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5th July 2024
From September, Dr Petra Jankowska will begin her role as the newly elected medical director, professional practice, clinical oncology at the Royal College of Radiologists. She caught up with Julie Penfold to discuss her aims in the role, her passion for clinical research and improving patient care and her hopes for the future of oncology.
With such an esteemed career in clinical oncology, one might imagine this was always the career that Dr Petra Jankowska had in mind. Yet, she didn’t always plan to be an oncologist.
‘I originally thought I was going to be a respiratory physician. I spun around doing lots of different jobs in my training that I thought would be good for respiratory medicine, but I ended up doing oncology and fell in love with it,’ she recalls.
Now, Dr Jankowska is a consultant clinical oncologist at the Beacon Centre at Musgrove Park Hospital in Taunton, Somerset, UK, where she specialises in the treatment of patients with lung cancer and head and neck cancer. She was instrumental in the development of what has become a centre of excellence for cancer treatments, cementing the Beacon Centre’s reputation nationally.
She relishes the fast-moving pace of both oncology and radiotherapy and the way in which this allows clinicians to support patients in different ways.
‘There are lots of developments happening in both radiotherapy and in systemic therapies,’ she explains. ‘It’s always interesting, no single day is the same as the next and it’s a specialty that really holds the patient at the centre of all of our endeavours.’
Dr Jankowska has a keen interest in peer review of radiotherapy contouring. ‘Peer review can help to foster a more open, transparent and supportive way of working while improving treatment outcomes,’ she says.
Following her election as the Royal College of Radiologists (RCR)’s next medical director, professional practice (MDPP), clinical oncology – a role that will commence on 1 September 2024 – Dr Jankowska hopes to support the wider implementation and development of radiotherapy contouring peer review in oncology services across the UK.
The second edition of the RCR’s guidance on target volume definition and peer review, which Dr Jankowska co-authored, was published in 2022. But peer review has as yet not been routinely rolled out in every UK centre, and it is Dr Jankowska’s ambition to see it implemented in all oncology departments.
‘The idea of peer review is it provides an opportunity to have a second look at your work,’ she says. ‘When you come to do contouring peer review with a colleague, you might spot a lymph node that you previously missed due to poor lighting or simply work fatigue, for example. We want treatments to be precise and accurate and peer review can ensure we get it right.’
Harnessing the use of artificial intelligence (AI) could help to streamline how peer review is carried out to free up clinicians’ time. This could be especially beneficial for departments that have a smaller number of clinicians who may otherwise have to carry out peer reviews with colleagues at other centres remotely, where this would also impact on the time of another clinician.
‘It may be that AI or computer-assisted learning machines could help by doing a first read or first contour of radiotherapy outlines, although we’re certainly not there yet,’ Dr Jankowska explains. ‘Most of the AI tools I’ve come across have been in the context of contouring the organs at risk rather than the actual cancer target, but it’s a step in the right direction.’
Musgrove Park Hospital already has several AI tools in use. One is used in radiology for triaging the many chest X-rays coming through from primary care. This helps with identifying abnormal X-rays that need to be prioritised for human reporting, and a similar tool is used in assessing X-rays of trauma patients to identify fractures.
AI tools are also used to identify small lung nodules – triaging them according to risk of malignancy – which is particularly useful in the context of lung cancer screening, she explains.
Also in the cancer diagnostic realm is the potential for increased use of what patients often refer to as the ‘blood test for cancer’, Dr Jankowska says. Genomic analysis for circulating tumour DNA in this way, even in advance of a biopsy being carried out, can help clinicians to look for molecular mutations of certain cancers and assess whether particular targeted treatments might be helpful.
In terms of radiotherapy developments, Dr Jankowska says: ‘The UK is a little behind Europe in terms of its proton and heavy ion work because of lack of infrastructure. But what we can do well is work collaboratively across the UK with our members and fellows to have a unified, non-postcode-lottery type of cancer care. That’s where we really can find our strength and follow a little in the footsteps of countries such as Denmark.’
One of the biggest challenges Dr Jankowska sees affecting cancer treatment trajectories is that delayed effects of radiation therapy can occur many months and often years after a patient has undergone treatment and this can have a significant impact on their quality of life. Late effects services can help with symptom management and offer much-needed patient support, which is something else that’s top priority for Dr Jankowska.
‘We have to move from a place where we follow up people for five years and then discharge them if they are cured after radical or adjuvant treatment,’ she says. ‘It’s important there is recognition that some of these treatments do cause late effects.
‘Having these services for patients enables them to get back into the system if they do have longer-term side effects. While it’s great if we’re getting better outcomes and people are living longer as a result of good treatments for cancer, it’s not so great if we’re not also managing those late side effects.’
Dr Jankowska’s recent clinical research has focused on how radiation can be combined with other systemic treatments, particularly immune checkpoint inhibitors such as the much-investigated programmed death-ligand 1 (PD-L1) expression.
‘We know that lots of cancers have a high expression of PD-L1 and we have a number of treatments for that expression,’ she explains, ‘and we also know radiotherapy can upregulate those receptors.’
When immune checkpoint inhibitors are used after patients have had radiotherapy, there’s a potential synergy in how the two treatments work together. This is seen when immunotherapy has been used after concurrent chemoradiotherapy for lung cancer that couldn’t be operated on but was non-metastatic and was therefore potentially curable.
‘Before the PACIFIC clinical trial, lung cancer five-year survival rates were in the region of 20-25% but that has almost doubled now to around 44%,’ Dr Jankowska says. ‘It’s a phenomenal difference and there’s definitely something about the synergy in which radiotherapy works with immune checkpoint inhibitors that needs more exploration.’
She next awaits the results from the CompARE trial. Her team contributed to the national recruitment of oropharyngeal cancer patients with intermediate or high-risk features to take part in the study. It compared a combination of the chemotherapy drug cisplatin and radiotherapy with four other treatments to see which is optimal, as well as considering how treatments affect people’s day-to-day lives.
The first data could be available as soon as mid-2025 and Dr Jankowska and her team are already eager to learn what the results will show and determine how they might have a positive impact on patient care and outcomes.
The two-month countdown to Dr Jankowska starting her MDPP role is almost here, and once underway she will combine this work with her consultant role at the Beacon Centre. ‘I won’t be relinquishing any of my clinical work as I don’t have that luxury,’ she explains. ‘I work in a rural district general hospital where we don’t have a wealth of doctors to take on some of my clinical work.’
But she views this as a distinct advantage and says doing something that’s completely different to the clinical role can be ‘invigorating’ and ensures her finger remains on the pulse of clinical practice and faculty activities. Indeed, combining her roles will enable her to keep abreast of new developments and the direction of travel within oncology and radiology nationally, across Europe and beyond.
‘This will help me to bring ideas back to my department and share learnings from my clinical work with the RCR’s members and fellows,’ she adds.
This dialogue with members and fellows is something she’s particularly keen to generate and she would like to see them all being really engaged with the Royal College so it can continue to be a growing support for them.
What will be central to this is members and fellows feeling valued and heard. ‘Part of this is recognising that our workforce is our biggest asset,’ she adds. With a keen interest in the development of supportive medical leadership, Dr Jankowska is primed and ready to nurture the current and future workforce to ensure the implementation of best practice across the sector for the benefit of clinicians and patients alike.
20th July 2023
Immune checkpoint inhibitors have transformed the management of non-small cell lung cancer, but how long should treatment be continued for optimal survival? Clinical writer Rod Tucker takes a closer look at the evidence.
It has long been recognised that a hallmark of cancer is immune evasion and that the immune system is held back by inhibitory immune checkpoint receptors and ligands. The discovery that immune checkpoint inhibitors (ICIs) could interrupt these immune checkpoints and thereby provide an anti-tumour effect, leading to cancer regression, was a major therapeutic advance in oncology.
The first ICI to receive FDA approval was ipilimumab in 2011 and, since then, there have been several other agents approved by regulatory authorities across the world.
Lung cancer is the leading cause of global cancer incidence and mortality and it accounts for an estimated two million diagnoses and 1.8 million deaths worldwide, with non-small cell lung cancer (NSCLC) responsible for more than 80% of cases.
ICIs have been deployed in the management of NSCLC and drugs such as nivolumab have proved to be very effective treatments. Nevertheless, an important and practical consideration is how long to continue with the therapy. Guidance on the use of ICIs, such as the advice in the UK from NICE for pembrolizumab in NSCLC, recommends that treatment is halted after two years. However, in its guidance, the clinical experts at NICE accept that the optimal treatment duration is unknown and they acknowledge that extended duration treatment courses are likely to be burdensome for patients, hence the restriction.
But is this somewhat arbitrary limit of two years sufficient to derive an optimal survival response, or should it be longer? In the absence of objective evidence, clinicians are left to ponder whether adhering to this duration best serves the interests of their patients. Although some evidence indicates a prolonged survival with ICIs after treatment has ceased, there is clearly a need for more definitive data.
CheckMate 153 was the first randomised trial to examine the optimal duration of ICI therapy in patients with NSCLC. The trial compared a fixed one-year treatment regimen with nivolumab to a continuous one with exploratory analyses examining the incidence of adverse events, progression-free survival and overall survival. The results suggested a significant progression-free survival advantage favouring continuous treatment (hazard ratio, HR = 0.56, 95% CI 0.37 to 0.84).
The longest safety and efficacy data for patients with advanced NSCLC comes from the phase Ib KEYNOTE-001 study using pembrolizumab and included both previously treated and treatment naive patients. The findings, published in 2019, offered an insight of the five-year survival in those with advanced disease and the results were impressive. After 60.6 months, among previously treated patients, the median overall survival was 10.5 months in previously treated patients compared to 22.3 months in treatment-naive cohort.
Nivolumab also appears to provide impressive five-year survival data. In a study of previously treated patients with advanced NSCLC given nivolumab, the estimated five-year overall survival rate (after 96 weeks of therapy) was 16%.
Although these findings make clear that ICIs do improve survival in the longer term following cessation of treatment, there still remains the unanswered question as to how long is enough to derive these survival benefits.
The findings of a recent retrospective analysis could furnish clinicians with the answer they have been looking for.
Cognisant that most ICI trials continued for up to two years, researchers from the University of Pennsylvania evaluated the association between duration of therapy with overall survival. Publishing their findings in the journal JAMA Oncology, the team compared overall survival in those who had received ICI treatment for two years and those whose therapy continued for longer.
Survival outcomes were dichotomised as either between 700 and 760 days (i.e. two years, fixed duration) or greater than 760 days (i.e. an indefinite duration). After various adjustments for potential confounders, survival was found to be 79% in the two-year fixed-duration group and 81% for the indefinite-duration group. The hazard ratio for death associated with fixed-duration ICI therapy compared with the indefinite-duration group was non-significant (HR = 1.33, 95% CI 0.78 – 2.25, p = 0.29).
While there are recognised limitations from retrospective analyses, these findings do suggest that up to two years of ICI therapy is sufficient and that a longer duration – which is more costly and burdensome for patients – offers no survival benefit.
While guidance restricting the use of ICI therapy in NSCLC to no longer than two years might appear somewhat random, the latest evidence, although prefaced by important caveats, does appear to support that premise. Furthermore, the latest data should also offer reassurance to clinicians that these current restrictions are unlikely to affect their ability to deliver optimal care for patients with NSCLC.
8th April 2022
A meta-analysis by researchers from Beijing Tongren Hospital, Capital Medical University, Beijing, China, has concluded that adding radiotherapy to immune checkpoint inhibitors (ICIs)for the treatment of patients with melanoma offers no overall survival benefit despite a significant improvement in 12-month progression-free survival.
According to the World Cancer Research Fund, melanoma is the 19th most commonly occurring cancer in men and women, with nearly 300,000 new cases reported in 2018. Among patients whose melanoma has undergone metastases, ICIs, monoclonal antibodies which target the programmed death cell protein 1 (PD-1), the programmed death-ligand 1 (PD-L1), or the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), represent the standard of care.
Nevertheless, while effective, when used as mono-therapy, ICIs produce an overall response rate ranging from 0% to 17%, though these figures increase to more than 33.3% when the agents are combined.
Radiotherapy is routinely used in treatment of solid cancers, such as hepatocellular carcinoma (HCC) and several preclinical and clinical studies have explored the efficacy of combining radiotherapy and ICIs in HCC and with promising outcomes. Moreover, a meta-analysis of 11 studies found that combining ICIs with radiotherapy showed better local efficacy than ICI mono-therapy for treating melanoma brain metastasis.
Despite this, few studies have systematically examined the combined effect of ICIs and radiotherapy in the treatment of patients with melanoma.
For the present study, the Chinese team set out to summarise the efficacy of radiotherapy in combination with ICIs in the treatment of non-brain metastatic melanoma. They included all available trials such as single-arm and control studies in which the endpoints of overall response rate (ORR), overall survival (OS) or progression-free survival (PFS) were reported. The team used regression analysis and presented their results using odds ratios.
Immune checkpoint inhibitors and radiotherapy outcomes
After an extensive literature search, 9 articles (7 retrospective studies and 2 prospective cohort trials) involving 624 patients were identified and included in the analysis.
Combing radiotherapy with ICIs led to a higher ORR compared with ICIs alone (35% vs 20.4%, p = 0.004) However, in terms of OS, the 12-month odds ratio (OR) comparing the combination to ICI treatment alone was 1.83 (95% CI 0.32 – 5.52, p = 0.69) and hence not significantly different.
While there was no significant difference between the two treatment options in PFS at 6-months (OR = 0.53, 95% CI 0.26 – 1.08, p = 0.08), this difference became significant at 12-months (OR = 0.48, 95% CI 0.29 – 0.80, p = 0.005).
Commenting on these findings, the authors highlighted that with most studies being retrospective in nature and no randomised trials, there was a need for prospective trials to further explore the efficacy of combining radiotherapy with ICIs in melanoma.
They concluded that while, at present, there was no evidence of a survival benefit by combining the two therapies, an improvement in PFS was evident but further high quality trials were required to confirm these findings.
Citation
Yin G et al. Efficacy of radiotherapy combined with immune checkpoint inhibitors in patients with melanoma: a systemic review and meta-analysis Melanoma Res 2022
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