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Sample records for primary advanced squamous

  1. [Primary orbital squamous cell carcinoma].

    PubMed

    Campos Arbulú, Ana L; Sadava, Emmanuel E; Sánchez Ruiz, Alejandro; Fernández Vila, Juan M; Dillon, Horacio S; Mezzadri, Norberto A

    2017-01-01

    Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis.

  2. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    SciTech Connect

    Strongin, Anna; Yovino, Susannah; Taylor, Rodney; Wolf, Jeffrey; Cullen, Kevin; Zimrin, Ann; Strome, Scott; Regine, William; Suntharalingam, Mohan

    2012-04-01

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm{sup 3}, and patients with a tumor volume <35 cm{sup 3} had a significantly better prognosis than those with a tumor volume >35 cm{sup 3} at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume <35 cm{sup 3} had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = < .001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p = < .001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm{sup 3} larger than tumors without locoregional failure (p = .028) and 27.1-cm{sup 3} larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer

  3. The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study.

    PubMed

    Solomon, Monica Charlotte; Vidyasagar, M S; Fernandes, Donald; Guddattu, Vasudev; Mathew, Mary; Shergill, Ankur Kaur; Carnelio, Sunitha; Chandrashekar, Chetana

    2016-12-01

    Oral squamous cell carcinomas comprise a heterogeneous tumor cell population with varied molecular characteristics, which makes prognostication of these tumors a complex and challenging issue. Thus, molecular profiling of these tumors is advantageous for an accurate prognostication and treatment planning. This is a retrospective study on a cohort of primary locally advanced oral squamous cell carcinomas (n = 178) of an Indian rural population. The expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of primary locally advanced oral squamous cell carcinomas was evaluated. A potential biomarker that can predict the tumor response to treatment was identified. Formalin-fixed paraffin-embedded tumor blocks of (n = 178) of histopathologically diagnosed cases of locally advanced oral squamous cell carcinomas were selected. Tissue microarray blocks were constructed with 2 cores of 2 mm diameter from each tumor block. Four-micron-thick sections were cut from these tissue microarray blocks. These tissue microarray sections were immunohistochemically stained for EGFR, p53, Bcl-2, cyclin D1 and p16. In this cohort, EGFR was the most frequently expressed 150/178 (84%) biomarker of the cases. Kaplan-Meier analysis showed a significant association (p = 0.038) between expression of p53 and a poor prognosis. A Poisson regression analysis showed that tumors that expressed p53 had a two times greater chance of recurrence (unadjusted IRR-95% CI 2.08 (1.03, 4.5), adjusted IRR-2.29 (1.08, 4.8) compared with the tumors that did not express this biomarker. Molecular profiling of oral squamous cell carcinomas will enable us to categorize our patients into more realistic risk groups. With biologically guided tumor characterization, personalized treatment protocols can be designed for individual patients, which will improve the quality of life of these patients.

  4. Pure Primary Ovarian Squamous Cell Carcinoma Perforating the Rectum

    PubMed Central

    Okada, Aiko; Haraguchi, Naotsugu; Tomimatsu, Takuji; Kimura, Tadashi

    2017-01-01

    Rectal perforation is uncommon in ovarian cancer, even in advanced stages. Pure primary ovarian squamous cell carcinoma is a very rare subtype of ovarian cancer and has not been reported to cause rectal perforation. A 50-year-old woman presented with rectal bleeding. Rectosigmoidoscopy suggested perforation of a pelvic tumor into the rectum. Abdominopelvic magnetic resonance imaging revealed a 9 cm heterogeneous mass in the pouch of Douglas. We performed complete cytoreduction, including an en-bloc resection of the tumor and rectosigmoid colon. Histopathology showed squamous cell carcinoma of the left ovary penetrating the rectal wall. A common symptom of rectal bleeding was caused by a very rare entity of ovarian cancer penetrating the rectal wall, but thorough evaluation led to its accurate diagnosis and appropriate treatment. PMID:28316851

  5. Advances in the management of cutaneous squamous cell carcinoma

    PubMed Central

    Parikh, Sonal A.

    2014-01-01

    Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas. PMID:25165569

  6. Current Management of Advanced Resectable Oral Cavity Squamous Cell Carcinoma

    PubMed Central

    Ow, Thomas J.

    2011-01-01

    The oral cavity is the most common site of head and neck squamous cell carcinoma, a disease which results in significant morbidity and mortality worldwide. Though the primary modality of treatment for patients with oral cavity cancer remains surgical resection, many patients present with advanced disease and are thus treated using a multi-disciplinary approach. Patients with extracapsular spread of lymphatic metastasis and surgical margins that remain positive have been found to be at high risk for local-regional recurrence and death from disease, and are most often recommended to receive both post-operative radiation as well as systemic chemotherapy. The basis for this approach, as well as scientific developments that underly future trials of novels treatments for patients with high-risk oral cavity cancer are reviewed. PMID:21461056

  7. [Advances of molecular targeted therapy in squamous cell lung cancer].

    PubMed

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  8. Emerging challenges of advanced squamous cell lung cancer

    PubMed Central

    Zhang, Yi-Chen; Zhou, Qing

    2016-01-01

    Squamous cell lung cancer (SQCLC) is an aggressive type of lung cancer and most are diagnosed at advanced stage. Patients with advanced SQCLC tend to be older, current or former smoker, with central type tumour located near large blood vessels and seldom with druggable genetic alternations. Consequently, progress of targeted therapy and antivascular agents available in lung adenocarcinoma could not be duplicated in this subset of patients. The treatment paradigms have long been dominant by cytotoxic agents and posed many therapeutic challenges. Until recent years, immune checkpoint inhibitors, other monoclonal antibodies and afatinib have been approved for treatment of advanced SQCLC, presenting a novel treatment landscape and initiating the era of precision medicine in this subset of patients. This review will summarise the recent treatment progresses in advanced SQCLC with a focus on checkpoint inhibitors of programmed cell death-1 receptor or its ligand, and discuss the emerging challenges in this new era. PMID:28255454

  9. Molecular events in relapsed oral squamous cell carcinoma: Recurrence vs. secondary primary tumor.

    PubMed

    Gleber-Netto, Frederico O; Braakhuis, Boudewijn J M; Triantafyllou, Asterios; Takes, Robert P; Kelner, Natalie; Rodrigo, Juan P; Strojan, Primož; Vander Poorten, Vincent; Rapidis, Alexander D; Rinaldo, Alessandra; Brakenhoff, Ruud H; Ferlito, Alfio; Kowalski, Luiz P

    2015-08-01

    Relapses have a great impact on both the morbidity and mortality rates of oral squamous cell carcinoma (OSCC) patients. Current classification criteria are imprecise and need improvements. Recent advances in understanding of OSCC relapses on a molecular level provide new possibilities to better classify true recurrences and second primary tumors. This review discusses the limitations of the current OSCC relapse classification method and presents possible alternatives to improve this classification based on molecular techniques. Moreover, these molecular techniques add to the further understanding of these lesions and may provide tools for clinical management.

  10. Metastatic Squamous Neck Cancer with Occult Primary Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Metastatic squamous neck cancer with occult primary occurs when squamous cell cancer spreads to lymph nodes in the neck from an undetectable primary tumor. Treatment includes surgery and radiation therapy. Learn about the diagnosis, survival, staging, and treatment of these tumors.

  11. Collision tumor of the thyroid gland: primary squamous cell and papillary thyroid carcinoma.

    PubMed

    Warman, Meir; Lipschitz, Noga; Ikher, Sergey; Halperin, Doron

    2011-01-01

    Introduction. Collision tumor of the thyroid gland is defined when independent and histologically distinct tumors coexist within the gland. The presence of both papillary and squamous cell carcinoma in the thyroid gland is unusual. Suggested etiologies include embryonic remanents of squamous epithelium, chronic inflammation, or thyroid malignancies promoting squamous metaplasia. Case Presentation. An elderly patient presented with a rapid enlargement of a long-standing right thyroid nodule. The tumor was locally invasive and unresectable. Pathology revealed the diagnosis of papillary and squamous cell carcinoma of the thyroid gland. Possible primary sites for squamous cell carcinoma in upper aerodigestive tract were excluded. The patient outcome was fatal although palliative chemoradiotherapy. Discussion. Collision tumor of papillary and squamous cell carcinoma of the thyroid gland is a rare entity that may imply bad prognosis, as to the presence of the squamous portion. The best treatment includes resection of the tumor; unfortunately it is not possible in most cases.

  12. Primary frontal sinus squamous cell carcinoma in a dog treated with surgical excision.

    PubMed

    Grimes, Janet A; Pagano, Candace J; Boudreaux, Bonnie B

    2017-01-01

    An 8-year-old castrated male mixed breed dog was presented for a squamous cell carcinoma of the left frontal sinus. A partial craniectomy was performed and polytetrafluoroethylene mesh was placed over the craniectomy site. The dog recovered well with a good cosmetic outcome. Histopathology confirmed primary frontal sinus squamous cell carcinoma.

  13. Influence of Pathological Nodal Status and Maximal Standardized Uptake Value of the Primary Tumor and Regional Lymph Nodes on Treatment Plans in Patients With Advanced Oral Cavity Squamous Cell Carcinoma

    SciTech Connect

    Liao, C.-T.; Wang, H.-M.; Chang, Joseph Tung-Chieh; Lin, C.-Y.; Ng, S.-H.; Huang, S.-F.; Chen, I.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2010-06-01

    Purpose: A better understanding of the prognostic factors in oral cavity squamous cell carcinoma (OSCC) may optimize the therapeutic approach. In this study, we sought to investigate whether the combination of clinical information, pathologic results, and preoperative maximal standardized uptake value (SUVmax) at the primary tumor and regional lymph nodes might improve the prognostic stratification in this patient group. Methods and Materials: A total of 347 consecutive OSCC patients were investigated. All participants underwent fluorodeoxyglucose-positron emission tomography within 2 weeks before surgery and neck dissection. The duration of follow-up was at least 24 months in all surviving patients. The optimal cutoff values for SUVmax at the primary tumor (SUVtumor-max) and regional lymph nodes (SUVnodal-max) were selected according to the 5-year disease-free survival (DFS) rate. Independent prognosticators were identified by Cox regression analysis. Results: In multivariate analysis, a cutoff SUVtumor-max of 8.6, a cutoff SUVnodal-max of 5.7, and the presence of pathologic lymph node metastases were found to be significant prognosticators for the 5-year DFS. A scoring system using these three prognostic factors was formulated to define distinct prognostic groups. The 5-year rates for patients with a score between 0 and 3 were as follows: neck control, 94%, 86%, 77%, 59% (p < 0.0001); distant metastases, 1%, 7%, 22%, 47% (p < 0.0001); disease-specific survival, 93%, 85%, 61%, 36%, respectively (p < 0.0001). Conclusion: Based on the study findings, the combined evaluation of pathologic node status and SUVmax at the primary tumor and regional lymph nodes may improve prognostic stratification in OSCC patients.

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

    ClinicalTrials.gov

    2013-07-01

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

  15. [Primary squamous cell carcinoma of the breast: rare form carcinoma].

    PubMed

    Maksimović, Sinisa

    2009-01-01

    Primary squamous cell carcinoma (SCC) is a rare form of breast carcinoma. Incidence is reported to be 0.1-3.6%. We report a case of a young woman, 37-year-old, with history of a lump in the upper outer quadrant of the left breast with ulceration of the skin surface. Menarche occurred at age of 12. The patient was married, had two deliveries and had her first child at age of 26. She did not use contraceptive pills. Diagnosis of the tumour of the breast was made at the Department of surgery in General Hospital in Bijeljina in September 2007. Clinical examination, mammography and ultrasonography were performed. Physical examination revealed a circumscribed and firm mass measuring 60 x 60 x 80 mm. Mammogram showed a round, high-density mass with almost regular but partially irregular margin. Ultrasonogram of the left breast tumor identified an irregularly shaped hypoechoic lesion. After clinical staging of the disease, we performed incision biopsy of the skin and tumour of the left breast with histopathology examination (standard hematoxylin and eosin). Patient had estrogen and progesteron receptors negative and was HER2/neu negative. After histopathology, patient's case was presented to the working group for breast tumors which decided to start with the neoadjuvant chemotherapy using platinum. After six cycles of neoadjuvant chemotherapy, regression of breast tumor was confirmed. Working group decided that radical mastectomy of left breast should be performed.

  16. Primary squamous cell carcinoma of the prostate: a case report of a rare clinical entity.

    PubMed

    Biswas, Tithi; Podder, Tarun; Lepera, Pamela A; Walker, Paul

    2015-11-01

    Primary squamous cell carcinoma of the prostate is a unique and rare clinicopathological entity with fewer than 100 cases reported in the literature. Because of its rarity, the optimal management is not well known. Here, we report a case of primary squamous cell carcinoma of the prostate which was treated with definitive concurrent chemo-radiotherapy with excellent outcome along with a brief review of the literature.

  17. Primary squamous cell carcinoma of the prostate: a case report of a rare clinical entity

    PubMed Central

    Biswas, Tithi; Podder, Tarun; Lepera, Pamela A; Walker, Paul

    2015-01-01

    Primary squamous cell carcinoma of the prostate is a unique and rare clinicopathological entity with fewer than 100 cases reported in the literature. Because of its rarity, the optimal management is not well known. Here, we report a case of primary squamous cell carcinoma of the prostate which was treated with definitive concurrent chemo-radiotherapy with excellent outcome along with a brief review of the literature. PMID:28031893

  18. Primary Cutaneous Lymphoma-Associated Pseudoepitheliomatous Hyperplasia Masquerading as Squamous Cell Carcinoma in a Young Adult.

    PubMed

    Ansari, Mahsa; Azmoodeh Ardalan, Farid; Najafi, Masoumeh; Goodarzi, Azadeh; Ghanadan, Alireza

    2015-12-01

    Primary cutaneous anaplastic large cell lymphoma is a T-cell malignancy with atypical CD30 positive lymphocytes. Pseudoepitheliomatous hyperplasia is an uncommon finding in primary cutaneous anaplastic large cell lymphoma, and may mimic squamous cell carcinoma as pseudomalignancy. Careful attention of a pathologist to correct diagnosis of pseudoepitheliomatous hyperplasia and its underlying causes will help physicians to avoid inappropriate management. Here, we present a 22-year-old man referred to our hospital with a solitary nodule persistent on his forearm which was diagnosed as squamous cell carcinoma in the first biopsy. The lesion recurred after two months and histopathologic and immunohistochemistry examination revealed anaplastic large cell lymphoma with florid pseudoepitheliomatous hyperplasia which masquerading as well-differentiated squamous cell carcinoma. Diagnosis of pseudoepitheliomatous hyperplasia must guide the pathologist to search for underlying causes, such as primary cutaneous lymphoma. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and this can result in inappropriate diagnosis and management.

  19. Primary invasive ocular squamous cell carcinoma in a horse.

    PubMed

    Kaps, Simone; Richter, Marianne; Philipp, Martin; Bart, Madeleine; Eule, Corinna; Spiess, Bernhard M

    2005-01-01

    A 12-year-old Haflinger gelding was presented to the veterinary medical teaching hospital of the University of Zurich with a light-pink raised mass on the temporal limbus and conjunctiva of the left eye. Squamous cell carcinoma was confirmed histologically after keratectomy and cryotherapy. Seven months later, a smooth pink, progressively enlarging mass was observed within the cornea of the left eye. Ultrasonographically, the mass was not only infiltrating the corneal stroma but seemed to protrude into the anterior chamber. The globe was surgically removed and submitted for pathology. A histologic diagnosis of corneal ocular squamous cell carcinoma with deep stromal invasion, infiltration of the uveoscleral meshwork and iridocorneal angle and resulting intraocular extension was made. This is the first detailed description of a limbal squamous cell carcinoma with invasion into the cornea and uvea in the horse.

  20. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

    SciTech Connect

    Pradier, Olivier . E-mail: opradier@gwdg.de; Christiansen, Hans; Schmidberger, Heinz; Martin, Alexios; Jaeckel, Martin C.; Steiner, Wolfgang; Ambrosch, Petra; Kahler, Elke; Hess, Clemens F.

    2005-12-01

    Purpose: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Patients and Methods: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO{sub 2} laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Results: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). Conclusion: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.

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

    ClinicalTrials.gov

    2015-03-03

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

  2. Nivolumab: a review in advanced squamous non-small cell lung cancer.

    PubMed

    Keating, Gillian M

    2015-11-01

    Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.

  3. Primary squamous cell carcinoma of the thyroid arising in Hashimoto's thyroiditis in an adolescent.

    PubMed

    Sanchez-Sosa, Sergio; Rios-Luna, Nina Paola; Tamayo, Bricia del Rosario; Simpson, Karen; Albores-Saavedra, Jorge

    2006-01-01

    Squamous cell carcinoma is a rare thyroid neoplasm that has been described exclusively in adults. We report what appears to be the first example of a primary squamous cell carcinoma of the thyroid gland arising in a background of Hashimoto's thyroiditis in an adolescent female. The tumor was well demarcated, confined to the right thyroid lobe, and did not metastasize, although follow up has been limited. The squamous cell carcinoma was well to moderately differentiated, and the stroma contained an abundant inflammatory infiltrate rich in lymphocytes and eosinophils. The lack of goblet cells, extracellular mucin, and extensive stromal sclerosis excluded the diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia. Immunohistochemical staining revealed focal expression of cytokeratin 7 and diffuse labeling with cytokeratin AE1/AE3. The squamous cell carcinoma overexpressed p53 protein and showed increased proliferative activity, as evidenced by the high MIB-1 labeling index. In contrast, the tumor did not show immunoreactivity for thyroglobulin or thyroid transcription factor 1.

  4. Primary squamous cell carcinoma of the thyroid gland: a case report and review.

    PubMed

    Shrestha, Merica; Sridhara, Shankar K; Leo, Leonard J; Coppit, George L; Ehrhardt, Nicole M

    2013-10-01

    Primary squamous cell carcinoma (SCC) of the thyroid gland is a rare malignancy that presents with advanced disease and poor prognosis. A 75-year-old woman with a history of Hashimoto thyroiditis presented with 6 months of dysphagia and stridor. Imaging revealed a thyroid mass invading the larynx. Primary SCC of the thyroid was diagnosed by histopathologic and immunohistochemical evaluation. Total thyroidectomy, total laryngectomy, bilateral modified neck dissection, and adjuvant radiotherapy (RT) were performed. Radiologic follow-up at 21 months demonstrated no disease and total length of survival was 31 months. Despite an aggressive T4aN0M0 tumor, survival in this case was more than double the median survival rate previously reported. Concomitant Hashimoto thyroiditis is rare and histopathologic and immunohistochemical evaluation is imperative for an accurate diagnosis. The case and literature reported here support that a thorough diagnostic workup of primary SCC of the thyroid with aggressive locoregional surgery and adjuvant RT may improve the length of survival. Copyright © 2013 Wiley Periodicals, Inc.

  5. Neoadjuvant chemoradiation for advanced primary vulvar cancer.

    PubMed

    van Doorn, H C; Ansink, A; Verhaar-Langereis, M; Stalpers, L

    2006-07-19

    In advanced stage primary vulvar cancer, treatment is tailored to individual patient needs. Combined treatment modalities have been developed, using chemotherapy, radiotherapy and surgery. To determine whether the combined treatment strategy using concurrent neoadjuvant chemoradiation therapy followed by surgery is effective and safe in vulvar cancer patients with advanced primary disease. Main outcomes of interest were: types of surgical intervention following chemoradiation and survival, recurrence and complication rates. We searched the Cochrane Gynaecological Cancer Review Group Specialised Register. The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (PubMed), EMBASE, CANCERLIT, other databases and reference lists of articles. The latest search was conducted on 12 March 2005. Studies of curative treatment of patients with advanced, primary squamous cell carcinoma of the vulva were included. Treatment included concurrent radiotherapy and chemotherapy, followed by surgery. Twenty-eight abstracts and papers were selected either by the search strategy or by checking the cross references. Randomised controlled trials (RCTs) were not available. Five studies met the inclusion criteria. (Eifel 1995; Landoni 1996; Montana 2000; Moore 1998; Scheistroen 1993). Two authors (HCvD, MV-L) independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. Chemotherapy was given uniformly within each of the five selected studies. However, four different chemoradiation schedules were applied. Radiotherapy dose fractionation techniques, fields and target definitions varied. Skin toxicity was observed in nearly all patients. Wound breakdown, infection, lymphedema, lymphorrhea and lymphoceles were also common. Operability was achieved in 63 to 92% of cases in the four studies using 5FU and CDDP or 5FU and MMC. In contrast, only 20% of

  6. Primary pure squamous cell carcinoma of the duodenum: a case report.

    PubMed

    Graur, Florin; Mois, Emil; Al Hajjar, Nadim

    2014-09-01

    Primary pure squamous cell carcinoma of the duodenum is a very rare type of duodenal neoplasm and is more likely to be presented as a metastatic tumor. The literature offers little information on this subject and includes very few articles and case reports. Laboratory tests, CT and ultrasound examinations, x-rays and immunohistochemical markers assisted us in making this rare diagnosis of primary squamous cell carcinoma of the duodenum in a 47 year old female patient, who presented with weight loss and melena. The 8 cm duodenal tumor with pancreas invasion was resected by a cephalic duodenopancreatectomy. The pathology examination revealed a primary duodenal squamous cell carcinoma moderately differentiated (G2), invasive in the head of the pancreas, with keratinization, stage II B (pT4N0MxL0V0R0). Positive outcome after surgery was highlighted, no recurrence being registered at the 6 month CT scan follow-up.

  7. Primary candidiasis and squamous cell carcinoma of the larynx: report of a case.

    PubMed

    Lee, Dong Hoon; Cho, Hyong Ho

    2013-02-01

    Primary candidiasis is rare and often confused with a pre-cancerous lesion, squamous cell carcinoma, or verrucous carcinoma. We report an extremely rare case of squamous cell carcinoma of the vocal cord following primary candidiasis. A 62-year-old man presented to our department reporting a 1-month history of hoarseness. He underwent laryngeal microscopic surgery for a presumptive diagnosis of glottic carcinoma. Histopathologic examination revealed candidiasis and scattered moderate dysplasia. He was treated with itraconazole for 4 weeks, and followed up without any recurrence of candidiasis. However, the 42-month follow-up examination revealed a focal whitish lesion on the right true vocal cord, and a repeat biopsy of this area revealed squamous cell carcinoma without evidence of candidiasis. The patient was treated with radiotherapy and remains well with no signs of tumor recurrence or candidiasis.

  8. Immunohistochemical Expression of Cathepsin D in Primary and Recurrent Squamous Cell Carcinoma.

    PubMed

    Satelur, Krishnanand P; Kumar, G S

    2017-09-01

    The aim of this study is to analyze and compare the immunohistochemical expression of cathepsin B in primary oral squamous cell carcinoma (OSCC) and recurrent OSCC. A total of 50 cases were studied immunohistochemically for rabbit polyclonal antihuman cathepsin D expression. A total of 10 cases of breast carcinoma were taken as positive controls. Immunohistochemical staining was performed using labeled streptavidin-biotin technique. All the 45 cases of OSCC, both primary and recurrent cases included, showed varying grades of cathepsin D immu-noreactivity. Statistical significance at 5% level was observed in cathepsin D expression between the different grades of well, moderate, and poorly differentiated primary squamous cell carcinomas. In the comparison of cathepsin D staining intensity among primary squamous cell carcinomas with and without recurrence, a statistical significance between the groups was observed when the p-value was at 10%, but the same comparison was not significant when the p-value was at 5%. Cathepsin D expression in primary squamous cell carcinomas with recurrences was very variable as compared with primary squamous cell carcinomas without recurrences. Comparison of cathepsin D expression in primary with their recurrent counterparts showed mostly similar intensity of expression in recurrent carcinomas, thus suggesting its limited usefulness in predicting recurrence. Although cathepsin D might have shown limited usefulness in predicting cancer recurrence, it, however, is a proven valuable tool to detect the aggressiveness of various other tumors, and if corroborated with a larger sample may hold the key to early, more effective, and more specific treatment modalities for cases of oral cancer also.

  9. Primary corneal papilloma and squamous cell carcinoma associated with pigmentary keratitis in four dogs.

    PubMed

    Bernays, M E; Flemming, D; Peiffer, R L

    1999-01-15

    Squamous cell carcinoma (SCC) and squamous papilloma are rarely reported as primary lesions of the cornea in dogs. One case of corneal papilloma and 3 cases of SCC, each arising as a primary central corneal neoplasm rather than spreading from adjacent limbal conjunctiva, were reviewed. The most common cause of SCC in animals is chronic exposure of lightly pigmented epithelium to UV light; however, all dogs in this study had a history of chronic pigmentary keratitis. Three of the 4 dogs were of brachycephalic breeds with naturally proptotic eyes and oversized palpebral fissures that may have exposed the cornea to greater excessive solar radiation. Alternatively, mechanical factors that caused chronic changes in the cornea may have been causative factors for induction of primary dysplastic or neoplastic changes. Primary corneal neoplasia should be considered in the differential diagnosis of corneal masses.

  10. Treatment of advanced squamous cell carcinoma of the lung: a review

    PubMed Central

    Mileham, Kathryn F.; Bonomi, Philip D.; Batus, Marta; Fidler, Mary J.

    2015-01-01

    Lung cancer remains the single deadliest cancer both in the US and worldwide. The great majority of squamous cell carcinoma (SCC) is attributed to cigarette smoking, which fortunately is declining alongside cancer incidence. While we have been at a therapeutic plateau for advanced squamous cell lung cancer patients for several decades, recent observations suggest that we are on the verge of seeing incremental survival improvements for this relatively large group of patients. Current studies have confirmed an expanding role for immunotherapy [including programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition], a potential opportunity for VEGFR inhibition, and even future targets in fibroblast growth factor receptor (FGFR) and PI3K-AKT that collectively should improve survival as well as quality of life for those affected by squamous cell lung cancer over the next decade. PMID:26629421

  11. Chromoendoscopy to detect early synchronous second primary esophageal carcinoma in patients with squamous cell carcinomas of the head and neck?

    PubMed

    Komínek, Pavel; Vítek, Petr; Urban, Ondřej; Zeleník, Karol; Halamka, Magdaléna; Feltl, David; Cvek, Jakub; Matoušek, Petr

    2013-01-01

    Objective. To evaluate the use of flexible esophagoscopy and chromoendoscopy with Lugol's solution in the detection of early esophageal carcinomas (second primary carcinomas) in patients with squamous cell carcinoma of the head and neck (HNSCC). Methods. All patients with newly diagnosed HNSCC underwent office-based Lugol's chromoendoscopy. After flexible esophagoscopy with white light, 3.0% Lugol's iodine solution was sprayed over the entire esophageal mucosa. Areas with less-intense staining (LVLs) were evaluated and biopsies taken. Results. 132 patients with HNSCC were enrolled in this study. The most frequent primary tumors were oropharyngeal (49/132), tumors of the oral cavity (36/132), and larynx (35/132). The majority of subjects (107/132 patients, 81.1%) had advanced HNSCC carcinomas (stages III and IV). Multiple LVLs were discovered in 24 subjects (18.2%) and no LVLs in 108 (81.8%) subjects. Fifty-five LVL biopsy specimens were obtained and assessed. Squamous cell carcinomas were detected in two patients, peptic esophagitis in 11 patients, gastric heterotopic mucosa in two patients, hyperplasia in two patients, and low- and high-grade dysplasia in three patients. Conclusion. Although only two patients with synchronous primary carcinomas were found among the patients, esophagoscopy should be recommended after detection of HNSCC to exclude secondary esophageal carcinoma or dysplasia.

  12. Histological differentiation of primary oral squamous cell carcinomas in an area of betel quid chewing prevalence.

    PubMed

    Fang, Ku-Hao; Kao, Huang-Kai; Cheng, Ming-Hui; Chang, Yu-Liang; Tsang, Ngan-Ming; Huang, Yu-Chen; Lee, Li-Yu; Yu, Jau-Song; Hao, Sheng-Po; Chang, Kai-Ping

    2009-12-01

    This study evaluated associations between the histological differentiation of oral squamous cell carcinoma and additional clinicopathological manifestations, adverse events after treatment, and the outcomes of patients in a region prevalent for betel quid chewing. Case series with chart review. Tertiary referral center. A total of 150 patients with primary oral squamous cell carcinomas who underwent surgery with or without adjuvant therapy were enrolled. Well, moderate, and poorly differentiated oral squamous cell carcinomas were reported in 54 (36%), 84 (56%), and 12 (8%) patients, respectively. There were no significant differences among different histological differentiations in age, sex, tumor, node, metastasis stage, bone invasion, depth of invasion, and history of carcinogen exposure. However, we found significant associations between tumor histological differentiation and nodal metastasis (P < 0.0001), extracapsular spread (P = 0.002), and perineural invasion (P < 0.0001). In the analysis of adverse events for survival during patient follow-up, oral squamous cell carcinomas with poor differentiation had a higher probability of developing neck recurrence (P = 0.001) and distant metastasis (P = 0.019), but not local recurrence or a second primary cancer. For survival analysis, univariate analysis showed that patient age, tumor stage, extracapsular spread, presence of perineural invasion, and tumor differentiation were significant factors. Multivariate analysis further demonstrated that poor differentiation (P = 0.007) was still a statistically significant factor. The current study demonstrates that poorer tumor histological classifications of oral squamous cell carcinoma are significantly associated with positive nodal status, extracapsular spread, perineural invasion of primary tumors, and the probability of developing neck recurrence and distant metastasis after treatment.

  13. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer

    PubMed Central

    Brahmer, Julie; Reckamp, Karen L.; Baas, Paul; Crinò, Lucio; Eberhardt, Wilfried E.E.; Poddubskaya, Elena; Antonia, Scott; Pluzanski, Adam; Vokes, Everett E.; Holgado, Esther; Waterhouse, David; Ready, Neal; Gainor, Justin; Frontera, Osvaldo Arén; Havel, Libor; Steins, Martin; Garassino, Marina C.; Aerts, Joachim G.; Domine, Manuel; Paz-Ares, Luis; Reck, Martin; Baudelet, Christine; Harbison, Christopher T.; Lestini, Brian; Spigel, David R.

    2015-01-01

    Background Patients with advanced squamous-cell non–small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint–inhibitor antibody, as compared with docetaxel in this patient population. Methods We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. Results The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P = 0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group. Conclusions Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.) PMID:26028407

  14. Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

    PubMed

    Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

    2015-01-01

    Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

  15. Unusual Presentation of Primary Squamous Cell Carcinoma of Mandible

    PubMed Central

    Shanmugasundaram, Karpagavalli; Subramanian, Sathasiva; Kumar, Vimal

    2016-01-01

    Carcinoma arising primarily from the jaw is a locally aggressive lesion with poor prognosis. Primary intraosseous carcinoma (PIOC) lesion develops either de novo remnants of odontogenic epithelium, odontogenic cyst/tumor, epithelium remnants, or/and salivary gland residues. We describe very interesting case of primary intraosseous carcinoma of mandible. This extensive lesion was sent for oncological opinion and further management. Due to the uncertainty of diagnostic criteria of PIOC, only few cases of this lesion with a typical presentation have been reported. This article presents a case of primary intraosseous carcinoma with a unique appearance and detailed review stating its clinicopathological correlation. PMID:28078158

  16. Advanced textile applications for primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Jackson, Anthony C.; Barrie, Ronald E.; Shah, Bharat M.; Shukla, Jay G.

    1992-01-01

    Advanced composite primary structural concepts were evaluated for low cost, damage tolerant structures. Development of advanced textile preforms for fuselage structural applications with resin transfer molding and powder epoxy materials are now under development.

  17. Advanced textile applications for primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Jackson, Anthony C.; Barrie, Ronald E.; Shah, Bharat M.; Shukla, Jay G.

    1992-01-01

    Advanced composite primary structural concepts have been evaluated for low cost, damage tolerant structures. Development of advanced textile preforms for fuselage structural applications with resin transfer molding and powder epoxy material is now under development.

  18. Primary Squamous Cell Carcinoma of the Pancreas as a Cause of Biliary Obstruction

    PubMed Central

    Mehta, Jeet; Nehme, Fredy; Salyers, William

    2016-01-01

    Primary squamous cell carcinoma of the pancreas (SCCP) is a rare neoplasm, given a lack of naturally occurring squamous cells within the pancreas, accounting for only 0.2% of all pancreatic cancers. The etiology is unknown. Symptomatology is non-specific and similar to other pancreatic neoplasms. No non-invasive testing can adequately rule in SCCP, and workup should proceed similarly to any pancreatic mass. Tissue sampling is required for diagnosis and guidance of further management, most commonly by endoscopic ultrasound with fine needle aspirate. SCCP is more aggressive than adenocarcinoma of the pancreas with a median survival of three and ten months for those treated with palliative and surgical intent, respectively. The optimal treatment regimen remains unknown, though the uses of radiation therapy, platinum-based regimens, gemcitabine, and 5-FU have all been reported with favorable results. We present a case of primary SCCP in an 81-year-old female who presented with jaundice. PMID:27909644

  19. [Primary squamous cell carcinoma of the ascending colon: report of a case and Korean literature review].

    PubMed

    Cho, Dong Keun; Kim, Sang Hun; Cho, Sung Bum; Lee, Wan Sik; Joo, Young Eun

    2014-08-01

    Primary squamous cell carcinoma of the colon is an extremely rare malignancy. A 48-year-old male visited our hospital for screening colonoscopy. Colonoscopic examination showed a 1 cm sized sessile polyp in the ascending colon. The patient underwent endoscopic mucosal resection (EMR) without any complication. The pathologic findings were compatible with squamous differentiation of tumor cells in inflammatory colonic mucosa. The tumor was confined to the mucosa and the margins of the excised tissue were found to be free of the tumor. There were no other primary sites and no distant metastases in the extensive evaluation using a whole body CT scan and PET-CT. Additional surgical resection was not done. Follow-up colonoscopy performed eight month later showed a whitish scar without evidence of local recurrence and follow-up PET-CT demonstrated no evidence of recurrence. Herein, we report a case of primary squamous cell carcinoma of the ascending colon presenting as a sessile polyp which was removed by EMR.

  20. Phase 1 study of erlotinib plus radiation therapy in patients with advanced cutaneous squamous cell carcinoma.

    PubMed

    Heath, C Hope; Deep, Nicholas L; Nabell, Lisle; Carroll, William R; Desmond, Renee; Clemons, Lisa; Spencer, Sharon; Magnuson, J Scott; Rosenthal, Eben L

    2013-04-01

    To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

    SciTech Connect

    Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle; Carroll, William R.; Desmond, Renee; Clemons, Lisa; Spencer, Sharon; Magnuson, J. Scott; Rosenthal, Eben L.

    2013-04-01

    Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.

  2. Combined radical radiation therapy and chemotherapy for primary squamous cell carcinoma of the anal canal

    SciTech Connect

    Cummings, B.J.; Rider, W.D.; Harwood, A.R.; Keane, T.J.; Thomas, G.M.; Erlichman, C.; Fine, S.

    1982-03-01

    Radical radiation therapy (5000 rads in 20 fractions in 4 weeks) combined with iv mitomycin (10 mg/m2) and 5-FU (1000 mg/m2/24 hours for 4 days) was used to treat 13 patients with locally advanced but operable squamous cell carcinoma of the anal canal. All patients achieved local control and retained anal continence, and none developed metastases. The patients were followed from 4 to 34 months (median, 12). Severe acute gastrointestinal toxic effects were seen in three patients; the same patients had significant thrombocytopenia or leukopenia. Treatment with this combined program may allow conservative management of squamous cell carcinoma of the anal canal and should be considered as an alternative to abdominoperineal resection.

  3. 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.

  4. [Combined therapy of locally advanced squamous epithelial cancers in the area of the head and neck].

    PubMed

    Fountzilas, G; Daniilidis, J; Kalogera-Fountzila, A; Apostolidis, T; Vritsios, A; Tourkantonis, A

    1988-04-01

    In an effort to improve treatment results in locally advanced squamous cell carcinoma of head and neck, we designed a multimodality treatment programme consisting of three cycles of inductive chemotherapy, after 2-3 weeks loco-regional therapy (surgery and/or radiotherapy), two more cycles of adjuvant chemotherapy with the same regimen were given finally. The chemotherapeutic regimen included cis-platinum 100 mg/m2 on day 1, 5-fluorouracil 100 mg/m2 on days 2-6 as a continuous infusion, bleomycin 15 units on days 15, 29; mitomycin-C 4 mg/m2 on day 2 and hydroxyurea 100 mg/m2 on days 22-26. From August 1984 onwards, 37 patients entered in this study. The group included 31 men and 6 women with a medium age of 54 (18-71) and a performance status of 80 (60-90). Primary sites were nasopharynx (13), oropharynx (5), hypopharynx (3), sinus (3), ethmoids (2), tongue (2), floor of the mouth (2), larynx (6) and unknown (1). 25 patients received 3 cycles of induction therapy whereas 22 completed the whole treatment programme. Following induction therapy, 28% of the patients demonstrated histologically confirmed CR, 40% PR and 32% SD, while after the full multimodality therapy 59% demonstrated CR, 36% PR and 5% SD. Follow-up is 9-36 months. Actual survival at 3 years is 80% for those with a CR post loco-regional therapy. Toxicities were leukopenia (40%), thrombocytopenia (20%), anaemia (40%), nausea and vomiting (60%), stomatitis (52%) diarrhoea (16%) and alopecia (79%). There was one death related to chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Thyroid gland invasion in advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Mangussi-Gomes, João; Danelon-Leonhardt, Fernando; Moussalem, Guilherme Figner; Ahumada, Nicolas Galat; Oliveira, Cleydson Lucena; Hojaij, Flávio Carneiro

    Squamous cell carcinoma of the larynx and hypopharynx has the potential to invade the thyroid gland. Despite this risk, the proposition of either partial or total thyroidectomy as part of the surgical treatment of all such cases remains controversial. To evaluate the frequency of invasion of the thyroid gland in patients with advanced laryngeal or hypopharyngeal squamous cell carcinoma submitted to total laryngectomy or pharyngolaryngectomy and thyroidectomy; to determine whether clinic-pathological characteristics can predict glandular involvement. A retrospective case series with chart review, from January 1998 to July 2013, was undertaken in a tertiary care university medical center. An inception cohort of 83 patients with larynx/hypopharynx squamous cell carcinoma was considered. All patients had advanced stage disease (clinically T3-T4) and underwent total laryngectomy or total pharyngolaryngectomy in association with thyroidectomy. Adjuvant therapy was indicated when tumor or neck conditions required. Frequency of thyroid cartilage invasion was calculated; univariate and multivariate analysis of demographic, clinical and pathological characteristics associated with cartilage invasion were performed. The overall frequency of invasion of the thyroid gland was 18.1%. Glandular involvement was associated with invasion of the following structures: anterior commissure (odds ratio=5.13; 95% confidence interval 1.07-24.5), subglottis (odds ratio=12.44; 95% confidence interval 1.55-100.00) and cricoid cartilage (odds ratio=15.95; 95% confidence interval 4.23-60.11). Invasion of the thyroid gland is uncommon in the context of laryngopharyngeal squamous cell carcinoma. Clinical and pathological features such as invasion of the anterior commissure, subglottis and cricoid cartilage are more associated with glandular invasion. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights

  6. HPV Status and second primary tumours in Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    2013-01-01

    Introductions The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCCs) is rising in developed nations. Studies have shown that these virally mediated tumours are epidemiologically, clinically, and biologically different than other head and neck squamous cell carcinomas and traditional concepts of field cancerization may not apply to HPV-related oropharyngeal cancer. Objective The purpose of this study was to evaluate the rate of second primary tumors and the diagnostic yield of field cancerization work up in the upper aerodigestive tract in patients with HPV-related and HPV-unrelated oropharyngeal squamous cell carcinoma. Design Retrospective review. Setting Tertiary cancer care centers in Alberta. Methods Retrospective review of 406 patients diagnosed with OPSCC in Alberta between 2005 and 2009. HPV-status of tumours was determined by tissue microarray using immunohistochemistry staining for p16. Main outcome measures Primary outcome: incidence of upper aerodigestive tract second primary tumours in p16-positive versus p16-negative OPSCC. Secondary outcomes: diagnostic yield of traditional field cancerization work-up in p16-positive versus negative patients. Results The overall rate of SPTs was 7.4% (30/406). The incidence rate of SPTs was significantly lower in p16-positive patients (0.7 per 100 patient-yrs vs. 8.5 in p16-negative, p < 0.0001). Field cancerization work-up for synchronous lesions in the upper aerodigestive tract, including panendoscopy and whole-body PET-CT, had decreased diagnostic yield in p16-positive patients (2.8% vs. 10.2% in HPV-negative patients, p=0.02). Conclusions Patients with HPV-related OPSCC, who are non-smokers have decreased risk of developing second primary tumours in the upper aerodigestive tract and have low yield on field cancerization work-up. This study provides further evidence that virally mediated OPSCC are distinct and may benefit from alternate diagnostic pathways. PMID:23718873

  7. First Reported Case of Primary Intrahepatic Cholangiocarcinoma with Pure Squamous Cell Histology: A Case Report

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Seligman, Barbara; Tuli, Sandeep S.; Heimann, David M.

    2015-01-01

    Patient: Male, 64 Final Diagnosis: Intrahepatic cholangiocarcinoma with pure squamous cell Symptoms: — Medication: — Clinical Procedure: — Specialty: — Objective: Rare disease Background: In the United States, approximately 2500 cases of cholangiocarcinoma occur each year. The average incidence is 1 case/100 000 persons each year. Surgical resection is the mainstay for the treatment of cholangiocarcinoma. The result of surgery depends on location of the tumor, extent of tumor penetration of the bile duct, tumor-free resection margins, and lymph node and distant metastases. There has been an increase in the incidence of intrahepatic cholangiocarcinoma (IHCC) globally over a period of 30 years from 0.32/100 000 to 0.85/100 000 persons each year. Epidemiologically, the incidence of IHCC has been increasing in the U.S. from year 1973 to 2010. Case Report: We are reporting a first case of primary intrahepatic cholangiocarcinoma of pure squamous cell histology. A 64-year-old man presented with right upper-quadrant pain, jaundice, and weight loss. Imaging studies revealed a large hepatobiliary mass, intrahepatic bile duct dilation, normal common duct, and absence of choledocholithiasis. Delayed-contrast magnetic resonance imaging of the abdomen showed peripheral enhancement of the central lesion, which is typical of cholangiocarcinoma in contrast to hepatocellular carcinoma or metastasis. Cancer antigen 19-9 was markedly elevated. Liver function tests were deranged. Endoscopic retrograde cholangiopancreatography showed high degree of left hepatic duct stricture. Brush cytopathology was positive for atypia. The patient underwent exploratory laparotomy for en-bloc resection of the hepatobiliary mass with colon resection, liver resection, and cholecystectomy. Histology revealed keratinizing squamous cell carcinoma. Based on these findings, a definitive diagnosis of well-differentiated squamous cell carcinoma of the intrahepatic bile duct was made. Conclusions

  8. Primary squamous cell carcinoma of the breast with unusual basal-HER2 phenotype.

    PubMed

    Shui, Ruohong; Li, Anqi; Yang, Fei; Zhou, Xiaoyan; Yu, Baohua; Xu, Xiaoli; Yang, Wentao

    2014-01-01

    To report three cases of primary squamous cell carcinoma of the breast with an unusual "basal-HER2" phenotype. Clinical data were analyzed. Morphological features were observed. Immunohistochemical study for ER, PR, HER2, Ki-67, CK 5/6, CK10/13, CK14, EGFR, P63 and FISH detection of HER2 gene amplification were performed. Three patients were all female with 26, 57 and 66 years old. The tumors were 3 cm, 4 cm and 5 cm in size respectively. Morphologically, all three tumors were pure squamous cell carcinoma and entirely composed metaplastic squamous cells. Two tumors were moderately differentiated and one was poorly differentiated. All three patients were positive for P63 or CK10/13. All three tumors exhibited basal-HER2 phenotype: negative for ER and PR, positive for HER2 protein and HER2 gene amplification, and positive for at least two basal markers. SCC with basal-HER2 phenotype is an extremely rare subset of breast carcinoma. Since it may have worse prognosis than typical basal-like SCC, recognization of this unusual SCC in routine work may have obvious clinical significance.

  9. Chemoradiotherapy for Synchronous Multiple Primary Cancers with Esophageal Squamous Cell Carcinoma: a Case-control Study

    PubMed Central

    Li, Qi-Wen; Zhu, Yu-Jia; Zhang, Wen-Wen; Yang, Han; Liang, Yao; Hu, Yong-Hong; Qiu, Bo; Liu, Meng-Zhong; Liu, Hui

    2017-01-01

    Objective: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CRT) in multiple primary cancers (MPC) of the upper digestive tract in esophageal squamous cell carcinoma (ESCC). Methods: In a screening of 1193 consecutive patients diagnosed with ESCC and received radiotherapy, 53 patients presenting synchronous MPC in the upper digestive tract were retrospectively investigated. 53 consecutive patients with esophageal non-multiple primary cancer (NPC), matched by stage, age and sex, served as control. All of the patients received concurrent CRT. The median radiation dose was 60 Gy. Chemotherapy regimens were based on platinum and/or 5-fluorouracil. Clinical outcomes and treatment toxicities were compared. Results: Clinic-pathologic characteristics were well balanced between groups. MPC mostly located in esophagus (43, 81.8%), followed by hypopharynx (8, 15.1%) and stomach (2, 3.8%). In MPC and NPC patients, 94.3% and 96.2% completed the intended treatment. The immediate response rate was 73.6% vs 75.5%, with complete response rate of 11.3% vs 24.5% and partial response rate of 62.3% vs 51.0%. Two-year overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS) and distant progression-free survival (DPFS) were 52.2% vs 68.9% (p=0.026), 32.9% vs 54.0% (p=0.032), 60.8% vs 87.8% (p=0.002) and 64.0% vs 70.8% (p=0.22), respectively. Acute grade 3-4 toxicities were observed in 64.2% vs 54.7%, significantly higher in radiation esophagitis (49.1% vs 28.3%, p<0.001), and mucositis (11.3% vs 00p=0.027). Conclusions: Compared with matched NPC, ESCC accompanied with synchronous MPC was related to significantly impaired survival, elevated risk of locoregional disease progression and higher incidence of severe esophagitis and mucositis, following concurrent chemoradiotherapy. Future study on reasons for decreased efficacy of chemoradiotherapy will help to optimize treatment. Advanced radiation techniques may play a role

  10. Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity

    PubMed Central

    Saxena, Chitrapriya; Aggarwal, Pooja; Wadhwan, Vijay; Bansal, Vishal

    2015-01-01

    Squamous cell carcinoma (SCC) arising from the wall of an odontogenic cyst (also known as primary intraosseous carcinoma) is a rare tumor which occurs only in jaw bones. This tumor was first described by Loos in 1913 as a central epidermoid carcinoma of the jaw. Primary intraosseous carcinomas (PIOC) may theoretically arise from the lining of an odontogenic cyst or de novo from presumed odontogenic cell rests. According to the new histological classification of tumors of the World Health Organization, odontogenic keratocyst is nowadays considered a specific odontogenic tumor and the PIOC derived from it is considered as a specific entity which is different from other PIOCs derived from the odontogenic cysts. The following report describes a case of such extremely rare entity that is primary intraosseous SCC of the mandible derived from an OKC in a 60-year-old male patient with brief review of literature. PMID:26980976

  11. Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity.

    PubMed

    Saxena, Chitrapriya; Aggarwal, Pooja; Wadhwan, Vijay; Bansal, Vishal

    2015-01-01

    Squamous cell carcinoma (SCC) arising from the wall of an odontogenic cyst (also known as primary intraosseous carcinoma) is a rare tumor which occurs only in jaw bones. This tumor was first described by Loos in 1913 as a central epidermoid carcinoma of the jaw. Primary intraosseous carcinomas (PIOC) may theoretically arise from the lining of an odontogenic cyst or de novo from presumed odontogenic cell rests. According to the new histological classification of tumors of the World Health Organization, odontogenic keratocyst is nowadays considered a specific odontogenic tumor and the PIOC derived from it is considered as a specific entity which is different from other PIOCs derived from the odontogenic cysts. The following report describes a case of such extremely rare entity that is primary intraosseous SCC of the mandible derived from an OKC in a 60-year-old male patient with brief review of literature.

  12. Recurrence of primary squamous cell carcinoma of the ileum diagnosed by elevation of serum SCC: report of a case.

    PubMed

    Mino, Kazuhiro; Kamii, Naoki; Kawanishi, Norio; Okada, Tadao; Todo, Satoru

    2012-06-01

    Primary squamous cell carcinoma of the intestine is extremely rare. This report describes a patient with primary squamous cell carcinoma of the small intestine. A 72-year-old Japanese woman was referred to our hospital because of a diagnosis of intestinal obstruction. She underwent laparotomy owing to the diagnosis of mechanical intestinal obstruction due to a pelvic mass after conservative treatment. The affected ileum was resected, and histopathological examination revealed proliferation of differentiated squamous cell carcinoma at the submucosal area with no adenocarcinoma component. At the 4th month after the operation, the level of serum squamous cell carcinoma (SCC) antigen was elevated. At 6 months after the operation, the serum SCC value was further elevated, and enhanced CT revealed two new pelvic tumors with enhancement at the mesentery and free space. A second laparotomy was performed 8 months after the operation. Histopathological examination showed differentiated squamous cell carcinoma as in the first operation. The level of serum SCC decreased at the 28th postoperative day. Chemotherapy including carboplatin and paclitaxel was performed as an adjuvant regimen. The patient has experienced no recurrence of squamous cell carcinoma for 55 months.

  13. Efficacy and safety of nivolumab in Japanese patients with advanced or recurrent squamous non-small cell lung cancer.

    PubMed

    Hida, Toyoaki; Nishio, Makoto; Nogami, Naoyuki; Ohe, Yuichiro; Nokihara, Hiroshi; Sakai, Hiroshi; Satouchi, Miyako; Nakagawa, Kazuhiko; Takenoyama, Mitsuhiro; Isobe, Hiroshi; Fujita, Shiro; Tanaka, Hiroshi; Minato, Koichi; Takahashi, Toshiaki; Maemondo, Makoto; Takeda, Koji; Saka, Hideo; Goto, Koichi; Atagi, Shinji; Hirashima, Tomonori; Sumiyoshi, Naoki; Tamura, Tomohide

    2017-03-07

    Limited treatment options are available for stage IIIB/IV non-small cell lung cancer (NSCLC). Nivolumab, a programmed cell death-1 immune checkpoint inhibitor antibody, has been shown to be effective for the treatment of NSCLC. This study investigated the effectiveness and safety of nivolumab in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum-containing chemotherapy. In this multicenter phase II study, patients were treated with nivolumab (3mg/kg, intravenously) every 2 weeks until progressive disease or unacceptable toxicity was seen. The primary endpoint was overall response rate (ORR) assessed by independent radiology review committee (IRC) and secondary endpoints included a study site-assessed ORR, overall survival (OS), progression-free survival (PFS), duration of response, time to response, best overall response (BOR), and safety. The study included 35 patients from 17 sites in Japan. Patients had IRC-assessed ORR of 25.7% (95% CI 14.2, 42.1) and the study site-assessed ORR was 20.0% (95% CI 10.0, 35.9). The median OS, median time to response and median PFS were 16.3 (95% CI 12.4-25.4), 2.7 (range 1.2-5.5) and 4.2 (95% CI 1.4-7.1) months, respectively. The IRC-assessed BOR was partial response, stable disease, and progressive disease for 25.7%, 28.6%, and 45.7% of patients, respectively. Treatment-related adverse events were reported in 24 patients (68.6%), most of which resolved with appropriate treatment including steroid therapy or ‎discontinuation of nivolumab. Nivolumab was effective and well tolerated in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum-containing chemotherapy. This article is protected by copyright. All rights reserved.

  14. Robotic surgery for primary head and neck squamous cell carcinoma of unknown site.

    PubMed

    Patel, Sapna A; Magnuson, J Scott; Holsinger, F Christopher; Karni, Ron J; Richmon, Jeremy D; Gross, Neil D; Bhrany, Amit D; Ferrell, Jay K; Ford, Samuel E; Kennedy, Aimee A; Méndez, Eduardo

    2013-11-01

    Identification of the primary site in head and neck squamous cell carcinoma (HNSCC) is crucial because it improves the patient's prognosis and minimizes morbidity from treatment. To determine the efficacy of transoral robotic surgery (TORS) in identifying unknown primary sites of head and neck squamous cell carcinoma. Retrospective, multi-institutional case series from January 1, 2010, to February 28, 2013, in which data were pooled from the following 6 institutions: University of Washington Medical Center, The University of Texas MD Anderson Cancer Center, University of Alabama-Birmingham Hospital, The University of Texas Medical School at Houston, Johns Hopkins Hospital, and Oregon Health Sciences University. All patients diagnosed as having HNSCC of an unknown primary site who underwent TORS to identify the primary site were included in the study. We excluded those with recurrent disease, a history of radiation therapy to the head and neck, or evidence of a primary tumor site based on previous biopsy results. Identification of the primary tumor site. Forty-seven patients were eligible for the study. The tumor site was identified by TORS in 34 of 47 patients (72.3%). The primary site was located in the base of tongue for 20 patients (58.8%) and the palatine tonsil for 13 patients (38.2%), with 1 patient having a primary site in both the base of tongue and the palatine tonsil. Suspicious physical examination findings were present in 23 of 47 patients (48.9%), with positive and negative predictive values of 56.5% and 25.0%, respectively. Of those who underwent any imaging, 16 patients had suspicious findings, with positive and negative predictive values of 50.0% and 16.7%, respectively. In 18 of 47 patients (38.3%), both preoperative radiographic and physical examination failed to suggest a primary site. Of these 18 patients, 13 (72.2%) were identified after undergoing TORS. We demonstrate that TORS is a useful approach to identify and treat the primary site in

  15. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer.

    PubMed

    Minami, Seigo; Kijima, Takashi

    2015-01-01

    Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR) mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be a pivotal drug when a combination maintenance therapy is used in practice. For future maintenance therapy, we need to explore reliable predictive selection or exclusion markers that can predict who will really benefit from maintenance therapy.

  16. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer

    PubMed Central

    Minami, Seigo; Kijima, Takashi

    2015-01-01

    Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR) mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be a pivotal drug when a combination maintenance therapy is used in practice. For future maintenance therapy, we need to explore reliable predictive selection or exclusion markers that can predict who will really benefit from maintenance therapy

  17. Salvage surgery for locoregional recurrences of advanced pharyngolaryngeal squamous cell carcinoma after organ preservation failure.

    PubMed

    López Delgado, I; Riestra Ayora, J; Arenas Brítez, O; García López, I; Martínez Guirado, T; Scola Yurrita, B

    2014-12-01

    Organ preservation treatment for advanced head and neck squamous cell carcinoma is associated with poor outcomes due to locoregional recurrences. Salvage surgery is the main therapeutic option for some of these patients. The aim of this study was to analyse the results of salvage surgery for advanced pharyngolaryngeal squamous cell carcinoma previously treated with radiochemotherapy. We performed a retrospective study on 38 patients (36 men, 2 women). The median age at diagnosis was 60 years with a mean follow-up period of 49.8 months. Recurrences were diagnosed at a mean of 395 days after finalising organ preservation treatment. Patients went under different salvage surgeries, including 22 total laryngectomies, 6 partial laryngectomies (3 transoral laser surgeries and 3 opened surgeries), 8 functional neck dissections and 2 tongue base surgeries. Nineteen patients had no postoperative complications after a mean hospital stay of 2 weeks. However, 5 patients died of significant recurrent bleedings. There were 4 salivary fistulas that responded to conservative management, while 7 patients had important pharyngostomas that required reconstruction with either regional or free flaps. The mean hospital stay was of 61.60 days for all patients. Five-year overall survival from diagnosis, overall survival after salvage surgery and survival after salvage surgery were 44.20, 37.90 and 45.70%, respectively. In summary, we conclude that salvage surgery is an optimal treatment for pharyngolaryngeal and regional recurrences and provides improvement in locoregional control and survival, despite the severe complications.

  18. Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer

    PubMed Central

    Kim, Young Saing; Ahn, Hee Kyung; Cho, Eun Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer. Methods For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis. Results The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001). Conclusions CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer. PMID:27621848

  19. Primary Pure Keratinising Squamous Cell Carcinoma: A Rare Malignancy with Aggressive Behaviour

    PubMed Central

    Pant, Leela; Garg, Malini; Singh, Garima; Singh, Sompal

    2016-01-01

    Primary well differentiated keratinising Squamous Cell Carcinoma (SCC) is a rare gall bladder malignancy accounting for 3.3% of all gall bladder carcinomas. Here we present a case of a 70-year-old female with complaints of dyspepsia and right upper quadrant pain for 3 months. Ultrasonography showed gall stones along with thickened and irregular gall bladder wall. Grossly an exophytic growth was noted involving large part of the body of gall bladder. Histological features were of well differentiated SCC with extensive keratinisation involving full thickness of the wall. No glandular component was seen. Metastasis from other primary was ruled out after thorough work-up. SCC of gall bladder has an infiltrative growth pattern and behaves aggressively. Early diagnosis plays the most important role in increasing the survival. PMID:27790451

  20. High-resolution CT findings of primary lung cancer with cavitation: a comparison between adenocarcinoma and squamous cell carcinoma.

    PubMed

    Kunihiro, Y; Kobayashi, T; Tanaka, N; Matsumoto, T; Okada, M; Kamiya, M; Ueda, K; Kawano, H; Matsunaga, N

    2016-11-01

    To evaluate the high-resolution computed tomography (CT) findings of primary lung cancer with cavitation and compare the findings in adenocarcinoma and squamous cell carcinoma. The high-resolution CT findings of tumours with cavitation were retrospectively evaluated in 60 patients. Forty-seven of the lesions were diagnosed as adenocarcinomas; 13 were diagnosed as squamous cell carcinomas. The diameters of the tumour and cavity, the maximum thickness of the cavity wall, shape of the cavity wall, the number of cavities, and the presence of ground-glass opacity, bronchial obstruction, intratumoural bronchiectasis, emphysema, and honeycombing were evaluated. The mechanisms of cavity formation were examined according to the pathological features. The maximum thickness of the cavity wall was significantly greater in squamous cell carcinomas than in adenocarcinomas (p=0.002). Ground-glass opacity and intratumoural bronchiectasis were significantly more common in adenocarcinomas than in squamous cell carcinomas (p<0.001 and p=0.040, respectively). Regarding the pathological findings, intratumoural bronchiectasis with or without alveolar wall destruction contributed to a significant difference between adenocarcinoma and squamous cell carcinoma (p<0.001; odds ratio [OR], 20.35; 95% confidence interval [CI], 3.87-107.10). The cavity wall tends to be thicker in squamous cell carcinomas than in adenocarcinomas. The presence of ground-glass opacity and intratumoural bronchiectasis is strongly suggestive of adenocarcinoma. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  1. Complete Remission of Locally Advanced Penile Squamous Cell Carcinoma after Multimodality Treatment

    PubMed Central

    Meng, Yifan; Bernie, Helen Levey; Weng, Tzu-Hua; Ling, Dean-An; Messing, Edward M.; Guancial, Elizabeth

    2016-01-01

    Treatment of locally advanced penile squamous cell carcinoma (pSCC) remains highly controversial secondary to disease rarity and lack of prospective randomized controlled trials. The current mainstays of care are multi-modality treatment with neoadjuvant chemotherapy and surgery. However, clinicians often have difficulty making recommendations for patients unable to tolerate chemotherapy or surgery due to scarcity of data to guide clinical decision-making. We report two cases of locally advanced pSCC that achieved complete remission after treatment with cisplatin-based neoadjuvant chemotherapy and surgery in one case, and concurrent cisplatin chemoradiation in a second, supporting the use of chemotherapy as part of first-line multimodal therapy. We also discuss additional treatment options for patients unable to tolerate traditional chemotherapy regimens. PMID:28191294

  2. Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Ko, Christine; Citrin, Deborah

    2008-01-01

    Background Squamous cell carcinomas of the head and neck (SCCHN) affect approximately 35,000 people in the United States yearly. Although survival has improved with advances in therapy, patients with advanced stages of SCCHN continue to have a poor prognosis. An understanding of rationale for treatment selection, newer developments in therapy, and treatment toxicity is critical. Methods Standard methods of treating locally advanced SCCHN are reviewed. Advances in medical and radiotherapeutic management are discussed and the toxicities of therapy are described. Results Post-operative chemoradiation is used in patients with high risk characteristics. Induction chemotherapy and altered fractionation radiation treatment have been evaluated as alternatives to definitive chemo-radiotherapy. Targeted agents such as cetuximab may prove to increase survival with minimal increase in toxicity profile. Technological improvements such as the use of intensity modulated radiation treatment (IMRT) have proven to decrease some debilitating side effects from radiation treatment. Conclusions Locally advanced SCCHN continues to present a therapeutic challenge. Survival, local control, and quality of life are all goals of treatment. The optimal method of treating locally advanced SCCHN is the subject of ongoing research. Long term side effects can be minimized with the use of newer technologies and with careful treatment planning. PMID:19036056

  3. Oral squamous cell carcinoma among Yemenis: Onset in young age and presentation at advanced stage

    PubMed Central

    Al-Mohaya, Maha; Abdulhuq, Mahmoud; Al-Mandili, Ahmad; Al-Anazi, Yousef

    2012-01-01

    Objectives: Oral cancer represents a health burden worldwide. Up to 90% of oral cancer cases are squamous cell carcinomas (SCC). The data on oral SCC in Yemen are lacking. The objective of this study therefore was to describe and analyze the demographic, clinical and histological characteristics of Yemeni patients with oral SCC. Study Design: In this cross-sectional study, two sets of retrospective data for Yemeni cancer patients were obtained officially by two different registries. Patients with oral SCC were included. Their ages were dichotomized using 40 and 45 years alternately as individual cut-points for young and old patients. The patients` demographic, clinical and histological characteristics were statistically analyzed. Results: There were 457 Yemenis with oral SCC; 253 patients (55.4%) were men. The overall mean age was 58.15±14.11 years. The tongue was the most affected oral sub-site accounting for 53% of the reported cases. The well and moderately differentiated oral SCC accounted for 55.5% and 25.6% of the total cases respectively. Noteworthy, 62 patients (14%) were affected by the age of ?40; this increased to 105 patients (23%) aged ?45 years. Additionally, a high proportion of oral SCC patients (62%, 283) were diagnosed at advanced tumor stages (regional extension or metastasized). The distributions of histological grades and tumor stages in young and old patients were significantly different (P=0.006 and 0.026 respectively). Conclusion: The relative frequency of oral SCC among Yemeni young people is high. Unfortunately, most of oral SCC patients in Yemen were diagnosed at advanced stage. Key words:Oral squamous cell carcinoma, Yemen, young patients, advanced stage. PMID:24558559

  4. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva.

    PubMed

    Gaudineau, A; Weitbruch, D; Quetin, P; Heymann, S; Petit, T; Volkmar, P; Bodin, F; Velten, M; Rodier, J F

    2012-10-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6-4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6-4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0-6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva.

  5. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva

    PubMed Central

    GAUDINEAU, A.; WEITBRUCH, D.; QUETIN, P.; HEYMANN, S.; PETIT, T.; VOLKMAR, P.; BODIN, F.; VELTEN, M.; RODIER, J.F.

    2012-01-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6–4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6–4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0–6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva. PMID:23205089

  6. Transoral laser microsurgery for locally advanced (T3-T4a) supraglottic squamous cell carcinoma: Sixteen years of experience.

    PubMed

    Vilaseca, Isabel; Blanch, José Luis; Berenguer, Joan; Grau, Juan José; Verger, Eugenia; Muxí, África; Bernal-Sprekelsen, Manuel

    2016-07-01

    Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function-preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy-free survival with preserved function was 74.5%. TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1050-1057, 2016. © 2016 Wiley Periodicals, Inc.

  7. Primary squamous cell carcinoma of the pancreas: a report of two cases and review of the literature.

    PubMed

    Ben Kridis, Wala; Khanfir, Afef; Toumi, Nabil; Ben Amar, Mohamed; Boudawara, Tahia; Frikha, Mounir

    2015-01-01

    Primary squamous cell carcinoma (SCC) of the pancreas is extremely rare. We herein report two such cases. Aside from various morphological characteristics, the clinical presentation of pancreatic SCC is the same as that of adenocarcinoma. The treatment is controversial, and the prognosis is poor.

  8. Isolation and characterization of cancer stem cells from primary head and neck squamous cell carcinoma tumors

    PubMed Central

    Kim, Hong S.; Pearson, Alexander T.; Nör, Jacques E.

    2017-01-01

    Summary Drug resistance remains a significant problem in the treatment of patients with head and neck squamous cell carcinoma (HNSCC). Recent reports showed that a sub-population of highly tumorigenic cells (cancer stem cells) is uniquely resistant to chemotherapy, and suggesting that these cells play an important role in the relapse of HNSCC. The development of methods for the isolation and culture of cancer stem cells is a key step to enable studies exploring the mechanisms underlying the role of these cells in chemoresistance. Here, we describe a method to isolate cancer stem cells from primary head and neck tumors and for the generation of orospheres, i.e. the culture of these cells in suspension in ultra-low attachment plates. PMID:26910078

  9. Combination chemotherapy for advanced squamous cell carcinoma of the head and neck.

    PubMed

    Coker, D D; Elias, E G; Chretien, P B; Gray, W C; Coleman, J J; Zentai, T A; Didolkar, M S; Morris, D M; Viravathana, T; Hebel, J R

    1981-01-01

    Fifty-one patients (32 previously untreated, 19 previously treated) with advanced squamous cell carcinoma of the head and neck received a single course of combination chemotherapy consisting of high dose cis-platinum (DDP), bleomycin (Bleo), +/- high dose methotrexate (MTX). Thirty-three (65%) patients responded to therapy; 5 (10%) of these patients had a complete response. Previously untreated patients and those who received the three drugs (DDP, Bleo and MTX) had the highest response rates. The duration of response was 8 to 12 weeks. Seven (15%) patients showed a two-year survival rate. All nonresponders were dead of disease within two years. Three (56%) of the five complete-response patients and 4 (21%) of the partial-response patients survived for two years. The role of preoperative chemotherapy in head and neck cancer is yet to be conclusively defined.

  10. Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

    PubMed

    De Paz, Dante; Kao, Huang-Kai; Huang, Yenlin; Chang, Kai-Ping

    2017-08-10

    Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients. In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy. Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

  11. CEP55 overexpression predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma

    PubMed Central

    Jiang, Wenpeng; Wang, Zhou; Jia, Yang

    2017-01-01

    Development of esophageal squamous cell carcinoma (ESCC) involves alterations in multiple genes with corresponding proteins. Recent studies have demonstrated that centrosomal protein 55 (CEP55) shares certain features with oncogenes, and CEP55 overexpression is associated with the development and progression of malignant tumors. The present study aimed to analyze, for the first time, whether CEP55 expression is related to clinicopothalogic features in the esophageal squamous cell carcinoma (ESCC), as well as patient survival. A total of 110 patients with mid-thoracic ESCC who suffered from Ivor-Lewis were enrolled. The CEP55 expression profile of these patients in tumour tissues and corresponding healthy esophageal mucosa (CHEM) was detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction analyses. Correlations between CEP55 expression and clinicopathological factors were analyzed using χ2 test. The log-rank test was employed to calculate survival rate. A Cox regression multivariate analysis was performed to determine independent prognostic factors. The results demonstrated that CEP55 expression in ESCC was significantly higher than that of CHEM (P<0.001). Overexpression of CEP55 was significantly associated with differentiation degree (P=0.022), T stage (P=0.019), lymph node metastasis (P=0.033), clinicopathological staging (P=0.002) and tumor recurrence (P=0.021) in locally advanced ESCC patients. In addition, CEP55 overexpression was significantly associated with reduced overall survival of patients after surgery (P=0.012). The 5-year survival rate of patients without CEP55 overexpression was significantly higher than that of patients with CEP55 overexpression (P=0.012). Therefore, these findings suggest that CEP55 overexpression correlates with poor prognosis in locally advanced ESCC patients. PMID:28123547

  12. Primary femininity: clinical advances and theoretical ambiguities.

    PubMed

    Kulish, N

    2000-01-01

    This paper examines the use of the term "primary femininity" in current psychoanalytic thinking. The concept of primary femininity arose in reaction to early theories about female sexuality and development; based on a model of male development, these presented problems when applied to females. The author attempts to demonstrate the clinical advances that have resulted from the idea of primary femininity. At the same time she argues that the idea has been used to carry widely differing meanings, and has reflected many writers' differing frames of reference, which range from gender identity through biological traits, object relations, genital anxieties, and bisexuality. Like the terms it originally was intended to replace or augment, it has come to be used reductionistically or loosely. The author warns against its misuse and argues that primary femininity is not a unitary concept, but rather encompasses a related group of ideas about the female body and mind.

  13. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    PubMed

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid.

  14. Primary Esophageal Intramural Squamous Cell Carcinoma Masquerading as a Submucosal Tumor: A Rare Presentation of a Common Disease

    PubMed Central

    Sonthalia, Nikhil; Jain, Samit S.; Surude, Ravindra G.; Pawar, Vinay B.; Udgirkar, Suhas; Rathi, Pravin M.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is the commonest primary malignant esophageal tumor, which typically presents as endoscopically visible surface mucosal ulcerations, irregularities, or polyploidal masses. We here report a rare case of primary ESCC with completely intramural growth under a normal looking intact nondysplastic surface squamous epithelium disguising as a submucosal tumor. Upper gastrointestinal endoscopy-guided mucosal biopsy was negative for malignancy. Endoscopic ultrasound (EUS) revealed a heteroechoic solid mass originating from the muscularis propria of the distal esophagus. Cytological study of EUS-guided fine needle aspiration from the mass was suggestive of squamous cell carcinoma, which was confirmed on immunohistochemistry. There was no evidence of metastatic origin of this tumor or continuous cancer involvement from the surrounding structures, including the head, neck, and lungs on bronchoscopy, computed tomography scan, and positron emission tomography scan. Exclusive intramural squamous cell carcinoma with normal overlying mucosa is an exceedingly rare presentation of primary ESCC with only four cases reported in the literature so far. A high index of suspicion is required by the gastroenterologists and pathologists in diagnosing these cases as these tumors closely mimic the mesenchymal submucosal tumors such as lipoma, leiomyoma, and gastrointestinal stromal tumors. EUS is an indispensable tool in making a preoperative diagnosis and therapeutic decision making. PMID:27721663

  15. Primary tumor induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma.

    PubMed

    Ishii, Hiroki; Chikamatsu, Kazuaki; Sakakura, Koichi; Miyata, Masanori; Furuya, Nobuhiko; Masuyama, Keisuke

    2010-05-01

    The main factor that affects the prognosis of patients with oral squamous cell carcinoma (OSCC) is regional lymph node metastases, which usually spreads first to the sentinel lymph nodes (SLNs). Recent studies have demonstrated that tumor cells in several malignancies can induce lymphangiogenesis in SLNs before metastasizing. To elucidate the mechanisms of tumor dissemination of OSCC, we investigated whether primary tumors induce lymphangiogenesis within SLNs in patients with OSCC. The mRNA expression of lymphatic-specific markers, including VEGFR-3, Prox-1, and LYVE-1 in 23 metastasis-negative SLNs obtained from 10 patients with OSCC, was investigated using a quantitative real-time RT-PCR assay, and compared with control lymph nodes from patients with non-cancerous diseases. In addition, VEGF-C and VEGF-D expressions of the primary tumor were examined by immunohistochemistry. In SLNs, there were highly significant correlations between the three lymphatic markers examined. Interestingly, the level of LYVE-1 expression in SLNs, despite the absence of metastasis, was significantly higher than in control lymph nodes. Moreover, SLNs from patients with VEGF-C-positive tumor showed a significantly higher expression of VEGFR-3 than those from patients with VEGF-C-negative tumor. Our findings suggest that in OSCC, the primary tumor actively induces lymphangiogenesis in SLNs prior to the onset of metastases, and where tumor-derived VEGF-C plays an important role.

  16. Gene expression profiling allows distinction between primary and metastatic squamous cell carcinomas in the lung.

    PubMed

    Talbot, Simon G; Estilo, Cherry; Maghami, Ellie; Sarkaria, Inderpal S; Pham, Duy Khanh; O-charoenrat, Pornchai; Socci, Nicholas D; Ngai, Ivan; Carlson, Diane; Ghossein, Ronald; Viale, Agnes; Park, Bernard J; Rusch, Valerie W; Singh, Bhuvanesh

    2005-04-15

    Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large "test" set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to

  17. Deletion and methylation of the tumour suppressor gene p16/CDKN2 in primary head and neck squamous cell carcinoma.

    PubMed Central

    González, M V; Pello, M F; López-Larrea, C; Suárez, C; Menéndez, M J; Coto, E

    1997-01-01

    AIMS: To study the homozygous deletion and methylation status of the 5' CpG island of the p16 and p15 genes (9p21) in a set of primary advanced head and neck squamous cell carcinomas (SCC) and to test whether inactivation of these genes by these mechanisms contributes to head and neck SCC development. METHODS: DNA was extracted from fresh tumours. Homozygous deletion was determined by the polymerase chain reaction (PCR) followed by hybridisation with the corresponding probe, radioactively labelled by the random priming method. Methylation status of the CpG island of the 5' region of these genes was assessed by digestion with the appropriate restriction enzymes followed by PCR and subsequent hybridisation with the corresponding probe. The presence of point mutations was determined by PCR-SSCP (single strand conformation polymorphism). RESULTS: The p16 and p15 genes were homozygously deleted in 20% and 10% of the tumours, respectively. No point mutations were found at p16 and p15. The 5' CpG island at the p16 gene was methylated in 20% of the cases. CONCLUSIONS: The tumour suppressor gene p16 is inactivated through homozygous deletion or methylation in a significant proportion of cases of head and neck SCC. Images PMID:9378820

  18. Determining the potential of desmoglein 3 as a sensitive and specific immunohistochemical marker for the detection of micrometastasis in patients with primary oral squamous cell carcinoma

    PubMed Central

    Spadigam, Anita; Dhupar, Anita

    2016-01-01

    Aim of the study Despite advances in surgical and radiotherapy techniques, the presence of lymph node metastasis drastically decreases the survival rate of patients with primary oral squamous cell carcinoma (OSCC). Thus the accurate pathological staging of the neck is critical. Desmoglein 3 (DSG3), a desmosomal cadherin protein is said to be highly expressed in head and neck squamous cell carcinoma (HNSCC) and in metastatic cervical lymph nodes, but absent in non-invaded nodes. With an aim to improve the sensitivity of tumour cell detection, we investigated the potential of DSG3 as an immunohistochemical marker for the detection of occult lymph node metastasis in patients with primary OSCC. Material and methods Forty-seven lymph node specimens from 10 patients who underwent neck dissection for primary OSCC were immunostained with DSG3. Results The DSG3 positivity was noted in the six positive lymph nodes. However, when using DSG3 as an immunohistochemical marker, no additional micrometastatic deposits were evident in the histologically negative nodes. Interestingly, tumour marker DSG3-positive macrophages could be identified within the subcapsular sinuses, medullary sinuses, and the interfollicular areas. Conclusions Our findings suggest that although DSG3 is overexpressed in HNSCC, it is not specific and may not prove to be a potent immunohistochemical marker to detect micrometastasis. The role of tumour marker-positive macrophages within the lymph nodes needs to be investigated further.

  19. Relation between the level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Xing, Yan; Zhang, Jianjun; Lin, Heather; Gold, Kathryn A; Sturgis, Erich M; Garden, Adam S; Lee, J Jack; William, William N

    2016-02-15

    The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. This study investigated the impact of the level of lymph node metastasis (LNM) on survival. The Surveillance, Epidemiology, and End Results registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. A multivariate Cox proportional hazards model was used to evaluate whether the level of LNM was an independent prognostic factor. Site-specific recursive-partitioning analysis was performed to classify patients into different risk groups. In all, 14,499 patients, including OC (n = 2463), OP (n = 8567), LAR (n = 2332), and HP patients (n = 1137), were analyzed. Both the American Joint Committee on Cancer (AJCC) N classification and the level of LNM showed significant effects on overall survival (OS) in patients with OC, OP, or LAR HNSCC but not in patients with HP HNSCC. In patients with N2 disease, the AJCC subclassification (N2a, N2b, or N2c) was significantly associated with the OS of patients with OP and LAR HNSCC but not with the OS of patients with OC or HP HNSCC, whereas the level of LNM (primary, secondary, or tertiary) was significantly associated with the OS of patients with OC, OP, and LAR HNSCC but not HP HNSCC. With recursive-partitioning analysis, a simple, primary site-specific prognostic tool integrating the AJCC T and N classifications and the level of LNM was designed, and it could be easily used by health care providers in clinic. The level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classifications in patients with locally advanced HNSCC. © 2015 American Cancer Society.

  20. Relationship between level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Xing, Yan; Zhang, Jianjun; Lin, Heather; Gold, Kathryn A.; Sturgis, Erich M.; Garden, Adam S.; Lee, J. Jack; William, William N.

    2015-01-01

    Background The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. We sought to investigate the impact of level of lymph node metastasis (LNM) on survival Methods The Surveillance, Epidemiology, and End Results (SEER) registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. Multivariate Cox proportional hazards model was used to evaluate whether level of LNM is an independent prognostic factor. Site-specific recursive-partitioning analysis (RPA) was performed to classify patients into different risk groups. Results Totally, 14,499 patients including OC (N=2,463), OP (N=8,567), LAR (N=2,332) and HP (N=1,137) were analyzed. Both AJCC N classification and level of LNM showed significant effects on overall survival (OS) in patients with OC, OP or LAR, but not in HP. In patients with N2 disease, AJCC subclassification (N2a, N2b, N2c) was significantly associated with OS of patients with OP and LAR, but not OC or HP, while level of LNM (primary, secondary, and tertiary) was significantly associated with OS in patients with OC, OP and LAR, but not HP. Using RPA, we designed a simple, primary site-specific prognostic tool integrating AJCC T classification, N classification, and level of LNM that can be easily utilized by health care providers in clinic. Conclusions Level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classification in patients with locally advanced HNSCC. PMID:26554754

  1. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    PubMed

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

  2. Integrated Analysis of Long Noncoding RNA and mRNA Expression Profile in Advanced Laryngeal Squamous Cell Carcinoma.

    PubMed

    Feng, Ling; Wang, Ru; Lian, Meng; Ma, Hongzhi; He, Ning; Liu, Honggang; Wang, Haizhou; Fang, Jugao

    2016-01-01

    Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the expression pattern and function of lncRNAs in laryngeal squamous cell carcinoma (LSCC) are still unclear. To investigate the aberrantly expressed lncRNAs and mRNAs in advanced LSCC, we screened lncRNA and mRNA expression profiles in 9 pairs of primary Stage IVA LSCC tissues and adjacent non-neoplastic tissues by lncRNA and mRNA integrated microarrays. Gene Ontology and pathway analysis were performed to find out the significant function and pathway of the differentially expressed mRNAs, gene-gene functional interaction network and ceRNA network were constructed to select core mRNAs, and lncRNA-mRNA expression correlation network was built to identify the interactions between lncRNA and mRNA. qRT-PCR was performed to further validate the expressions of selected lncRNAs and mRNAs in advanced LSCC. We found 1459 differentially expressed lncRNAs and 2381 differentially expressed mRNAs, including 846 up-regulated lncRNAs and 613 down-regulated lncRNAs, 1542 up-regulated mRNAs and 839 down-regulated mRNAs. The mRNAs ITGB1, HIF1A, and DDIT4 were selected as core mRNAs, which are mainly involved in biological processes, such as matrix organization, cell cycle, adhesion, and metabolic pathway. LncRNA-mRNA expression correlation network showed LncRNA NR_027340, MIR31HG were positively correlated with ITGB1, HIF1A respectively. LncRNA SOX2-OT was negatively correlated with DDIT4. qRT-PCR further validated the expression of these lncRNAs and mRNAs. The work provides convincing evidence that the identified lncRNAs and mRNAs are potential biomarkers in advanced LSCC for further future studies.

  3. Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy

    PubMed Central

    2011-01-01

    Background To establish recurrence patterns among locally advanced head and neck non-nasopharyngeal squamous cell carcinoma (HNSCC) patients treated with radical (chemo-) radiotherapy and to correlate the sites of loco-regional recurrence with radiotherapy doses and target volumes Method 151 locally advanced HNSCC patients were treated between 2004-2005 using radical three-dimensional conformal radiotherapy. Patients with prior surgery to the primary tumour site were excluded. The sites of locoregional relapses were correlated with radiotherapy plans by the radiologist and a planning dosimetrist. Results Median age was 59 years (range:34-89). 35 patients had stage III disease, 116 patients had stage IV A/B. 36 patients were treated with radiotherapy alone, 42 with induction chemotherapy, 63 with induction and concomitant chemoradiotherapy and 10 concomitant chemoradiotherapy. Median follow-up was 38 months (range 3-62). 3-year cause specific survival was 66.8%. 125 of 151 (82.8%) achieved a complete response to treatment. Amongst these 125 there were 20 local-regional recurrence, comprising 8 local, 5 regional and 7 simultaneous local and regional; synchronous distant metastases occurred in 7 of the 20. 9 patients developed distant metastases in the absence of locoregional failure. For the 14 local recurrences with planning data available, 12 were in-field, 1 was marginal, and 1 was out-of-field. Of the 11 regional failures with planning data available, 7 were in-field, 1 was marginal and 3 were out-of-field recurrences. Conclusion The majority of failures following non-surgical treatment for locally advanced HNSCC were loco-regional, within the radiotherapy target volume. Improving locoregional control remains a high priority. PMID:21609453

  4. Combined nimotuzumab with chemoradiotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma: A retrospective study.

    PubMed

    Lai, Xiaojing; Gu, Qing; Zheng, Xiao; Liu, Guan; Feng, Wei; Lin, Xiao; Mao, Weimin

    2016-10-01

    To observe the efficacy and toxicities of combined nimotuzumab with chemoradiotherapy as the first-line treatment to advanced esophageal squamous cell carcinoma (ESCC). The clinical data of 43 patients with local advanced or metastatic ESCC treated with nimotuzumab combined with chemoradiotherapy in our hospital were included in this retrospective study. The overall response, adverse events, overall survival (OS), and progressive-free survival (PFS) were analyzed. At 1 month after the treatment, objective response rate (complete response [CR] + partial response [PR]) was 65.12%, and disease control rate (CR + PR + stable disease [SD]) was 86.05%, with one patient (2.33%) showing CR, 27 (62.79%) patients with PR, 9 (20.93%) with SD, and 6 (13.95%) with progressive disease, respectively. The median OS was 15.5 months, and the median PFS was 8.83 months. Multivariate analysis showed that the patients with more cycles (>6 times) of nimotuzumab treatment had better PFS and OS than those with fewer cycles (≤6 times). Patients received high-dose radiation (>55 Gy) had a better PFS than those patients received low-dose radiation (≤55 Gy). Three patients suffered severe esophageal fistula, and three patients showed superficial skin erosion. Chemoradiotherapy in combination with more than 6 weekly doses of nimotuzumab (>1400 mg) had a survival benefit to the patients with advanced ESCC. High-dose radiation therapy for primary tumor has been confirmed to improve PFS in these patients. Patients treated with nimotuzumab showed no increased risk of adverse events.

  5. Primary intraosseous squamous cell carcinoma arising in dentigerous cyst: Report of 2 cases and review of the literature

    PubMed Central

    Camps-Font, Octavi; López-Ramírez, Marta; Vidal-Bel, August

    2015-01-01

    Dentigerous cysts are one of the most common odontogenic cysts of the oral cavity. Odontogenic cysts can give rise to a variety of neoplasms. Carcinoma arising in a dentigerous cyst is extremely rare, with a review of literature showing near 30 cases. The present report describes 2 cases of primary intraosseous squamous cell carcinoma originated from a dentigerous cyst. The first one refers to a 57-year old female with a persistent lesion in the left retromolarregion and diagnosed with squamous cell carcinoma originated fromthe incomplete excision of the lower third molar follicle during its surgical extraction. The second case describes the case of an 18-year old male with an impacted upper canine with previous history of infection and swelling of the oral cavity. The histopathological study revealed the malignization of the follicle surrounding the dental crown. These two cases confirmed the importance of the histopathological study of all the tissue samples obtained from surgical procedures. Although the development of a malignant lesion from a dentigerous cyst is rare and its clinical-radiological features are apparently innocuous, this entity should be considered as a differential diagnosis. Key words:Dentigerous cyst, odontogenic cyst, squamous cell carcinoma, primary intraosseous squamous cell carcinoma, odontogenic carcinoma. PMID:26644846

  6. The Level of Squamous Cell Carcinoma Antigen and Lymph Node Metastasis in Locally Advanced Cervical Cancer.

    PubMed

    Lekskul, Navamol; Charakorn, Chuenkamon; Lertkhachonsuk, Arb-Aroon; Rattanasiri, Sasivimol; Israngura Na Ayudhya, Nathpong

    2015-01-01

    This study aimed to determine the utility and a cut-off level of serum squamous cell carcinoma antigen (SCC-Ag) to predict lymph node metastasis in locally advanced cervical cancer cases. We also investigated the correlation between SCC-Ag level and lymph node status. From June 2009 to June 2014, 232 patients with cervical cancer stage IB2-IVA, who were treated at Ramathibodi Hospital, were recruited. Receiver operating characteristic (ROC) curves were used to identify the best cut-off point of SCC-Ag level to predict lymph node metastasis. Quantile regression was performed to evaluate the correlation between SCC-Ag levels and pelvic lymph node metastasis, paraaortic lymph node metastasis, and parametrial involvement as well as tumor size. Pelvic lymph node metastasis and paraaortic lymph node metastasis were diagnosed in 46.6% and 20.1% of the patients, respectively. The median SCC-Ag level was 6 ng/mL (range, 0.5 to 464.6 ng/ mL). The areas under ROC curves between SCC-Ag level and pelvic lymph node metastasis, paraaotic lymph node metastasis, parametrial involvements were low. SCC-Ag level was significantly correlated with paraaortic lymph node status (p=0.045) but not with pelvic lymph node status and parametrial involvement. SCC-Ag level was also related to the tumor diameter (p<0.05). SCC-Ag level is not a good predictor for pelvic and paraaortic lymph node metastasis. However, it is still beneficial to assess the tumor burden of squamous cell carcinoma of the cervix.

  7. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

    PubMed Central

    Pivot, X; Raymond, E; Laguerre, B; Degardin, M; Cals, L; Armand, J P; Lefebvre, J L; Gedouin, D; Ripoche, V; Kayitalire, L; Niyikiza, C; Johnson, R; Latz, J; Schneider, M

    2001-01-01

    This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11531245

  8. Phase II trial of biweekly docetaxel, cisplatin, and 5-fluorouracil chemotherapy for advanced esophageal squamous cell carcinoma.

    PubMed

    Tanaka, Yoshihiro; Yoshida, Kazuhiro; Yamada, Atsuko; Tanahashi, Toshiyuki; Okumura, Naoki; Matsuhashi, Nobuhisa; Yamaguchi, Kazuya; Miyazaki, Tatsuhiko

    2016-06-01

    The prognosis of esophageal cancer patients is still unsatisfactory. Although a docetaxel, cisplatin, and 5-Fu (DCF) regimen has been reported, it is often difficult to accomplish because of severe toxicity. Therefore, we developed a new biweekly DCF (Bi-DCF) regimen and previously reported the recommended dose in a phase I dose-escalation study. We then performed a phase II study of Bi-DCF for advanced esophageal squamous cell carcinoma (SCC). Patients with clinical stage II/III were eligible. Patients received 2 courses of chemotherapy: docetaxel 35 mg/m(2) with cisplatin 40 mg/m(2) on days 1 and 15 and 400 mg/m(2) 5-fluorouracil on days 1-5 and 15-19 every 4 weeks. After completion of the chemotherapy, patients received esophagectomy. The primary endpoint was the completion rate of protocol treatment. Thirty-two patients were enrolled. The completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery) was 100 %. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (31.3 %). No treatment-related death was observed, and the incidence of operative morbidity was tolerable. The overall response rate after the chemotherapy was 90.3 %. This Bi-DCF regimen was well tolerated and highly active. This trial was registered with the University Hospital Medical Information Network (No. UMIN 000014625).

  9. Oesophageal squamous cell carcinoma (ESCC): Advances through omics technologies, towards ESCC salivaomics.

    PubMed

    González-Plaza, Juan José; Hulak, Nataša; García-Fuentes, Eduardo; Garrido-Sánchez, Lourdes; Zhumadilov, Zhaxybay; Akilzhanova, Ainur

    2015-08-01

    Oesophageal Squamous Cell Carcinoma (ESCC) is one of the two main subtypes of oesophageal cancer, affecting mainly populations in Asia. Though there have been great efforts to develop methods for a better prognosis, there is still a limitation in the staging of this affection. As a result, ESCC is detected at advances stages, when the interventions on the patient do not have such a positive outcome, leading in many cases to recurrence and to a very low 5-year survival rate, causing high mortality. A way to decrease the number of deaths is the use of biomarkers that can trace the advance of the disease at early stages, when surgical or chemotherapeutic methodologies would have a greater effect on the evolution of the subject. The new high throughput omics technologies offer an unprecedented chance to screen for thousands of molecules at the same time, from which a new set of biomarkers could be developed. One of the most convenient types of samples is saliva, an accessible body fluid that has the advantage of being non-invasive for the patient, being easy to store or to process. This review will focus on the current status of the new omics technologies regarding salivaomics in ESCC, or when not evaluated yet, the achievements in related diseases.

  10. Diagnosis of primary squamous cell carcinoma of the pancreas using endoscopic ultrasound-guided core needle biopsy.

    PubMed

    Kashani, Amir; Kahn, Melissa; Jamil, Laith H

    2015-05-16

    Primary squamous cell carcinoma (SCC) of the pancreas is a particularly rare entity. Diagnosis of this tumor is tentatively made after ruling out metastatic SCC from another primary site and adenosquamous carcinoma (ASC) of the pancreas. Here we discuss the case of a 76-year-old woman who was found to have a solitary pancreatic lesion and multiple hepatic lesions. Results of computed tomography-guided biopsy of the liver lesions were consistent with a metastatic carcinoma displaying squamous differentiation; therefore, an endoscopic ultrasound (EUS)-guided core-needle biopsy (CNB) of the pancreatic mass was performed. Meticulous histopathological examination of the pancreatic specimen at multiple levels revealed moderately well-differentiated SCC with no glandular component. An extensive metastatic work-up did not reveal an extra-pancreatic origin for this SCC; hence, a diagnosis of primary SCC of the pancreas was established. To our knowledge, this is the first report of the diagnosis of a primary SCC of the pancreas using EUS-guided CNB. We believe that CNB has a diagnostic yield equivalent to that of fine-needle aspiration for recognizing pancreatic adenocarcinoma; however, when cytological examinations reveal atypical squamous epithelial cells suggestive of malignancy, CNB may provide a better tissue specimen, from which to determine the presence of a glandular component. Such an assessment will differentiate pancreatic SCC from ASC.

  11. Advances of gene therapy for primary immunodeficiencies

    PubMed Central

    Candotti, Fabio

    2016-01-01

    In the recent past, the gene therapy field has witnessed a remarkable series of successes, many of which have involved primary immunodeficiency diseases, such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome. While such progress has widened the choice of therapeutic options in some specific cases of primary immunodeficiency, much remains to be done to extend the geographical availability of such an advanced approach and to increase the number of diseases that can be targeted. At the same time, emerging technologies are stimulating intensive investigations that may lead to the application of precise genetic editing as the next form of gene therapy for these and other human genetic diseases. PMID:27508076

  12. Clinical implication of computed tomography findings in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Ryu, In Sun; Lee, Jeong Hyun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Cho, Kyung-Ja

    2015-10-01

    Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72%) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73%) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80%, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78%. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP.

  13. MAGE-A antigens in patients with primary oral squamous cell carcinoma.

    PubMed

    Müller-Richter, Urs D A; Dowejko, Albert; Peters, Silvia; Rauthe, Stephan; Reuther, Tobias; Gattenlöhner, Stefan; Reichert, Torsten E; Driemel, Oliver; Kübler, Alexander C

    2010-06-01

    MAGE-A antigens are only expressed on tumor cells. The aim of this study was to identify their expression in patients with oral squamous cell carcinoma (OSCC). Forty-seven patients with primary OSCC was selected retrospectively. Histo-pathological sections were stained immunohistochemically with MAGE-A antibody 57B. The results were evaluated regarding tumor size (T), lymph-node metastasis (N), blood vessel infiltration (V), lymph vessel infiltration (L), grading (G), and sex. MAGE-A antigens were expressed in 55% of all patients. Expression increased with tumor size (T1 = 56%; T2 = 44%; T3 = 67%; T4 = 71%). Lymph-node metastasis had no influence (N0 and N1 about 50%). Tumors with blood and lymph vessel infiltration had higher expression (V0 = 50%; V1 = 100%; L0 = 46%; L1 = 71%). Less-differentiated tumors showed higher rates (G1 = 50%; G2 = 45%; G3 = 83%). OSCC in men were positive in 62% and in women in 38%. MAGE-A antigens are frequently expressed in OSCC. Their expression seems to increase with tumor dedifferentiation.

  14. Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

    PubMed Central

    Grossi, F; Rijavec, E; Genova, C; Barletta, G; Biello, F; Maggioni, C; Burrafato, G; Sini, C; Dal Bello, M G; Meyer, K; Roder, J; Roder, H; Grigorieva, J

    2017-01-01

    Background: VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed. Methods: The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted. Results: Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately. Conclusions: The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC. PMID:27898657

  15. Prevalence of regional and distant metastasis in cats with advanced oral squamous cell carcinoma: 49 cases (2005-2011).

    PubMed

    Soltero-Rivera, Maria M; Krick, Erika L; Reiter, Alexander M; Brown, Dorothy C; Lewis, John R

    2014-02-01

    The objective of this study was to evaluate the prevalence of regional and distant metastasis in cats with advanced oral squamous cell carcinoma (SCC) in a retrospective case series. Forty-nine cats with cytologically- or histopathologically-confirmed oral SCC presented to the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania. History, clinical and laboratory results, diagnostic imaging findings and survival times were obtained from the medical records of patients who received diagnostic evaluation for metastasis. The prevalence of metastasis was assessed by means of mandibular lymph node cytology and three-view thoracic radiography. The prevalence of mandibular lymph node metastasis was 31% (15/49). Evidence of possible thoracic metastasis was seen in 10% (5/49) of cases. Of the patients with mandibular lymph node metastasis, 53% (8/15) were maxillary, 27% mandibular (4/15), 13% sublingual (2/15) and 7% caudal pharyngeal (1/15). Pulmonary metastasis was seen in three mandibular, one maxillary and one sublingual mass. Forty-one patients died or were euthanased owing to progression of local disease, and seven patients were lost to follow-up. The prevalence of regional metastasis in this study was more common than most previously reported studies, while the rate of pulmonary metastasis was higher than has previously been published. Although significant conclusions cannot be drawn, control of the primary tumor, regardless of tumor size at diagnosis, appears to be an important factor in improving survival time, and therefore treatment of metastasis may be important in those cases where long-term control of the primary tumor is possible.

  16. Non-coding RNAs deregulation in oral squamous cell carcinoma: advances and challenges.

    PubMed

    Yu, T; Li, C; Wang, Z; Liu, K; Xu, C; Yang, Q; Tang, Y; Wu, Y

    2016-05-01

    Oral squamous cell carcinoma (OSCC) is a common cause of cancer death. Despite decades of improvements in exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. The difficulty of early diagnosis and the high prevalence of metastasis associated with OSCC contribute to its dismal prognosis. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest in the research for predictive biomarkers. Non-coding RNAs (ncRNAs) are promising biomarkers. Among numerous kinds of ncRNAs, short ncRNAs, such as microRNAs (miRNAs), have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. In contrast to miRNAs, long non-coding RNAs (lncRNAs) are much less known concerning their functions in human cancers especially in OSCC. The present review highlighted the roles of miRNAs and newly discovered lncRNAs in oral tumorigenesis, metastasis, and their clinical implication.

  17. Advancements in the Management of HPV-Associated Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Zeitlin, Ross; Nguyen, Harrison P.; Rafferty, David; Tyring, Stephen

    2015-01-01

    Head and neck carcinomas have long been linked to alcohol and tobacco abuse; however, within the last two decades, the human papillomavirus (HPV) has emerged as a third etiology and is specifically associated with head and neck squamous cell carcinomas (HNSCC). In this anatomical region, the oncogenic HPV-16 mediates transformation and immortalization of epithelium, most commonly in the oropharynx. Nevertheless, the recent identification of novel HPV mechanisms thought to be specific to oropharyngeal carcinogenesis has coincided with observations that HPV-associated HNSCC has differing clinical behavior—in terms of natural history, therapeutic response, and prognosis—than HPV-negative head and neck tumors. Taken together with the growing incidence of HPV transmission in younger populations, these discoveries have sparked a rapid expansion in both laboratory and clinical studies on the infection and disease. Herein, we review the clinical characteristics of HPV-associated HNSCC, with particular emphasis on recent advancements in our understanding of the management of this infectious malignancy. PMID:26239449

  18. Combined-modality treatment for advanced oral tongue squamous cell carcinoma

    SciTech Connect

    Fan, K.-H.; Lin, C.-Y. |; Kang, C.-J.; Huang, S.-F.; Chen, I.-H.; Liao, C.-T. |; Wang, H.-M. |; Cheng, A.-J. |; Chang, J.T.-C. ||. E-mail: jtchang@adm.cgmh.org.tw

    2007-02-01

    Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.

  19. Primary squamous cell carcinoma of the external auditory canal: surgical treatment and long-term outcomes.

    PubMed

    Mazzoni, A; Danesi, G; Zanoletti, E

    2014-04-01

    This study was conducted on patients with squamous cell carcinoma of the external auditory canal and temporal bone treated with surgery alone or surgery plus postoperative radiotherapy. It was designed as a retrospective investigation with complete long-term follow-up covering the years from 1983 to 2008. The setting was a tertiary referral centre. Forty-one consecutive cases underwent surgery involving en bloc lateral or subtotal temporal bone resection, parotidectomy and neck dissection plus radiotherapy in advanced cases. The Pittsburgh staging system was adopted. No cases were lost to follow-up, which ranged from 2 to 220 months, while for survivors ranged from 60 to 220 months and included clinical examinations and imaging. Outcome was expressed as NED (no evidence of disease), DOC (dead of other causes), DOD (dead of disease), AWD (alive with disease), disease-free survival (DFS) and disease-specific survival (DSS). Results were expressed with raw data and Kaplan Meyer curves. Patients with T1 and T2 disease had a DFS of 67% and a DSS of 92%. For T3 and T4 cases, the DFS was 41% and DSS was 48%. All treatment failures were due to local recurrences. The cases classified as T4 because the lesion extended from the cartilage canal to the periauricular soft tissues, or from the anterior wall to the parotid space, had a better outcome than the other T4 cases: this different prognosis suggests the need to stage tumours differently. Nodal disease coincided with a worse outcome due to local recurrence.

  20. Solid-type primary intraosseous squamous-cell carcinoma in the mandible: Report of a rare case.

    PubMed

    Alotaibi, Ohoud; Al-Zaher, Nabil; Alotaibi, Faiza; Khoja, Hatim; Qannam, Ahmed

    2016-09-01

    Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that has an exquisitely exclusive affection to the jawbone. It is defined as squamous cell carcinoma arising within the jaw and developing from residual odontogenic epithelium or from a preexisting odontogenic cyst or tumor. The solid-type of this tumor is a central jaw carcinoma arising de novo and has no initial connection with the oral mucosa. Herein, we report a case of solid-type PIOSCC involving the mandible in a 37-year-old male patient elucidating its histopathological and imaging findings. The patient underwent surgical resection followed by post-operative adjuvant radiotherapy. The close 2-year follow up of the patient revealed neither locoregional nor distant metastasis.

  1. Induction chemotherapy followed by concurrent chemoradiotherapy for advanced stage oropharyngeal squamous cell carcinoma with HPV and P16 testing.

    PubMed

    Flavill, Eric; Fang, Yisheng V; Miles, Brett; Truelson, John; Perkins, Steve

    2014-05-01

    The objective was to report our experience with advanced stage oropharyngeal squamous cell carcinoma treated sequentially with induction chemotherapy followed by concurrent chemoradiotherapy. Retrospective chart review identified 49 eligible patients with advanced stage oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiotherapy. HPV and p16(INK4A) testing was performed on pathology specimens. Follow-up of over 11 months was required unless a death or treatment failure occurred before that time. Treatment with induction chemotherapy followed by concurrent chemoradiotherapy resulted in 44/48 (90%) complete durable response. One death occurred from pulmonary embolism. Toxicity profiles were comparable to other published data. Average follow-up was 3.9 years. Oncologic failure rates among subgroups showed 5.7% failure for HPV+/p16+ cancer, 9.1% failure for HPV-/p16+ cancer, 100% failure for HPV-/p16- cancer, 0% failure for nonsmokers, and 17.9% failure for smokers. This study showed favorable outcomes in terms of durable oncologic response and acceptable toxicity profiles. It is notable that 36/49 patients were HPV+/p16+ and 11/49 were HPV-/p16+. Only 2 patients were HPV-/p16-, and both died as a result of oncologic failures. This highlights the importance of obtaining HPV and p16 testing in studies evaluating the efficacy of treatments for oropharyngeal squamous cell carcinoma.

  2. Incidence and Outcomes of Patients With Oral Cavity Squamous Cell Carcinoma and Fourth Primary Tumors

    PubMed Central

    Adel, Mohamad; Liao, Chun-Ta; Lee, Li-Yu; Hsueh, Chuen; Lin, Chien-Yu; Fan, Kang-Hsing; Wang, Hung-Ming; Ng, Shu-Hang; Lin, Chih-Hung; Tsao, Chung-Kan; Huang, Shiang-Fu; Kang, Chung-Jan; Fang, Ku-Hao; Wang, Yu-Chien; Chang, Kai-Ping; Fang, Tuan-Jen; Yang, Lan Yan; Yen, Tzu-Chen

    2016-01-01

    Abstract The aim of this study was to explore the incidence and outcomes of patients with oral cavity squamous cell carcinoma (OSCC) and fourth primary tumors (PTs) in a betel-chewing endemic area. We retrospectively examined the records of 1836 OSCC patients who underwent radical tumor resection between 1996 and 2014. The outcome measures included the incidence and number of multiple PTs, the main risk factors, and their associations with overall survival (OS). Of the 1836 patients, 1400 (76.3%) had a single PT, 344 (18.7%) a second PT, 67 (3.6%) a third PT, and 25 (1.4%) a fourth PT. Univariate analyses (log-rank test) identified the following factors as significantly associated with a fourth PT: simultaneous first and second PTs, betel quid chewing, buccal subsite, and pT3–4 status. After allowance for the potential confounding effect of other risk factors, all of these factors retained their independent prognostic significance in stepwise multivariate analyses, the only exception being betel chewing. The incidences of second, third, and fourth PTs at 5 and 10 years were 20.2%/34.6%, 4.0%/8.6%, and 1.0%/2.3%, respectively. The 5 and 10-year OS rates (calculated from the diagnosis of each PTs) for patients with a single, second, third, and fourth PTs were 68%/61%, 43%/37%, 45%/39%%, and 30%/30%, respectively (P < 0.0001). Among patients with a fourth PT, those who underwent radical surgery showed a significantly higher 3-year OS than those who did not (57% vs 13%; P = 0.0442). Fourth PTs are rarely observed in OSCC patients in a betel quid-chewing endemic area. Long-term survival rates of patients treated with radical surgery seems acceptable, being 4-fold higher than their counterparts. PMID:27015170

  3. Primary squamous cell carcinoma of the endometrium unrelated to human papilloma virus: a molecular study.

    PubMed

    Giordano, Giovanna; Pizzi, Silvia; Azzoni, Cinzia; Bottarelli, Lorena; D'Adda, Tiziana

    2013-07-01

    In this paper we report a molecular study of a case of Primary Endometrial Squamous Carcinoma (PESC), in which a Human Papilloma Virus (HPV) infection had been previously excluded by Polymerase Chain Reaction (PCR). The studies performed in an effort to explain the carcinogenesis included immunohistochemical over-expression of p53 and p16 proteins as previously observed in our own papers, plus microsatellite analysis of D10S1765 at 10q23.3 (PTEN) and TP53 at 17p13.1 (P53) as well as the methylation status of the of BRCA1 and p16 promoters using specific PCRs. In this rare malignancy, we found allelic imbalance (AI) at 17p13.1 (P53). Instead, AI at D10S1765 (PTEN) gene was absent. The genetic alteration of p53, with hyper-expression of p53 protein and an absence of abnormalities in the PTEN gene are consistent with the similarities between Uterine Serous Carcinoma (USC) and our case of PESC. The aberrant methylation of both p16 and BCAR1 promoters was not detected in our case. This finding too could imply that ESC is more similar to Uterine Serous Carcinoma than Uterine Endometrioid Carcinoma (UEC). Moreover, the lack of aberrant methylation of p16, which is in accordance with over-expression of p16 immunoreactivity, in the absence of HPV infection may be related to other unknown genetic alterations. In our opinion, it is hard to reach any definite conclusion concerning the carcinogenesis of PESC, because of its rarity and the very few molecular studies reported in the literature. Further studies with more numerous cases and larger molecular analyses are mandatory for this malignancy, to confirm whether it is more closely related to papillary endometrial cancer than to endometrioid carcinoma.

  4. Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma.

    PubMed

    Nishio, Kensuke; Motozawa, Keiko; Omagari, Daisuke; Gojoubori, Takahiro; Ikeda, Takayuki; Asano, Masatake; Gionhaku, Nobuhito

    2016-01-01

    Matrix metalloproteinases (MMPs) and tumor-associated macrophages (TAMs) play important roles in tumor growth. The present study investigated the expression levels of MMP2 and MMP9 in relation to the distribution of TAMs in the primary and metastatic regions of oral squamous cell carcinoma. Twenty-nine cases of oral squamous cell carcinoma (OSCC) with regional lymph node metastasis were selected from available documents in the archives of the Department of Pathology, Nihon University School of Dentistry. Four-micrometer-thick sections were prepared from the primary and metastatic regions. Each section was subjected to immunohistochemical staining using anti-MMP2, anti-MMP9, and anti-CD68 antibodies. The distribution and localization of MMPs and TAMs were compared between primary and metastatic regions. The expression levels of both MMPs were higher in the metastatic regions of lingual and gingival cancers. Statistically significant differences were observed in both T1 and T2 cases. In contrast to the higher expression of MMPs in metastatic regions, a higher number of TAMs were distributed in the primary regions. From these results, MMP expression levels and the numbers of TAMs were expected to have an inverse relationship between the primary and metastatic regions of OSCC. (J Oral Sci 58, 59-65, 2016).

  5. Laparoscopic Cytoreduction for Primary Advanced Ovarian Cancer

    PubMed Central

    Hojat, Rod; Johnson, Jil; Fenton, Bradford

    2010-01-01

    Introduction: We evaluated the feasibility of laparoscopic cytoreduction for primary advanced ovarian cancer. Methods: All patients with presumed stage 3/4 primary ovarian cancer underwent attempted laparoscopic cytoreduction. All patients had CT evidence of omental metastasis and ascites. A 5-port (5-mm) transperitoneal approach was used. A bilateral salpingo-oophorectomy, supracervical hysterectomy, and omentectomy were performed with PlasmaKinetic (PK) cutting forceps. A laparoscopic 5-mm Argon-Beam Coagulator was used to coagulate tumor in the pelvis, abdominal peritoneum, intestinal mesentery, and diaphragm. Results: Nine of 11 cases (82%) were successfully de-bulked laparoscopically without conversion to laparotomy. Median operative time was 2.5 hours, and median blood loss was 275 mL. All tumors were debulked to <2 cm and 45% had no residual disease. Stages were 1–3B, 7–3C, and 1–4. Median length of stay was one day. Median VAS pain score was 4 (discomforting). Two of 11 patients (18%) had postoperative complications. Conclusion: Laparoscopic cytoreduction was successful and resulted in minimal morbidity. Because of our small sample size, additional studies are needed. PMID:20529532

  6. Laparoscopic cytoreduction for primary advanced ovarian cancer.

    PubMed

    Fanning, James; Hojat, Rod; Johnson, Jil; Fenton, Bradford

    2010-01-01

    We evaluated the feasibility of laparoscopic cytoreduction for primary advanced ovarian cancer. All patients with presumed stage 3/4 primary ovarian cancer underwent attempted laparoscopic cytoreduction. All patients had CT evidence of omental metastasis and ascites. A 5-port (5-mm) transperitoneal approach was used. A bilateral salpingo-oophorectomy, supracervical hysterectomy, and omentectomy were performed with PlasmaKinetic (PK) cutting forceps. A laparoscopic 5-mm Argon-Beam Coagulator was used to coagulate tumor in the pelvis, abdominal peritoneum, intestinal mesentery, and diaphragm. Nine of 11 cases (82%) were successfully debulked laparoscopically without conversion to laparotomy. Median operative time was 2.5 hours, and median blood loss was 275 mL. All tumors were debulked to <2 cm and 45% had no residual disease. Stages were 1-3B, 7-3C, and 1-4. Median length of stay was one day. Median VAS pain score was 4 (discomforting). Two of 11 patients (18%) had postoperative complications. Laparoscopic cytoreduction was successful and resulted in minimal morbidity. Because of our small sample size, additional studies are needed.

  7. Primary squamous cell carcinoma with mucormycosis in a diabetic foot ulcer.

    PubMed

    Mandal, Palash Kumar; Bhattacharyya, Nirmal Kumar; Mookerjee, Sekhar Kumar; Chaudhuri, Bhaskarnarayan

    2013-02-01

    The diabetic foot ulcer is one of the major complications of diabetes mellitus leading to prolonged hospital stay. Non-healing foot ulcers in diabetes may be due to peripheral neuropathy and/or vasculopathy. Non-healing occurs following a trivial trauma due to loss of local immunity and increased infection by bacteria and fungus. Candida and mucormycosis are common fungal infection in diabetic foot ulcer. Squamous cell carcinoma in any non-healing ulcer is a common occurrence. But squamous cell carcinoma in non-healing diabetic foot ulcer is rarely reported. Here, mucormycosis in a diabetic foot ulcer which turned into squamous cell carcinoma is reported in a 62-year-old male with poor glycaemic control for last 21 years who presented with a non-healing ulcer of 8 months' duration over dorsum of left forefoot. Microbiological examination revealed presence of mucormycosis infection and histopathology of ulcer showed infiltrating well-differentiated squamous cell carcinoma. The clinicians and pathologists should be aware of these combinations because only eradication of mucormycosis may not cure the ulcer, rather presence of squamous cell carcinoma may be ignored that may be an immediate threat to the patient's life.

  8. Integrated Analysis of Long Noncoding RNA and mRNA Expression Profile in Advanced Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Lian, Meng; Ma, Hongzhi; He, Ning; Liu, Honggang; Wang, Haizhou; Fang, Jugao

    2016-01-01

    Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the expression pattern and function of lncRNAs in laryngeal squamous cell carcinoma (LSCC) are still unclear. To investigate the aberrantly expressed lncRNAs and mRNAs in advanced LSCC, we screened lncRNA and mRNA expression profiles in 9 pairs of primary Stage IVA LSCC tissues and adjacent non-neoplastic tissues by lncRNA and mRNA integrated microarrays. Gene Ontology and pathway analysis were performed to find out the significant function and pathway of the differentially expressed mRNAs, gene-gene functional interaction network and ceRNA network were constructed to select core mRNAs, and lncRNA-mRNA expression correlation network was built to identify the interactions between lncRNA and mRNA. qRT-PCR was performed to further validate the expressions of selected lncRNAs and mRNAs in advanced LSCC. We found 1459 differentially expressed lncRNAs and 2381 differentially expressed mRNAs, including 846 up-regulated lncRNAs and 613 down-regulated lncRNAs, 1542 up-regulated mRNAs and 839 down-regulated mRNAs. The mRNAs ITGB1, HIF1A, and DDIT4 were selected as core mRNAs, which are mainly involved in biological processes, such as matrix organization, cell cycle, adhesion, and metabolic pathway. LncRNA-mRNA expression correlation network showed LncRNA NR_027340, MIR31HG were positively correlated with ITGB1, HIF1A respectively. LncRNA SOX2-OT was negatively correlated with DDIT4. qRT-PCR further validated the expression of these lncRNAs and mRNAs. The work provides convincing evidence that the identified lncRNAs and mRNAs are potential biomarkers in advanced LSCC for further future studies. PMID:28033431

  9. Primary squamous cell carcinoma of the rectum: An update and implications for treatment

    PubMed Central

    Guerra, Glen R; Kong, Cherng H; Warrier, Satish K; Lynch, Andrew C; Heriot, Alexander G; Ngan, Samuel Y

    2016-01-01

    AIM: To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). METHODS: A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. RESULTS: The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC’s are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the

  10. Primary squamous cell carcinoma of the rectum: An update and implications for treatment.

    PubMed

    Guerra, Glen R; Kong, Cherng H; Warrier, Satish K; Lynch, Andrew C; Heriot, Alexander G; Ngan, Samuel Y

    2016-03-27

    To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC's are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the optimal treatment remains as

  11. EAGLES study: First-line Bevacizumab in Combination with Chemotherapy in Elderly Patients with Advanced, Metastatic, Non-squamous Non-small Cell Lung Cancer.

    PubMed

    DE Marinis, Filippo; Bidoli, Paolo; Luciani, Andrea; Amoroso, Domenico; Tonini, Giuseppe; Bertolini, Alessandro; Brandes, Alba A; Migliorino, Maria Rita; Favaretto, Adolfo; Gridelli, Cesare

    2017-05-01

    The management of elderly patients with advanced non-squamous NSCLC includes several strategies. Patients (≥70 years) were randomly assigned to bevacizumab (7.5 mg/kg i.v. on day 1) plus gemcitabine (1,200 mg/m(2) i.v. on days 1-8) (arm A) or bevacizumab (7.5 mg/kg i.v.) and cisplatin (60 mg/m(2) i.v.) plus gemcitabine (1,000 mg/m(2) i.v. on days 1-8) (arm B), to independently evaluate treatments. The primary endpoint was progression-free rate at 6 months; secondary endpoints included progression-free survival (PFS) and safety profiles. At 6 months, 5 (11.6%) patients in arm A and 5 patients (12.5%) in arm B were found to be progression-free. Median PFS was 4.8 months in arm A and 6.5 months in arm B, respectively. In our experience, combination of bevacizumab and chemotherapy had encouraging anti-tumor efficacy as first-line therapy in elderly patients with non-squamous NSCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Prognostic value of hypoxia-associated markers in advanced larynx and hypopharynx squamous cell carcinoma.

    PubMed

    Bernstein, Jonathan M; Andrews, Timothy D; Slevin, Nick J; West, Catharine M L; Homer, Jarrod J

    2015-01-01

    To determine the prognostic value of hypoxia-associated markers carbonic anhydrase-9 (CA-9) and hypoxia-inducible factor-1α (HIF-1α) in advanced larynx and hypopharynx squamous cell carcinoma (SCCa) treated by organ preservation strategies. Retrospective cohort study. Pretreatment CA-9 and HIF-1α expression, clinicopathologic data, and tumor volume were analyzed in a series of 114 patients with T3-4 SCCa larynx or hypopharynx treated by (chemo)radiation. Adverse prognostic factors for locoregional control were T4 classification (P = 0.008), and for disease-specific survival were CA-9 positivity (P = 0.039), T4 classification (P = 0.001), larger tumor volume (P = 0.004), N1-3 classification (P = 0.002), and pretreatment hemoglobin < 13.0 g/dl (P = 0.014). With increasing CA-9 expression, there was a trend to increasing tumor recurrence (P trend = 0.009) and decreasing survival (P trend = 0.002). On multivariate analysis, independent variables were T4 classification (hazard ratio [HR] 13.54, P = 0.01) for locoregional failure, and CA-9 positivity (HR = 8.02, P = 0.042) and higher tumor volume (HR = 3.33, P = 0.007) for disease-specific mortality. This is the first study to look specifically at T3 and T4 SCCa larynx and hypopharynx for a relationship between hypoxia-associated marker expression and clinical outcome. Pretreatment immunohistochemical CA-9 expression is an adverse prognostic factor for disease-specific survival, indicating that CA-9 expression may confer a more aggressive tumor phenotype. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Rapid hyperfractionated radiotherapy. Clinical results in 178 advanced squamous cell carcinomas of the head and neck

    SciTech Connect

    Nguyen, T.D.; Demange, L.; Froissart, D.; Panis, X.; Loirette, M.

    1985-07-01

    The authors present a series of 178 patients with Stage III or IV squamous cell carcinoma of the head and neck treated by rapid irradiation using multiple and small fractions per day. An initial group of 91 patients (G1) received a total dose of 72 Gy in 80 sessions and 10 days, according to the following split course schedule: J1 to J5, 36 Gy in 40 sessions, eight daily fractions of .9 Gy separated by 2 hours; J6 to J20, rest period; J21 to J25, same as in J1 except that the spinal cord was shielded. This protocol was altered for the following 87 patients (G2) by lessening the total dose to 60 to 66 Gy and the number of fractions to 60. The rest period was lengthened to 4 weeks. All patients but five completed the whole program and the minimal follow-up period was 24 months. At the end of irradiation, 121 patients achieved a total remission, but local recurrences occurred in 56%. Moreover, acute intolerance was considered as severe in 34% of G1 patients, and included extensive mucosal necrosis and bleeding. Although this rate was significantly reduced in G2 patients, late complications were observed in 20 of the 25 survivors, and included trismus, cervical sclerosis, and recurrent laryngeal edema. The crude survival rate is 13% at 2 years. Although this study was not randomized, this particular type of accelerated and hyperfractionated combination of irradiation did not really improve the clinical results in advanced carcinoma of the head and neck. Other schedules and probably other tumors, less extended, should be tested.

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

    SciTech Connect

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

    2006-07-15

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

  15. p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary.

    PubMed

    Keller, Lanea M; Galloway, Thomas J; Holdbrook, Thomas; Ruth, Karen; Yang, Donghua; Dubyk, Cara; Flieder, Douglas; Lango, Miriam N; Mehra, Ranee; Burtness, Barbara; Ridge, John A

    2014-12-01

    The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP). Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC). A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p < .0001), absence of macroscopic extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade (p = 0.007). The prognostic implication of worse overall survival (OS) with macroscopic ECE (p = .009) remained significant when limited to patients who were p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between squamous cell CUP and known-primary cancer. The majority of patients with squamous cell CUP were p16+, indicative of HPV association. P16 staining and ECE seem to be the most prognostic features in squamous cell CUP. © 2014 Wiley Periodicals, Inc.

  16. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma

    PubMed Central

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-01-01

    Abstract Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and “en bloc” removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of

  17. Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in advanced non-squamous NSCLC.

    PubMed

    Wang, Bao-Xiao; Ou, Wei; Mao, Xiao-Yong; Liu, Zui; Wu, Hui-Qi; Wang, Si-Yu

    2017-09-01

    Brain metastases remain lethal in lung cancer patients. The impacts of epidermal growth factor receptor (EGFR) mutations and EGFR tyrosine kinase inhibitors (TKIs) on the incidence of brain metastases in patients with advanced non-squamous non-small cell lung cancer (NSCLC) are still uncertain. A total of 1672 patients with advanced non-squamous NSCLC with a definitive report on EGFR mutation status between January 2005 and June 2013 were retrospectively analyzed. The impacts of EGFR mutation status and EGFR TKIs use on the incidence of brain metastases and survival were investigated. Of the 1672 patients, 465 (27.8%) had an EGFR mutation, and 1207 (72.2%) did not. Four hundred and eighteen (25.0%) patients had baseline brain metastases. The cumulative incidence of brain metastases for patients in EGFR+ group was significantly higher than patients in EGFR- group (HR, 1.27; 95% CI 1.06-1.52; P=0.008). The cumulative incidence of brain metastases was also higher for patients who received an EGFR-TKI as their first-line treatment than those who received other first-line treatment (HR, 1.36; 95% CI 1.14-1.64; P=0.001). Patients harboring EGFR mutations had prolonged overall survival (OS) than patients with wild-type EGFR (HR, 0.47; 95% CI 0.41-0.54; P<0.001; median, 25.2 vs. 12.9 months). Both the EGFR mutation-positive status and the use of a TKI are associated with higher incidence of brain metastases for patients with advanced non-squamous NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The primary growth of laryngeal squamous cell carcinoma cells in vitro is effectively supported by paired cancer-associated fibroblasts alone.

    PubMed

    Wang, Mei; Wu, Chunping; Guo, Yu; Cao, Xiaojuan; Zheng, Wenwei; Fan, Guo-Kang

    2017-05-01

    significant differences in the proliferation capacity of laryngeal squamous cell carcinoma cells cocultured with cancer-associated fibroblasts were detected during subculturing. High level of chemokine (C-X-C motif) ligand 12 was detected in the culture supernatant of cancer-associated fibroblasts. The tumor-supporting effect of cancer-associated fibroblasts was significantly inhibited by AMD3100. Our findings demonstrate that the paired laryngeal cancer-associated fibroblasts alone are sufficient to support the primary growth of laryngeal squamous cell carcinoma cells in vitro and that the chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 axis is one of the major contributors.

  19. Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

    PubMed Central

    Bansal, Pranshu; Osman, Diaa; Gan, Gregory N.; Simon, George R.; Boumber, Yanis

    2016-01-01

    Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). With the discovery of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2), RET, and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding. PMID:27200298

  20. (18)F-FDG-PET/CT versus panendoscopy for the detection of synchronous second primary tumors in patients with head and neck squamous cell carcinoma.

    PubMed

    Haerle, Stephan K; Strobel, Klaus; Hany, Thomas F; Sidler, Daniel; Stoeckli, Sandro J

    2010-03-01

    This study assesses the additional value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/CT ((18)F-FDG-PET/CT) with respect to synchronous primaries in patients undergoing panendoscopy for staging of head and neck squamous cell carcinoma. In all, 311 patients underwent both modalities. Cytology, histology, and/or clinical/imaging follow-up served as reference standard. The prevalence of second primary tumors detected by panendoscopy was 4.5%, compared with 6.1% detected by (18)F-FDG-PET/CT. The sensitivity for panendoscopy was 74%, the specificity was 99.7%, the positive predictive value (PPV) was 93%, and the negative predictive value (NPV) was 98%. The sensitivity for (18)F-FDG-PET/CT was 100%, the specificity was 95.7%, the PPV was 59%, and the NPV was 100%. (18)F-FDG-PET/CT is superior to panendoscopy. With a negative (18)F-FDG-PET/CT, the extent of endoscopy can be reduced to the area of the primary tumor. Due to the costs, (18)F-FDG-PET/CT is recommended only in advanced disease to assess potential distant disease. In early-stage cancer, panendoscopy is accurate enough to rule out secondary tumors.

  1. Defining the concept of locally advanced squamous cell carcinoma of the vulva: a new perspective based on standardization of criteria and current evidence.

    PubMed

    Aragona, Alejandro M; Soderini, Alejandro H; Cuneo, Nicasio A

    2014-10-01

    The phrase "locally advanced carcinoma of the vulva" has often been mentioned in the literature, though not accurately defined, or even leading to the interpretation overlapping. Grounded on cervical cancer experience, we are able to state that designing a tailored primary strategy based on clinically measurable adverse prognostic factors represents the cornerstone of therapy. This fact urged us to rethink about the real usefulness of the concept of locally advanced squamous cell carcinoma of the vulva. We will refer to this concept as a clinical entity emerging from a rigorous workup which is a valuable guiding tool in the context of a thorough debate about the best primary treatment approach to be used. Furthermore, bulky tumors of the vulva have been associated with a worse prognosis on several occasions. Some authors have questioned the fact that tumor size has not been considered in the staging system. Finally, a standardized definition will help us compare the results obtained, which is extremely necessary given the worldwide low prevalence of this disease.

  2. Defining the concept of locally advanced squamous cell carcinoma of the vulva: a new perspective based on standardization of criteria and current evidence

    PubMed Central

    Soderini, Alejandro H.; Cuneo, Nicasio A.

    2014-01-01

    The phrase "locally advanced carcinoma of the vulva" has often been mentioned in the literature, though not accurately defined, or even leading to the interpretation overlapping. Grounded on cervical cancer experience, we are able to state that designing a tailored primary strategy based on clinically measurable adverse prognostic factors represents the cornerstone of therapy. This fact urged us to rethink about the real usefulness of the concept of locally advanced squamous cell carcinoma of the vulva. We will refer to this concept as a clinical entity emerging from a rigorous workup which is a valuable guiding tool in the context of a thorough debate about the best primary treatment approach to be used. Furthermore, bulky tumors of the vulva have been associated with a worse prognosis on several occasions. Some authors have questioned the fact that tumor size has not been considered in the staging system. Finally, a standardized definition will help us compare the results obtained, which is extremely necessary given the worldwide low prevalence of this disease. PMID:25142626

  3. Inactivation of p16INK4a in primary tumors and cell lines of head and neck squamous cell carcinoma.

    PubMed

    Kim, H S; Chung, W B; Hong, S H; Kim, J A; Na, S Y; Jang, H J; Sohn, Y K; Kim, J W

    2000-10-31

    Inactivation of the p16INK4a gene by mutation and deletion is common in head and neck squamous cell carcinoma (HNSCC). The present study demonstrates that hypermethylation of the 5' CpG islands can serve as an alternative mechanism for the inactivation of the p16INK4a gene in this tumor. We studied 11 HNSCC cell lines and 17 oral squamous cell carcinoma (OSCC) primary tumors for p16INK4a gene status by protein/mRNA and DNA genetic/epigenetic analyses to determine the incidence of its inactivation. Our study indicates that: (1) inactivation of p16 protein is frequent in HNSCC cell lines (6/11, 54.5%) and OSCC primary tumors (15/17, 88.2%), (2) inactivation of p16INK4a protein is commonly associated with the presence of gene alteration such as mutation, homozygous deletion and especially aberrant methylation, and (3) genomic sequencing of bisulfite-modified DNA shows that the carcinoma develops a heterogeneous pattern of hypermethylation.

  4. Primary squamous cell carcinoma of the rectum: a case report and literature review

    PubMed Central

    Vyas, Neil; Ahmad, Sumair; Bhuiyan, Khaled; Catalano, Carmine; Alkhawam, Hassan; Sogomonian, Robert; Nguyen, James; Walfish, Aaron; Aron, Joshua

    2016-01-01

    Squamous cell carcinoma (SCC) of the rectum is a rare occurrence with an incidence rate of 0.1–0.25% per 1,000 cases. Herein, we report a case of a 52-year-old female who presented with a 2-month history of diffuse lower abdominal pain and hematochezia. Abdominal CT scan revealed a 7-cm irregular rectal mass, and the biopsy showed SCC. PMID:27406458

  5. Morphologic Accuracy in Differentiating Primary Lung Adenocarcinoma From Squamous Cell Carcinoma in Cytology Specimens

    PubMed Central

    Zakowski, Maureen F.; Rekhtman, Natasha; Auger, Manon; Booth, Christine N.; Crothers, Barbara; Ghofrani, Mohiddean; Khalbuss, Walid; Laucirica, Rodolfo; Moriarty, Ann T.; Tabatabai, Z. Laura; Barkan, Güliz A.

    2017-01-01

    Context The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material. Objective To evaluate the accuracy and interobserver variability among cytopathologists in subtyping non–small cell lung carcinoma using cytologic preparations. Design Nine cytopathologists from different institutions submitted cases of non–small cell lung carcinoma with surgical follow-up. Cases were independently, blindly reviewed by each cytopathologist. A diagnosis of ADC or squamous cell carcinoma was rendered based on the Diff-Quik, Papanicolaou, and hematoxylin-eosin stains. The specimen types included fine-needle aspiration from lung, lymph node, and bone; touch preparations from lung core biopsies; bronchial washings; and bronchial brushes. A major disagreement was defined as a case being misclassified 3 or more times. Results Ninety-three cases (69 ADC, 24 squamous cell carcinoma) were examined. Of 818 chances (93 cases × 9 cytopathologists) to correctly identify all the cases, 753 correct diagnoses were made (92% overall accuracy). Twenty-five of 69 cases of ADC (36%) and 7 of 24 cases of squamous cell carcinoma (29%) had disagreement (P = .16). Touch preparations were more frequently misdiagnosed compared with other specimens. Diagnostic accuracy of each cytopathologist varied from 78.4% to 98.7% (mean, 91.7%). Conclusion Lung ADC can accurately be distinguished from squamous cell carcinoma by morphology in cytologic specimens with excellent interobserver concordance across multiple institutions and levels of cytology experience. PMID:27552093

  6. Primary squamous cell carcinoma of the rectum: a case report and literature review.

    PubMed

    Vyas, Neil; Ahmad, Sumair; Bhuiyan, Khaled; Catalano, Carmine; Alkhawam, Hassan; Sogomonian, Robert; Nguyen, James; Walfish, Aaron; Aron, Joshua

    2016-01-01

    Squamous cell carcinoma (SCC) of the rectum is a rare occurrence with an incidence rate of 0.1-0.25% per 1,000 cases. Herein, we report a case of a 52-year-old female who presented with a 2-month history of diffuse lower abdominal pain and hematochezia. Abdominal CT scan revealed a 7-cm irregular rectal mass, and the biopsy showed SCC.

  7. Differential targets of CpG island hypermethylation in primary and metastatic head and neck squamous cell carcinoma (HNSCC)

    PubMed Central

    Smiraglia, D; Smith, L; Lang, J; Rush, L; Dai, Z; Schuller, D; Plass, C

    2003-01-01

    Head and neck squamous cell carcinomas (HNSCC) often metastasise to the cervical lymph nodes. It is known for HNSCC as well as other cancers that progression from normal tissue to primary tumour and finally to metastatic tumour is characterised by an accumulation of genetic mutations. DNA methylation, an epigenetic modification, can result in loss of gene function in cancer, similar to genetic mutations such as deletions and point mutations. We have investigated the DNA methylation phenotypes of both primary HNSCC and metastatic tumours from 13 patients using restriction landmark genomic scanning (RLGS). With this technique, we were able to assess the methylation status of an average of nearly 1300 CpG islands for each tumour. We observed that the number of CpG islands hypermethylated in metastatic tumours is significantly greater than what is found in the primary tumours overall, but not in every patient. Interestingly, the data also clearly show that many loci methylated in a patient's primary tumour are no longer methylated in the metastatic tumour of the same patient. Thus, even though metastatic HNSCC methylate a greater proportion of CpG islands than do the primary tumours, they do so at different subsets of loci. These data show an unanticipated variability in the methylation state of loci in primary and metastatic HNSCCs within the same patient. We discuss two possible explanations for how different epigenetic events might arise between the primary tumour and the metastatic tumour of a person. PMID:12525538

  8. Treatment Outcomes of Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy

    PubMed Central

    Chen, Yen-Hao; Lu, Hung-I.; Chien, Chih-Yen; Lo, Chien-Ming; Wang, Yu-Ming; Chou, Shang-Yu; Su, Yan-Ye; Shih, Li-Hsueh; Li, Shau-Hsuan

    2017-01-01

    The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3–4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3–4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival. PMID:28134308

  9. Comprehensive Genomic Profiling of Advanced Esophageal Squamous Cell Carcinomas and Esophageal Adenocarcinomas Reveals Similarities and Differences.

    PubMed

    Wang, Kai; Johnson, Adrienne; Ali, Siraj M; Klempner, Samuel J; Bekaii-Saab, Tanios; Vacirca, Jeffrey L; Khaira, Depinder; Yelensky, Roman; Chmielecki, Juliann; Elvin, Julia A; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S

    2015-10-01

    Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations. Next-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of >650× for all coding exons of 315 cancer-related genes plus selected introns from 28 genes frequently rearranged in cancer. Results from a single sample were evaluated for all classes of genomic alterations (GAs) including point mutations, short insertions and deletions, gene amplifications, homozygous deletions, and fusions/rearrangements. Clinically relevant genomic alterations (CRGAs) were defined as alterations linked to approved drugs and those under evaluation in mechanism-driven clinical trials. There were no significant differences by sex for either tumor type, and the median age for all patients was 63 years. All ESCCs and EACs were at an advanced stage at the time of sequencing. All 71 ESCCs and 231 EACs featured GAs on profiling, with 522 GAs in ESCC (7.4 per sample) and 1,303 GAs in EAC (5.6 per sample). The frequency of clinically relevant GAs in ESCC was 94% (2.6 per sample) and 93% in EAC (2.7 per sample). CRGAs occurring more frequently in EAC included KRAS (23% EAC vs. 6% ESCC) and ERBB2 (23% EAC vs. 3% ESCC). ESCC samples were enriched for CRGA in PIK3CA (24% ESCC vs. 10% EAC), PTEN (11% ESCC vs. 4% EAC), and NOTCH1 (17% ESCC vs. 3% EAC). Other GAs that differed significantly between histologic tumor types included SMAD4 (14% EAC

  10. Human papillomavirus as prognostic marker with rising prevalence in neck squamous cell carcinoma of unknown primary: A retrospective multicentre study.

    PubMed

    Schroeder, Lea; Boscolo-Rizzo, Paolo; Dal Cin, Elisa; Romeo, Salvatore; Baboci, Lorena; Dyckhoff, Gerhard; Hess, Jochen; Lucena-Porcel, Carlota; Byl, Anne; Becker, Nikolaus; Alemany, Laia; Castellsagué, Xavier; Quer, Miquel; León, Xavier; Wiesenfarth, Manuel; Pawlita, Michael; Holzinger, Dana

    2017-03-01

    Patients with neck squamous cell carcinomas of unknown primary tumour (NSCCUP) present with lymph node metastasis without evidence for a primary tumour. Most patients undergo an aggressive multimodal treatment, which induces severe, potentially unnecessary toxicity. Primary tumours of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers for HPV transformation in NSCCUP could allow focussing on the oropharynx in primary tumour search and could be of value for choice and extent of treatment. In a retrospective multicentre study (Germany, Italy and Spain), we analysed metastatic lymph nodes from 180 NSCCUP patients for the presence of HPV DNA, HPV E6*I mRNA and cellular p16(INK4a) overexpression, a surrogate marker for HPV-induced transformation. HPV status, defined as positivity for viral mRNA with at least one additional marker, was correlated with clinical parameters and survival outcome. A substantial proportion (16%) of NSCCUP were HPV-driven, mainly by HPV16 (89%). HPV prevalence increased with year of diagnosis from 9% during 1998-2004 to 23% during 2005-2014 (p = 0.007). HPV-driven NSCCUP had significantly better overall and progression-free survival rates (p ≤ 0.008). Based on this survival benefit, it is contended that HPV RNA status should be included in NSCCUP diagnosis and in therapeutic decision-making. Deintensification of radiation in patients with HPV-driven NSCCUP, while concurrently concentrating on the oropharynx appears to be a promising therapeutic strategy, the efficacy of which should be assessed in prospective trials. To our knowledge, this is the largest study on HPV in NSCCUP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Framework for advancing improvement in primary care.

    PubMed

    Kates, Nick; Hutchison, Brian; O'Brien, Patricia; Fraser, Brenda; Wheeler, Susan; Chapman, Cheryl

    2012-01-01

    A consistent feature of effective healthcare delivery systems is a strong and well-integrated primary care sector. This paper presents a framework that describes the key elements of high-performing primary care and the supports required to attain it. The framework was developed by the Quality Improvement and Innovation Partnership in Ontario (now part of Health Quality Ontario) to guide the process of primary care transformation. The first section of this paper presents and describes the framework, the second proposes implementation strategies and the third identifies system-level structures and policies needed to support primary care transformation. The framework has three components: (1) the major constituencies that primary care serves – patients, families and their local communities; (2) the desired outcomes of primary care (better health, better care, better value); and (3) the attributes that will enable primary care organizations to attain these outcomes. These attributes are a population focus, patient engagement, partnerships with health and community services, innovation, performance measurement and quality improvement and team-based care.Proposed transformation strategies include building system capacity and capability, ensuring access to resources, providing support from coaches and employing effective spread and sustainability strategies. Broader system-level structures and policies necessary to support and sustain a high-performing and continually improving primary care sector include clear goals; a comprehensive approach to performance measurement; systematic evaluation of innovation; funding incentives aligned with quality outcomes; a system of local primary care organizations; support for inter-professional teams; funding for research to inform primary care policy, management and practice; patient enrolment with primary care providers; and mechanisms to support coordination and integration.

  12. Two different scenarios of squamous cell carcinoma within advanced Basal cell carcinomas: cases illustrating the importance of serial biopsy during vismodegib usage.

    PubMed

    Zhu, Gefei A; Sundram, Uma; Chang, Anne Lynn S

    2014-09-01

    Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment. The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected. These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.

  13. Primary Pure Squamous Cell Carcinoma of the Gallbladder Locally Invading the Liver, Duodenum, and Stomach: A Case Report and Literature Review

    PubMed Central

    Alpuerto, Aldrin C.; Mora, Maximo E.

    2017-01-01

    Primary pure squamous cell carcinoma (SCC) of the gallbladder is an exceptionally rare type of tumor that comprises only 1% of all gallbladder cancer. SCC of the gallbladder portends a worse prognosis than the more common adenocarcinoma variant because of its aggressive invasion to local structures and because it is often diagnosed at an advanced stage. Owing to its rarity, diagnosis and management can be challenging. Herein, we present the case of a 75-year-old female complaining of abdominal pain, nausea, and vomiting. Computed tomography and ultrasonography results of the abdomen were consistent with acute cholecystitis and cholelithiasis. Histologic evaluation of the resected mass revealed a malignant tumor with prominent keratinization, confirming the diagnosis of an invasive primary pure SCC of the gallbladder. Microscopic examination showed direct infiltration to the liver, duodenum, and stomach. This case report describes the hospital course of a patient with SCC of the gallbladder and suggests that gallbladder cancer should be considered as part of the differential diagnosis in elderly patients presenting with acute cholecystitis. In addition, this article will review existing literature to examine the utility of different diagnostic techniques and treatment modalities available in the management of gallbladder cancer. PMID:28251014

  14. Response evaluation after chemoradiotherapy for advanced staged oropharyngeal squamous cell carcinoma: a nationwide survey in the Netherlands.

    PubMed

    Schouten, Charlotte S; Hoekstra, Otto S; Leemans, C René; Castelijns, Jonas A; de Bree, Remco

    2015-11-01

    Following failure of chemoradiotherapy (CRT) for advanced staged oropharyngeal squamous cell carcinomas (OPSCC), residual tumor can often be treated successfully with salvage surgery, if detected early. Current clinical practice in the VU University Medical Center is to perform routine response evaluation, i.e., examination under general anesthesia (EUA), 12 weeks after treatment. However, in the Netherlands there is no consensus on response evaluation in patients with advanced oropharyngeal cancer. Questionnaire on current clinical practice concerning response evaluation after CRT for advanced OPSCC in all eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group. The response rate was 100%. Response evaluation was routinely performed with various methods in five institutions (62.5%) and in one institute (12.5%) only if clinical evaluation was difficult. Two centers (25%) did not perform response evaluation. In case of suspicion of residual disease during follow-up, six centers (75%) performed imaging prior to EUA and two centers (25%) only if clinical evaluation was difficult. Diagnostic techniques used prior to EUA were MRI (87.5%), diffusion-weighted MRI (37.5%), 18F-FDG-PET-CT (75-87.5%) and CT (37.5%). This survey shows a substantial variation in the diagnostic policy concerning response evaluation after CRT for advanced OPSCC in the Netherlands. There is a need for guidelines for response evaluation in patients with advanced oropharyngeal cancer.

  15. Primary bone carcinosarcoma of the fibula with chondrosarcoma and squamous cell carcinoma components

    PubMed Central

    Ishida, Mitsuaki; Kodama, Narihito; Takemura, Yoshinori; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Matsusue, Yoshitaka; Okabe, Hidetoshi

    2013-01-01

    Carcinosarcoma is defined as a malignant neoplasm that is composed of both carcinomatous and sarcomatous components. The occurrence of carcinosarcoma in the bone is extremely rare. In this report, we describe the third documented de novo case of carcinosarcoma of the bone. A 59-year-old Japanese female presented with a painful tumor in her right lower leg. Plane radiography revealed an osteolytic destructive lesion with periosteal reaction and mineralization in the right fibula. Resection of the fibula tumor was performed under a clinical diagnosis of chondrosarcoma. Histopathological study revealed that the tumor was comprised of three components. The main component was proliferation of small round to short spindle cells (approximately 50%), and the remaining components were chondrosarcoma (30%) and squamous cell carcinoma (20%). Immunohistochemically, SOX9 was expressed in the small round to spindle cells and chondrosarcoma component, and p63 and p40 were expressed in all three components. Accordingly, an ultimate diagnosis of carcinosarcoma of the bone was made. The clinicopathological analysis of carcinosarcoma of the bone revealed that this type of tumor affects the middle-aged to elderly persons and occurs in the long bone. All three de novo cases had chondrosarcoma and squamous cell carcinoma components. One of the 3 patients died of the disease. The histogenesis of carcinosarcoma of the bone remains a matter of controversy, although a multpotential stem cell theory has been proposed. Additional studies are required to clarify the clinical behavior and histogenesis of carcinosarcoma of the bone. PMID:24133601

  16. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  17. Definitive radiotherapy for locally advanced squamous cell carcinoma of the vulva and technical issues: a case report

    NASA Astrophysics Data System (ADS)

    Kumar, Gokula; Norhafizah, I.; Shazril, I.; Nursyatina, AR; Aziz, MZ Abdul; Zin, Hafiz M.; Zakir, MK; Norjayadi; Norliza, AS; Ismail, A.; Khairun, N.

    2017-05-01

    This case report describes a complex radical 3D-Conformal Radiotherapy treatment planning, dosimetric issues and outcome of definitive treatment of un-resectable carcinoma of the vulvar in a 42-year old lady. The patient presented with large fungating mass of the vulva which was biopsy confirmed as Keratinizing Squamous Cell Carcinoma. Further staging investigation revealed locally advanced disease (T4), with bilateral inguinal lymph nodes involvement. There is no systemic metastasis or intra-pelvic nodes. The patient was seen by Gynae-Oncology team and the disease was deemed un-resectable without significant morbidity. She was treated to a total dose of 64.8Gy in 36 fractions over 7 weeks with concurrent weekly Cisplatinum in 2 phases. 3D-Conformal radiotherapy technique using the modified segmental boost technique (MSBT, large PA and small AP photon fields with inguinal electron matching) was used. TLD chips were used for in-vivo dose verification in phase 1 and 2 of the treatment. At completion of planned radiotherapy, patient had a complete clinical response, grade 2-3 skin toxicity, grade 2 rectal toxicity, and grade 2 dysuria Vulval Squamous Cell Carcinomas are very radiosensitive tumours and the skills of the treating Radiation Oncologist, Dosimetrists, Physicist, Radiation Therapist and also nurses is of foremost importance is ensuring good clinical outcomes.

  18. Planned neck dissection after chemoradiotherapy in advanced oropharyngeal squamous cell cancer: the role of US, MRI and FDG-PET/TC scans to assess residual neck disease.

    PubMed

    Pellini, Raul; Manciocco, Valentina; Turri-Zanoni, Mario; Vidiri, Antonello; Sanguineti, Giuseppe; Marucci, Laura; Sciuto, Rosa; Covello, Renato; Sperduti, Isabella; Kayal, Ramy; Anelli, Vincenzo; Pichi, Barbara; Mercante, Giuseppe; Spriano, Giuseppe

    2014-12-01

    To investigate the ability of neck ultrasounds (US), magnetic resonance imaging (MRI) and positron emission tomography (FDG-PET/TC) in detecting residual nodal disease after chemoradiotherapy in patients with advanced oropharyngeal squamous cell carcinoma (OPSCC). From 2006 to 2009, 36 consecutive patients affected by OPSCC with bulky nodal disease (>3 cm), treated with primary concurrent chemoradiotherapy, were enrolled prospectively. Nodal response to treatment was assessed by using US, MRI and FDG-PET/CT. Planned neck dissection (ND) was performed in all the patients, and the histopathological node status was compared to the imaging findings in order to establish sensitivity, specificity, accuracy and predictive values of each technique. Metastatic disease was assessed in 18/37 (48.6%) hemi-necks, always localized in levels II-IV. US showed greater sensitivity (77.8%) and, combined with FDG-PET/TC, produced the highest negative predictive value (93.3%). US, MRI and FDG-PET/TC scans showed the highest specificity (100%), accuracy (93.8%) and positive predictive values (100%). In the presence of advanced OPSCC with bulky nodal disease, US combined with FDG-PET/TC could be a reliable and cost-effective strategy to identify patients with complete nodal response to chemoradiotherapy that might not require post-treatment ND but only observation. When residual disease in the neck was detected, selective ND was recommended. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  19. Significance of nuclear p-mTOR expression in advanced oral squamous cell carcinoma with extracapsular extension of lymph node metastases.

    PubMed

    Chen, Tseng-Cheng; Wu, Chen-Tu; Wang, Cheng-Ping; Yang, Tsung-Lin; Lou, Pei-Jen; Ko, Jenq-Yuh; Chang, Yih-Leong

    2015-05-01

    Traditional dichotomous extranodal extension (ENE) grading could not differentiate the risk of subsequent failure in advanced stage oral squamous cell carcinoma (OSCC) patients with ENE. This study investigated nuclear phosphorylated mammalian target of rapamycin (p-mTOR) expression in extranodal tumours and correlated this with clinical outcomes. A total of 218 advanced stage OSCC patients with neck lymph node metastasis were enrolled. Paired paraffin-embedded primary tumour and metastatic lymph node sections were stained with antibody against p-mTOR. Tumours with moderate-to-strong staining in ≧50% of tumour cells were recorded as being positive p-mTOR expression. The correlation of nuclear p-mTOR expression in extranodal tumours with clinicopathologic parameters was analysed. Nuclear p-mTOR expression in primary and extranodal tumours was highly associated with a lower grade of differentiation. The 5-year disease-free survival (DFS) of the patients without ENE, with and without positive nuclear p-mTOR expression in extranodal tumours was 54.3%, 23.4% and 55.2%, respectively. The 5-year overall survival (OS) of the patients without ENE, with and without nuclear p-mTOR expression in extranodal tumours was 55%, 18.7% and 51.3%, respectively. The patients with nuclear p-mTOR expression in extranodal tumours had significantly worse regional and distant disease control. Multivariate analysis also confirmed that nuclear p-mTOR expression in extranodal tumours was a significant independent adverse factor. Nuclear p-mTOR expression can be used as a prognostic indicator predictive of DFS and OS in advanced OSCC patients with ENE. There might be a possibility for targeted therapy in this group of patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Primary processes in sensory cells: current advances.

    PubMed

    Frings, Stephan

    2009-01-01

    In the course of evolution, the strong and unremitting selective pressure on sensory performance has driven the acuity of sensory organs to its physical limits. As a consequence, the study of primary sensory processes illustrates impressively how far a physiological function can be improved if the survival of a species depends on it. Sensory cells that detect single-photons, single molecules, mechanical motions on a nanometer scale, or incredibly small fluctuations of electromagnetic fields have fascinated physiologists for a long time. It is a great challenge to understand the primary sensory processes on a molecular level. This review points out some important recent developments in the search for primary processes in sensory cells that mediate touch perception, hearing, vision, taste, olfaction, as well as the analysis of light polarization and the orientation in the Earth's magnetic field. The data are screened for common transduction strategies and common transduction molecules, an aspect that may be helpful for researchers in the field.

  1. Evaluation of microRNA expression in head and neck squamous cell carcinoma cell lines and in primary culture of oral keratinocytes.

    PubMed

    Andreghetto, Flavia Maziero; Klingbeil, Maria Fatima Guarizo; Soares, Renata Machado; Sitnik, Roberta; Pinto Junior, Décio Dos Santos; Mathor, Monica Beatriz; Nunes, Fabio Daumas; Severino, Patricia

    2011-12-01

    Functional in vitro studies are fundamental to understand the role of microRNAs, small non coding RNA molecules that function as post-transcriptional regulators, in cancer. The objective of this study was to determine the applicability of head and neck squamous cell carcinoma cell lines and human oral keratinocytes as models for functional studies on microRNAs previously identified as deregulated in head and neck squamous cell carcinomas. The expression level of four microRNAs was assessed in cell lines and in primary cultures of oral keratinocytes using specific real-time polymerase chain reactions. The identity of oral squamous cell carcinoma cell lines was confirmed by means of STR (short tandem repeats) profiling. The possible impact of feeder-layer gene expression in global microRNA expression results from keratinocyte primary culture was also evaluated. Significant differences in microRNA gene expression were observed among squamous cell carcinoma cell lines, particularly among cells lines from distinct subsites, as well as between primary culture of human keratinocytes and immortalized keratinocyte cell lines. Primary cultures of human keratinocytes and diverse tumor cell lines are relatively easy to obtain. However, each cell model possesses a characteristic phenotype; whereas one may be useful for a specific study, it may be inappropriate for another. Therefore, it is imperative that suitable cell lines are cautiously selected for functional studies in cancer.

  2. Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib.

    PubMed

    de Vos, J; Ramos Vega, S; Noorman, E; de Vos, P

    2012-09-01

    In human medicine, primary frontal sinus squamous cell carcinoma (pFS-SCC) is not frequently reported. In veterinary medicine, frontal sinus SCC is exclusively described as an extension of nasal cavity SCC. To our knowledge, this is the first publication concerning canine pFS-SCC, diagnosed using histology or cytology and medical imaging, in three dogs. The tumours extended into the orbit or brain cavity, without nasal involvement. Treatment was initiated with piroxicam-carboplatin. Prolongation of carboplatin delivery with a low dose intensity was performed on dogs with a favourable initial response. Dog 1 achieved a complete remission (CR), but was euthanized 344 days after start of therapy. Dog 2, still alive 3 years after start of therapy and in CR, received 14 carboplatin deliveries. In dog 3, after changing the treatment protocol into piroxicam-toceranib, a significant tumour reduction occurred, but the dog was euthanized after 195 days because of a relapse.

  3. Paclitaxel plus cisplatin vs. 5-fluorouracil plus cisplatin as first-line treatment for patients with advanced squamous cell esophageal cancer.

    PubMed

    Liu, Ying; Ren, Zhonghai; Yuan, Long; Xu, Shuning; Yao, Zhihua; Qiao, Lei; Li, Ke

    2016-01-01

    Paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin treatments are effective strategies for patients with advanced esophageal squamous cell carcinoma. This study was to evaluate the safety and efficacy of paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin as first-line chemotherapy for patients with advanced esophageal squamous cell carcinoma. A total of 398 patients with advanced esophageal squamous cell carcinoma who received chemotherapy were included and divided into 2 groups: paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group. 195 patients received paclitaxel plus cisplatin and 203 patients received 5-fluorouracil plus cisplatin. The objective response rates were 42.5% and 38.4% for paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group, respectively (P=0.948). The median progression-free survival was 7.85 months (95% CI, 6.77-8.94 months) for the paclitaxel plus cisplatin group and 6.53 months (95% CI, 5.63-7.43 months) for the 5-fluorouracil plus cisplatin group with significant difference (P=0.02). The median overall survival was 13.46 months (95% CI, 12.01-14.91 months) for the paclitaxel plus cisplatin group and 12.67 months (95% CI, 11.87-13.47 months) for the 5-fluorouracil plus cisplatin group (P=0.204). The first-line chemotherapy of paclitaxel plus cisplatin had better median progression-free survival than 5-fluorouracil plus cisplatin in patients with advanced esophageal squamous cell carcinoma with tolerable toxicities.

  4. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2017-01-19

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  5. Esophageal squamous cell carcinoma (ESCC): advance in genomics and molecular genetics.

    PubMed

    Chen, J; Kwong, D L; Cao, T; Hu, Q; Zhang, L; Ming, X; Chen, J; Fu, L; Guan, X

    2015-01-01

    Esophageal cancer is aggressive and has poor prognosis. Esophageal squamous cell carcinoma (ESCC) is histologically the most prevalent type of esophageal cancer and ranked as the sixth leading cause of cancer death worldwide. In recent years, cancer has been widely regarded as genetic disease, as well as epigenetic abnormalities including DNA methylation, histone deacetylation, chromatin remodeling, gene imprinting and noncoding RNA regulation. In this review, we will provide a general overview of genes, proteins and microRNAs that are involved in the development of ESCC, which aims to enhance our understanding of molecular mechanisms implicated in ESCC development and progression.

  6. Increase in primary surgical treatment of T1 and T2 oropharyngeal squamous cell carcinoma and rates of adverse pathologic features: National Cancer Data Base.

    PubMed

    Cracchiolo, Jennifer R; Baxi, Shrujal S; Morris, Luc G; Ganly, Ian; Patel, Snehal G; Cohen, Marc A; Roman, Benjamin R

    2016-05-15

    There has been increasing interest in the primary surgical treatment of patients with early T classification (T1-T2) oropharyngeal squamous cell carcinoma (OPSCC), with the stated goal of de-escalating or avoiding adjuvant treatment. Herein, the authors sought to determine the degree to which this interest has translated into changes in practice patterns, and the rates of adverse postoperative pathologic features. Patients with T1 to T2 OPSCC in the National Cancer Data Base who were treated from 2004 through 2013 were categorized as receiving primary surgical or primary radiation-based treatment. Trends in treatment selection and factors related to the selection of primary surgery were examined. The rates of adverse pathologic features including positive surgical margins, extracapsular spread (ECS), and advanced T and N classifications after surgery were analyzed. Of 8768 patients with T1 to T2 OPSCC, 68% underwent primary surgical treatment, increasing from 56% in 2004 to 82% in 2013 (P<.0001). The highest versus lowest volume hospitals treated 78% versus 59% of patients with primary surgery (odds ratio, 2.23; 95% confidence interval, 1.55-3.22 [P<.0001]). Higher lymph node classification was found to be predictive of lower rates of primary surgery, but the majority of patients with clinical N2/N3 disease underwent primary surgery. Among patients treated with surgery, positive surgical margins were present in 24% and ECS in 25% of patients. The rate of positive surgical margins decreased over time (P<.0001) and was observed less often at high-volume centers (P<.0001). Among candidates for single-modality therapy (those with clinical T1-T2/N0-N1 disease), 33% had positive surgical margins and/or ECS and 47% had at least 1 adverse feature (T3-T4 disease, N2-N3 disease, positive surgical margins, and/or ECS). Primary surgical treatment among patients with early T classification OPSCC has become more widespread. Cancer 2016;122:1523-32. © 2016 American Cancer

  7. Squamous differentiation in primary urothelial carcinoma of the urinary tract as seen by MAC387 immunohistochemistry.

    PubMed

    Lopez-Beltran, Antonio; Requena, Maria J; Alvarez-Kindelan, Jose; Quintero, Ana; Blanca, Ana; Montironi, Rodolfo

    2007-03-01

    Squamous differentiation (SqD) is variably present in urinary tract tumours, but its significance remains unclear. In this study, SqD was assessed by immunohistochemistry using the monoclonal antibody Mac387 in 145 urothelial tumours (bladder, n = 115; renal pelvis, n = 30). Mac387 detects the myelomonocytic L1 antigen; a member of the calgranulin family shared by epithelial cells and keratinocytes. L1 antigen was shown in SqD in urothelial carcinomas of the bladder or the renal pelvis, including 11 cases with focal SqD unrecognised by conventional analysis. SqD is more frequent in renal pelvic tumours (p = 0.027) and increases with grade/stage mainly in bladder carcinoma (grade, p = 0.05; stage, p = 0.005). Stage Ta/T1 bladder carcinomas with SqD recurred more (p = 0.021). In conclusion, Mac387 efficiently shows SqD in urothelial tumours.

  8. Intracystic Primary Squamous Cell Carcinoma of the Breast: A Challenging Diagnosis

    PubMed Central

    Fraga, João; Simões, Teresa

    2016-01-01

    We report a case of a 36-year-old woman that presented with a painful mass in the outer quadrants of the left breast that had grown rapidly. Physical examination revealed a well circumscribed elastic mass and breast ultrasound showed a cyst measuring 26 mm with vegetation growing on the inner wall. Microscopic evaluation, after fine needle aspiration cytology (FNAC), suggested benign lesion. Tumorectomy was performed and the final diagnosis was a pure squamous cell carcinoma (SCC) of the breast. A simple mastectomy with sentinel node biopsy was performed. The histological study of the specimen revealed residual SCC and the sentinel lymph node was negative. The patient received 6 cycles of adjuvant chemotherapy and adjuvant radiotherapy. Four years later, the patient is free of disease. PMID:27747114

  9. Nimotuzumab plus paclitaxel and cisplatin as the first line treatment for advanced esophageal squamous cell cancer: A single centre prospective phase II trial.

    PubMed

    Lu, Ming; Wang, Xicheng; Shen, Lin; Jia, Jun; Gong, Jifang; Li, Jie; Li, Jian; Li, Yan; Zhang, Xiaotian; Lu, Zhihao; Zhou, Jun; Zhang, Xiaodong

    2016-04-01

    Nimotuzumab (N) is a humanized anti-epidermal growth factor receptor monoclonal antibody. This prospective, single-armed, open label phase II study was conducted to evaluate the efficacy and safety of the combination of paclitaxel (T)/cisplatin (P) with nimotuzumab (N) as first-line treatment in advanced esophageal squamous cell carcinoma (ESCC). Patients with pathologic confirmed unresectable locally advanced or metastatic ESCC were treated with the TPN regimen: nimotuzumab 200 mg weekly, paclitaxel 175 mg/m(2) on day 1 and cisplatin 30 mg/m(2) on days 1 and 2; repeat cycle every 3 weeks for six cycles. Radiotherapy was allowed to be admitted after four cycles of TPN treatment. The primary endpoint was the objective response rate (ORR). The secondary endpoint was the overall survival (OS), duration of disease control (DDC) and toxicities. From March 2011 to April 2013, a total of 59 patients were enrolled and 56 were eligible for the final analysis. Overall RR was 51.8% and disease control rate (DCR) (CR + PR + SD) was 92.9%. Local treatment (radiotherapy or surgery) followed by chemotherapy improved the duration of disease control for patients with metastatic disease and local-regional advanced disease to 8.2 months and more than 23 months, respectively. The OS for patients with metastatic disease was 14.0 months (95% CI: 6.8-21.2 months). The most common G3/4 toxicities were neutropenia (46.4%), nausea (48.3%), alopecia (78.6%), anorexia (42.8%), vomiting (55.4%), arthralgia (62.5%) and anorexia (5%). Adding nimotuzumab to the standard TP regiment was safe, and well tolerated. The TPN regimen is an effective combination as the first-line chemotherapy for the patients with advanced ESCC, and appears more active than current standard regimens. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  10. Impact of Adding Concomitant Chemotherapy to Hyperfractionated Accelerated Radiotherapy for Advanced Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Nuyts, Sandra Dirix, Piet; Clement, Paul M.J.; Poorten, Vincent Vander; Delaere, Pierre; Schoenaers, Joseph; Hermans, Robert; Bogaert, Walter van den

    2009-03-15

    Purpose: To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m{sup 2}) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 73) treated with the same schedule, but without concomitant Cx, between 2001 and 2004. Results: The locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2-year disease-free survival rates were 74% and 60%, respectively. In comparison with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall survival (p = 0.09) was observed. All patients were treated to full radiation dose according to protocol, although the Cx schedule had to be adjusted in 12 patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3 acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p < 0.001) were significantly higher in the chemoradiotherapy group compared with patients treated with RT alone. Conclusion: With this chemoradiotherapy regimen, excellent LRC and survival rates were achieved, with acceptable acute toxicity.

  11. Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck

    SciTech Connect

    Giri, P.G.; Gemer, L.S. )

    1991-09-01

    The authors treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.

  12. 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.

  13. Primary cN0 lip squamous cell carcinoma and elective neck dissection: Systematic review and meta-analysis.

    PubMed

    Bhandari, Kishor; Wang, Dian-can; Li, Shan-chang; Jiang, Bing-hua; Guo, Yu-xing; Koirala, Ujjwal; Du, Xiao-yan

    2015-09-01

    Management of clinically negative lymph nodes (cN0) in primary lip squamous cell carcinoma (SCC) has always been a controversial topic. A systematic review of English-language electronic databases using Medline, Embase, Cochrane library, Google Scholar, SCI, and specific journals on the subject matter was done. Only the studies mentioning primary nonmetastatic lip SCC with cN0 neck treated by surgery only and having at least 2 years of follow-up data were selected. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analysis was followed. The pooled estimate of occult metastasis in neck dissected specimen was 0.17 (95% confidence interval [CI], 0.10-0.28) and that of delayed nodal metastasis in patients without neck dissection was 0.08 (95% CI, 0.01-0.18). The results do not prove sufficient to justify elective treatment of the neck in primary cN0 lip SCC and close observation would be a viable option in such cases. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1392-1400, 2015. © 2014 Wiley Periodicals, Inc.

  14. A Case of Primary Combined Squamous Cell Carcinoma with Neuroendocrine (Atypical Carcinoid) Tumor in the Floor of the Mouth

    PubMed Central

    Terada, Kazuhiro; Uchida, Fumihiko; Kanno, Naomi; Yanagawa, Toru; Bukawa, Hiroki

    2016-01-01

    The combined squamous cell carcinoma (SCC) with neuroendocrine (atypical carcinoid (AC)) tumor is extremely rare in the head and neck. We present here the first case of SCC with AC arising in the floor of the mouth of 65-year-old man. The tumor is comprised of two components of SCC and AC in the biopsy specimen. Neuroendocrine tumor component was classified as AC from the punctate necrosis and 2–10>/10 HPF. Immunohistochemical staining was HMW-CK/34B (+) and P63 (+) in SCC and synaptophysin (+) and CD56 (+) in AC. The pathological diagnosis of SCC with AC was made from both the morphological and immunological exam. Concurrent chemoradiotherapy was performed with radiotherapy 70.2 Gy and chemotherapy of CDDP and VP-16. Although the treatment effect was complete response both of primary tumor and of neck metastases, the recurrence of the primary tumor was after 6 months. Bilateral modified radical neck dissection and tumor resection of the floor of the mouth with reconstructive surgery of anterior lateral thigh free flap were performed. Although the primary and neck tumor did not recur, the multiple lung metastases and mediastinum lymph node metastases occurred at 6 months after surgery. PMID:28116178

  15. Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

    ClinicalTrials.gov

    2017-05-19

    Carcinoma, Squamous Cell of Head and Neck; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

  16. Recent advances in primary ciliary dyskinesia.

    PubMed

    Takeuchi, Kazuhiko; Kitano, Masako; Ishinaga, Hajime; Kobayashi, Masayoshi; Ogawa, Satoru; Nakatani, Kaname; Masuda, Sawako; Nagao, Mizuho; Fujisawa, Takao

    2016-06-01

    Primary ciliary dyskinesia (PCD) is a genetic disease inherited in an autosomal recessive manner. The prevalence of PCD is estimated to be 1 in 20,000 live births. Congenital abnormality of the primary cilia results in situs inversus in 50% of patients. Decreased function of motile cilia causes chronic rhinosinusitis, otitis media with effusion, bronchiectasis and infertility. Cases with situs inversus are considered to show "Kartagener's syndrome", and diagnosis is not difficult. However, in cases without situs inversus, the diagnosis is much more troublesome. PCD without situs inversus is thus probably underdiagnosed. Prolonged chronic cough represents an important symptom that is seen in most patients. The diagnosis of PCD requires the presence of the characteristic clinical phenotypes and either: (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of respiratory epithelium; or (2) identification of mutation in one of the genes known to be associated with PCD. Nasal nitric oxide concentration is extremely low in PCD, and this could be useful for screening of the disease. At present, no fundamental therapies are available for PCD. Diagnosis in the early stages is important to prevent progression of bronchiectasis and deterioration of lung function by guidance for daily life, immunization, cessation of smoking and prompt therapy at the time of respiratory tract infection. Since PCD is inherited in an autosomal-recessive manner, genetic counseling is necessary after definite diagnosis.

  17. Ultra-deep targeted sequencing of advanced oral squamous cell carcinoma identifies a mutation-based prognostic gene signature

    PubMed Central

    Huang, Po-Jung; Huang, Yi; Hsu, An; Tang, Petrus; Chang, Yu-Sun; Chen, Hua-Chien; Yen, Tzu-Chen

    2015-01-01

    Background Patients with advanced oral squamous cell carcinoma (OSCC) have heterogeneous outcomes that limit the implementation of tailored treatment options. Genetic markers for improved prognostic stratification are eagerly awaited. Methods Herein, next-generation sequencing (NGS) was performed in 345 formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC patients. Genetic mutations on the hotspot regions of 45 cancer-related genes were detected using an ultra-deep (>1000×) sequencing approach. Kaplan-Meier plots and Cox regression analyses were used to investigate the associations between the mutation status and disease-free survival (DFS). Results We identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA, CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14 genes were found to predict DFS. A mutation-based signature affecting ten genes (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was devised to predict DFS. Two different resampling methods were used to validate the prognostic value of the identified gene signature. Multivariate analysis demonstrated that presence of a mutated gene signature was an independent predictor of poorer DFS (P = 0.005). Conclusions Genetic variants identified by NGS technology in FFPE samples are clinically useful to predict prognosis in advanced OSCC patients. PMID:25980437

  18. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells

    PubMed Central

    Oliveira-Costa, Joao Paulo; de Carvalho, Alex Fiorini; da Silveira, Giorgia Gobbi; Amaya, Peter; Wu, Yongqi; Park, Kyoung-Joo Jenny; Gigliola, Mabel Pinilla; Lustberg, Maryam; Buim, Marcilei Eliza Cavicchioli; Ferreira, Elisa Napolitano; Kowalski, Luiz Paulo; Chalmers, Jeffrey J.; Soares, Fernando Augusto; Carraro, Dirce Maria; Ribeiro-Silva, Alfredo

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs. PMID:26041877

  19. Impact of p16 expression, nodal status, and smoking on oncologic outcomes of patients with head and neck unknown primary squamous cell carcinoma.

    PubMed

    Dixon, Peter R; Au, Michael; Hosni, Ali; Perez-Ordonez, Bayardo; Weinreb, Ilan; Xu, Wei; Song, Yuyao; Huang, Shao Hui; O'Sullivan, Brian; Goldstein, David P; de Almeida, John R

    2016-09-01

    The prognostic significance of human papillomavirus (HPV) in the context of head and neck squamous cell carcinoma (HNSCC) of cancer of unknown primary (CUP) origin is unclear. Patients treated for CUP at the Princess Margaret Cancer Centre between 2001 and 2013 were stratified by p16 status and retrospectively reviewed. Of the 73 patients included, those with p16-positive tumors (63%) had less advanced nodal status (N1-N2b; 52% vs 89%; p = .035) and less aggressive treatment. Patients with p16-positive tumors had improved 3-year disease-free survival (DFS; 79% vs 56%; p = .012) independent of nodal status and treatment in multivariable analysis (hazard ratio [HR] = 0.27; 95% confidence interval [CI] = 0.08-0.95). Among patients with CUP, p16-positive status is an independent predictor of DFS but not overall survival (OS). © 2016 Wiley Periodicals, Inc. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38: 1347-1353, 2016. © 2016 Wiley Periodicals, Inc.

  20. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells.

    PubMed

    Oliveira-Costa, Joao Paulo; de Carvalho, Alex Fiorini; da Silveira, da Giorgia Gobbi; Amaya, Peter; Wu, Yongqi; Park, Kyoung-Joo Jenny; Gigliola, Mabel Pinilla; Lustberg, Maryam; Buim, Marcilei Eliza Cavicchioli; Ferreira, Elisa Napolitano; Kowalski, Luiz Paulo; Chalmers, Jeffrey J; Soares, Fernando Augusto; Carraro, Dirce Maria; Ribeiro-Silva, Alfredo

    2015-08-28

    Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs.

  1. Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

    SciTech Connect

    Balermpas, Panagiotis; Michel, Yvonne; Wagenblast, Jens; Seitz, Oliver; Sipek, Florian; Rödel, Franz; Rödel, Claus; Fokas, Emmanouil

    2013-07-15

    Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

  2. [Nimotuzumab Combined with Chemotherapy as Second- or Later-line 
in the Treatment of Advanced Lung Squamous Cell Carcinoma].

    PubMed

    Luo, Yang; Li, Junling; Wang, Yan; Hao, Xuezhi; Qu, Fenglian

    2016-10-20

    Epidermal growth factor receptor (EGFR) is commonly overexpressed in lung squamous cell carcinoma and has been associated with impaired prognosis. The aim of this study was to observe the efficacy and safety of nimotuzumab, a anti-EGFR monoclonal antibody, combined with chemotherapy as second- or later-line in the treatment of advanced lung squamous cell carcinoma. A retrospective analysis of clinical data was conducted in 13 patients with advanced lung squamous cell carcinoma, who were administered with nimotuzumab combined with chemotherapy as second-line or later-line treatment. The efficacy of therapy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and safety by National Cancer Institute Common Toxicity Criteria (NCI-CTC) 4.0. Of the 13 advanced squamous-cell lung cancer patients, one patient had complete response (CR), 2 patients had partial response (PR), 4 cases had stable disease (SD), and 6 patients had progressive disease. The overall response rate (ORR) was 23.1% and clinical benefit rate (CBR) was 53.8%. EGFR expression were detected by immunohistochemistry in 6 patients and the results showed 5 patients were EGFR 3+ and the other was EGFR 2+. Of these 6 EGFR positive patients, 1 case had CR, 1 case had PR and 4 cases had SD; ORR was 33.3% and CBR was 100.0%. Grade 3/4 hematological toxicities were observed in 3 (23.1%) patients, and non-hametological toxicities were mild. Nimotuzumab-associated skin rash was found in 2 (15.4%) patients. Nimotuzumab combined with chemotherapy as second- or later-line therapy for advanced squamous cell lung carcinoma was active and well-tolerated, especially for those patients with EGFR positive.

  3. Recent Advances in Biomarkers and Potential Targeted Therapies in Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Yavrouian, Eric J.; Sinha, Uttam K.

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a devastating tumor of the upper aerodigestive tract with no significant change in treatment modality or improvement in survival over the last several decades. Biomarkers are important biological molecules that can be utilized in tumor detection, prognosis, and as targeted therapies. There are several important biomarkers and potential targets in the forefront, including biomarkers of tumorigenesis, signal transduction molecules, proteins involved in angiogenesis, and oncogenic viruses. The clinical applications of these biomarkers are in various states from in vitro and in vivo models, phase II and III clinical trials, to accepted modes of treatment in patients with HNSCC. Given the potential improvement in prognosis that biomarkers and their targeted therapies may have on the treatment of HNSCC, their investigation is both important and essential. PMID:22523710

  4. SU-E-T-275: Radiobiological Evaluation of Intensity Modulated Radiotherapy Treatment for Locally Advanced Head and Neck Squamous Cell Carcinomas

    SciTech Connect

    Rekha Reddy, B.; Ravikumar, M.; Tanvir Pasha, C.R; Anil Kumar, M.R; Varatharaj, C.; Pyakuryal, A; Narayanasamy, Ganesh

    2014-06-01

    Purpose: To evaluate the radiobiological outcome of Intensity Modulated Radiotherapy Treatment (IMRT) for locally advanced head and neck squamous cell carcinomas using HART (Histogram Analysis in Radiation Therapy; J Appl Clin Med Phys 11(1): 137–157, 2010) program and compare with the clinical outcomes. Methods: We have treated 20 patients of stage III and IV HNSCC Oropharynx and hypopharynx with accelerated IMRT technique and concurrent chemotherapy. Delineation of tumor and normal tissues were done using Danish Head and Neck Cancer Group (DAHANCA) contouring guidelines and radiotherapy was delivered to a dose of 70Gy in 35 fractions to the primary and involved lymph nodes, 63Gy to intermediate risk areas and 56 Gy to lower risk areas, Monday to Saturday, 6 Days/week using 6 MV Photons with an expected overall treatment time of 6 weeks. The TCP and NTCP's were calculated from the dose-volume histogram (DVH) statistics using the Poisson Statistics (PS) and JT Lyman models respectively and the Resultwas correlated with clinical outcomes of the patients with mean follow up of 24 months. Results: Using HART program, the TCP (0.89± 0.01) of primary tumor and the NTCP for parotids (0.20±0.12), spinal cord (0.05±0.01), esophagus (0.30±0.2), mandible (0.35±0.21), Oral cavity (0.37±0.18), Larynx (0.30±0.15) were estimated and correlated with clinical outcome of the patients. Conclusion: Accelerated IMRT with Chemotherapy is a clinical feasible option in the treatment of locally advanced HNSCC with encouraging initial tumour response and acceptable acute toxicities. The correlation between the clinical outcomes and radiobiological model estimated parameters using HART programs are found to be satisfactory.

  5. Survival after free flap reconstruction in patients with advanced oral squamous cell carcinoma.

    PubMed

    de Vicente, Juan Carlos; Rodríguez-Santamarta, Tania; Rosado, Pablo; Peña, Ignacio; de Villalaín, Lucas

    2012-02-01

    The purpose of the present study was to assess the effect of free-flap reconstruction on the survival of patients treated for oral squamous cell carcinoma. The present study was based on a retrospective cohort of 98 patients. Of the 98 patients, 49 underwent surgical reconstruction with microvascular tissue transfer (test group) and in 49 (control group), only local or regional flaps were used. For the free-flap group, the average follow-up period was 34.6 months. For the control group, the average follow-up was 39.8 months. At the end of the follow-up period, 23 (47%) and 33 (67.3%) patients had died of oral squamous cell carcinoma in the microvascular reconstructive and control group, respectively. The difference in the final status between the 2 groups was statistically significant (P = .03). In the free-flap group, the mean and median survival time was 65 and 60 months. In the locoregional flap group, the mean and median survival time was 54 and 24 months, respectively. No difference was seen in the survival time between the free-flap and local flap groups (P = .2). Univariate Kaplan-Meier analysis revealed that positive surgical margins were significantly associated with shortened survival in the free-flap group and that recurrence was significant in both reconstructive groups. On multivariate Cox regression analysis, the status of the resection margin (P = .07) and tumor recurrence (P < .0005) showed a significant relationship with survival. Patients with free-flap reconstruction of surgically created defects after oral cancer resection showed a trend toward better 5-year survival. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Squamous differentiation in primary urothelial carcinoma of the urinary tract as seen by MAC387 immunohistochemistry

    PubMed Central

    Lopez‐Beltran, Antonio; Requena, Maria J; Alvarez‐Kindelan, Jose; Quintero, Ana; Blanca, Ana; Montironi, Rodolfo

    2007-01-01

    Squamous differentiation (SqD) is variably present in urinary tract tumours, but its significance remains unclear. In this study, SqD was assessed by immunohistochemistry using the monoclonal antibody Mac387 in 145 urothelial tumours (bladder, n = 115; renal pelvis, n = 30). Mac387 detects the myelomonocytic L1 antigen; a member of the calgranulin family shared by epithelial cells and keratinocytes. L1 antigen was shown in SqD in urothelial carcinomas of the bladder or the renal pelvis, including 11 cases with focal SqD unrecognised by conventional analysis. SqD is more frequent in renal pelvic tumours (p = 0.027) and increases with grade/stage mainly in bladder carcinoma (grade, p = 0.05; stage, p = 0.005). Stage Ta/T1 bladder carcinomas with SqD recurred more (p = 0.021). In conclusion, Mac387 efficiently shows SqD in urothelial tumours. PMID:16882698

  7. Prevalence of Primary HPV in Djibouti: Feasibility of Screening for Early Diagnosis of Squamous Intraepithelial Lesions.

    PubMed

    Petrelli, Alessio; Di Napoli, Anteo; Giorgi Rossi, Paolo; Rossi, Alessandra; Luccini, Daniele; Di Marco, Ilaria; Traoré, Amadou Laico; Gillio Tos, Anna; Trevisan, Morena; Mirisola, Concetta; Costanzo, Gianfranco

    2016-10-01

    In many African Sub-Saharan countries, human papilloma virus (HPV) prevalence data are not available. The current study estimated the prevalence of HPV virus in the female population of Djibouti. Approximately 1000 asymptomatic women 16 to 64 years old were enrolled from 3 of the main health structures of Djibouti in 2014 and 2015; 998 cervical samples were tested for HPV-DNA of high risk types, 499 during the first year, and 499 during the second. Positive samples were typed with an HPV genotyping kit. The women were an average age of 38.8 years (SD, 10.2); 54 women tested positive for HPV (prevalence rate, 5.4% [95% confidence interval, 4.0-6.8]). The highest prevalence was observed among the women younger than 35 years. HPV66 was the most prevalent (15.4% of the infections), followed by HPV31 and HPV52 (10.8% both) and HPV16 (9.2%). All 54 women who tested HPV-positive underwent a Pap test, which was positive in 8 cases (14.8%): 2 high-grade squamous intraepithelial lesion (HSIL) and 6 low-grade (LSIL). The HPV prevalence shows a curve by age similar to that of other African countries. The proportion of HPV16 is among the lowest ever seen in similar studies. The findings suggest to Djibouti the choice of a strategy of screening that includes forms of cytological triage, thus limiting recourse to colposcopy.

  8. Involvement of CELSR3 Hypermethylation in Primary Oral Squamous Cell Carcinoma.

    PubMed

    Khor, Goot Heah; Froemming, Gabrielle Ruth Anisah; Zain, Rosnah Binti; Abraham, Thomas Mannil; Lin, Thong Kwai

    2016-01-01

    Promoter hypermethylation is a frequent epigenetic mechanism for gene transcription repression in cancer and is one of the hallmarks of the disease. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) contributes to cell contact-mediated communication. Dysregulation of promoter methylation has been reported in various cancers. The objectives of this study were to investigate the CELSR3 hypermethylation level in oral squamous cell carcinomas (OSCCs) using methylation-sensitive high-resolution melting analysis (MS-HRM) and to correlate CELSR3 methylation with patient demographic and clinicopathological parameters. Frozen tissue samples of healthy subjects' normal mucosa and OSCCs were examined with regard to their methylation levels of the CELSR3 gene using MS-HRM. MS-HRM analysis revealed a high methylation level of CELSR3 in 86% of OSCC cases. Significant correlations were found between CELSR3 quantitative methylation levels with patient ethnicity (P=0.005), age (P=0.024) and pathological stages (P=0.004). A moderate positive correlation between CELSR3 and patient age was also evident (R=0.444, P=0.001). CELSR3 promoter hypermethylation may be an important mechanism involved in oral carcinogenesis. It may thus be used as a biomarker in OSCC prognostication.

  9. Expression of Ki67 and P53 in primary squamous cell carcinoma of the larynx.

    PubMed

    Ashraf, Mohamad Javad; Maghbul, Maryam; Azarpira, Negar; Khademi, Bighan

    2010-01-01

    We studied a series of untreated laryngeal carcinomas in an attempt to determine the relationship between Ki67 and p53 expression and clinicopathological findings. The relationship between expression of these markers in non-tumoral tissue was also evaluated in order to investigate the possible role of immunohistochemistry as a diagnostic aid in evaluating laryngeal biopsies. Samples from 54 patients with laryngeal squamous cell carcinoma (SCC) were analyzed retrospectively. The uninvolved vocal cord was evaluated as a non-tumoral sample. Paraffin sections of tumors were immunohistochemically stained for p53 and Ki67 expression. Overall, p53 expression was found in 35 (64.8%) of the patients. There was a significant correlation among tumoral p53 expression and tumor location, tumor stage and lymph node involvement. Most grade I tumors had a Ki67 labeling index <50% and a labeling index ≥ 50 was found mainly in high-grade tumors. Tumoral Ki67 expression correlated significantly with tumor grade and mitotic count. There was no correlation between Ki67 labeling index and tumor region. In non-tumoral tissue, 95% of high-grade pre-neoplastic lesions revealed a high expression of Ki67. Non-tumoral p53 expression did not correlate with histological findings. p53 and Ki67 expression in tumoral tissue may be a prognostic marker in patients with laryngeal SCC. Evaluation of the proliferative index in biopsy samples of dysplastic laryngeal mucosa is potentially useful for predicting the progression toward carcinoma.

  10. Radical radiotherapy compared with surgery for advanced squamous cell carcinoma of the base of tongue.

    PubMed

    van de Pol, Marjan; Levendag, Peter C; de Bree, Remco R; Franssen, Jan Huib; Smeele, Ludwig E; Nijdam, Wideke M; Jansen, Peter P; Meeuwis, Cees A; Leemans, C René

    2004-01-01

    This study reports on T3/T4 base of tongue (BOT) tumors treated at the Erasmus MC (Rotterdam) with external beam radiotherapy (EBRT) and brachytherapy (BT). Local control, survival, and functional outcome are compared to results obtained in similar patients treated at the Vrije University Medical Center (VUMC, Amsterdam) by surgery and postoperative RT (PORT). At Rotterdam 46/2 Gy was given to the primary and bilateral neck, followed by an implant using low-dose-rate (LDR 24-35 Gy; median 27 Gy), or fractionated high-dose-rate (fr. HDR 20-28 Gy; median 24 Gy). A neck dissection (ND) was performed in case of N+ disease. 67% of BOT tumors had a T4 cancer. At Amsterdam surgery (S) followed by PORT 40-70 Gy (median 60 Gy) was performed; 26% BOT tumors were T4. Sex, age and nodal distribution were similar. Actuarial local control and survival were computed. Performance Status Scale (PSS) scores were established. Xerostomis was determined on visual analog scales (VAS). Local failure at 5-years was 37% (Rotterdam) vs. 9% (Amsterdam) (p < 0.01). The overall survival was not significantly different (median 2.5 years vs. 2.9 years, respectively [p = 0.47]). The PSS favored brachytherapy. Both groups were equally affected by xerostomia. The 5-year local control was 65% with EBRT and BT. This result is strongly affected by 4 patients with residual disease after implantation. The Rotterdam patients had more advanced BOT tumors (67% vs. 26% T4), explaining the higher local failure rate. Given the organ preservation properties of radiotherapy-only and the better PSS scores, the jury is still out on the optimal treatment for BOT tumors.

  11. Advances in primary lithium liquid cathode batteries

    NASA Astrophysics Data System (ADS)

    Blomgren, George E.

    1989-05-01

    Recent work on cell development and various aspects of cell chemistry and cell development of lithium/thionyl chloride liquid cathode batteries is reviewed. As a result of safety studies, a number of cell sizes can now be considered satisfactory for many applications and the energy densities of these cells is higher than any other developed battery system. Primary batteries operate with low to moderate currents and the anode delay effect appears to be under reasonable control. Reserve cells are in the design stage and operate at high to very high power densities as well as very high energy densities. The nature of the anode film and the operation of the lithium anode has been studied with substantial success and understanding has grown accordingly. Also, studies of the structure of the electrolyte and the effects on the electrolyte of impurities and additives have led to improved understanding in this area as well. Work in progress on new electrolytes is reviewed. The state of the art of mathematical modeling is also discussed and it is expected that this work will continue to develop.

  12. Advanced nurse roles in UK primary care.

    PubMed

    Sibbald, Bonnie; Laurant, Miranda G; Reeves, David

    2006-07-03

    Nurses increasingly work as substitutes for, or to complement, general practitioners in the care of minor illness and the management of chronic diseases. Available research suggests that nurses can provide as high quality care as GPs in the provision of first contact and ongoing care for unselected patients. Reductions in cost are context dependent and rarely achieved. This is because savings on nurses' salaries are often offset by their lower productivity (due to longer consultations, higher patient recall rates, and increased use of tests and investigations). Gains in efficiency are not achieved when GPs continue to provide the services that have been delegated to nurses, instead of focusing on the services that only doctors can provide. Unintended consequences of extending nursing roles include loss of personal continuity of care for patients and increased difficulties with coordination of care as the multidisciplinary team size increases. Rapid access to care is, however, improved. There is a high capital cost involved in moving to multidisciplinary teams because of the need to train staff in new ways of working; revise legislation governing scope of practice; address concerns about legal liability; and manage professional resistance to change. Despite the unintended consequences and the high costs, extending nursing roles in primary care is a plausible strategy for improving service capacity without compromising quality of care or health outcomes for patients.

  13. Home administration of maintenance pemetrexed for patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and phase II feasibility study design

    PubMed Central

    2013-01-01

    Background Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting. Methods Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0–1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m2 every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients’ quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011. Discussion This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home

  14. Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma

    PubMed Central

    Lin, Dong; Ma, Longfei; Ye, Ting; Pan, Yunjian; Shao, Longlong; Song, Zuodong; Jiang, Shujun

    2017-01-01

    Background For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). Methods We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. Results A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. Conclusions Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation. PMID:28275480

  15. Advances of Salivary Proteomics in Oral Squamous Cell Carcinoma (OSCC) Detection: An Update

    PubMed Central

    Sannam Khan, Rabia; Khurshid, Zohaib; Akhbar, Shazia; Faraz Moin, Syed

    2016-01-01

    Oral cancer refers to malignancies that have higher morbidity and mortality rates due to the late stage diagnosis and no early detection of a reliable diagnostic marker, while oral squamous cell carcinoma (OSCC) is amongst the world’s top ten most common cancers. Diagnosis of cancer requires highly sensitive and specific diagnostic tools which can support untraceable hidden sites of OSCC, yet to be unleashed, for which plenty of biomarkers are identified; the most recommended biomarker detection medium for OSCC includes biological fluids, such as blood and saliva. Saliva holds a promising future in the search for new clinical biomarkers that are easily accessible, less complex, accurate, and cost effective as well as being a non-invasive technique to follow, by analysing the malignant cells’ molecular pathology obtained from saliva through proteomic, genomic and transcriptomic approaches. However, protein biomarkers provide an immense potential for developing novel marker-based assays for oral cancer, hence this current review offers an overall focus on the discovery of a panel of candidates as salivary protein biomarkers, as well as the proteomic tools used for their identification and their significance in early oral cancer detection. PMID:28248250

  16. Development of Marjolin's ulcer within one month of burn injury with synchronous primary lung squamous cell carcinoma in an elderly patient: report of a case with allelotyping.

    PubMed

    Wooldridge, Adam N; Griesser, Michael J; Scharschmidt, Thomas; Iwenofu, O Hans

    2011-12-01

    Marjolin's ulcer defines the occurrence of malignancy, usually squamous cell carcinoma, in the setting of a post-traumatic scar often following thermal injury. The latency period from the time of injury to the onset of malignant transformation averages 30 years with the earliest documented incidence occurring 6 weeks after injury. In addition, the occurrence of multiple primary malignancies is a rare event. To our knowledge, we report the first case in the literature of a well-differentiated squamous cell carcinoma developing within 1 month of thermal injury to an elderly patient's right index finger with an incidental synchronous primary lung moderately differentiated squamous cell carcinoma that was morphologically and genetically different as confirmed by allelotyping. There is scant precedent literature on acute Marjolin's ulcers, and the most acute cases have arisen 6 weeks post-burn. There is also little published literature on the incidence of multiple primary malignancies. The quoted incidence of this event is <1%. Clinicians should be aware of the possibility of malignant transformation at the site of prior thermal injury. Biopsy remains the gold standard for diagnosis for Marjolin's ulcer. MRI is the most important diagnostic imaging tool because it will demonstrate the margins and extent of the lesion. Due to the aggressive nature of Marjolin's ulcer, treatment is usually surgical and dependent upon grading. When multiple lesions are detected after staging of a presumed neoplasm, the possibility of multiple primary maligancies should be considered. Allelotyping is a process that can be utilized to determine if multiple masses are related.

  17. Nuclear DNA content and p53 overexpression in stage I squamous cell carcinoma of the tongue compared with advanced tongue carcinomas.

    PubMed Central

    Högmo, A; Kuylenstierna, R; Lindholm, J; Nathansson, A; Auer, G; Munck-Wikland, E

    1998-01-01

    AIMS: To evaluate the predictive value of the nuclear DNA content (image cytometry) and p53 overexpression (immuno-histochemistry using antibody CM-1) in uniformly treated stage I carcinomas of the mobile tongue. Also, to compare stage I carcinomas with advanced tongue carcinomas (stages II-IV). METHODS: Archival formalin fixed, paraffin wax embedded tumour specimens from 54 patients with stage I squamous cell carcinoma and 37 patients with advanced squamous cell carcinoma were analysed. Mean follow up time of the stage I carcinomas was 71 months (median, 62.5; range, 6-175). RESULTS: Twenty three patients (stage I) had recurring disease: 10 had local recurrence (in the tongue) and 13 had regional recurrence (cervical metastases). Locally recurring stage I carcinomas had a more pronounced DNA deviation than the other stage I carcinomas and this degree of deviation was comparable with the DNA content of advanced carcinomas. Stage I carcinomas that developed regional recurrences overexpressed p53 more frequently. In Cox multivariate regression analysis of time to recurrence, DNA deviation was a significant parameter in tumours that recurred locally (p = 0.032). p53 overexpression was the only parameter close to significance for regional recurrence (p = 0.065). CONCLUSIONS: Nuclear DNA content and p53 immunostaining are of value for the prediction of recurrence of stage I squamous cell carcinomas of the mobile tongue. Stage I tongue carcinomas that are prone to local recurrence show the same DNA content as do advanced tongue carcinomas. PMID:10193521

  18. Primary oral squamous cell carcinoma: an analysis of 703 cases in southern Taiwan.

    PubMed

    Chen, Y K; Huang, H C; Lin, L M; Lin, C C

    1999-03-01

    We retrospectively analyzed the records of 703 cases of oral squamous cell carcinoma (SCC) collected from 1 January 1985 to 31 December 1996 at a teaching hospital in southern Taiwan, to identify the characteristics of patients and factors associated with survival. There was an overwhelming male predominance (male:female = 15:1). The mean age of the patients was 52. The peak age of oral SCC patients declined from 50 to 59 years in the first six years (1985-1990) and 40-49 years in the last six years (1991-1996). The most common site of oral SCC was the buccal mucosa with 263 patients (37.4%). Most patients (346/703 patients; 49.2%) had stage III cancer. The most common site of occurrence of SCC was the buccal mucosa (263/703 patients; 37.4%), both overall and in patients who chewed betel quid alone or in combination with cigarette smoking and/or alcohol consumption; the tongue was the most common site among patients without any oral habits (18/48 patients; 37.5%). Furthermore, the age of occurrence was on average 6-12 years younger among patients who chewed betel quid than in those who did not. Of the 703 patients, 496 received treatment with surgery, chemotherapy, and/or radiation therapy. Of these, 209 (42.1%) died. The cancer stage significantly influenced mortality: the 5-year survival rate in patients treated from 1985 to 1991 was 72% in those with stage I, 38.9% in those with stage II, 26.7% in those with stage III, and 11.8% in those with stage IV cancer. Six variables were found to significantly affect survival: tumor size, lymph node involvement, surgery, betel quid chewing, staging, and histological differentiation (all p < 0.05, Kaplan-Meier analysis with log rank test). Of these, surgery and cancer stage independently affected survival in a proportional hazards model (both p < 0.0001). Therefore, the early surgical intervention, and the withdrawal from oral habits, especially betel quid chewing, will be advantageous to patients' survival.

  19. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Montejo, Michael E.; Shrieve, Dennis C.; Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O.; Agarwal, Neeraj; Hitchcock, Ying J.

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  20. Erlotinib and chemoradiation in patients with surgically resected locally advanced squamous cell carcinoma of the head and neck: a GICOR phase I trial.

    PubMed

    Arias de la Vega, F; Contreras, J; de Las Heras, M; de la Torre, A; Arrazubi, V; Herruzo, I; Prieto, I; García-Saenz, J A; Romero, J; Calvo, F A

    2012-04-01

    Standard treatment of advanced squamous cell carcinoma of the head and neck (SCCHN) is concurrent chemoradiation. Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor, which has shown activity in SCCHN. Phase I study aims to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of adding erlotinib to chemoradiation therapy in patients with surgically resected locally advanced SCCHN. Inclusion criteria--SCCHN patients with T3 or T4 primary lesion (except T3N0 with negative resection margins); pathologic N2-N3 disease; poor prognostic findings; age 18-70 years; Eastern Cooperative Oncology Group performance status of zero to one; no evidence of metastasis; adequate organic function and written informed consent. Study design--dose-escalating phase I study with three cohorts of three to six patients each that received increasing doses of erlotinib (100-150 mg/day p.o.) and cisplatin (30-40 mg/m(2) i.v., day 1) for 7 weeks. Radiotherapy--standard regimen of 1.8 Gy daily (5 fractions/week) to a maximum total dose of 63 Gy in 7 weeks. Thirteen male (median age: 57 years) were enrolled. Overall, the regimen was well tolerated. Two of three patients treated at dose level III (erlotinib: 150 mg/day; cisplatin: 40 mg/m(2)) developed DLT consisting of grade 3 infection and grade 3 mucositis. Other toxic effects included diarrhea, asthenia, and rash. Recommended dose for additional studies: erlotinib 150 mg/day p.o.; cisplatin 30 mg/m(2)/week i.v. Erlotinib can be safely combined with chemoradiation without requiring dose reduction of chemo- or radiotherapy in this postsurgical population.

  1. Squamous cell carcinoma of unknown primary site presenting with an abdominal wall lesion as the primary symptom: A case report and review of the literature

    PubMed Central

    ZHANG, YINGLI; CHEN, BO; ZHU, JIANQING; CHEN, LU

    2015-01-01

    Squamous cell carcinoma of unknown primary site (SC CUP) is a rare malignant tumor, and its histogenesis and appropriate treatment are unclear. To the best of our knowledge, this type of carcinoma with abdominal wall lesions as the primary presenting symptom 3 months after laparoscopic surgery, has not been previously described in the literature. In the present study, a postmenopausal 54-year-old female patient was diagnosed with pain from the right abdominal puncture site 3 months after laparoscopic unilateral left salpingo-oophorectomy at a local hospital, at which time the left ovary and Fallopian tube were free of malignant tumor. Computed tomography (CT) imaging showed a subcutaneous nodule with a size of 6.2×3.3 cm. A wide excision of the lesion with safety margins and repair of the abdominal wall was performed, and the histopathological results and various investigations lead to the diagnosis of metastatic well-differentiated SC CUP. The patient underwent three surgeries and eight cycles of Taxol and cisplatin/carboplatin chemotherapy, and received a total of 10.8 Gy palliative radiation. However, the patient succumbed to intestinal bleeding, thrombocytopenia and multiple organ failure with pelvic recurrence and liver metastases at 10 months post-diagnosis. The prognosis of SC CUP, particularly with multiple metastases, is extremely poor. Although chemotherapy, surgery and radiotherapy have a certain role in the treatment, no regimen has been established as a standard therapy and palliative care could be recommended. PMID:26622812

  2. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    SciTech Connect

    Du, Zhongli; Zhang, Wencheng; Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen; Xiao, Zefen; Tan, Wen; and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  3. Paclitaxel plus cisplatin vs. 5-fluorouracil plus cisplatin as first-line treatment for patients with advanced squamous cell esophageal cancer

    PubMed Central

    Liu, Ying; Ren, Zhonghai; Yuan, Long; Xu, Shuning; Yao, Zhihua; Qiao, Lei; Li, Ke

    2016-01-01

    Paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin treatments are effective strategies for patients with advanced esophageal squamous cell carcinoma. This study was to evaluate the safety and efficacy of paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin as first-line chemotherapy for patients with advanced esophageal squamous cell carcinoma. A total of 398 patients with advanced esophageal squamous cell carcinoma who received chemotherapy were included and divided into 2 groups: paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group. 195 patients received paclitaxel plus cisplatin and 203 patients received 5-fluorouracil plus cisplatin. The objective response rates were 42.5% and 38.4% for paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group, respectively (P=0.948). The median progression-free survival was 7.85 months (95% CI, 6.77-8.94 months) for the paclitaxel plus cisplatin group and 6.53 months (95% CI, 5.63-7.43 months) for the 5-fluorouracil plus cisplatin group with significant difference (P=0.02). The median overall survival was 13.46 months (95% CI, 12.01-14.91 months) for the paclitaxel plus cisplatin group and 12.67 months (95% CI, 11.87-13.47 months) for the 5-fluorouracil plus cisplatin group (P=0.204). The first-line chemotherapy of paclitaxel plus cisplatin had better median progression-free survival than 5-fluorouracil plus cisplatin in patients with advanced esophageal squamous cell carcinoma with tolerable toxicities. PMID:27822423

  4. Head and neck cutaneous squamous cell carcinoma metastatic to cervical sublevel IIb lymph nodes occurred from primary sites involving the auricle and adjacent neck.

    PubMed

    Maher, Nigel Gordon; Hoffman, Gary Russell

    2014-03-01

    Neck dissections that include sublevel IIb increase the risk of postoperative shoulder dysfunction. The purpose of this investigation was to document the incidence of level IIb metastatic lymphatic spread in a group of patients undergoing neck dissection as part of the surgical management of cutaneous squamous cell carcinoma of the head and neck. A retrospective review of the pathology records taken from 1 surgeon from June 2006 through June 2013 was carried out. The predictor variable was the primary tumor site. The outcome variable was the metastatic nodal involvement according to neck level and sublevel. Secondary variables included T stage, pathologist, tumor depth, and the presence of perineural, perilymphatic, and perivascular invasion. Data analyses were by descriptive statistics. Thirty-six patients with a total of 40 neck dissections met the inclusion criteria. The average primary site tumor depth was 14.7 mm, and there were 16 cases of poorly differentiated squamous cell carcinoma. Sublevel IIb was involved in 7.5% of cases, all of which occurred from lateralized primary sites of the head and neck. Cutaneous squamous cell carcinoma arising from the auricle and neck sites adjacent to sublevel IIb may have increased risk of metastatic involvement of sublevel IIb nodes. Further studies with larger numbers are required to determine the risk of metastasis to sublevel IIb from midline sites of the face. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  5. Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: a longitudinal population study

    PubMed Central

    2013-01-01

    Background Treatment for advanced stage oropharyngeal squamous cell carcinoma (OPSCC) includes combined chemoradiation therapy or surgery followed by radiation therapy alone or in combination with chemotherapy. The goal of this study was to utilize available evidence to examine survival outcome differences in patients with advanced stage OPSCC treated with these different modalities. Methods Patients with advanced stage OPSCC were identified. Primary outcome measurements were disease specific and overall survival rates with differences examined via Kaplan-Meier and logistic regression analysis. Results 344 patients were enrolled. 94 patients underwent triple modality therapy inclusive of surgery followed by adjuvant combined chemotherapy and radiation therapy (S-CRT). 131 had surgery and radiation therapy (S-RT), while 56 had chemoradiation (CRT) therapy as their primary treatment. A total of 63 patients had single modality radiation therapy and were excluded from analysis due to the large number of palliative patients. Kaplan-Meier overall survival analysis showed that therapy with S-CRT had the highest disease specific survival at five years (71.1%). This is contrasted against S-RT and CRT, with five year survival rates at 53.9%, and 48.6%, respectively. Cox regression showed that the comparison of S-CRT vs. S-RT, and CRT is associated with statistically significant increased hazard ratios of 1.974, and 2.785, indicating that both S-RT and CRT are associated with a reduced likelihood of survival at 5 years when compared to S-CRT. Conclusions In this population based cohort study S-CRT is associated with a 17–22% 5 year disease specific survival benefit compared to CRT or S-RT. PMID:23663568

  6. Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: a longitudinal population study.

    PubMed

    O'Connell, Daniel; Seikaly, Hadi; Murphy, Russell; Fung, Charles; Cooper, Tim; Knox, Aaron; Scrimger, Rufus; Harris, Jeffrey R

    2013-01-01

    Treatment for advanced stage oropharyngeal squamous cell carcinoma (OPSCC) includes combined chemoradiation therapy or surgery followed by radiation therapy alone or in combination with chemotherapy. The goal of this study was to utilize available evidence to examine survival outcome differences in patients with advanced stage OPSCC treated with these different modalities. Patients with advanced stage OPSCC were identified. Primary outcome measurements were disease specific and overall survival rates with differences examined via Kaplan-Meier and logistic regression analysis. 344 patients were enrolled. 94 patients underwent triple modality therapy inclusive of surgery followed by adjuvant combined chemotherapy and radiation therapy (S-CRT). 131 had surgery and radiation therapy (S-RT), while 56 had chemoradiation (CRT) therapy as their primary treatment. A total of 63 patients had single modality radiation therapy and were excluded from analysis due to the large number of palliative patients. Kaplan-Meier overall survival analysis showed that therapy with S-CRT had the highest disease specific survival at five years (71.1%). This is contrasted against S-RT and CRT, with five year survival rates at 53.9%, and 48.6%, respectively. Cox regression showed that the comparison of S-CRT vs. S-RT, and CRT is associated with statistically significant increased hazard ratios of 1.974, and 2.785, indicating that both S-RT and CRT are associated with a reduced likelihood of survival at 5 years when compared to S-CRT. In this population based cohort study S-CRT is associated with a 17-22% 5 year disease specific survival benefit compared to CRT or S-RT.

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

    PubMed Central

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

    2016-01-01

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

  8. Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan

    PubMed Central

    Matsuda, Satoru; Kawakubo, Hirofumi; Ando, Nobutoshi; Kitagawa, Yuko

    2016-01-01

    Multidisciplinary treatment comprising surgery, chemotherapy, and radiotherapy for resectable esophageal squamous cell carcinoma (ESCC) is widely used with improved prognosis. Transthoracic esophagectomy (TTE) with extended lymph node (LN) dissection, known as three field LN dissection, has been recommended for ESCC using open thoracotomy or the thoracoscopic approach. The Japan Clinical Oncology Group (JCOG) trial (JCOG1409) is investigating the patients’ long term survival using the thoracoscopic approach that has been shown to reduce the incidence of postoperative respiratory complication. For perioperative treatment, neoadjuvant chemotherapy using cisplatin plus 5-fluorouracil (5-FU), has been accepted as the standard of care in Japan based on the JCOG9907 trial. In Western countries, neoadjuvant chemoradiotherapy was shown to prolong overall survival for esophageal cancer, including ESCC. Although surgery has been recognized as an initial curative treatment for esophageal cancer, definitive chemoradiotherapy is an alternative treatment for patients who are unable to undergo thoracotomy or who decline to undergo surgery. This article reviews multidisciplinary treatment advances for ESCC. However, current standard treatments are country dependent and the ongoing trial may help standardize ESCC treatment across various societies. PMID:27384595

  9. Positron Emission Tomography for Neck Evaluation Following Definitive Treatment with Chemoradiotherapy for Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Bar-Ad, Voichita; Mishra, Mark; Ohri, Nitin; Intenzo, Charles

    2013-01-01

    Objectives The objective of the current review was to assess published data on the role of Positron Emission Tomography (PET) for evaluation of nodal residual disease after definitive chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods Studies were identified by searching PubMed electronic databases. Only studies using a post-chemoradiotherapy PET for nodal residual disease evaluation were included in the present review. Both prospective and retrospective studies were included. Information regarding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET for detecting nodal residual disease after definitive chemoradiotherapy for HNSCC was extracted and analyzed. Results Twenty published studies were included in the present review. Existing data suggest that a negative post-chemoradiotherapy PET scan is associated with a negative predictive value up to 100%. The sensitivity of PET in detecting nodal residual disease is greater for scans performed ≥ 10 weeks after definitive treatment with chemoradiotherapy for HNSCC. Conclusions Further studies are needed to quantify the reliability of PET in detecting nodal residual disease after chemoradiotherapy for locoregionally advanced HNSCC. The optimal timing of PET imaging after chemoradiotherapy remains to be defined. PMID:21864252

  10. Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment.

    PubMed

    Langer, Corey J; Obasaju, Coleman; Bunn, Paul; Bonomi, Philip; Gandara, David; Hirsch, Fred R; Kim, Edward S; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Socinski, Mark A; Spigel, David R; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-12-01

    Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs.

  11. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

    PubMed Central

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  12. Hypofractionated Accelerated Radiotherapy With Concurrent Chemotherapy For Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Sanghera, Paul; McConkey, Chris; Ho, Kean-Fatt; Glaholm, John; Hartley, Andrew . E-mail: andrew.hartley@uhb.nhs.uk

    2007-04-01

    Purpose: To investigate the tumor control rates in locally advanced head-and-neck cancer using accelerated hypofractionated radiotherapy with chemotherapy. Methods and Materials: The data from patients with squamous cell cancer of the larynx, oropharynx, oral cavity, and hypopharynx (International Union Against Cancer Stage II-IV), who received accelerated hypofractionated radiotherapy with chemotherapy between January 1, 1998, and April 1, 2005, were retrospectively analyzed. Two different chemotherapy schedules were used, carboplatin and methotrexate, both single agents administered on an outpatient basis. The endpoints were overall survival, local control, and disease-free survival. Results: A total of 81 patients were analyzed. The 2-year overall survival rate was 71.6% (95% confidence interval [CI], 61.5-81.8%). The 2-year disease-free survival rate was 68.6% (95% CI, 58.4-78.8%). The 2-year local control rate was 75.4% (95% CI, 65.6-85.1%). When excluding patients with Stage II oral cavity, larynx, and hypopharynx tumors, 68 patients remained. For these patients, the 2-year overall survival, local control, and disease-free survival rate was 67.6% (95% CI, 56.0-79.2%), 72.0% (95% CI, 61.0-83.0%), and 64.1% (95% CI, 52.6-75.7%), respectively. Conclusion: Accelerated hypofractionated radiotherapy and synchronous chemotherapy can achieve high tumor control rates while being resource sparing and should be the subject of prospective evaluation.

  13. Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16INK4a Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma

    PubMed Central

    Yoo, Su Hyun; Son, Eun-Mi; Sung, Chang Okh

    2013-01-01

    Background Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site. Methods We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract. Results All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA. Conclusions Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract. PMID:24421848

  14. Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

    PubMed

    Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

    2014-07-01

    Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

  15. Role of difucosylated Lewis Y antigen in outcome of locally advanced cervical squamous cell carcinoma treated with cisplatin regimen.

    PubMed

    Leone, Julieta; Perez, Juan E; Dominguez, Maria E; Iturbe, Julian; Leone, José P; Mac Donnell, Maria C; Grosman, Gabriel; Vallejo, Carlos T; Leone, Bernardo A; Zwenger, Ariel O

    2016-07-30

    Several mechanisms are involved in the development of resistance to therapy in locally advanced cervical squamous cell carcinoma (LACSCC). Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients treated with different chemotherapy regimens. 126 LACSCC patients at FIGO stages IIB-IVA were selected from the GOCS database: 74 patients included in 3 different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbine-cisplatin) and 52 patients treated with standard radiochemotherapy based on cisplatin (RCBC). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed. Median age was 45.6 years (range: 24.9-80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Tumors with expansive growth showed higher grade (p = 0.0024), mitotic index (p = 0.0505), tumor necrosis (p = 0.0191), LeY+ (p = 0.0034) and CD44+/LeY+ coexpression (p = 0.0334). CD44+ cells were present in 91.3% of patients with local recurrence (p = 0.0317). Advanced stage was associated with LeY+ tumors. Patients treated with RCBC had worse DFS and OS when their tumors expressed LeY (p = 0.0083 and p = 0.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression. In our cohort of LACSCC patients, the coexpression of CD44 and LeY was not associated with worse outcome. However, in the subgroup of patients receiving RCBC, LeY expression was correlated with shorter DFS and OS.

  16. Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma

    PubMed Central

    KAWANO, SHINTARO; ZHENG, YANQUN; OOBU, KAZUNARI; MATSUBARA, RYOTA; GOTO, YUICHI; CHIKUI, TORU; YOSHITAKE, TADAMASA; KIYOSHIMA, TAMOTSU; JINNO, TEPPEI; MARUSE, YASUYUKI; MITATE, EIJI; KITAMURA, RYOJI; TANAKA, HIDEAKI; TOYOSHIMA, TAKESHI; SUGIURA, TSUYOSHI; NAKAMURA, SEIJI

    2016-01-01

    The administration of pre-operative chemotherapy with S-1 and concurrent radiotherapy at a total dose of 30 Gy was clinicopathologically evaluated as a treatment for locally advanced oral squamous cell carcinoma (OSCC) in the present study. The participants comprised 81 patients with OSCC, consisting of 29 patients with stage II disease, 12 patients with stage III disease and 40 patients with stage IV disease. All patients received a total radiation dose of 30 Gy in daily fractions of 2 Gy, 5 times a week, for 3 weeks, and the patients were concurrently administered S-1 at a dose of 80–120 mg, twice daily, over 4 consecutive weeks. Radical surgery was performed in all cases at 2–6 weeks subsequent to the end of pre-operative chemoradiotherapy. The most common adverse event was oropharyngeal mucositis, but this was transient in all patients. No severe hematological or non-hematological toxicities were observed. The clinical and histopathological response rates were 70.4 and 75.3%, respectively. Post-operatively, local failure developed in 6 patients (7.4%) and neck failure developed in 2 patients (2.5%). Distant metastases were found in 7 patients (8.6%). The overall survival rate, disease-specific survival rate and locoregional control rate at 5 years were 87.7, 89.9 and 90.6%, respectively. Locoregional recurrence occurred more frequently in patients that demonstrated a poor histopathological response compared with patients that demonstrated a good response (P<0.01). These results indicate that pre-operative S-1 chemotherapy with radiotherapy at a total dose of 30 Gy is feasible and effective for patients with locally advanced OSCC, and that little or no histopathological response may be a risk factor for locoregional recurrence in this treatment. PMID:27123119

  17. Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-08

    Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

  18. Discovery of the primary site of esophageal squamous cell carcinoma based on axillary lymph nodes metastasis detected with fluorodeoxyglucose positron-emission tomography: report of a case.

    PubMed

    Hagiwara, Nobutoshi; Matsutani, Takeshi; Nomura, Tsutomu; Miyashita, Masao; Yamashita, Naoyuki; Wachi, Eiko; Uchida, Eiji

    2014-01-01

    A 60-year-old Japanese man with no chief complaints underwent 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) during a medical check-up. FDG-PET revealed high tracer uptake in the left supraclavicular and axillary regions but no significant uptake in the esophageal region. However, upper gastrointestinal endoscopy revealed an ulcerative tumor in the middle third of the esophagus. Endoscopic biopsy revealed moderately differentiated squamous cell carcinoma. The patient underwent chemoradiotherapy. Follow-up FDG-PET and computed tomography after therapy revealed a complete response in the lymph nodes. The patient underwent subtotal esophagectomy with gastric tube reconstruction through the posterior mediastinum. However, metastasis to the axillary lymph nodes was detected 16 months after surgery, and lymph node dissection was performed. To our knowledge, this is the first reported case in which the primary site of esophageal squamous cell carcinoma was discovered on the basis of axillary lymph node metastasis detected with FDG-PET.

  19. Primary intraosseous squamous cell carcinoma of the mandible arising from an infected odontogenic cyst: A case report and review of the literature

    PubMed Central

    Grisar, Koenraad; Schol, Matthias; Hauben, Esther; Schoenaers, Joseph; Politis, Constantinus

    2016-01-01

    Primary intraosseous squamous cell carcinoma (PIOSCC) derived from a odontogenic cyst is a rare form of odontogenic carcinoma. The incidence of carcinomas arising from odontogenic cysts is particularly uncommon and is reported to occur in 1–2 individuals for every 1,000 cases. The present case describes a 25-year-old man who was initially diagnosed with a chronically infected odontogenic cyst of the mandible. Biopsy and subsequent histology revealed the presence of squamous cell carcinoma. Therefore, neck dissection and hemimandibulectomy were performed. Ultimately, the situation in the mouth healed, though with a severe amount of scarring. Although the development of PIOSCC from an odontogenic cyst is rare, it should be included in the differential diagnosis for jaw bone radiolucency. PMID:28105241

  20. Recent advances in the epidemiology of primary biliary cirrhosis.

    PubMed

    Gross, Rebekah G; Odin, Joseph A

    2008-05-01

    Since initial reports in the mid-1970s provided epidemiology data on primary biliary cirrhosis (PBC), many studies have characterized the variable frequency of this disease in diverse populations worldwide and sought to identify associated risk factors. Recent research confirms earlier work suggesting that the incidence and prevalence of PBC are on the rise, although geographic variation persists. Analysis of familial and geographic clustering supports the hypothesis that development and progression of the disease hinge on a complex interplay between genetic and environmental risk factors. International clinical data systems are needed to advance PBC epidemiologic research. Given this complexity, international clinical data systems are needed to advance PBC epidemiologic research.

  1. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  2. Frequent loss of heterozygosity in human primary squamous cell and colon carcinomas at 7q31.1: evidence for a broad range tumor suppressor gene.

    PubMed

    Zenklusen, J C; Thompson, J C; Klein-Szanto, A J; Conti, C J

    1995-03-15

    Consistent deletions and loss of heterozygosity (LOH) in polymorphic markers in a determinate chromosomal fragment are known to be indicative of a closely mapping tumor suppressor gene. Deletion of the long arm of chromosome 7 is a frequent trait in many kinds of human primary tumors. We studied LOH of 14 markers on chromosome 7q in order to determine the location of a putative tumor suppressor gene in human primary squamous cell carcinoma of the head and neck and in human primary colon carcinomas. Samples were obtained from 18 primary squamous cell carcinomas of the head and neck and 18 primary colon carcinomas surgically removed from patients at the Fox Chase Cancer Center. Loss of heterozygosity was studied performing PCR amplifications of a set of 14 CA microsatellite repeats encompassing 7q21-qter. Of 18 squamous cell carcinomas of the head and neck cases studied, 12 had LOH at one or more loci on 7q. Fifty-three percent of 15 informative cases had LOH of the CA microsatellite dinucleotide repeat marker D7S522 at 7q31.1-7q31.2. Eleven of 18 colon carcinoma cases had LOH of one or more markers assayed, and the maximum LOH (80% of 10 informative cases) was at D7S522. Distributions of percentage of LOH in both tumor types were normally distributed around microsatellite D7S522. The high incidence of LOH in both tumor types studied suggests that a tumor suppressor gene relevant to the development of epithelial cancers is present on the 7q31.1-31.2, confirming our previous functional evidence for a tumor suppressor gene on chromosome 7.

  3. Analysis of the invasive edge in primary and secondary oral squamous cell carcinoma: An independent prognostic marker: A retrospective study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Soumya, M; D'mello, Sarah; Kuriakose, Moni Abraham; Govindan, Sindhu

    2016-01-01

    Background and Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck carcinomas and corresponds to 95% of all oral cancers with an increasing morbidity and mortality. Its prognosis is affected by several clinicopathologic factors, one of which is pattern of invasion (POI). The histological features of OSCC may differ widely, but there is general agreement that the most useful prognostic information can be deduced from the invasive front of the tumor. In this retrospective study, our aim was to compare the POI, the status of connective tissue and the status of inflammation at the tumor–host interface in primary and recurrent (secondary) OSCC and test the validity of POI, to serve as a potential marker to assess the prognosis of the patient. Materials and Methods: Differentiation of tumors, POI, status of connective tissue and inflammation was assessed in 168 cases of primary and recurrent cases of OSCC. Statistical Analysis: Fisher's exact test was used to determine the statistical significance and P < 0.05 was considered to be statistically significant. Results: Our study showed that majority of the primary and secondary tumors were well differentiated, 117 [95.9%] and 34 [73.9%], respectively. Predominant POI in the primary and secondary tumor group was Pattern II and least was Pattern V. Worst pattern in primary tumor and highest distribution was seen for Pattern III (53.3%), and least for Pattern V (0.00%). In secondary tumors, the predominant worst pattern was Pattern IV (50.0%) and least distribution was seen for Pattern I (0.00%). Connective tissue status for both primary and secondary tumors showed the predominance of loose type (85.2% and 79.2%) and least was variable type (0.8% and 0.6%), respectively. Status of inflammation in the primary tumor group showed a predominance of moderate grade of inflammation (50.0%) and very mild grade of inflammation (6.6%) was the least type. In the secondary tumor group, moderate grade

  4. Maintenance therapy with pemetrexed and bevacizumab versus pemetrexed monotherapy after induction therapy with carboplatin, pemetrexed, and bevacizumab in patients with advanced non-squamous non small cell lung cancer.

    PubMed

    Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Yokomura, Koshi; Koshimizu, Naoki; Sato, Masaki; Toyoshima, Mikio; Shirai, Toshihiro; Masuda, Masafumi; Yamada, Takashi; Imokawa, Shiro; Suda, Takafumi

    2016-05-01

    Single agent maintenance therapy is widely accepted for advanced non-squamous non small cell lung cancer (NSCLC). However, there is no consensus on the initial and maintenance phase regimens, and the clinical benefit of adding bevacizumab to cytotoxic drugs in the maintenance phase remains unclear. Chemotherapy-naïve patients with non-squamous NSCLC were randomly assigned to maintenance therapy with pemetrexed and bevacizumab or pemetrexed alone, after achieving disease control after four cycles of induction therapy with carboplatin (area under the curve = 6), pemetrexed (500 mg/m(2)), and bevacizumab (15 mg/kg). The primary end-point was 1-year progression-free survival (PFS) rate. One hundred ten patients were enrolled in the study, with 55 patients assigned to the two groups. The mean 1-year PFS rate was 43.9% (95% confidence interval [CI]: 29.6-59.2%) in the combination maintenance group and 35.2% (95% CI: 22.1-51.0%) in the pemetrexed maintenance group, and the difference was not significant (p = 0.433). Median PFS measured from enrolment was 11.5 months (95% CI: 7.1-19.0) in the combination maintenance group and 7.3 months (95% CI: 5.7-14.1, hazard ratio: 0.73, 95% CI: 0.44-1.19, log-rank p = 0.198) in the pemetrexed maintenance group. Nasal haemorrhage, hypertension, and proteinuria were significantly more frequent in the combination maintenance group, but they were mild and tolerable. Both maintenance therapy with pemetrexed alone and pemetrexed and bevacizumab in combination were feasible in patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin, pemetrexed, and bevacizumab. According to the selection design, differences in the superiority between these maintenance therapies were not demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Management of locally advanced primary mediastinal synovial sarcoma

    PubMed Central

    Chatterjee, Ambarish S; Kumar, Rajiv; Purandare, Nilendu; Jiwnani, Sabita; Karimundackal, George; Pramesh, CS

    2017-01-01

    Primary mediastinal synovial sarcoma (PMSS) is a relatively rare disease, and patients are treated predominantly with surgery for resectable disease. Management of locally advanced borderline resectable and unresectable PMSS is not only challenging but also lacks standard guidelines. We present three patients with PMSS, who were unresectable or borderline resectable at presentation and were treated with neoadjuvant chemotherapy followed by surgery and postoperative radiotherapy. PMID:28360472

  6. Hsp90 Inhibitor AT13387 in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2017-09-15

    Human Papillomavirus Infection; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  7. nab-Paclitaxel-based induction chemotherapy with or without cetuximab for locally advanced head and neck squamous cell carcinoma.

    PubMed

    Adkins, Douglas; Ley, Jessica; Oppelt, Peter; Wildes, Tanya M; Gay, Hiram A; Daly, Mackenzie; Rich, Jason; Paniello, Randal C; Jackson, Ryan; Pipkorn, Patrik; Nussenbaum, Brian; Trinkaus, Kathryn; Thorstad, Wade

    2017-09-01

    To explore the effect of incorporating cetuximab into induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC). Retrospective comparative analysis of two consecutive prospective phase II trials was performed: trial 1 with nab-paclitaxel/cisplatin/5-FU and cetuximab (APF-C; n=30) and trial 2 with APF (n=30). Patients were scheduled to receive chemoradiation therapy (CRT) with cisplatin. T2-4 classification oropharynx (OP)/larynx/hypopharynx SCC were included. Cumulative incidence of death of disease (CIDD), overall survival (OS), and cumulative incidence of relapse were compared between APF-C and APF. No significant differences in patient or tumor characteristics were noted between the groups. Median follow-up of surviving patients was 52 (25-95) months. Relapse occurred in 5 (17%) patients treated with APF-C and in 2 (7%) treated with APF (p=0.37). In human papillomavirus (HPV)-related OPSCC (n=34), the CIDD at 52months was 3.4% with APF-C and 2.6% with APF and the two-year OSs were 94%. In HPV-unrelated HNSCC (n=25), the CIDD at 52months was 4.4% with APF-C and 3.3% with APF and two-year OSs were 83% and 92%, respectively. CIDD or OS did not differ when stratified by treatment group and HPV status (CIDD: p=0.80; OS: p=0.30). This exploratory retrospective comparative analysis demonstrated no significant difference in CIDD, OS, or cumulative incidence of relapse between patients treated with APF-C or APF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The GNAS1 T393C polymorphism predicts survival in patients with advanced squamous cell carcinoma of the larynx.

    PubMed

    Lehnerdt, Goetz F; Franz, Peter; Winterhoff, Sebastian; Bankfalvi, Agnes; Grehl, Sara; Lang, Stephan; Schmid, Kurt W; Siffert, Winfried; Jahnke, Klaus; Frey, Ulrich H

    2008-12-01

    In previous studies, we have demonstrated that the T-allele of a specific single nucleotide polymorphism (SNP) in the Galphas gene (T393C) correlates with increased Galphas expression and hence apoptosis. The T-allele was associated with a favorable outcome in a variety of human cancers, for example, carcinoma of the urinary bladder, kidney, colorectal, oro- and hypopharynx. The prognostic value of the T393C SNP was retrospectively evaluated in an unselected series of patients treated with curative intent for laryngeal squamous cell carcinomas including all tumor stages with different therapeutic regimens. DNA analysis was performed using DNA from paraffin-embedded tissue samples from 157 patients (142 men, 15 women) with a median follow-up of 68 (3-143) months. The various genotypes were correlated with the overall survival. Survival was significantly dependent on the T393C genotype in advanced American Joint Committee on Cancer (AJCC) stages (III-IV) with an apparent gene-dose effect (P = .0437). Five-year survival rates were 76% for TT, 49% for TC, and 43.5% for CC. In multivariate analysis including age at diagnosis, AJCC stage, grade, gender, and T393C genotypes, patients with CC genotype displayed a higher risk for death with a hazard ratio of 2.59 (95% confidence interval: 1.01-6.64, P = .047) compared with the reference group consisting of T393 homozygous individuals. The T393C SNP is a prognostic marker that could help to identify high risk patients suffering from head and neck cancer.

  9. Chemoradiotherapy for locally advanced squamous cell carcinoma of the oropharynx: Does completion of systemic therapy affect outcomes?

    PubMed

    Baine, Michael; Dorius, Tim; Bennion, Nathan; Alam, Morshed; Smith, Lynette; Zhen, Weining; Ganti, Apar

    2017-10-01

    Current standard of care for locally advanced squamous cell carcinoma of the oropharynx (LA-OPC) consists of concurrent chemoradiotherapy. Due to toxicities associated with this treatment, a significant portion of patients are unable to complete the systemic therapy portion of their treatment course. The impact of incomplete systemic therapy on patient outcomes remains unclear. Demographic, treatment, and outcome data were retrospectively collected for patients with LA-OPC treated definitively with concurrent chemoradiotherapy between 2007 and 2014. Overall and disease-free survivals were estimated via the Kaplan Meier method. Log rank test was used to compare distributions of survival amongst groups. Cox regression was utilized for all multivariate analyses. P values of <0.05 were considered statistically significant. In total, 73 patients with LA-OPC were identified with a median follow-up of 3.4years. Concurrent systemic therapy regimens consisted of bolus cisplatin every 3weeks (76.7%), weekly cetuximab (20.5%) and weekly cisplatin (2.7%). Forty-three patients (58.9%) were able to complete the prescribed concurrent systemic regimens. Upon multivariate analyses, patients who did not complete systemic therapy were noted to have a non-significant trend towards increased distant failure (20.0% vs 7.0%, p=0.12). Additionally, patients who did not complete systemic therapy were noted to have a near significant trend towards increased risk of death (36.7% vs 17.9%, p=0.053). These results suggest that completing systemic therapy may affect survival in patients undergoing definitive radiotherapy with concurrent systemic therapy for LA-OPC. Further, this data demonstrates that though local recurrences are not affected when planned systemic therapy cycles are omitted, the risk of distant failure may increase. These associations require further study to clarify the effect Incomplete systemic therapy has on outcomes for LA-OPC. Copyright © 2017 Elsevier Ltd. All rights

  10. Recent advances in primary palate and midface morphogenesis research.

    PubMed

    Diewert, V M; Wang, K Y

    1992-01-01

    During the sixth week of human development, the primary palate develops as facial prominences enlarge around the nasal pits to form the premaxillary region. Growth of craniofacial components changes facial morphology and affects the extent of contact between the facial prominences. Our recent studies have focused on developing methods to analyze growth of the primary palate and the craniofacial complex to define morphological phases of normal development and to determine alterations leading to cleft lip malformation. Analysis of human embryos in the Carnegie Embryology Collection and mouse embryos of cleft lip and noncleft strains showed that human and mouse embryos have similar phases of primary palate development: first, an epithelial seam, the nasal fin, forms; then a mesenchymal bridge develops through the nasal fin and enlarges rapidly. A robust mesenchymal bridge must form between the facial prominences before advancing midfacial growth patterns tend to separate the facial components as the medial nasal region narrows and elongates, the nasal pits narrow, and the primary choanae (posterior nares) open posterior to the primary palate. In mouse strains with cleft lip gene, maxillary growth, nasal fin formation, and mesenchymal replacement of the nasal fin were all delayed compared with noncleft strains of mice. Successful primary palate formation involves a sequence of local cellular events that are closely timed with spatial changes associated with craniofacial growth that must occur within a critical developmental period.

  11. A Phase Ib Open-Label Multicenter Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers.

    PubMed

    Paik, Paul K; Shen, Ronglai; Berger, Michael F; Ferry, David; Soria, Jean-Charles; Mathewson, Alastair; Rooney, Claire; Smith, Neil R; Cullberg, Marie; Kilgour, Elaine; Landers, Donal; Frewer, Paul; Brooks, Nigel; André, Fabrice

    2017-09-15

    Purpose: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in approximately 20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with antitumor activity in FGFR1-amplified SQCLC cell lines and patient-derived xenografts.Experimental Design: On the basis of these data, we performed a phase I study of AZD4547 in patients with previously treated stage IV FGFR1-amplified SQCLCs (NCT00979134). FGFR1 amplification (FGFR1:CEP8 ≥ 2) was determined by FISH. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, pharmacodynamics, and molecular analyses.Results: Fifteen FGFR1-amplified patients were treated. The most common related adverse events (AE) were gastrointestinal and dermatologic. Grade ≥3-related AEs occurred in 3 patients (23%). Thirteen patients were evaluable for radiographic response assessment. The overall response rate was 8% (1 PR). Two of 15 patients (13.3%) were progression-free at 12 weeks, and the median overall survival was 4.9 months. Molecular tests, including next-generation sequencing, gene expression analysis, and FGFR1 immunohistochemistry, showed poor correlation between gene amplification and expression, potential genomic modifiers of efficacy, and heterogeneity in 8p11 amplicon.Conclusions: AZD4547 was tolerable at a dosage of 80 mg oral twice a day, with modest antitumor activity. Detailed molecular studies show that these tumors are heterogeneous, with a range of mutational covariates and stark differences in gene expression of the 8p11 amplicon that likely explain the modest efficacy of FGFR inhibition in this disease. Clin Cancer Res; 23(18); 5366-73. ©2017 AACR. ©2017 American Association for Cancer Research.

  12. ACR Appropriateness Criteria® management of locoregionally advanced squamous cell carcinoma of the vulva.

    PubMed

    Kidd, Elizabeth; Moore, David; Varia, Mahesh A; Gaffney, David K; Elshaikh, Mohamed A; Erickson, Beth; Jhingran, Anuja; Lee, Larissa J; Mayr, Nina A; Puthawala, Ajmel A; Rao, Gautam G; Small, William; Wahl, Andrew O; Wolfson, Aaron H; Yashar, Catheryn M; Yuh, William; Cardenes, Higinia Rosa

    2013-08-01

    Locoregionally advanced vulvar cancer (LRAVC) is a rare disease that presents many challenging medical decisions. An expert panel was convened to reach consensus on the most appropriate pretreatment assessment and therapeutic interventions in LRAVC patients. The American College of Radiology Appropriateness Criteria are evidenced-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journal and the application of a well-established consensus methodology (modified Delphi) to rate appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to formulate recommendations. Three clinical variants were developed to address common scenarios in the management of LRAVC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches, with numerical ratings and descriptive commentary. In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate management of patients with LRAVC.

  13. Promoting Advance Directives Among Elderly Primary Care Patients

    PubMed Central

    Wissow, Lawrence S; Belote, Amy; Kramer, Wade; Compton-Phillips, Amy; Kritzler, Robert; Weiner, Janathan P

    2004-01-01

    OBJECTIVE To determine efficient ways of promoting advance directives among heterogeneous populations of elderly ambulatory patients. DESIGN One-year quasi-experimental trial. SETTING Five suburban and urban health centers in one region of a large managed care organization. One additional suburban center served as a control site. PARTICIPANTS Individuals ages 65 and older (N= 2,120) who were continuously enrolled and had a health maintenance visit with their primary care provider during the study year. INTERVENTION Physician education (oral and written) and physician and patient prompts to discuss advance directives. MAIN RESULTS Sixty-six (7.8%) of patients at the intervention centers completed new advance directives, versus 9 of 1,277 (<1%) at the comparison center (P < .001). Patients 75 and older were twice as likely (odds ratio [OR], 2.0; 95% confidence limits [CL], 1.2 to 3.3) as those 65 to 74 to file a new advance directive, and the odds were twice as great (OR, 2.6; 95% CL, 1.4 to 4.6) at centers serving communities with median household income over the state median. Gender, recent hospitalization, emergency room visits, and number of chronic conditions were not related to making new directives nor was predominant ethnicity of the center community (African-American versus white). Adjusted for these factors, the intervention resulted in a 20-fold increase (95% CL, 10.4 to 47.8) in the odds of creating a new advance directive. Doctors reported barriers of time and unwillingness to press discussions with patients. CONCLUSIONS A replicable intervention largely targeting doctors achieved a modest increase in advance directives among elderly ambulatory patients. Future interventions may need to target lower-income patients, “younger” elderly, and more specifically address doctors’ attitudes and comfort discussing advance directives. PMID:15333059

  14. The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review.

    PubMed

    Boscolo-Rizzo, Paolo; Schroeder, Lea; Romeo, Salvatore; Pawlita, Michael

    2015-12-01

    A subset of head and neck squamous cell carcinoma, which mainly arise from the crypt epithelium of the palatine and lingual tonsils, may be caused by high-risk human papillomavirus (HPV) infections. This topographical restriction together with other overlapping clinical features have led investigators to suspect that HPV plays a role in squamous cell carcinoma of unknown primary (SCCUP) site metastatic to neck lymph nodes. We performed a systematic review of articles listed in PubMed to identify studies testing HPV and/or p16(INK4a) status (p16) in tissue samples from initial and definitive SCCUP. The prevalence of HPV-related (HPV DNA-positive and/or p16 positive) SCCUP was calculated for all the SCCUP, initial SCCUP, suspected definitive SCCUP, and true definitive SCCUP whenever a minimum of 10 cases of each category was identified. In addition, data concerning patients' diagnostic work-up, the HPV detection methods, and the correlations between HPV-status, the localization of the occult primary tumor, and the clinical outcome were also extracted. Eighteen retrospective cohort studies, assessing a total of 659 patients, met the inclusion criteria. The overall median prevalences of HPV-DNA(pos), of p16(pos), and of positivity for both HPV markers were, respectively, 37.0, 48.5, and 36.0 %. Patients with diagnosis of initial SCCUP had overall median prevalences of HPV-DNA(pos), of p16(pos), and of positivity for both HPV markers, respectively, of 81.8, 86.2, and 80.8 %. The data uncovered by this systematic review confirm that SCCUP is frequently causally associated to HPV-driven oropharyngeal squamous cell carcinomas. This finding supports the view that HPV-status could be routinely assessed in SCCUP patients as it may lead to identifying the primary tumor and the decision to de-escalate treatment.

  15. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-09-25

    Head and Neck Squamous Cell Carcinoma; Human Papillomavirus Negative; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

  16. [Clinical evaluations of neoadjuvant chemotherapy with DN and FP regimens for patients with middle or lower thoracic locally advanced esophageal squamous cell carcinoma].

    PubMed

    Yang, Hongxia; Yao, Juan; Wen, Hong; Yu, Lan; Liu, Wu; Liang, Hua; Han, Shuhong

    2015-05-19

    To explore the efficacies and side effects of neoadjuvant chemotherapy with DN (docetaxel plus cisplatin) and FP (nedaplatin plus cisplatin) regimens for patients with upper or middle thoracic locally advanced esophageal squamous cell carcinoma. From January 2008 to January 2012, a total of 124 patients with upper or middle thoracic locally advanced esophageal squamous cell carcinoma were randomized into DN group (n = 64) and FP group (n = 60). Both groups received neoadjuvant chemotherapy. The treatment schedule was recycled every 3 weeks. After 2 cycles, those with potential surgical resection underwent surgery. The 2-year overall, locoregional relapse-free and distant metastasis-free survival rates in DN and FP groups were 71.1% and 66.7%, 65.0% and 63.0%, 78.3% and 74.3% respectively (P > 0.05). The incidence of leucopenia was higher in DN group than that in FP group (P < 0.05). And the occurrence rates of gastrointestinal toxicity and mucositis were significantly higher in FP group than those in DN group. No perioperative mortality occurred with a low incidence of postoperative complications. The rates of overall response, resection, postoperative complications and pathological complete rates response were similar in two groups. And the rates of downstage and R0 resection were significantly higher in DN group than those in FP group (P < 0.05). For patients with middle or lower thoracic locally advanced esophageal squamous cell carcinoma, neoadjuvant chemotherapies of docetaxel and nedaplatin may achieve excellent outcomes in clinical response and 2-year survival rate. And the side effects are clinically acceptable.

  17. Squamous cell carcinoma of cervical lymph nodes from an unknown primary site: The impact of neck dissection.

    PubMed

    Lou, Jianlin; Wang, Shengye; Wang, Kejing; Chen, Chao; Zhao, Jianqiang; Guo, Liang

    2015-10-01

    To investigate the treatment strategies of squamous cell carcinoma of cervical lymph nodes from an unknown primary site (SCCUP) and the value of neck dissection (ND). The study included 133 patients referred to the Zhejiang Cancer Hospital from 2001 to 2012, with 109 males and 24 females. Distribution of patients by N status was as follows: N1 - 14 cases; N2a - 21 cases; N2b - 78 cases; N2c - 7 cases; and N3 - 13 cases. 104 patients underwent surgeries of ND while 29 patients underwent nonsurgical treatment. Among 104 patients, 24 underwent classic radical ND, 16 modified ND, 53 selective ND, and 11 extended ND. The selection of surgical strategy was determined by the extent and location of disease. According to the range of ND, 50 patients underwent ND for Levels I-V, 46 for Levels II-V, 4 for Levels I-III, 3 for Levels II-VI, and 1 for Levels I-VI. The data were analyzed with SPSS version 16.0. The differences between groups were calculated by χ2 tests. The actual overall survival (OS) rates were calculated by the Kaplan-Meier method. Different factors affecting the OS were determined by the log-rank test on univariate analysis. Cox regression was used to evaluate the multivariate analysis. The 5-year OS rate of the whole cohort was 67.1%; and the median survival time was 70.0 months. The 5-year OS of ND group and of the non-ND group were 71.3% and 53.2%, respectively (P = 0.061). Cox analysis indicated that N stage (P = 0.000), bilateral neck metastasis (P = 0.001), extracapsular spread (ES) (P = 0.016), and ND (P = 0.028) were independent prognostic factors for the OS of SCCUP. 25 patients (18.8%) had neck recurrence or residue. The locoregional failure rate of ND group and of the non-ND group were 13.5% and 37.9%, respectively (P = 0.003). Logistic regression analysis indicated that higher N stage was the main risk factor for locoregional failure (P = 0.015). N stage, bilateral neck metastasis, ES, and ND were the main factors for the survival rate of SCCUP

  18. Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck

    SciTech Connect

    Tishler, Roy B. . E-mail: roy_tishler@dfci.harvard.edu; Posner, Marshall R.; Norris, Charles M.; Mahadevan, Anand; Sullivan, Christopher; Goguen, Laura; Wirth, Lori J.; Costello, Rosemary; Case, MaryAnn; Stowell, Sara; Sammartino, Dan; Busse, Paul M.; Haddad, Robert I.

    2006-07-15

    Purpose: In a Phase I/II trial, we investigated concurrent weekly docetaxel and concomitant boost radiation in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) after induction chemotherapy. Patients and Methods: Patients presented with American Joint Committee on Cancer Stage III/IV and were treated initially with induction chemotherapy using cisplatinum/5-fluorouracil (PF), carboplatinum-5-FU, or docetaxel-PF. Patients then received docetaxel four times weekly with concomitant boost (CB) radiation (1.8 Gy once-daily X20, 1.8/1.5 Gy twice a day). Fifteen patients each received 20 mg/M{sup 2} and 25 mg/M{sup 2}. Results: Thirty-one patients were enrolled and 30 were evaluable for response and toxicity. Median follow-up was 42 months (range, 27-63 months). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, and unknown primary 4. Eighty-seven percent of patients had N2/N3 disease; 60% had T3/T4 disease. Twenty percent of patients had a complete response (CR) to induction chemotherapy. After chemoradiotherapy, 21 of 30 patients had a CR, 2 had progressive disease, and 7 had partial response (PR). Nineteen of 26 patients presenting with neck disease had neck dissections, and 7 of 19 were positive. Ninety-three percent of all patients were rendered disease-free after all planned therapy. Treatment failed in 8 patients, and 7 have died of disease. An additional patient died with no evidence of disease. Twenty-one patients (70%) are currently alive with no evidence of disease. No acute dose-limiting toxicity was observed at either dose level. Conclusions: This intensive treatment regimen of concurrent docetaxel/concomitant boost radiation and surgery after induction chemotherapy in poor prognosis patients yields good local regional control and survival. Docetaxel/CB chemoradiotherapy represents an aggressive alternative regimen to platinum-based chemoradiotherapy or surgery in patients who have a poor response to

  19. Stenting as a palliative method in the management of advanced squamous cell carcinoma of the oesophagus and gastro-oesophageal junction

    PubMed Central

    Kużdżał, Jarosław

    2016-01-01

    Advanced squamous cell carcinoma of the oesophagus and gastroesophageal junction usually requires palliative treatment, and the method of choice is stenting. There are several types of stents currently available, including: self-expandable metallic stents (fully or partially covered); self-expandable plastic stents; biodegradable stents. Each of the mentioned stents has its advantages and limitations, and requires a proper, patient-tailored selection. Due to the close anatomical relationship between the oesophagus and bronchial tree, some patients may require bilateral stenting. Oesophageal stenting may not only be considered as a palliative procedure, but can also be implemented to alleviate dysphagia during preoperative chemotherapy and/or radiotherapy. PMID:28133493

  20. Biweekly Carboplatin Plus Gemcitabine as First-Line Treatment of Elderly Patients With Advanced Squamous Non-Small-cell Lung Cancer: A Multicenter Phase I-II Trial by the Hellenic Oncology Research Group.

    PubMed

    Karampeazis, Athanasios; Vamvakas, Lambros; Kentepozidis, Nikolaos; Polyzos, Aris; Chandrinos, Vassilis; Rigas, Georgios; Christofyllakis, Charalambos; Kotsakis, Athanasios; Hatzidaki, Dora; Pallis, Athanasios G; Georgoulias, Vassilis

    2016-11-01

    The present study was a phase I/II study to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities of the biweekly carboplatin/gemcitabine combination and evaluate its safety and efficacy in patients aged ≥ 70 years with advanced squamous non-small-cell lung cancer (NSCLC). Patients aged ≥ 70 years with advanced or metastatic squamous NSCLC received escalated doses of carboplatin (area under the curve [AUC] 2-2.5 intravenously) and gemcitabine (800-1100 mg/m(2) intravenously) every 2 weeks (phase I). In the phase II, the drugs were administered at their previously defined MTDs (carboplatin, AUC 2.5; gemcitabine, 1100 mg/m(2)). The primary endpoint was the overall response rate. A total of 69 patients were enrolled (phase I, n = 15). The median age was 76 years (range, 70-84 years); 52 patients had stage IV disease, and 61 and 8 patients had Eastern Cooperative Oncology Group performance status of 0 to 1 and 2, respectively. The MTDs could not be reached at the predefined last dose levels. The dose-limiting toxicities were grade 5 renal toxicity and grade 3 thrombocytopenia. In the phase II study, the overall response rate was 35.8% (95% confidence interval [CI], 23.0%-48.8%). In the intention-to-treat analysis, the median progression-free survival was 6.7 months (95% CI, 4.2-8.8 months), and the median overall survival was 13.3 months (95% CI, 7.1-19.6 months). Grade 3 or 4 neutropenia was observed in 7 patients (12.3%), grade 3 or 4 thrombocytopenia in 4 patients (7.1%), and grade 2 or 3 fatigue in 10 patients (17.5%). One toxic death occurred in the phase I of the study. The biweekly regimen of gemcitabine and carboplatin showed satisfactory efficacy and a favorable toxicity profile in elderly patients with advanced or metastatic squamous cell NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2012-12-13

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

  2. Safety Analyses of Pemetrexed-cisplatin and Pemetrexed Maintenance Therapies in Patients With Advanced Non-squamous NSCLC: Retrospective Analyses From 2 Phase III Studies.

    PubMed

    Langer, Corey J; Paz-Ares, Luis G; Wozniak, Antoinette J; Gridelli, Cesare; de Marinis, Filippo; Pujol, Jean-Louis; San Antonio, Belen; Chen, Jian; Liu, Jingyi; Oton, Ana B; Visseren-Grul, Carla; Scagliotti, Giorgio V

    2017-09-01

    In a phase III study, maintenance pemetrexed showed superior survival over placebo (PARAMOUNT) for patients with advanced non-squamous non-small cell lung cancer (NSCLC) who completed 4 cycles of pemetrexed plus cisplatin (PC) induction therapy, with low incidence of treatment-emergent adverse events (TEAEs) generally associated with pemetrexed. Prior analyses did not account for toxicities carried over from induction; thus, the current analysis was developed to understand toxicities that may be attributed to pemetrexed maintenance versus PC induction, and how treatment duration affects toxicity. Selected clinically relevant TEAEs were explored in 2 analyses: assessing induction versus maintenance treatment in PARAMOUNT, and comparing PC from PARAMOUNT with toxicity data from a previous phase III study that established the role of PC in front-line therapy of non-squamous NSCLC (JMDB trial). In PARAMOUNT, the incidence of most drug-related TEAEs was higher during induction than maintenance, for both the pemetrexed and placebo randomized populations. The majority of TEAEs during maintenance, except renal events, were carried over from induction with no change in severity from the end of induction; the incidence of TEAEs associated with pemetrexed maintenance was low. The cross-trial analysis showed that 6 cycles of PC in JMDB compared with 4 cycles in PARAMOUNT increased grade 1/2 fatigue (34.1% vs. 25.0%), anemia (24.0% vs. 13.5%), and renal events (11.8% vs. 3.6%). Safety data presented here support the favorable risk benefit of 4 cycles of PC followed by maintenance pemetrexed in patients with advanced non-squamous NSCLC. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Capecitabine and Lapatinib Ditosylate in Treating Patients With Squamous Cell Cancer of the Head and Neck

    ClinicalTrials.gov

    2017-01-24

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

  4. Primary Metastatic Squamous Cell Carcinoma of the Male Urethra Presenting with Scrotal Abscess and Subsequent Development of Fournier's Gangrene.

    PubMed

    Moore, Sarah J; Rashidipour, Omid; Moore, Ronald B

    2016-01-01

    This male patient presented with a scrotal abscess and urinary obstruction. The patient's history included a perineal abscess and the development of urethrocutaneous fistulae (watering-can perineum). He underwent multiple debridement procedures without resolution. During the fifth debridement for Fournier's gangrene, a biopsy revealed invasive squamous cell carcinoma. The patient was bedridden because of the large mass, a wide en bloc resection with lymphadenectomy and reconstruction was performed revealing a large (22 cm) squamous cell carcinoma originating from the urethra. He also received palliative chemoradiotherapy and hip hemiarthroplasty. Unfortunately, he succumbed to the disease. Given the recognized relationship between inflammation and the development of cancer, it is important to entertain a differential diagnosis of cancer, especially with erosive infections. This case report highlights the all too common late presentation of urethral cancer. Interestingly, despite correction of the bedridden state with palliative surgery, the patient did not perceive an improvement in quality of life based on the FACT-G questionnaire.

  5. Evaluation of advanced access in the national primary care collaborative.

    PubMed

    Pickin, Mark; O'Cathain, Alicia; Sampson, Fiona C; Dixon, Simon

    2004-05-01

    An aim of the National Primary Care Collaborative is to improve quality and access for patients in primary care using principles of Advanced Access. To determine whether Advanced Access led to improved availability of appointments with general practitioners (GPs) and to examine GPs' views of the process. Observational study. Four hundred and sixty-two general practices in England participating in four waves of the collaborative during 2000 and 2001. Regression analysis of the collaborative's monthly data on the availability of GP appointments for the 352 practices in waves 1-3, and a postal survey of lead GPs in all four waves. The main outcome measures were the change in mean time to the third available appointment with GPs, and the proportion of GPs thinking it worthwhile participating in the collaborative. The time to the third available appointment improved from a mean of 3.6 to 1.9 days, difference = 1.7 days, 95% confidence interval (CI)= 1.4 to 2.0 days. It improved in two-thirds of practices (66% [219/331]), remained the same in 16% (53/331), and worsened in 18% (59/331). The majority of GPs in all four waves, 83% (308/371, 95% CI = 79 to 87), felt that it was worthwhile participating in the collaborative, although one in 12 practices would not recommend it. One-fifth of GPs cited a lack of resources as a constraint, and some expressed concerns about the trade-off between immediate access and continuity of care. Advanced Access helped practices to improve availability of GP appointments, and was well received by the majority of practices.

  6. Evaluation of Advanced Access in the National Primary Care Collaborative

    PubMed Central

    Pickin, Mark; O'Cathain, Alicia; Sampson, Fiona C; Dixon, Simon

    2004-01-01

    Background: An aim of the National Primary Care Collaborative is to improve quality and access for patients in primary care using principles of Advanced Access. Aims: To determine whether Advanced Access led to improved availability of appointments with general practitioners (GPs) and to examine GPs' views of the process. Design: Observational study. Setting: Four hundred and sixty-two general practices in England participating in four waves of the collaborative during 2000 and 2001. Method: Regression analysis of the collaborative's monthly data on the availability of GP appointments for the 352 practices in waves 1–3, and a postal survey of lead GPs in all four waves. The main outcome measures were the change in mean time to the third available appointment with GPs, and the proportion of GPs thinking it worthwhile participating in the collaborative. Results: The time to the third available appointment improved from a mean of 3.6 to 1.9 days, difference = 1.7 days, 95% confidence interval (CI) = 1.4 to 2.0 days. It improved in two-thirds of practices (66% [219/331]), remained the same in 16% (53/331), and worsened in 18% (59/331). The majority of GPs in all four waves, 83% (308/371, 95% CI = 79 to 87), felt that it was worthwhile participating in the collaborative, although one in 12 practices would not recommend it. One-fifth of GPs cited a lack of resources as a constraint, and some expressed concerns about the trade-off between immediate access and continuity of care. Conclusion: Advanced Access helped practices to improve availability of GP appointments, and was well received by the majority of practices. PMID:15113514

  7. A Phase II Trial of Induction nab-Paclitaxel and Cetuximab Given With Cisplatin and 5-Fluorouracil Followed by Concurrent Cisplatin and Radiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Adkins, Douglas; Ley, Jessica; Trinkaus, Kathryn; Thorstad, Wade; Lewis, James; Wildes, Tanya; Siegel, Barry A.; Dehdashti, Farrokh; Gay, Hiram; Mehan, Paul; Nussenbaum, Brian

    2013-01-01

    Background Complete Response (CR) at the primary tumor site as assessed by clinical examination following induction chemotherapy with cisPlatin and 5-Fluorouracil (5-FU)[PF] is a favorable predictive factor for overall survival and disease-control in patients with locally advanced squamous cell carcinoma of the head and neck. In most series, the rate of CR at the primary site after induction PF was 20–30%. We evaluated the efficacy and feasibility of induction nAb-paclitaxel and Cetuximab given with PF (ACPF) followed by definitive chemoradiation (CRT) in a phase II trial. Methods Patients with HNSCC were treated with ACPF (nab-paclitaxel 100 mg/m2/week; cetuximab 250 mg/m2/week; cisplatin 75 mg/m2 Day 1; 5-fluorouracil 750 mg/m2/day Days 1–3) every 21 days for 3 cycles followed by CRT (cisplatin 100 mg/m2 on days 1,22 and 43 of RT). CR at the primary tumor site after 2 cycles of ACPF was the primary endpoint. Results Thirty patients were enrolled, of which 22 (73%) had large (T3/T4) primary tumors. The CR rate at the primary tumor site after 2 cycles of ACPF was 53% and the overall response rate was 100%. Twenty-nine (96%) patients completed 3 cycles of ACPF, 26 (90%) completed definitive radiation therapy (RT) per protocol and 22 of the 27 evaluable patients (81%) received > 2 of the 3 planned doses of cisplatin with RT. The estimated 2-year overall and progression-free survivals were 84% and 65%, respectively. Conclusion Induction ACPF resulted in a high CR rate (53%) at the primary tumor site even in large tumors and did not adversely affect delivery of definitive CRT. Further investigation of ACPF is warranted. PMID:22991252

  8. The oncologic radicality of supracricoid partial laryngectomy with cricohyoidopexy in the treatment of advanced N0-N1 laryngeal squamous cell carcinoma.

    PubMed

    De Virgilio, Armando; Fusconi, Massimo; Gallo, Andrea; Greco, Antonio; Kim, Se-Heon; Conte, Michela; Alessi, Simone; Tombolini, Mario; de Vincentiis, Marco

    2012-04-01

    The aim of the study was to evaluate the oncologic outcome of our series of advanced laryngeal squamous cell carcinomas, primarily treated by supracricoid laryngectomy with cricohyoidopexy or total laryngectomy, to compare the two therapeutic modalities. Retrospective controlled study. We retrospectively reviewed the medical files, operative charts, and pathology reports of 83 patients who underwent total laryngectomy or supracricoid laryngectomy with cricohyoidopexy between February 1999 and March 2009. We only included cases in which both surgical treatments were feasible. Endpoints included local control, locoregional control, overall survival, and disease-specific survival. When we stratified the patients according to T stage, no statistically significant differences emerged in terms of overall and disease-specific survival. When we compared total laryngectomy to cricohyoidopexy in N1 patients, 3-year overall survival and disease-specific survival differences were statistically relevant (P = .022 and P = .030, respectively). Total laryngectomy warranted better results in term of overall and disease-specific survival, although the differences were not statistically significant. Local and locoregional control in the two treatment groups were overlapping, showing that cricohyoidopexy (when technically feasible) could be a valid surgical option in selected advanced laryngeal squamous cell carcinoma. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  9. Synchronous metastatic squamous cell carcinoma to the colon and cervical lymph nodes from a carcinoma of unknown primary site: A case report.

    PubMed

    Ito, Homare; Miyakura, Yasuyuki; Tsukui, Hidenori; Naoi, Daishi; Tahara, Makiko; Morimoto, Mitsuaki; Koinuma, Koji; Horie, Hisanaga; Lefor, Alan Kawarai; Sata, Naohiro

    2016-05-12

    Metastatic squamous cell carcinoma (SCC) from an unknown primary site to the colon has not been reported previously. A 75-year-old woman presented with a mass in the left submandibular region. Biopsy revealed a Class V lesion, but the histologic type was undetermined. Surgical resection of the left submandibular gland with cervical lymph node dissection was performed. However, SCC was seen in the lymph nodes only, with no tumor in the submandibular gland. Three months after surgery, computed tomography revealed that the preoperatively diagnosed lesion in the transverse colon had grown considerably. A laparoscopic right hemicolectomy was performed. Histological examination showed features of SCC, similar to the findings in the cervical lymph nodes. We report a rare case of synchronous metastatic SCC to the colon and cervical lymph nodes from a carcinoma of unknown primary site. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

  10. Case report of primary renal pelvis squamous cell carcinoma coexisting with long-standing calculi in left kidney on 18F-FDG PET/CT

    PubMed Central

    Deng, Shengming; Zhang, Bin; Huang, Ying; Li, Jihui; Sang, Shibiao; Zhang, Wei

    2017-01-01

    Abstract Rationale: Primary renal pelvis squamous cell carcinoma (SCC) is an extremely rare neoplasm. In many patients, the SCC was associated with renal calculi. Patient concerns: A 61-year-old male presented with intermittent pain at the left lumbar region for 3 days. The PET/CT images demonstrated increased 18F-FDG uptake in the upper pole of the left kidney and left renal hilar lymph nodes. Diagnoses: Pathologic examination revealed well-moderately differentiated renal pelvis SCC with lymphatic metastasis. Interventions: The patient underwent a left nephrectomy a few days after the initial staging PET/CT study. Outcomes: No growing lesion or metastasis was observed during a 6-month follow-up. Lessons: Our case demonstrates that 18F-FDG PET/CT is a useful diagnostic tool to evaluate primary renal pelvic SCC and detect metastatic lymph nodes in patients with long-standing calculi. PMID:28296764

  11. What is the role of postoperative re-irradiation in recurrent and second primary squamous cell cancer of head and neck? A literature review according to PICO criteria.

    PubMed

    Merlotti, Anna; Mazzola, Rosario; Alterio, Daniela; Alongi, Filippo; Bacigalupo, Almalina; Bonomo, Pierluigi; Maddalo, Marta; Russi, Elvio Grazioso; Orlandi, Ester

    2017-03-01

    Re-irradiation has been increasingly offered as a potential effective treatment for head and neck squamous cell carcinoma (HNSCC) loco-regional recurrence as well as second primary tumor in previously irradiated area. This review focused on the role of postoperative re-irradiation (POreRT) in terms of feasibility, toxicity and long-term outcomes in HNSCC patients. The key issue for the research was formulated in two questions according to the PICO (population, intervention, control, and outcomes) criteria. A total of 16 publications met the inclusion criteria for a total of 919 patients; in 522 patients POreRT was performed. POreRT in recurrent and second primary HNSCC seems to be feasible in highly selected patients with the intent to guarantee an acceptable LC compared to surgery alone. The optimal RT schedule remains unclear due to the heterogeneity of literature data.

  12. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    ClinicalTrials.gov

    2017-09-08

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  13. Dysphagia with a thyroid nodule: is there a primary aerodigestive malignancy?

    PubMed

    Michalopoulos, Konstantinos; Gunasekaran, Sinnappa; Moor, James W; Bem, Chris

    2008-03-01

    Three cases of laryngopharyngeal primary squamous cell carcinoma presenting with thyroid nodules are described. The key message to take away from these cases is that patients with advanced malignancy of the upper aerodigestive tract can present with a thyroid nodule.

  14. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial.

    PubMed

    Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel; Lu, Shun; Syrigos, Konstantinos; Lee, Ki Hyeong; Göker, Erdem; Georgoulias, Vassilis; Li, Wei; Isla, Dolores; Guclu, Salih Z; Morabito, Alessandro; Min, Young J; Ardizzoni, Andrea; Gadgeel, Shirish M; Wang, Bushi; Chand, Vikram K; Goss, Glenwood D

    2015-08-01

    There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov, NCT01523587. 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1-10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months [95% CI 1·9-2·9] vs 1·9 months [1·9-2·2]; hazard ratio [HR] 0·82 [95% CI 0·68-1·00], p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months [IQR 13·8-22·4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months [95% CI 7·2-8·7] vs 6·8 months [5·9-7·8]; HR 0·81 [95% CI 0·69-0·95], p=0·0077), as were progression

  15. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation

    PubMed Central

    Oh, Jinju; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2016-01-01

    Objective The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. Methods A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. Results Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). Conclusion Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival. PMID:27462593

  16. Subungual squamous cell carcinoma*

    PubMed Central

    Padilha, Carolina Barbosa de Sousa; Balassiano, Laila Klotz de Almeida; Pinto, Julyana Calegari; de Souza, Flávia Crespo Schueler; Kac, Bernard Kawa; Treu, Curt Mafra

    2016-01-01

    Although subungual squamous cell carcinoma is rare, it is the most common primary malignant neoplasms in this location. The higher incidence occurs in the fingernails, but involvement of the toenails is also possible. Subungual squamous cell carcinoma often looks like other more common benign lesions, such as fungal infection, onychomycosis, or viral wart. These factors, together with a general lack of awareness of this disease among physicians, often result in delayed diagnosis. Therefore, it is underdiagnosed, with few reports in the literature. The authors present a case of a man with a diagnosis of subungual squamous cell carcinoma in the hallux, without bone involvement, which was submitted to the appropriate surgical treatment. PMID:28099608

  17. Outcomes and prognostic factors of chemotherapy for patients with locally advanced or metastatic pulmonary squamous cell carcinoma

    PubMed Central

    Minami, Seigo; Ogata, Yoshitaka; Ihara, Shouichi; Yamamoto, Suguru; Komuta, Kiyoshi

    2016-01-01

    Background Pulmonary squamous cell carcinoma has not benefited from improvements in chemotherapy over the past decade, compared with non-squamous non-small-cell lung cancer. Nowadays, treatment strategies differ between squamous and non-squamous non-small-cell lung cancers. This study aimed to investigate the percentage of patients treated with first-, second-, or third-line chemotherapy and the characteristics of patients for whom chemotherapy has been beneficial. Method Data on patients with stage IIIB or IV squamous cell carcinoma diagnosed between June 2007 and March 2015, and on patients who had received first-, second-, or third-line chemotherapy between June 2007 and November 2015 at our hospital, were retrospectively extracted from our institutional medical charts. We also compared patients who were treated with chemotherapy (chemotherapy group) and patients who were not (non-chemotherapy group) using multivariate logistic regression and multivariate Cox hazard analyses, respectively. Results During the study period, 103, 63, and 32 patients received first-, second-, and third-line chemotherapy, respectively. Fifty-one patients did not receive chemotherapy. Factors predicting unlikely chemotherapy included age ≥75 years, Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ≥2, Charlson comorbidity index ≥2, hemoglobin <12.2 g/dL, red cell distribution width ≥13.9%, and serum sodium <140 mEq/L. Factors predicting survival for each line of chemotherapy included the following: ECOG-PS ≥2 for first-line; ECOG-PS ≥2 and lymphocyte count for second-line; and ECOG-PS ≥2, body mass index <18.5 kg/m2, and hemoglobin and lactate dehydrogenase levels for third-line. Conclusion Approximately 66% of patients received first-line chemotherapy. Of those, 66% and 33% received second- and third-line chemotherapy, respectively. ECOG-PS was always an essential prognostic factor when considering introducing chemotherapy and proceeding with additional

  18. A Rare Case of a Primary Squamous Cell Carcinoma of the Stomach Presenting as a Submucosal Mass

    PubMed Central

    von Waagner, Wolf; Wang, Zhuo; Picon, Antonio I.

    2015-01-01

    We report a case of a 70-year-old man, with a status after aortic valve replacement, who presented with melena and hypotension. On physical examination, he was hypotensive, but he responded to resuscitation. Esophagogastroduodenoscopy revealed a submucosal mass in the gastric fundus. Imaging of the chest, abdomen, and pelvis showed no evidence of local or distant metastasis. He underwent a partial diaphragmatic resection, gastrectomy, lymphadenectomy, and Roux-en-Y esophagojejunostomy. Pathology showed a gastric squamous cell carcinoma (SCC) invading the diaphragm, with negative margins of resection, and one positive perigastric lymph node. He received chemoradiation, but the patient expired 27 months after surgery. PMID:26185704

  19. Primary squamous cell carcinoma of the thyroid. Initial assessment and follow-up using (18)F-FDG PET/CT.

    PubMed

    Caballero Gullón, L; Carmona González, E; Martínez Estévez, A; Gómez Camarero, M P; Corral, J J; Borrego Dorado, I

    Squamous cell carcinoma of thyroid is an uncommon, very aggressive neoplasm, having a poor prognosis and poor response to chemotherapy and radiotherapy. Surgery is the initial treatment of choice, although it often presents as a widespread disease at the time of diagnosis, usually with cervical swelling that causes most of the symptoms due to local infiltration or metastasis. Local infiltration from adjacent tumour and metastatic disease needs to be excluded from other primary epidermoid carcinomas, in order to make a correct diagnosis. This also requires the typical cytokeratin pattern seen in histological studies. The case is presented of a 53 year-old man with a medical history of hepatocarcinoma, with a cervical hypermetabolic lesion detected in an (18)F-FDG PET/CT performed to exclude widespread disease. The follow-up of this lesion with this technique and its usefulness is also described. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  20. E-2D Advanced Hawkeye: primary flight display

    NASA Astrophysics Data System (ADS)

    Paolillo, Paul W.; Saxena, Ragini; Garruba, Jonathan; Tripathi, Sanjay; Blanchard, Randy

    2006-05-01

    This paper is a response to the challenge of providing a large area avionics display for the E-2D AHE aircraft. The resulting display design provides a pilot with high-resolution visual information content covering an image area of almost three square feet (Active Area of Samsung display = 33.792cm x 27.0336 cm = 13.304" x 10.643" = 141.596 square inches = 0.983 sq. ft x 3 = 2.95 sq. ft). The avionics display application, design and performance being described is the Primary Flight Display for the E-2D Advanced Hawkeye aircraft. This cockpit display has a screen diagonal size of 17 inches. Three displays, with minimum bezel width, just fit within the available instrument panel area. The significant design constraints of supporting an upgrade installation have been addressed. These constraints include a display image size that is larger than the mounting opening in the instrument panel. This, therefore, requires that the Electromagnetic Interference (EMI) window, LCD panel and backlight all fit within the limited available bezel depth. High brightness and a wide dimming range are supported with a dual mode Cold Cathode Fluorescent Tube (CCFT) and LED backlight. Packaging constraints dictated the use of multiple U shaped fluorescent lamps in a direct view backlight design for a maximum display brightness of 300 foot-Lamberts. The low intensity backlight levels are provided by remote LEDs coupled through a fiber optic mesh. This architecture generates luminous uniformity within a minimum backlight depth. Cross-cockpit viewing is supported with ultra-wide field-of-view performance including contrast and the color stability of an advanced LCD cell design supports. Display system design tradeoffs directed a priority to high optical efficiency for minimum power and weight.

  1. p16 expression in cutaneous squamous carcinomas with neck metastases: a potential pitfall in identifying unknown primaries of the head and neck.

    PubMed

    Beadle, Beth M; William, William N; McLemore, Michael S; Sturgis, Erich M; Williams, Michelle D

    2013-11-01

    Human papillomavirus (HPV) positivity (+) has been used to identify oropharyngeal squamous carcinomas (SCCs) presenting as unknown primaries in the neck. p16 overexpression correlates with HPV+ in the oropharynx; however, the use of p16 alone as a surrogate marker of oropharyngeal HPV+ tumors has not been validated. We immunohistochemically analyzed p16 expression in surgically resected aggressive cutaneous head and neck SCC primaries and their nodal metastases from 24 patients to determine the potential overlap of p16 expression outside of the oropharynx. Five of 24 primary tumors (20.8%) and 3 lymph node metastases (12.5%) in levels II, III, and V, and the periparotid region diffusely expressed p16. HPV (high-risk types by in situ hybridization) was negative. p16 expression is relatively common in lymph node-positive cutaneous head and neck SCCs; thus, p16 expression as an independent biomarker and mechanism to determine the oropharyngeal source of an unknown primary is not advised. Copyright © 2012 Wiley Periodicals, Inc.

  2. Effect of different segmentation algorithms on metabolic tumor volume measured on 18F-FDG PET/CT of cervical primary squamous cell carcinoma

    PubMed Central

    Xu, Weina; Yu, Shupeng; Ma, Ying; Liu, Changping

    2017-01-01

    Background and purpose It is known that fluorine-18 fluorodeoxyglucose PET/computed tomography (CT) segmentation algorithms have an impact on the metabolic tumor volume (MTV). This leads to some uncertainties in PET/CT guidance of tumor radiotherapy. The aim of this study was to investigate the effect of segmentation algorithms on the PET/CT-based MTV and their correlations with the gross tumor volumes (GTVs) of cervical primary squamous cell carcinoma. Materials and methods Fifty-five patients with International Federation of Gynecology and Obstetrics stage Ia∼IIb and histologically proven cervical squamous cell carcinoma were enrolled. A fluorine-18 fluorodeoxyglucose PET/CT scan was performed before definitive surgery. GTV was measured on surgical specimens. MTVs were estimated on PET/CT scans using different segmentation algorithms, including a fixed percentage of the maximum standardized uptake value (20∼60% SUVmax) threshold and iterative adaptive algorithm. We divided all patients into four different groups according to the SUVmax within target volume. The comparisons of absolute values and percentage differences between MTVs by segmentation and GTV were performed in different SUVmax subgroups. The optimal threshold percentage was determined from MTV20%∼MTV60%, and was correlated with SUVmax. The correlation of MTViterative adaptive with GTV was also investigated. Results MTV50% and MTV60% were similar to GTV in the SUVmax up to 5 (P>0.05). MTV30%∼MTV60% were similar to GTV (P>0.05) in the 50.05) in the 100.05) in the SUVmax of at least 15 group. MTViterative adaptive was similar to GTV in both total and different SUVmax groups (P>0.05). Significant differences were observed among the fixed percentage method and the optimal threshold percentage was inversely correlated with SUVmax. The iterative adaptive segmentation algorithm led

  3. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  4. Advanced primary peritoneal carcinoma: clinicopathological and prognostic factor analyses

    PubMed Central

    Zhang, Chao; Li, Xiao-ping; Cui, Heng; Shen, Dan-hua; Wei, Li-hui

    2008-01-01

    Objective: To investigate the factors favoring a positive prognosis for advanced primary peritoneal carcinoma (PPC). Methods: Twenty-four cases meeting the criteria for PPC were analyzed retrospectively for the clinicopathologic profiles. Immunohistochemistry was used to determine the expressions of p53, Top2α, Ki-67 and Her-2/neu. Then all these clinicopathological factors and molecular markers were correlated with the prognosis. Results: There were 15 cases of primary peritoneal serous papillary carcinoma (PPSPC), 6 cases of mixed epithelial carcinoma (MEC) and 3 cases of malignant mixed Mullerian tumor (MMMT). All patients underwent cytoreductive surgery with optimal debulking achieved in 3 cases. Among those receiving first-line chemotherapy, 13 patients received the TP regimen (paclitaxel-cisplatin or carboplatin) and 7 patients received the PAC regimen (cisplatin-doxorubicin-cyclophosphamide). The median overall survival of all patients was 42 months, while the breakdown for survival time for patients with PPSPC, MMT and MEC was 44, 13 and 19 months, respectively. The expressions of p53, Top2α and Ki-67 were all demonstrated in 11 cases respectively. None showed the expression of Her-2/neu. There were significant differences in the median survival between patients with PPSPC and those with MMMT (44 months vs 13 months, P<0.05), also between patients receiving TP combination and those receiving the PAC regimen (75 months vs 28 months, P<0.05). Another significant difference in the median progression-free survival (PFS) was identified between patients with positive p53 immunostaining and those with negative p53 immunostaining (15 months vs 47 months, P<0.05), whereas age, menopausal status, residual tumor size and the other molecular factors did not significantly impact survival. Conclusion: Patients with PPC should be treated with a comprehensive management plan including appropriate cytoreductive surgery and responsive chemotherapy. Overestimating an

  5. Summary of major radiation fractionation and chemotherapy trials for organ preservation therapy in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Parsons, James T; Greene, Bruce D

    2015-01-01

    To review radiation fractionation and chemotherapy trials for patients undergoing organ preservation therapy for locally advanced head and neck squamous cell carcinoma. Radiation therapy fractionation and chemotherapy trial results as well as historical evidence are systematically reviewed. Trial results, which involve nearly 30,000 patients, have been interpreted, compared, and presented in a structured manner to demonstrate the changing approaches in treatment over the years from the 1960s to the present. The review includes data from the split-course radiation therapy era, meta-analyses of chemotherapy and radiation therapy fractionation trials, cetuximab trials, "triple-drug trials," and modern trials of induction chemotherapy followed by concomitant chemotherapy and radiation therapy. This summary will be useful to clinicians making treatment decisions today and to investigators designing trials in the future. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  6. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma: A Case Report and Literature Review.

    PubMed

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-05-01

    Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches.A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy.The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery.Patients with advanced stage tumors of the

  7. Bevacizumab plus chemotherapy for advanced non-squamous non-small-cell lung cancer with malignant pleural effusion.

    PubMed

    Kitamura, Kazuhiro; Kubota, Kaoru; Ando, Masahiro; Takahashi, Satoshi; Nishijima, Nobuhiko; Sugano, Teppei; Toyokawa, Masaru; Miwa, Koji; Kosaihira, Seiji; Noro, Rintaro; Minegishi, Yuji; Seike, Masahiro; Yoshimura, Akinobu; Gemma, Akihiko

    2013-02-01

    The presence of malignant pleural effusion (MPE) indicates a poorer prognosis for patients with non-small-cell lung cancer (NSCLC) and impairs their quality of life. Because vascular endothelial growth factor (VEGF) is the key mediator MPE production, we evaluated the efficacy and safety of chemotherapy plus bevacizumab, an anti-VEGF antibody, in non-squamous NSCLC patients with MPE, especially regarding the control of pleural effusions. From November 1, 2009 to September 30, 2011, medical charts of 13 consecutive patients with MPE who received bevacizumab plus chemotherapy as the initial or secondary treatment were retrospectively analyzed. Of the 13 patients, 6 did not undergo pleurodesis, 3 were unsuccessfully treated by pleurodesis, 2 had encapsulated pleural effusion, and 2 had no re-expansion of the lung. Twelve patients (92.3 %) achieved MPE control lasting >8 weeks following bevacizumab plus chemotherapy. Five of 10 patients with measurable lesions had confirmed partial responses. Of 3 patients without measurable lesions, one had confirmed CR. Median progression-free survival time without re-accumulation of MPE was 312 days. Grade 3 or 4 neutropenia, thrombocytopenia, hypertension, or proteinuria was observed in 2, 2, 1, or 1 patient, respectively. This is the first study to report that bevacizumab plus chemotherapy is highly effective for the management of MPE in non-squamous NSCLC patients. Prospective clinical trials are warranted to investigate the efficacy of bevacizumab for MPE.

  8. Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.

    PubMed

    De Castro, J; González-Larriba, J L; Vázquez, S; Massutí, B; Sanchez-Torres, J M; Dómine, M; Garrido, P; Calles, A; Artal, A; Collado, R; García, R; Sereno, M; Majem, M; Macías, J A; Juan, O; Gómez-Codina, J; Hernández, B; Lázaro, M; Ortega, A L; Cobo, M; Trigo, J M; Carcereny, E; Rolfo, C; Macia, S; Muñoz, J; Diz, P; Méndez, M; Rosillo, F; Paz-Ares, L; Cardona, J V; Isla, D

    2017-02-01

    First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.

  9. Concurrent Chemoradiotherapy With Paclitaxel and Nedaplatin Followed by Consolidation Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix: Preliminary Results of a Phase II Study

    SciTech Connect

    Zhang Meiqin; Liu Suping; Wang, Xiang-E.

    2010-11-01

    Purpose: To evaluate the efficacy and toxicities of concurrent chemoradiotherapy (CCRT) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma. Methods and Materials: Patients with LASCC (FIGO Stage IIB-IIIB) were treated with pelvic external beam radiotherapy (45 Gy for Stage IIB and 50 Gy for Stage III) and high-dose-rate intracavitary brachytherapy (50 Gy for Stage IIB and 35 Gy for Stage III). The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III. Concurrent chemotherapy with paclitaxel (35 mg/m{sup 2}) and nedaplatin (20 mg/m{sup 2}) was given every week for 6 weeks. Consolidation chemotherapy with paclitaxel (135 mg/m{sup 2}) and nedaplatin (60 mg/m{sup 2}) was administered every 3 weeks for 4 cycles. Results: All patients completed CCRT, and 28 of 34 patients completed consolidation chemotherapy. The complete response rate was 88% (95% CI, 73-96%). The most common Grade 3 or higher toxicities were leukopenia/neutropenia (10.9% of the cycles). During a median follow up of 23 months (range, 14-30 months), 5 patients had locoregional failure and 1 patient had distant metastasis. The estimated 2-year progression-free survival and overall survival were 82% (95% CI, 68-95%) and 93% (95% CI, 83-100%), respectively. Grade 3 late complications occurred in 3 patients (9%). Conclusions: CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma. Further randomized trials of comparing this regimen with the standard treatment are worth while.

  10. Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma.

    PubMed

    Lee, Jen Y; Garcia-Murillas, Isaac; Cutts, Rosalind J; De Castro, David Gonzalez; Grove, Lorna; Hurley, Tara; Wang, Fuqiang; Nutting, Christopher; Newbold, Katie; Harrington, Kevin; Turner, Nicholas; Bhide, Shreerang

    2017-09-05

    Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT, which causes significant morbidity. We assessed the role of circulating HPV DNA in identifying 'true' residual disease. We prospectively recruited test (n=55) and validation (n=33) cohorts. HPV status was confirmed by E7 RT-PCR. We developed a novel amplicon-based next generation sequencing assay (HPV16-detect) to detect circulating HPV DNA. Circulating HPV DNA levels post-CCRT were correlated to disease response (PET-CT). In pre-CCRT plasma, HPV-detect demonstrated 100% sensitivity and 93% specificity, and 90% sensitivity and 100% specificity for the test (27 HPV+) and validation (20 HPV+) cohorts, respectively. Thirty-six out of 37 patients (test and validation cohort) with complete samples-set had negative HPV-detect at end of treatment. Six patients underwent ND (3) and repeat primary site biopsies (3) for positive PET-CT but had no viable tumour. One patient had positive HPV-detect and positive PET-CT and liver biopsy, indicating 100% agreement for HPV-detect and residual cancer. We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis. HPV DNA post-treatment correlates with clinical response.

  11. Ifosfamide and mesna for the treatment of advanced squamous cell head and neck cancer. A GETLAC study.

    PubMed

    Cervellino, J C; Araujo, C E; Pirisi, C; Francia, A; Cerruti, R

    1991-01-01

    High-dose ifosfamide/mesna was administrated to 28 mostly pretreated patients with locally advanced and metastatic head and neck cancer who failed conventional surgery/radiation treatment. Primary sites include tongue (5), salivary gland (3), floor of mouth (5), oropharynx (2), hypopharynx (5) and larynx (8). The dose and schedule of ifosfamide (IF) was 3.5 g/m2 8 h, i.v. infusion, days 1-5, every 28 days, and mesna was given as 20% of IF dose intravenous bolus injection at 0, 2, 4, 6 and 8 h; mesna 40% of IF dose was given by oral route at 10 and 12 h, days 1-5, every 28 days. All patients were evaluable for both toxicity and response. 14 patients had received prior treatment with surgery plus radiation therapy and 14 patients radiation therapy. Following chemotherapy, 4 patients (14.2%) achieved complete remission and 8 patients (28.5%) achieved partial remission, with an overall response rate of 42.7%. Toxicity was reported for 186 cycles and ranged from mild to moderate: anemia 4, leukopenia 6, thrombopenia 1, nausea and vomiting 12, alopecia 28, microscopic hematuria 3, increased transaminase 1. No CNS symptoms and renal toxicity were registered. Median duration of survival is 11+ months (range 3+ to 18+ months). Nine patients died. We conclude that ifosfamide/mesna at this dose and schedule has a significant activity in recurrent head and neck cancer, and produces minimal toxicity.

  12. Preliminary safety, pharmacokinetics, and efficacy of regorafenib, cisplatin, and pemetrexed in patients with advanced non-squamous non-small cell lung cancers

    PubMed Central

    Hellmann, Matthew D; Sturm, Isrid; Trnkova, Zuzana Jirakova; Lettieri, John; Diefenbach, Konstanze; Rizvi, Naiyer A.; Gettinger, Scott N.

    2016-01-01

    Structured Abstract Purpose The addition of bevacizumab, an anti-angiogenesis agent, to cytotoxic chemotherapy improves survival in patients with advanced non-squamous non-small cell lung cancers (nsNSCLCs). Regorafenib is an oral multi-targeted kinase inhibitor with potent anti-angiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. This phase I trial evaluated the safety, pharmacokinetics, and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Methods Chemotherapy-naïve patients with advanced nsNSCLCs were treated with regorafenib 60mg/day continuously and cisplatin 75mg/m2 plus pemetrexed 500mg/m2 once every three weeks for up to six cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Results Nine patients enrolled prior to premature termination of the study due to slow recruitment and a change in the development strategy of regorafenib by the study sponsor, partially due to slow enrollment. Five patients experienced at least one treatment-related Grade 3 adverse event. No grade 4–5 toxicity occurred. 5 of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range 1.5–15.1). Minor pharmacokinetic (PK) interactions between regorafenib and chemotherapy were observed. Conclusions Regorafenib had acceptable tolerability and minor PK interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. Encouraging activity was appreciated in chemotherapy-naïve patients with advanced nsNSCLCs. However, the small number of patients treated limits conclusions that can be drawn from these results. PMID:26003007

  13. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study.

    PubMed

    Langer, Corey J; Gadgeel, Shirish M; Borghaei, Hossein; Papadimitrakopoulou, Vassiliki A; Patnaik, Amita; Powell, Steven F; Gentzler, Ryan D; Martins, Renato G; Stevenson, James P; Jalal, Shadia I; Panwalkar, Amit; Yang, James Chih-Hsin; Gubens, Matthew; Sequist, Lecia V; Awad, Mark M; Fiore, Joseph; Ge, Yang; Raftopoulos, Harry; Gandhi, Leena

    2016-11-01

    Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC. In this randomised, open-label, phase 2 cohort of a multicohort study (KEYNOTE-021), patients were enrolled at 26 medical centres in the USA and Taiwan. Patients with chemotherapy-naive, stage IIIB or IV, non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were randomly assigned (1:1) in blocks of four stratified by PD-L1 tumour proportion score (<1% vs ≥1%) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m(2) every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy. The primary endpoint was the proportion of patients who achieved an objective response, defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked, independent central review, in the intention-to-treat population, defined as all patients who were allocated to study treatment. Significance threshold was p<0·025 (one sided). Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned study treatment. This trial, which is closed for enrolment but continuing for follow-up, is registered with ClinicalTrials.gov, number NCT02039674. Between Nov 25, 2014, and Jan 25, 2016

  14. Phase II study of concurrent selective lymph node late course accelerated hyper-fractionated radiotherapy and pemetrexed and cisplatin for locally advanced oesophageal squamous cell carcinoma

    PubMed Central

    Fu, C; Guo, L; Li, H; Huang, W; Gong, H; Sun, M; Wang, Z; Zhou, T; Liu, C

    2014-01-01

    Objective: To determine the clinical efficacy and toxicity of pemetrexed combined with low-dose cisplatin (CDDP) concurrent with late-course accelerated hyperfractionated (LCAF) intensity-modulated radiation therapy (IMRT) in patients with inoperable locally advanced oesophageal squamous cell carcinoma (ESCC). Methods: Patients with locally advanced ESCC (less than or equal to 75 years of age, clinical stages IIB–IVA and Karnofsky performance status ≥70) were enrolled into the study. A target group size of 22 was projected based on the estimation that 2-year overall survival (OS) would increase from 20% to 40%. Patients were treated with pemetrexed, low-dose CDDP and LCAF IMRT concurrently. The main objective of the study was for a 2-year OS, and the secondary objectives were progression-free survival (PFS), objective response, locoregional failure rate, and acute and late toxicities. Results: 25 patients were recruited from October 2008 to July 2011. The median OS was 21 months, with 2- and 5-year OS rates of 44% and 44%, respectively. The median PFS was 18.2 months. The objective response rate was 96% (24/25), with 11 complete responses and 13 partial responses. The locoregional failure rate was 16%. Grades 4 and 5 acute toxicity rates were 8% and 4%, respectively, while no Grade 3 or greater late toxicity was observed. Conclusion: The findings of this Phase II study indicated that the therapeutic regimen appears to achieve an excellent response rate and favourable survival for locally advanced ESCC. However, the severe acute side effects should be considered cautiously in further studies. Advances in knowledge: To our knowledge, this is the first study that introduced pemetrexed and low-dose CDDP combined with LCAF IMRT to treat locally advanced ESCC. The 5-year OS rate was as high as 44%, which was more favourable than other studies. PMID:24666012

  15. Primary radical radiotherapy for squamous cell carcinoma of the middle ear and external auditory cana--an historical series.

    PubMed

    Pemberton, L S; Swindell, R; Sykes, A J

    2006-06-01

    To evaluate patients treated with radical radiotherapy alone for squamous cell carcinoma of the middle ear (MEC) and external auditory canal (EAC) in terms of freedom from local recurrence, cancer-specific survival and morbidity. Between 1965 and 1988, 123 patients were treated, 70 with MEC and 53 with EAC. The median age was 64 years (range 21-86) and 78% presented as late stage. The median dose was 55 Gy (range 39-55) in 16 once daily fractions (range 13-21). At 5 and 10 years, respectively, freedom from local recurrence was 56 and 56%, disease-free survival was 45 and 43%, cancer-specific survival was 53 and 51%, and overall survival was 40 and 21%. Cancer-specific survival was significantly worse with late stage as opposed to early stage (P = 0.0026), as was local recurrence (P = 0.0088). No differences in survival and local control were seen according to site. Radionecrosis developed in 6% of patients. Combined treatment using radiotherapy and radical surgery is often favoured. This large series shows that radical radiotherapy achieves comparable results in terms of local control and cancer-specific survival. Our radiotherapy regimen is now 55 Gy in 20 daily fractions to reduce late morbidity. Radiotherapy alone remains a viable option, especially as morbidity can be minimised and target volume delineation optimised using computer planning in the future.

  16. A randomized, phase 2 study comparing pemetrexed plus best supportive care versus best supportive care as maintenance therapy after first-line treatment with pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer.

    PubMed

    Mubarak, Nabil; Gaafar, Rabab; Shehata, Samir; Hashem, Tarek; Abigeres, Dani; Azim, Hamdy A; El-Husseiny, Gamal; Al-Husaini, Hamed; Liu, Zhixin

    2012-09-24

    Maintenance therapy for non-small cell lung cancer (NSCLC) aims to extend disease control after first-line chemotherapy with active and well-tolerated agents. The utility of continuation maintenance therapy requires further research. This multicenter, randomized, phase 2 study compared continuation maintenance therapy with pemetrexed (500 mg/m2 every 21 days) and best supportive care (BSC) versus BSC alone in patients with advanced, non-squamous NSCLC who had not progressed after 4 cycles of induction chemotherapy with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). The primary endpoint was progression-free survival (PFS) from randomization, was analyzed using a Cox model, stratified for the tumor response at the end of induction therapy, at a one-sided alpha of 0.2. Secondary endpoints: response and disease control rates, overall survival (OS), one year survival rates, and treatment-emergent adverse events (TEAEs). A total of 106 patients commenced induction therapy, of whom 55 patients were randomized to maintenance pemetrexed/BSC (n = 28) or BSC (n = 27). Although the median PFS time for maintenance phase for both arms was 3.2 months, the one-sided p-value for the PFS HR comparison was less than the prespecified limit of 0.2 (HR = 0.76, two-sided 95% confidence interval [CI]: 0.42 to 1.37; one-sided p-value = 0.1815), indicating that PFS was sufficiently long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS results were observed for the overall study period (induction plus maintenance) and when the PFS analysis was adjusted for sex, baseline disease stage, and the ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2 months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8 months (95% CI: 6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for both arms for the maintenance phase and the overall study period. Both the induction and continuation

  17. First-line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib monotherapy in East Asian patients with locally advanced or metastatic non-squamous non-small cell lung cancer: a randomised, phase 3 trial.

    PubMed

    Yang, James Chih-Hsin; Kang, Jin Hyoung; Mok, Tony; Ahn, Myung-Ju; Srimuninnimit, Vichien; Lin, Chia-Chi; Kim, Dong-Wan; Tsai, Chun-Ming; Barraclough, Helen; Altug, Sedat; Orlando, Mauro; Park, Keunchil

    2014-09-01

    In the Iressa Pan-ASia Study (IPASS), gefitinib claimed improved progression-free survival (PFS) versus carboplatin-paclitaxel in clinically selected lung cancer patients. The primary objective of this study was to assess the PFS of pemetrexed-cisplatin (PC) followed by gefitinib maintenance versus gefitinib monotherapy in an IPASS-like population. In this open-label, randomised, phase 3 trial, eligible patients were ⩾18 years, chemonaïve, East Asian, light ex-smokers/never-smokers with advanced non-squamous non-small cell lung cancer, an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and unknown epidermal growth factor receptor (EGFR) mutation status who enrolled at 12 sites in Asia. Patients randomly received (1:1) pemetrexed (500 mg/m(2)) plus cisplatin (75mg/m(2)) for six 21-day cycles, followed by gefitinib maintenance or gefitinib monotherapy (250 mg/day). Patient tissue was retrospectively analysed for EGFR mutations. This study is registered with ClinicalTrials.gov, NCT01017874. Between 23rd November 2009 and 27th April 2012, 253 patients entered, and 236 patients were randomly assigned to and treated with PC therapy (N=114) and gefitinib monotherapy (N=118). Between-arm baseline characteristics were balanced. PFS was not significantly different between treatment arms (p=0.217). The unadjusted hazard ratio (HR) was 0.85 (95% confidence interval (CI) 0.63-1.13). The HR should be cautiously interpreted as it was not constant. EGFR mutation status was determined for 74 tissue samples; 50 (67.6%) had mutations. In a pre-specified subgroup analysis, only the treatment-by-EGFR mutation interaction was significant (p=0.008) for PFS. For the entire treatment period, a higher proportion of patients in the PC/gefitinib arm versus gefitinib experienced possibly drug-related grade 3-4 treatment-emergent adverse events (39 of 114 [34%] versus 19 of 118 [16%]; p=0.002). In the intention-to-treat (ITT) population, PFS was not significantly different

  18. Inability of PET/CT to identify a primary sinonasal inverted papilloma with squamous cell carcinoma in a patient with a submandibular lymph node metastasis: A case report

    PubMed Central

    ZHANG, SI-CONG; WEI, LIN; ZHOU, SHUI-HONG; ZHAO, KUI

    2015-01-01

    The present study describes the first reported case of a sinonasal inverted papilloma (IP) with squamous cell carcinoma (SCC) that presented as a cancer of unknown primary in the English-language literature. In July 2010, a 66-year old male presented with a 6-month history of a painless, progressive mass in the right submandibular region. Physical examination revealed a 3×4-cm smooth, non-tender mass and subsequently, excision of the right submandibular gland was performed. Post-operative pathological examination indicated poorly-differentiated SCC of the submandibular lymph node. Positron-emission tomography/computed tomography (PET/CT) was unable to identify the primary tumour site in this case, and 14 months later the patient presented with nasal obstruction, leading to the diagnosis of right sinonasal IP with coexistent SCC. The patient received pre-operative radiotherapy, a right total maxillectomy and post-operative radiotherapy. However, the patient succumbed to a distant metastasis 37 months after the initial presentation. 18F-fluorodeoxyglucose uptake on PET/CT may be not a reliable predictor of malignancy in sinonasal IPs. Therefore, we suggest emphasis of the use of multiple biopsies for suspected sinonasal IPs in order to improve diagnostic accuracy. PMID:26622564

  19. Primary healthcare NZ nurses' experiences of advance directives: understanding their potential role.

    PubMed

    Davidson, Raewyn; Banister, Elizabeth; de Vries, Kay

    2013-07-01

    Advance directives are one aspect of advance care planning designed to improve end of life care. The New Zealand Nurses Organisation released their first mission statement in 2010 concerning advance directives suggesting an increase in the use of these. A burgeoning older population, expected to rise over the next few years, places the primary healthcare nurse in a pivotal role to address the challenges in constructing advance directives. While literature supports the role for primary healthcare nurses in promoting advance directives, no research was found on this role in the New Zealand context. This paper presents results of a qualitative study conducted in New Zealand with 13 senior primary healthcare nurses with respect to their knowledge, attitudes, and experiences of advance directives. Results of the analysis revealed a dynamic process involving participants coming to understand their potential role in this area. This process included reflection on personal experience with advance directives; values and ethics related to end of life issues; and professional actions.

  20. Concomitant chemoradiotherapy versus altered fractionation radiotherapy in the radiotherapeutic management of locoregionally advanced head and neck squamous cell carcinoma: An adjusted indirect comparison meta-analysis.

    PubMed

    Gupta, Tejpal; Kannan, Sadhana; Ghosh-Laskar, Sarbani; Agarwal, Jai Prakash

    2015-05-01

    Treatment intensification by using chemoradiotherapy (CRT) or altered fractionation radiotherapy (RT) improves outcomes in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). Two comprehensive meta-analyses with similar control arms (conventionally fractionated RT) were compared indirectly. The hazard ratio (HR) of death with 95% confidence interval (CI) for the overall comparison of altered fractionation RT with concomitant CRT was 1.13 (95% CI, 0.97-1.29; p = .07) suggesting no significant difference between both approaches. Compared to concomitant CRT, the HR for death was 1.01 (95% CI, 0.89-1.15; p = .82); 1.22 (95% CI, 0.94-1.59; p = .13); and 1.22 (95% CI, 1.07-1.39; p = .002) for hyperfractionated RT; accelerated RT without total dose reduction; and accelerated RT with total dose reduction, respectively. Concomitant CRT and hyperfractionated RT are comparable to one another on indirect comparison in the radiotherapeutic management of locoregionally advanced HNSCC. Any form of acceleration (with or without total dose reduction) may not compensate fully for lack of chemotherapy. © 2014 Wiley Periodicals, Inc.

  1. Neutrophil-to-lymphocyte ratio as a prognostic biomarker for patients with locally advanced esophageal squamous cell carcinoma treated with definitive chemoradiotherapy

    PubMed Central

    Zhou, Xi-Lei; Li, Yong-Qiang; Zhu, Wei-Guo; Yu, Chang-Hua; Song, Ya-Qi; Wang, Wan-Wei; He, Dong-Cheng; Tao, Guang-Zhou; Tong, Yu-Suo

    2017-01-01

    The present study evaluated the clinical and prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (dCRT). A total of 517 patients with ESCC were enrolled and analysed retrospectively. The NLR was calculated at three time points: baseline, post-treatment, and at the time of tumor progression. Elevated NLR was defined as a ratio ≥5. High NLR at baseline was present in 204 (39%) patients and was significantly correlated with larger tumour size, advanced TNM stage, worse ECOG performance status, and dCRT response (p < 0.05). At a median follow-up of 17 months, patients with higher NLR at baseline had poorer progression-free survival (PFS) and overall survival (OS). On multivariate analysis, elevated NLR at baseline was independently associated with PFS and OS (HR = 1.529, p < 0.001 for PFS; HR = 1.856, p < 0.001 for OS). In addition, patients with high pre- and post-treatment NLR demonstrated worse clinical outcomes than other groups. Our results suggest that NLR is an independent prognostic indicator for patients with ESCC undergoing dCRT and changes in NLR level with treatment may indicate therapeutic benefit. PMID:28195186

  2. The Older Adult With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: Knowledge Gaps and Future Direction in Assessment and Treatment.

    PubMed

    Maggiore, Ronald; Zumsteg, Zachary S; BrintzenhofeSzoc, Karlynn; Trevino, Kelly M; Gajra, Ajeet; Korc-Grodzicki, Beatriz; Epstein, Joel B; Bond, Stewart M; Parker, Ira; Kish, Julie A; Murphy, Barbara A; VanderWalde, Noam A

    2017-07-15

    Older adults with head and neck squamous cell carcinoma (HNSCC) pose unique treatment and supportive care challenges to oncologists and other cancer care providers. The majority of patients with HNSCC present with locoregionally advanced disease, for which combined-modality treatment integrating chemotherapy and radiation therapy is often necessary to maximize tumor control. However, applying these approaches to an older population with concomitant comorbidities and a higher risk of functional impairments remains challenging and is exacerbated by the paucity of studies involving older adults. The purpose of this article is to identify knowledge gaps in the evaluation and management of older adults with HNSCC-particularly those undergoing concurrent chemoradiation therapy-and their caregivers through a review of the literature conducted by clinicians, researchers, and patient advocates. The findings highlight the importance of a geriatric assessment and the therapeutic paradigms and challenges relevant to this population. Furthermore, we identify the need for additional research and interventions related to key supportive care issues that arise during and after treatment in older adults with locoregionally advanced HNSCC. On the basis of our findings, we prioritize these issues to guide future patient-oriented research endeavors to address these knowledge gaps and thus better serve this growing patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Surgical treatment of primary disease for penile squamous cell carcinoma: A Surveillance, Epidemiology, and End Results database analysis.

    PubMed

    Zhu, Yao; Gu, Wei-Jie; Wang, Hong-Kai; Gu, Cheng-Yuan; Ye, Ding-Wei

    2015-07-01

    Current guidelines recommend penile sparing surgery (PSS) for selected penile cancer cases. The present study described the use of PSS in a population-based cohort, and also examined the role of PSS on penile cancer-specific mortality (PCSM). Data from the Surveillance, Epidemiology, and End Results (SEER) database were used to identify individuals that were diagnosed with penile squamous cell carcinoma between 1998 and 2009 and treated with surgery. Patients were sorted into two groups: Local tumor excision (LTE) and partial/total penectomy (PE). Factors associated with the receipt of LTE and PCSM following LTE were examined. In addition, PCSM was compared between LTE and PE following propensity score matching. Of the 1,292 eligible patients, 24.2% underwent LTE. For stage T1 disease, the rates of LTE increased moderately from 29 to 40% over the last decade. Following multivariate analyses, young age, African descent, a tumor size of <3 cm and stage T1 disease were identified to positively influence the receipt of LTE. With a median follow-up period of 55 months, the four-year PCSM rate was 9.8% in patients treated with LTE. Older age, a tumor size of 3-4 cm and regional/distant disease (SEER stage) were significant predictors of PCSM. Furthermore, in matched cohorts with stage T1 disease, the four-year PCSM rates were 8.9 and 10.0% for patients that received LTE or PE, respectively (P=0.93). In conclusion, underuse of PSS is pronounced in the general community with significant age and ethnicity disparities. The current population-based study provides evidence supporting the oncological safety of PSS compared with PE in early-stage disease.

  4. Impact of cisplatin dose intensity on human papillomavirus-related and -unrelated locally advanced head and neck squamous cell carcinoma.

    PubMed

    Spreafico, Anna; Huang, Shao Hui; Xu, Wei; Granata, Roberta; Liu, Chen-Shin; Waldron, John N; Chen, Eric; Ringash, Jolie; Bayley, Andrew; Chan, Kelvin K W; Hope, Andrew J; Cho, John; Razak, Albiruni A R; Hansen, Aaron; Jang, Raymond; Perez-Ordonez, Bayardo; Weinreb, Ilan; Bossi, Paolo; Orlandi, Ester; Licitra, Lisa F; Song, Yuyao; O'Sullivan, Brian; Siu, Lillian L; Kim, John

    2016-11-01

    The aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV-) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). A pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000-2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV-. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV- cohorts separately. A total of 404 HPV+ and 255 HPV- LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5-11.9) years. Three-year OS for cisplatin <200, =200, and >200 mg/m(2) subgroups were 52%, 60%, and 72% (P = 0.001) for the HPV- and 91%, 90%, and 91% (P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m(2) for the HPV- (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3-0.7, P < 0.001) but not for HPV+ (HR 0.6, 95% CI: 0.4-1.1, P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset (N = 107) with cisplatin >200 mg/m(2) (HR 0.5, 95% CI: 0.2-1.1, P = 0.07). A survival benefit of cisplatin dose >200 mg/m(2) is evident for HPV- LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Concomitant consumption of marijuana, alcohol and tobacco in oral squamous cell carcinoma development and progression: recent advances and challenges.

    PubMed

    Lopes, Caio Fabio Baeta; de Angelis, Bruno Brandão; Prudente, Henrique Maciel; de Souza, Bernardo Vieira Goulart; Cardoso, Sérgio Vitorino; de Azambuja Ribeiro, Rosy Iara Maciel

    2012-08-01

    Oral squamous cell carcinoma (OSCC) corresponds to 95% of all malignant tumours of the mouth. The association between alcohol and tobacco is the major risk factor for this disease, increasing the chances for the development of OSCC by 35-fold. The plant, Cannabis sativa is smoked as cigarettes or blunts and is commonly used in association with tobacco and alcohol. Any type of smoking habit exposes individuals to a wide range of carcinogens or pro-carcinogens, such as polycyclic aromatic hydrocarbons, as well as some ethanol derived substances such as acetaldehyde (AA), and all are genotoxic in the same way. In addition, ethanol acts in the oral mucosa as a solvent and therefore increases the cellular membrane permeability to carcinogens. Carcinogens found in tobacco are also concentrated in marijuana, but the latter also contains high levels of cannabinoids, bioactive compounds responsible for several effects such as euphoria and analgesia. However, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the major psychotropic cannabinoid found in plants, causes a reduction of cellular metabolism and induction of apoptosis, both of which are anti-neoplastic properties. Apart from limited epidemiologic and experimental data, the effects of concomitant chronic exposure to marijuana (or Δ(9)-THC), tobacco and alcohol in OSCC development and progression is poorly known. This paper reviews the most recent findings on the effects of marijuana over cellular proliferation, as well as in the risk for OSCC, with emphasis on its interaction with tobacco and ethanol consumption.

  6. Epithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases.

    PubMed

    Toll, Agustí; Masferrer, Emili; Hernández-Ruiz, M E; Ferrandiz-Pulido, Carla; Yébenes, Mireia; Jaka, Ane; Tuneu, Anna; Jucglà, Anna; Gimeno, Javier; Baró, Teresa; Casado, Beatriz; Gandarillas, Alberto; Costa, Irmgard; Mojal, Sergi; Peña, Raul; de Herreros, Antonio García; García-Patos, Vicenç; Pujol, Ramon M; Hernández-Muñoz, Inmaculada

    2013-11-01

    Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epithelial to mesenchymal transition (EMT) is a process involving loss of intercellular adhesion, acquisition of a mesenchymal phenotype and enhanced migratory potential; epithelial markers, such as E-cadherin, are down-regulated and mesenchymal proteins (Vimentin), increased. To investigate the expression of EMT markers in metastatic SCC (MSCC) and their corresponding metastases, and to correlate them with clinico-pathological factors associated with an increased risk of metastasis. We performed a retrospective study that included 146 cSCC samples (51 primary non-metastatic, 56 primary metastatic, 39 lymphatic metastases). Immunohistochemistry for E-cadherin, Vimentin, Snail, beta-catenin, Twist, Zeb1 and Podoplanin was performed. Loss of membranous E-cadherin was observed in 77% cSCCs, with no differences between MSCC and non-MSCC. Among the transcriptional factors controlling EMT, no significant Snail1 expression was detected. Twist, Zeb1, Vimentin, beta-catenin and Podoplanin were significantly overexpressed in MSCCs. Twist ectopic expression in SCC13 cells induced Zeb1, Vimentin and Podoplanin expression and E-cadherin delocalization. These changes resulted in a scattered migration pattern in vitro. Expression of EMT markers was decreased in the metastases when compared with the corresponding primary tumors. These results suggest that a partial EMT, characterized by the expression of Twist but without a total E-cadherin depletion, is involved in the acquisition of invasive traits by cSCC, but the process is downregulated in lymph node metastases. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Primary Tumor-Secreted Lymphangiogenic Factors Induce Pre-Metastatic Lymphvascular Niche Formation at Sentinel Lymph Nodes in Oral Squamous Cell Carcinoma

    PubMed Central

    Wakisaka, Naohiro; Hasegawa, Yasuhisa; Yoshimoto, Seiichi; Miura, Kouki; Shiotani, Akihiro; Yokoyama, Junkichi; Sugasawa, Masashi; Moriyama-Kita, Makiko; Endo, Kazuhira; Yoshizaki, Tomokazu

    2015-01-01

    Objectives The objectives of this study were to evaluate the formation of lymphvascular niches in lymph nodes of patients with oral squamous cell carcinoma (OSCC), and investigate the roles of lymphangiogenic and angiogenic factors, such as vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D, expressed in the primary tumors. Materials and Methods Forty-four patients with previously untreated clinically late T2 or T3 OSCC of cN0 were evaluated for primary tumors and 166 sentinel lymph nodes (SLNs). Primary tumors were immunohistochemically analyzed for expressions of VEGFs. Densities of lymphatic vessels (LVDpodoplanin) and high endothelial venules (HEVD) in the SLNs were also calculated using antibodies for each marker, podoplanin and MECA-79, respectively. Results In 25 patients, all lymph nodes were metastasis-negative, whereas, in 19 patients, metastasis was positive for at least one lymph node (either at SLN, non-SLN, or nodal recurrence). From the analyses of 140 SLNs without metastasis, LVDpodoplanin in 50 SLNs of metastasis-positive cases was significantly higher than that in 90 SLNs of metastasis-negative cases (p = 0.0025). HEVD was not associated with lymph node metastasis. The patients with VEGF-A-High or VEGF-D-High tumors had significantly higher LVDpodoplanin than patients with their Low counterparts (p = 0.0233 and p = 0.0209, respectively). In cases with lymph node metastasis, the VEGF-D-expression score was significantly higher than in those without lymph node metastasis (p = 0.0006). Conclusions These results suggest that lymph node lymphangiogenesis occurs before metastasis in OSCC. VEGF-A and VEGF-D play critical roles in this process. VEGF-D is a potential predictive marker of positive lymph node metastasis in cN0 patients. PMID:26630663

  8. Tumor-associated carbonic anhydrase XII is linked to the growth of primary oral squamous cell carcinoma and its poor prognosis.

    PubMed

    Chien, Ming-Hsien; Ying, Tsung-Ho; Hsieh, Yi-Hsien; Lin, Chien-Huang; Shih, Chun-Han; Wei, Lin-Hung; Yang, Shun-Fa

    2012-05-01

    The pattern of protein expression in tumors is under the influence of nutrient stress, hypoxia, and low pH, which determines the survival of neoplastic cells and the development of tumors. Carbonic anhydrase (CA) XII is a transmembrane enzyme that catalyzes the reversible hydration of cell-generated carbon dioxide into protons and bicarbonate. Hypoxic conditions activate its transcription and translation, and enhanced expression is often present in several types of tumors. However, CA XII expression in oral squamous cell carcinoma (OSCC) and its correlation with patients' prognosis have not been investigated so far. In this study, we detected the expression of CA XII in 264 patients with OSCC using tissue microarrays (TMAs), and evaluated its correlation with clinicopathologic factors and disease prognosis. CA XII expression was present in 185/264 (70%) cases and was associated with more-advanced clinical stages (p=0.003), a larger tumor size (p<0.001), and postoperative recurrence (p=0.047), but was not associated with positive lymph node metastasis or distal metastasis. Importantly, CA XII expression was correlated with a poorer patient prognosis in a univariate (p=0.034, log-rank test) survival analysis. According to our results, the expression of CA XII in OSCC samples can predict the progression of OSCC and survival of OSCC patients.

  9. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-01-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment. PMID:24403269

  10. Advanced endodontic developments in pulpectomy of primary teeth.

    PubMed

    Yanko, Nataliia; Khmil, Olena; Kaskova, Lyudmyla; Vashchenko, Irina

    2016-01-01

    To appraise studies about pulpectomy in primary teeth with nickel-titanium rotary files and smear layer removal and to find out may these developments enhance pulpectomy outcomes in primary teeth. A systematic search was implemented for PubMed, Google and Google Scholar between the years 1995-January 2016 to identify eligible studies. Studies design was established according to the CEBM recommendations. Evidence quality of studies was appraised by risk of bias. Six studies about pulpectomy met the inclusion criteria, of which five were randomized controlled trials. Only one research demonstrates the enhanced outcome of pulpectomy in primary teeth with smear layer removal. Chosen studies have low overall evidence quality. Given the paucity, high heterogeneity of high-quality articles and their level of bias, recommendation for the use of nickel-titanium rotary files and smear layer removal in pulpectomy in primary teeth can yet not be formulated.

  11. Clonality analysis in primary oral squamous cell carcinoma and related lymph-node metastasis revealed by TP53 and mitochondrial DNA next generation sequencing analysis.

    PubMed

    Morandi, Luca; Tarsitano, Achille; Gissi, Davide; Leonardi, Elisa; Balbi, Tiziana; Marchetti, Claudio; Montebugnoli, Lucio; Foschini, Maria Pia

    2015-03-01

    The chance of developing a neck nodal metastasis after initial treatment of oral squamous cell carcinoma varies from 12.4% to 62%. Despite being the main reason for cancer-related mortality, nodal metastases are still rarely subjected to molecular analyses, and our knowledge of the clonal heterogeneity of multiple lesions within the same patient is limited. The aim of the present study was to evaluate the relationship between primary oral cancer and lymph node metastasis in a series of patients with synchronous and metachronous metastases by 2 clonality tests: mt-DNA and TP53 sequence analysis. The study population consisted of 10 consecutive patients. Data identified in this study demonstrate that our assay based on next-generation analysis of TP53 and mt-DNA is simple, is reliable, allows high throughput, and may be applied to retrospective cases. The combination of mt-DNA and TP53 data analysis helped us to evaluate more precisely and consistently the genetic relationship among different tumor clones.

  12. Advancing primary care to promote equitable health: implications for China

    PubMed Central

    2012-01-01

    China is a country with vast regional differences and uneven economic development, which have led to widening gaps between the rich and poor in terms of access to healthcare, quality of care, and health outcomes. China's healthcare reform efforts must be tailored to the needs and resources of each region and community. Building and strengthening primary care within the Chinese health care system is one way to effectively address health challenges. This paper begins by outlining the concept of primary care, including key definitions and measurements. Next, results from a number of studies will demonstrate that primary care characteristics are associated with savings in medical costs, improvements in health outcomes and reductions in health disparities. This paper concludes with recommendations for China on successfully incorporating a primary care model into its national health policy, including bolstering the primary care workforce, addressing medical financing structures, recognizing the importance of evidence-based medicine, and looking to case studies from countries that have successfully implemented health reform. PMID:22264309

  13. Oral health-related quality of life and depression/anxiety in long-term recurrence-free patients after treatment for advanced oral squamous cell cancer.

    PubMed

    Hassel, Alexander J; Danner, Daniel; Freier, Kolja; Hofele, Christof; Becker-Bikowski, Kirsten; Engel, Michael

    2012-06-01

    This report focuses on the association between oral health-related quality of life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients who were recurrence-free for 8 years after treatment for advanced oral squamous cell. Participants were 24 patients (mean age 55 years, 75% men) treated with neoadjuvant concurrent radiochemotherapy followed by surgery with a mean recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP) and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2). OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged correlation analysis, the correlation between OHRQoL to t1 and depression to t2 was significant and greater than the non-significant correlation for depression to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than vice versa. However, the difference in the correlation coefficients was not significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL measured with the OHIP was impaired in comparison to the normal population. In the limitations of the study design and bearing the small sample size in mind, the results give evidence that OHRQoL predicts psychological outcomes, namely depression and anxiety, better than vice versa.

  14. Prognostic Value of Neutrophil-Related Factors in Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin-Based Concurrent Chemoradiotherapy.

    PubMed

    Wang, Yan-Yang; Bai, Zhou-Lan; He, Jian-Li; Yang, Yan; Zhao, Ren; Hai, Ping; Zhe, Hong

    2016-01-01

    The aim of this study was to explore the relationship between neutrophil-related factors, including neutrophil-lymphocyte ratio (NLR) and the responses of neutrophil to granulocyte colony-stimulating factors (RNG), and the prognosis of patients with locally advanced cervical squamous cell carcinoma (LACSCC) undergoing cisplatin-based concurrent chemoradiotherapy (CCCRT). A total of sixty LACSCC patients were enrolled in this study. We analyzed the association of NLR or RNG with clinicopathologic characteristics of these patients. The prognostic factors were evaluated by univariate and multivariate survival analysis. The optimal cut-off value of the NLR was determined to be 2.0 for the overall survival (OS). A higher level of the NLR was associated with younger age (P = 0.017) and higher baseline platelet count (P = 0.040). NLR was identified to be the only independent prognostic factor for OS by multivariate analysis (P = 0.037). The median RNG was 3.01, with a range of 1.19-16.84. RNG level was significantly associated with lymph node metastasis of these patients (P = 0.023). And higher RNG was identified as being a closely independent poor prognostic factor for OS (P = 0.055). This study showed that NLR and RNG may be used as potential biomarkers for survival prediction in patients with LACSCC receiving CCCRT.

  15. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: Results of a phase II study

    SciTech Connect

    Vrdoljak, Eduard . E-mail: eduard.vrdoljak@st.hinet.hr; Prskalo, Tomislav; Omrcen, Tomislav; Situm, Kristina; Boraska, Tihana; Frleta Ilic, Nives; Jankovic, Stjepan; Hamm, Wolfgang

    2005-03-01

    Purpose: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). Methods and materials: Forty-four patients with biopsy-proven LASCC were enrolled. FIGO Stages IB2 bulky to IVA were entered into this study. Patients were assigned to receive external radiotherapy (50 Gy in 25 fractions); then ifosfamide 2 g/m{sup 2} plus cisplatin 75 mg/m{sup 2} was applied during two low-dose-rate brachytherapy applications, and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy. The planned dose to point A was 85 Gy. Results: All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy. The average duration of radiation was 45.1 days. The clinical complete response rate was 100%. Grade 3 and 4 leukopenia occurred in 25% and 11% of the cycles, respectively. After a median follow-up of 34 months (range, 20-54 months), the recurrence-free and the overall survival rates were 84% and 91%, respectively. Major delayed local complications occurred in 7 cases (16%). Conclusions: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri. A randomized trial is planned.

  16. Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma

    PubMed Central

    Lee, Li-Yu; Lin, Chien-Yu; Wang, Hung-Ming; Ng, Shu-Hang; Chen, Shu-Jen; Yen, Tzu-Chen

    2016-01-01

    TP53 mutations have been linked to reduced survival in patients with oral cavity squamous cell carcinoma (OSCC). However, the impact of different types of TP53 mutations remains unclear. Here, we demonstrate that the carriage of missense mutations in the TP53 DNA binding domain (DBD missense mutations) is associated with decreased disease-specific survival (DSS) compared with wild-type TP53 (P=0.002) in a cohort of 345 OSCC patients. In contrast, DSS of patients bearing all of the remaining TP53 mutations did not differ from that observed in wild-type TP53 patients (P=0.955). Our classification method for TP53 mutations was superior to previously reported approaches (disruptive, truncating, Evolutionary Action score, mutations in L2/L3/LSH) for distinguishing between low- and high-risk patients. When analyzed in combination with traditional clinicopathological factors, TP53 DBD missense mutations were an independent prognostic factor for shorter DSS (P=0.014) alongside with advanced AJCC T- and N-classifications and the presence of extracapsular spread. A scoring system that included the four independent prognostic factors allowed a reliable patient stratification into distinct risk groups (high-risk patients, 16.2%). Our results demonstrate the usefulness of TP53 DBD missense mutations combined with clinicopathological factors for improving the prognostic stratification of OSCC patients. PMID:27283772

  17. Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma.

    PubMed

    Lapke, Nina; Lu, Yen-Jung; Liao, Chun-Ta; Lee, Li-Yu; Lin, Chien-Yu; Wang, Hung-Ming; Ng, Shu-Hang; Chen, Shu-Jen; Yen, Tzu-Chen

    2016-07-12

    TP53 mutations have been linked to reduced survival in patients with oral cavity squamous cell carcinoma (OSCC). However, the impact of different types of TP53 mutations remains unclear. Here, we demonstrate that the carriage of missense mutations in the TP53 DNA binding domain (DBD missense mutations) is associated with decreased disease-specific survival (DSS) compared with wild-type TP53 (P=0.002) in a cohort of 345 OSCC patients. In contrast, DSS of patients bearing all of the remaining TP53 mutations did not differ from that observed in wild-type TP53 patients (P=0.955). Our classification method for TP53 mutations was superior to previously reported approaches (disruptive, truncating, Evolutionary Action score, mutations in L2/L3/LSH) for distinguishing between low- and high-risk patients. When analyzed in combination with traditional clinicopathological factors, TP53 DBD missense mutations were an independent prognostic factor for shorter DSS (P=0.014) alongside with advanced AJCC T- and N-classifications and the presence of extracapsular spread. A scoring system that included the four independent prognostic factors allowed a reliable patient stratification into distinct risk groups (high-risk patients, 16.2%). Our results demonstrate the usefulness of TP53 DBD missense mutations combined with clinicopathological factors for improving the prognostic stratification of OSCC patients.

  18. Association of p53 codon 72 polymorphism with risk of second primary malignancy in patients with squamous cell carcinoma of the head and neck

    PubMed Central

    Li, Fanglin; Sturgis, Erich M; Chen, Xingming; Zafereo, Mark E.; Wei, Qingyi; Li, Guojun

    2010-01-01

    BACKGROUND p53 plays a critical role in cellular anti-cancer mechanisms, and has been correlated with second primary malignancy (SPM) development. A common polymorphism in codon 72 of the p53 results in an amino acid substitution and could influence p53 function. We hypothesized that p53 codon 72 polymorphism may be associated with risk of SPMs and SPM-free survival among patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS A total of 1,271 patients, who were diagnosed with incident SCCHN between May 1995 and January 2007, were genotyped and followed for SPM development. Log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk between the different genotype groups. RESULTS We found a significantly reduced SPM-free survival for patients with variant Pro72 allele compared with patients with Arg 72 homozygous genotype (Log-rank test, p = 0.005). Compared to SCCHN patients with the p53 72Arg/Arg genotype, there was a significantly greater risk of SPM associated with the p53 72Arg/Pro genotype (HR, 1.75, 95% CI, 1.17–2.61) and the combined p53 72Arg/Pro + Pro/Pro (HR, 1.58, 95%CI, 1.07–2.34). Furthermore, stratification analyses showed that the risk of SPM associated with p53 variant genotypes (Arg/Pro + Pro/Pro) was more pronounced in several subgroups. CONCLUSIONS Our findings suggest that p53 codon 72 polymorphism could be a risk marker for genetic susceptibility to SPM of patients with primary SCCHN. PMID:20225330

  19. First-line bevacizumab, cisplatin and vinorelbine plus maintenance bevacizumab in advanced non-squamous non-small cell lung cancer chemo-naïve patients.

    PubMed

    Leon, Luis; Vázquez, Sergio; Gracia, José Manuel; Casal, Joaquín; Lazaro, Martín; Firvida, José Luis; Amenedo, Margarita; Santome, Lucia; Macia, Sonia

    2012-07-01

    The aim of this study was to evaluate efficacy and safety of first-line treatment with bevacizumab, cisplatin and vinorelbine and bevacizumab maintenance in non-squamous, non-small cell lung cancer (NSCLC). Forty-nine patients with stage IIIB plus pleural effusion or stage IV NSCLC were included in a Phase II clinical trial. Treatment consisted of 3-week cycles of bevacizumab (15 mg/kg on day 1), cisplatin (80 mg/m(2) on day 1) and vinorelbine (25 mg/m(2) on days 1 and 8). After 6 cycles, non-progressing patients received bevacizumab maintenance therapy. The primary end point was progression-free survival (PFS), calculated using the Kaplan-Meier method. Thirteen (29%) of 45 evaluable patients presented a partial response. PFS and overall survival were 6.0 months (95% confidence interval (CI) 4.5 - 7.5) and 14.7 months (95% CI 8.4 - 21), respectively. Fourteen patients (28%) experienced grade 3 - 4 neutropenia and 7 (14%) experienced febrile neutropenia during the combination treatment. During the maintenance phase, the most frequent grade 3 - 4 adverse event was hypertension. Neither grade 3 - 4 thrombocytopenia nor toxic death was observed. The studied regimen achieved a similar efficacy to other regimens containing platinum doublets. The data provide further evidence that bevacizumab may be used in combination with multiple standard platinum-based doublets in this setting.

  20. Primary electric power generation systems for advanced-technology engines

    NASA Technical Reports Server (NTRS)

    Cronin, M. J.

    1983-01-01

    The advantages of the all electric airplane are discussed. In the all electric airplane the generator is the sole source of electric power; it powers the primary and secondary flight controls, the environmentals, and the landing gear. Five candidates for all electric power systems are discussed and compared. Cost benefits of the all electric airplane are discussed.

  1. Resin transfer molding for advanced composite primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Markus, Alan; Palmer, Ray

    1991-01-01

    Resin Transfer Molding (RTM) has been identified by Douglas Aircraft Company (DAC) and industry to be one of the promising processes being developed today which can break the cost barrier of implementing composite primary structures into a commercial aircraft production environment. The RTM process developments and scale-up plans Douglas Aircrart will be conducting under the NASA ACT contract are discussed.

  2. Universal Primary Education in Kenya: Advancement and Challenges

    ERIC Educational Resources Information Center

    Ngugi, Margaret; Mumiukha, Catherine; Fedha, Flora; Ndiga, Beatrice

    2015-01-01

    Universalisation of primary education (UPE) has been a global issue since the early sixties, yet several decades later and even in the 21st century, many countries in Sub-Saharan Africa are still grappling with it. Unlike their counterparts in the developed world, its realisation in developing countries has been faced with a myriad of constraints.…

  3. Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Herchenhorn, Daniel; Dias, Fernando L.; Viegas, Celia M.P.; Federico, Miriam H.; Araujo, Carlos Manoel M.; Small, Isabelle; Bezerra, Marcos; Fontao, Karina M.D.; Knust, Renata E.; Ferreira, Carlos G.; Martins, Renato G.

    2010-11-01

    Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.

  4. Cost-effectiveness of bevacizumab-based therapy versus cisplatin plus pemetrexed for the first-line treatment of advanced non-squamous NSCLC in Korea and Taiwan.

    PubMed

    Ahn, Myung-Ju; Tsai, Chun-Ming; Hsia, Te-Chun; Wright, Elaine; Chang, John Wen-Cheng; Kim, Heung Tae; Kim, Joo-Hang; Kang, Jin Hyoung; Kim, Sang-We; Bae, Eun-Jin; Kang, Mijeong; Lister, Johanna; Walzer, Stefan

    2011-06-01

    The aim of this analysis is to investigate the mean incremental costs and life expectancy associated with two first-line treatments for advanced non-squamous non-small cell lung cancer (NSCLC) in Korea and Taiwan; bevacizumab plus cisplatin and gemcitabine (BevCG) and cisplatin plus pemetrexed (CP). A health economic (area under curve) model with three health states was developed to assess health outcomes (life-years gained [LYG]), direct costs, and incremental cost-effectiveness ratio (ICER). Progression-free survival (PFS) and overall survival (OS) were derived from randomized clinical trials and used in an indirect comparison in order to estimate their cost effectiveness. A life-time horizon was used. Costs and outcomes were discounted yearly by 5% in Korea and by 3% in Taiwan. The incremental LYG for the BevCG patients compared with patients treated with CP were 1.10 (13.2 months) in Korea and 1.19 (14.3 months) in Taiwan. The incremental costs were 37,439,968 ($ 33,322) in Korea and NT$ 1,910,615 ($ 64,541) in Taiwan. The incremental cost-effectiveness ratio was 34,064,835 ($ 30,318) in Korea and NT$ 1,607,960 ($ 54,317) in Taiwan. The inputs tested in one-way sensitivity analyses had very little impact on the overall cost effectiveness. This analysis shows that BevCG is more costly but is also associated with additional life-years in Korea and Taiwan. The ICER per LYG suggests that BevCG is a cost-effective therapy when compared to CP for patients with advanced NSCLC in Korea and Taiwan. © 2011 Blackwell Publishing Asia Pty Ltd.

  5. Subsite, T Class, and N Class Cannot be Used to Exclude the Retropharyngeal Nodes From Treatment De-Intensification in Advanced Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Spector, Matthew E.; Chinn, Steven B.; Bellile, Emily; Gallagher, K. Kelly; Kang, Stephen Y.; Moyer, Jeffrey S.; Prince, Mark E.; Wolf, Gregory T.; Bradford, Carol R.; McHugh, Jonathan B.; Carey, Thomas E.; Worden, Francis P.; Eisbruch, Avraham; Ibrahim, Mohannad; Chepeha, Douglas B.

    2016-01-01

    Importance Understanding the drainage patterns to the retropharyngeal nodes is an important consideration in oropharyngeal squamous cell carcinoma (OPSCC) because treatment of these nodes is related to increased morbidity. Prediction of these drainage patterns could not only help minimize treatment morbidity, but could also prevent failures in at-risk patients, as de-escalation trials are underway for this disease. Objective To evaluate the prevalence of pathologic retropharyngeal adenopathy (RPA) in OPSCC relative to involvement of the oropharyngeal subsite, number of neck nodes, T classification and N classification. Design Retrospective review from 2003–2010 Setting Academic Referral Center Participants 205 previously untreated, advanced stage (III, IV), pathologically confirmed patients with OPSCC Exposure: Concurrent chemoradiation Main Outcome Measures Radiologic evidence of pathologic RPA was tabulated and related to involvement of the oropharyngeal subsite, number of neck nodes, T classification and N classification. Results Pathologic RPA was identified in 18% of patients. There were pathologic retropharyngeal lymph nodes in 12/89 (13%) base of tongue cancers, 24/109 (22%) tonsil cancers, and 1/7 (14%) other oropharyngeal subsite cancers. Increasing prevalence of RPA was positively correlated with closer proximity to the posterior tonsillar pillar. A multivariate predictive regression model using the oropharyngeal subsite, involvement of the posterior tonsillar pillar, number of metastatic nodes, T classification, and N classification, showed that the number of metastatic nodes was statistically significant with an odds ratio of 1.436 (p=0.0001, 95% confidence interval: 1.203 – 1.714). Conclusions and Relevance The prevalence of pathologic RPA in this cohort was 18% and patients with multiple nodes had the highest risk for pathologic RPA, followed by involvement of the posterior tonsillar pillar. However, this data suggests that there is no clear

  6. Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinoma.

    PubMed

    Geiger, Jessica L; Lazim, Ahmed F; Walsh, Francis J; Foote, Robert L; Moore, Eric J; Okuno, Scott H; Olsen, Kerry D; Kasperbauer, Jan L; Price, Daniel L; Garces, Yolanda I; Ma, Daniel J; Neben-Wittich, Michelle A; Molina, Julian R; Garcia, Joaquin J; Price, Katharine A R

    2014-04-01

    Standard treatment for patients with poor-risk, resected head and neck squamous cell carcinoma (HNSCC) is adjuvant radiation therapy combined with high-dose cisplatin. Many patients are treated with weekly cisplatin; it is not known whether weekly and high-dose cisplatin are equivalent. This study compares the outcomes of patients with locally-advanced HPV-negative HNSCC and HPV/p16-positive oropharynx HNSCC treated with adjuvant chemoradiation therapy with either high-dose or weekly cisplatin. Retrospective review of patients with Stage III/IV HNSCC who had surgery followed by adjuvant chemoradiation therapy at Mayo Clinic, Rochester. HPV and/or p16 status was available for all oropharynx patients. 104 Patients (51 high-dose, 53 weekly) were analyzed. The 3-year overall survival was 84% and 75% for patients who received high dose and weekly cisplatin, respectively (p=0.30). The 3-year recurrence free survival was 71% and 74% in the high dose and weekly cisplatin group, respectively (p=0.95). Patients with HPV/p16-positive oropharynx cancer who received adjuvant chemoradiation therapy with high-dose and weekly cisplatin had three-year overall survival rates of 91% and 86% (p=0.56), and 3-year recurrence free survival of 84% and 82% (p=0.93). Extracapsular extension did not affect prognosis in either group. No significant survival difference was seen between patients with locally advanced HNSCC treated with adjuvant chemoradiation therapy with high-dose or weekly cisplatin, although there was a trend for improved survival with high-dose cisplatin. Weekly cisplatin in the adjuvant setting may be a better treatment for patients with HPV-positive oropharynx cancer to preserve survival and minimize toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Non-invasive prediction of the tumor growth rate using advanced diffusion models in head and neck squamous cell carcinoma patients.

    PubMed

    Fujima, Noriyuki; Sakashita, Tomohiro; Homma, Akihiro; Harada, Taisuke; Shimizu, Yukie; Tha, Khin Khin; Kudo, Kohsuke; Shirato, Hiroki

    2017-05-16

    We assessed parameters of advanced diffusion weighted imaging (DWI) models for the prediction of the tumor growth rate in 55 head and neck squamous cell carcinoma (HNSCC) patients. The DWI acquisition used single-shot spin-echo echo-planar imaging with 12 b-values (0-2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, tri-exponential, stretched exponential and diffusion kurtosis imaging models. We directly measured the tumor growth rate from two sets of different-date imaging data. We divided the patients into a discovery group (n = 40) and validation group (n = 15) based on their MR acquisition dates. In the discovery group, we performed univariate and multivariate regression analyses to establish the multiple regression equation for the prediction of the tumor growth rate using diffusion parameters. The equation obtained with the discovery group was applied to the validation group for the confirmation of the equation's accuracy. After the univariate and multivariate regression analyses in the discovery-group patients, the estimated tumor growth rate equation was established by using the significant parameters of intermediate diffusion coefficient D2 and slow diffusion coefficient D3 obtained by the tri-exponential model. The discovery group's correlation coefficient between the estimated and directly measured tumor growth rates was 0.74. In the validation group, the correlation coefficient (r = 0.66) and intra-class correlation coefficient (0.65) between the estimated and directly measured tumor growth rates were respectively good. In conclusion, advanced DWI model parameters can be a predictor for determining HNSCC patients' tumor growth rate.

  8. Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV.

    PubMed

    Horn, L-C; Hommel, N; Roschlau, U; Bilek, K; Hentschel, B; Einenkel, J

    2012-07-01

    Different patterns of invasion (PIs) have prognostic impact in several types of cancer and are associated with different grades of peritumoral stromal remodeling, characterized by the desmoplastic stromal response (DSR). One key regulator influencing cellular motility and peritumoral stromal response is c-met/HGF. This study evaluates the association between different PI, peritumoral DSR and its correlation to the expression of c-met/HGF in squamous cell carcinomas of the uterine cervix (CX). 131 advanced stage CX (FIGO III/IV) were re-evaluated histologically regarding PI, using a two-level scoring system. The tumor grows in solid cords/trabeculae in finger-like PI and in very small groups or single cells in spray-like PI. DSR was categorized as none/weak and moderate/strong. The tumors were stained with antibodies against c-met and HGF. The staining of >30% of tumor cells was defined as overexpression. The PI was correlated to the prognostic outcome, different categories of DSR and expression status of c-met and HGF. 66.4% of the tumors showed a finger-like, and 33.6% a spray-like PI. The spray-like PI showed a reduced two-year overall survival when compared to the finger-like PI (14.0% vs. 29.1%, respectively; p=0.012), and was associated with moderate/strong DSR. The majority of the tumors showed overexpression of c-met (85.4%) and HGF (74.8%). There was no correlation between the expression status of c-met/HGF and the FIGO stage, peritumoral DSR or the prognostic outcome. Spray-like PI is of prognostic impact in cervical carcinoma FIGO III/IV and is associated with strong peritumoral stromal remodeling. There is no prognostic impact of the immunohistochemical expression of c-met/HGF in advanced stage cervical carcinomas. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Tinhofer, Ingeborg; Hristozova, Tsvetana; Stromberger, Carmen; KeilhoIz, Ulrich; Budach, Volker

    2012-08-01

    Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.

  10. Changes in Unknown Primary Squamous Cell Carcinoma of the Head and Neck at Initial Presentation in the Era of Human Papillomavirus.

    PubMed

    Motz, Kevin; Qualliotine, Jesse R; Rettig, Eleni; Richmon, Jeremy D; Eisele, David W; Fakhry, Carole

    2016-03-01

    The presence of human papillomavirus (HPV) in unknown primary squamous cell carcinoma (UPSCC) of the head and neck at initial presentation focuses the investigation for the primary tumor on the oropharynx. The trends, frequency, and detection rate of UPSCCs have not been evaluated in the context of HPV tumor status. To determine the frequency of UPSCC over time and to evaluate the proportion of HPV-positive UPSCCs. Retrospective, single-institutional case series of patients diagnosed with UPSCC and evaluated at the Johns Hopkins Hospital from January 1, 2005, to June 1, 2014. Human papillomavirus tumor status was determined by p16 immunohistochemical analysis and/or high-risk HPV DNA by in situ hybridization as clinically available. Number and clinical characteristics of UPSCC cases over time. Eighty-four UPSCC cases were eligible for analysis. The mean age of the patients was 57.3 years (range 29-80 years), and 88.1% (n = 74) were male. The frequency of UPSCC increased significantly over time (P for trend = .01) and was significantly higher during later calendar periods (14 cases during 2005-2008 vs 39 cases during 2012-2014, P = .03). A total of 69 cases (90.7%) with available HPV tumor status were HPV-positive. The patients with HPV-positive UPSCC were significantly more likely to be male (91% vs 42.9%, P = .005) and younger (56.1 vs 67.7 years, P = .002) than the HPV-negative patients with UPSCC. The overall primary tumor site detection rate was 59.3% (n = 48). There was a nonsignificant increase in the detection rate from calendar periods 2005-2008 to 2012-2014 (50.0% vs 64.9%, P = .38). Since transoral robotic surgery was adopted in the diagnostic evaluation of UPSCC in 2011, a nonsignificant increase in the detection of primary tumors was observed (53.8% vs 64.3%, P = .34). The frequency of UPSCC has increased significantly in recent calendar periods, and most cases are HPV-positive. As expected, patients with HPV-positive UPSCC

  11. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  12. [Clinical Significance of Tumor Marker Detection in Patients 
with Advanced Squamous Cell Carcimoma of the Lung].

    PubMed

    Liang, Ping; Li, Junling

    2016-10-20

    背景与目的 肺鳞癌由于发病隐匿,早期无明显症状,往往到晚期才得以诊断。本研究旨在描述性分析晚期肺鳞癌患者的基本特征和多种肿瘤标志物检测水平及阳性率情况,评价其临床价值。方法 以2011年1月-2015年12月期间于中国医学科学院肿瘤医院诊治的晚期肺鳞癌患者作为研究对象,通过病历回顾收集相关资料,描述性分析晚期肺鳞癌患者基本特征、肿瘤标志物检测水平和阳性率。结果 260例患者的平均年龄为(59.4±9.2)岁,男性223例(85.8%),女性37例(14.2%)。203例(78.1%)有吸烟史,8例(3.1%)有癌症家族史。细胞角质蛋白19的片断(cytokerantin 19 fragment, CYFRA21-1)的检测阳性率最高(71.2%)。不同肿瘤原发灶(tumor, T)分期和淋巴结受累(node, N)分期患者五种指标检测水平无统计学差异(P>0.05),仅鳞状细胞癌相关抗原(squamous cell carcinoma antigen, SCC)在不同T分期的检测阳性率有统计学差异(P=0.035)。二联阳性率最高的为CYFRA21-1+蛋白质类的癌胚抗原(carcinogen-embryonic antigen, CEA),阳性率为82.7%,三联阳性率最高的为癌抗原12-5(cancer antigen 125, CA125)+CYFRA21-1+CEA,阳性率为84.6%,四联阳性率最高为CA125+CYFRA21-1+CEA+酶类标志物神经烯醇化酶(neuron specific enolase, NSE),阳性率为85.0%,五联的阳性率为86.2%。结论 CYFRA21-1的检测阳性率最高,单项肿瘤标志物的检测灵敏度较低,联合检测可提高对肺鳞癌的诊断灵敏度,首选CA125、CYFRA21-1和CEA联合。.

  13. Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

    PubMed Central

    Hu, Guofang; Wang, Zhehai; Wang, Yuan; Zhang, Qingqing; Tang, Ning; Guo, Jun; Liu, Liyan; Han, Xiao

    2016-01-01

    Background To retrospectively evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (dCRT) with cisplatinum/paclitaxel versus cisplatinum/5-fluorouracil in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received nonsurgical treatment. Methods This study retrospectively evaluated 202 patients with locally advanced ESCC treated at Shandong Cancer Hospital between January 2009 and December 2013. All the patients initially received dCRT, including platinum and paclitaxel or 5-fluorouracil, with concurrent 1.8 or 2 Gy/fraction radiation (total dose, 54–60 Gy). The patient population was divided into two treatment groups: 105 patients who received the cisplatinum/paclitaxel regimen were allocated to group A, and 97 patients who received the cisplatinum/5-fluorouracil regimen were allocated to group B. We compared the progression-free survival (PFS) and overall survival (OS) by various clinical variables, including prior treatment characteristics, major toxicities (mainly in grade 3 and 4 hematological), and response to dCRT. We used the receiver operating curve analysis to determine the optimal cutoff value of clinical stage and radiation dose. The Kaplan–Meier method was used for survival comparison and Cox regression for multivariate analysis. Results Median PFS and OS in group A were significantly better compared with group B (median PFS, 15.9 versus 13.0 months, P=0.016 and median OS, 33.9 versus 23.1 months, P=0.014, respectively). The 1- and 2-year survival rates of the two groups were 82.9% versus 76.3%, and 61.9% versus 47.6%, respectively. The complete response and response rate were 17.1% versus 7.2% (P=0.032) and 52.4% versus 30.9% (P=0.042) in group A and B, respectively. Meanwhile, group B was associated with a significantly lower rate of grade 3/4 overall toxicity than group A (P=0.039). Conclusion Our data showed that patients with locally advanced ESCC in group A had longer PFS and OS compared with

  14. The American Medical Student Association's contributions to advancing primary care.

    PubMed

    Hedgecock, Joan; Steyer, Terrence E

    2008-11-01

    The American Medical Student Association (AMSA) Foundation is the programming arm of AMSA. The AMSA Foundation has administered several Title VII contracts designed to enhance the primary care education, leadership development, and cultural competence of the next generation of physicians, dentists, and other graduate-level health professionals. The authors discuss several AMSA programs developed with Title VII funding: Generalist Physicians in Training; Promoting, Reinforcing, and Improving Medical Education; National Primary Care Week; Leadership Seminar Series; and Achieving Diversity in Dentistry and Medicine. This article summarizes the work of these programs and discusses the impact that decreased funding has had on the training of our nation's future health professionals.This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs.

  15. Recent advances in treatment of severe primary immunodeficiencies

    PubMed Central

    Gennery, Andrew

    2015-01-01

    Primary immunodeficiencies are rare, inborn errors that result in impaired, disordered or uncontrolled immune responses. Whilst symptomatic and prophylactic treatment is available, hematopoietic stem cell transplantation is an option for many diseases, leading to cure of the immunodeficiency and establishing normal physical and psychological health. Newborn screening for some diseases, whilst improving outcomes, is focusing research on safer and less toxic treatment strategies, which result in durable and sustainable immune function without adverse effects. New conditioning regimens have reduced the risk of hematopoietic stem cell transplantation, and new methods of manipulating stem cell sources should guarantee a donor for almost all patients. Whilst incremental enhancements in transplantation technique have gradually improved survival outcomes over time, some of these new applications are likely to radically alter our approach to treating primary immunodeficiencies. PMID:26918153

  16. Resin transfer molding for advanced composite primary wing and fuselage structures

    NASA Technical Reports Server (NTRS)

    Markus, Alan

    1992-01-01

    The stitching and resin transfer molding (RTM) processes developed at Douglas Aircraft Co. are successfully demonstrating significant cost reductions with good damage tolerance properties. These attributes were identified as critical to application of advanced composite materials to commercial aircraft primary structures. The RTM/stitching developments, cost analyses, and test results are discussed of the NASA Advanced Composites Technology program.

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

    ClinicalTrials.gov

    2017-03-01

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

  18. Primary Microcephaly Gene MCPH1 Shows Signatures of Tumor Suppressors and Is Regulated by miR-27a in Oral Squamous Cell Carcinoma

    PubMed Central

    Venkatesh, Thejaswini; Nagashri, Mathighatta Nagaraj; Swamy, Shivananda S.; Mohiyuddin, S. M. Azeem; Gopinath, Kodaganur S.; Kumar, Arun

    2013-01-01

    Mutations in the MCPH1 (microcephalin 1) gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS) gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC) samples, and observed that 14/71 (19.72%) informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22%) and 19/25 (76%) OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3′-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a. PMID:23472065

  19. p73 G4C14-to-A4T14 polymorphism and risk of second primary malignancy after index squamous cell carcinoma of head and neck

    PubMed Central

    Li, Fanglin; Sturgis, Erich M; Zafereo, Mark E; Liu, Z; Wang, L-E; Wei, Qingyi; Li, Guojun

    2009-01-01

    P73 plays an important role in modulating cell-cycle control, inducing apoptosis, and inhibiting cell growth. A novel non-coding p73 G4C14-to-A4T14 exon 2 polymorphism was associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that p73 G4C14-to-A4T14 polymorphism modulates risk of second primary malignancies (SPM) in patients after index SCCHN. We followed a cohort of 1,384 patients diagnosed with incident SCCHN between May 1995 and January 2007 for SPM development. Log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk between the different genotype groups. Our results showed that patients carrying the p73 variant AT allele were less likely to develop SPM compared to the patients with p73 GC/GC genotype (Log-rank test, P = 0.013). Compared to the p73 GC/GC genotype, there was a significantly reduced risk of SPM associated with the p73 GC/AT genotype (HR, 0.61, 95% CI, 0.40-0.93) and the combined p73 GC/AT+AT/AT genotypes (HR, 0.59, 95% CI, 0.39-0.89), but a non-significantly reduced risk for p73 AT/AT genotype (HR, 0.44, 95% CI, 0.14-1.41). The p73 AT allele was significantly associated with risk of SPM in an allele dose-response manner (P = 0.011 for trend). The risk of SPM associated with p73 variant genotypes (GC/AT+AT/AT) was more pronounced in several subgroups (e.g., older patients, men, minorities, ever smokers and ever drinkers). Our results support that this p73 polymorphism may be a marker for risk of SPM among patients with an incident SCCHN. PMID:19585505

  20. Longitudinal evaluation of restricted mouth opening (trismus) in patients following primary surgery for oral and oropharyngeal squamous cell carcinoma.

    PubMed

    Scott, B; D'Souza, J; Perinparajah, N; Lowe, D; Rogers, S N

    2011-03-01

    Trismus is a serious problem for some patients after oral and oropharyngeal cancer, and it has a detrimental impact on quality of life and function. We know of few published papers that include preoperative assessment in reports on the longitudinal outcomes of mouth opening after oral and oropharyngeal surgery. We prospectively measured mouth opening in patients who had primary surgery for oral and oropharyngeal cancer from baseline to six months to find out the characteristics at baseline and at discharge of those who develop trismus at six months. Ninety-eight patients were eligible between February 2007 and March 2008, and 64 (65%) were recruited into the study. The range of mouth opening was measured on three occasions: before operation, on the ward before discharge from hospital, and at follow-up six months after operation. Using a criterion of 35 mm or less as an indication of trismus, 30% (19/63) had trismus before operation, 65% (37/57) at hospital discharge, and 54% (26/48) at six month follow-up. Patients at high risk of trismus were those with T stage 3 or 4 cancers who required free flap reconstruction and adjuvant radiotherapy; radiotherapy was the most significant factor at six months. Trismus at discharge was a prediction of trismus at six months. Interventions such as spatulas or a passive jaw mobiliser should be targeted at patients at high risk early in the postoperative phase. The efficacy of such interventions needs further research.

  1. Cooperative Research and Development of Primary Surface Recuperator for Advanced Microturbine Systems

    SciTech Connect

    Escola, George

    2007-01-17

    Recuperators have been identified as key components of advanced gas turbines systems that achieve a measure of improvement in operating efficiency and lead the field in achieving very low emissions. Every gas turbine manufacturer that is studying, developing, or commercializing advanced recuperated gas turbine cycles requests that recuperators operate at higher temperature without a reduction in design life and must cost less. The Solar Cooperative Research and Development of Primary Surface Recuperator for Advanced Microturbine Systems Program is directed towards meeting the future requirements of advanced gas turbine systems by the following: (1) The development of advanced alloys that will allow recuperator inlet exhaust gas temperatures to increase without significant cost increase. (2) Further characterization of the creep and oxidation (dry and humid air) properties of nickel alloy foils (less than 0.13 mm thick) to allow the economical use of these materials. (3) Increasing the use of advanced robotic systems and advanced in-process statistical measurement systems.

  2. Systematic Review and Meta-analysis of Conventionally Fractionated Concurrent Chemoradiotherapy versus Altered Fractionation Radiotherapy Alone in the Definitive Management of Locoregionally Advanced Head and Neck Squamous Cell Carcinoma.

    PubMed

    Gupta, T; Kannan, S; Ghosh-Laskar, S; Agarwal, J P

    2016-01-01

    Treatment intensification either by using concurrent chemoradiotherapy (CCRT) or altered fractionation radiotherapy (AFRT) improves outcomes of locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The superiority of one approach over the other, however, remains to be firmly established. The aim of the present study was to compare outcomes of CCRT versus AFRT in the definitive non-surgical management of locoregionally advanced HNSCC for evidence-based decision making. An electronic search of Medline via PubMed was conducted with no language, year, or publication status restrictions. The Cochrane Central Register of Controlled Trials (CENTRAL) and Database of Abstracts of Reviews of Effectiveness (DARE) were also searched electronically. Only randomised controlled trials assigning HNSCC patients randomly to conventionally fractionated CCRT or AFRT alone were included. Data were extracted independently by two reviewers and pooled using the Cochrane methodology for meta-analysis and expressed as a hazard ratio with 95% confidence intervals. Overall survival was the primary outcome of interest, whereas disease-free survival, locoregional control and toxicity were secondary end points. Five randomised controlled trials (involving 1117 patients and 627 deaths) directly comparing conventionally fractionated CCRT with AFRT alone were included. The risk of bias in included studies was low for efficacy outcomes, but high for toxicity outcomes. The overall pooled hazard ratio of death was 0.73 (95% confidence interval = 0.62-0.86), which significantly favoured conventionally fractionated CCRT over AFRT alone (P < 0.0001). Similarly, disease-free survival (hazard ratio = 0.79, 95% confidence interval = 0.68-0.92; P = 0.002) and locoregional control (hazard ratio = 0.71, 95% confidence interval = 0.59-0.84; P < 0.0001) were significantly improved with CCRT. There were no significant differences in the incidence of severe acute toxicity (dermatitis and mucositis

  3. Ixabepilone in Treating Patients With Metastatic or Recurrent Squamous Cell Cancer of the Head and Neck

    ClinicalTrials.gov

    2013-02-26

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

  4. Lessons Learned from an Advanced Access Trial Within a Canadian Armed Forces Primary Care Clinic.

    PubMed

    Singh, P Tony

    2017-01-01

    Accessibility is a key element of an effective primary care system. Literature has outlined that primary care practices have successfully employed an advanced access scheduler to improve accessibility to booked appointments and consequently enhance patient experience and outcomes. In 2015, a Canadian Armed Forces (CAF) primary care facility in Ottawa trialed an advanced access scheduler. Based on the unique characteristics of a CAF medical clinic and the patient population, this trial produced six critical lessons, which include maintenance of a stable base of clinicians, correcting rostering mismatches, eliminating appointment backlogs, acquiring required information systems, improved understanding of patient demand and communicating changes effectively. These lessons may be utilized by similar organizations to successfully integrate an advanced access scheduler within their primary care facilities.

  5. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    SciTech Connect

    Boscolo-Rizzo, Paolo; Gava, Alessandro; Baggio, Vittorio; Marchiori, Carlo; Stellin, Marco; Fuson, Roberto; Lamon, Stefano; Da Mosto, Maria Cristina

    2011-05-01

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age ({+-}5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m{sup 2}, and a continuous infusion of 5-fluorouracil, 1,000 mg/m{sup 2}/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  6. Vocal handicap and quality of life after treatment of advanced squamous carcinoma of the larynx and/or hypopharynx.

    PubMed

    Azevedo, Elma Heitmann Mares; Montoni, Neyller; Gonçalves Filho, João; Kowalski, Luiz Paulo; Carrara-de Angelis, Elisabete

    2012-03-01

    To evaluate and correlate voice-specific quality of life (QOL) and health-related QOL (HR-QOL) after treatment for advanced cancer of the larynx and/or hypopharynx. Cross-sectional study. Patients submitted to partial laryngectomy (PL), salvage PL (sPL), concomitant radiotherapy and chemotherapy (RT+Chemo), total laryngectomy (TL), salvage TL (sTL), total pharyngolaryngectomy (TP) and salvage total pharyngolaryngectomy (sTP). The following questionnaires were used: (1) Voice Handicap Index (VHI) and (2) University of Washington Quality of Life Questionnaire (UW-QOL; version 4). Eighty-four patients participated in the study. All the patients PL (10), sPL (1), and RT+Chemo (24) communicated by laryngeal voice. Of the 49 patients submitted to total removal of the larynx, 30 communicated with alaryngeal phonation, the major part being tracheoesophageal prosthesis (17). The worst subscale of VHI for the total patient group was functional (mean=13.15), and the value of the total score was 31. Patients submitted to PL, RT+Chemo, and TL presented slight handicap (medians of 27, 14, and 21.5, respectively). Patients treated with sTL, TP, and sTP presented moderate handicap (medians of 45, 37.5, and 31.5, respectively). HR-QOL was considered between good and excellent for 78.6% of the patients, and poor for 21.4%. The correlation between voice-specific QOL and HR-QOL was significant (P=0.0001). Patients treated for advanced cancer of the larynx/hypopharynx present slight to moderate voice handicap and good/excellent HR-QOL. Stricter analysis of both the VHI and UW-QOL data suggests that more attention be given to the vocal handicap of the individual patient. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  7. cRGD peptide installation on cisplatin-loaded nanomedicines enhances efficacy against locally advanced head and neck squamous cell carcinoma bearing cancer stem-like cells.

    PubMed

    Miyano, Kazuki; Cabral, Horacio; Miura, Yutaka; Matsumoto, Yu; Mochida, Yuki; Kinoh, Hiroaki; Iwata, Caname; Nagano, Osamu; Saya, Hideyuki; Nishiyama, Nobuhiro; Kataoka, Kazunori; Yamasoba, Tatsuya

    2017-09-10

    Recalcitrant head and neck squamous cell carcinoma (HNSCC) usually relapses after therapy due to the enrichment of drug resistant cancer stem-like cells (CSCs). Nanomedicines have shown potential for eradicating both cancer cells and CSCs by effective intratumoral navigation for reaching particular cell populations and controlling drug delivery. The installation of ligands on nanomedicines is an attractive approach for improving the delivery to CSCs within tumors, though the development of CSC-selective ligand-receptor systems has been challenging. Herein, we found that the CSC subpopulation in HNSCC cells overexpresses αvβ5 integrins, which is preferentially expressed in tumor neovasculature and cancer cells, and can be effectively targeted by using cyclic Arg-Gly-Asp (cRGD) peptide. Thus, in this study, we propose installing cRGD peptide on micellar nanomedicines incorporating cisplatin for improving their activity against CSCs and enhancing survival. Both cisplatin-loaded micelles (CDDP/m) and cRGD-installed CDDP/m (cRGD-CDDP/m) were effective against HNSCC SAS-L1-Luc cells in vitro, though cRGD-installed CDDP/m was more potent than CDDP/m against the CSC fraction. In vivo, the cRGD-CDDP/m also showed significant antitumor activity against HNSCC orthotopic tumors, i.e. SAS-L1 and HSC-2. Moreover, cRGD-CDDP/m rapidly accumulated into the lymph node metastasis of SAS-L1 tumors, effectively inhibiting their growth, and prolonging mice survival. These findings indicate cRGD-installed nanomedicines as an advantageous strategy for targeting CSCs in HNSCC, and particularly, cRGD-CDDP/m as a significant therapeutic strategy against regionally advanced HNSCC. Copyright © 2017. Published by Elsevier B.V.

  8. Receptor for advanced glycation end product blockade enhances the chemotherapeutic effect of cisplatin in tongue squamous cell carcinoma by reducing autophagy and modulating the Wnt pathway.

    PubMed

    Zhao, Ziming; Wang, Hongyu; Zhang, Liao; Mei, Xifan; Hu, Jing; Huang, Keqiang

    2017-02-01

    Tongue squamous cell carcinoma (TSCC) is one of the most severe types of cancer with poor outcomes. Cisplatin is used widely to treat cancer cells, but many patients develop acquired drug resistance. The receptor for advanced glycation end products (RAGE) is expressed widely in TSCC and associated with drug-induced chemotherapy resistance. However, the effect of RAGE and cisplatin on Tca-8113 cells remains unknown. We assayed the combined use of RAGE blockade and cisplatin effect on Tca-8113 cells' viability by MTT and apoptosis rate of Tca-8113 cells on RAGE blockade+cisplatin treatment; cisplatin alone; or RAGE blockade alone by flow cytometry. We observed the expressions of autophagy-related proteins beclin1, LC3II, p62; Wnt signaling-related proteins β-catenin, GSK3β, WNT5A, ROR-2; and apoptosis-related protein cleaved caspase-3, bcl-2-associated X proteins using western blot. We determined WNT5A and beclin1 expression on Tca-8113 cells by immunofluorescence. We further observed autophagy vacuoles by monodansylcadaverine staining. We found that RAGE blockade and cisplatin significantly decreased cell viability and increased the cell apoptosis rate compared with cisplatin alone. Furthermore, RAGE blockade suppressed the canonical Wnt pathway proteins β-catenin and GSK-3β, but upregulated noncanonical WNT5A and receptor ROR-2. We show that RAGE blockade suppressed the levels of autophagy-related protein LC3II/I, beclin1, accelerated degradation of autophagy for the increasing p62 expression, and increased cell apoptosis for the increasing expressions of cleaved caspase-3 and bcl-2-associated X proteins. We observed the location of WNT5A and beclin1 expressions on cells by immunofluorescence and their trends were consistent with western blotting. Taken together, our findings suggested that RAGE blockade+cisplatin improved chemotherapeutic effects by reducing autophagy and regulating Wnt/β-catenin to suppress the progression of TSCC.

  9. Cost‐effectiveness of neoadjuvant concurrent chemoradiotherapy versus esophagectomy for locally advanced esophageal squamous cell carcinoma: A population‐based matched case‐control study

    PubMed Central

    Lin, Chen‐Yuan; Fang, Hsin‐Yuan; Feng, Chun‐Lung; Li, Chia‐Chin

    2015-01-01

    Abstract Background Neoadjuvant concurrent chemoradiotherapy (NCCRT) is often considered for locally‐advanced esophageal squamous cell carcinoma (LA‐ESCC) patients; however, no data regarding the cost‐effectiveness of this treatment is available. Our study aimed to evaluate the cost‐effectiveness of NCCRT versus esophagectomy for LA‐ESCC at population level. Methods We identified LA‐ESCC patients diagnosed within 2008–2009 and treated with either NCCRT or esophagectomy through the Taiwan Cancer Registry. We included potential confounding covariables (age, gender, residency, comorbidity, social‐economic status, disease stage, treating hospital level and surgeon's experience, and the use of endoscopic ultrasound before treatment) and used propensity score (PS) to construct a 1:1 population. The duration of interest was three years within the date of diagnosis. Effectiveness was measured as overall survival. We took the payer's perspective and converted the cost to 2014 United States dollars (USD). In sensitivity analysis, we evaluated the potential impact of an unmeasured confounder on the statistical significance of incremental net benefit at suggested willingness‐to‐pay. Results Our study population constituted 150 PS matched subjects. The mean cost (2014 USD) and survival (year) were higher for NCCRT compared with esophagectomy (US$91,460 vs. $75,836 for cost; 2.2 vs. 1.8 for survival) with an estimated incremental cost‐effectiveness ratio of US$39,060/life‐year. Conclusions When compared to esophagectomy, NCCRT is likely to improve survival and is probably more cost‐effective. Cost‐effectiveness results should be interpreted with caution given our results were sensitive to potential unmeasured confounder(s) in sensitivity analysis. PMID:27148413

  10. Advances in non-surgical management of primary liver cancer

    PubMed Central

    Chen, Xiao; Liu, Hai-Peng; Li, Mei; Qiao, Liang

    2014-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC. PMID:25469032

  11. Multimodality therapy including salvage surgical resection and intraoperative radiotherapy for patients with squamous-cell carcinoma of the anus with residual or recurrent disease after primary chemoradiotherapy.

    PubMed

    Hallemeier, Christopher L; You, Y Nancy; Larson, David W; Dozois, Eric J; Nelson, Heidi; Klein, Kristi A; Miller, Robert C; Haddock, Michael G

    2014-04-01

    For patients with residual or recurrent squamous-cell carcinoma of the anus after primary chemoradiotherapy, the standard treatment is surgical salvage. Patients with unresectable or borderline unresectable disease have poor outcomes, thus adjunctive treatments should be explored. The aim of this study is to report outcomes for patients with residual/recurrent anal cancer treated with multimodality therapy including salvage surgical resection and intraoperative radiotherapy. This is an observational study. This study was conducted at a tertiary referral center. Thirty-two patients were treated between 1993 and 2012. Median age was 53 years (range, 34-87). Salvage treatment was performed for residual disease (n = 9), first recurrence (n = 17), or second recurrence (n = 6) after primary chemoradiotherapy. Patients with recurrent disease received preoperative external beam reirradiation with concurrent chemotherapy. All patients underwent salvage surgical resection and intraoperative radiotherapy. Extent of surgical resection was R0 (negative margins, n = 16), R1 (microscopic residual, n = 13), or R2 (macroscopic residual, n = 3). The median intraoperative radiotherapy dose was 12.5 Gy. Treatment-related adverse events were classified according to the National Cancer Institute - Common Toxicity Criteria. Overall and disease-free survival were estimated by using the Kaplan-Meier technique. Central, local-regional, and distant failure were estimated by the use of the cumulative incidence method. Median length of hospital stay was 9 days. Mortality at 30 days after surgery and intraoperative radiotherapy was 0%. Fifteen patients (47%) experienced a total of 16 grade 3 treatment-related adverse events (wound complication (n = 6), bowel obstruction (n = 5), and ureteral obstruction (n = 3)). The 5-year estimates of overall and disease-free survival were 23% and 17%. The 5-year estimates of central, local-regional, and distant failure were 21%, 51%, and 40%. This was a

  12. Value of adjuvant misonidazole in the definitive irradiation of advanced head and neck squamous cancer: an RTOG pilot study (78-02)

    SciTech Connect

    Fazekas, J.T.; Goodman, R.L.; McLean, C.J.

    1981-12-01

    This RTOG Phase II trial was instituted to determine the toxicity and potential value of the electron-affinic agent, Misonidazole, adjunctive to definitive radiotherapy of T3 and T4 squamous cancers of the oral cavity, oropharynx, or hypopharynx. The fractionation schema was altered to deliver two separate treatments (250 rad and 210 rad) on each day when Misonidazole was administered, while maintaining relatively ''standard'' fractionation (5 fractions and 1000 rad per week). In order to achieve effective enhancement while minimizing toxicity, Misonidazole doses were limited to 2.5 gm/m/sup 2/ once per week, not to exceed 24 gm total cumulative in 6 weeks. The dosage was reduced to 2.0 gm/m/sup 2//wk after the first 30 patients were entered. Among the 50 patients entered, toxicity was confined to the nervous system, with one-third of the patients experiencing mild or moderate peripheral neuropathies and an equal number developing nausea and/or vomiting following p.o. drug administration. Encephalopathy occurred in 10% of the 30 patients receiving 2.5 mg/m/sup 2/ dosage. Serum drug levels and cumulative Misonidazole doses did not correlate well with toxicity or response except in comparison of the ''no response'' to the ''complete response'' categories. Immediate mucosal and skin reactions were not enhanced and unusual late normal tissue effects were not encountered. Complete disappearance of all visible and palpable primary tumor was noted in 67% of the 36 patients who completed the adjuvant sensitizer program. Tumor response and survival did not generally correlate with measured (serum) Misonidazole concentration; recurrence was also independent of these measured levels. These preliminary results seemed sufficiently encouraging to warrant a Phase III (randomized) study, now underway by the RTOG.

  13. Quantitative Immunohistochemical Analyses of the Expression of E-Cadherin, Thrombomodulin, CD44H and CD44v6 in Primary Tumours of pharynx/larynx Squamous Cell Carcinoma and their Lymph Node Metastases

    PubMed Central

    Gaspar, Rocío Hernández; de los Toyos, Juan R.; Marcos, César Álvarez; Riera, José Ramón; Sampedro, Andrés

    1999-01-01

    The quantitative expression of E‐cadherin, thrombomodulin, CD44H and CD44v6 in 32 specimens of primary tumours of pharynx/larynx squamous cell carcinoma and their lymph node metastases was studied by immunohistochemistry. With the aim of obtaining comparative and objective data, image acquisition conditions were kept unaltered for all the measurements and the immunostaining intensity was quantified by applying an image processing system. On the one hand, correlations were only observed between CD44H and CD44v6, both in primary tumours and metastases, and between E‐cadherin and TM in metastases. On the other hand, statistical analyses of paired data did not show significant differences in the expression of these markers between the two tumour sites. In agreement with previous reports, E‐cadherin expression was rather low or negative in primary tumours and metastases of the three poorly differentiated specimens we studied, as well as that of TM, but otherwise some of these samples showed intermediate immunostaining levels of CD44H/CD44v6. It may be concluded from the present study that the quantitative expression of these adhesion molecules in well established lymph node metastases of pharynx/larynx squamous cell carcinoma is essentially unaltered in relation to their primary sites. PMID:10609562

  14. c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

    SciTech Connect

    Baschnagel, Andrew M.; Williams, Lindsay; Hanna, Alaa; Chen, Peter Y.; Krauss, Daniel J.; Pruetz, Barbara L.; Akervall, Jan; Wilson, George D.

    2014-03-01

    Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16

  15. A randomized, phase 2 study comparing pemetrexed plus best supportive care versus best supportive care as maintenance therapy after first-line treatment with pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer

    PubMed Central

    2012-01-01

    Background Maintenance therapy for non-small cell lung cancer (NSCLC) aims to extend disease control after first-line chemotherapy with active and well-tolerated agents. The utility of continuation maintenance therapy requires further research. Methods This multicenter, randomized, phase 2 study compared continuation maintenance therapy with pemetrexed (500 mg/m2 every 21 days) and best supportive care (BSC) versus BSC alone in patients with advanced, non-squamous NSCLC who had not progressed after 4 cycles of induction chemotherapy with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). The primary endpoint was progression-free survival (PFS) from randomization, was analyzed using a Cox model, stratified for the tumor response at the end of induction therapy, at a one-sided alpha of 0.2. Secondary endpoints: response and disease control rates, overall survival (OS), one year survival rates, and treatment-emergent adverse events (TEAEs). Results A total of 106 patients commenced induction therapy, of whom 55 patients were randomized to maintenance pemetrexed/BSC (n = 28) or BSC (n = 27). Although the median PFS time for maintenance phase for both arms was 3.2 months, the one-sided p-value for the PFS HR comparison was less than the prespecified limit of 0.2 (HR = 0.76, two-sided 95% confidence interval [CI]: 0.42 to 1.37; one-sided p-value = 0.1815), indicating that PFS was sufficiently long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS results were observed for the overall study period (induction plus maintenance) and when the PFS analysis was adjusted for sex, baseline disease stage, and the ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2 months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8 months (95% CI: 6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for both arms for the maintenance phase and the overall study period. Both the

  16. Primary radiation therapy for locally advanced breast cancer

    SciTech Connect

    Sheldon, T.; Hayes, D.F.; Cady, B.; Parker, L.; Osteen, R.; Silver, B.; Recht, A.; Come, S.; Henderson, I.C.; Harris, J.R.

    1987-09-15

    The optimal local-regional treatment for patients with Stage III breast cancer has not been determined. To evaluate the effectiveness of radiation therapy as local treatment for such patients, the results of 192 patients (five with bilateral disease) treated with radiation therapy without mastectomy between July 1, 1968 and December 31, 1981 were reviewed. Excisional biopsy (gross tumor removal) was performed in only 54 of the 197 breasts. Patients typically received 4500 to 5000 cGy in 5 weeks to the breast and draining lymph nodes; a local boost to areas of gross disease was delivered to 157 patients. Multi-agent chemotherapy was given to 53 patients. The median follow-up was 65 months. The actuarial probability of survival for the entire group was 41% at 5 years and 23% at 10 years. The probability of relapse-free survival (RFS) was 30% at 5 years and 19% at 10 years. The addition of multi-agent chemotherapy was associated with a significantly improved 5-year RFS (40% versus 26%, P = 0.02). The 5-year survival rate was 51% for patients who received adjuvant multi-agent chemotherapy and 38% for patients who did not (P = 0.16). The actuarial rate of local-regional tumor control (not censored for distant failure) for all patients was 73% at 5 years and 68% at ten years, and the crude incidence of local-regional control was 78%. Local-regional tumor control was principally influenced by radiation dose. Patients who received 6000 cGy or greater to the primary site had a better 5-year rate of control in the breast than did patients who received less than 6000 cGy (83% versus 70%, P = 0.06). Significant complications were seen in 15 patients (8%); these included moderate or severe arm edema in six patients and brachial plexopathy in four patients. Cosmetic results at last evaluation were excellent or good in 56% of evaluable patients, fair in 25%, and poor in 19%.

  17. Should PET/CT be implemented in the routine imaging work-up of locally advanced head and neck squamous cell carcinoma? A prospective analysis.

    PubMed

    Cacicedo, Jon; Fernandez, Iratxe; Del Hoyo, Olga; Dolado, Ainara; Gómez-Suarez, Javier; Hortelano, Eduardo; Sancho, Aintzane; Pijoan, Jose I; Alvarez, Julio; Espinosa, Jose M; Gaafar, Ayman; Bilbao, Pedro

    2015-08-01

    The objective of this study was to determine the incremental staging information provided by positron emission tomography/computed tomography (PET/CT) and its impact on management plans in patients with untreated stage III-IV head and neck squamous cell carcinoma (HNSCC). We prospectively studied, between September 2011 and February 2013, 84 consecutive patients [median age 63.5 years (39-84); 73 men] with histologically confirmed HNSCC. First, based on a conventional work-up (physical examination, CT imaging of the head, neck and chest), the multidisciplinary Head and Neck Tumour Board documented the TNM stage and a management plan for each patient, outlining the modalities to be used, including surgery, radiation therapy (RT), chemotherapy or a combination. After release of the PET/CT results, new TNM staging and management plans were agreed on by the multidisciplinary Tumour Board. Any changes in stage or intended management due to the PET/CT findings were then analysed. The impact on patient management was classified as: low (treatment modality, delivery and intent unchanged), moderate (change within the same treatment modality: type of surgery, radiation technique/dose) or high (change in treatment intent and/or treatment modality → curative to palliative, or surgery to chemoradiation or detection of unknown primary tumour or a synchronous second primary tumour). TNM stage was validated by histopathological analysis, additional imaging or follow-up. Accuracy of the conventional and PET/CT-based staging was compared using McNemar's test. Conventional and PET/CT stages were discordant in 32/84 (38 %) cases: the T stage in 2/32 (6.2 %), the N stage in 21/32 (65.7 %) and the M stage 9/32 (28.1 %). Patient management was altered in 22/84 (26 %) patients, with a moderate impact in 8 (9.5 %) patients and high impact in 14 (16.6 %) patients. PET/CT TNM classification was significantly more accurate (92.5 vs 73.7 %) than conventional staging with a p value < 0

  18. A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer

    PubMed Central

    Yu, Hui; Zhang, Jian; Wu, Xianghua; Luo, Zhiguo; Wang, Huijie; Sun, Si; Peng, Wei; Qiao, Jie; Feng, Yu; Wang, Jialei; Chang, Jianhua

    2014-01-01

    Current pemetrexed/platinum chemotherapy does not produce a satisfactory therapeutic response in advanced lung cancer patients. The aim of this study was to determine whether the administration of gefitinib, a tyrosine kinase inhibitor (TKI), intercalated with pemetrexed/platinum could improve the efficacy in chemotherapy-naïve patients with advanced non-squamous NSCLC without subsequent gefitinib maintenance therapy. Treatment-naïve patients with stage IIIB or IV NSCLC were randomly assigned to receive pemetrexed (500 mg/m2 d1) and either cisplatin (75 mg/m2 d1) or carboplatin (AUC = 5 d1) plus gefitinib (250 mg/d on days 3 to 16 of a 3-week cycle) (PC-G) or pemetrexed–platinum (PC) alone. Randomization was stratified according to the tobacco smoking status and EGFR mutational status of the patients. The primary endpoint was the non-progression rate (NPR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and biosafety. The NPR at 12 weeks was 84.5% for the PC-G treatment arm and 83.1% for the PC treatment arm (P = 0.87). Median PFS was 7.9 months for the PC-G arm and 7.0 months for the PC arm (P = 0.57). The ORR was 50.0% for the PC-G arm and 47.4% for the PC arm (P = 0.78). Median survival was 25.4 mo for the PC-G arm and 20.8 mo for the PC arm (P = 0.54). The incidence of adverse events was similar between the two treatment arms, except for a higher incidence of skin rash with PC-G. Predefined subgroup analyses demonstrated that PC-G significantly increased the PFS compared with the PC regimen in patients with EGFR mutations (P = 0.017). Although gefitinib intercalated with pemetrexed/platinum chemotherapy did not improve the NPR at 12 weeks compared with chemotherapy, an improvement in the PFS for the intercalated treatment arm was seen in the subgroup of patients with EGFR mutations. PMID:24755888

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

    ClinicalTrials.gov

    2017-04-11

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

  20. Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study.

    PubMed

    Psyrri, A; Fortpied, C; Koutsodontis, G; Avgeris, M; Kroupis, C; Goutas, N; Menis, J; Herman, L; Giurgea, L; Remenár, É; Degardin, M; Pateras, I S; Langendijk, J A; van Herpen, C M L; Awada, A; Germà-Lluch, J R; Kienzer, H R; Licitra, L; Vermorken, J B

    2017-09-01

    EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status.

  1. Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Schell, Amy; Ley, Jessica; Wu, Ningying; Trinkaus, Kathryn; Wildes, Tanya Marya; Michel, Loren; Thorstad, Wade; Gay, Hiram; Lewis, James; Rich, Jason; Diaz, Jason; Paniello, Randal C; Nussenbaum, Brian; Adkins, Douglas R

    2015-01-01

    We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30–58) months versus 52 (range: 13–84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC. PMID:25619559

  2. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Budach, W; Hehr, T; Budach, V; Belka, C; Dietz, K

    2006-01-01

    Background Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. Methods Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. Results Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). Conclusion RT combined with simultaneous 5-FU

  3. Concurrent Radiotherapy with Carboplatin and Cetuximab for the Treatment of Medically Compromised Patients with Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Saigal, Kunal; Santos, Edgardo S.; Tolba, Khaled; Kwon, Deukwoo; Elsayyad, Nagy; Abramowitz, Matthew C.; Mandalia, Amar; Samuels, Michael Andrew

    2014-01-01

    Background: Cetuximab (Cx) + radiation therapy (RT) is well-tolerated and has improved survival in patients (pts) with locoregionally advanced head and neck squamous cell carcinomas (LA-HNSCC). However, its efficacy when compared to HD-DDP + RT has been questioned. At our institution, low-dose weekly carboplatin is added to Cx + RT for patients unsuitable for HD-DDP. Methods: We reviewed records of 16 patients with LA-HNSCC treated with definitive Cx + carboplatin + RT at the University of Miami from 2007 to 2011. Median follow-up was 24 months (range: 1–69 months). Results: Median age: 71.5 years (range: 57–90 years); 15 male, 1 female. ECOG PS 0 = 15, 1 = 1. TNM staging was: T1 = 1, T2 = 5, T3 = 8, T4 = 2; N stage: N0 = 8, N1 = 5, N2a = 2, N2b = 1. All patients received weekly carboplatin (AUC 1.5–2), Cx given conventionally and daily conventionally fractionated RT. Median total weeks of concurrent systemic therapy = 7 (range: 3–8 weeks). RT was delivered to a median total dose of 70 Gy (range 30–74 Gy). Of the 15 evaluable patients, there were: 12 CR, 2 PR, and 1 PD. There were three local in-field failures, two regional failures, and three distant failures. At last follow-up, 8/15 patients remained with NED. Three-year locoregional recurrence was 28.3% (95% CI: 7.7–53.9%). Mean percentage of weight loss was 14% (range: 6–26%). Two patients required systemic therapy dose reduction. Three patients experienced a treatment delay and three did not finish RT as planned including a patient who received only 30 Gy due to death secondary to MI during treatment. Conclusion: In this small retrospective series, carboplatin/Cx/RT was well-tolerated and efficacious in patients unsuitable for HD-DDP having LA-HNSCC. Acute toxicities were similar to Cx + RT, likely due to the non-overlapping toxicity profiles of the two systemic agents. We hypothesize that the addition of a well

  4. Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

    PubMed

    Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

    2016-06-01

    Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost

  5. Late Consequential Surgical Bed Soft Tissue Necrosis in Advanced Oropharyngeal Squamous Cell Carcinomas Treated With Transoral Robotic Surgery and Postoperative Radiation Therapy

    SciTech Connect

    Lukens, J. Nicholas; Lin, Alexander; Gamerman, Victoria; Mitra, Nandita; Grover, Surbhi; McMenamin, Erin M.; Weinstein, Gregory S.; O'Malley, Bert W.; Cohen, Roger B.; Orisamolu, Abimbola; Ahn, Peter H.; Quon, Harry

    2014-08-01

    Purpose: A subset of patients with oropharyngeal squamous cell carcinoma (OP-SCC) managed with transoral robotic surgery (TORS) and postoperative radiation therapy (PORT) developed soft tissue necrosis (STN) in the surgical bed months after completion of PORT. We investigated the frequency and risk factors. Materials and Methods: This retrospective analysis included 170 consecutive OP-SCC patients treated with TORS and PORT between 2006 and 2012, with >6 months' of follow-up. STN was defined as ulceration of the surgical bed >6 weeks after completion of PORT, requiring opioids, biopsy, or hyperbaric oxygen therapy. Results: A total of 47 of 170 patients (28%) had a diagnosis of STN. Tonsillar patients were more susceptible than base-of-tongue (BOT) patients, 39% (41 of 104) versus 9% (6 of 66), respectively. For patients with STN, median tumor size was 3.0 cm (range 1.0-5.6 cm), and depth of resection was 2.2 cm (range 1.0-5.1 cm). Median radiation dose and dose of fraction to the surgical bed were 6600 cGy and 220 cGy, respectively. Thirty-one patients (66%) received concurrent chemotherapy. Median time to STN was 2.5 months after PORT. All patients had resolution of STN after a median of 3.7 months. Multivariate analysis identified tonsillar primary (odds ratio [OR] 4.73, P=.01), depth of resection (OR 3.12, P=.001), total radiation dose to the resection bed (OR 1.51 per Gy, P<.01), and grade 3 acute mucositis (OR 3.47, P=.02) as risk factors for STN. Beginning May 2011, after implementing aggressive avoidance of delivering >2 Gy/day to the resection bed mucosa, only 8% (2 of 26 patients) experienced STN (all grade 2). Conclusions: A subset of OP-SCC patients treated with TORS and PORT are at risk for developing late consequential surgical bed STN. Risk factors include tonsillar location, depth of resection, radiation dose to the surgical bed, and severe mucositis. STN risk is significantly decreased with carefully avoiding a radiation dosage of >2 Gy/day to the

  6. Late consequential surgical bed soft tissue necrosis in advanced oropharyngeal squamous cell carcinomas treated with transoral robotic surgery and postoperative radiation therapy.

    PubMed

    Lukens, J Nicholas; Lin, Alexander; Gamerman, Victoria; Mitra, Nandita; Grover, Surbhi; McMenamin, Erin M; Weinstein, Gregory S; O'Malley, Bert W; Cohen, Roger B; Orisamolu, Abimbola; Ahn, Peter H; Quon, Harry

    2014-08-01

    A subset of patients with oropharyngeal squamous cell carcinoma (OP-SCC) managed with transoral robotic surgery (TORS) and postoperative radiation therapy (PORT) developed soft tissue necrosis (STN) in the surgical bed months after completion of PORT. We investigated the frequency and risk factors. This retrospective analysis included 170 consecutive OP-SCC patients treated with TORS and PORT between 2006 and 2012, with >6 months' of follow-up. STN was defined as ulceration of the surgical bed >6 weeks after completion of PORT, requiring opioids, biopsy, or hyperbaric oxygen therapy. A total of 47 of 170 patients (28%) had a diagnosis of STN. Tonsillar patients were more susceptible than base-of-tongue (BOT) patients, 39% (41 of 104) versus 9% (6 of 66), respectively. For patients with STN, median tumor size was 3.0 cm (range 1.0-5.6 cm), and depth of resection was 2.2 cm (range 1.0-5.1 cm). Median radiation dose and dose of fraction to the surgical bed were 6600 cGy and 220 cGy, respectively. Thirty-one patients (66%) received concurrent chemotherapy. Median time to STN was 2.5 months after PORT. All patients had resolution of STN after a median of 3.7 months. Multivariate analysis identified tonsillar primary (odds ratio [OR] 4.73, P=.01), depth of resection (OR 3.12, P=.001), total radiation dose to the resection bed (OR 1.51 per Gy, P<.01), and grade 3 acute mucositis (OR 3.47, P=.02) as risk factors for STN. Beginning May 2011, after implementing aggressive avoidance of delivering >2 Gy/day to the resection bed mucosa, only 8% (2 of 26 patients) experienced STN (all grade 2). A subset of OP-SCC patients treated with TORS and PORT are at risk for developing late consequential surgical bed STN. Risk factors include tonsillar location, depth of resection, radiation dose to the surgical bed, and severe mucositis. STN risk is significantly decreased with carefully avoiding a radiation dosage of >2 Gy/day to the surgical bed. Copyright © 2014 Elsevier Inc. All

  7. An Ultra-Deep Targeted Sequencing Gene Panel Improves the Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

    PubMed

    Liao, Chun-Ta; Chen, Shu-Jen; Lee, Li-Yu; Hsueh, Chuen; Yang, Lan-Yan; Lin, Chien-Yu; Fan, Kang-Hsing; Wang, Hung-Ming; Ng, Shu-Hang; Lin, Chih-Hung; Tsao, Chung-Kan; Chen, I-How; Chang, Kai-Ping; Huang, Shiang-Fu; Kang, Chung-Jan; Chen, Hua-Chien; Yen, Tzu-Chen

    2016-02-01

    An improved prognostic stratification of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically positive (pN+) nodes is urgently needed. Here, we sought to examine whether an ultra-deep targeted sequencing (UDT-Seq) gene panel may improve the prognostic stratification in this patient group.A mutation-based signature affecting 10 genes (including genetic mutations in 6 oncogenes and 4 tumor suppressor genes) was devised to predict disease-free survival (DFS) in 345 primary tumor specimens obtained from pN+ OSCC patients. Of the 345 patients, 144 were extracapsular spread (ECS)-negative and 201 were ECS-positive. The 5-year locoregional control, distant metastases, disease-free, disease-specific, and overall survival (OS) rates served as outcome measures.The UDT-Seq panel was an independent risk factor (RF) for 5-year locoregional control (P = 0.0067), distant metastases (P = 0.0001), DFS (P < 0.0001), disease-specific survival (DSS, P < 0.0001), and OS (P = 0.0003) in pN+ OSCC patients. The presence of ECS and pT3-4 disease were also independent RFs for DFS, DSS, and OS. A prognostic scoring system was formulated by summing up the significant covariates (UDT-Seq, ECS, pT3-4) separately for each survival endpoint. The presence of a positive UDT-Seq panel (n = 77) significantly improved risk stratification for all the survival endpoints as compared with traditional AJCC staging (P < 0.0001). Among ECS-negative patients, those with a UDT-Seq-positive panel (n = 31) had significantly worse DFS (P = 0.0005) and DSS (P = 0.0002). Among ECS-positive patients, those with a UDT-Seq-positive panel (n = 46) also had significantly worse DFS (P = 0.0032) and DSS (P = 0.0098).Our UDT-Seq gene panel consisting of clinically actionable genes was significantly associated with patient outcomes and provided better prognostic stratification than traditional AJCC staging. It was also able to predict prognosis in

  8. [Prognostic and predictive value of koilocytosis, expression of e6 hpv types 16/18, p16ink4a, p53 in locally advanced squamous cell carcinomas of oral cavity and oropharynx, associated with human papillomavirus].

    PubMed

    Riaboshapka, A N

    2014-11-01

    To determine the predictive and prognostic value of koilocytosis, expression of E6 HPV types 16/18, p16INK4a, p53 in patients with locally advanced HPV-associated squamous cell carcinoma of oral cavity and oropharynx. In biopsy specimens of squamous cell carcinomas of oral cavity and oropharynx from 60 patients performed koylocytes count, immunohistochemical detection of HPV 16/18 types E6 protein, proteins p16INK4a and p53. Koilocytosis was detected in 50 patients (83.3%); in all 60 patients (100%) were simultaneous expression of p16INK4a and E6 HPV types 16/18; p53 expression was found in 37 patients (61.7%). After combined treatment (induction chemotherapy followed by radiotherapy) stable disease (SD) was detected in 11 patients (18.3%), partial response (PR) - in 25 patients (41.7%), complete response (CR) - in 24 patients (40.0%). There were no cases of disease progression. Treatment effect correlated with expression of p16INK4a (ρ = 0.3, p = 0.024) and expression of p53 (ρ = - 0.3, p = 0.019). Patients with a low expression of p16INK4a (2 points) and high expression of p53 (4 "+") had a high level of SD and had no CR. For all patients, the median of overall survival (OS) was 17 months, 1-year cumulative survival rate was 66.7%, 2-year cumulative survival rate - 35.0%. Median of overall survival was correlated with koilocytosis (ρ=0.5, p<0,001) and expression of E6 HPV types 16/18 (ρ=0.9, p<0.001), p16INK4a (ρ=0.9, p=0.037), p53 (ρ=-0.9; p<0.001). Patients with low expression of p53 (0 and 1 "+") had cumulative 1-year survival rates 87% and 90%, respectively (p<0.001), 2-year survival rates - 52% and 80%, respectively (p=0.015). In the Cox proportional hazards model the significant prognostic factors were prevalence of primary tumor (OR 2.2, 95% CI 1.3 - 3.5, p=0.003) and p53 expression (OR 1.3, 95% CI 1.1=1.7, p=0.016). High expression of p16INK4a associated with a high effect of combined treatment, high expression of a p53 - with low effect of

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

    ClinicalTrials.gov

    2017-04-14

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  10. Primary Care Advanced Practice RNs' Knowledge of Posttraumatic Stress Disorder and Screening.

    PubMed

    Link, Kimberly A; Smith, Lynette S

    2017-09-01

    Individuals with posttraumatic stress disorder (PTSD) may seek treatment for their symptoms within the primary care setting. Research suggests PTSD often goes undiagnosed in primary care. Primary care providers (PCPs) might have deficiencies in their knowledge of PTSD screening and screening practices. A descriptive cross-sectional study design was used to examine primary care advanced practice RNs' (APRN) knowledge of PTSD screening and screening practices, along with subjective norms, attitudes, and self-efficacy regarding PTSD screening. Deficiencies in knowledge of PTSD screening and screening practices were identified. Discrepancies were found between reported subjective norms and screening practices, and most participants reported low self-efficacy and stated screening was not important. Numerous barriers to screening were identified. Additional education and training may be needed to improve primary care APRNs' PTSD screening knowledge and screening practices. [Journal of Psychosocial Nursing and Mental Health Services, 55(9), 23-32.]. Copyright 2017, SLACK Incorporated.

  11. Perspectives on the value of advanced medical imaging: a national survey of primary care physicians.

    PubMed

    Hughes, Christine M; Kramer, Erich; Colamonico, Jennifer; Duszak, Richard

    2015-05-01

    To understand perceptions of primary care physicians (PCPs) about the value of advanced medical imaging. A national quantitative survey of 500 PCPs was conducted using an online self-administered questionnaire. Questions focused on advanced medical imaging (CT, MRI, and PET) and its perceived impact on the delivery of patient care. Responses were stratified by physician demographics. Large majorities of the PCPs indicated that advanced imaging increases their diagnostic confidence (441; 88%); provides data not otherwise available (451; 90%); permits better clinical decision making (440; 88%); increases confidence in treatment choices (438; 88%), and shortens time to definitive diagnosis (430; 86%]). Most (424; 85%) believe that patient care would be negatively affected without access to advanced imaging. PCPs whose clinical careers predated the proliferation of advanced imaging modalities (>20 years of practice) assigned higher value to advanced imaging on several dimensions compared with younger physicians whose training overlapped widespread technology availability. By a variety of metrics, large majorities of PCPs believe that advanced medical imaging provides considerable value to patient care. Those whose careers predated the widespread availability of advanced imaging tended to associate it with even higher value. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  12. 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.

    PubMed

    Frank, Steven J; Rosenthal, David I; Petsuksiri, Janjira; Ang, K Kian; Morrison, William H; Weber, Randal S; Glisson, Bonnie S; Chao, K S Clifford; Schwartz, David L; Chronowski, Gregory M; El-Naggar, Adel K; Garden, Adam S

    2010-11-15

    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. 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 the survival rates calculated using the Kaplan-Meier method. 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. 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. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. 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

    SciTech Connect

    Frank, Steven J.; Rosenthal, David I.; Petsuksiri, Janjira; Ang, K. Kian; Morrison, William H.; Weber, Randal S.; Glisson, Bonnie S.; El-Naggar, Adel K.; Garden, Adam S.

    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 the 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.

  14. [SIB-IMRT radiotherapy given concomitantly with cisplatin for locally advanced squamous cell head and neck cancer (SCHNC). Evaluation of the early results and toxicity].

    PubMed

    Kiprian, Dorota; Jarząbski, Andrzej; Pawłowska, Beata; Michalski, Wojciech; Kawecki, Andrzej

    2011-09-01

    Concomitant radiochemotherapy become the treatment of choice for locally advanced SCHNC. This strategy of treatment has a limitation, which is an acute and late toxicity. The IMRT technique provides the possibility of better sparing of healthy tissue. Radiobiological and clinical data also suggest that accelerated fractionation and higher dose per fraction given in GTV may produce better locoregional control. Therefore it might be expected that concomitant chemotherapy and SIB-IMRT radiotherapy could increase locoregional control and reduce acute and late radiation reactions. The evaluation of early results and toxicity of this treatment modality is presented. The evaluation of the early results and toxicity of SIB-IMRT radiotherapy given concomitantly with cisplatin for locally advanced squamous cell head and neck cancer (SCHNC). SIB-IMRT technique was applied. The boost volume was limited to the GTV + 3mm margin (macroscopic tumor extension was defined on the basis of CT and/or MRI examinations). Dose per fraction given to this volume was 2.25 Gy up to 67.5 Gy of total dose. The PTV-CTV + 3mm - was defined as an area of increased risk of microscopic spread. Dose per fraction given to this volume was 2 Gy up to 60 Gy. The PTV1-ETV+ 3mm (electively irradiated volume) received dose per fraction -1.8 Gy up to 54-56 Gy. Overall treatment time was 6 weeks (5 fractions per week, 30 fractions). Concomitant chemotherapy consisted of cisplatin in daily dose100mg/m2 given two times during irradiation (1 and 22 day of treatment). The evaluation of early tolerance was performed once weekly during the treatment than during the follow up every 2 months. The early reactions were scored according to the EORTC/RTOG scale. Between June 2006 and December 2009 99 patients diagnosed with III and IV clinical stage of SCHNC were treated with this method. 65 patients were diagnosed with oropharyngeal cancer, 18 with laryngeal cancer and 16 with hypopharyngeal cancer. PEG was performed at

  15. Usefulness of Interim FDG-PET After Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Sequential Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

    SciTech Connect

    Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon; Nam, Soon Yuhl; Choi, Seung-Ho; Roh, Jong-Lyel; Lee, Sang-wook; Song, Si Yeol; Lee, Jeong Hyun; Kim, Jae Seung; Cho, Kyung-Ja; Kim, Sung-Bae

    2011-09-01

    Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors before definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.

  16. Advanced composite structural concepts and material technologies for primary aircraft structures

    NASA Technical Reports Server (NTRS)

    Jackson, Anthony

    1991-01-01

    Structural weight savings using advanced composites have been demonstrated for many years. Most military aircraft today use these materials extensively and Europe has taken the lead in their use in commercial aircraft primary structures. A major inhibiter to the use of advanced composites in the United States is cost. Material costs are high and will remain high relative to aluminum. The key therefore lies in the significant reduction in fabrication and assembly costs. The largest cost in most structures today is assembly. As part of the NASA Advanced Composite Technology Program, Lockheed Aeronautical Systems Company has a contract to explore and develop advanced structural and manufacturing concepts using advanced composites for transport aircraft. Wing and fuselage concepts and related trade studies are discussed. These concepts are intended to lower cost and weight through the use of innovative material forms, processes, structural configurations and minimization of parts. The approach to the trade studies and the downselect to the primary wing and fuselage concepts is detailed. The expectations for the development of these concepts is reviewed.

  17. Does Advanced Access improve access to primary health care? Questionnaire survey of patients.

    PubMed

    Salisbury, Chris; Goodall, Stephen; Montgomery, Alan A; Pickin, D Mark; Edwards, Sarah; Sampson, Fiona; Simons, Lucy; Lattimer, Val

    2007-08-01

    General practices in England have been encouraged to introduce Advanced Access, but there is no robust evidence that this is associated with improved access in ways that matter to patients. To compare priorities and experiences of patients consulting in practices which do or do not operate Advanced Access. Patient questionnaire survey. Forty-seven practices in 12 primary care trust areas of England. Questionnaire administered when patients consulted. Of 12,825 eligible patients, 10,821 (84%) responded. Most (70%) were consulting about a problem they had had for at least 'a few weeks'. Patients obtained their current appointment sooner in Advanced Access practices, but were less likely to have been able to book in advance. They could usually see a doctor more quickly than those in control practices, but were no more satisfied overall with the appointment system. The top priority for patients was to be seen on a day of choice rather than to be seen quickly, but different patient groups had different priorities. Patients in Advanced Access practices were no more or less likely to obtain an appointment that matched their priorities than those in control practices. Patients in both types of practice experienced problems making contact by telephone. Patients are seen more quickly in Advanced Access practices, but speed of access is less important to patients than choice of appointment; this may be because most consultations are about long-standing problems. Appointment systems need to be flexible to accommodate the different needs of different patient groups.

  18. Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues….

    PubMed

    Leary, Alexandra; Cowan, Renee; Chi, Dennis; Kehoe, Sean; Nankivell, Matthew

    2016-01-01

    Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies.

  19. Successful multimodality treatment for locally advanced primary thymic adenocarcinoma: report of a case.

    PubMed

    Haruki, Tomohiro; Wakahara, Makoto; Taniguchi, Yuji; Nakamura, Yoshinobu; Nishimura, Motonobu; Nakamura, Hiroshige

    2016-08-31

    Although the optimal treatment strategy for locally advanced thymic carcinomas has yet to be determined, complete resection of the tumor after induction chemoradiotherapy (CRT) can sometimes provide a good chance of being cured. A 61-year-old woman was diagnosed with locally advanced primary thymic carcinoma, which invaded bilateral brachiocephalic veins and superior vena cava with intraluminal tumor thrombus. Induction CRT was performed, and a partial response to the treatment was achieved. Subsequent radical surgery was successfully performed by the median full sternotomy with a right transmanubrial osteomuscular sparing approach (TMA). The patient is currently alive and has remained disease-free for a year. The TMA is useful for extensive surgery of locally advanced thymic carcinoma because it can provide good exposure of the operative field without post-operative functional limitation of upper limbs.

  20. Immunohistochemical characterization of mammary squamous cell carcinoma of the dog.

    PubMed

    Sassi, Francesco; Sarli, Giuseppe; Brunetti, Barbara; Morandi, Federico; Benazzi, Cinzia

    2008-11-01

    Squamous cell carcinoma of the mammary gland is rare in both veterinary and human medicine. Whereas human metaplastic and squamous variants are known, the objectives of the current study were to ascertain the presence of such entities in canine mammary tumors and to distinguish them from other (epidermal, sweat gland) squamous tumors that may develop in the same area. A panel of antibodies (anti-cytokeratin [CK] 19, CK 14, CK 5/6, pancytokeratin, and vimentin) was used on 18 mammary gland malignancies with squamous features and 16 malignant skin tumors (11 squamous cell carcinomas of the skin and 5 sweat glands). Fifteen of the 18 mammary carcinomas were classified as metaplastic carcinomas, and the remaining 3 were classified as squamous cell carcinomas. The 2 most useful markers to establish the histogenesis of mammary tumors were pancytokeratin and CK 19. All other antibodies were equally expressed (CK 14 and 5/6) in all histotypes. The antibody panel discriminated primary epidermal squamous tumors (pancytokeratin positive and CK 19 negative) from gland-derived squamous neoplasms (pancytokeratin positive and CK 19 positive) but failed to distinguish primary mammary tumors from other squamous tumors of glandular origin.

  1. Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy.

    PubMed

    Ji, W H; Jiang, Y H; Ji, Y L; Li, B; Mao, W M

    2016-07-01

    The study aimed to evaluate the prognostic significance of prechemotherapy neutrophil to lymphocyte ratio and platelet to lymphocyte ratio, and preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in locally advanced esophageal squamous cell cancer. We analyzed retrospectively locally advanced esophageal squamous cell cancer patients who had received neoadjuvant chemotherapy before undergoing a radical esophagectomy between 2009 and 2012. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio before chemotherapy and before the surgery were calculated. Univariate analyses showed that prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.048, hazard ratio = 2.86; 95% confidence interval: 1.01-8.12) and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.025, hazard ratio = 5.50; 95% confidence interval: 1.23-24.55) were associated significantly with overall survival (OS), and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.026, hazard ratio = 3.18; 95% confidence interval: 1.15-8.85) was associated significantly with progression-free survival. However, only prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.024, hazard ratio = 3.50; 95% confidence interval: 1.18-10.40) remained significantly associated with OS in multivariate analyses. Neither preoperative neutrophil to lymphocyte ratio nor platelet to lymphocyte ratio was associated with OS or progression-free survival. The prechemotherapy neutrophil to lymphocyte ratio >5 to preoperative neutrophil to lymphocyte ratio ≤5 group showed significantly worse OS than the prechemotherapy neutrophil to lymphocyte ratio ≤5 to preoperative neutrophil to lymphocyte ratio ≤5 group (P = 0.050). The prechemotherapy platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio ≤130 group (P = 0.016) and platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio >130 group (P = 0.042) showed significantly worse OS than the

  2. Atypical squamous epithelium in cytologic specimens from the pancreas: cytological differential diagnosis and clinical implications.

    PubMed

    Layfield, L J; Cramer, H; Madden, J; Gopez, E V; Liu, K

    2001-07-01

    Atypical squamous epithelium is an uncommon finding in cytologic specimens obtained from pancreatic lesions. A variety of pathologic conditions can result in the presence of these cells, including primary or metastatic carcinomas, chronic pancreatitis, and squamous metaplasia related to pancreatic or biliary duct stent placement. Primary adenosquamous and squamous-cell carcinomas of the pancreas are rare, representing 3.4% and 1.4 % of pancreatic carcinomas, respectively. Cytologic separation of these malignancies from less ominous metaplasias has immense clinical importance. We reviewed Indiana University Hospital's and Duke University's experiences with atypical squamous epithelium occurring within pancreatic aspirates. Study cases were identified using a computer to search the cytology records of these two institutions. Nine cases with a diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or atypical squamous epithelium were retrieved from the two institutions' Department of Pathology files. One case of pure squamous-cell carcinoma occurred in a patient with a known pulmonary primary; a single case of adenosquamous carcinoma was diagnosed in a patient with a coexistent endometrial primary; a single sample of adenocarcinoma with squamous differentiation was diagnosed in a patient without other known disease; and four primary squamous-cell carcinomas of the pancreas were detected. In addition, a single case of atypical squamous metaplasia associated with a stent was identified, and one case of atypical squamous epithelium associated with chronic pancreatitis was diagnosed. Despite the reactive atypia present in the examples of metaplastic squamous epithelium, separation of these cases from true squamous-cell carcinoma and adenosquamous carcinoma was achievable by cytologic evaluation. No cytologic criteria aided in separating primary pancreatic carcinomas with squamous differentiation from metastatic lesions. In this study, we report our findings in a

  3. Primary Metastatic Squamous Cell Carcinoma of the Male Urethra Presenting with Scrotal Abscess and Subsequent Development of Fournier’s Gangrene

    PubMed Central

    Moore, Sarah J.; Rashidipour, Omid; Moore, Ronald B.

    2016-01-01

    This male patient presented with a scrotal abscess and urinary obstruction. The patient’s history included a perineal abscess and the development of urethrocutaneous fistulae (watering-can perineum). He underwent multiple debridement procedures without resolution. During the fifth debridement for Fournier’s gangrene, a biopsy revealed invasive squamous cell carcinoma. The patient was bedridden because of the large mass, a wide en bloc resection with lymphadenectomy and reconstruction was performed revealing a large (22 cm) squamous cell carcinoma originating from the urethra. He also received palliative chemoradiotherapy and hip hemiarthroplasty. Unfortunately, he succumbed to the disease. Given the recognized relationship between inflammation and the development of cancer, it is important to entertain a differential diagnosis of cancer, especially with erosive infections. This case report highlights the all too common late presentation of urethral cancer. Interestingly, despite correction of the bedridden state with palliative surgery, the patient did not perceive an improvement in quality of life based on the FACT-G questionnaire. PMID:27721660

  4. Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

    PubMed

    Patel, Umang Jash

    2013-03-01

    A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours.

  5. Advanced Practice Registered Nurses: Gateway to Screening for Bipolar Disorder in Primary Care

    PubMed Central

    Kriebel-Gasparro, Ann Marie

    2016-01-01

    Objective: The goal of this mixed methods descriptive study was to explore Advanced Practice Registered Nurses’ (APRNs’) knowledge of bipolar disorder (BPD) and their perceptions of facilitators and barriers to screening patients with known depression for BPD. Methods: A mixed method study design using surveys on BPD knowledge and screening practices as well as focus group data collection method for facilitators and barriers to screening. Results: 89 APRNs completed the survey and 12 APRNs participated in the focus groups. APRNs in any practice setting had low knowledge scores of BPD. No significant differences in screening for BPD for primary and non primary care APRNs. Qualitative findings revealed screening relates to tool availability; time, unsure of when to screen, fear of sigma, symptoms knowledge of BPD, accessible referral system, personal experiences with BPD, and therapeutic relationships with patients. Conclusion: Misdiagnosis of BPD as unipolar depression is common in primary care settings, leading to a long lag time to optimal diagnosis and treatment. The wait time to diagnosis and treatment could be reduced if APRNs in primary care settings screen patients with a diagnosis of depression by using validated screening tools. These results can inform APRN practice and further research on the effectiveness of screening for reducing the morbidity and mortality of BPDs in primary care settings; underscores the need for integration of mental health care into primary care as well as the need for more APRN education on the diagnosis and management of bipolar disorders. PMID:27347256

  6. Squamous Cell Carcinoma of the Pancreas in a Patient with Germline BRCA2 Mutation-Response to Neoadjuvant Radiochemotherapy

    PubMed Central

    Schultheis, Anne M.; Nguyen, Gia Phuong; Ortmann, Monika; Kruis, Wolfgang; Büttner, Reinhard; Schildhaus, Hans-Ulrich; Markiefka, Birgid

    2014-01-01

    Primary squamous cell carcinoma of the pancreas is a rare malignant neoplasia, accounting for approximately 0.5–2% of all malignant pancreatic tumors. These lesions are characterized by poor prognosis. Here we report on a case of a 57-year-old female patient with known BRCA2 germline mutation presenting with primary squamous cell carcinoma of the pancreas as the only malignancy. The tumor was locally advanced at the first presentation but responded almost completely to neoadjuvant radio-chemotherapy. Our case highlights the facts (i) that pancreatic carcinomas belong to the tumor spectrum of patients with the BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) and (ii) that tumors of the pancreas can represent the first or even the only manifestation of HBOC. Furthermore, this case of a nonkeratinizing squamous cell carcinoma indicates that HBOC-associated carcinomas of the pancreas might be characterized by a broader morphological spectrum than was previously thought. Since BRCA mutations cause deficiency of DNA double-strand breakage repair in tumors, neoadjuvant treatment regimens might become a reasonable option in HBOC-associated pancreatic carcinomas. To our knowledge, this is the first reported case of a primary pancreatic squamous cell carcinoma in a patient with this particular genetic background of BRCA2-associated HBOC. PMID:24959366

  7. A phase II study of capecitabine and cisplatin (XP) as first-line chemotherapy in patients with advanced esophageal squamous cell carcinoma.

    PubMed

    Lee, Jeeyun; Im, Young-Hyuck; Cho, Eun Yoon; Hong, Yong Sang; Lee, Hyo Rak; Kim, Hyo Song; Kim, Mi-Jin; Kim, Kwhanmien; Kang, Won Ki; Park, Keunchil; Shim, Young Mog

    2008-06-01

    The combination of 5-fluorouracil (5-FU) and cisplatin (FP) remains the mostly used regimen for metastatic esophageal squamous carcinoma. This phase II study assessed the efficacy and safety of capecitabine/cisplatin (XP) as a first-line chemotherapy in a homogenous cohort of patients with metastatic or recurrent esophageal squamous cell carcinoma. Patients received 60 mg/m(2) of cisplatin intravenously (IV) on day 1 and capecitabine 1,250 mg/m(2)/dose orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until the documented disease progression, unacceptable toxicity, or patient's refusal. Immunohistochemical studies against thymidylate synthase (TS) and thymidine phosphorylase (TP) were performed to seek predictive markers for treatment response. Between December 2003 and March 2006, 45 patients entered the study. All patients had histologically proven squamous cell carcinoma of the esophagus. The overall response rate (ORR) was 57.8% (95% CI, 43.3-72.2) with 0 CR and 26 PRs. The median duration of response in responders was 4.6 months (1.0-15.6 months). With a median follow-up duration of 25.7 months (10.8-42.6 months), the median time to progression was 4.7 months (95% CI, 2.5-7.0) and the median survival time was 11.2 months (95% CI, 8.5-13.9). Common grade 3 or 4 non-hematological adverse events were anorexia (18/191, 9.4%), fatigue (9/191, 4.7%), constipation (6/191, 3.1%), hand-foot syndrome (6/191, 3.1%) and diarrhea (4/191, 2.1%). The most common grade 3 or 4 hematological adverse events were neutropenia (33/191, 17.3%), followed by leucopenia (11/191, 5.8%), anemia (2/191, 1.0%) and thrombocytopenia (1/191, 0.5%). There was no treatment-related death. Neither TS nor TP showed predictive value for treatment response. The XP regimen demonstrated a promising antitumor activity in metastatic esophageal squamous cell carcinoma, which may potentially replace the FP regimen.

  8. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2017-09-14

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer

  9. Advanced primary pulmonary lymphoepithelioma-like carcinoma: clinical manifestations, treatment, and outcome

    PubMed Central

    Lin, Chun-Yu; Chen, Ying-Jen; Hsieh, Meng-Heng; Wang, Chih-Wei

    2017-01-01

    Background Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. Methods This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. Results Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. Conclusions Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment. PMID:28203414

  10. Advancing general practice nursing in Australia: roles and responsibilities of primary healthcare organisations.

    PubMed

    Lane, Riki; Halcomb, Elizabeth; McKenna, Lisa; Zwar, Nicholas; Naccarella, Lucio; Davies, Gawaine Powell; Russell, Grant

    2016-04-21

    Objectives Given increased numbers and enhanced responsibilities of Australian general practice nurses, we aimed to delineate appropriate roles for primary health care organisations (PHCOs) to support this workforce.Methods A two-round online Delphi consensus process was undertaken between January and June 2012, informed by literature review and key informant interviews. Participants were purposively selected and included decision makers from government and professional organisations, educators, researchers and clinicians from five Australian states and territoriesResults Of 56 invited respondents, 35 (62%) and 31 (55%) responded to the first and second invitation respectively. Participants reached consensus on five key roles for PHCOs in optimising nursing in general practice: (1) matching workforce size and skills to population needs; (2) facilitating leadership opportunities; (3) providing education and educational access; (4) facilitating integration of general practice with other primary care services to support interdisciplinary care; and (5) promoting advanced nursing roles. National concerns, such as limited opportunities for postgraduate education and career progression, were deemed best addressed by national nursing organisations, universities and peak bodies.Conclusions Advancement of nursing in general practice requires system-level support from a range of organisations. PHCOs play a significant role in education and leadership development for nurses and linking national nursing organisations with general practices.What is known about the topic? The role of nurses in Australian general practice has grown in the last decade, yet they face limited career pathways and opportunities for career advancement. Some nations have forged interprofessional primary care teams that use nurses' skills to the full extent of their scope of practice. PHCOs have played important roles in the development of general practice nursing in Australia and internationally

  11. Persistent tracheostomy after primary chemoradiation for advanced laryngeal or hypopharyngeal cancer.

    PubMed

    Tennant, Paul A; Cash, Elizabeth; Bumpous, Jeffrey M; Potts, Kevin L

    2014-11-01

    Despite the demonstrated survival equivalence between chemoradiation and ablative surgery as primary treatment for advanced laryngeal and hypopharyngeal cancers, a subset of patients who undergo organ-preservation therapy have persistent tracheostomy requirement after completion of treatment. Patients who received primary chemoradiation for advanced laryngeal or hypopharyngeal cancer in a 3-year interval were identified. Rate of persistent posttreatment tracheostomy requirement was evaluated. The 12-month overall mortality rate was compared between patients who did and did not receive a tracheostomy before treatment. In 60 patients identified for this study, T3/T4 status and hemilarynx fixation at the time of presentation were associated with persistent tracheostomy requirement 6 and 12 months posttreatment (p = .022; p < .001; and p = .032; p = .0495, respectively). Twelve-month mortality was higher in T3/T4 patients who received pretreatment tracheostomy (p = .034). Patients with advanced laryngeal or hypopharyngeal cancer who require tracheostomy before treatment have low rates of decannulation and higher short-term mortality than those who do not require tracheostomy before organ-preservation therapy. © 2013 Wiley Periodicals, Inc.

  12. Chest wall resection and reconstruction for locally advanced primary breast cancer.

    PubMed

    Hille, Ursula; Soergel, Philipp; Zardo, Patrick; Pertschy, Stefanie; Busch, Kai; Fischer, Stefan

    2013-06-01

    We sought to evaluate clinical and oncologic outcomes of selected patients with locally advanced breast cancer undergoing full thickness chest wall resection (FTCWR) and reconstruction in a multidisciplinary setting. Between 2008 and 2010, five women underwent FTCWR followed by chest wall repair for locally advanced primary breast cancer. In all cases, chest wall repair was performed with a Peri-Guard Repair Patch (Synovis, St. Paul, MN, USA). At follow-up (7-12 months) quality of life, respiratory function and oncologic status were assessed. Successful chest wall resection and repair were achieved in all patients. Plastic reconstruction of post-mastectomy tissue defects was necessary in one case. One patient was treated by breast conserving therapy. Chest ultrasound imaging confirmed absence of adhesions, haematoma or seroma and normal expansion and respiratory movement of the underlying lung in all patients. On follow-up all patients reported good quality of life. Multidisciplinary surgical approaches to chest wall resection and reconstruction in selected patients with locally advanced primary breast cancer are feasible, safe, associated with short operation time and hospital stay and negligible morbidity.

  13. Laparoscopic-assisted cytoreduction for primary advanced ovarian cancer: success, morbidity and survival.

    PubMed

    Fanning, James; Yacoub, Emmanuel; Hojat, Rod

    2011-10-01

    The purpose of this paper is to evaluate laparoscopic-assisted cytoreduction for primary advanced ovarian cancer: feasibility, morbidity, response to chemotherapy and survival. All patients with presumed stage 3/4 primary ovarian cancer underwent attempted laparoscopic cytoreduction. All patients had CT evidence of omental metastasis and ascites. A five port (5-mm) transperitoneal approach was used. A bilateral salpingo-oophorectomy, supracervical hysterectomy and omentectomy were performed with the PlasmaKinetic (PK) cutting forceps. A laparoscopic 5-mm Argon-Beam Coagulator was used to coagulate tumor in the pelvis, abdominal peritoneum, intestinal mesentery, and diaphragm. Twenty-three cases (92%) were successfully cytoreduced laparoscopically without conversion to laparotomy. Median operative time was 2.3h and median blood loss was 340 cc. All tumors were debulked to less than 2 cm and 36% had no residual disease. Median length of stay was 1 day. Median VAS pain score was 4-discomforting. Six patients (24%) had post-operative complications, none grades 3-4. Median overall survival is 3.5 years. Laparoscopic-assisted cytoreduction for primary advanced ovarian cancer was successful, resulting in minimal morbidity, and acceptable survival. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Endothelial P-selectin expression is reduced in advanced primary melanoma and melanoma metastasis.

    PubMed Central

    Nooijen, P. T.; Westphal, J. R.; Eggermont, A. M.; Schalkwijk, C.; Max, R.; de Waal, R. M.; Ruiter, D. J.

    1998-01-01

    Some malignant tumors induce a cellular immune response that results in the formation of an inflammatory infiltrate and subsequent tumor regression. The infiltrating leukocytes extravasate from the bloodstream after binding to adhesion receptors on the surface of the endothelium. One of these receptors is the P-selectin molecule (CD62P) that is constitutively present on normal capillaries. We observed that P-selectin expression is absent from the microvasculature in advanced primary melanoma and in melanoma metastasis in contrast to benign melanocytic lesions where P-selectin expression was identical to that in normal skin. We suggest that one of the mechanisms by which advanced melanoma lesions evade inflammatory regression operates via a decrease of endothelial P-selectin expression. Images Figure 1 PMID:9502409

  15. Advanced training for primary care and general practice nurses: enablers and outcomes of postgraduate education.

    PubMed

    Hallinan, Christine M; Hegarty, Kelsey L

    2016-01-01

    The aims of the present study were to understand enablers to participation in postgraduate education for primary care nurses (PCNs), and to explore how postgraduate education has advanced their nursing practice. Cross-sectional questionnaires were mailed out in April 2012 to current and past students undertaking postgraduate studies in primary care nursing at The University of Melbourne, Victoria, Australia. Questionnaires were returned by 100 out of 243 nurses (response rate 41%). Ninety-one per cent (91/100) of the respondents were first registered as nurses in Australia. Fifty-seven per cent were hospital trained and 43% were university educated to attain their initial nurse qualification. The respondents reported opportunities to expand scope of practice (99%; 97/98), improve clinical practice (98%; 97/99), increase work satisfaction (93%; 91/98) and increase practice autonomy (92%; 89/97) as factors that most influenced participation in postgraduate education in primary care nursing. Major enablers for postgraduate studies were scholarship access (75%; 71/95) and access to distance education (74%; 72/98). Many respondents reported an increased scope of practice (98%; 95/97) and increased job satisfaction (71%; 70/98) as an education outcome. Only 29% (28/97) cited an increase in pay-rate as an outcome. Of the 73 PCNs currently working in general practice, many anticipated an increase in time spent on the preparation of chronic disease management plans (63%; 45/72), multidisciplinary care plans (56%; 40/72) and adult health checks (56%; 40/72) in the preceding 12 months. Recommendations emerging from findings include: (1) increased access to scholarships for nurses undertaking postgraduate education in primary care nursing is imperative; (2) alternative modes of course delivery need to be embedded in primary care nursing education; (3) the development of Australian primary care policy, including policy on funding models, needs to more accurately reflect the

  16. Squamous cell carcinoma of cervix metastatic to ileal loop

    SciTech Connect

    Hulecki, S.J.; Klein, F.A.; Davis, J.E.

    1985-12-01

    A case is presented of squamous cell carcinoma of the cervix with an isolated metastasis to an ileal loop six years after diversion and seven years after definitive treatment of the primary lesion with irradiation.

  17. Thermal Analysis of the Advanced Technology Large Aperture Space Telescope (ATLAST) 8 Meter Primary Mirror

    NASA Technical Reports Server (NTRS)

    Hornsby, Linda; Stahl, H. Philip; Hopkins, Randall C.

    2010-01-01

    The Advanced Technology Large Aperture Space Telescope (ATLAST) preliminary design concept consists of an 8 meter diameter monolithic primary mirror enclosed in an insulated, optical tube with stray light baffles and a sunshade. ATLAST will be placed in orbit about the Sun-Earth L2 and will experience constant exposure to the sun. The insulation on the optical tube and sunshade serve to cold bias the telescope which helps to minimize thermal gradients. The primary mirror will be maintained at 280K with an active thermal control system. The geometric model of the primary mirror, optical tube, sun baffles, and sunshade was developed using Thermal Desktop(R) SINDA/FLUINT(R) was used for the thermal analysis and the radiation environment was analyzed using RADCAD(R). A XX node model was executed in order to characterize the static performance and thermal stability of the mirror during maneuvers. This is important because long exposure observations, such as extra-solar terrestrial planet finding and characterization, require a very stable observatory wave front. Steady state thermal analyses served to predict mirror temperatures for several different sun angles. Transient analyses were performed in order to predict thermal time constant of the primary mirror for a 20 degree slew or 30 degree roll maneuver. This paper describes the thermal model and provides details of the geometry, thermo-optical properties, and the environment which influences the thermal performance. All assumptions that were used in the analysis are also documented. Parametric analyses are summarized for design parameters including primary mirror coatings and sunshade configuration. Estimates of mirror heater power requirements are reported. The thermal model demonstrates results for the primary mirror heated from the back side and edges using a heater system with multiple independently controlled zones.

  18. Thermal Analysis of the Advanced Technology Large Aperture Space Telescope (ATLAST) 8 Meter Primary Mirror

    NASA Technical Reports Server (NTRS)

    Hornsby, Linda; Stahl, H. Philip; Hopkins, Randall C.

    2010-01-01

    The Advanced Technology Large Aperture Space Telescope (ATLAST) preliminary design concept consists of an 8 meter diameter monolithic primary mirror enclosed in an insulated, optical tube with stray light baffles and a sunshade. ATLAST will be placed in orbit about the Sun-Earth L2 and will experience constant exposure to the sun. The insulation on the optical tube and sunshade serve to cold bias the telescope which helps to minimize thermal gradients. The primary mirror will be maintained at 280K with an active thermal control system. The geometric model of the primary mirror, optical tube, sun baffles, and sunshade was developed using Thermal Desktop(R) SINDA/FLUINT(R) was used for the thermal analysis and the radiation environment was analyzed using RADCAD(R). A XX node model was executed in order to characterize the static performance and thermal stability of the mirror during maneuvers. This is important because long exposure observations, such as extra-solar terrestrial planet finding and characterization, require a very stable observatory wave front. Steady state thermal analyses served to predict mirror temperatures for several different sun angles. Transient analyses were performed in order to predict thermal time constant of the primary mirror for a 20 degree slew or 30 degree roll maneuver. This paper describes the thermal model and provides details of the geometry, thermo-optical properties, and the environment which influences the thermal performance. All assumptions that were used in the analysis are also documented. Parametric analyses are summarized for design parameters including primary mirror coatings and sunshade configuration. Estimates of mirror heater power requirements are reported. The thermal model demonstrates results for the primary mirror heated from the back side and edges using a heater system with multiple independently controlled zones.

  19. Thermal analysis of the Advanced Technology Large Aperture Space Telescope (ATLAST) 8-meter primary mirror

    NASA Astrophysics Data System (ADS)

    Hornsby, Linda; Hopkins, Randall C.; Stahl, H. Philip

    2010-07-01

    The Advanced Technology Large Aperture Space Telescope (ATLAST) preliminary design concept consists of an 8 meter diameter monolithic primary mirror enclosed in an insulated, optical tube with stray light baffles and a sunshade. ATLAST will be placed in orbit about the Sun-Earth L2 point and will experience constant exposure to the sun. The insulation on the optical tube and sunshade serve to cold bias the telescope which helps to minimize thermal gradients. The objective is to maintain the primary mirror at 280K with an active thermal control system. The geometric model of the primary mirror, optical tube, sun baffles, and sunshade was developed using Thermal Desktop®1. A detailed model of the primary mirror was required in order to characterize the static performance and thermal stability of the mirror during maneuvers. This is important because long exposure observations, such as extra-solar terrestrial planet finding and characterization, require a very stable observatory wave front. Steady state thermal analyses served to predict mirror temperatures for several different sun angles. Transient analyses were performed in order to predict thermal time constant of the primary mirror for a 20 degree slew and a 30 degree roll maneuver. This paper describes the thermal model and provides details of the geometry, thermo-optical properties, and the solar environment that influences the thermal performance. All assumptions that were used in the analysis are also documented. Estimates of mirror heater power requirements are reported. The thermal model is used to predict gradients across and through the primary mirror using an idealized boundary temperature on the back and sides of the mirror of 280 K.

  20. Primary care physician assistant and advance practice nurses roles: Patient healthcare utilization, unmet need, and satisfaction.

    PubMed

    Everett, Christine M; Morgan, Perri; Jackson, George L

    2016-12-01

    Team-based care involving physician assistants (PAs) and advance practice nurses (APNs) is one strategy for improving access and quality of care. PA/APNs perform a variety of roles on primary care teams. However, limited research describes the relationship between PA/APN role and patient outcomes. We examined multiple outcomes associated with primary care PA/APN roles. In this cross-sectional survey analysis, we studied adult respondents to the 2010 Health Tracking Household Survey. Outcomes included primary care and emergency department visits, hospitalizations, unmet need, and satisfaction. PA/APN role was categorized as physician only (no PA/APN visits; reference), usual provider (PA/APN provide majority of primary care visits) or supplemental provider (physician as usual provider, PA/APN provide a subset of visits). Multivariable logistic and multinomial logistic regressions were performed. Compared to people with physician only care, patients with PA/APNs as usual providers [5-9 visits RRR=2.4 (CI 1.8-3.4), 10+ visits RRR=3.0 (CI 2.0-4.5): reference 2-4 visits] and supplemental providers had increased risk of having 5 or more primary care visits [5-9 visits RRR=1.3 (CI 1.0-1.6)]. Patients reporting PA/APN as supplemental providers had increased risk of emergency department utilization [2+ visits: RRR 1.8 (CI 1.3, 2.5)], and lower satisfaction [very dissatisfied: RRR 1.8 (CI 1.03-3.0)]. No differences were seen for hospitalizations or unmet need. Healthcare utilization patterns and satisfaction varied between adults with PA/APN in different roles, but reported unmet need did not. These findings suggest a wide range of outcomes should be considered when identifying the best PA/APN role on primary care teams. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. HPV-associated oropharyngeal squamous cell carcinoma.

    PubMed

    Smith, Timothy J; Mendez, Anthony; Donald, Carrlene; Nagel, Thomas Harold

    2017-01-01

    Human papillomavirus (HPV) can infect the tonsillar tissues of the oropharynx and is associated with oropharyngeal squamous cell carcinoma. This article provides an overview to guide primary care providers in screening patients for oropharyngeal cancer and making appropriate referrals. The article also reviews available HPV vaccines and immunization adherence rates.

  2. Misonidazole and unconventional radiation in advanced squamous cell carcinoma of the esophagus: a phase II study of the Radiation Therapy Oncology Group

    SciTech Connect

    Ydrach, A.A.; Marcial, V.A.; Parsons, J.; Concannon, J.; Asbell, S.O.; George, F.

    1982-03-01

    This is a report on Radiation Therapy Oncology Group (RTOG) Protocol78-32, a Phase I/II prospective study aimed at determining tolerance, tumor response, and survival of squamous cell carcinoma of the esophagus treated with unorthodox fractionation radiotherapy combined with misonidazole. Misonidazole was administered by mouth 4 to 6 hr prior to radiation, at a dose of 1.0 to 1.25 Gm/.m/sup 2/; blood levels were measured at about 4 hr after intake of the drug and reported in micrograms/ml. Radiotherapy was administered at 4 to 6 hr post-misonidazole dose and given with 400 rad fractions, alternating 2 or 3 times/week, up to 4,800 rad. A total of 43 patients were entered; 26 are evaluated for survival at 1 year post accession. Thirty patients (88%) received the planned radiation course. Twenty-eight patients (78%) received the planned misonidazole dosage. Tumor response, evaluated in 18 patients, showed a complete regression (C.R.) in only 2 patients (11%); and partial response (P.R.) in 6 patients (33%). Eight patients (44%) showed no tumor response to planned therapy. Toxicity was acceptable and in 38 evaluated patients only 4 reported (11%) nausea and vomiting, 7 reported mild paresthesias (18%). The median survival was only five months. In 26 patients evaluated for 1 year survival determination, only 1 survived (3.8%) this period. In view of the poor tumor response and low survival observed, we do not recommend that this particular fractionation regimen with misonidazole be used in a Phase III randomized trial in squamous cell carcinoma of the esophagus.

  3. Locally advanced primary recto-sigmoid cancers: Improved survival with multivisceral resection.

    PubMed

    Laurence, Graham; Ahuja, Vanita; Bell, Ted; Grim, Rod; Ahuja, Nita

    2017-09-01

    Multivisceral resection (MVR) is considered a radical operation with many surgeons only using it as a last resort. However, when locally advanced colorectal cancers invade adjacent organs, MVR is an important consideration for select patients. The current study addresses the outcomes of MVR in locally advanced recto-sigmoid cancer patients subsequent to these recommendations and hypothesizes that MVR yields improved survival. SEER data (1988-2008) was used to identify all eligible patients with MVR. Patients were limited to single primary locally advanced non-metastatic colorectal cancers originating from the sigmoid and rectum. A total of 4111 locally advanced non-metastatic recto sigmoid cancer patients were included in the study. Cox regression analysis showed variables predictive of MVR were female (OR = 1.95) and late year period (OR = 1.90). Kaplan Meier analysis showed that five-year survival was highest for MVR (52.7%, 48 months), followed by standard surgery (SS; 38.9%, 32 months) and no surgery (NS; 16.6%, 12 months, P < 0.001). With radiation treatment, five year survival improved for all groups, with the highest being MVR (57%, 52 months). With no radiation treatment, five year survival decreased for all groups, with the highest being MVR (45.1%, 44 months), followed by SS (27.3%, 19 months), and NS (8.7%, 6 months, P < 0.001). The present study supports that MVR offers greater survival advantage in patients with locally advanced colorectal cancer. MVR are extensive surgical procedures with significant associated morbidity that usually require specialized training and sometimes the coordination of multiple surgical specialists. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. GPs' views on managing advanced chronic kidney disease in primary care: a qualitative study.

    PubMed

    Tonkin-Crine, Sarah; Santer, Miriam; Leydon, Geraldine M; Murtagh, Fliss E M; Farrington, Ken; Caskey, Fergus; Rayner, Hugh; Roderick, Paul

    2015-07-01

    Chronic kidney disease (CKD) has become a significant part of the GP's workload since the introduction of the National Institute for Health and Care Excellence guidelines in 2008. Patients with advanced CKD (stages G4 and G5) often have comorbidities, varied disease progression, and are likely to be older. GPs may experience difficulties with management decisions for patients with advanced CKD, including when to refer to nephrology. To explore GPs' views of managing patients with advanced CKD and referral to secondary care. Qualitative study with GPs in four areas of England: London, Bristol, Birmingham, and Stevenage. Semi-structured interviews with 19 GPs. Transcribed interviews were thematically analysed. GPs had little experience of managing patients with advanced CKD, including those on dialysis or having conservative care (treatment without dialysis or a transplant), and welcomed guidance. Some GPs referred patients based on renal function alone and some used wider criteria including age and multimorbidity. GPs reported a tension between national guidance and local advice, and some had learnt from experience that patients were discharged back to primary care. GPs with more experience of managing CKD referred patients later, or sometimes not at all, if there were no additional problems and if dialysis was seen as not in the patient's interests. GPs want guidance on managing older patients with advanced CKD and comorbidities, which better incorporates agreement between local and national recommendations to clarify referral criteria. GPs are not generally aware of conservative care programmes provided by renal units, however, they appear happy to contribute to such care or alternatively, lead conservative management with input from renal teams. © British Journal of General Practice 2015.

  5. GPs’ views on managing advanced chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Tonkin-Crine, Sarah; Santer, Miriam; Leydon, Geraldine M; Murtagh, Fliss EM; Farrington, Ken; Caskey, Fergus; Rayner, Hugh; Roderick, Paul

    2015-01-01

    Background Chronic kidney disease (CKD) has become a significant part of the GP’s workload since the introduction of the National Institute for Health and Care Excellence guidelines in 2008. Patients with advanced CKD (stages G4 and G5) often have comorbidities, varied disease progression, and are likely to be older. GPs may experience difficulties with management decisions for patients with advanced CKD, including when to refer to nephrology. Aim To explore GPs’ views of managing patients with advanced CKD and referral to secondary care. Design and setting Qualitative study with GPs in four areas of England: London, Bristol, Birmingham, and Stevenage. Method Semi-structured interviews with 19 GPs. Transcribed interviews were thematically analysed. Results GPs had little experience of managing patients with advanced CKD, including those on dialysis or having conservative care (treatment without dialysis or a transplant), and welcomed guidance. Some GPs referred patients based on renal function alone and some used wider criteria including age and multimorbidity. GPs reported a tension between national guidance and local advice, and some had learnt from experience that patients were discharged back to primary care. GPs with more experience of managing CKD referred patients later, or sometimes not at all, if there were no additional problems and if dialysis was seen as not in the patient’s interests. Conclusion GPs want guidance on managing older patients with advanced CKD and comorbidities, which better incorporates agreement between local and national recommendations to clarify referral criteria. GPs are not generally aware of conservative care programmes provided by renal units, however, they appear happy to contribute to such care or alternatively, lead conservative management with input from renal teams. PMID:26120137

  6. Recent advances in the diagnosis and treatment of primary biliary cholangitis

    PubMed Central

    Huang, Ying-Qiu

    2016-01-01

    Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients. PMID:27957241

  7. [Primary care nurses' difficulties in advance care planning processes: A qualitative study].

    PubMed

    Granero-Moya, Nani; Frías-Osuna, Antonio; Barrio-Cantalejo, Inés M; Ramos-Morcillo, Antonio Jesús

    2016-12-01

    To know the primary care nurses' difficulties to promote advance care planning process with patients in the end of life. Phenomenological qualitative methodology. Health Management Area North of Jaén. Primary care nurses. Purposive sampling. Fourteen in-depth interviews were conducted until the speeches saturation. Content analysis in four steps: transcription, coding, obtaining results and conclusions verification. Supported whit the software Nvivo 8. Triangulation of results between researchers. Professionals' difficulties: Lack of knowledge about the topic, lack of communication skills, lack of experience and presence of negative emotions. In the health institution lack of time and interference with other professionals is a barrier. Also the patient's attitude and the family are identified as an obstacle because few people speak about the end of life. Finally, our society prevents open discussion about issues related to death. Professional learning about advanced care planning, training in communication skills and emotional education are necessary. Health managers should consider the fact that early interventions for planning health decisions require training, time and continued attention. If a cultural change does not happen, an evasive way to face the end of life will persist. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  8. Dysphagia with a thyroid nodule: is there a primary aerodigestive malignancy?

    PubMed Central

    Michalopoulos, Konstantinos; Gunasekaran, Sinnappa; Moor, James W; Bem, Chris

    2008-01-01

    Summary Three cases of laryngopharyngeal primary squamous cell carcinoma presenting with thyroid nodules are described. The key message to take away from these cases is that patients with advanced malignancy of the upper aerodigestive tract can present with a thyroid nodule. PMID:18344472

  9. Swallowing outcomes for patients with oropharyngeal squamous cell carcinoma treated with primary (chemo)radiation therapy receiving either prophylactic gastrostomy or reactive nasogastric tube: A prospective cohort study.

    PubMed

    Goff, D; Coward, S; Fitzgerald, A; Paleri, V; Moor, J W; Patterson, J M

    2017-01-27

    There is currently no consensus on the optimal feeding route for an oropharyngeal squamous cell cancer (OPSCC) patient without pre-existing dysphagia undergoing chemoradiotherapy. This study aimed to compare the swallowing outcomes for OPSCC patients fed via either prophylactic RIG (pRIG) or reactive nasogastric tube (rNGT). A prospective cohort study. Four head and neck cancer centres in the North of England Cancer Network. Fifty-three participants with OPSCC, on a normal diet pre-(chemo) radiotherapy. Swallowing outcomes for patients with rNGT and pRIG were compared using the following outcome measures administered prospectively at pre-treatment, three and 12 months post-treatment: MD Anderson Dysphagia Inventory (MDADI), Performance Status Scales (Normalcy of Diet), timed water swallow test. Twenty-three patients received pRIG while 30 were planned for a rNGT. No differences in demographics were found between the groups. The rNGT group had a clinically significant higher score on MDADI at 12 months post-treatment. No significant difference was found on a timed water swallow test or diet texture scale. There is no statistical difference for swallowing outcomes in either group. However, patients' in the rNGT group reported a clinically meaningful difference at 1 year, with a trend for them to do better across all measures. Neither group returned to their baseline swallowing function. Further research with a larger sample size is indicated. © 2017 John Wiley & Sons Ltd.

  10. Frozen Section Evaluation of Margin Status in Primary Squamous Cell Carcinomas of the Head and Neck: A Correlation Study of Frozen Section and Final Diagnoses.

    PubMed

    Layfield, Eleanor M; Schmidt, Robert L; Esebua, Magda; Layfield, Lester J

    2017-08-23

    Frozen section is routinely used for intraoperative margin evaluation in carcinomas of the head and neck. We studied a series of frozen sections performed for margin status of head and neck tumors to determine diagnostic accuracy. All frozen sections for margin control of squamous carcinomas of the head and neck were studied from a 66 month period. Frozen and permanent section diagnoses were classified as negative or malignant. Correlation of diagnoses was performed to determine accuracy. One thousand seven hundred and ninety-six pairs of frozen section and corresponding permanent section diagnoses were obtained. Discordances were found in 55 (3.1%) pairs. In 35 pairs (1.9%), frozen section was reported as benign, but permanent sections disclosed carcinoma. In 21 cases, the discrepancy was due to sampling and in the remaining cases it was an interpretive error. In 20 cases (1.1%), frozen section was malignant, but the permanent section was interpreted as negative. Frozen section is an accurate method for evaluation of operative margins for head and neck carcinomas with concordance between frozen and permanent results of 97%. Most errors are false negative results with the majority of these being due to sampling issues.

  11. Total pelvic exenteration for the treatment of advanced primary or recurrent pelvic neoplasia.

    PubMed

    Carballo, Laura; Enríquez-Navascués, José M; Saralegui, Yolanda; Placer, Carlos; Timoteo, Ander; Borda, Nerea; Carrillo, Alberto; Sainz-Lete, Aitor

    2015-03-01

    Complete resection with clear margins in locally advanced pelvic visceral tumors, primary or recurrent, occasionally requires total pelvic exenteration (TPE). We reviewed the results of EFA in 34 consecutive patients operated on between June 2006 and December 2013. Median age was 62 (40-82) years; 24 (70%) were male. The tumor origin most frequent was advanced primary rectal tumor (APRT), with 19 cases (55.9%) and most common type of exenteration was supraelevator (61.8%). R₀ resection was achieved in 24 (70.6%) patients and in 16 (85%) of the APRT. Fifteen (79%) patients had pT₄ APRT, and 4 (20%) pN +. Reconstruction of the bowel and bladder was performed with two stomas in 17 cases (50%), colorectal anastomosis and Bricker in 11 (32.3%) and wet double barreled colostomy in 6 (17.6%). There was no postoperative mortality; 23 (67,5%) patients had complications, and 5 (14.6%) required a postoperative reoperation to solve them. Median follow-up was 23 (13-45) months. Overall survival (OS) and disease free survival (DFS) at 2 years were 67% and 58% respectively, and the median OS and DFS was 59 months (95% CI 26-110) and 39 months (95% CI 14-64), respectively. The DFS of R₀ was significantly better (p=0.003) than R₁. TPE is a potentially curative procedure for advanced pelvic visceral malignancies with similar morbi-mortality than other extended excisional surgery. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Recent advances in transplantation for primary immune deficiency diseases: a comprehensive review.

    PubMed

    de la Morena, M Teresa; Nelson, Robert P

    2014-04-01

    Hematopoietic cell transplantation (HCT) is a curative therapeutic option for severe combined immunodeficiency (SCID), a group of diseases which otherwise carry life expectancies that are of limited duration and quality. Survival following HCT for SCID has improved from approximately 23 to 91 % over the last 40 years. Success with SCID prompted efforts to apply HCT to the therapeutic challenge of well over 20 molecularly defined primary immune deficiency diseases (PID). Such success is due to both early recognition of PIDs and advances in the field of transplantation. Such advances include high-resolution HLA DNA donor-recipient matching, expansion of donor sources, better tolerated conditioning, new antibiotics, and wider availability. International collaborative efforts have provided patients and caregivers information that permit better treatment decisions now, and direct clinicians and investigators to ensure progress in the future. Pioneers in screening for SCID have taken steps to correct the fundamental challenge to successful treatment, which is the rapid discovery and characterization of cases and offering the transplant option to an affected child early in life; blood spot testing for T and B cell receptor quantification is now available to a growing fraction of newborns. Organizations including the Primary Immune Deficiency Treatment Consortium in the USA, The European Society for Primary Immunodeficiency, the European Group for Blood and Marrow Transplantation, the Pediatric Blood and Marrow Transplant Consortium, the United States Immunodeficiency Network, the Immune Deficiency Foundation, and the Jeffrey Modell Foundation are contributing mightily to increase awareness and standardize optimal utilization to the benefit of patients. This review will update the allergist-immunologist concerning disease presentations, indications for transplantation, methodologies, conditioning regimens, and clinical outcomes for patients with PID for which timely HCT is

  13. Stability of the HER2 gene after primary chemotherapy in advanced breast cancer.

    PubMed

    Varga, Zsuzsanna; Caduff, Rosmarie; Pestalozzi, Bernhard

    2005-02-01

    We investigated whether alterations of the Her2 gene could be detected in breast cancer samples following primary chemotherapy in advanced breast cancer. The prospective study involved 23 patients with stage-II, -III or -IV breast cancer. All patients were treated with two to six cycles of fluorouracil-epirubicin and/or cyclophosphamid/epi-docetaxel. The Her2 protein and gene were assessed both on core needle biopsies prior to and on surgical specimens after completing chemotherapy using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. Estrogen and progesterone receptors (ER/PR) were also determined on both samples using IHC. Her2 status was modified in eight patients using IHC (35%) and in three patients using FISH (13%). Changes in ER/PR expression were detected in seven patients (30%). Our data suggest that alterations of the Her2 gene can occur, although not usually after primary or neoadjuvant chemotherapy. However, changes in ER/PR status seem to be a more common event; thus, both can lead to different therapeutic options. Intratumoral heterogeneity as well as sampling variations can contribute to modification of the Her2 status after primary chemotherapy.

  14. Diagnosis and management of endometriosis: the role of the advanced practice nurse in primary care.

    PubMed

    Mao, Alexandra J; Anastasi, Joyce K

    2010-02-01

    To discuss the etiology, clinical presentation, diagnosis, and management of endometriosis for the advanced practice nurse (APN) in primary care. Selected research, clinical studies, clinical practice guidelines, and review articles. Commonly encountered by the APN in primary care, endometriosis is a chronic, progressive inflammatory disease characterized by endometrial lesions, cysts, fibrosis, or adhesions in the pelvic cavity, causing chronic pelvic pain and infertility in women of reproductive age. Because of its frequently normal physical examination findings, variable clinical presentations, and nonspecific, overlapping symptoms with other conditions, endometriosis can be difficult to diagnose. As there currently are no accurate noninvasive diagnostic tests specific for endometriosis, it is imperative for the APN to become knowledgeable about the etiology, clinical presentation, diagnosis, and current treatment options of this disease. The APN in primary care plays an essential role in health promotion through disease management and infertility prevention by providing support and much needed information to the patient with endometriosis. APNs can also facilitate quality of care and manage treatments effectively to improve quality of life, reduce pain, and prevent further progression of disease. Practice recommendations include timely diagnosis, pain management, infertility counseling, patient education, and support for quality of life issues.

  15. Prevalence and Outcomes of Head and Neck versus Non-Head and Neck Second Primary Malignancies in Head and Neck Squamous Cell Carcinoma: An Analysis of the Surveillance, Epidemiology, and End Results Database

    PubMed Central

    Birkeland, Andrew C.; Rosko, Andrew J.; Chinn, Steven B.; Prince, Mark E.; Sun, Gordon H.; Spector, Matthew E.

    2016-01-01

    Background/Aims Patients with head and neck squamous cell carcinoma (HNSCC) are at risk for second primary malignancies (SPMs). The prevalence, distribution and survival of head and neck versus non-head and neck SPMs are not fully elucidated. The objective of this study was to quantify the rate of second primary malignancies in patients with HNSCC. Methods Population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Prevalence and location of SPM, and survival data were analyzed. Results There were 58,363 HNSCC patients, and the prevalence of HNSCC and non-HNSCC SPMs was 3.0% (1,746) and 8.8% (5,109), respectively. Overall survival (OS) was higher in patients with a HNSCC SPM compared to non-HNSCC SPM (p<0.001), with no difference in disease-specific survival(DSS). Patients with SPM in the lung and esophagus had worse OS (p<0.001), and patients with SPM in the prostate and breast had better OS(p<0.001). Conclusion In HNSCC patients who develop SPM, nearly 75% are non-HNSCC SPM. Patients with non-HNSCC SPMs have lower OS. Future clinical practice guidelines should take the risks and locations of SPM development into consideration for screening. PMID:26910465

  16. Weekly chemotherapy with radiation versus high-dose cisplatin with radiation as organ preservation for patients with HPV-positive and HPV-negative locally advanced squamous cell carcinoma of the oropharynx.

    PubMed

    Dobrosotskaya, Irina Y; Bellile, Emily; Spector, Matthew E; Kumar, Bhavna; Feng, Felix; Eisbruch, Avraham; Wolf, Gregory T; Prince, Mark E P; Moyer, Jeffrey S; Teknos, Theodoros; Chepeha, Douglas B; Walline, Heather M; McHugh, Jonathan B; Cordell, Kitrina G; Ward, P Daniel; Byrd, Serena; Maxwell, Jessica H; Urba, Susan; Bradford, Carol R; Carey, Thomas E; Worden, Francis P

    2014-05-01

    Optimal treatment for locally advanced squamous cell carcinoma of the oropharynx (SCCOP) is not well defined. Here we retrospectively compare survival and toxicities from 2 different organ preservation protocols. The matched dataset consisted of 35 patients from each trial matched for age, stage, smoking, and tumor human papillomavirus (HPV) status. Patients in the University of Michigan Cancer Center (UMCC) trial 9921 were treated with induction chemotherapy (IC) followed by high-dose cisplatin and radiation in responders or surgery in nonresponders. Patients in the UMCC trial 0221 were treated with weekly carboplatin and paclitaxel and radiation. Survival was comparable for both studies and did not differ significantly across each trial after stratifying by HPV status. Grade 3 and 4 toxicities were more frequent in UMCC 9921. At 6 months posttreatment, gastrostomy tube (G-tube) dependence was not statistically different. These data suggest that survival outcomes in patients with locally advanced SCCOP are not compromised with weekly chemotherapy and radiation therapy, and such treatment is generally more tolerable. Copyright © 2013 Wiley Periodicals, Inc.

  17. Pretreatment Primary Tumor SUVmax Measured by FDG-PET and Pathologic Tumor Depth Predict for Poor Outcomes in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

    SciTech Connect

    Liao, C.-T.; Chang, Joseph T.-C.; Wang, H.-M.; Ng, S.-H.; Hsueh, C.; Lee, L.-Y.; Lin, C.-H.; Chen, I.-H.; Huang, S.-F.

    2009-03-01

    Purpose: The pathologic tumor depth is an independent prognosticator for local control (LC) and survival in patients with oral cavity squamous cell carcinoma (OSCC). We sought to investigate the prognostic value of the preoperative maximal standardized uptake value (SUVmax) at the primary tumor in OSCC patients with pathologically positive lymph nodes. Methods and Materials: A total of 109 OSCC patients with pathologically positive lymph nodes were investigated. All patients underwent 2-deoxy-2[(18)F]fluoro-D-glucose-positron emission tomography within 2 weeks before surgery and neck dissection. All patients were followed for {>=}24 months after surgery or until death. The optimal cutoff value for the primary tumor SUVmax was selected according to the 5-year LC rate. Independent prognosticators were identified by Cox regression analysis. Results: The median follow-up for all patients was 26 months (39 months for surviving patients). A cutoff SUVmax of 19.3 provided the greatest prognostic information for the 5-year LC rate (55% vs. 88%, p = 0.0135). A tumor depth {>=}12 mm appeared to be the most appropriate cutoff for predicting the 5-year LC rate (76% vs. 95%, p = 0.0075). A scoring system using the primary tumor SUVmax and tumor depth was formulated to define distinct prognostic groups. Patients with both a SUVmax of {>=}19.3 and tumor depth of {>=}12 mm (n = 8) had significantly poorer 5-year LC, 5-year disease-free, 5-year disease-specific, and 5-year overall survival rates compared with the other patient groups. Conclusion: The combination of the primary tumor SUVmax ({>=}19.3) and pathologic tumor depth ({>=}12 mm) identified a subgroup of OSCC patients at greatest risk of poor LC and death.

  18. Talactoferrin in Treating Patients With Relapsed or Refractory Non-Small Cell Lung Cancer or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-07-30

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

  19. DNA methylation profiling revealed promoter hypermethylation-induced silencing of p16, DDAH2 and DUSP1 in primary oral squamous cell carcinoma.

    PubMed

    Khor, Goot Heah; Froemming, Gabriele Ruth Anisah; Zain, Rosnah Binti; Abraham, Mannil Thomas; Omar, Effat; Tan, Su Keng; Tan, Aik Choon; Vincent-Chong, Vui King; Thong, Kwai Lin

    2013-01-01

    Hypermethylation in promoter regions of genes might lead to altered gene functions and result in malignant cellular transformation. Thus, biomarker identification for hypermethylated genes would be very useful for early diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). The objectives of this study were to screen and validate differentially hypermethylated genes in OSCC and correlate the hypermethylation-induced genes with demographic, clinocopathological characteristics and survival rate of OSCC. DNA methylation profiling was utilized to screen the differentially hypermethylated genes in OSCC. Three selected differentially-hypermethylated genes of p16, DDAH2 and DUSP1 were further validated for methylation status and protein expression. The correlation between demographic, clinicopathological characteristics, and survival rate of OSCC patients with hypermethylation of p16, DDAH2 and DUSP1 genes were analysed in the study. Methylation profiling demonstrated 33 promoter hypermethylated genes in OSCC. The differentially-hypermethylated genes of p16, DDAH2 and DUSP1 revealed positivity of 78%, 80% and 88% in methylation-specific polymerase chain reaction and 24% and 22% of immunoreactivity in DDAH2 and DUSP1 genes, respectively. Promoter hypermethylation of p16 gene was found significantly associated with tumour site of buccal, gum, tongue and lip (P=0.001). In addition, DDAH2 methylation level was correlated significantly with patients' age (P=0.050). In this study, overall five-year survival rate was 38.1% for OSCC patients and was influenced by sex difference. The study has identified 33 promoter hypermethylated genes that were significantly silenced in OSCC, which might be involved in an important mechanism in oral carcinogenesis. Our approaches revealed signature candidates of differentially hypermethylated genes of DDAH2 and DUSP1 which can be further developed as potential biomarkers for OSCC as diagnostic, prognostic and

  20. Outcomes of Ahmed glaucoma valve implantation in advanced primary congenital glaucoma with previous surgical failure

    PubMed Central

    Huang, Jingjing; Lin, Jialiu; Wu, Ziqiang; Xu, Hongzhi; Zuo, Chengguo; Ge, Jian

    2015-01-01

    Purpose The purpose of this study was to evaluate the intermediate surgical results of Ahmed glaucoma valve (AGV) implantation in patients less than 7 years of age, with advanced primary congenital glaucoma who have failed previous surgeries. Patients and methods Consecutive patients with advanced primary congenital glaucoma that failed previous operations and had undergone subsequent AGV implantation were evaluated retrospectively. Surgical success was defined as 1) intraocular pressure (IOP) ≥6 and ≤21 mmHg; 2) IOP reduction of at least 30% relative to preoperative values; and 3) without the need for additional surgical intervention for IOP control, loss of light perception, or serious complications. Results Fourteen eyes of eleven patients were studied. Preoperatively, the average axial length was 27.71±1.52 (25.56–30.80) mm, corneal diameter was 14.71±1.07 (13.0–16.0) mm, cup-to-disc ratio was 0.95±0.04 (0.9–1.0), and IOP was 39.5±5.7 (30–55) mmHg. The mean follow-up time was 18.29±10.96 (5–44, median 18) months. There were significant reductions in IOPs and the number of glaucoma medications (P<0.001) postoperatively. The IOPs after operation were 11.3±3.4, 13.6±5.1, 16.3±2.7, and 16.1±2.6 mmHg at 1 month, 6 months, 12 months, and 18 months, respectively. Kaplan–Meier estimates of the cumulative probability of valve success were 85.7%, 71.4%, and 71.4% at 6, 12, and 18 months, respectively. Severe surgical complications, including erosion of tube, endophthalmitis, retinal detachment, choroidal detachment, and delayed suprachoroidal hemorrhage, occurred in 28.6% cases. Conclusion AGV implantation remains a viable option for patients with advanced primary congenital glaucoma unresponsive to previous surgical intervention, despite a relatively high incidence of severe surgical complications. PMID:26082610

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

    ClinicalTrials.gov

    2015-09-28

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

  2. Urothelial and Squamous Cell Carcinoma of Renal Pelvis – A Rare Case Report

    PubMed Central

    Hippargi, Surekha B.; Kumar, Mayank

    2016-01-01

    Primary malignant tumors of the renal pelvis are relatively rare. Urothelial carcinoma of renal pelvis accounts for 7% of all renal neoplasms, with Squamous Cell Carcinoma (SCC) forming a very small percentage of these cases. Urothelial and SCC of renal pelvis is still a rarer entity. This malignancy of the renal pelvis lacks the characteristic presentation of common renal cell carcinoma and usually presents at an advanced disease stage. We report a case of urothelial and SCC of renal pelvis in a 61-year-old male who presented with non-specific clinical complaints like dysuria and right flank pain. PMID:27790450

  3. [Towards universal access to health care: incorporation of advanced practice nurses in primary care].

    PubMed

    Aguirre-Boza, Francisca; Achondo, Bernardita

    2016-10-01

    To move towards universal access to health, the Pan American Health Organization recommends strengthening primary health care (PHC). One of the strategies is to increase the number qualified professionals, both medical and non-medical, working in PHC. In Chile there is a lack of professionals in this level of care, hampering the provision of health. Physicians still prefer secondary and tertiary levels of health. International experience has shown that advanced practice nurses (APN), specialists in PHC are cost-effective professionals able to deliver a complete and quality care to patients. Strong evidence demonstrates the benefits that APN could provide to the population, delivering nursing care that incorporates medical tasks, for example in patients with chronic diseases, allowing greater availability of medical hours for patients requiring more complex management. The success in the implementation of this new role requires the support of the health team, especially PHC physicians, endorsing and promoting the benefits of the APN for the population.

  4. Long-term efficacy and safety of alemtuzumab in advanced primary cutaneous T-cell lymphomas.

    PubMed

    de Masson, A; Guitera, P; Brice, P; Moulonguet, I; Mouly, F; Bouaziz, J-D; Battistella, M; Madelaine, I; Roux, J; Ram-Wolff, C; Cayuela, J-M; Bachelez, H; Bensussan, A; Michel, L; Bagot, M

    2014-03-01

    Alemtuzumab has been proposed as salvage therapy for refractory cutaneous T-cell lymphomas (CTCLs). Long-term follow-up data are scarce. To assess the efficacy and safety of alemtuzumab in the treatment of advanced CTCL. A multicentre retrospective analysis was carried out of 39 patients with advanced CTCL treated with alemtuzumab between 2003 and 2013. Thirty-nine patients (median age 62 years, range 20-83) with Sézary syndrome (SS, n = 23) or advanced mycosis fungoides (MF, n = 16) received alemtuzumab 30 mg two to three times per week for a median duration of 12 weeks (range 1-35). Fifteen patients received maintenance therapy for a median duration of 24 weeks (range 6-277). Eleven patients (28%) had transformed disease (MF, n = 10; SS, n = 1). After a median follow-up of 24 months (range 0.3-124), eight patients (21%) were still alive. The overall response rate was 51% in the whole study group (partial response, n = 13; complete response, n = 7); 70% in patients with SS and 25% in patients with MF (P = 0.009). The median time to progression was 3.4 months (range 0.4-42). Six patients (15%; SS, n = 5; MF, n = 1) remained progression free for > 2 years (median 56 months, range 28-117). Five patients experienced cutaneous large T-cell transformation during alemtuzumab treatment and one patient developed primary cutaneous large B-cell lymphoma. Twenty-four patients (62%) had a grade three or higher infectious adverse event and 10 (26%) a haematological toxicity, which led to treatment discontinuation in 17 cases (44%) and death in two (5%). Alemtuzumab may induce long-term remission in SS but seems ineffective in MF and transformed CTCL. © 2014 British Association of Dermatologists.

  5. Squamous cell carcinoma of the breast diagnosis by vacuum-assisted core biopsy.

    PubMed

    Guerriero, Gabriella; Zagami, Maria Giovanna; Montesano, Marilena; Primavera, Angelo; Carino, Rita; Battista, Cleonice; Rabitti, Carla; Altomare, Vittorio

    2005-01-01

    Squamous cell breast carcinoma is a rare occurrence. Often the tumor is metastatic from an extramammary primary tumor. In order to determine the nature of the lesion, extensive sampling is necessary. We report a case of primary squamous cell carcinoma of the breast diagnosed by vacuum-assisted core biopsy.

  6. The primary treatment of advanced vocal cord cancer: laryngectomy or radiotherapy

    SciTech Connect

    van den Bogaert, W.; Ostyn, F.; van der Schueren, E.

    1983-03-01

    When different treatment modalities yield equal results in cancer treatment, the least mutilating is preferred. If results are different, however, the survival rate after treatment must be weighed against the quality of life. Considerable controversy exists concerning the primary treatment modality for advanced glottic cancer, with some authors defending surgery (with or without radiotherapy) and others defending radiotherapy as sole treatment, with laryngectomy reserved for local failures. From a group of 102 patients with T3 and T4 tumors, 65 were treated with a laryngectomy. Uncorrected survival at 5 years was 48%, local control was 75%. A group of 35 patients were treated with radiotherapy. Survival was 22% at 5 years, local control 23%, with rescue surgery 37%. These unfavorable results are related to the negative selection of patients for radiotherapy (inoperable, bad cooperation). In 14 patients who were operable but refused laryngectomy the final local control was 53%, with voice preservation in 34%; survival, however, remained low (27% at 5 years). Primary surgery seems to provide better chances for ultimate survival than radiotherapy alone. At the moment, it is not yet clear if a proportion of patients can be selected for whom a more conservative attitude can be allowed, with laryngectomy reserved for poor regression or recurrences after radiotherapy.

  7. Efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy for locally advanced head and neck squamous cell carcinoma classified as clinical nodal stage N2c, N3, or N2b with supraclavicular lymph node metastases.

    PubMed

    Izawa, Naoki; Onozawa, Yusuke; Hikosaka, Tomomi; Hamauchi, Satoshi; Tsushima, Takahiro; Todaka, Akiko; Machida, Nozomu; Haraguchi, Yutaka; Ogawa, Hirofumi; Nishimura, Tetsuo; Nakagawa, Masahiro; Fuke, Tomohito; Iida, Yoshiyuki; Kamijo, Tomoyuki; Onitsuka, Tetsuro; Boku, Narikazu; Yasui, Hirofumi; Yokota, Tomoya

    2015-06-01

    We evaluated the efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) with a high risk of distant metastases compared with CRT alone. We retrospectively analyzed 29 HNSCC patients with clinical nodal stage N2c, N3, or N2b disease and supraclavicular lymph node metastases receiving CRT alone (CRT group; n = 16) or TPF induction chemotherapy followed by CRT (TPF group; n = 13) between April 2008 and May 2012. The median follow-up periods were 14.5 (range 5.0-65.0) and 25.0 (range 14.0-32.0) months for CRT and TPF groups, respectively. A greater proportion of patient characteristics in the CRT group had advanced T and N stages. The overall response rate to induction TPF was 50.0%; grade 3-4 toxicities included neutropenia, febrile neutropenia, anorexia, and hyponatremia. Complete response rates after CRT completion were 55.5% in the TPF and 42.9% in the CRT group; median overall survival was not reached in the TPF group and was 14.0 months in the CRT group (p = 0.037). Multivariate analysis revealed that induction TPF and T stage were independent prognostic factors [hazard ratio (HR) = 0.196; 95% confidence interval (CI) 0.043-0.898; p = 0.036, HR = 9.966; 95% CI 2.270-43.75; p = 0.002, respectively). TPF followed by CRT is tolerated and may be an option for the treatment of locally advanced stage N2c, N3, or N2b HNSCC.

  8. Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

    SciTech Connect

    Rades, Dirk Stoehr, Monika; Kazic, Nadja; Hakim, Samer G.; Walz, Annette; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week. Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin {>=}12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin {>=}12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p < .001), surgery (RR, 2.67; 95% CI, 1.28-5.88; p = .008), and no radiotherapy interruptions (RR, 3.32; 95% CI, 1.26-8.79; p = .015). Improved MFS was associated with KPS 90-100 (RR, 3.41; 95% CI, 1.46-8.85; p = .012). Conclusions: Significant predictors for outcome in Stage IV head and neck cancer were performance status, stage, surgery, pre-radiotherapy hemoglobin level, and interruptions during radiotherapy >1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results.

  9. Primary ICD-therapy in patients with advanced heart failure: selection strategies and future trials.

    PubMed

    Frankenstein, Lutz; Zugck, Christian; Nelles, Manfred; Schellberg, Dieter; Remppis, Andrew; Katus, Hugo

    2008-09-01

    For allocation of primary ICD-therapy, a possible lower limit of inclusion criteria--defining overly advanced heart failure--is less well investigated. Also, a multi-variable approach to stratification beyond ejection fraction (LVEF) appears warranted. We examined whether adding a selection limit of peak VO(2) primary ICD-therapy. All cause mortality was considered as end point. Median follow-up was 45 (18-86) months. ICD was not a significant predictor of outcome either for the entire population, or grouped according to aetiology of CHF. Still, 3-year mortality was 15% (ICD-patients) Vs. 28% (non-ICD-patients); P = 0.05; under combination medical therapy. Inversely, in ICD-patients medical combination therapy conveyed a significant survival benefit (P < 0.001). Consequently, the number-needed-to-treat was eight under combination therapy and the size estimate amounts to 300 patients for a prospective trial in this cohort. A cut-off of LVEF primary ICD-therapy. Our results indicate the need for a specific randomized trial in this cohort. The according mortality data and a size estimate are provided.

  10. 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

  11. Prevalence and Outcomes of Head and Neck versus Non-Head and Neck Second Primary Malignancies in Head and Neck Squamous Cell Carcinoma: An Analysis of the Surveillance, Epidemiology, and End Results Database.

    PubMed

    Birkeland, Andrew C; Rosko, Andrew J; Chinn, Steven B; Prince, Mark E; Sun, Gordon H; Spector, Matthew E

    2016-01-01

    Patients with head and neck squamous cell carcinoma (HNSCC) are at risk for second primary malignancies (SPMs). The prevalence, distribution, and patient survival in head and neck versus non-head and neck SPMs are not fully elucidated. The objective of this study was to quantify the rate of SPMs in patients with HNSCC. This is a population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Prevalence and location of SPMs, and survival data were analyzed. There were 58,363 HNSCC patients, and the prevalence of HNSCC and non-HNSCC SPMs was 3.0% (1,746) and 8.8% (5,109), respectively. Overall survival (OS) was higher in patients with HNSCC SPMs compared to non-HNSCC SPMs (p < 0.001), with no difference in disease-specific survival. Patients with SPMs in the lung and esophagus had a worse OS (p < 0.001), and patients with SPMs in the prostate and breast had a better OS (p < 0.001). In HNSCC patients who develop SPMs, nearly 75% are non-HNSCC SPMs. Patients with non-HNSCC SPMs have a lower OS. Future clinical practice guidelines should take the risks and locations of SPM development into consideration for screening. © 2016 S. Karger AG, Basel.

  12. Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma.

    PubMed

    Zilberg, Catherine; Lee, Matthew Weicai; Yu, Bing; Ashford, Bruce; Kraitsek, Spiridoula; Ranson, Marie; Shannon, Kerwin; Cowley, Mark; Iyer, N Gopalakrishna; Palme, Carsten E; Ch'ng, Sydney; Low, Tsu-Hui Hubert; O'Toole, Sandra; Clark, Jonathan R; Gupta, Ruta

    2017-10-06

    Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (<45 years). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression.Modern Pathology advance online publication, 6 October 2017; doi:10.1038/modpathol.2017.128.

  13. Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance.

    PubMed

    Liu, Shutong; Ren, Bo; Gao, Hang; Liao, Suchan; Zhai, Ying-Xian; Li, Shirong; Su, Xue-Jin; Jin, Ping; Stroncek, David; Xu, Zhixiang; Zeng, Qinghua; Li, Yulin

    2017-09-06

    In order to improve therapy for head and neck squamous cell carcinoma (HNSCC), biomarkers associated with local and/or distant tumor relapses and cancer drug resistance are urgently needed. This study identified a potential biomarker, Bcl-2 associated athanogene-1 (BAG-1), that is implicated in HNSCC insensitive to cisplatin and tumor progression. Primary and advanced (relapsed from parental) University of Michigan squamous cell carcinoma cell lines were tested for sensitivity to cisplatin and gene expression profiles were compared between primary (cisplatin sensitive) and the relapsed (cisplatin resistant) cell lines by using Agilent microarrays. Additionally, differentially expressed genes phosphorylated AKT, and BAG-1, and BCL-xL were evaluated for expression using HNSCC tissue arrays. Advanced HNSCC cells revealed resistant to cisplatin accompanied by increased expression of BAG-1 protein. siRNA knockdown of BAG-1 expression resulted in significant improvement of HNSCC sensitivity to cisplatin. BAG-1 expression enhanced stability of BCL-xL and conferred cisplatin resistant to the HNSCC cells. In addition, high levels of expression of phosphorylated AKT, BAG-1, and BCL-xL were observed in advanced HNSCC compared to in that of primary HNSCC. Increased expression of BAG-1 was associated with cisplatin resistance and tumor progression in HNSCC patients and warrants further validation in larger independent studies. Over expression of BAG-1 may be a biomarker for cisplatin resistance in patients with primary or recurrent HNSCCs and targeting BAG-1 could be helpful in overcoming cisplatin resistance.

  14. Palliative treatment of patients with inoperable locally advanced, recurrent or metastatic head and neck squamous cell cancer, using a low-dose and personalized chemotherapeutic regimen

    PubMed Central

    Bishnoi, Rohit; Bennett, Jeffery; Reisman, David N.

    2017-01-01

    Inoperable or metastatic head and neck squamous cell cancer (HNSCC) is known to be associated with a poor patient prognosis. First line therapies include a Taxol, platinum-based antineoplastic and fluorouracil (FU) treatment regimen (TPF) or a platinum-based antineoplastic, FU and EGFR inhibitor treatment regimen (PFE). The toxicity of these regimens is one of the major limiting factors, particularly for palliative treatment. The present study is a retrospective study of 15 patients with HNSCC, where the treatment goal was palliative. Of the 15 patients, 8 received a TPF, while 7 received a PFE. A total of 129 treatment cycles were administered with a median of 9 cycles (range, 3–14). Chemotherapy began with low doses and was subsequently titrated up based on tolerance and response. Positive responses were noted with the lower doses compared with the conventional doses, and maximal doses were not required. The median dose of cisplatin, paclitaxel and 5-FU administered was 40 mg/m2, 80 mg/m2 and 360 mg/m2/day for 5 days, respectively. Cetuximab was used at a standard dose. At the initial follow-up (mean, 64 days; 3 cycles), a 100% disease control rate (DCR) and 80% overall response rate (ORR) was achieved. A positive response, 60% DCR and 60% ORR, was maintained until the late stages of the study (mean, 217 days; 9 cycles). Following termination of chemotherapy after >9 cycles, 4 patients remained disease free for ~1 year. A total of 3 patients exhibited a pathologic complete response despite radiologically exhibiting residual disease. The median progression-free survival time was 10.03 months and the overall survival time was 15.77 months. The only grade 3 hematologic toxicity noted was neutropenia in 3 (20%) patients. Grade 3 vomiting was noted in 1 (6.67%) patient and grade 3 stomatitis was noted in 1 (6.67%) patient. Due to low toxicity patients exhibited improved tolerance to this approach, particularly in terms of palliative care. Furthermore, these results

  15. Patterns of Treatment Failure and Postrecurrence Outcomes Among Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Chemoradiotherapy Using Modern Radiation Techniques.

    PubMed

    Leeman, Jonathan E; Li, Jin-Gao; Pei, Xin; Venigalla, Praveen; Zumsteg, Zachary S; Katsoulakis, Evangelia; Lupovitch, Eitan; McBride, Sean M; Tsai, Chiaojung J; Boyle, Jay O; Roman, Benjamin R; Morris, Luc G T; Dunn, Lara A; Sherman, Eric J; Lee, Nancy Y; Riaz, Nadeem

    2017-05-25

    Even though 15% to 50% of patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence, relatively little is known regarding patterns of treatment failure and postrecurrence outcomes after chemoradiotherapy using modern radiation techniques (intensity-modulated radiotherapy [IMRT]). Recurrence patterns are significantly affected by variations in the quality of radiotherapy, which may confound findings from multicenter trials. To assess patterns of treatment failure and postrecurrence outcomes for patients with HNSCC treated with contemporary radiotherapy techniques. This large single-institution cohort study reviewed the outcomes of 1000 consecutive patients with stage III to IVB oropharyngeal carcinoma (n = 703), laryngeal carcinoma (n = 126), or hypopharyngeal carcinoma (n = 46) treated with definitive IMRT with or without concurrent chemotherapy, as well as patients with oral cavity carcinoma (n = 125) treated with postoperative IMRT with or without concurrent systemic therapy, from December 1, 2001, to December 31, 2013, with a median follow-up of 65.1 months among surviving patients. Data analysis was performed from January 31, 2016, to February 17, 2017. Patterns of treatment failure and overall survival following locoregional failure or distant metastasis. Among the 1000 patients (186 women and 814 men; mean [SD] age, 59.3 [10.8] years), there were no marginal or isolated out-of-radiation-field failures. Among subsites, the cumulative incidence of local failure was highest among patients with oral cavity carcinoma vs those with oropharyngeal carcinoma (hazard ratio, 5.2; 95% CI, 3.1-8.6; P < .001). Furthermore, patients with oral cavity carcinoma experienced significantly shorter survival following distant metastasis (hazard ratio, 3.66; 95% CI, 1.98-6.80; P < .001). Patients with oropharyngeal carcinoma positive for human papillomavirus or p16 lived longer after locoregional failure compared with patents with

  16. Vulvar Recurrences After Intensity-modulated Radiation Therapy for Squamous Cell Carcinoma of the Anus.

    PubMed

    Bagshaw, Hilary P; Sause, William T; Gawlick, Ute; Kim, H Tae; Whisenant, Jonathan; Cannon, George M

    2016-07-19

    The objective is to determine localregional control (LRC), distant metastasis free survival, disease-free survival, overall survival (OS), and toxicity for patients with squamous cell carcinoma of the anus treated with definitive chemotherapy and intensity-modulated radiation therapy (IMRT). We conducted a retrospective review of patients treated using IMRT for squamous cell carcinoma of the anus at our institution since 2005. Patients with local recurrences were identified and reviewed. The Kaplan-Meier curves were used for LRC and OS. From 2005 to 2014, 52 patients were treated with IMRT-based chemoradiation for squamous cell carcinoma of the anus. Median dose to the primary tumor was 54 Gy. LRC, distant metastasis free survival, OS, and disease-free survival were 92.3%, 88.5%, 86.5%, and 84.6%, respectively, with a median follow-up of 20 months. Two local failures occurred at the anal primary site and 2 in the vulva. Despite subsequent palliative radiotherapy and chemotherapy, neither patient with a vulvar recurrence achieved disease control. In a cohort of patients treated with IMRT-based chemoradiation, 2 vulvar recurrences were identified within the avoided external genitalia despite limited recurrence rates within the cohort overall. This experience suggests that for patients with a locally advanced primary tumor and bulky bilateral inguinal or pelvic disease, the in-transit vulvar dermal lymphatics may be at risk for subclinical involvement and subsequent recurrence. If substantiated by a similar pattern of recurrence at other institutions, the external genitalia may need to be reclassified from an avoidance structure to a clinical treatment volume in patients with locally advanced anal cancer.

  17. 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.

  18. Cost-Effectiveness of Neoadjuvant Chemotherapy versus Primary Surgery in Elderly Patients with Advanced Ovarian Cancer.

    PubMed

    Poonawalla, Insiya B; Lairson, David R; Chan, Wenyaw; Piller, Linda B; Du, Xianglin L

    2015-06-01

    The use of neoadjuvant chemotherapy (NAC) in the treatment of advanced ovarian cancer has increased in recent years. There is uncertainty about NAC's effectiveness and no study of its cost-effectiveness compared with that of standard primary debulking surgery (PDS). To seek answers to three important questions: 1) What is the lifetime cost of treating elderly patients with advanced ovarian cancer, based on the primary treatment received? 2) Are the extra costs expended by the NAC group worth any extra survival advantage? 3) Would NAC potentially benefit a particular subgroup and serve as a cost-effective first-line treatment approach? A cohort of elderly women (≥65 years) with stage III/IV ovarian cancer was identified from the Surveillance, Epidemiology and End Results-Medicare linked database from January 1, 2000, to December 31, 2009. Cost analysis was conducted from a payer perspective, and direct medical costs incurred by Medicare were integrated for each patient. Cumulative treatment costs were estimated with a phase-of-care approach, and effectiveness was measured as years of survival. Incremental cost-effectiveness ratio (ICER) and propensity-score-adjusted net monetary benefit regression was used to estimate the cost-effectiveness of NAC per life-year gained. Analyses were further stratified by risk group categorization on the basis of tumor stage, patient age, and comorbidity score. Average lifetime cost for treatment with NAC was $17,417 more than with PDS. With only 0.1 incremental life-year gained, the ICER estimate was $174,173. Stratification, however, helped to delineate the treatment effect. Patients in the high-risk subgroup incurred $34,390 and 0.8 life-years more than did patients in the PDS subgroup, with a corresponding ICER of $42,987. In the non-high-risk subgroup, NAC use was dominated by PDS (more costly, less effective). Administering NAC before surgery to patients in the high-risk subgroup was cost-effective at "normal" levels of

  19. 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

  20. Advancing team-based primary health care: a comparative analysis of policies in western Canada.

    PubMed

    Suter, Esther; Mallinson, Sara; Misfeldt, Renee; Boakye, Omenaa; Nasmith, Louise; Wong, Sabrina T

    2017-07-17

    We analyzed and compared primary health care (PHC) policies in British Columbia, Alberta and Saskatchewan to understand how they inform the design and implementation of team-based primary health care service delivery. The goal was to develop policy imperatives that can advance team-based PHC in Canada. We conducted comparative case studies (n = 3). The policy analysis included: Context review: We reviewed relevant information (2007 to 2014) from databases and websites. Policy review and comparative analysis: We compared and contrasted publically available PHC policies. Key informant interviews: Key informants (n = 30) validated narratives prepared from the comparative analysis by offering contextual information on potential policy imperatives. Advisory group and roundtable: An expert advisory group guided this work and a key stakeholder roundtable event guided prioritization of policy imperatives. The concept of team-based PHC varies widely across and within the three provinces. We noted policy gaps related to team configuration, leadership, scope of practice, role clarity and financing of team-based care; few policies speak explicitly to monitoring and evaluation of team-based PHC. We prioritized four policy imperatives: (1) alignment of goals and policies at different system levels; (2) investment of resources for system change; (3) compensation models for all members of the team; and (4) accountability through collaborative practice metrics. Policies supporting team-based PHC have been slow to emerge, lacking a systematic and coordinated approach. Greater alignment with specific consideration of financing, reimbursement, implementation mechanisms and performance monitoring could accelerate systemic transformation by removing some well-known barriers to team-based care.

  1. Metastatic squamous cell carcinoma in a cat.

    PubMed

    Dhaliwal, Ravinder S; Kufuor-Mensah, Eric

    2007-02-01

    A 7-year-old, spayed female Persian cat was referred for evaluation of progressive paraplegia. The cat was thin, cachectic and paraplegic on presentation. The survey radiographs showed a left caudal pulmonary lesion and lytic skeletal lesions at the right iliac crest and left distal scapula. Due to a poor prognosis for complete recovery, the owner opted for euthanasia. Post-mortem examination revealed bilaterally small and irregular kidneys, lysis of the left iliac crest and left distal scapula and a dilated left ventricular lumen with a thin interventricular septum. Histologically, all the lesions were determined to be squamous cell carcinoma. It appears that the origin or the primary site of the malignancy in this case is pulmonary as cardiac and skeletal tissues are primarily mesenchymal in origin and are less likely to develop a primary epithelial malignancy. To the best of our knowledge, there is no description of cardiac or skeletal metastatic squamous cell carcinoma in a cat.

  2. Incidentally detected squamous cell carcinoma of renal pelvis in patients with staghorn calculi: case series with review of the literature.

    PubMed

    Jain, Ayushi; Mittal, Deepti; Jindal, Arpita; Solanki, Ranjana; Khatri, Suman; Parikh, Archana; Yadav, Kamlesh

    2011-01-01

    Squamous cell carcinoma of the renal pelvis is a rare neoplasm, often unsuspected clinically due to its rarity and ambiguous clinical and radiological features, and hence patients present at advanced stages resulting in poor prognosis. We report here four cases of incidentally diagnosed primary renal squamous cell carcinoma, treated at our hospital over a short span of one year, and review the relevant literature. Mean age of the patients (3 males, 1 female) was 60 years. All suffered from staghorn stones. Interestingly, renal carcinoma was unsuspected clinically in all patients. In one case, a computerised tomography scan showed a suspicious nodule. All underwent nephrectomy for nonfunctioning kidney. In just two cases, tumor was identified on gross examination, while the other two only showed thickened pelvis. Our series emphasises the need for pelvicalyceal biopsy during treatment for long-standing nephrolithiasis, and thorough sampling of the renal pelvis in nephrectomy specimen of such patients.

  3. Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

    ClinicalTrials.gov

    2014-06-05

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

  4. Kinetics and advanced digester design for anaerobic digestion of water hyacinth and primary sludge

    SciTech Connect

    Chynoweth, D.P.; Dolenc, D.A.; Ghosh, S.; Henry, M.P.; Jerger, D.E.; Srivastava, V.J.

    1982-01-01

    A research program centered around a facility located at Walt Disney World (WDW) is in progress to evaluate the use of water hyacinth (WH) for secondary and tertiary wastewater treatment, to optimize growth of WH under these conditions, and to convert the resultant primary sludge (PS) and WH to methane via anaerobic digestion. This article describes the status of the biogasification component of this program, which includes baseline and advanced digestion experiments with individual feeds and blends and the design of an experimental test unit (ETU) to be installed at WDW. Experiments with several blends demonstrated that methane yields can be predicted from the fractional content and methane yield of each component. The process was found to adhere to the Monod kinetic model for microbial growth, and associated kinetic parameters were developed for various feed combinations. A novel upflow digester is achieving significantly higher conversion than a stirred-tank digester. Of several pretreatment techniques used, only alkaline treatment resulted in increased biodegradability. A larger scale (4.5 m/sup 3/) experimental test unit is being designed for installation at WDW in 1982. 13 figures, 4 tables.

  5. Performic acid (PFA): tests on an advanced primary effluent show promising disinfection performance.

    PubMed

    Gehr, R; Chen, D; Moreau, M

    2009-01-01

    Performic acid, or PFA (CH(2)O(3)), is a well-known oxidizing agent and disinfectant in the medical field and food industry. It has recently become available on a commercial scale for potential use in wastewater disinfection. This study investigated its application to an advanced primary effluent which is recalcitrant to disinfection by UV and peracetic acid (PAA). Methods were developed for determining PFA concentrations in stock solutions as well as in residual concentrations in the wastewater. Batch and continuous-flow pilot studies showed a correlation between log fecal coliform removals and PFA doses. A PFA dose of approximately 3.4 mg/L and a contact time of 45 minutes could achieve 3-logs removal, and almost total disinfection could be achieved using a dose of 6 mg/L. The by-products of PFA addition are hydrogen peroxide and formic acid (CHOOH), neither of which is considered to be toxic to aquatic fauna at the doses required for disinfection.

  6. Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma

    SciTech Connect

    Salama, Joseph K.; Vokes, Everett E.; Chmura, Steven J.; Milano, Michael T.; Kao, Johnny; Stenson, Kirsten M.; Haraf, Daniel J. . E-mail: dharaf@radonc.uchicago.edu

    2006-02-01

    Purpose: To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation. Methods and Materials: Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n = 14), cisplatin plus FHX (n = 23), paclitaxel plus FHX (n = 42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n = 26), and irinotecan plus FHX (n = 10). Results: The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%, respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage. Conclusion: For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for

  7. Squamous carcinoma of the nasopharynx

    SciTech Connect

    Moloy, P.J.; Chung, Y.T.; Krivitsky, P.B.; Kim, R.C.

    1985-07-01

    Nasophryngeal carcinoma is an unusual neoplasm among squamous cell carcinomas of the head and neck. The tumor is rare in most parts of the world but is strikingly common in several Asian subpopulations, notably Chinese in Hong Kong and Guangdong Province. The Epstein-Barr virus is intimately related to the disease and elicits the formation of antibodies that are useful for diagnosis and follow-up study. The virus has not been conclusively shown to cause nasopharyngeal cancer, however. Histologically, nasopharyngeal carcinoma is anaplastic in 75% of cases and better differentiated in 25% of patients. All tumors are treated by high-dose radiation to the primary site and both sides of the neck. Surgical treatment, in the neck only, is reserved for irradiation failures. The prognosis is better in patients younger than 40 years, in patients without clinical cervical nodal involvement and, unexpectedly, in patients with anaplastic tumors. 18 references, 2 figures, 2 tables.

  8. Helicobacter Pylory infection in patients with esophageal squamous cell carcinoma

    PubMed Central

    Poyrazoglu, Omer Bilgehan; Dulger, Ahmet Cumhur; Gultepe, Bilge Sumbul

    2017-01-01

    OBJECTIVE: Esophageal squamous cell carcinoma is one of the most common esophageal diseases in the developing world, but the relationship between esophageal squamous cell carcinoma and Helicobacter pylori infection remains a neglected topic. The primary objective of this study was to determine the association between Helicobacter pylori infection and esophageal squamous cell carcinoma. A second purpose was to determine the incidence and factors associated with Helicobacter pylori infection following esophagectomy. METHOD: The microorganism was identified by testing the gastric biopsy materials from 95 esophageal squamous cell carcinoma patients (66 females; 39 were esophagectomized) for urease activity in a medium containing urea and a power of hydrogen detection reagent and comparing the results with those from a healthy population. Differences in patient characteristics were assessed with chi-square tests and t-tests for categorical and continuous factors, respectively. RESULTS: The patients with esophageal squamous cell carcinoma had a significantly lower prevalence of Helicobacter pylori compared with the healthy population (p<0.001). The naive and esophagectomized patients, in contrast, showed no significant differences in Helicobacter pylori infection (p>0.005). Patients with esophageal squamous cell carcinoma showed a significant association between leukocytosis and hypoglobulinemia and the presence of Helicobacter pylori infection (p=0.023 and p=0.045, respectively). CONCLUSION: These results suggest that Helicobacter pylori is not an etiological factor in patients with esophageal squamous cell carcinoma. We found a statistically significant negative correlation between esophageal squamous cell cancer and Helicobacter pylori infection. These findings may guide new strategies for esophageal squamous cell carcinoma therapy. PMID:28355360

  9. Advance Care Planning in Patients with Primary Malignant Brain Tumors: A Systematic Review.

    PubMed

    Song, Krystal; Amatya, Bhasker; Voutier, Catherine; Khan, Fary

    2016-01-01

    Advance care planning (ACP) is a process of reflection and communication of a person's future health care preferences, and has been shown to improve end-of-life (EOL) care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumors (pmBT). A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus, and Web of Science) up to July 2016. Manual search of bibliographies of articles and gray literature search were also conducted. Two independent reviewers selected studies, extracted data, and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program's appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included [1 randomized controlled trial (RCT), 17 cohort studies, 1 qualitative study] with 4686 participants. All studies scored "low to moderate" on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision-making. However, the effect of the intervention on quality of life and care at the EOL were unclear. There was a low rate of use of ACP discussions at the EOL. Advance directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with lack of

  10. Advance Care Planning in Patients with Primary Malignant Brain Tumors: A Systematic Review

    PubMed Central

    Song, Krystal; Amatya, Bhasker; Voutier, Catherine; Khan, Fary

    2016-01-01

    Advance care planning (ACP) is a process of reflection and communication of a person’s future health care preferences, and has been shown to improve end-of-life (EOL) care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumors (pmBT). A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus, and Web of Science) up to July 2016. Manual search of bibliographies of articles and gray literature search were also conducted. Two independent reviewers selected studies, extracted data, and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program’s appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included [1 randomized controlled trial (RCT), 17 cohort studies, 1 qualitative study] with 4686 participants. All studies scored “low to moderate” on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision-making. However, the effect of the intervention on quality of life and care at the EOL were unclear. There was a low rate of use of ACP discussions at the EOL. Advance directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with

  11. Intensity Modulated Radiotherapy Improves Target Coverage and Parotid Gland Sparing When Delivering Total Mucosal Irradiation in Patients With Squamous Cell Carcinoma of Head and Neck of Unknown Primary Site

    SciTech Connect

    Bhide, Shreerang Clark, Catherine; Harrington, Kevin; Nutting, Christopher M.

    2007-10-01

    Head and neck squamous cell carcinoma with occult primary site represents a controversial clinical problem. Conventional total mucosal irradiation (TMI) maximizes local control, but at the expense of xerostomia. IMRT has been shown to spare salivary tissue in head and cancer patients. This study has been performed to investigate the potential of IMRT to perform nodal and TMI and also allow parotid gland sparing in this patient group. Conventional radiotherapy (CRT) and IMRT plans were produced for six patients to treat the ipsilateral (involved) post-operative neck (PTV1) and the un-operated contralateral neck and mucosal axis (PTV2). Plans were produced with and without the inclusion of nasopharynx in the PTV2. The potential to improve target coverage and spare the parotid glands was investigated for the IMRT plans. There was no significant difference in the mean doses to the PTV1 using CRT and IMRT (59.7 and 60.0 respectively, p = 0.5). The maximum doses to PTV1 and PTV2 were lower for the IMRT technique as compared to CRT (P = 0.008 and P < 0.0001), respectively, and the minimum doses to PTV1 and PTV2 were significantly higher for IMRT as compared to CRT (P = 0.001 and P = 0.001), respectively, illustrating better dose homogeneity with IMRT. The mean dose to the parotid gland contralateral to PTV1 was significantly lower for IMRT (23.21 {+-} 0.7) as compared to CRT (50.5 {+-} 5.8) (P < 0.0001). There was a significant difference in parotid dose between plans with and without the inclusion of the nasopharynx. IMRT offers improved dose homogeneity in PTV1 and PTV2 and allows for parotid sparing.

  12. More Accurate Definition of Clinical Target Volume Based on the Measurement of Microscopic Extensions of the Primary Tumor Toward the Uterus Body in International Federation of Gynecology and Obstetrics Ib-IIa Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Xie, Wen-Jia; Wu, Xiao; Xue, Ren-Liang; Lin, Xiang-Ying; Kidd, Elizabeth A.; Yan, Shu-Mei; Zhang, Yao-Hong; Zhai, Tian-Tian; Lu, Jia-Yang; Wu, Li-Li; Zhang, Hao; Huang, Hai-Hua; Chen, Zhi-Jian; Li, De-Rui; Xie, Liang-Xi

    2015-01-01

    Purpose: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). Patients and Methods: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. Results: Microscopic extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. Conclusion: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.

  13. A phase II study of pemetrexed monotherapy in chemo-naïve Eastern Cooperative Oncology Group performance status 2 patients with EGFR wild-type or unknown advanced non-squamous non-small cell lung cancer (HANSHIN Oncology Group 002).

    PubMed

    Hata, Akito; Katakami, Nobuyuki; Fujita, Shiro; Nanjo, Shigeki; Takeshita, Jumpei; Tanaka, Kosuke; Kaneda, Toshihiko; Nishiyama, Akihiro; Nishimura, Takashi; Nakagawa, Atsushi; Otsuka, Kojiro; Morita, Satoshi; Urata, Yoshiko; Negoro, Shunichi

    2015-06-01

    The aim of our study was to investigate the efficacy and safety of pemetrexed monotherapy in chemo-naïve Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 patients with epidermal growth factor receptor (EGFR) wild-type or unknown advanced non-squamous non-small cell lung cancer (NSCLC). Pemetrexed was administered at 500 mg/m(2) triweekly until progression with supplementations in chemo-naïve ECOG PS 2 patients with EGFR wild-type or unknown advanced non-squamous NSCLC. Between September 2009 and April 2013, twenty-eight patients were enrolled. Median age was 75 (range 59-89). Nineteen (68 %) of 28 were ever smoker, and 18 (64 %) had pulmonary emphysema. Sixteen (57 %) had comorbidities such as hypertension, heart disease, and/or diabetes. In 26 eligible patients, the overall response rate, disease control rate, median PFS, and median overall survival were 11.5, 53.8 %, 3.0 [95 % confidence interval (CI) 1.9-5.7] months and 9.5 (95 % CI 3.3-12.5) months, respectively. Median administered course number was 3 (range 1-14). Median duration of PS maintenance ≤2 was 4.9 (95 % CI 1.3-9.7) months. Common (≥10 %) grade 3/4 toxicities included 7 (27 %) neutropenia, 7 (27 %) leukopenia, 4 (15 %) fatigue, and 3 (12 %) thrombocytopenia. Febrile neutropenia and interstitial lung disease were not observed. There were no treatment-related deaths. Pemetrexed monotherapy demonstrated moderate efficacy and good safety in chemo-naïve PS 2 patients with EGFR wild-type or unknown non-squamous NSCLC. It can be a therapeutic option in "frail" PS 2 non-squamous NSCLC patients without the indication of combination regimens, if the patient is EGFR wild-type.

  14. Weekly nanoparticle albumin-bound paclitaxel in combination with cisplatin versus weekly solvent-based paclitaxel plus cisplatin as first-line therapy in Chinese patients with advanced esophageal squamous cell carcinoma

    PubMed Central

    Wang, Hai-ying; Yao, Zhi-hua; Tang, Hong; Zhao, Yan; Zhang, Xiao-san; Yao, Shu-na; Yang, Shu-jun; Liu, Yan-yan

    2016-01-01

    Objective More effective regimens for advanced esophageal squamous cell carcinoma (ESCC) are urgently needed. Therefore, a retrospective study concerning the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin (nab-TP) versus solvent-based paclitaxel plus cisplatin (sb-TP) as a first-line therapy was conducted in Chinese patients with advanced ESCC. Methods From June 2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2) on the first and eighth days (30 minutes infusion) and cisplatin (75 mg/m2) on the second day every 21 days (nab-TP arm). Also, 43 patients were treated with solvent-based paclitaxel (80 mg/m2) intravenously on the first and eighth days and the same dose of cisplatin (sb-TP arm). The two groups were compared in terms of objective response rate (ORR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety profile. OS and PFS were estimated using Kaplan–Meier methods to determine associations between chemotherapy regimens and survival outcomes. Results Nab-TP demonstrated a higher ORR (50% vs 30%; P=0.082) and disease control rate (81% vs 65%; P=0.124) than sb-TP. Median OS was similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269). However, nab-TP resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3–6.9]) than sb-TP (5.0 months [95% confidence interval: 4.4–5.6]) (P=0.029). The most common adverse events included anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia in both the groups and no statistically significant differences were observed between the groups. With statistically significant differences, significantly less grade ≥3 peripheral neuropathy, arthralgia, and myalgia occurred in the nab-TP arm (all P<0.05). Dose reduction, treatment delays, and second-line therapy were similar between the two regimens. There were no treatment-related deaths in either group. Conclusion Nab-paclitaxel plus cisplatin is found

  15. Economic analysis of FDG-PET-guided management of the neck after primary chemoradiotherapy for node-positive head and neck squamous cell carcinoma.

    PubMed

    Pryor, David I; Porceddu, Sandro V; Scuffham, Paul A; Whitty, Jennifer A; Thomas, Paul A; Burmeister, Bryan H

    2013-09-01

    The aim of this economic analysis was to model different strategies using pre-treatment nodal stage or nodal response assessment with CT or positron emission tomography (PET)/CT to determine the need for neck dissection. A cost-minimization analysis was developed on the basis of probability data from a prospective study of PET-guided management of the neck in patients achieving a complete response at the primary site. Costs were derived from our institution's activity-based clinical costing system. The effect of uncertainty was tested with sensitivity and scenario analyses including nationally representative cost data. Strategies incorporating PET had a 7% rate for neck dissection compared with 44% for CT-guided and 90% for planned neck dissection. The cost per patient was A$16,502 for planned neck dissection, A$8014 for CT-guided, and A$2573 for PET-guided. A policy with PET used only for incomplete response on CT was the least-cost strategy (A$2111). Policies incorporating PET remained the most efficient for all sensitivity/scenario analyses. The incorporation of PET/CT into nodal response assessment significantly reduced the number of unnecessary neck dissections and generated considerable cost savings in our cohort. Copyright © 2012 Wiley Periodicals, Inc.

  16. Detection of disseminated tumor cells in locally advanced breast cancer patients before primary systemic therapy.

    PubMed

    Solá, Montserrat; Margelí, Mireia; Castellá, Eva; Cirauqui, Beatriz; Mariscal, Antonio; Rull, Miquel; Julian, Juan F; Luna, Miquel; Vallejo, Virginia; Fraile, Manuel

    2013-10-01

    To assess the prevalence and prognostic power of disseminated tumor cells (DTC) in patients with locally advanced breast cancer (LABC) before primary systemic therapy (PST). LABC patients attending our Breast Unit were studied between 2002 and 2012, all of them being considered for PST. To determine the presence of DTC, posterior iliac crest aspirates were obtained and marrow samples were processed by gradient separation with Ficoll (Lymphoprep(®)) and immunohistochemical staining using the antiCK A45-B/B3 (EPIMET) antibody. Clinicopathologic variables were recorded before and after PST to assess response. Disease-free survival (DFS) and overall survival (OS) were determined after follow-up. The presence of DTC as a predictor of response to PST and as a prognostic tool for OS and DSF was evaluated. DTC were observed in 26% of 47 patients included in the study. PST consisted of chemotherapy in 94% and hormone therapy in 6%. Breast-conserving therapy was attained in 33%. Mean follow-up was 68 months. Complete clinical response (CR) after PST was seen in 26%, disease recurrence in 38%, and cancer-related death in 8%; tumor size and negative estrogen receptors were significant predictors of CR and mastectomy was associated with DFS. Persistent axillary disease after PST and previous recurrence were predictive of OS. DTC were detected more often in patients who did not achieve CR and those who presented recurrence. DTC detection was a significant prognostic factor for a worse OS (OR = 7.62; CI95%: 1.46-39.61; p = 0.009) and a decreased survival time (62 versus 82 months, p = 0.004). Presence of DTC before PST was found in a significant number of patients with LABC. DTC were found to be a significant prognostic factor for cancer-related death. DTC could be a surrogate predictor of response to PST and also of disease recurrence in LABC patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Primary Ciliary Dyskinesia. Recent Advances in Diagnostics, Genetics, and Characterization of Clinical Disease

    PubMed Central

    Daniels, Leigh Anne; Davis, Stephanie D.; Zariwala, Maimoona A.; Leigh, Margaret W.

    2013-01-01

    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6–8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment of PCD is not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD. PMID:23796196

  18. Radiotherapy and Hyperthermia for Treatment of Primary Locally Advanced Cervix Cancer: Results in 378 Patients

    SciTech Connect

    Franckena, Martine Lutgens, Ludy C.; Koper, Peter C.; Kleynen, Catharina E.; Steen-Banasik, Elsbieta M. van der; Jobsen, Jan J.; Leer, Jan Willem; Creutzberg, Carien L.; Dielwart, Michel F.; Norden, Yvette van; Canters, Richard A.M.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2009-01-01

    Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival, and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses. Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors. Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.

  19. Safety profiles of first-line therapies for metastatic non-squamous non-small-cell lung cancer.

    PubMed

    Losanno, Tania; Gridelli, Cesare

    2016-06-01

    Lung cancer still represents the leading cause of death for cancer. About the 70% of diagnosis are in advanced-stage. Non-small-cell lung cancer (NSCLC) represents the 85% of all diagnosed lung cancers and non-squamous histology represents the 40% of all NSCLC. First-line therapies increase survival, control symptoms and improve quality of life, compared with best supportive care. It is crucial to choose a treatment with a low impact on patient's life considering the related toxicities. Adverse events (AEs) of first-line therapies for non-squamous NSCLC are here reviewed and discussed, from evidences in clinical trials conducting to drugs approval. For advanced disease, palliation and preserving patients QoL are still the primary goal of treatment. Therefore, differing toxicity profiles are often a deciding factor in first-line and also maintenance setting for non-squamous NSCLC. Special attention is necessary to renal function and drugs' nephrotoxicity. Moreover, it is to consider the specific AEs of drugs classes: hypertension, bleeding, and proteinuria, for anti-VEGF therapy; skin toxicity, diarrhea, interstitial lung disease for TKIs; vision disorders, and hepatotoxicity for ALK-inhibitor. It is important to select patients for a treatment on the basis of their comorbidities and the presence of risk factors.

  20. A comparative study of target volumes based on 18F-FDG PET-CT and ten phases of 4DCT for primary thoracic squamous esophageal cancer

    PubMed Central

    Guo, Yanluan; Li, Jianbin; Zhang, Peng; Zhang, Yingjie

    2017-01-01

    Purpose To investigate the correlations in target volumes based on 18F-FDG PET/CT and four-dimensional CT (4DCT) to detect the feasibility of implementing PET in determining gross target volumes (GTV) for tumor motion for primary thoracic esophageal cancer (EC). Methods Thirty-three patients with EC sequentially underwent contrast-enhanced 3DCT, 4DCT, and 18F-FDG PET-CT thoracic simulation. The internal gross target volume (IGTV)10 was obtained by combining the GTV from ten phases of 4DCT. The GTVs based on PET/CT images were defined by setting of different standardized uptake value thresholds and visual contouring. The difference in volume ratio, conformity index (CI), and degree of inclusion (DI) between IGTV10 and GTVPET was compared. Results The images from 20 patients were suitable for further analysis. The optimal volume ratio of 0.95±0.32, 1.06±0.50, 1.07±0.49 was at standardized uptake value (SUV)2.5, SUV20%, or manual contouring. The mean CIs were from 0.33 to 0.54. The best CIs were at SUV2.0 (0.51±0.11), SUV2.5 (0.53±0.13), SUV20% (0.53±0.12), and manual contouring (0.54±0.14). The mean DIs of GTVPET in IGTV10 were from 0.60 to 0.90, and the mean DIs of IGTV10 in GTVPET ranged from 0.35 to 0.78. A negative correlation was found between the mean CI and different SUV (P=0.000). Conclusion None of the PET-based contours had both close spatial and volumetric approximation to the 4DCT IGTV10. Further evaluation and optimization of PET as a tool for target identification are required. PMID:28123302

  1. Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients.

    PubMed

    Reddy, B K M; Lokesh, V; Vidyasagar, M S; Shenoy, K; Babu, K G; Shenoy, A; Naveen, T; Joseph, Bindhu; Bonanthaya, R; Nanjundappa; Bapsy, P P; Loknatha; Shetty, Jayarama; Prasad, Krishna; Tanvir Pasha, C R

    2014-05-01

    Overexpression of epidermal growth factor receptor (EGFR) in many cancers makes it an attractive therapeutic target. This study evaluated the clinical utility of nimotuzumab, a monoclonal anti-EGFR antibody, used concurrently with radiotherapy (RT) and chemoradiotherapy (CRT) in squamous cell carcinoma of the head and neck (SCCHN). This open-label study randomized 92 treatment-naïve patients (1:1) with advanced SCCHN into chemoradiation (CRT ± nimotuzumab) or radiation (RT ± nimotuzumab) group by investigator's discretion; these were further randomized into CRT + nimotuzumab or CRT and RT + nimotuzumab or RT groups, respectively. Treatment included 6 cycles each of cisplatin (50 mg/week), nimotuzumab (200 mg/week), and RT (total dose, 60-66 Gy). Response (tumor size reduction) was assessed at Month 6 post-treatment and survival, at Month 60. Forty and 36 patients in the chemoradiation and radiation groups, respectively (intent-to-treat population) were evaluated. Overall response at Month 6 post-treatment was 100% with CRT + nimotuzumab, 70% with CRT, 76% with RT + nimotuzumab, and 37% with RT. At Month 60, overall survival was 57% with CRT + nimotuzumab, 26% with CRT (P = 0.03), 39% with RT + nimotuzumab, and 26% with RT (P > 0.05). Median overall survival was not reached for CRT + nimotuzumab; it was 21.94 months for CRT (P = 0.0078), 14.36 months for RT + nimotuzumab, and 12.78 months for RT (P = 0.45). Risk of death was 64% lower with CRT + nimotuzumab than with CRT (95%CI: 0.37, 1.56), and 24% lower with RT + nimotuzumab than with RT (95%CI: 0.16, 0.79). Thus nimotuzumab was safe and well tolerated with few mild to moderate self-limiting adverse events. Concurrent use of nimotuzumab with CRT/RT is safe and provides long-term survival benefit. Copyright © 2014. Published by Elsevier Ltd.

  2. A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma

    PubMed Central

    Chung, Christine H.; Rudek, Michelle A.; Kang, Hyunseok; Marur, Shanthi; John, Pritish; Tsottles, Nancy; Bonerigo, Sarah; Veasey, Andy; Kiess, Ana; Quon, Harry; Cmelak, Anthony; Murphy, Barbara A.; Gilbert, Jill

    2015-01-01

    Introduction Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC). Material and Methods Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6 mg/ml*min and paclitaxel 175 mg/m2 every 21 days as IC. Afatinib was started at a dose of 20 mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40 mg/m2 weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0. Results Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20 mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30 mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities. Conclusions The MTD of afatinib given with carboplatin AUC 6 mg/ml*min and paclitaxel 175 mg/m2 is 20 mg daily. Combination of afatinib at doses higher than 20 mg with carboplatin and paclitaxel should be administered with caution due to the toxicities. PMID:26705063

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

    ClinicalTrials.gov

    2017-03-07

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

  4. p16(INK4a) is a marker of good prognosis for primary invasive penile squamous cell carcinoma: a multi-institutional study.

    PubMed

    Gunia, Sven; Erbersdobler, Andreas; Hakenberg, Oliver W; Koch, Stefan; May, Matthias

    2012-03-01

    We assessed the prognostic role of p16(INK4a) expression in penile cancer with respect to cancer specific survival. Based on a multi-institutional collaboration wax embedded tissues from 92 surgically treated patients, including 27 with total and 65 with partial penectomy, were retrospectively evaluated. After a central histopathological review by 1 pathologist a tissue microarray was constructed for p16(INK4a) immunostaining. Two independent pathologists evaluated p16(INK4a) expression, which was correlated with cancer specific survival. The κ statistic was used to assess interobserver variability. Univariate and multivariate Cox proportional hazards analysis was applied to assess the independent effects of prognostic factors on cancer specific survival during a median postoperative followup of 32 months (IQR 6-66). The κ statistic revealed excellent interobserver agreement (κ 0.934, p <0.001). Two and 5-year cancer specific survival rates for the entire study cohort were 86% and 74%, respectively. The 2 and 5-year rates for patients without and with p16(INK4a) expression differed significantly (73% and 57% vs 95% and 85%, respectively, p = 0.011). Univariate analysis revealed p16(INK4a) expression as a significant prognostic factor with respect to cancer specific survival (p = 0.018). Multivariate analysis identified koilocytosis (HR 0.24, 95% CI 0.07-0.83, p = 0.024), p16(INK4a) expression (HR 0.44, 95% CI 0.23-0.84, p = 0.013), and histological stage (HR 3.54, 95% CI 1.88-6.67, p <0.001) and grade (HR 2.47, 95% CI 1.00-6.09, p = 0.049) as independent prognostic factors for cancer specific survival. Results show that p16(INK4a) seems to be a prognostic parameter for primary invasive penile cancer with excellent interobserver reproducibility. At pathology laboratories without antibodies against p16(INK4a) conventional histological determination of koilocytosis by the pathologist also appears to provide important prognostic information for cancer specific

  5. Providing Retraining and Advancement Training for Primary/Elementary School Teachers at the State Level in Great Britain and the USA

    ERIC Educational Resources Information Center

    Chychuk, Antonina

    2017-01-01

    In Great Britain and the USA the normative basis of primary/elementary school teachers' qualification advancement is being actively developed, i. e. this issue is considered at the state level. For a long time the development of retraining and advancement training system for primary/elementary school teachers has been grounded on conceptual…

  6. Centralized primary care of advanced ovarian cancer improves complete cytoreduction and survival - A population-based cohort study.

    PubMed

    Dahm-Kähler, Pernilla; Palmqvist, Charlotte; Staf, Christian; Holmberg, Erik; Johannesson, Liza

    2016-08-01

    To evaluate centralized primary care of advanced ovarian and fallopian tube cancers in a complete population cohort in relation to complete cytoreduction, time interval from surgery to chemotherapy and relative survival. A regional population-based cohort study of women diagnosed with primary ovarian and fallopian tube cancers and included in the Swedish Quality Registry (SQR) during 2008-2013 in a region where primary care of advanced stages was centralized in 2011. Surgical, oncological characteristics, outcomes, follow-ups and relative survivals were analyzed. There were 817 women diagnosed with ovarian and fallopian tube cancers during 2008-2013 and 523 were classified as FIGO stage III-IV and further analyzed. Primary debulking surgery (PDS) was performed in 81% and neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in 11%. Complete cytoreduction at PDS was performed in 37% before compared to 49% after centralization (p<0.03). The chemotherapy protocols were identical in the cohorts and they received and completed the planned chemotherapy equally. The time interval between PDS and chemotherapy was 36days (median) before compared to 24days after centralization (p<0.01). The relative 3-year survival rate in women treated by PDS was 44% compared to 65% after centralization and the estimated excess mortality rate ratio (EMRR) was reduced (RR 0.58; 95% CI 0.42-0.79). Comparing the complete cohorts before and after centralization, regardless primary treatment, the relative 3-year survival rate increased from 40% to 61% with reduced EMRR (RR 0.59; 95% CI 0.45-0.76). Centralized primary care of advanced ovarian and fallopian tube cancers increases complete cytoreduction, decreases time interval from PDS to chemotherapy and improves relative survival significantly. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Introducing Cytology-Based Theranostics in Oral Squamous Cell Carcinoma: A Pilot Program.

    PubMed

    Patrikidou, Anna; Valeri, Rosalia Maria; Kitikidou, Kyriaki; Destouni, Charikleia; Vahtsevanos, Konstantinos

    2016-04-01

    We aimed to evaluate the feasibility and reliability of brush cytology in the biomarker expression profiling of oral squamous cell carcinomas within the concept of theranostics, and to correlate this biomarker profile with patient measurable outcomes. Markers representative of prognostic gene expression changes in oral squamous cell carcinoma was selected. These markers were also selected to involve pathways for which commercially available or investigational agents exist for clinical application. A set of 7 markers were analysed by immunocytochemistry on the archival primary tumour material of 99 oral squamous cell carcinoma patients. We confirmed the feasibility of the technique for the expression profiling of oral squamous cell carcinomas. Furthermore, our results affirm the prognostic significance of the epidermal growth factor receptor (EGFR) family and the angiogenic pathway in oral squamous cell carcinoma, confirming their interest for targeted therapy. Brush cytology appears feasible and applicable for the expression profiling of oral squamous cell carcinoma within the concept of theranostics, according to sample availability.

  8. Squamous cell carcinoma of rectum presenting in a man: a case report

    PubMed Central

    2010-01-01

    Background Primary squamous cell carcinomas of the colorectum are very uncommon. Until now, to the best of our knowledge, only 114 cases of squamous cell carcinoma in the colorectum exist in the reported literature. Here we report a case of squamous cell carcinoma of the rectum in the ethnic Kashmiri population in northern India. Case Presentation The case of a 60-year-old male patient (Asian) with a pure squamous cell carcinoma of the rectum is presented here. The patient underwent a curative surgery with concomitant chemotherapy. Two years after the initial curative resection of the tumor he is still alive. Conclusion The prognosis for squamous cell carcinoma of the colorectum is worse than for that of adenocarcinoma, because of the delayed diagnosis. The etiopathogenicity of squamous cell carcinoma of the colorectum is discussed. Surgical resection of the lesion seems to be the treatment of choice. Chemotherapy also helps in improvement of the prognosis. PMID:21118539

  9. Parameters of Stromal Activation and Epithelial to Mesenchymal Transition as Predictive Biomarkers for Induction Chemotherapy in Patients With Locally Advanced Oral Cavity and Oropharyngeal Squamous Cell Cancer.

    PubMed

    Geweiler, Jana; Inhestern, Johanna; Berndt, Alexander; Guntinas-Lichius, Orlando

    2016-12-01

    Induction chemotherapy (IC) is likely to be effective for biologically distinct subgroups of oral cancer and biomarker development may lead to identification of those patients. We evaluated immune cell infiltration, stroma formation and structure of the invasive front as well as the immunohistochemical expression of alpha smooth muscle actin (ASMA), CD163, E-cadherin, N-cadherin, and the laminin gamma 2 chain in pretreatment biopsy specimens and surgical resections after IC in 20 patients with locally advanced oral cancer who were treated in a prospective, ongoing, phase II trial on IC using docetaxel, cisplatin, and 5-fluorouracil (TPF). Significant negative prognostic factors for incomplete pathological tumor response to IC were alcohol abuse (P=0.032), cN+ (P=0.042), and <30% tumor reduction after first cycle of IC (P=0.034). Of the investigated histological parameters and biomarkers only a low membrane-bound expression of E-cadherin showed a trend to be associated with incomplete response to IC (P=0.061). Low expression of ASMA in stromal vessels and a strong tumor invasion front were significantly associated to tumor recurrence (P=0.024 and P=0.004, respectively). The median follow-up of all patients was 35 months. Alcohol abuse (P<0.001), <30% tumor reduction after first cycle of IC (P=0.005), and a strong tumor invasion front (P=0.019) were negative prognostic factors for overall survival. A strong predictive biomarker among the investigated parameters for benefitting from TPF IC could not be found. The extent of the tumor invasion front was a negative prognostic marker for recurrence and survival in oral cancer treated by TPF IC followed by surgery and postoperative radiochemotherapy.

  10. Aurora-A signaling is activated in advanced stage of squamous cell carcinoma of head and neck cancer and requires osteopontin to stimulate invasive behavior

    PubMed Central

    Su, Li-Jen; Chuang, Hui-Ching; Shiu, Li-Yen; Huang, Chao-Cheng; Fang, Fu-Min; Yu, Chun-Chieh; Su, Huei-Ting; Chen, Chang-Han

    2014-01-01

    The clinical significances, cellular effects, and molecular mechanisms by which Aurora-A mediate its invasive effects in HNSCC are still unclear. Here, we found that Aurora-A expression is significantly higher in tumor tissues on 14-microarray of HNSCC in Oncomine-databases. The activity of Aurora-A was not only found in HNSCC specimens, but also significantly correlated with advanced-T-classification, positive-N-classification, TNM-stage and the poor 5-year survival rate. HNSCC-microarray profile showed that osteopontin and Aurora-A exhibited positive correlation. Stimulation of HNC cells with osteopontin results in an increase in Aurora-A expression where localized at the centrosome. Functionally, Aurora-A had the abilities to stimulate cell motility in HNC cells through increase ERK1/2 activity under osteopontin stimulation. Conversely, depletion of Aurora-A expression by siRNAs suppressed ERK1/2 activity as well as inhibition of cell invasiveness. Treatment with anti-CD44 antibodies in HNC cells not only caused a decrease of mRNA/protein of Aurora-A and ERK1/2 activity upon osteopontin stimulation, but also affected the abilities of Aurora-A-elicited cell motility. Finally, immunohistochemical/Western-blotting analysis of human aggressive HNSCC specimens showed a significant positively correlation between osteopontin-Aurora-A and ERK1/2. These findings suggest that Aurora-A is not only an important prognostic factor but also a new therapeutic target in the osteopontin/CD44/ERK pathway for HNSCC treatment. PMID:24810160

  11. Parameters of Stromal Activation and Epithelial to Mesenchymal Transition as Predictive Biomarkers for Induction Chemotherapy in Patients With Locally Advanced Oral Cavity and Oropharyngeal Squamous Cell Cancer

    PubMed Central

    Geweiler, Jana; Inhestern, Johanna; Berndt, Alexander; Guntinas-Lichius, Orlando

    2016-01-01

    Objectives Induction chemotherapy (IC) is likely to be effective for biologically distinct subgroups of oral cancer and biomarker development may lead to identification of those patients. Methods We evaluated immune cell infiltration, stroma formation and structure of the invasive front as well as the immunohistochemical expression of alpha smooth muscle actin (ASMA), CD163, E-cadherin, N-cadherin, and the laminin gamma 2 chain in pretreatment biopsy specimens and surgical resections after IC in 20 patients with locally advanced oral cancer who were treated in a prospective, ongoing, phase II trial on IC using docetaxel, cisplatin, and 5-fluorouracil (TPF). Results Significant negative prognostic factors for incomplete pathological tumor response to IC were alcohol abuse (P=0.032), cN+ (P=0.042), and <30% tumor reduction after first cycle of IC (P=0.034). Of the investigated histological parameters and biomarkers only a low membrane-bound expression of E-cadherin showed a trend to be associated with incomplete response to IC (P=0.061). Low expression of ASMA in stromal vessels and a strong tumor invasion front were significantly associated to tumor recurrence (P=0.024 and P=0.004, respectively). The median follow-up of all patients was 35 months. Alcohol abuse (P<0.001), <30% tumor reduction after first cycle of IC (P=0.005), and a strong tumor invasion front (P=0.019) were negative prognostic factors for overall survival. Conclusion A strong predictive biomarker among the investigated parameters for benefitting from TPF IC could not be found. The extent of the tumor invasion front was a negative prognostic marker for recurrence and survival in oral cancer treated by TPF IC followed by surgery and postoperative radiochemotherapy. PMID:27416733

  12. Doublet chemotherapy with cisplatin and pemetrexed is associated with a favorable outcome in patients with advanced non-squamous non-small-cell lung cancer who are eligible for bevacizumab and maintenance therapy

    PubMed Central

    Nakashima, Kazuhisa; Murakami, Haruyasu; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Endo, Masahiro; Takahashi, Toshiaki

    2016-01-01

    The previous AVAPERL trial demonstrated that induction therapy with first-line cisplatin (CDDP), pemetrexed (PEM) and bevacizumab (BEV), followed by continuation maintenance therapy with PEM+BEV, improved the progression-free survival (PFS) and overall survival (OS) compared with BEV alone (median PFS, 10.2 vs. 6.6 months and median OS, 19.8 vs. 15.9 months, respectively) in patients with advanced non-squamous non-small-cell lung cancer (non-Sq NSCLC). However, those findings were based on selected patients who were eligible for BEV and maintenance therapy. To assess the efficacy of CDDP+PEM as first-line therapy in selected patients depending on their eligibility for BEV and maintenance therapy, consecutive patients with non-Sq NSCLC who received first-line chemotherapy with CDDP+PEM at the Shizuoka Cancer Center (Shizuoka, Japan) between July, 2009 and December, 2013 were retrospectively reviewed. A total of 160 patients were assessed, including 92 who were eligible and 68 who were not eligible for BEV treatment. In the BEV-eligible group, CDDP+PEM treatment followed by maintenance PEM exhibited significantly superior efficacy compared with that in the BEV-ineligible group (median PFS, 5.8 vs. 4.8 months, respectively, P=0.013; and median OS, 21.3 vs. 12.6 months, respectively, P=0.0025). In the BEV-eligible group, 60 patients were suitable for maintenance therapy with PEM (group A) and 32 patients were unsuitable (group B). In the BEV-ineligible group, 31 patients were suitable for maintenance therapy with PEM (group C) and 37 patients were unsuitable (group D). In group A, the median PFS and OS were 6.9 and 31.8 months, respectively, compared with 2.4 and 10.5 months in group B, 6.1 and 18.5 months in group C, and 2.8 and 7.7 months in group D. The PFS and OS in group A were significantly better compared with those in the other groups. Thus, the PFS and OS with CDDP+PEM were favorable among patients with advanced non-Sq NSCLC who were eligible for BEV and