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British Medical Journal – A (relatively) risky business: the link between prostatic radiotherapy and second malignancies

This article published yesterday in the British Medical Journal and showing the link between radiotherapy and secondary tumour, AVO1highlights the need for a more targeted radiotherapy – i.e. Proton Beam Therapy

There is a well recognized association between exposure to radiation and carcinogenesis. The development of second malignancies after therapeutic radiation depends on the primary malignancy, the dose to tissues at risk, and specific characteristics of the patient. There is a strong association between radiotherapy and second malignancies in people with Hodgkin’s lymphoma and patients with other cancers treated with radiotherapy.  Data linking radiotherapy for prostate cancer and subsequent malignancy have been less clear. Defining such a link has been difficult because the population is older and has a limited natural lifespan with prominent competing health risks. In addition, the relatively small number of outcomes in these analyses limits their statistical validity. Previous systematic reviews and one small meta-analysis reported inconsistent conclusions.

In a linked paper, Wallis and colleagues (doi:10.1136/bmj.i851) refresh the existing data with an updated comprehensive systematic review and meta-analysis of 21 studies evaluating the association between prostatic irradiation and likelihood of a second malignancy. Their analysis suggests an increased risk of bladder (odds ratio 1.39), rectal (1.62), and colorectal (1.68) cancers. A subgroup analysis of patients treated with radiotherapy compared with those treated surgically confirmed this risk. This analysis deals with a limitation of previous studies that used the general public as a control group, despite the known diagnostic bias toward identification of cancer in men with prostate cancer.

Previous studies have adopted variable “lag times” (ranging from two months to over 10 years) to define a tumor as “radiation induced.” The latency of such tumors likely varies by tissue type, individual biology, and age at exposure, among other factors. Importantly, in the absence of a clear biologically justified “lag time” for analysis, Wallis and colleagues confirmed that risk estimates after adjustment for “lag times” of both five or 10 years were consistent with their pooled risk estimates.

From the perspective of the radiation oncologist, this study “firms up” the suspicion that irradiation of the prostate increases the risk of second bladder and colorectal cancers in a time dependent manner. A pragmatist, however, might ask, what are the real world implications for individual patients? Despite an impressive relative risk, the absolute risk remains small, and the cancers discovered, although certainly requiring treatment, might not be lethal. This is particularly true of smaller bladder cancers discovered incidentally during cystoscopy for radiation related hematuria, which is a relatively common event. Indeed, there seems to be no survival difference between men with bladder cancers linked to previous prostate irradiation and bladder cancers identified in patients treated with surgery. Ultimately, clinicians and patients must decide together whether, for example, the roughly 1.4-1.7-fold increase in relative risk of a second malignancy after a 10 year lag period justifies alternative treatments. Young patients with few comorbidities might be more likely to factor this risk into their decision making, whereas older patients or those with competing health risks, might not and indeed should not.

Wallis and colleagues found a notable effect of “tissue volume,” and brachytherapy (high radiation dose to a small volume of tissue) was not associated with a detectable increase in risk. Therefore, the current move towards smaller tighter treatment volumes might well shift the contemporary risk back towards unity. Many studies included in this analysis were performed at a time when older poorly targeted radiation techniques were used, and large volumes of normal pelvic tissue were irradiated during treatment

While the absolute risk of second malignancy seems small, there might be subgroups with higher absolute risks and others for whom risks are negligible. Prospective analyses with large multi-institutional databases and registries could identify the predisposing characteristics of patients and culpable technical factors associated with radiation associated malignancies. Combination of these analyses with paired biologic samples of tumor and normal tissue might additionally permit investigation of subtle genetic or epigenetic factors that influence the likelihood of tumors associated with radiation.

For now, we note the risk of second malignancy after prostate irradiation confirmed by Wallis and colleagues and believe that management discussions and consent forms should feature this information. This analysis further supports the move towards even more tightly targeted external radiation techniques. Perhaps most important, this study confirms our belief that second malignancy should be added to the already long list of avoidable hazards associated with treatment for those men with low risk prostate cancer who simply need no treatment at all. Concern about second malignancies should not, however, stand in the way of an effective and well studied treatment being given to men with higher grade, lethal prostate cancer for whom the potential benefit simply dwarfs the risk.

Full article here

Advanced Oncotherapy – Birmingham University Supporting Cancer Treatment Research

The University of Birmingham is supporting ground-breaking research to create a proton Computed Tomography (CT) image that will help to facilitate the treatment of cancer patients in the UK. The researchers are using the University’s centrally funded HPC service, which was built by OCF, to simulate 1000 million protons, which takes just 3% of the time with HPC comparted with a desktop machine.

Proton therapy targets tumours very precisely using a proton beam and can cause less damage to surrounding tissue than conventional radiotherapy, which often makes it a beneficial treatment for children.

Full article here

Proton beam unit ‘for 700 patients’

Proton beam unit ‘for 700 patients’

Editor – Health News

The first cancer patients to get proton beam therapy at a UK centre will be treated in Newport by Christmas 2016. Experts say it should “transform” treatment for 700 patients a year, including children with hard to reach tumours. A former clinic will be converted and also offer traditional radiotherapy and chemotherapy.

Proton Partners International (PPI) set out its plans, saying it will cost the NHS less than sending patients abroad. Protons can be directed at tumours more precisely than X-rays and they stop once they hit the target rather than carrying on through the body. It makes operating on children’s tumours – and cancers close to sensitive areas like the spinal cord – more exact.

Full story here

Global proton therapy market will hit $1 billion by 2019

by Lauren Dubinsky , Staff Writer at DOTmed.com

Proton Beam Therapy machine

In 2014, there were 141 operational proton therapy treatment rooms globally, but by 2019 that number will jump to 330, according to a new MEDraysintell report. In addition, the proton therapy world market is expected to hit $1 billion by 2019.

“There is a growing [amount] of clinical evidence regarding the efficacy of proton therapy, that will progressively be used to treat a broader number of indications,” Paul-Emmanuel Goethals, co-founder of MEDraysintell, told DOTmed News. “In addition, the emergence of lower-cost/compact PT systems, is allowing more centers to be installed.”

The high cost of the systems was the main hurdle that stood in the way of widespread adoption of proton therapy technology. To solve that, almost all of the proton therapy manufacturers offer or are developing compact proton therapy systems.

Link here to full article

Shareprophets – How Advanced Oncotherapy Might Rise – Now a £20m Placing of New Shares Is Spoken For.

By Malcolm Stacey | Tuesday 5 May 2015

Disclosure: I own shares in one or more of the stocks mentioned. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from ShareProphets). I have no business relationship with any company whose stock is mentioned in this article.

Hello Share Trimmers. Investors in Advanced Oncotherapy (AVO) are in a peculiar situation. For though our shares are now trading at just a touch over 8p, they could be worth a lot more.

The share price has been held down by a huge placing of extra shares. These shares were lapped up by institutions and existing big shareholders.

We‘re told that this placing was over-subscribed. This suggests to me that the participants could have even paid a bit more for the new stock.

Two or three weeks ago, Advanced was on a massive roll. The stock rose to around 16p a shares from about 3p, just a few months before that.

So shareholders, myself included, were sitting on a huge profit at 16p. We should have cashed in then, as shares started to decay, helped by the company’s announcement that a placing was to take place.

It’s a wonderful thing hindsight, and I kick myself that instead of selling shares at the 15p point, I actually bought more. so my paper profits so far are not that great.

So what happens now? Well, the placing raised a massive £20 million. A large chunk will be used to build its exciting new machines for zapping cancer cells with proton beams.

That extra cash should be applauded by all shareholders as it means the project is now well on course. Perhaps it will stun the medical world, though I understand there is a little competition somewhere out there.

Now it has this money in the bag, Advanced’s future looks tempting to this medical layman. I do know that some very big cheeses in the cancer world are involved in this venture, some of them holding large numbers of shares.

The share is now little more than 8p, but I can now see acceleration, now that the placing is out of the way.

It’s a popular view, anyway, in the Punter’s Return. More here

Malcolm Stacey has been writing about shares for more than 20 years. His first book “The Armchair Tycoon” was first published in 1998 but a revised 2014 e-version is now available. To obtain a FREE copy fill in the form HERE

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