Targeting proliferation and survival pathways in head and neck cancer for therapeutic benefit

Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. Recent studies have elucidated a key signaling axis, the EGFR-STAT3-Bcl-XL signaling axis, that is aberrantly activated in a majority of HNSCC and contributes to the proliferation and survival of malignant cells. Considerable effort is being placed on developing highly specific inhibitors of different components of this pathway. This review highlights the progress that is being made towards achieving potent inhibition of the EGFR-STAT3-Bcl-XL signaling axis in HNSCC and the promising therapeutic strategies that are currently under development for this disease.     

The prognostic significance of ALI,PLR,and Ki-67 expression in stageⅢ–Ⅳinoperable non-small cell lung cancer

Objective The aim of the study was to investigate and compare the prognostic value of advanced inflammatory index,platelet/lymphocyte ratio(PLR),and Ki-67 expression in stageⅢ–Ⅳinoperable non-small cell lung cancer(NSCLC)before treatment.Methods The clinical data of 98 inoperable patients with stageⅢ–ⅣNSCLC in our hospital(Fifth Department of Oncology,Hebei General Hospital,Shijiazhuang,China)before treatment were retrospectively analyzed,and advanced lung cancer inflammation index(ALI)was calculated using body mass index(BMI)×serum albumin(ALB)÷neutrophil/lymphocyte ratio(NLR).he optimal cutoff values of ALI and PLR for predicting prognosis is determined.Chi-square test was used to analyze the relationship between patients and clinical characteristics.Kaplan-Meier method was used to calculate the total survival of patients,and log-rank test was used for comparison.Independent prognostic factors were assessed by univariate and multivariate analyses.Spearman correlation was used to analyze the relationship among ALI,PLR,and Ki-67.Results In our study of the 98 cases,the survival time of the patients with ALI<18 was significantly lower than that of patients with ALI>18(P<0.001),with a median survival time of 10 months and 25 months,respectively.The survival time of patients with a PLR<185 was significantly higher than that of patients with a PLR>185(median survival time was 27 months vs.10 months,P<0.001).The higher the Ki-67 expression,the shorter the survival time(P<0.005).The combined ALI and PLR detection results indicated that the survival time of patients with high ALI and low PLR was significantly longer than that of patients with low ALI and high PLR(P<0.001).Univariate analysis showed that smoking history,degree of differentiation,KPS score,Ki-67 expression,ALI value,and PLR affected the prognosis of patients.Multivariate analysis showed that KPS score,ALI value,and Ki-67 expression were independent prognostic factors.Conclusion ALI,PLR,and Ki-67 expression are important predictors of stage III-IV inoperable NSCLC.In terms of the prognostic value,ALI seems to have the best ability to predict patient survival.In addition,the combined detection of ALI and PLR levels before treatment seems to be more helpful in improving our prediction of patient prognosis.Moreover,it is expected to play a role in future clinical applications.     

Large-scale molecular characterization and analysis of gastric cancer

The recent effort by The Cancer Genome Atlas （TCGA） Network has revealed that gastric cancer, which is a leading cause of cancerrelated deaths worldwide with a 5-year survival rate less than 25%, is a much more heterogeneous disease than previously thought. And yet, conventional treatment approaches and clinical trials have assumed it is a single disease. Although it is well known that under the microscope, gastric cancer cells appear quite different, the current classification scheme recognizes two main categories of gastric cancer： diffuse and intestinal.     

Chemotherapy for cholangiocarcinoma:An update

Cholangiocarcinomas(bile duct cancers) are a heterogeneous group of malignancies arising from the epithelial cells of the intrahepatic,perihilar and extrahepatic bile ducts.Patients diagnosed with cholangiocarcinoma must be evaluated by a multidisciplinary team and be treated with individualized management.First of all,it is very important to define the potential resectability of the tumor because surgery is the main therapeutic option for these patients.Overall,cholangiocarcinomas have a very poor prognosis.The 5 year survival rate is 5%-10%.In cases with a potentially curative surgery,5 year survival rates of 25%-30% are reported.Therefore,it is necessary to increase the cure rate from surgery,exploring the survival benefit of any adjuvant strategy.It is difficult to clarify the role of adjuvant treatment in localized and locally advanced cholangiocarcinomas.There are limited data and the role of adjuvant chemotherapy/chemoradiation in patients with resected biliary tract cancer is poorly defined.The most relevant studies in the adjuvant setting are one from Japan,the well known ESPAC-3 and BILCAP from the United Kingdom and a meta-analysis.We show the results of these trials.According to medical oncology guidelines,postoperative adjuvant therapy is widely recommended for all patients with intrahepatic or extrahepatic cholangiocarcinoma who have microscopically positive resection margins,as well as for those with a complete resection but node-positive disease.Clinical trials are ongoing.The locally advanced cholangiocarcinoma setting includes a heterogeneous mix of patients:(1) patients who have had surgery but with macroscopic residual disease;(2) patients with locally recurrent disease after potentially curative treatment;and(3) patients with locally unresectable disease at presentation.In these patients,surgery is not an option and chemoradiation therapy can prolong overall survival and provide control of symptoms due to local tumor effects.Nowadays,no neoadjuvant therapy can be considered a standard approach for the treatment of patients with cholangiocarcinoma.There are promising results and randomized trials are needed in patients with a metastatic cholangiocarcinoma.In systemic therapy,no single drug or combination has consistently increased median survival beyond the expected 8-12 mo.It is always recommended that patients enrol in clinical trials.Clinical trials have shown that the more standard chemotherapy for a first line regimen of gemcitabine plus cisplatin(or oxaliplatin as a potentially better tolerated agent) is superior to gemcitabine alone.Leucovorinmodulated 5-fluorouracil,capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status.After progression in patients with an adequate performance status,active regimens that could be considered include gemcitabine plus capecitabine,or erlotinib plus bevacizumab,for second line treatment.     

Prognostic value and predictive threshold of tumor volume for patients with locally advanced nasopharyngeal carcinoma receiving intensity-modulated radiotherapy

Background:Gross target volume of primary tumor (GTV?P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity?modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to ifnd a suitable cut?off value of GTV?P for prognosis prediction. Methods:Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver oper?ating characteristic (ROC) curves were used to identify the cut?off values of GTV?P for the prediction of different end?points [overall survival (OS), local relapse?free survival (LRFS), distant metastasis?free survival (DMFS), and disease?free survival (DFS)] and to test the prognostic value of GTV?P when compared with that of the American Joint Committee on Cancer T staging system. Results:The 358 patients with locally advanced NPC were divided into two groups by the cut?off value of GTV?P as determined using ROC curves: 219 (61.2%) patients with GTV?P≤46.4mL and 139 (38.8%) with GTV?P>46.4mL. The 3?year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV?P≤46.4mL than in those with GTV?P>46.4mL (allP<0.05). Multivariate analysis indicated that GTV?P>46.4mL was an independent unfavorable prognostic factor for patient survival. The ROC curve veriifed that the predictive ability of GTV?P was superior to that of T category (P<0.001). The cut?off values of GTV?P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4mL, respectively. Conclusion:In patients with locally advanced NPC, GTV?P>46.4mL is an independent unfavorable prognostic indi?cator for survival after IMRT, with a prognostic value superior to that of T category.     

BRAIN TUMORS OF THE FIRST YEAR OF LIFE:CLINICAL AND SURGICAL MANAGEMENT

Brain tumors incidence in pediatric age hasbeen estimated between 1.3 to 5% with a relativeincidence of 1.4 to 11% during the first year oflife; the improvement in instrumental deviceshas lead to a relative increase in precocious diag-nosis. The choice to study brain tumors of the firstyear of life as a separate topic from pediatric ageones depends on the observation that these le-sions have peculiar clinical, topographic and tis-sular characteristics. The survival rate of thesepatients is very poor if compared with that found     

Squamous cell carcinoma metastatic to cervical lymph nodes from unknown primary origin: the impact of chemoradiotherapy

The management of cervical lymph node metastases of squamous cell carcinoma from an unknown primary site is still a therapeutic challenge.We report here our experience in treating these patients with chemoradiotherapy as a curative approach.Data from 40 patients were reviewed.In total,20(50%) patients underwent excisional biopsy.All patients underwent radiotherapy,which was delivered to both sides of the neck and pharyngeal mucosa(extensive field),and concurrent chemotherapy consisting of weekly cisplatin at a dose of 40 mg/m2.The clinical stage of the cervical nodes at presentation was N1 in 25%,N2 in 60%,and N3 in 15%.Most patients(75%) developed at least grade 3 mucositis.Eight patients(20%) had grade 3 xerostomia and 18 patients(45%) required esophageal dilation for stricture.The 5-year overall survival(OS) rate of all patients was 67.5%.The 5-year OS rates of patients with N1,N2,and N3 lesions were 100%,67%,and 41%,respectively(P = 0.046).The 5-year progression-free survival rate was 62.5%.In multivariate analysis,only N stage significantly affected OS(P = 0.022).Emergence of the occult primary was very limited(1 patient only).Our results suggest that extensive irradiation of both sides of the neck and pharyngeal mucosa with concurrent chemotherapy results in a lower emergence of primary tumor.Because the survival of patients with unknown primary is comparable to that of patients with known primary,an attempt at cure should always be made.     

Development and validation of a nomogram for predicting the survival of patients with non-metastatic nasopharyngeal carcinoma after curative treatment

Background:The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopatho-logic factors for predicting the overall survival (OS) of non-metastatic nasopharyngeal carcinoma (NPC) patients after curative treatments. Methods:We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy (IMRT) between 2001 and 2010 were also retrieved to examine the extensibil-ity of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index (c-index). Results:We identiifed and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging sys-tem for predicting the survival in both the primary cohort (0.69 vs. 0.62) and the IMRT cohort (0.67 vs. 0.63). Conclusion:We developed and validated a novel nomogram that outperformed the TNM staging system in predict-ing the OS of non-metastatic NPC patients who underwent curative therapy.     

Shared decision-making in older patients with cancer - What does the patient want?

Shared decision-making in cancer care, where we move away from the paternalistic “the doctor knows best” attitude to involving the patient in decisions regarding her or his health, is now universally accepted in western societies. However, in many situations this is easier said than done. For instance, if the interaction with the patient is not performed in a skillful manner, shared decision-making can make the patient feel unsafe – shouldn't the specialist know how to treat a serious disease such as cancer? Why would the doctor ask the patient about this? In other cases, what the patient wants in unrealistic, for example a severely frail patient aged 85 years with more than one life-limiting comorbidity who is diagnosed with an advanced cancer and has a goal of living to be at least 100 years. And what does a patient with advanced dementia want in the context of a cancer disease? In this perspectives piece, we will describe different scenarios that may arise within geriatric oncology and shared decision-making, make recommendations about how to handle such situations, and provide some food for thought.     

Progress of introduction of artificial respirator at home--the knowledge I have gained from a 19 year-old patient requiring a home respiratory management care and through the friendship with his family members

The patient developed right cerebellar hemorrhage at the age of 15 and spent four years at hospital. The patient and the family members had a strong wish to bring the patient back home and the patient was admitted to the hospital to undergo guidance about home medical care. The patient had paralysis of right upper and lower extremities and generalized strong ataxic motion and was under gastric feeding and had underwent tracheotomy to cope with hypoventilation, which required use of an artificial respirator at night hours. Since the patient was still as young as 19, we want to have the patient "go home" as they wanted. Fortunately, the mother who had to play key roles was still young and the parents worked at home. It didn't take long for them to master the techniques though they had various anxieties. It is considered important in the guidance on home medical care to what degrees the caregivers accept the condition of the patient and can imagine the long lasting care at home. We provided assistance while repeatedly interviewing with the patient and family members considering the significance to confirm their willingness and psychological condition. As a result, the patient was discharged from the hospital in two months. Now, two years have passed, and the patient is still cared at home and the possibility of the patient is sought for. The progress is reported here in this article.     

Patient navigation: an update on the state of the science

Although patient navigation was introduced 2 decades ago, there remains a lack of consensus regarding its definition, the necessary qualifications of patient navigators, and its impact on the continuum of cancer care. This review provides an update to the 2008 review by Wells et al on patient navigation. Since then, there has been a significant increase in the number of published studies dealing with cancer patient navigation. The authors of the current review conducted a search by using the keywords "navigation" or "navigator" and "cancer." Thirty-three articles published from November 2007 through July 2010 met the search criteria. Consistent with the prior review, there is building evidence of some degree of efficacy of patient navigation in terms of increasing cancer screening rates. However, there is less recent evidence concerning the benefit of patient navigation with regard to diagnostic follow-up and in the treatment setting, and a paucity of research focusing on patient navigation in cancer survivorship remains. Methodological limitations were noted in many studies, including small sample sizes and a lack of control groups. As patient navigation programs continue to develop across North America and beyond, further research will be required to determine the efficacy of cancer patient navigation across all aspects of the cancer care continuum.     

Three Cases of Hepatoma

Three cases of primary neoplasm of the liver are presented. The first patient, with a tumour mass in the right lobe, showed a small area of calcification within the tumour. The second patient, with a tumour in the left lobe showed radiological features simulating enlargement of the spleen. A third patient, whose tumour was discovered at post-mortem is presented briefly. Evaluation of the pattern of liver calcification in the diagnosis of hepatoma is stressed and the role of Alpha-fetoprotein estimation is also discussed.     

Home medical care service and regional medical plan

A home medical service should be promoted as an individual medical plan which proactively copes with health problems in daily living. It is categorized into 3 phases: Health for a patient without long-term disabilities, QOL for a patient with long-term disabilities and Peaceful Death for a terminal patient.     

Palliative home care

Palliative home care supports the quality of life (QOL) of a patient and family as a whole. Team care is an effective method corresponding to the various needs of the patient and family. Cooperation of various types of professions can meet the need for high-quality outpatient medical care. Social work serves as a coordinator of the care team. One of its important tasks in palliative home care is support of the patient discharge procedure from the hospital. Discharge from the hospital must be carried out before the patient's condition worsens. Prompt support of the discharge is indispensable so that the patient may spend substantial time with high QOL at home. Palliative home care means care for the dying. Therefore, spirituality issues are important. Palliative home care must respect and understand the spirituality of the patient and family. The patient can be discharged from the hospital in peace when there is general support for the physical, psycho-social and spiritual needs of both patient and family.     

Richter's syndrome presenting as a nasal lymphoma

Richter's syndrome (RS) is a high-grade large cell lymphoma arising in patients with B-cell chronic lymphocytic leukemia (CLL). The prognosis of RS is very poor and the development of RS is a serious complication of CLL. We present a case of a patient with a 4-year history of B-cell CLL who developed diffuse large B-cell nasal lymphoma. The patient exhibited good response to chemotherapy and irradiation and achieved complete remission. Five months later, the patient suffered leptomeningeal involvement and has been treated with repeated intrathecal chemotherapy. Leukemic cells of the patient expressed CD13. CD13+ CLLs have been reported to have an unfavorable prognosis and this case may support the view.     

Design of a clinical deep-body hyperthermia system based on the 'coaxial TEM' applicator

The design of a clinical deep-body hyperthermia system based on the 'coaxial TEM' applicator is presented. The 'coaxial TEM' applicator produces a radiative circumferential RF field, and the adjustable aperture width of this applicator allows the optimization of field dimensions and penetration depth. A new type of open water bolus, in which the patient is almost freely floating, avoids physical stresses on the patient, provides an optimal coupling of the EM energy into the patient, and may limit aberrant heating. A convenient patient position is possible with this system and discomfort is expected to be minimal. Preliminary phantom experiments with the clinical applicator resulted in typical SAR distributions of a radiative circumferential field applicator with the central interference at maximum.