Sunday, August 16, 2015

Prostate Cancer News - 2015-08-15


Prostate Cancer News - 2015-08-15

General Case Management

Prostate Cancer Advocacy: Making it Count - Cancer Answers
I thought of the man who spoke to me about fighting metastatic prostate cancer. He felt not enough was being done. I sensed urgency in his voice. But though I heard fight in his voice, I also heard desperation — the fear of not knowing about tomorrow.
Well, none of us are guaranteed tomorrow. So it’s the quality of our days that counts.
I started the Blue Cure Foundation, a prostate cancer nonprofit, after being diagnosed with prostate cancer at age 35. My background was in marketing, and I felt my talents could be used to place a greater spotlight on the disease — in ways that haven’t been done. I wanted to change the conversation from ceaseless focus on fundraising solely for a cure that’s been sought for decades. I wanted us to consider cancer’s many causes and how we can reduce risk, improve outcomes, push for more accurate screenings and fight the complacency I find, as if prostate cancer is both the old and new normal.
Rallying the Prostate Cancer Community - Cancer Answers
“We don’t have it in our budget.”
That’s the excuse I hear too often from hospitals or cancer centers when I ask them to light a building blue one evening during September’s National Prostate Cancer Awareness Month.
They spend money lighting buildings pink in October for Breast Cancer Awareness Month. They support runs that benefit other cancers. They have lavish advertising budgets. But no, they can’t manage one night’s support for prostate cancer – the most commonly diagnosed male cancer in America.
GPs ‘more cost effective’ for prostate cancer aftercare | Irish Examiner
The NCRI’s new study, published in the journal Supportive Care in Cancer, revealed specialist aftercare for this type of cancer is no longer “sustainable” here due to the country’s rising number of prostate cancer survivors. It suggests survivors should switch to GP follow-up sessions instead as it is a more viable option and will not adversely affect the quality of aftercare received.

What IS an “N-of-1″ clinical trial? | THE "NEW" PROSTATE CANCER INFOLINK
N-of-1 clinical trials are basically trials of specific therapies in a single patient with very highly defined characteristics — often including a complete genetic profile as well as a whole bunch of other data. It would be impossible here to get into all the details about how N-of-1 clinical trials should be used and when they provide data that may be helpful in the management of larger number of patients, so here are a series of resources for those who might be interested in learning more — because we are going to be hearing about N-of-1 clinical trials in prostate cancer soon:
Latest prostate cancer findings may help determine the most suitable treatment for the condition : MEDICINE & HEALTH : Science Times
Prostate cancer may actually be five different diseases masked in one, scientists conclude after conducting a study that might help in designing the best treatment for this condition. A team of experts from the Cancer Research U.K. said that they were finally able to categorize the prostate cancer tumors into five distinct groups depending on their composite genes.
Prostate Cancer - Pipeline Review Report H1 2015 | Medgadget
This report provides comprehensive information on the therapeutic development for Prostate Cancer, complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA) and molecule type, along with latest updates, and featured news and press releases. It also reviews key players involved in the therapeutic development for Prostate Cancer and special features on late-stage and discontinued projects.

Prostate Cancer on the Web-Expedient Tool for Patients' Decision-Making?
Many patients diagnosed with cancer search for health information on the Web. We aimed to assess the quality and reliability of online health information on prostate cancer.
Google, Yahoo, and Bing were searched for the term "prostate cancer." After selecting the most frequented websites, quality was measured by
  • Quality assessed using
  • Popularity assessed  using
  • LIDA tool.used to investigate 
    • accessibility, 
    • usability, and 
    • reliability
Quality, accessibility, and usability of websites on prostate cancer provided a high rating in the current analysis. These findings are encouraging in view of the growing frequency of patients' access of health information online.
Evaluation of medical information quality

Choices you Make

Are Vitamin E Supplements Healthy or Harmful?
Prostate Cancer: A 2011 study funded by the National Cancer Institute examined whether vitamin E might help prevent prostate cancer. Earlier research had found no benefit or harm from vitamin E. This large study of 35,533 men over a periodhttps://blogger.googleusercontent.com/img/proxy/AVvXsEjj6l737MK0YexSa5XXZkGlzKKW6EolcbMLmLqBurYRzdwSUA6VT-B2s7U3QlQwX-LoOBvccajk7EdDHY26Mmmr1Ufmc_-WDs3YbAthMrJrk7rxR1y-QUCpOhbZNJnqIUG_KVdhZ8cMkWkXODk_ZPT1VyY= of three years came up with a surprising result. Healthy men taking vitamin E actually had a higher incidence of prostate cancer than other men
Access : The effect of bicycling on PSA levels: a systematic review and meta-analysis : Prostate Cancer and Prostatic Diseases
Our findings suggest that there is no effect of cycling on PSA; however, the limited number of trials and the absence of randomized controlled trials limit the interpretation of our results. Additionally, the median sample size only consisted of 42 subjects. Therefore, our study may have low statistical power to detect a difference in PSA.
Prostate Cancer and Prostatic Diseases - Physical activity and its mechanistic effects on prostate cancer
Over the past decade, data have emerged demonstrating the association between physical activity and prostate cancer risk. Although the precise biological mechanisms are not yet understood, it is postulated that physical activity may reduce the risk of prostate cancer directly or indirectly via inter-related biological pathways. In addition, several studies have shown decreased or inhibited growth of prostate cancer cells, increased apoptosis of prostate cancer cells, delayed tumor formation and suppressed metastasis. Furthermore, these studies hypothesize a variety of biological pathways mediating the growth inhibitory and pro-apoptotic effects of physical activity on human prostate cancer cells.

Screening and Diagnosis

You Were Wondering: When to screen for prostate cancer?
When to start screening is based on individual risk, but age 40 is a reasonable time to start screening for those at highest risk with genetic predispositions or strong family histories of prostate cancer at a young age. Otherwise healthy men at high risk with a family history or African American men should get screened between ages 40 and 45.
Dr. Samadi: New Study Showing Prostate Cancer Screening Improved by Complete Family History | Long Island New York
A new study is showing the increasing importance of understand and having a complete family history of prostate cancer and the correlation to gauging personal risk with greater accuracy.
Much research over the past few decades, has shown having a first, second or third-degree relative with prostate cancer raises a Caucasian man’s risks of the disease. For Caucasian males, a complete family history of prostate cancer among close and distant relatives may gauge personal risk with greater accuracy.
If an extensive family history exists and men are aware, it provides awider range to estimate individual risks that are potentially more accurate than those based on typical family health histories. Both maternal and paternal history are equally important.
Is histological prostate inflammation in an initial prostate biopsy a predictor of prostate cancer on repeat biopsy?
A histological inflammatory finding at the initial prostate biopsy was negatively associated with prostate cancer detection in repeat biopsy. This result could be useful to determine the need for repeat prostate biopsy in patients with persistently elevated prostate-specific antigen.

Biopsies, Genomics and Pathology

UroNav Fusion Biopsy System Offered at Dr. Samadi's Prostate Cancer Center... -- NEW YORK, Aug. 11, 2015 /PRNewswire/ --
NEW YORK, Aug. 11, 2015 /PRNewswire/ -- Renowned Urologist and Robotic Prostate Cancer Surgeon, Dr. David Samadi, solely offers the revolutionary UroNav Fusion Biopsy System for MRI-Guided Fusion Biopsy in men with an elevated PSA. Innovated from the company, Invivo, the UroNav brings the power of MRI Guided Biopsy to diagnosing prostate cancer. This technique has tremendously improved the detection and differentiation of high and low-risk prostate cancers. Integrating the use of an MRI makes for a much more accurate diagnosis, especially when it comes to the staging of the prostate cancer. 
The biology and pathology of “young age” prostate cancer | THE "NEW" PROSTATE CANCER INFOLINK
A recent article in the Journal of Clinical Pathology reviews available data about the epidemiology, biology, and clinical pathology of “young age” prostate cancer, which the authors define as clinically significant cancer in men under 55 years of age.
This review article by Hussein et al. is now available in full, on line, on the Medscape web site, and will probably be of significant interest to support group leaders, other prostate cancer educators, and men diagnosed with prostate cancer at such younger ages.
mpMRIs, targeted biopsies, and the accuracy of Gleason grading | THE "NEW" PROSTATE CANCER INFOLINK
A new study that is in press on line in the Journal of Urology addresses, very reasonably, the question of whether using targeted biopsy methods based on multiparametric MRI (mpMRI) data is improving our ability to accurately assess patient’s Gleason grades and scores prior to decisions about treatment.
According to the abstract of this new paper by the French clinical research team (Lanz et al., based in Paris), the answer appears to be a definitive “Maybe”.
A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score.
Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group.
The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.
We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including asimplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.
Molecular Profiles Can be Used for Early Detection of Aggressive Prostate Cancer - Cancer Therapy Advisor
In a first-ever study, findings identified five gene sets that can predict clinical outcome in independent patient cohorts with prostate cancer, according to researchers in England.1  
Combining gene copy number and gene expression data has yielded a new 100-gene risk-stratification signature for prostate cancer that appears to outperform prostate specific antigen (PSA) and Gleason scores, and might allow early detection of the most aggressive cases.
The five faces of prostate cancer? - Cancer Research UK - Science blog
Dr Lamb’s team has shown, for the first time, that prostate cancer can be divided into five distinct groups, each of which has a unique molecular signature that appears to predict how well a patient will do after surgery.
They found that by using this group of 100 genes – or gene signature – prostate cancer patients who’d had surgery to remove their prostate could be divided into five distinct sub-groups.
  • One group had lots of DNA deletions and consequently low activity of certain genes
  • Another had high amounts of DNA repetition which resulted in increased activity of specific genes.
  • Two more groups had very few copy-number alterations, or changes in activity.
  • The fifth and final group had some – but not too many – copy-number alterations.
Multimodal image-guided prostate fusion biopsy based on automatic deformable registration.
The prostate TRUS images are automatically segmented with a Hough transform-based random forest approach. The registration is based on the Coherent Point Drift algorithm to align surfaces elastically and to propagate the deformation field calculated from thin-plate splines to the whole gland.
RESULTS - The method, which has minimal requirements and temporal overhead in the existing clinical workflow, is evaluated in terms of surface distance and landmark registration error with respect to the clinical ground truth. Evaluations on agar-gelatin phantoms and clinical data of 13 patients confirm the validity of this approach.
MAPPING MOLECULES TO FIGHT CANCER
The Cancer Genome Atlas project, or TCGA, is a collaborative effort between the NHGRI and the National Cancer Institute. Since 2006, Hutter and her team have worked to characterize the various cancers in more precise terms. In nine years, they have mapped thousands of gene sequences, constructing molecular models, or “maps,” of the numerous types of tumors. By examining patterns of molecular changes between the healthy tissue and the tumor, the TCGA team was able to construct maps that will help doctors understand cancer better.
With these molecular-level models, Hutter hopes to change the medical field’s way of thinking about cancer as a single entity. “Five to ten years from now, people are never going to just say, ‘I have liver cancer,’” she explained. With this new research, doctors will be able to classify cancer in an entirely new way, giving individuals the tools to understand and describe their illness in more specific terms.

Tests

Cancer-detecting dogs approved for NHS trial | Life and style | The Guardian
Dogs capable of sniffing out cancer have been approved for use in a trial by the NHS. The charity Medical Detection Dogs has gained approval from Milton Keynes University Hospital for further trials, after an initial study showed specially trained dogs can detect prostate tumours in urine in 93% of cases.
It is hoped canine testing could help show up inaccuracies in the traditional Prostate-Specific Antigen (PSA) test, used to determine if men need a biopsy. The test has a high “false positive” rate, and many men are unnecessarily referred for the invasive procedure.
Smart Technology Could Improve Prostate Cancer Diagnosis - Aug 10 2015 12:27 PM - University of Birmingham - Labmate Online
A smart sensor chip able to pick up on subtle differences in glycoprotein molecules and believed to have ability to improve the accuracy and efficiency of prostate cancer diagnosis has been developed by scientists at the University of Birmingham.
The team of chemical engineers and chemists created the chip with synthetic receptors along a 2D surface to identify specific, targeted glycoprotein molecules that are differentiated by their modified carbohydrate chains, unlike current tests which rely heavily on antibodies which are less robust and have been shown to have a high rate of false-positive readings.

Imaging

Prostate Cancer and Prostatic Diseases - Magnetic resonance imaging on disease reclassification among active surveillance candidates with low-risk prostate cancer: a diagnostic meta-analysis
MRI, especially multiparametric (MP)-MRI, has a moderate diagnostic accuracy as a significant predictor of disease reclassification among AS candidates. The high NPV and specificity for the prediction of biopsy reclassification upon clinical follow-up suggest that negative prostate MRI findings may support a patient remaining under AS. Although the PPV and sensitivity for the prediction were relatively low, the presence of a suspicious lesion >10 mm lesion may suggest an increased risk for disease progression.

Treatment

Active Surveillance

Prostate cancer: Avoiding excess confirmatory biopsies : Nature Reviews Urology : Nature Publishing Group
A new predictive model could help omit unnecessary confirmatory biopsy in men with prostate cancer at low risk of reclassification on active surveillance.
The retrospective study, performed by researchers from the Memorial Sloan Kettering Cancer Center, NY, USA, included 392 patients diagnosed with Gleason score 6 prostate cancer upon initial biopsy.
Designing Normative Messages About Active Surveillance for Men With Localized Prostate Cancer.
The authors examined the acceptability of normative messages about active surveillance as a management option for patients with low-risk prostate cancer. Men with a diagnosis of localized prostate cancer who were recruited through prostate cancer support organizations completed a web-based survey (N = 331). They rated messages about active surveillance for believability, accuracy, and importance for men to hear when making treatment decisions.
The message "You don't have to panic … you have time to think about your options" was perceived as believable, accurate, and important by more than 80% of the survivors. In contrast, messages about trust in the active surveillance protocol and "knowing in plenty of time" if treatment is needed were rated as accurate by only about 36% of respondents.
For active surveillance to be viewed as a reasonable alternative, men will need reassurance that following an active surveillance protocol is likely to allow time for curative treatment if the cancer progresses.

Surgery

Similar to horseshoes and hand grenades
Close Surgical Margins Raise Risk of Prostate Cancer Return - Renal and Urology News
Close surgical margins in radical prostatectomy specimens are associated with biochemical recurrence (BCR) rates similar to those of positive surgical margins, according to a new study.
In study of 609 patients who underwent radical prostatectomy for prostate cancer, patients who had close and positive surgical margins on final pathology had 3-year BCR-free survival rates of 70.4% and 74.5%, respectively, a non-significant difference between the groups, Michael J. Whalen, MD, of the Icahn School of Medicine at Mount Sinai Hospital in New York, and colleagues reported. By comparison, patients with negative margins had a 3-year BCR-free survival rate of 90%, which was significantly higher than the rates for patients with close and positive margins. On multivariable analysis, patients with close margins had a 2.7-fold increased risk of BCR compared with those who had negative margins.

Radiation

New Data on Prostate Cancer, Salvage Radiation, and Survival
Patients experiencing biochemical failure — defined as an increase in prostate-specific antigen (PSA) level — after prostatectomy for prostate cancer often receive salvage radiation therapy (SRT) to control the disease and prevent metastases.
However, despite SRT, some patients still exhibit biochemical failure. Now, a long-term, single-center study, published online July 9 in the American Journal of Clinical Oncology, has demonstrated that outcomes for 61 men who experienced a biochemical recurrence after surgery, including a subset of 34 men who experienced failure twice (once after surgery and once after SRT), are robust.
The median overall survival was 13.6 years for the men in the study who had two biochemical recurrences and 14.7 years for the men who had just the one recurrence after surgery, report the authors, led by D. Nathan Kim, MD, PhD, from Texas Oncology in Waco.
Furthermore, the 10-year prostate-cancer-specific, metastasis-free, and castration-resistant-free survival (from the time of PSA failure after SRT) rates were all in excess of 70% for the men who had two biochemical recurrences.
Prostate Cancer and Prostatic Diseases - The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation therapy
Following radical prostatectomy, success of adjuvant and salvage radiation therapy (RT) is dependent on the absence of micrometastatic disease. However, reliable prognostic/predictive factors for determining this are lacking. Therefore, novel biomarkers are needed to assist with clinical decision-making in this setting. Enumeration of circulating tumor cells (CTCs) using the regulatory-approved Cell Search System (CSS) is prognostic in metastatic prostate cancer. We hypothesize that CTCs may also be prognostic in the post-prostatectomy setting. Our results suggest that CTCs may be indicative of disseminated disease and assessment of CTCs during RT may be helpful in clinical decision-making to determine, which patients may benefit from RT versus those who may benefit more from systemic treatments.
Men with intermediate- or high-risk prostate cancer experienced higher survival rates when given increased radiation doses than men with low-risk disease, according to researchers from Penn Medicine. In addition, men with low-risk disease but with already-high survival rates were unaffected by higher radiation doses.
Anusha Kalbasi, MD, and colleagues compared the survival rates of 42,481 men who were diagnosed between 2004 and 2006 and followed through 2012 and linked those rates with increased radiation doses in the National Cancer Database. The researchers investigated whether “radiation dose reduction for patients with low-risk prostate cancer could achieve similar cure rates while avoiding the increased risk of side effects associated with higher radiation doses,” said Kalbasi, a resident in the department of radiation oncology at the Perelman School of Medicine at the University of Pennsylvania. -
Judge Tells Aetna to Pay for Proton RT for Prostate Cancer
CORPUS CHRISTI, Texas, Aug. 6, 2015 /PRNewswire/ -- Today, Robert C. Hilliard of Hilliard Munoz Gonzales LLP (HMG) obtained an Order from a Newton County judge granting a restraining order against Aetna Insurance, preventing the insurance company from denying life-saving cancer treatment for his client, Bobby Allen Bean
Mr. Bean, a 1973 graduate of Newton County High School who has lived in Newton with his wife for over forty years, is suffering from advanced prostate cancer and is currently being treated at Houston's MD Anderson. Based upon Mr. Bean's medical history, his doctors have recommended that he receive Proton Radiation Therapy; the only other options to treat the cancer are too risky for Mr. Bean because he also suffers from insulin-dependent Type 2 diabetes. Despite his doctor's recommendations, his medical insurance carrier, Aetna, has refused to cover the treatment, claiming that it is "experimental."

Hormone

Androgen Deprivation for Localized Prostate Cancer Ups Cardiac Risks - Renal and Urology News
Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists is associated with an increased risk of cardiac events in elderly men with localized prostate cancer and a decent life expectancy, new findings suggest.
“Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged life expectancy,” the authors concluded in a paper published online ahead of print in BJU International. “Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT.”

Chemo

​How Tokai Pharmaceuticals is using precision medicine for prostate cancer - Boston Business Journal
Morrison says that study turned out to be key to Tokai’s pitch to investors. Her company already had Phase 2 data showing that its drug, called galeterone, worked in those same patients, who have a shortened version of something called the androgen receptor. In August of that year, the FDA had already approved Tokai’s reworked late-stage trial to focus on just those patients, which make up around a fifth of all patients with the disease. As long as galeterone’s demonstrated ability to stop the growth of prostate cancer in those patients held up, the trial had a high probability of success, since the NEJM study seemed to ensure that the drugs galeterone was being compared to — Zytiga, sold by Johnson & Johnson (NYSE: JNJ), and Xtandi, sold by Astellas ­— would have no effect at all.
New approach to decades old treatment yields increased survival for some prostate cancer patients - Medical News Today
For more than 60 years, the standard of care for patients with prostate cancer fueled by androgen hormones that has spread to other parts of the body has been androgen deprivation therapy (ADT). While the response rate is high, resistance to ADT often occurs. Generally, when ADT is no longer working, chemotherapy is administered for these patients. Research coordinated by the ECOG-ACRIN Cancer Research Group, supported in part by the National Cancer Institute, and published in the current online version of The New England Journal of Medicine, examined the outcomes of giving the chemotherapy drug docetaxel at the start of ADT. Results showed an increased survival of 13.6 months for patients treated with ADT plus docetaxel than with ADT alone. 
Androgen pathway resistance in prostate cancer and therapeutic implications.
Metastatic prostate cancer is an incurable disease that is treated with a variety of hormonal therapies targeting various nodes of the androgen receptor (AR) pathway. Invariably patients develop resistance and become castration resistant. Common treatments for castration-resistant disease include novel hormonal therapies, such as abiraterone and enzalutamide, chemotherapy, immunotherapy and radiopharmaceuticals. As this disease generally remains incurable, understanding the molecular underpinnings of resistance pathways is critical in designing therapeutic strategies to delay or overcome such resistance.

New Techniques

Researchers develop "intelligent" training tool to treat prostate cancer
Researchers at Carnegie Mellon University have developed a new approach to improve training for cryosurgery, a procedure used to treat prostate cancer by freezing and destroying the diseased tissues. The new approach will shorten the learning curve and improve the quality of the minimally invasive treatment by reducing complications, shortening recovery times and lowering health care costs.
Yoed Rabin, a professor of mechanical engineering and a board member of the American College of Cryosurgery, has led the development of this first computerized training tool. This intelligent training tool provides feedback to the trainee and offers advice on how to maximize the freezing of cancer tumors while preserving the healthy tissues surrounding the site.

Side Effects

Prostate Cancer May Impact Relationship Satisfaction Among Couples - Cancer Therapy Advisor
Results showed that both patients and spouses experienced reduced mental and physical health at 1 month after surgery, but health was mostly improved at 6 and 12 months.
Researchers found that patient's physical health correlated with patient's relationship satisfaction, and both patient's and spouse's mental health were associated with their own relationship satisfaction.
Another Side Effect of Cancer: Suicidal Thoughts
In a survey of prostate cancer survivors, Recklitis and his colleagues found that 12 percent of respondents experienced suicidal ideation in the previous year. Physical and emotional health, pain, work status, and incomewere found to be contributing factors. Depressed mood was linked with suicidal ideation. So was having a previous mental health condition[RC1] . There was no link between suicidal ideation and age. Type of treatment, recurrence, or time since diagnosis didn’t matter.

Advanced/Recurrence

Stretching survival from advanced prostate cancer | afr.com
A new study has confirmed that men with metastatic, hormone-sensitive prostate cancer can gain more than a year of survival when they simultaneously receive hormone-blocking medications and chemotherapy right after diagnosis.
Case Study: Newly Diagnosed Metastatic Prostate Cancer
Final CHAARTED data now published in NEJM | THE "NEW" PROSTATE CANCER INFOLINK
The final results of the CHAARTED trial, recommending early treatment with the combination of androgen deprivation therapy (ADT) and chemotherapy, at least in men with extensive metastasis at diagnosis, have just been published this week by Sweeney et al. in The New England Journal of Medicine (NEJM). The combination of these data with the data reported from the STAMPEDE trial at ASCO in 2015 has now provided compelling evidence supporting combination therapy (with ADT and docetaxel-based chemotherapy) for men newly diagnosed with metastatic prostate cancer — and most particularly for those men initially diagnosed with more extensive forms of metastatic disease.
Long-term Outcome of Prostate Cancer Patients Who Exhibit Biochemical Failure Despite Salvage Radiation Therapy After Radical Prostatectomy.
Salvage radiation therapy (SRT) is an effective treatment for recurrent prostate cancer (PCa) after radical prostatectomy. We report the long-term outcome of men who developed biochemical recurrence (BCR) after SRT and were treated >14 years ago. Extended  follow-up demonstrates that despite SRT failure, prostate cancer-specific survival (PCSS) was 84% and remains high in select patients. Early failure (≤1 y after SRT) predicted for significantly worse outcome and may represent a subgroup with more aggressive disease that may be considered for further prospective clinical studies.

No comments:

Post a Comment