‘Tailored' prostate cancer treatment can give men extra time
Scientists have said a new drug combination has had an 'extraordinary' effect on some patients with no other hope, keeping the disease at bay for more than four years.
The Neptunes trial found that the drug cocktail could extend life when conventional hormone therapies have stopped working, shrinking tumours when given to the right patients.
Hormone-based drugs that block the production of testosterone, slowing or halting the growth of tumours, have become a front-line treatment for many men with metastatic prostate cancer that has spread to other organs.
However, the cancer eventually becomes resistant and finds a path to keep spreading.
The Telegraph is campaigning for the introduction of targeted prostate cancer screening to boost early diagnosis.
A late diagnosis of the disease has been linked to a far worse survival rate. Men diagnosed at an early stage have five-year survival rates of almost 100 per cent, compared to rates of around 50 per cent once it has spread beyond the prostate.
Dr Gianmarco Leone, an oncology researcher from the UCL Cancer Institute and the study's lead author, said the trial's findings were particularly promising because the 74 patients enrolled all had advanced cancer and limited options.
He said: 'With the standard options, the time that these patients could still benefit from treatment was measured in months, definitely not years. But for a small group of patients, we've seen these extraordinary responses where we were able to achieve long-term benefits.'
Previous attempts to use immunotherapy to treat prostate cancer have been largely unsuccessful, with less than 10 per cent of patients responding to the drugs in trials.
Compared with other cancers, many prostate tumours are 'immune-cold', which means they either cannot be recognised by the immune system or have a physical or chemical barrier that repels immune cells.
But the new research discovered that certain sub-populations of patients with advanced prostate cancer can be exceptions to the rule.
The trial by oncologists at University College London Hospitals (UCLH) examined the effect of a combination of immunotherapy drugs – nivolumab and ipilimumab.
Some 70 per cent of patients whose tumours have 'mismatch repair deficiency' – which have up to 20 times as many DNA mutations as other tumours – responded to immunotherapy, delaying disease progression by an average of 10 months.
In men with prostate cancer caused by the BRCA2 gene, which is better known for its link to breast cancer, 50 per cent responded to the drugs and subsequently went into remission for an average of 17 months.
Among men with a high concentration of immune cells around the tumour, 43 per cent had a positive response to the treatment.
As a result, a handful of participants were able to fend off the disease's progression for more than four years.
Dr Mark Linch, a senior author of the study and consultant oncologist at UCLH, said the results pointed towards more personalised approaches tailored to an individual's tumours being the future of advanced cancer treatment.
He said: 'I've been pushing this personalised approach, as unfortunately despite my advice, over the years, the pharmaceutical companies have tended to run very large trials in unselected populations [of prostate cancer patients].
'And while that's been a winner for lung cancers, melanomas and other tumour types, it's not worked for prostate cancer. So this was our effort to test a new strategy.'
Other scientists said they were particularly excited by the response rate in metastatic prostate cancer patients with mismatch repair deficiency.
Nick James, a professor of prostate and bladder cancer research at The Institute of Cancer Research, London, said far more men should be tested in case they have mismatch repair deficiency and could benefit from the new treatment.
Prof James said: 'This testing is not something that's done very much. So there are probably some patients who might benefit, who we're not testing and therefore never get this treatment.'
However, current statistics have shown that mismatch repair deficiency is only present in around 2 per cent of patients, while BRCA gene mutations occur in less than 10 per cent.
Although the Neptunes trial included 74 patients, other experts said they were keen to see the approach tested in a larger study of hundreds of patients with such sub-types of advanced prostate cancer.
They added that trials could combine it with hormone therapy to see if a dual approach would improve response rates even further.
Prof Prasanna Sooriakumaran, a professor of urology at the University of Oxford, said: 'It's really promising because prostate cancer was not previously thought to be very immunogenic.'
'Now we should see whether immunotherapy can have a synergistic effect with the proven treatments which are known to work.'
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Reuters
42 minutes ago
- Reuters
Biomechanics study shows how T. rex and other dinosaurs fed on prey
WASHINGTON, Aug 15 (Reuters) - Tyrannosaurus subdued prey with raw power, using bone-crushing bite force. But other meat-eating dinosaurs that rivaled T. rex in size used different approaches. Giganotosaurus relied more on slashing and ripping flesh. And the long and narrow snout of Spinosaurus was well-adapted for catching fish. Researchers have documented the feeding biomechanics of meat-eating dinosaurs in a comprehensive analysis of the skull design and bite force of 17 species that prowled the landscape at various times from the dawn to the twilight of the age of dinosaurs. The study found that Tyrannosaurus possessed by far the highest estimated bite force, with a heavily reinforced skull and massive jaw muscles. But it showed that other dinosaur predators evolved successful approaches to bringing down prey even without matching the T. rex chomp. "We found that large predatory dinosaurs didn't all evolve the same kind of skull to deal with the challenges of feeding at massive size," said vertebrate paleontologist Andre Rowe of the University of Bristol in England, lead author of the study published this month in the journal Current Biology, opens new tab. "Some, like T. rex, reinforced the skull to tolerate extremely high bite forces and the associated skull stresses. Others, like Allosaurus or Spinosaurus, went with lighter or possibly flexible builds that spread out stress in different ways. There's no single 'correct' way to be a giant meat-eater, and that's the point," Rowe added. The study focused on species within the group, or clade, called theropods that includes the meat-eating dinosaurs. They ran from Herrerasaurus, which lived in Argentina about 230 million years ago and is one of the earliest-known dinosaurs, all the way to T. rex, which was present in western North America when an asteroid struck Earth 66 million years ago and ended the age of dinosaurs. The researchers used three-dimensional models of the skulls of the 17 species, including two different specimens of Tyrannosaurus, and applied a method for simulating how structures respond to physical stress. They estimated muscle forces using digital muscle reconstructions based on living relatives of the dinosaurs - birds and crocodiles - then applied those forces to the skull models to simulate bites. "Our focus wasn't raw bite force. We were testing how the skulls distributed that force under load, and how these distributions varied by each lineage of carnivores," Rowe said. The early theropods examined in the study such as Herrerasaurus, which lived during the middle of the Triassic Period, and Dilophosaurus, which lived early in the Jurassic Period, exhibited much lower stress resistance than their later counterparts. They were lightly built dinosaurs and not well adapted to high bite forces, Rowe said. The increase in bite force and skull strength unfolded gradually over time, reaching its apex with Tyrannosaurus and its close relatives in a lineage called tyrannosaurs such as Daspletosaurus and Albertosaurus, which like T. rex appeared late in the Cretaceous Period. "In tyrannosaurs, there's a big jump in skull strength and bite mechanics, coinciding with deeper skulls, more robust bone architecture and changes in jaw muscle attachment. So the ramp-up wasn't immediate. It evolved over time and in certain lineages more than others," Rowe said. Tyrannosaurus, Giganotosaurus and Spinosaurus were three of the largest theropods, but their skulls were quite different. Perhaps the largest-known Tyrannosaurus is a specimen named Sue at the Field Museum in Chicago, at 40-1/2 feet (12.3 meters) long. Giganotosaurus and Spinosaurus rivaled T. rex in size. Giganotosaurus lived in Argentina in the middle of the Cretaceous, while Spinosaurus inhabited North Africa at around the same time, both predating Tyrannosaurus by roughly 30 million years. "Giganotosaurus was large, but its skull wasn't built for the same kind of high-force feeding as T. rex. Spinosaurus had a long, narrow snout, which is consistent with a diet focused on fishing, though we have fossilized evidence that it ate other animals, such as pterosaurs," Rowe said, referring to the flying reptiles that were cousins of the dinosaurs. One of the key takeaway messages, Rowe said, is that giant body size did not funnel all theropods toward the same design. Stronger bite force was one strategy, but not the only one, Rowe added. "Some animals win with raw power, others by striking quickly or repeatedly. What we're seeing here is a spectrum of ecological adaptations. These animals weren't all trying to be T. rex clones. They were solving the same problem in different ways," Rowe added. "That kind of evolutionary flexibility," Rowe added, "probably helped them dominate ecosystems for so long."
Daily Mail
an hour ago
- Daily Mail
Dying patients bundled into ambulances and transferred in their final hours after 'cruel' managers shut hospice without warning
Dying patients were bundled into emergency ambulances and moved in their final hours after managers shut down a hospice without warning. Nurses on duty at the Sue Ryder Wheatfields Hospice, in Leeds, were left in tears after being told to ring relatives of end-of-life patients with the distressing news that their loved ones were being immediately transferred. One nurse told the Mail she was disgusted by hospice management, who she claims sat in their offices eating an Indian takeaway while nurses scrambled to hand over their vulnerable patients to paramedics. In total, seven terminally ill residents were moved in emergency ambulances to alternative hospices across Yorkshire between 5pm and midnight on a Friday evening in August last year. Another patient was discharged home. One woman died within five hours of being moved, while another two patients had passed away within 48 hours. At least two families lodged formal complaints about their treatment in the aftermath. Recalling the distressing closure shift last summer, the female nurse told the Mail she knew nothing about the decision to shut until the angry son of a woman who was 'actively dying' started berating her about his mother's transfer. The nurse, who asked not to be named, said she had since sought treatment for depression because she felt guilty about the way several patients had been treated in their final hours. She tearfully explained: 'I was sitting at the bedside of a lady who I'd been nursing for a couple of weeks when her son came into the room and started saying, ''Call yourself a nurse, you're disgusting, how could you do this to my mum?'' 'He told me the hospice was closing immediately and his mum was being transferred in 10 minutes, he couldn't believe I didn't know anything about it. 'It was really upsetting, I was really taken aback I just didn't know what to say. 'Then one of the managers came down and confirmed it. She said it was because they didn't have enough staff, but that was not the case. We had a full compliment of doctors and nurses on that evening and over the weekend. I just started crying, it was so cruel. Within five minutes the first ambulance had arrived.' The short notice closure was the culmination of a 'chaotic' few months at the hospice, which staff alleged had become an 'unsafe and toxic' place to work because of the 'autocratic' behaviour of four of the most senior leaders – then interim service director, Sonia Clarke, head of clinical services, Victoria Hogg, head of operations, Quentin Krang, and chief nursing officer, Jane Turner. Two months later, in October last year, around 24 nurses and healthcare assistants lodged a formal grievance, via the Royal College of Nursing, with bosses at Sue Ryder, the national charity which runs the hospice with 30 per cent funding from the NHS. The hospice re-opened a month later but at least 20 staff have since left, with one lodging legal action, in the form of an employment tribunal, against the organisation. The nurses' grievance claimed the 'distressing' decision to close the unit at the 11th hour was deliberately concealed from them by managers, who then 'spun' an 'inaccurate narrative' to families of patients and local news outlets that they had no choice to do so because of staffing shortages. In reality, both medical and nursing staff levels were sufficient and instead nurses say the decision was made after whistleblowing allegations about the hospice's poor leadership had been lodged with the charity. Tracey Taylor Huckfield, the chief people and culture officer at Sue Ryder, who responded to the grievance, which was independently investigated, admitted the closure was 'distressing' because of a lack of communication with staff and that some did hear about it from relatives of a patient. She accepted the reasons for the closure communicated to families and the media 'were not the complete facts' and that 'whistleblowing concerns' had previously been raised. But she said that 'given the sensitivity and confidentiality of some matters' managers had 'no choice' but to be economical with the truth. Ms Taylor Huckfield accepted there was a lack of trust between managers and nurses, whose well-being had been neglected, and the senior leadership team did order a takeaway on the night the hospice closed because they were 'flagging.' However, she claimed all staff had been told to go and 'help themselves' if they wanted to eat. She dismissed the majority of the nurses' concerns, saying 'while this collective grievance highlights there have been issues and problems in communication, it is not considered that a serious breach of the organisation's values and behaviours has taken place.' However, nursing staff, who are being supported by whistleblowing charity Protect, were unconvinced and branded the investigation a 'whitewash.' They also lodged complaints about Sue Ryder to the Charity Commission, local Labour MP Alex Sobel, West Yorkshire Integrated Care Board and the Care Quality Commission, who carried out an emergency inspection in March. The Mail understands the CQC are preparing to publish their report, which staff expect to be critical of hospice management, in the coming days. One senior nurse, who has worked in the profession for almost four decades, including 10 years at the hospice, told the Mail: 'We feel let down. We've had to fight alone to get justice for the patients, their families and the people of Leeds who rely on these services. 'Wheatfields Hospice has been all but destroyed, the majority of the experienced nurses have resigned and it lurches from one crisis to the next. The CQC have already told us that, if it were not for our tenacity, this deplorable action by Sue Ryder would have gone unnoticed by regulators. 'It's really upsetting to watch relatives whose loved ones have died or are being cared for by the hospice running marathons, climbing mountains and raising money for this charity, when the reality is large amounts of their hard-fundraised money is going on lawyers' fees as they continue to try to discredit and get rid of staff who tried to blow the whistle. We have repeatedly complained to the national leadership of Sue Ryder, who have failed us. The charity is an absolute disgrace.' James Sanderson, chief executive of Sue Ryder, told the Mail the 'difficult decision' to close Wheatfields Hospice was made for 'patient safety reasons.' He claimed that the grievance, although not upheld, highlighted poor communication between senior leaders and nursing staff which has since been improved by the installation of a new management team. 'The decision (to close) was not taken lightly as we were acutely aware of the impact this would have on our patients, but we were left with no other option,' he said. 'Every healthcare setting must adhere to strict, safe staffing levels and we were unable to meet these due to sickness, vacancies and an investigation into the behaviours and working practices of some employees. 'We received and responded to two complaints from families whose loved ones had to be moved from the hospice and apologised for the distress. 'We stand by our decision to temporarily close. We will not compromise on patient safety.' A spokesman for the West Yorkshire Integrated Care Board said they were 'aware' of last August's closure, adding that they were working closely with Sue Ryder and were involved in 'decisions' about patient care to ensure it was of the highest quality. The CQC said they 'will publish our findings once our standard factual accuracy and quality assurance processes are complete.'
Daily Mail
2 hours ago
- Daily Mail
Shocking discovery reveals millions are living with undiagnosed neurological disorder
Many girls face years-long delays in receiving autism diagnoses, with many not diagnosed until adulthood, new research has shown. Diagnosing autism - which impacts more than 5million adults and over 2million children in the US - can be difficult because there is no definitive medical test, such as blood draws or MRI scans, to diagnose the disorder. Doctors instead must look at the child or adult's developmental history and behavior to make a diagnosis. In the recent study by Epic Research, researchers reviewed records from more than 338,000 patients who received their first autism spectrum disorder diagnosis between 2015 and 2024. They found that the median age at autism diagnosis declined slightly from seven years of age in 2015 to six years in 2024, thanks to improved understanding of the condition. However, they discovered that male patients are increasingly diagnosed earlier with the median age at diagnosis dropping from seven years in 2015 to five in 2024. This contrasts with the trend for females, with the median age of diagnosis remaining around the age of eight over the same period. Digging into the data further, the researchers discovered among male patients diagnosed with autism in 2024, 44 percent were under age five, compared to 34 percent for females. They said that this indicated that more than half of these female patients were diagnosed later than age five and 'might have benefitted from earlier diagnosis'. They also found that the proportion of female patients diagnosed as adults (aged 19 plus) was 25 percent in 2024, while 12 percent of males were diagnosed with autism as adults in the same year. Dr Brian Harris, a behavioral health and development physician at Orlando Health who was not involved in the study, says the diagnosis gap between girls and boys is largely due to the traditional diagnosis model. Offering an explanation as to why the gap exists, he says: 'Despite the benefits of early diagnosis and intervention, most autistic children are not diagnosed until they begin school, by which time they and their peers are expressing rigid gender-based stereotypes. 'That may be why the behavior of a loud and rowdy autistic boy catches attention while that of a quiet girl expressing subtler symptoms may not. 'In other words, the model we've been using to diagnose ASD is a male model, but we are changing that. 'Specialists at all levels are being trained to recognize symptoms in boys and girls because a diagnosis provides clarity, enhances understanding, and opens access to support, resources and services that can be life-changing.' Early research from the 1960s and 1970s estimated autism affected just two to four out of every 10,000 children, but the condition was poorly understood at the time. While diagnosis rates have steadily climbed over the years, they were already much higher by 2000, when the CDC reported a prevalence of 1 in 150 children aged eight or younger. This then jumped to one in 44 in 2018, one in 36 in 2020, and one in every 31 children in 2022 - a rate of 32.2 per 1,000. By comparison, early studies from the 1960s and 1970s estimated autism rates to be as low as 1 in 5,000. The most recent CDC report found wide geographic variation, with diagnosis rates ranging from roughly one in 100 in parts of south Texas to a striking one in 19 in San Diego. It also highlighted shifting demographic patterns: autism diagnoses were more frequent among Asian, Black, and Hispanic children than among White children — a trend first observed in the 2020 data. Researchers say the sharp rise in recent decades can be partially explained by improved screening, increased public awareness, and better access to services. While some blame an ultra-processed diet, chemicals and pesticides for the rise. The average age for an autism diagnoses is five, though the vast majority of parents notice differences in their children, particularly around social skills, as early as two years old. Looking ahead, Professor Rinehart says more research needs to be done to better understand the autistic gait. This will be particularly beneficial to children so that treatment plans can be tailored for their individual movement styles as they develop.
