and therapeutic management of a patient with squamous cell carcinoma of an unknown primary (SCCUP) has considerably evolved over recent decades and will likely continue to change as a result of the improving ability to identify small primary tumors and better tailor the implementation of multimodality therapy. By application of the general principles of head and neck oncology, physicians and surgeons are often able to achieve satisfactory control of the disease in patients with SCCUP. Copyright © 2015 Elsevier Inc. All rights reserved.

Dana-Farber Cancer Institute: Mapping the Function of Rare Oncogenic Variants | Office of Cancer Genomics

Cancer.gov

Although some oncogenes and tumor suppressor genes are recurrently mutated at high frequency, the majority of somatic sequence alterations found in cancers occur at low frequency, and the functional consequences of the majority of these mutated alleles remain unknown. We are developing a scalable systematic approach to interrogate the function of cancer-associated gene variants. Read the abstract

Usefulness of esophagogastroduodenoscopy and 18F-fluorodeoxyglucose positron-emission tomography in detecting synchronous multiple primary cancers with oral cancer.

PubMed

Ishibashi-Kanno, Naomi; Yamagata, Kenji; Uchida, Fumihiko; Hasegawa, Shogo; Yanagawa, Toru; Bukawa, Hiroki

2017-12-01

The purpose of this study is to compare the value of screening for synchronous multiple primary cancers in other organs by esophagogastroduodenoscopy (EGD) or 18 F-fluorodeoxyglucose positron-emission tomography (PET-CT) in patients newly diagnosed with oral cancer. We retrospectively examined consecutive Japanese patients who were diagnosed with oral squamous cell carcinoma (OSCC) and were screened for synchronous multiple primary cancers in other organs by EGD and/or PET-CT between January 2010 and December 2015 at our institution. The study included 190 patients (106 males and 84 females) from 36 to 93 years of age (median age 68.8 years). The patients were screened by EGD, PET-CT, or both before beginning treatment for OSCC. Of 190 Japanese patients with OSCC, 15 had multiple primary cancers: 13 patients had double cancer and two had triple cancers. The sites of the 17 multiple primary cancers were gastric (6), esophageal (4), and lung (3), and ovarian, colon, liver, and thyroid (1 each). All of the gastric and esophageal cancers were found by EGD and were not detected by PET-CT. For three patients, the detection of multiple cancers affected the treatment modality or order of treatment selected for the OSCC. In two cases, the oral cancer and multiple primary cancer(s) in another organ were resected simultaneously by joint surgical teams. PET-CT for oral cancer patients is an effective supporting diagnostic tool. However, the ability of PET-CT has some limitations. Especially for early detection of the upper gastrointestinal cancers, it is necessary to be supplemented by EGD.

Safety and benefit of curative surgical resection for esophageal squamous cell cancer associated with multiple primary cancers.

PubMed

Otowa, Y; Nakamura, T; Takiguchi, G; Yamamoto, M; Kanaji, S; Imanishi, T; Oshikiri, T; Suzuki, S; Tanaka, K; Kakeji, Y

2016-03-01

Enhancements in surgical techniques have led to improved outcomes for esophageal cancer. Recent findings have showed that esophageal cancer is frequently associated with multiple primary cancers, and surgical resection is usually complicated in such cases. The aim of this study was to clarify the clinical significance of surgery for patients with esophageal squamous cell cancer associated with multiple primary cancers. The clinical outcomes of surgical resection for esophageal cancer were compared among 79 patients with antecedent and/or synchronous cancers (Multiple cancer group) and 194 patients without antecedent and/or synchronous cancers (Single cancer group). The most common site of multiple primary cancers was the pharynx (36 patients; 29.7%), followed by the stomach (24 patients; 19.8%). The reconstruction method was more complicated in the Multiple cancer group as a result of the prolonged surgery time and increased blood loss. However, postoperative morbidity and overall survival (OS) did not differ between the two groups. After esophagectomy, metachronous cancers were observed in 26 patients, with 30 regions in total, and 93.1% were found to be curable. Sex was the only independent risk factors for developing metachronous cancer after esophagectomy. The presence of antecedent and synchronous cancers complicates the surgical resection of esophageal cancer; however, no differences were found in the OS and postoperative morbidity between the two groups. Therefore, surgical intervention should be selected as a first-line treatment. Because second primary cancers are often observed in esophageal cancer, we recommend a close follow-up using esophagogastroduodenoscopy and contrast-enhanced computed tomography. Copyright © 2015 Elsevier Ltd. All rights reserved.

Local control of metastatic lung tumors treated with SBRT of 48 Gy in four fractions: in comparison with primary lung cancer.

PubMed

Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro; Shinkai, Tetsu; Kubo, Yoshiro; Sugawara, Yoshifumi; Inoue, Takeshi; Sakai, Shinya; Aono, Shoji; Takahashi, Tadaaki; Semba, Takatoshi; Uwatsu, Kotaro

2010-02-01

The optimal dose of stereotactic body radiotherapy (SBRT) for metastatic lung tumors has not been clarified. Local control rates of metastatic lung tumors treated with SBRT of 48 Gy in four fractions, which is one of the common dose schedules for Stage I primary lung cancer in Japan, were examined. Between 2006 and 2008, 12 metastatic lung tumors (colorectal cancer, 7; others, 5) in 10 patients and 56 lesions of Stage I primary lung cancer (T1, 43; T2, 13) in 52 patients were treated with SBRT of 48 Gy in four fractions at the isocenter. Two-year overall survival rates were 86% for patients with metastatic lung tumors and 96% for patients with Stage I primary lung cancer (P = 0.4773). One- and 2-year local control rates were 48% and 25% for metastatic lung tumors, and 91% and 88% for Stage I primary lung cancer, respectively (P < 0.0001). The local control rates after SBRT of 48 Gy in four fractions were significantly worse in metastatic lung tumors compared with Stage I primary lung cancer. In SBRT, metastatic lung tumors should be clearly differentiated from primary lung cancer and should be given higher doses.

Squamous Cell Cancer of The Lung with Synchronous Renal Cell Carcinoma

PubMed Central

Ateş, İhsan; Yazıcı, Ozan; Ateş, Hale; Yazılıtaş, Doğan; Özcan, Ayşe Naz; Ağaçkıran, Yetkin; Zengin, Nurullah

2016-01-01

Coexistence of two or more primary cancers is a relatively rare case. Not with standing that the coexistence of multiple primary cancers is often discussed in the literature, there is a small number of publications concerning the coexistence of squamous cell lung carcinoma and renal cancer. In this case report, detection of both squamous cell lung carcinoma and primary renal cancer in one male patient is going to be discussed. PMID:29404140

Head and neck second primary cancer rates in the human papillomavirus era: A population-based analysis.

PubMed

Diaz, Dayssy Alexandra; Reis, Isildinha M; Weed, Donald T; Elsayyad, Nagy; Samuels, Michael; Abramowitz, Matthew C

2016-04-01

Patients with head and neck cancer are at high risk for second primary malignancies. Human papillomavirus (HPV)-driven tumors are generally high-grade oropharyngeal cancers. We analyzed the incidence of second primary malignancy of the head and neck in patients with primary squamous cell carcinoma (SCC) of the head and neck and temporal trends in the HPV era. The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with SCC of the head and neck (range, 1973-2008). Cumulative incidence rates of second primary malignancy of the head and neck were compared based on competing risk analysis. A total of 104,639 cases were included in this study, of which 4616 patients had second primary malignancy of the head and neck. Oropharyngeal cancer incidence increased over time. Estimated incidence rate/10,000 person-years (105.5, 80.6, and 50.2 for 1973-1989, 1990-1999, and 2000-2008, respectively) and cumulative incidence rates (10-year rates of 6.68%, 5.72%, and 4.59% for 1973-1989, 1990-1999, and 2000-2008, respectively) of second primary malignancies of the head and neck for patients with oropharyngeal cancer decreased over time (p < .001). The second primary malignancy of the head and neck incidence rate was significantly lower in patients with high-grade oropharyngeal cancer from 2000 to 2008 (30.3 vs 65.5 and 54.6 from 1973-1989 and 1990-1999, respectively; p < .001). The incidence of second primary malignancy of the head and neck in patients with head and neck cancer has decreased over time. This is driven by lower rates in patients with high-grade oropharyngeal cancer, is temporally related with increases in HPV-associated oropharyngeal cancer, and suggests that incidence rates of second primary malignancy of the head and neck may be lower for HPV-associated cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E873-E883, 2016. © 2015 Wiley Periodicals, Inc.

Multiple neoplasms, single primaries, and patient survival

PubMed Central

Amer, Magid H

2014-01-01

Background Multiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined. Methods This was a retrospective review of clinical data for all consecutive patients with histologically confirmed cancer, with emphasis on single versus multiple primary neoplasms. Second primaries discovered at the workup of the index (first) primary were termed simultaneous, if discovered within 6 months of the index primary were called synchronous, and if discovered after 6 months were termed metachronous. Results Between 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies; these included two primaries (n=284), and three or more primaries (n=38). Forty-seven patients had synchronous primaries and 275 had metachronous primaries. Patients with multiple primaries were predominantly of Caucasian ancestry (91.0%), with a tendency to develop thrombosis (20.2%), had a strong family history of similar cancer (22.3%), and usually presented with earlier stage 0 through stage II disease (78.9%). When compared with 1,551 patients with a single primary, these figures were 8.9%, 15.6%, 18.3%, and 50.9%, respectively (P≤0.001). Five-year survival rates were higher for metachronous cancers (95%) than for synchronous primaries (59%) and single primaries (59%). The worst survival rate was for simultaneous concomitant multiple primaries, being a median of 1.9 years. The best survival was for patients with three or more primaries (median 10.9 years) and was similar to the expected survival for the age-matched and sex-matched general population (P=0.06991). Conclusion Patients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent clinical behavior with longer survival rates, possibly related to genetic predisposition. PMID:24623992

42 CFR 81.5 - Use of personal and medical information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... claimants under DOL regulations 20 CFR part 30: (a) Year of birth (b) Cancer diagnosis (by ICD-9 code) for primary and secondary cancers (c) Date of cancer diagnosis (d) Gender (e) Race/ethnicity (if the claim is for skin cancer or a secondary cancer for which skin cancer is a likely primary cancer) (f) Smoking...

42 CFR 81.5 - Use of personal and medical information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... claimants under DOL regulations 20 CFR part 30: (a) Year of birth (b) Cancer diagnosis (by ICD-9 code) for primary and secondary cancers (c) Date of cancer diagnosis (d) Gender (e) Race/ethnicity (if the claim is for skin cancer or a secondary cancer for which skin cancer is a likely primary cancer) (f) Smoking...

42 CFR 81.5 - Use of personal and medical information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... claimants under DOL regulations 20 CFR part 30: (a) Year of birth (b) Cancer diagnosis (by ICD-9 code) for primary and secondary cancers (c) Date of cancer diagnosis (d) Gender (e) Race/ethnicity (if the claim is for skin cancer or a secondary cancer for which skin cancer is a likely primary cancer) (f) Smoking...

42 CFR 81.5 - Use of personal and medical information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... claimants under DOL regulations 20 CFR part 30: (a) Year of birth (b) Cancer diagnosis (by ICD-9 code) for primary and secondary cancers (c) Date of cancer diagnosis (d) Gender (e) Race/ethnicity (if the claim is for skin cancer or a secondary cancer for which skin cancer is a likely primary cancer) (f) Smoking...

42 CFR 81.5 - Use of personal and medical information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... claimants under DOL regulations 20 CFR part 30: (a) Year of birth (b) Cancer diagnosis (by ICD-9 code) for primary and secondary cancers (c) Date of cancer diagnosis (d) Gender (e) Race/ethnicity (if the claim is for skin cancer or a secondary cancer for which skin cancer is a likely primary cancer) (f) Smoking...

Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer

MedlinePlus

... and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer The U.S. Preventive Services Task Force ( ... and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer. This final recommendation statement applies to ...

Application of Cox model in coagulation function in patients with primary liver cancer.

PubMed

Guo, Xuan; Chen, Mingwei; Ding, Li; Zhao, Shan; Wang, Yuefei; Kang, Qinjiong; Liu, Yi

2011-01-01

To analyze the distribution of coagulation parameters in patients with primary liver cancer; explore the relationship between clinical staging, survival, and coagulation parameters by using Coxproportional hazard model; and provide a parameter for clinical management and prognosis. Coagulation parameters were evaluated in 228 patients with primary liver cancer, 52 patients with common liver disease, and 52 normal healthy controls. The relationship between primary livercancer staging and coagulation parameters wasanalyzed. Follow-up examinations were performed. The Cox proportional hazard model was used to analyze the relationship between coagulationparameters and survival. The changes in the coagulation parameters in patients with primary liver cancer were significantly different from those in normal controls. The effect of the disease on coagulation function became more obvious as the severity of liver cancer increased (p<0.05). The levels of D-dimer, fibrinogen degradation products (FDP), fibrinogen (FIB), and platelets (PLT) were negatively correlated with the long-term survival of patients with advanced liver cancer. The stages of primary liver cancer are associated with coagulation parameters. Coagulation parameters are related to survival and risk factors. Monitoring of coagulation parameters may help ensure better surveillance and treatment for liver cancer patients.

[The role of whole body 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in the management of unknown primary tumors].

PubMed

Wu, Zhi-Jian; Zhang, Yong-Xue; Wei, Hao; Jia, Qing

2007-08-28

To assess the role of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in the management of unknown primary primary (CUP) with metastatic loci. Thirty-four patients of CUP with metastatic loci who had undergone unsuccessful conventional diagnostic work-up underwent (18)F-FDG PET/CT. The images thus obtained were analyzed with visual and semi-quantitative methods. Histopathology, cytology, and/or follow-up were used to evaluate the PET/CT results. In 20 of the 34 patients (18)F-FDG PET/CT showed focal tracer accumulations corresponding to potential primary tumor sites located in the lung (n = 9), colon (n = 3), rectum (n = 2), pancreas (n = 1), right aryepiglottic wall (n = 1), esophagus (n = 1), breast (n = 1), and ovary (n = 2). The detection rate of primary tumor by (18)F-FDG PET/CT was 50.0% (17/34), the primary tumors were identified in the lung (n = 8), colon (n = 2), rectum (n = 1), pancreas (n = 1), right aryepiglottic wall (n = 1), esophagus (n = 1), ovary (n = 2), and breast (n = 1). The false positive rate was 8.8% (3/34) with the diagnosis of primary tumor in the lung (n = 1), colon (n = 1), and rectum (n = 1) to be identified as false. In 14 of the 34 patients, (18)F-FDG PET/CT did not reveal lesions suspected to be the primary tumor sites in 13 patients, and it was impossible to identify one lesion as the most likely primary tumor in one patient due to the presence of multiple hot spots in several organs. The (18)F-FDG PET/CT findings affected the medical management in 17 of the 34 (50.0%) patients due to the finding of primary sites and/or additional metastases. (18)F-FDG PET/CT has relevant impact on the therapeutic management of patients with unknown primary tumor. It is recommended that (18)F-FDG PET/CT be performed in the patient with unknown primary tumor after unsuccessful conventional diagnostic workup.

Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-01-24

Ovarian Papillary Serous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer

Second primary cancers -  causes, incidence and the future.

PubMed

Koubková, L; Hrstka, R; Dobes, P; Vojtesek, B; Vyzula, R

2014-01-01

Thanks to continually improving screening programs, diagnostic, and treatment methods, the survival rate in newly diagnosed cancer patients is increasing. With this improvement in survival, attention is now being focused on potential longterm complications such as multiple primary tumors, which represent a leading cause of late nonrelapse mortality. The number of patients who survive cancer dia-gnosis is growing by 2% each year. Multiple primary neoplasms have become the third most common finding in oncology since 1890s, when they were first described. This review aims to summarize recent information regarding the multiple primary neoplasms, elucidate the definition, etiology, association with the primary cancer treatment, genetic and environmental dispositions and finally, it recapitulates new approaches to identification of the risk factors for multiple cancers.

Does remnant gastric cancer really differ from primary gastric cancer? A systematic review of the literature by the Task Force of Japanese Gastric Cancer Association.

PubMed

Shimada, Hideaki; Fukagawa, Takeo; Haga, Yoshio; Oba, Koji

2016-04-01

Remnant gastric cancer, most frequently defined as cancer detected in the remnant stomach after distal gastrectomy for benign disease and those cases after surgery of gastric cancer at least 5 years after the primary surgery, is often reported as a tumor with poor prognosis. The Task Force of Japanese Gastric Cancer Association for Research Promotion evaluated the clinical impact of remnant gastric cancer by systematically reviewing publications focusing on molecular carcinogenesis, lymph node status, patient survival, and surgical complications. A systematic literature search was performed using PubMed/MEDLINE with the keywords "remnant," "stomach," and "cancer," revealing 1154 relevant reports published up to the end of December 2014. The mean interval between the initial surgery and the diagnosis of remnant gastric cancer ranged from 10 to 30 years. The incidence of lymph node metastases at the splenic hilum for remnant gastric cancer is not significantly higher than that for primary proximal gastric cancer. Lymph node involvement in the jejunal mesentery is a phenomenon peculiar to remnant gastric cancer after Billroth II reconstruction. Prognosis and postoperative morbidity and mortality rates seem to be comparable to those for primary proximal gastric cancer. The crude 5-year mortality for remnant gastric cancer was 1.08 times higher than that for primary proximal gastric cancer, but this difference was not statistically significant. In conclusion, although no prospective cohort study has yet evaluated the clinical significance of remnant gastric cancer, our literature review suggests that remnant gastric cancer does not adversely affect patient prognosis and postoperative course.

Radiological manifestations of metastasis to the ovary.

PubMed

Willmott, Fredric; Allouni, Kader Abdel; Rockall, Andrea

2012-07-01

MRI is an effective tool for detection of ovarian neoplastic lesions. However, there are no highly specific radiological features that differentiate primary from metastatic ovarian masses. Histological diagnosis preoperatively is not always possible as there is a risk of disseminating an otherwise early stage primary ovarian cancer. The preoperative diagnosis of an ovarian lesion is therefore heavily dependent on the radiological features. The radiologist must rely on a combination of knowing the natural history of any known primary cancer, together with the radiological features such as bilaterality, mucinous appearance, pseudomyxoma as well as the clinical progress of the primary tumour in order to evaluate and predict the likelihood of metastatic disease. Even if a non-ovarian primary cancer is known, an ovarian mass cannot always be assumed to be a secondary lesion. Some tumours, such as BRAC-positive breast cancer, are known to have a high rate of concomitant primary ovarian cancer. Conversely, other tumours, such as gastric and appendiceal cancer, are known to have a high rate of ovarian metastatic disease. However, histology remains the only true way to determine an ovarian metastasis from a primary lesion.

Belinostat and Carboplatin in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Carboplatin or Cisplatin

ClinicalTrials.gov

2017-10-18

Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer

Investigation of c-KIT and Ki67 expression in normal, preneoplastic and neoplastic canine prostate.

PubMed

Fonseca-Alves, Carlos Eduardo; Kobayashi, Priscilla Emiko; Palmieri, Chiara; Laufer-Amorim, Renée

2017-12-06

c-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines. Eleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive. The present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer.

Environmental and Occupational Interventions for Primary Prevention of Cancer: A Cross-Sectorial Policy Framework

PubMed Central

Espina, Carolina; Porta, Miquel; Schüz, Joachim; Aguado, Ildefonso Hernández; Percival, Robert V.; Dora, Carlos; Slevin, Terry; Guzman, Julietta Rodriguez; Meredith, Tim; Landrigan, Philip J.

2013-01-01

Background: Nearly 13 million new cancer cases and 7.6 million cancer deaths occur worldwide each year; 63% of cancer deaths occur in low- and middle-income countries. A substantial proportion of all cancers are attributable to carcinogenic exposures in the environment and the workplace. Objective: We aimed to develop an evidence-based global vision and strategy for the primary prevention of environmental and occupational cancer. Methods: We identified relevant studies through PubMed by using combinations of the search terms “environmental,” “occupational,” “exposure,” “cancer,” “primary prevention,” and “interventions.” To supplement the literature review, we convened an international conference titled “Environmental and Occupational Determinants of Cancer: Interventions for Primary Prevention” under the auspices of the World Health Organization, in Asturias, Spain, on 17–18 March 2011. Discussion: Many cancers of environmental and occupational origin could be prevented. Prevention is most effectively achieved through primary prevention policies that reduce or eliminate involuntary exposures to proven and probable carcinogens. Such strategies can be implemented in a straightforward and cost-effective way based on current knowledge, and they have the added benefit of synergistically reducing risks for other noncommunicable diseases by reducing exposures to shared risk factors. Conclusions: Opportunities exist to revitalize comprehensive global cancer control policies by incorporating primary interventions against environmental and occupational carcinogens. PMID:23384642

Extracellular vesicle-mediated transfer of processed and functional RNY5 RNA

PubMed Central

Chakrabortty, Sudipto K.; Prakash, Ashwin; Nechooshtan, Gal; Hearn, Stephen; Gingeras, Thomas R.

2015-01-01

Extracellular vesicles (EVs) have been proposed as a means to promote intercellular communication. We show that when human primary cells are exposed to cancer cell EVs, rapid cell death of the primary cells is observed, while cancer cells treated with primary or cancer cell EVs do not display this response. The active agents that trigger cell death are 29- to 31-nucleotide (nt) or 22- to 23-nt processed fragments of an 83-nt primary transcript of the human RNY5 gene that are highly likely to be formed within the EVs. Primary cells treated with either cancer cell EVs, deproteinized total RNA from either primary or cancer cell EVs, or synthetic versions of 31- and 23-nt fragments trigger rapid cell death in a dose-dependent manner. The transfer of processed RNY5 fragments through EVs may reflect a novel strategy used by cancer cells toward the establishment of a favorable microenvironment for their proliferation and invasion. PMID:26392588

Using radioactive drugs could lead to better imaging of prostate cancer | Center for Cancer Research

Cancer.gov

Medical imaging (x-ray, ultrasound, MRI, CT, PET scan) is a noninvasive way to view the internal structures of the body. However, these tools are not ideal for detecting cancer that has spread, or metastasized, because the precise location of these cancer cells is unknown. Researchers are now testing an experimental radiotracer called 18F-DCFPyL to help find sites of cancer in the body.  Learn more...

What is the lifetime risk of developing cancer?: the effect of adjusting for multiple primaries

PubMed Central

Sasieni, P D; Shelton, J; Ormiston-Smith, N; Thomson, C S; Silcocks, P B

2011-01-01

Background: The ‘lifetime risk' of cancer is generally estimated by combining current incidence rates with current all-cause mortality (‘current probability' method) rather than by describing the experience of a birth cohort. As individuals may get more than one type of cancer, what is generally estimated is the average (mean) number of cancers over a lifetime. This is not the same as the probability of getting cancer. Methods: We describe a method for estimating lifetime risk that corrects for the inclusion of multiple primary cancers in the incidence rates routinely published by cancer registries. The new method applies cancer incidence rates to the estimated probability of being alive without a previous cancer. The new method is illustrated using data from the Scottish Cancer Registry and is compared with ‘gold-standard' estimates that use (unpublished) data on first primaries. Results: The effect of this correction is to make the estimated ‘lifetime risk' smaller. The new estimates are extremely similar to those obtained using incidence based on first primaries. The usual ‘current probability' method considerably overestimates the lifetime risk of all cancers combined, although the correction for any single cancer site is minimal. Conclusion: Estimation of the lifetime risk of cancer should either be based on first primaries or should use the new method. PMID:21772332

A cohort study on the evolution of psychosocial problems in older patients with breast or colorectal cancer: comparison with younger cancer patients and older primary care patients without cancer.

PubMed

Deckx, Laura; van Abbema, Doris L; van den Akker, Marjan; van den Broeke, Carine; van Driel, Mieke; Bulens, Paul; Tjan-Heijnen, Vivianne C G; Kenis, Cindy; de Jonge, Eric T; Houben, Bert; Buntinx, Frank

2015-07-09

Although older cancer survivors commonly report psychosocial problems, the impact of both cancer and ageing on the occurrence of these problems remains largely unknown. The evolution of depression, cognitive functioning, and fatigue was evaluated in a group of older cancer patients in comparison with a group of younger cancer patients and older persons without cancer. Older (≥70 years) and younger cancer patients (50-69 years) with breast or colorectal cancer stage I-III, and older persons without cancer (≥70 years) were included. Data were collected at baseline and one year follow-up and were available for 536 persons. Depression was evaluated with the 15-item Geriatric Depression Scale. Cognitive functioning was measured with the cognitive functioning subscale of the European Organization for Research and Treatment of Cancer. Fatigue was measured with a Visual Analogue Scale. Risk factors for depression, cognitive functioning, and fatigue were analysed using multivariate logistic regression analyses. Risk factors included cancer- and ageing-related factors such as functional status, cancer treatment, and comorbidities. The evolution of psychosocial problems was similar for the group of older (N = 125) and younger cancer patients (N = 196): an increase in depression (p < 0.01), slight worsening in cognitive functioning (p = 0.01), and no clear change in fatigue. Also, compared to the group of people without cancer (N = 215), the differences were small and after one year of follow-up only depression was more frequent in older cancer patients compared to older persons without cancer (18% versus 9%, p = 0.04). In multivariate analyses the main risk factors for psychosocial problems after one year follow-up were changes in functional status and presence of baseline depression, fatigue, or cognitive impairment. Over the course of one year after a diagnosis of cancer, cancer patients face increasing levels of depression and increasing difficulties in cognitive functioning. The main risk factor for psychosocial problems was presence of the problem at baseline. This calls for regular screening for psychosocial problems and exchange of information on psychosocial functioning between different health care providers and settings during the treatment and follow-up trajectory of cancer patients.

Colorectal cancer screening: Estimated future colonoscopy need and current volume and capacity.

PubMed

Joseph, Djenaba A; Meester, Reinier G S; Zauber, Ann G; Manninen, Diane L; Winges, Linda; Dong, Fred B; Peaker, Brandy; van Ballegooijen, Marjolein

2016-08-15

In 2014, a national campaign was launched to increase colorectal cancer (CRC) screening rates in the United States to 80% by 2018; it is unknown whether there is sufficient colonoscopy capacity to reach this goal. This study estimated the number of colonoscopies needed to screen 80% of the eligible population with fecal immunochemical testing (FIT) or colonoscopy and determined whether there was sufficient colonoscopy capacity to meet the need. The Microsimulation Screening Analysis-Colon model was used to simulate CRC screening test use in the United States (2014-2040); the implementation of a national screening program in 2014 with FIT or colonoscopy with 80% participation was assumed. The 2012 Survey of Endoscopic Capacity (SECAP) estimated the number of colonoscopies that were performed and the number that could be performed. If a national screening program started in 2014, by 2024, approximately 47 million FIT procedures and 5.1 million colonoscopies would be needed annually to screen the eligible population with a program using FIT as the primary screening test; approximately 11 to 13 million colonoscopies would be needed annually to screen the eligible population with a colonoscopy-only screening program. According to the SECAP survey, an estimated 15 million colonoscopies were performed in 2012, and an additional 10.5 million colonoscopies could be performed. The estimated colonoscopy capacity is sufficient to screen 80% of the eligible US population with FIT, colonoscopy, or a mix of tests. Future analyses should take into account the geographic distribution of colonoscopy capacity. Cancer 2016;122:2479-86. © 2016 American Cancer Society. © 2016 American Cancer Society.

Risk of treatment related death and febrile neutropaenia with taxane-based adjuvant chemotherapy for breast cancer in a middle income country outside a clinical trial setting.

PubMed

Phua, Chee Ee; Bustam, Anita Zarina; Yusof, Mastura Md; Saad, Marniza; Yip, Cheng-Har; Taib, Nor Aishah; Ng, Char Hong; Teh, Yew Ching

2012-01-01

The risk of treatment-related death (TRD) and febrile neutropaenia (FN) with adjuvant taxane- based chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage in recent years. This study aims to determine these rates in patients treated in University Malaya Medical Centre (UMMC). Patients who were treated with adjuvant taxane-based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates were then determined retrospectively from medical records. TRD was defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. FN was defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L. A total of 622 patients received adjuvant chemotherapy during this period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4 taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens. The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the patients. The FN rate was 10% and there was no TRD. Adjuvant taxane-based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary prophylactic G-CSF should be considered for patients with any additional risk factor for FN.

Postoperative Management of Multiple Primary Cancers Associated with Non-small Cell Lung Cancer.

PubMed

Shoji, Fumihiro; Yamazaki, Koji; Miura, Naoko; Katsura, Masakazu; Oku, Yuka; Takeo, Sadanori; Maehara, Yoshihiko

2018-06-01

Modern treatment for primary cancers has improved survival. Therefore, increased numbers of patients with multiple primary cancers (MPC) associated with lung cancer may be expected. The aim of the present study was to report MPC associated with lung cancer and discuss patients' characteristics and postoperative management. Overall, 973 consecutive patients who underwent surgery for non-small cell lung cancer (NSCLC) were retrospectively studied. NSCLC with MPC was observed in 148 patients (15.2%). MPC comprised 24 synchronous (2.5%) and 124 metachronous (12.7%) diseases. Of the 124 metachronous patients, NSCLC was detected before cancers were detected in other organs (lung cancer first (LCF)) in 25 (20.2%) patients and subsequently in other organs after treatment (other organs, primary cancer-first (OCF)) in 99 (79.8%) patients. MPC was significantly associated with advanced age (p<0.0001) and chronic obstructive pulmonary disease (COPD) (p=0.0040). The leading sites of MPC in patients with synchronous tumors and those with OCF were the digestive organs. In contrast, the leading site of MPC in patients with LCF was the lung. In the latter, at least two primary lung cancers were detected within 5 years as well as 5 years after surgery for the treatment of the first detected lung cancer, while primary cancers of other organs were detected within 5 years. Advanced age and COPD may represent a high-risk of MPCs. Therefore, we recommend careful follow-up to detect MPC in the lung as well as the digestive organs beyond 5 years after treatment of the first cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Multiple Primary Cancer Monograph

Cancer.gov

To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

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

Survival rates of invasive breast cancer among ethnic Chinese women born in East Asia and the United States.

PubMed

Chuang, Shu-Chun; Chen, Wenping; Hashibe, Mia; Li, Gang; Zhang, Zuo-Feng

2006-01-01

Few studies have compared the breast cancer survival rates of US born ethnic Chinese women and the survival rates of Chinese immigrants. The main purpose of this study is to explore the difference of breast cancer survival rates between the two populations and compare the survival rates to those of Caucasians born in the US. Between 1973 and 2002, 365,215 women who had been diagnosed with primary invasive breast cancer (ICD-O-2 C500:C509) were recorded in the Surveillance, Epidemiology, and End Results (SEER) registries. Of the 316,881 breast cancer patients who were white, 180,835 (57%) were born in the United States, 20,983 (7%) were born elsewhere, and 115,063 (36%) had unknown birthplaces. Among the 3,634 breast cancer patients who were ethnically Chinese, 952 (26%) patients were born in the US, 1,356 (37%) were born in East Asia, 146 (4%) were born elsewhere, and 1,180 (33%) had unknown birthplaces. We compared the survival rates and estimated the risk ratios (RRs) by the Kaplan-Meier estimates and the Cox proportional hazards models. A lower 5-year overall survival rate of breast cancer was observed among Chinese women born in East Asia (0.74, 95% CI=0.72-0.77) than those born in the U.S. (0.79, 95% CI=0.76-0.81), with an adjusted hazards ratio of 1.22 (95% CI=1.06-1.40). The 5-year survival rates for SEER stage were higher among Chinese women born in the U.S. (localized: 0.90, 95% CI=0.87-0.93; regional: 0.71, 95% CI=66-0.77; distant: 0.16, 95% CI=0.06-0.25) than that among Chinese women born in East Asia (localized: 0.86, 95% CI=0.83-0.89; regional: 0.68, 95% CI=0.63-0.73; distant: 0.16, 95% CI=0.07-0.25). Higher 5-year survival rates among Chinese women born in the U.S. in comparison to Chinese women born in East Asia were also observed in different calendar years (1973-1980, 1981-1990, 1991-2002), in surgery and radiation therapy. Our analysis showed that among the Chinese breast cancer patients, women born in East Asia had lower 5-year survival rates than women born in the United States. SEER stage, grade, and tumor size appear to be important prognostic factors. The poor 5-year survival rates among Chinese women born in East Asia indicate potential problems of accessing medical facilities for early detection, diagnosis and treatment because of potential language and culture barriers, lower education level, as well as stress of the first generation of migrant Chinese women in the United States.

Dana-Farber Cancer Institute: Mapping the Function of Rare Oncogenic Variants | Office of Cancer Genomics

Cancer.gov

Although some oncogenes and tumor suppressor genes are recurrently mutated at high frequency, the majority of somatic sequence alterations found in cancers occur at low frequency, and the functional consequences of the majority of these mutated alleles remain unknown. We are developing a scalable systematic approach to interrogate the function of cancer-associated gene variants. Read the abstract: Kim et al., 2016

Overcoming Endocrine Resistance by Targeting ER/FoxA1/IL 8 Axis

DTIC Science & Technology

2016-10-01

INTRODUCTION Approximately 75% of breast cancers express the hormone estrogen receptor α (ER). As a critical determinant in estrogen response and oncogenic...factor of estrogen receptor α (ER)–chromatin binding and function, yet its aberration in endocrine-resistant (Endo-R) breast cancer is unknown. Here, we...positive tumors. FOXA1 | estrogen receptor | breast cancer | transcriptional reprogramming | endocrine resistance About 75% of breast cancers express

Doing More for More: Unintended Consequences of Financial Incentives for Oncology Specialty Care.

PubMed

O'Neil, Brock; Graves, Amy J; Barocas, Daniel A; Chang, Sam S; Penson, David F; Resnick, Matthew J

2016-02-01

Specialty care remains a significant contributor to health care spending but largely unaddressed in novel payment models aimed at promoting value-based delivery. Bladder cancer, chiefly managed by subspecialists, is among the most costly. In 2005, Centers for Medicare and Medicaid Services (CMS) dramatically increased physician payment for office-based interventions for bladder cancer to shift care from higher cost facilities, but the impact is unknown. This study evaluated the effect of financial incentives on patterns of fee-for-service (FFS) bladder cancer care. Data from a 5% sample of Medicare beneficiaries from 2001-2013 were evaluated using interrupted time-series analysis with segmented regression. Primary outcomes were the effects of CMS fee modifications on utilization and site of service for procedures associated with the diagnosis and treatment of bladder cancer. Rates of related bladder cancer procedures that were not affected by the fee change were concurrent controls. Finally, the effect of payment changes on both diagnostic yield and need for redundant procedures were studied. All statistical tests were two-sided. Utilization of clinic-based procedures increased by 644% (95% confidence interval [CI] = 584% to 704%) after the fee change, but without reciprocal decline in facility-based procedures. Procedures unaffected by the fee incentive remained unchanged throughout the study period. Diagnostic yield decreased by 17.0% (95% CI = 12.7% to 21.3%), and use of redundant office-based procedures increased by 76.0% (95% CI = 59% to 93%). Financial incentives in bladder cancer care have unintended and costly consequences in the current FFS environment. The observed price sensitivity is likely to remain a major issue in novel payment models failing to incorporate procedure-based specialty physicians. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Estrogen Alone and Health Outcomes in Black Women by African Ancestry: A Secondary Analyses of a Randomized Controlled Trial

PubMed Central

Chlebowski, Rowan T.; Barrington, Wendy; Aragaki, Aaron K.; Manson, JoAnn E.; Sarto, Gloria; O’Sullivan, Mary Jo; Wu, Daniel; Cauley, Jane A.; Qi, Lihong; Wallace, Robert L.; Prentice, Ross L.

2016-01-01

OBJECTIVE In postmenopausal Black women in the Women’s Health Initiative (WHI) randomized trial, estrogen alone reduced breast cancers but its comprehensive influence on health outcomes in Black women is unknown. Therefore, we examined this issue in the WHI overall and by African ancestry. METHODS 1,616 Black women with prior hysterectomy, including 1061 with percent African ancestry determination, at 40 US centers were randomly assigned to conjugated equine estrogen (0.625 mg/d) or placebo for 7.2 years (median) intervention with 13 years cumulative follow-up. Coronary heart disease (CHD) and breast cancer were primary efficacy and safety outcomes, respectively. A global index also included stroke, colorectal cancer, hip fracture, pulmonary embolism and death. RESULTS Black women in the estrogen alone group compared to Black women in the placebo group had fewer breast cancers (17 vs. 40, hazard ratio [HR] 0.47 95% confidence interval [CI] 0.26–0.82). In women with >80% African ancestry, breast cancer HR was lower (0.32 95% CI 0.12–0.86, trend p=0.04 for ancestry effect). Most other outcomes including CHD, stroke, hip fracture and the global index were null with estrogen use in Black women; a global index effect was more favorable in younger Black women (HR 0.65 95% CI 0.43–0.98). CONCLUSIONS In Black postmenopausal women with prior hysterectomy, estrogen alone significantly reduced breast cancer incidence with no adverse influence on CHD, venous thromboembolism or all-cause mortality. Favorable estrogen alone global index effects in younger Black women warrant further study. PMID:27749739

miRNA-regulated delivery of lincRNA-p21 suppresses β-catenin signaling and tumorigenicity of colorectal cancer stem cells.

PubMed

Wang, Jun; Lei, Zeng-jie; Guo, Yan; Wang, Tao; Qin, Zhong-yi; Xiao, Hua-liang; Fan, Li-lin; Chen, Dong-feng; Bian, Xiu-wu; Liu, Jia; Wang, Bin

2015-11-10

Cancer stem cells (CSCs) are key cellular targets for effective cancer therapy, due to their critical roles in cancer progression and chemo/radio-resistance. Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) are important players in the biology of cancers. However, it remains unknown whether lncRNAs could be exploited to target CSCs. We report that large intergenic non-coding RNA p21 (lincRNA-p21) is a potent suppressor of stem-like traits of CSCs purified from both primary colorectal cancer (CRC) tissues and cell lines. A novel lincRNA-p21-expressing adenoviral vector, which was armed with miRNA responsive element (MRE) of miR-451 (Ad-lnc-p21-MRE), was generated to eliminate CRC CSCs. Integration of miR-451 MREs into the adenovirus efficiently delivered lincRNA-p21 into CSCs that contained low levels of miR-451. Moreover, lincRNA-p21 inhibited the activity of β-catenin signaling, thereby attenuating the viability, self-renewal, and glycolysis of CSCs in vitro. By limiting dilution and serial tumor formation assay, we demonstrated that Ad-lnc-p21-MRE significantly suppressed the self-renewal potential and tumorigenicity of CSCs in nude mice. Importantly, application of miR-451 MREs appeared to protect normal liver cells from off-target expression of lincRNA-p21 in both tumor-bearing and naïve mice. Taken together, these findings suggest that lncRNAs may be promising therapeutic molecules to eradicate CSCs and MREs of tumor-suppressor miRNAs, such as miR-451, may be exploited to ensure the specificity of CSC-targeting strategies.

Low Rate of Cervical Cancer Screening among Women with Hematologic Malignancies after Stem Cell Transplant.

PubMed

Hwang, Jessica P; Ahmed, Sairah; Ariza-Heredia, Ella J; Duan, Zhigang; Zhao, Hui; Schmeler, Kathleen M; Ramondetta, Lois; Parker, Susan L; Suarez-Almazor, Maria E; Ferrajoli, Alessandra; Shih, Ya-Chen Tina; Giordano, Sharon H; Chiao, Elizabeth Y

2018-05-01

Annual cervical cancer screening with Papanicolaou (Pap) and human papillomavirus (HPV) testing after stem cell transplant (SCT) is recommended, but the uptake is unknown. We aimed to determine the prevalence and predictors of cervical cancer screening in patients with hematologic malignancies. We searched MarketScan Commercial Claims database for women who underwent allogeneic or autologous SCT. The primary outcome was cervical cancer screening, defined as procedures or abnormal results for HPV and/or Pap testing according administrative codes within 2 years after SCT. A multivariable logistic regression model was fitted with cancer type, SCT year, age, geographic area, insurance plan, comorbidity, and presence of graft-versus-host disease (GVHD).The study included 1484 patients; 1048 patients (70.6%) had autologous and 436 (29.4%) allogeneic SCT. Mean age was 52.5 years. Overall, 660 patients (44.5%) had screening within 2 years after SCT, 214 (49.1%) with allogeneic SCT and 446 (42.6%) with autologous SCT (P = .02). In the allogeneic SCT group, patients with GVHD had a lower rate of screening than patients without GVHD (42.5% versus 55.4%, P < .01), and GVHD was associated with lower odds of screening (odds ratio, .50; 95% confidence interval, .32 to .79). In the autologous SCT group, patients with comorbid medical conditions had a lower rate of screening than patients without comorbidity (36.0% versus 45.7%, P < .01). In both allogeneic and autologous SCT groups older patients had lower odds of screening. Cervical cancer screening rates after SCT are low, particularly in patients with GVHD, who are at significant risk of second malignancies. Future work is needed to develop strategies to increase uptake. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A Multi-Institutional Prospective Trial Confirms Noninvasive Blood Test Maintains Predictive Value in African American Men.

PubMed

Punnen, Sanoj; Freedland, Stephen J; Polascik, Thomas J; Loeb, Stacy; Risk, Michael C; Savage, Stephen; Mathur, Sharad C; Uchio, Edward; Dong, Yan; Silberstein, Jonathan L

2018-06-01

The 4Kscore® test accurately detects aggressive prostate cancer and reduces unnecessary biopsies. However, its performance in African American men has been unknown. We assessed test performance in a cohort of men with a large African American representation. Men referred for prostate biopsy at 8 Veterans Affairs medical centers were prospectively enrolled in the study. All men underwent phlebotomy for 4Kscore test assessment prior to prostate biopsy. The primary outcome was the detection of Grade Group 2 or higher cancer on biopsy. We assessed the discrimination, calibration and clinical usefulness of 4Kscore to predict Grade Group 2 or higher prostate cancer and compared it to a base model consisting of age, digital rectal examination and prostate specific antigen. Additionally, we compared test performance in African American and nonAfrican American men. Of the 366 enrolled men 205 (56%) were African American and 131 (36%) had Grade Group 2 or higher prostate cancer. The 4Kscore test showed better discrimination (AUC 0.81 vs 0.74, p <0.01) and higher clinical usefulness on decision curve analysis than the base model. Test prediction closely approximated the observed risk of Grade Group 2 or higher prostate cancer. There was no difference in test performance in African American and nonAfrican American men (0.80 vs 0.84, p = 0.32), The test outperformed the base model in each group. The 4Kscore test accurately predicts aggressive prostate cancer for biopsy decision making in African American and nonAfrican American men. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Functional study of risk loci of stem cell-associated gene lin-28B and associations with disease survival outcomes in epithelial ovarian cancer.

PubMed

Lu, Lingeng; Katsaros, Dionyssios; Mayne, Susan T; Risch, Harvey A; Benedetto, Chiara; Canuto, Emilie Marion; Yu, Herbert

2012-11-01

Several single-nucleotide polymorphisms (SNPs) of the stem cell-associated gene lin-28B have been identified in association with ovarian cancer and ovarian cancer-related risk factors. However, whether these SNPs are functional or might be potential biomarkers for ovarian cancer prognosis remains unknown. The purposes of this study were to investigate the functional relevance of the identified lin-28B SNPs, as well as the associations of genotype and phenotype with epithelial ovarian cancer (EOC) survival. We analyzed five SNPs and mRNA levels of lin-28B in 211 primary EOC tissues using Taqman(®) SNP genotyping assays and SYBR green-based real-time PCR, respectively. The RNA secondary structures at the region of a genome-wide association-identified intronic rs314276 were analyzed theoretically with mfold and experimentally with circular dichroism spectroscopy. We found that rs314276 was a cis-acting expression quantitative trait locus (eQTL) in both additive and dominant models, while rs7759938 and rs314277 were significant or of borderline significance in dominant models only. The rs314276 variant significantly affects RNA secondary structure. No SNPs alone were associated with patient survival. However, we found that among patients initially responding to chemotherapy, those with higher lin-28B expression had higher mortality risk (hazard ratio =3.27, 95% confidence interval: 1.63-6.56) and relapse risk (hazard ratio = 2.53, 95% confidence interval: 1.41-4.54) than those with lower expression, and these associations remained in multivariate analyses. These results suggest that rs314276 alters RNA secondary structure and thereby influences gene expression, and that lin-28B is a cancer stem cell-associated marker, which may be a pharmaceutical target in the management of EOC.

Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.

PubMed

Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

2017-10-03

SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m 2 ) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort ( N = 19; unselected population, including three patients with MET -amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m 2 . Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m 2 in the dose-expansion cohort, comprising patients with MET -amplified tumors ( N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m 2 has acceptable tolerability and modest antitumor activity in patients with MET -amplified gastric cancer.

Perspectives on death and an afterlife in relation to quality of life, depression, and hopelessness in cancer patients without evidence of disease and advanced cancer patients.

PubMed

van Laarhoven, Hanneke W M; Schilderman, Johannes; Verhagen, Constans A H H V M; Vissers, Kris C; Prins, Judith

2011-06-01

It is unknown whether cancer patients with different life expectancies have different attitudes and emotions toward death and an afterlife. Also, it is unclear whether these attitudes and emotions toward death and afterlife influence patients' distress. To assess the relationship of attitudes and emotions towards death and an afterlife with quality of life, depression and hopelessness in cancer patients without evidence of disease and advanced cancer patients facing death. Ninety-one cancer patients without evidence of disease and 57 advanced cancer patients completed the Dutch Attitudes Toward Death and Afterlife Scale. Emotions toward death were measured using the Self-Confrontation Method. Quality of life was measured with the Satisfaction with Life Scale and the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire. Depression and hopelessness were measured with the Beck Depression Inventory for Primary Care and the Beck Hopelessness Scale. Average scores on attitudes and emotions toward death and an afterlife were not significantly different between the two groups. However, in the no evidence of disease group, a negative association between negative emotions and social functioning was observed, which was not present in the advanced cancer group. In the advanced cancer group, associations were observed that were not present in the no evidence of disease group: positive associations between an explicitly religious attitude and global health status and between reincarnation belief and role and cognitive functioning, and a negative association between other-directed emotions and social functioning. Patients without evidence of disease and advanced cancer patients do not differ in attitudes or emotions toward death, but the relationship between these attitudes and emotions and aspects of quality of life varies. When there is no evidence of disease, negative emotions play the most important role, whereas in the advanced cancer situation, attitudes toward death and an afterlife, which may provide meaning and value, become more prominent. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

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

2018-03-16

High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

42 CFR 82.18 - How will NIOSH calculate internal dose to the primary cancer site(s)?

Code of Federal Regulations, 2010 CFR

2010-10-01

... primary cancer site(s)? 82.18 Section 82.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND... Dose Reconstruction Process § 82.18 How will NIOSH calculate internal dose to the primary cancer site(s... cancer covered by a claim is in a tissue not covered by existing ICRP models, NIOSH will use the ICRP...

42 CFR 82.18 - How will NIOSH calculate internal dose to the primary cancer site(s)?

Code of Federal Regulations, 2011 CFR

2011-10-01

... primary cancer site(s)? 82.18 Section 82.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND... Dose Reconstruction Process § 82.18 How will NIOSH calculate internal dose to the primary cancer site(s... cancer covered by a claim is in a tissue not covered by existing ICRP models, NIOSH will use the ICRP...

42 CFR 82.18 - How will NIOSH calculate internal dose to the primary cancer site(s)?

Code of Federal Regulations, 2013 CFR

2013-10-01

... primary cancer site(s)? 82.18 Section 82.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND... Dose Reconstruction Process § 82.18 How will NIOSH calculate internal dose to the primary cancer site(s... cancer covered by a claim is in a tissue not covered by existing ICRP models, NIOSH will use the ICRP...

42 CFR 82.18 - How will NIOSH calculate internal dose to the primary cancer site(s)?

Code of Federal Regulations, 2014 CFR

2014-10-01

... primary cancer site(s)? 82.18 Section 82.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND... Dose Reconstruction Process § 82.18 How will NIOSH calculate internal dose to the primary cancer site(s... cancer covered by a claim is in a tissue not covered by existing ICRP models, NIOSH will use the ICRP...

42 CFR 82.18 - How will NIOSH calculate internal dose to the primary cancer site(s)?

Code of Federal Regulations, 2012 CFR

2012-10-01

... primary cancer site(s)? 82.18 Section 82.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND... Dose Reconstruction Process § 82.18 How will NIOSH calculate internal dose to the primary cancer site(s... cancer covered by a claim is in a tissue not covered by existing ICRP models, NIOSH will use the ICRP...

Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-07-01

Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

[Gas gangrene of the abdominal wall due to underlying GI pathology: seven cases].

PubMed

Monneuse, O; Gruner, L; Barth, X; Malick, P; Timsit, M; Gignoux, B; Tissot, E

2007-01-01

Gas gangrene of the abdominal wall is a rare clinical occurrence with high rates of morbidity and mortality. The primary source of the infection is often unknown. To analyze the primary underlying intestinal etiologies and diagnostic approaches of gas gangrene of the abdominal wall, and to highlight specific treatment problems, particularly that of constructing a colostomy exteriorized through a massively infected abdominal wall. Seven cases of abdominal wall gas gangrene due to a gastrointestinal etiology were identified. (Cases arising from proctologic sources or related to recent abdominal surgery were excluded.) During the same period, 39 other patients presenting with abdominal wall gangrene from non-intestinal sources were treated. The etiologies were: perforated sigmoid diverticulitis (n=2), perforated appendicitis (n=1), acute pancreatitis with associated cecal perforation (n=1), and perforated colorectal cancer (n=3). Four of the seven patients died despite treatment (mortality of 57%). The clinical presentations of these seven cases demonstrate that a GI source must be suspected whenever a patient presents with abdominal wall gas gangrene, even when there are no specific GI symptoms. Imaging, particularly with CT scan, is essential both to visualize the extent of tissue necrosis and to reveal underlying primary GI pathology. This optimizes the surgical approach both by allowing for complete debridement and drainage of infected tissue, and by focussing the intervention on correction of the underlying primary GI source of infection.

IGF-IEc expression is increased in secondary compared to primary foci in neuroendocrine neoplasms.

PubMed

Alexandraki, Krystallenia I; Philippou, Anastassios; Boutzios, Georgios; Theohari, Irini; Koutsilieris, Michael; Delladetsima, Ioanna Kassiani; Kaltsas, Gregory A

2017-10-03

Different Insulin-like growth factor-I (IGF-I) mRNA transcripts are produced by alternative splicing and particularly the IGF-IEc isoform has been implicated in the development and/or progression of various types of cancer. In the present study, we examined the potential role of IGF-IEc expression as a new immunohistochemical marker of aggressiveness in neuroendocrine neoplasms (NENs). We utilized immunohistochemical analysis in tissue specimens of 47 patients with NENs, to evaluate the expression of IGF-IEc (%) and Ki-67 proliferation index (%). Specimens from patients with tumors of different tissue origin, of either primary or metastatic lesions and of different grade were examined. Cytoplasmic IGF-IEc staining was found in 23 specimens of NENs or NECs: 10 pancreatic, 4 small bowel, 3 gastric, 1 lung, 1 uterine and 4 poorly differentiated of unknown primary origin. Ki-67 and IGF-IEc expression was positively correlated in all the samples studied (r=0.31, p=0.03). IGF-1Ec expression was more prevalent in specimens originating from metastatic foci with high Ki-67 compared to primary sites with low Ki-67 expression (p=0.036). These findings suggest a possible role of IGF-IEc in NEN tumorigenesis and progression to metastases that could be used as an additional new marker of a more aggressive behavior and a potential drugable target.

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis.

PubMed

Zhang, Rong-Xin; Ma, Wen-Juan; Gu, Yu-Ting; Zhang, Tian-Qi; Huang, Zhi-Mei; Lu, Zhen-Hai; Gu, Yang-Kui

2017-07-27

It is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients. One hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients. One hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910). This study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

Long-term risks of subsequent primary neoplasms among survivors of childhood cancer.

PubMed

Reulen, Raoul C; Frobisher, Clare; Winter, David L; Kelly, Julie; Lancashire, Emma R; Stiller, Charles A; Pritchard-Jones, Kathryn; Jenkinson, Helen C; Hawkins, Michael M

2011-06-08

Survivors of childhood cancer are at excess risk of developing subsequent primary neoplasms but the long-term risks are uncertain. To investigate long-term risks of subsequent primary neoplasms in survivors of childhood cancer, to identify the types that contribute most to long-term excess risk, and to identify subgroups of survivors at substantially increased risk of particular subsequent primary neoplasms that may require specific interventions. British Childhood Cancer Survivor Study--a population-based cohort of 17,981 5-year survivors of childhood cancer diagnosed with cancer at younger than 15 years between 1940 and 1991 in Great Britain, followed up through December 2006. Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of subsequent primary neoplasms. After a median follow-up time of 24.3 years (mean = 25.6 years), 1354 subsequent primary neoplasms were ascertained; the most frequently observed being central nervous system (n = 344), nonmelanoma skin cancer (n = 278), digestive (n = 105), genitourinary (n = 100), breast (n = 97), and bone (n = 94). The overall SIR was 4 times more than expected (SIR, 3.9; 95% confidence interval [CI], 3.6-4.2; AER, 16.8 per 10,000 person-years). The AER at older than 40 years was highest for digestive and genitourinary subsequent primary neoplasms (AER, 5.9 [95% CI, 2.5-9.3]; and AER, 6.0 [95%CI, 2.3-9.6] per 10,000 person-years, respectively); 36% of the total AER was attributable to these 2 subsequent primary neoplasm sites. The cumulative incidence of colorectal cancer for survivors treated with direct abdominopelvic irradiation was 1.4% (95% CI, 0.7%-2.6%) by age 50 years, comparable with the 1.2% risk in individuals with at least 2 first-degree relatives affected by colorectal cancer. Among a cohort of British childhood cancer survivors, the greatest excess risk associated with subsequent primary neoplasms at older than 40 years was for digestive and genitourinary neoplasms.

Colony-stimulating factor use and impact on febrile neutropenia among patients with newly diagnosed breast, colorectal, or non-small cell lung cancer who were receiving chemotherapy.

PubMed

McCune, Jeannine S; Sullivan, Sean D; Blough, David K; Clarke, Lauren; McDermott, Cara; Malin, Jennifer; Ramsey, Scott

2012-01-01

To determine the impact of primary prophylactic colony-stimulating factor (CSF) use on febrile neutropenia in a large patient population receiving contemporary chemotherapy regimens to treat breast cancer, colorectal cancer, or non-small cell lung cancer (NSCLC). Retrospective claims analysis. The Surveillance, Epidemiology, and End Results (SEER)-Puget Sound cancer registry and insurance claims records. A total of 2728 patients aged 25 years or older who received a diagnosis of breast cancer (998 patients), colorectal cancer (688 patients), or NSCLC (1042 patients) between January 1, 2002, and December 31, 2005, and received chemotherapy. Initial chemotherapy regimen, CSF use (filgrastim or pegfilgrastim), and febrile neutropenia events were evaluated after the first chemotherapy administration. Subsequently, febrile neutropenia rates in patients receiving primary prophylactic CSF were compared with febrile neutropenia rates in patients receiving CSF in settings other than primary prophylaxis or not at all. The impact of primary prophylactic CSF could not be assessed for patients with colorectal cancer or NSCLC because only 1 and 18 febrile neutropenia events, respectively, occurred in those receiving primary prophylactic CSF. Of the 998 patients with breast cancer, 72 (7.2%) experienced febrile neutropenia, 28 of whom received primary prophylactic CSF. In the patients with breast cancer, we observed that primary prophylactic CSF use was associated with reduced febrile neutropenia rates; however, the analysis may have been confounded by unmeasured factors associated with febrile neutropenia. The impact of primary prophylactic CSFs on febrile neutropenia rates could not be demonstrated. Given the substantive cost of CSFs to pharmacy budgets, there are numerous opportunities for pharmacists to optimize CSF use. Research studies are needed to evaluate if guideline-directed prescribing of primary prophylactic CSFs can improve clinical outcomes. © 2012 Pharmacotherapy Publications, Inc.

Learning the Landscape: Implementation Challenges of Primary Care Innovators around Cancer Survivorship Care

PubMed Central

O’Malley, Denalee; Hudson, Shawna V.; Nekhlyudov, Larissa; Howard, Jenna; Rubinstein, Ellen; Lee, Heather S.; Overholser, Linda S.; Shaw, Amy; Givens, Sarah; Burton, Jay S.; Grunfeld, Eva; Parry, Carly; Crabtree, Benjamin F.

2016-01-01

PURPOSE This study describes the experiences of early implementers of primary care-focused cancer survivorship delivery models. METHODS Snowball sampling was used to identify innovators. Twelve participants (five cancer survivorship primary care innovators and seven content experts) attended a working conference focused on cancer survivorship population strategies and primary care transformation. Data included meeting discussion transcripts/field notes, transcribed in-depth innovator interviews, and innovators’ summaries of care models. We used a multi-step immersion/crystallization analytic approach, guided by a primary care organizational change model. RESULTS Innovative practice models included: 1) a consultative model in a primary care setting; 2) a primary care physician (PCP)-led, blended consultative/panel-based model in an oncology setting; 3) an oncology nurse navigator in a primary care practice; and 4) two sub-specialty models where PCPs in a general medical practice dedicated part of their patient panel to cancer survivors. Implementation challenges included: (1) lack of key stakeholder buy-in; (2) practice resources allocated to competing (non-survivorship) change efforts; and (3) competition with higher priority initiatives incentivized by payers. CONCLUSIONS Cancer survivorship delivery models are potentially feasible in primary care; however, significant barriers to widespread implementation exist. Implementation efforts would benefit from increasing the awareness and potential value-add of primary care-focused strategies to address survivors’ needs. PMID:27277895

FANCA safeguards interphase and mitosis during hematopoiesis in vivo

PubMed Central

Abdul-Sater, Zahi; Cerabona, Donna; Sierra Potchanant, Elizabeth; Sun, Zejin; Enzor, Rikki; He, Ying; Robertson, Kent; Goebel, W. Scott; Nalepa, Grzegorz

2015-01-01

Fanconi anemia (FA/BRCA) signaling network controls multiple genome-housekeeping checkpoints, from interphase DNA repair to mitosis. The in vivo role of abnormal cell division in FA remains unknown. Here, we quantified the origins of genomic instability in FA patients and mice in vivo and ex vivo. We found that both mitotic errors and interphase DNA damage significantly contribute to genomic instability during FA-deficient hematopoiesis and in non-hematopoietic human and murine FA primary cells. Super-resolution microscopy coupled with functional assays revealed that FANCA shuttles to the pericentriolar material (PCM) to regulate spindle assembly at mitotic entry. Loss of FA signaling rendered cells hypersensitive to spindle chemotherapeutics and allowed escape from the chemotherapy-induced spindle assembly checkpoint. In support of these findings, direct comparison of DNA cross-linking and antimitotic chemotherapeutics in primary FANCA−/− cells revealed genomic instability originating through divergent cell cycle checkpoint aberrations. Our data indicate that the FA/BRCA signaling functions as an in vivo gatekeeper of genomic integrity throughout interphase and mitosis, which may have implications for future targeted therapies in FA and FA-deficient cancers. PMID:26366677

Structure of the dimerization domain of DiGeorge Critical Region 8

PubMed Central

Senturia, Rachel; Faller, Michael; Yin, Sheng; Loo, Joseph A; Cascio, Duilio; Sawaya, Michael R; Hwang, Daniel; Clubb, Robert T; Guo, Feng

2010-01-01

Maturation of microRNAs (miRNAs, ∼22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298–352) at 1.7 Å resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis. PMID:20506313

Adult Liver Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

Cancer.gov

Hepatocellular carcinoma is the most common type of adult primary liver cancer. The Barcelona Clinical Liver Cancer (BCLC) Staging System is used to stage liver cancer. Learn more about risk factors, signs and symptoms, tests to diagnose, prognosis, and stages of adult primary liver cancer.

Risk of second primary cancer among women with breast cancer: a population-based study in Granada (Spain).

PubMed

Molina-Montes, Esther; Pollán, Marina; Payer, Tilman; Molina, Elena; Dávila-Arias, Cristina; Sánchez, María-José

2013-08-01

The higher risk of developing new cancers in breast cancer survivors is a public health concern. Our aim was to examine risk of second primary cancers among women diagnosed with breast cancer. We studied two cohorts of female cancer patients identified in a population-based cancer registry in Granada (Spain): women first diagnosed with a primary breast cancer (n=5897) and those with a primary cancer in another site (n=22,814), followed during 1985-2007 for second cancers and breast cancer occurrence, respectively. We used Standardized Incidence Ratios (SIRs) to estimate second cancer risk by age (<50y, ≥50y), time since diagnosis (≤5y, >5y) and calendar periods (≤1995, >1996). SIR for breast cancer was calculated in the second cohort. The risk of developing second cancers (n=314) was 39% higher (95% CI=1.23-1.54) among breast cancer patients, and particularly high among women under 50 (SIR=1.96, 95% CI=1.48-2.44). Excess risk for endometrial cancer (SIR=3.04, 95% CI=2.14-3.94) was statistically significant and remained so in women over 50. Younger women were at higher risk of second ovarian cancer (SIR=4.90, 95% CI=1.27-8.53). Increased SIRs were observed during the first five years after breast cancer diagnosis, whereas SIRs decreased thereafter. Breast cancer incidence (n=171) was not higher among women previously diagnosed with other cancer types (SIR=0.86, 95% CI=0.74-1.00). Women diagnosed with breast cancer have a higher incidence of second primary cancers, particularly of endometrial cancer in women over 50 at diagnosis, and ovarian cancer in younger women. These findings may be explained by treatment-related effects or shared risk factors. Copyright © 2013 Elsevier Inc. All rights reserved.

Increasing preoperative body size in breast cancer patients between 2002 and 2016: implications for prognosis.

PubMed

Wisse, Agatha; Tryggvadottir, Helga; Simonsson, Maria; Isaksson, Karolin; Rose, Carsten; Ingvar, Christian; Jernström, Helena

2018-05-26

Overweight and obesity are increasing worldwide, but the extent in breast cancer patients is unknown. The two aims were to study secular trends in preoperative body mass index (BMI), waist circumference, and breast volume and their impacts on clinical outcome. BMI, waist circumference, and breast volume were measured preoperatively in 24-99-year-old primary breast cancer patients (n = 640) in Sweden 2002-2016. The measurements were analyzed alone and combined in relation to recurrence and overall survival (OS). BMI, waist circumference, and breast volume increased 2002-2016 (p trends  < 0.0001). Of these, a breast volume ≥ 850 mL was associated with the strongest recurrence-risk (adjusted hazard ratio [ adj HR] 1.67; 95% CI 1.17-2.39), especially combined with waist circumference ≥ 80 cm ( adj HR 2.07; 95% CI 1.25-3.44), while BMI ≥ 25 kg/m 2 or large waist circumference conferred almost a twofold risk for death (both Log-Rank p ≤ 0.0001). Chemotherapy seemed to counteract the negative impact of a high BMI or large waist circumference on OS. Large breast volume was the strongest predictor for recurrence in all treatment groups. In conclusion, preoperative BMI, waist circumference, and breast volume increased between 2002 and 2016. Larger body size negatively impacted breast cancer-free interval and OS. If confirmed, body measurements may help select patients requiring more individualized treatment.

Constitutional and occupational risk factors associated with bladder cancer

PubMed Central

Ferrís, J.; Garcia, J.; Berbel, O.; Ortega, J.A.

2016-01-01

Objective Bladder carcinoma (BC) is the fourth most common type of cancer in males from Western countries, with primary prevention an important healthcare challenge. We review the associated constitutional and occupational risk factors (RF), with greater or lesser scientific evidence, in the etiology of BC. Material and methods Literature review of the last 25 years of the constitutional and occupational RF associated with BC, conducted on MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors and Bladder cancer. Results The main RF were (a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); (b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); (c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); (d) occupational, which represent 5–10% of BC RF; and (f) occupations with high BC risk, such as aluminum production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels. Conclusions BC is the end result of the variable combination of constitutional and environmental RF, the majority of which are unknown. The most significant constitutional RF are related to age, gender, race, ethnicity geographic location and genetic polymorphisms. The main occupational RF are those related to aromatic amines and polycyclic aromatic hydrocarbons. PMID:23664103

Constitutional and occupational risk factors associated with bladder cancer.

PubMed

Ferrís, J; Garcia, J; Berbel, O; Ortega, J A

2013-09-01

Bladder carcinoma (BC) is the fourth most common type of cancer in males from Western countries, with primary prevention an important healthcare challenge. We review the associated constitutional and occupational risk factors (RF), with greater or lesser scientific evidence, in the aetiology of BC. Literature review of the last 25 years of the constitutional and occupational RF associated with BC, conducted on MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk factors/Genetic factors/Genetic polymorphisms/Epidemiology/Occupational factors and Bladder cancer. The main RF were a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); d) occupational, which represent 5%-10% of BC RF; and f) occupations with high BC risk, such as aluminium production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels. BC is the end result of the variable combination of constitutional and environmental RF, the majority of which are unknown. The most significant constitutional RF are related to age, gender, race, ethnicity geographic location and genetic polymorphisms. The main occupational RF are those related to aromatic amines and polycyclic aromatic hydrocarbons. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Prognostic relevance of epithelial-mesenchymal transition and proliferation in surgically treated primary parotid gland cancer.

PubMed

Busch, Alina; Bauer, Larissa; Wardelmann, Eva; Rudack, Claudia; Grünewald, Inga; Stenner, Markus

2017-05-01

Cancer of the major salivary glands comprises a morphologically diverse group of rare tumours of largely unknown cause. Epithelial-mesenchymal transition (EMT) has been shown to play a significant prognostic role in various human cancers. The aim was to assess the expression of EMT markers in different histological subtypes of parotid gland cancer (PGC) and analyse their prognostic value. We examined 94 PGC samples (13 histological subtypes) for the expression of MIB-1, epithelial cadherin (E-cadherin), β-catenin, vimentin and cytokeratin 8/18 (CK8/18) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. We detected all analysed EMT and proliferation markers in specifically different constellations within the examined histological subtypes of PGC. We found high epithelial marker expressions (CK8/18, E-cadherin, membranous β-catenin) only in a distinct variety of carcinomas. A high proliferation rate (high MIB-1 expression) as well as a combination of high CK8/18 and low vimentin expression was associated with a significantly worse survival. Our findings indicate that activation of the EMT pathway is a relevant explanation for tumour progression in individual histological subtypes of malignant parotid gland lesions, but by far not in all. Evidence of EMT activation in PGC cannot be seen as an isolated prognostic factor. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

β5 Integrin Up-Regulation in Brain-Derived Neurotrophic Factor Promotes Cell Motility in Human Chondrosarcoma

PubMed Central

Li, Te-Mao; Fong, Yi-Chin; Liu, Shan-Chi; Chen, Po-Chun; Tang, Chih-Hsin

2013-01-01

Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF) is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes. We also found that BDNF increased the migration and expression of β5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF expression markedly inhibited migratory activity. BDNF-mediated migration and β5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt, and NF-κB inhibitors or mutants also abolished BDNF-promoted migration and integrin expression. The PI3K, Akt, and NF-κB signaling pathway was activated after BDNF treatment. Taken together, our results indicate that BDNF enhances the migration of chondrosarcoma by increasing β5 integrin expression through a signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF-κB. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. PMID:23874483

A spatial and temporal analysis of four cancers in African gold miners from Southern Africa.

PubMed

Harington, J S; McGlashan, N D; Bradshaw, E; Geddes, E W; Purves, L R

1975-06-01

The pattern of cancer in African gold miners over the 8-year period 1964-71, comprising 2,926,461 man-years of employment was studied. Of the 1344 cancers found, primary liver cancer accounted for 52-8%, oesophageal cancer 12-1%, cancer of the respiratory system 5-4% and cancer of the bladder 4-8%. Analysis of the spatial distribution of these four cancers, both on subcontinental and local scale, showed distinct gradients of occurrence between areas of significantly higher and lower incidence than expected. In the case of primary liver cancer in Mozambique and oesophageal cancer in the Transkei, the spatial distribution reflects closely that found in the general resident population of each territory. The crude incidence rate of primary liver cancer in gold miners from Mozambique dropped sharply over the period of the survey.

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Andersson, Roland

2016-10-01

To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion. Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS. Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis. LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

An Innovative Approach to Improve Completeness of Treatment and Other Key Data Elements in a Population-Based Cancer Registry: A15-Month Data Submission.

PubMed

Hsieh, Mei-Chin; Mumphrey, Brent; Pareti, Lisa; Yi, Yong; Wu, Xiao-Cheng

2017-01-01

BACKGROUND: In order to comply with the Louisiana legislative obligation and meet funding agencies’ requirement of case completeness for 12-month data submission, hospital cancer registries are mandated to submit cancer incidence data to the Louisiana Tumor Registry (LTR) within 6 months of diagnosis. However, enforcing compliance with timely reporting may result in incomplete data on adjuvant treatment received by the LTR. Although additional treatment information can be obtained via retransmission of the North American Association of Central Cancer Registries (NAACCR)–modified abstracts, consolidating multiple NAACCR-modified abstracts for the same case is extremely time consuming. To avoid a huge amount of work while obtaining timely and complete data, the LTR has requested hospital cancer registries resubmit their data 15 months after the close of the diagnosis year. The purpose of this report is to assess the improvement in the completeness of data items related to treatment, staging and site specific factors. METHODS: The LTR requested that hospital cancer registries resubmit 15-month data between April 1, 2016 and April 15, 2016 for cases diagnosed in 2014. Microsoft Visual Studio Visual Basic script was used to link and compare resubmitted data with existing data in the LTR database. Data elements used for matching same patient/tumor were name, Social Security number, date of birth, primary site, laterality, and hospital identifier number. Treatment data items were compared as known vs none/ unknown and known vs known with different code. Matched records with updated information were imported into the LTR database and flagged as modified abstract records for manual consolidation. Nonmatched records were also loaded in the LTR database as potential new cases for further investigation. RESULTS: A total of 25,207 resubmitted NAACCR abstracts were received from 38 hospitals and freestanding radiation centers. About 11.1% had at least 1 update related to treatment and/or other data item; an average of 3.3 updates per updated abstract. The majority of the updates (45.7%) for treatment were changes from none/unknown to known value and 42.6% of the updates were related to radiation treatment fields. In addition, 172 potential new cases were identified. Approximately 10.5% (18 cases) of these new cases were confirmed to be truly missed cases after investigation. CONCLUSION: The 15-month data resubmission is a cost-effective approach to obtaining complete information on treatment and other key data items from reporting facilities and can also be used to identify potential missed cases.

[Change in Perioperative Hemostatic Function in Patients Undergoing Hepatic Resection for Primary and Metastatic Liver Cancer].

PubMed

Komasawa, Nobuyasu; Ueki, Ryusuke; Atagi, Kazuaki; Nishi, Shinichi

2015-08-01

Patients undergoing primary hepatic resection often develop hemostatic dysfunction associated with cirrhosis. We retrospectively surveyed pre- and postoperative prothrombin time (PT) and the PT expressed as international normalized ratio (PT-INR) in 39 patients undergoing primary liver resection. We also compared PT changes between primary and metastatic cancer cases (8 cases). Postoperative PT-INR was 1.40 ± 0.38, which was significantly prolonged compared to preoperative PT-INR of 1.08 ± 0.07. Preoperative PT was over 70% in all 39 patients undergoing primary liver resection, whereas postoperative PT was less than 60% in 13 of 39 patients. No significant difference was found in preoperative PT-INR between primary and metastatic cancer cases, but postoperative PT-INR was significantly prolonged in primary cancer cases. Patients undergoing primary liver resection are susceptible to hemostatic dysfunction, even with preoperative PT levels within normal limits.

MIF Drives Pancreatic Cancer Aggressiveness by Downregulating NR3C2 | Center for Cancer Research

Cancer.gov

Pancreatic cancer, while relatively rare, is an aggressive disease ranked as the fourth leading cause of cancer-related death in the US. Because most patients are diagnosed at an advanced stage and their tumors resist available treatments, novel therapeutic targets are urgently needed. Macrophage Migration Inhibitory Factor (MIF) is a proinflammatory cytokine that is elevated in pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, and may provide a molecular link between inflammation and cancer, though the mechanism is unknown.

Cancer-Associated Fibroblasts in a Human HEp-2 Established Laryngeal Xenografted Tumor Are Not Derived from Cancer Cells through Epithelial-Mesenchymal Transition, Phenotypically Activated but Karyotypically Normal

PubMed Central

Wang, Mei; Wu, Chun-Ping; Pan, Jun-Yan; Zheng, Wen-Wei; Cao, Xiao-Juan; Fan, Guo-Kang

2015-01-01

Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression and even initiation. However, the origins of CAFs in various cancer types remain controversial, and one of the important hypothesized origins is through epithelial-mesenchymal transition (EMT) from cancer cells. In this study, we investigated whether the HEp-2 laryngeal cancer cells are able to generate CAFs via EMT during tumor formation, which is now still unknown. The laryngeal xenografted tumor model was established by inoculating the HEp-2 laryngeal cancer cell line in nude mice. Primary cultured CAFs from the tumor nodules and matched normal fibroblasts (NFs) from the adjacent connective tissues were subcultured, purified, and verified by immunofluorescence. Migration, invasion, and proliferation potentials were compared between the CAFs and NFs. A co-culture of CAFs with HEp-2 cells and a co-injection of CAFs with HEp-2 cells in nude mice were performed to examine the cancer-promoting potential of CAFs to further verify their identity. Karyotypic analyses of the CAFs, NFs, and HEp-2 cells were conducted. A co-culture of NFs with HEp-2 cells was also performed to examine the expression of activated markers of CAFs. A pathological examination confirmed that the laryngeal xenografted tumor model was successfully established, containing abundant CAFs. Immunocytochemical staining verified the purities and identities of the CAFs and NFs. Although the CAFs manifested higher migration, invasion, proliferation, and cancer-promoting capacities compared with the NFs, an analysis of chromosomes revealed that both the CAFs and NFs showed typical normal mouse karyotypes. In addition, the NFs co-cultured with HEp-2 cells did not show induced expressions of activated markers of CAFs. Our findings reveal that the CAFs in the HEp-2 established laryngeal xenografted tumor are not of laryngeal cancer origin but of mouse origin, indicating that the HEp-2 laryngeal cancer cells cannot generate their own CAFs via EMT in this model. PMID:25658113