Clinical Outcomes of Patients with Resected Oral Cavity Cancer and Simultaneous Second Primary Malignancies

Objectives

Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme.

Methods

A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures.

Results

Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001).

Conclusion

OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis.     

Bladder Cancer After Radiotherapy for Prostate Cancer

External beam radiotherapy (EBRT) is frequently used in the management of prostate cancer (PCa) as definitive, postoperative, or salvage local treatment. Although EBRT plays a central role in the management of PCa, complications remain a troubling by-product. Several studies have demonstrated an association between radiotherapy and elevated risk of acute and late toxicities. A secondary malignancy induced by initial therapy represents one of the most serious complications related to definitive cancer treatment. The radiation-related secondary primary malignancy risk increases with increasing survival time. Transitional cell carcinoma of the bladder is the most frequent secondary primary malignancy occurring after radiotherapy and is described as more aggressive; it may be diagnosed later because some radiation oncologists believe that the hematuria that occurs after prostate EBRT is normal. Some patients treated for localized PCa will subsequently develop invasive bladder cancer requiring surgical intervention. Patients with PCa treated with EBRT should be monitored closely for the presence of bladder cancer.Key words: Bladder cancer, Prostate cancer, Radiotherapy, External beam radiotherapyThe phenomenon of radiation-inducing the carcinogenesis has been well described in literature for decades. The correlation between ionizing radiation and DNA damage has been discussed in several studies.^1–4 Most of these studies evaluated the growth of solid tumors in a large population exposed to moderate to heavy doses of radiation, such as factory workers, patients exposed to a large number of diagnostic radiographic studies, and survivors of atomic and nuclear explosions. ¹ The casual effects of radiation exposure with subsequent mutagenesis are quite clear, shown both in vivo and in vitro.² Previous radiotherapy (RT) for prostate cancer (PCa) may play an important role in the development of secondary primary bladder cancer. This is a fairly uncommon event but a very real entity, of which both urologists and radiation oncologists need to be aware.     

Risk of Second Primary Cancer among Prostate Cancer Patients in Korea: A Population-Based Cohort Study

As patients with prostate cancer have a long life expectancy, there is increasing interest in predicting the risk of development of a second primary cancer (SPC), and we therefore designed this study to estimate the overall risk of developing SPCs among Korean prostate cancer patients. We used a population-based cohort from the Korean Central Cancer Registry composed of 55,378 men diagnosed with a first primary prostate cancer between 1993 and 2011. Standardized incidence ratios (SIRs) of SPCs were analyzed by age at diagnosis, latency period, period of diagnosis, and type of initial treatment. Survival analysis was stratified by development of SPC. Men with primary prostate cancer had an overall lower risk of developing an SPC [SIR = 0.75; 95% CI, 0.72−0.78], which was significant for SPCs of the esophagus, stomach, rectum, liver, gallbladder, bile duct, pancreas, larynx, lung, and bronchus. In contrast, there were significant increases in the risk of bladder and thyroid cancers, which tended to decrease after longer follow-up. Patients who received initial radiation therapy had an increased risk of subsequent rectal cancer, although this was still lower than that of the general male population. Other urinary tract cancers including those of the kidney, renal pelvis, and ureter tended to be associated with a higher risk of developing an SPC, but this difference did not reach statistical significance. The patients with prostate cancer and SPC had lower overall survival rates than those with one primary prostate cancer. Our findings suggest that men with prostate cancer have a 25% lower risk of developing an SPC in Korea, but a higher risk of developing subsequent bladder and thyroid cancers, which suggests the need for continued cancer surveillance among prostate cancer survivors.     

The Impact of Second Primary Malignancies on Head and Neck Cancer Survivors: A Nationwide Cohort Study

Background

Head and neck cancer (HNC) is associated with a high rate of developing second primary malignancies(SPMs). But the impact on survival remains poorly understood before. Therefore, we want to estimate the impact of SPMs on HNC survivors.

Methods and Findings

Between 1986 and 2008, a total of 9,996 SPMs were recorded for 93,891 patients with an initial diagnosis of HNC by the Taiwan Cancer Registry. Patients were followed with national death registry database to 2011.Using the Kaplan–Meier method, a time-dependent covariate was employed to compare the survival rates between patients with and without SPMs. A Cox proportional hazards model that treated age and sex as confounders was used to examine the hazard ratios of SPMs. The relative survival rates were calculated using age- and sex-specific life tables for the population. Parametric mixture cure fraction models were then employed to estimate the percentage of cancer survivors who would be cured. Use of the Kaplan–Meier method showed that the crude survival rates differed significantly for patients with and patients without SPMs (log-rank test <0.01). For the results of Cox proportional hazards regression analysis, SPMs had a significant influence on survival rates with univariate (HR 2.59,95% CI 2.53to 2.65) and multivariate analysis (HR 2.34, 2.28 to 2.40). Patients with SPMs of nasopharyngeal carcinoma (NPC) had the highest cure rate at 39%, where as esophageal and lung cancer had the worst prognosis, with a cure rate of 11%.

Conclusions

A worse prognosis was found for second primary cancer such as esophageal or lung cancer. Patients and healthcare providers must strongly consider and have a high clinical suspicion of these SPMs.     

Multifunctional Nanoparticles for Prostate Cancer Therapy

The relapse of cancer after first line therapy with anticancer agents is a common occurrence. This recurrence is believed to be due to the presence of a subpopulation of cells called cancer stem cells in the tumor. Therefore, a combination therapy which is susceptible to both types of cells is desirable. Delivery of this combinatorial approach in a nanoparticulate system will provide even a better therapeutic outcome in tumor targeting. The objective of this study was to develop and characterize nanoparticulate system containing two anticancer agents (cyclopamine and paclitaxel) having different susceptibilities toward cancer cells. Both drugs were entrapped in glyceryl monooleate (GMO)-chitosan solid lipid as well as poly(glycolic-lactic) acid (PLGA) nanoparticles. The cytotoxicity studies were performed on DU145, DU145 TXR, and Wi26 A4 cells. The particle size of drug-loaded GMO-chitosan nanoparticles was 278.4 ± 16.4 nm with a positive zeta potential. However, the PLGA particles were 234.5 ± 6.8 nm in size with a negative zeta potential. Thermal analyses of both nanoparticles revealed that the drugs were present in noncrystalline state in the matrix. A sustained in vitro release was observed for both the drugs in these nanoparticles. PLGA blank particles showed no cytotoxicity in all the cell lines tested, whereas GMO-chitosan blank particles showed substantial cytotoxicity. The types of polymer used for the preparation of nanoparticles played a major role and affected the in vitro release, cytotoxicity, and uptake of nanoparticles in the all the cell lines tested.KEY WORDS: cancer stem cells, cyclopamine, glyceryl monooleate, nanoparticles, PLGA     

Randomization to Screening for Prostate,Lung, Colorectal and Ovarian Cancers and Thyroid Cancer Incidence in Two Large Cancer Screening Trials

Background

Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials.

Methods

We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST). In the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), we assessed the association between randomization to regular screening for said cancers versus usual medical care and thyroid cancer risk. Over a median 6 and 11 years of follow-up in NLST and PLCO, respectively, we identified 60 incident and 234 incident thyroid cancer cases. Cox proportional hazards regression was used to calculate the cause specific hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer.

Results

In NLST, randomization to lung CT scan was associated with a non-significant increase in thyroid cancer risk (HR  = 1.61; 95% CI: 0.96–2.71). This association was stronger during the first 3 years of follow-up, during which participants were actively screened (HR  = 2.19; 95% CI: 1.07–4.47), but not subsequently (HR  = 1.08; 95% CI: 0.49–2.37). In PLCO, randomization to cancer screening compared with usual care was associated with a significant decrease in thyroid cancer risk for men (HR  = 0.61; 95% CI: 0.49–0.95) but not women (HR  = 0.91; 95% CI: 0.66–1.26). Similar results were observed when restricting to papillary thyroid cancer in both NLST and PLCO.

Conclusion

Our study suggests that certain medical encounters, such as those using low-dose helical CT scan for lung cancer screening, may increase the detection of incidental thyroid cancer.     

以前列腺干细胞抗原为靶点的前列腺癌免疫治疗研究进展

前列腺干细胞抗原(PSCA)为细胞膜表面抗原,在正常前列腺组织中低表达,在雄激素依赖性和非依赖性前列腺癌组织中高表达,有较高的组织特异性,是前列腺癌治疗的理想靶标,近年来以PSCA为靶点的前列腺癌治疗性疫苗的研究已成为热点。我们简要综述以PSCA为靶点治疗前列腺癌的研究进展。     

Evaluation of NUF2 and GMNN Expression in Prostate Cancer: Potential Biomarkers for Prostate Cancer Screening

Background:Prostate cancer (PC) is one of the most abundant cancers among men, and In Iran, has been responsible for 6% of all deaths from cancer in men. NUF2 and GMNN genes are considered as loci of susceptibility to tumorigenesis in humans. Alterations in expression of these genes have been reported in various malignancies. The aim of our study was to test whether different NUF2 and GMNN expression levels are associated with PC incidence and hence, might be considered as new molecular tools for PC screening.Methods:Biopsy samples from 40 PC patients and 41 healthy Iranian men were used to determine the relative gene expression. After RNA extraction and cDNA synthesis, samples were analyzed using TaqMan Quantitative Real time PCR. Patients’ background information, included smoking habits and family histories of PC, were recorded. Stages and grades of their PC were classified by the TNM tumor, node, metastasis (TMN) staging system based on standard guidelines.Results:NUF2 expression did not significantly differ between the groups, while GMNN expression was significantly greater in the PC specimens than in the controls.Conclusion:Regarding the significant role of GMNN in various tumor phenotypes, and its importance in PC progression, the alteration in GMNN expression in PC samples vs. controls indicate that the genetic profiling of this cancer might be considered to personalize therapy for each patient in the future.Key Words: Family history, Geminin (GMNN), Tumor staging, NUF2, Prostate cancer     

Analysis of Prostate Deformation during a Course of Radiation Therapy for Prostate Cancer

Purpose

Accurate analysis of the correlation between deformation of the prostate and displacement of its center of gravity (CoG) is important for efficient radiation therapy for prostate cancer. In this study, we addressed this problem by introducing a new analysis approach.

Method

A planning computed tomography (CT) scan and 7 repeat cone-beam CT scans during the course of treatment were obtained for 19 prostate cancer patients who underwent three-dimensional conformal radiation therapy. A single observer contoured the prostate gland only. To evaluate the local deformation of the prostate, it was divided into 12 manually defined segments. Prostate deformation was calculated using in-house developed software. The correlation between the displacement of the CoG and the local deformation of the prostate was evaluated using multiple regression analysis.

Results

The mean value and standard deviation (SD) of the prostate deformation were 0.6 mm and 1.7 mm, respectively. For the majority of the patients, the local SD of the deformation was slightly lager in the superior and inferior segments. Multiple regression analysis revealed that the anterior-posterior displacement of the CoG of the prostate had a highly significant correlation with the deformations in the middle-anterior (p < 0.01) and middle-posterior (p < 0.01) segments of the prostate surface (R² = 0.84). However, there was no significant correlation between the displacement of the CoG and the deformation of the prostate surface in other segments.

Conclusion

Anterior-posterior displacement of the CoG of the prostate is highly correlated with deformation in its middle-anterior and posterior segments. In the radiation therapy for prostate cancer, it is necessary to optimize the internal margin for every position of the prostate measured using image-guided radiation therapy.     

The Case for Hypofractionation of Localized Prostate Cancer

An optimal treatment regimen for localized prostate cancer (PCa) is yet to be determined. Increasing evidence reveals a lower α/β ratio for PCa with hypofractionated radiation therapy (HFRT) regimens introduced to exploit this change in therapeutic ratio. HFRT also results in shortened overall treatment times of 4 to 5 weeks, thus reducing staffing and machine burden, and, more importantly, patient stress. This review evaluates pretreatment characteristics, outcomes, and toxicity for 15 HFRT studies on localized PCa. HFRT results in comparable or better biochemical relapse-free survival and toxicity and is a viable option for localized PCa.Key words: Localized prostate cancer, Hypofractionation, Short-course radiotherapy, Dose escalation, Biologic equivalenceMultiple randomized dose-escalation trials for localized prostate cancer (PCa) have shown improved biochemical relapse-free survival (bRFS) rates for higher total doses using conventionally fractionated radiotherapy (CFRT), though at a cost of longer treatment duration.^1–4 The increased treatment time requires increased access to radiation treatment facilities, with additional burden on both patients and staff. To address the issue of prolonged treatment duration while maintaining equivalent bRFS, an increasing number of studies have pursued the role of hypofractionated radiotherapy (HFRT) with higher daily doses delivered in a shorter total amount of time. This treatment paradigm assumes a low α/β ratio for PCa, as demonstrated in several recent studies, with higher α/β ratios for normal surrounding tissues.^5–7 By employing HFRT, the increased daily radiation doses exploit the aforementioned α/β ratios by allowing equivalent tumor kill as with CFRT, while also allowing for normal tissue repair.With longer-term and randomized HFRT data now reported in the literature, it seems appropriate to address whether the time has come to make HFRT the new standard. This article seeks to review the current literature and the role of HFRT in the modern era of radiotherapy for localized PCa.     

Incidental Prostate Cancer at the Time of Cystectomy: The Incidence and Clinicopathological Features in Chinese Patients

Objectives

To evaluate the incidence and the clinicopathological features of incidental prostate cancer detected in radical cystoprostatectomy (RCP) specimens in Chinese men and to estimate the oncological risk of prostate apex-sparing surgery for such patients.

Methods

The clinical data and pathological feature of 504 patients who underwent RCP for bladder cancer from January 1999 to March 2013 were retrospectively reviewed. Whole mount serial section of the RCP specimens were cut transversely at 3–4 mm intervals and examined in same pathological institution.

Results

Thirty-four out of 504 patients (6.8%) had incidental prostate cancer with a mean age of 70.3 years. 12 cases (35.2%) were diagnosed as significant disease. 4 cases were found to have apex involvement of adenocarcinoma of the prostate while in 5 cases the prostate stroma invasion by urothelial carcinoma were identified (one involved prostate apex). The mean follow-up time was 46.4±33.8 months. Biochemical recurrence occurred in 3 patients but no prostate cancer-related death during the follow-up. There was no statistical significance in cancer specific survival between the clinically significant and insignificant cancer group.

Conclusions

The prevalence of incidental prostate cancer in RCP specimens in Chinese patients was remarkably lower than in western people. Most of the incidental prostate cancer was clinically insignificant and patient''s prognosis was mainly related to the bladder cancer. Sparing the prostate apex was potentially associated with a 1.0% risk of leaving significant cancer of the prostate or urothelial carcinoma.     

前列腺癌鼠模型

前列腺癌鼠模型是研究前列腺癌的重要工具,目前常见以下4类：自发和诱发鼠模型,异种移植鼠模型,转基因鼠模型和基因敲除鼠模型。简要综述了前列腺癌鼠模型的研究进展。     

Vascular Targeted Photodynamic Therapy for Localized Prostate Cancer

Survival for men diagnosed with prostate cancer directly depends on the stage and grade of the disease at diagnosis. Prostate cancer screening has greatly increased the ability to diagnose small and low-grade cancers that are amenable to cure. However, widespread prostate-specific antigen screening exposes many men with low-risk cancers to unnecessary complications associated with treatment for localized disease without any survival advantage. One challenge for urological surgeons is to develop effective treatment options for low-risk disease that are associated with fewer complications. Minimally invasive ablative treatments for localized prostate cancer are under development and may represent a preferred option for men with low-risk disease who want to balance the risks and benefits of treatment. Vascular targeted photodynamic therapy (VTP) is a novel technique that is being developed for treating prostate cancer. Recent advances in photodynamic therapy have led to the development of photosynthesizers that are retained by the vascular system, which provides the opportunity to selectively ablate the prostate with minimal collateral damage to other structures. The rapid clearance of these new agents negates the need to avoid exposure to sunlight for long periods. Presented herein are the rationale and preliminary data for VTP for localized prostate cancer.Key words: Prostate cancer, localized; Minimally invasive ablative treatment for prostate cancer; Photodynamic therapy; WST-09; WST-11; Vascular targeted photodynamic therapy; Padoporfin; Palladium bacteriopheophorbideProstate cancer represents the second most common cause of cancer-related deaths in American men; it is estimated that 27,000 men in the United States died from the disease in 2007.¹ Survival for men with prostate cancer directly depends on the stage and grade of the disease at the time of diagnosis.² These sobering mortality statistics and the more favorable prognosis associated with early detection provide the primary justification for prostate cancer screening, which is performed by measuring the level of serum prostate-specific antigen (PSA) and conducting a digital rectal examination (DRE). It is estimated that 50% of men over the age of 50 years are screened annually for prostate cancer.³Despite widespread acceptance, prostate cancer screening is debated,^4,5 and recommendations for prostate cancer screening are inconsistent. Screening protagonists emphasize that radical prostatectomy increases prostate cancer survival in men with localized disease,⁶ and that the recently observed progressive and significant decline in prostate cancer mortality rates is the direct result of PSA screening and aggressive intervention.⁷ Screening antagonists emphasize the indolent natural history of most prostate cancers detected by screening,⁸ and that the vast majority of men who are treated for prostate cancer do not recognize any survival advantage from early detection and are simply left suffering the ravages of treatment.⁹Both sides of the screening debate have valid arguments. In the absence of widespread screening, many men are denied an opportunity to cure their disease. These men will experience the otherwise preventable consequences of disease progression, which include the development of androgen-insensitive disease¹⁰ and death. However, widespread screening exposes many men to unnecessary complications associated with treatment for localized disease. The challenges are to identify and treat only those cancers that have the biological potential to cause serious and preventable consequences, or to develop treatment options that are associated with fewer complications.