ORCID Profile
0000-0002-0515-6130
Current Organisation
The Institute of Cancer Research
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Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475018
Abstract: Table S1. Frequency of DILD as per category
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6528971.V1
Abstract: AbstractPurpose: Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. Patients and Methods: A total of 2,499 consecutive patients with advanced cancer on phase I clinical trials were included. DILD was identified by a dedicated radiologist and investigators, categorized per internationally recognized radiological patterns, and graded per Common Terminology Criteria for Adverse Events (CTCAE) and the Royal Marsden Hospital (RMH) DILD score. Clinical and radiological features of DILD were analyzed. Results: Sixty patients overall (2.4%) developed DILD. Median time to onset of DILD was 63 days (range, 14–336 days). A total of 45% of patients who developed DILD were clinically asymptomatic. Incidence was highest in patients receiving drug conjugates (7.4%), followed by inhibitors of the PI3K/AKT/mTOR pathway (3.9%). The most common pattern seen was hypersensitivity pneumonitis (33.3%), followed by nonspecific interstitial pneumonia (30%), and cryptogenic organizing pneumonia (26.7%). A higher DILD score [OR, 1.47, 95% confidence interval (CI), 1.19–1.81 i P /i 0.001] and the pattern of DILD (OR, 5.83 for acute interstitial pneumonia 95% CI, 0.38–90.26 i P /i = 0.002) were significantly associated with a higher CTCAE grading. The only predictive factor for an improvement in DILD was an interruption of treatment (OR, 0.05 95% CI, 0.01–0.35 i P /i = 0.01). Conclusions: DILD in early-phase clinical trials is a toxicity of variable onset, with erse clinical and radiological findings. Radiological findings precede clinical symptoms. The extent of the affected lung parenchyma, scored by the RMH DILD score, correlates with clinical presentation. Most events are low grade, and improve with treatment interruption, which should be considered early. /
Publisher: American Association for Cancer Research (AACR)
Date: 15-09-2020
DOI: 10.1158/1078-0432.CCR-20-0454
Abstract: Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. A total of 2,499 consecutive patients with advanced cancer on phase I clinical trials were included. DILD was identified by a dedicated radiologist and investigators, categorized per internationally recognized radiological patterns, and graded per Common Terminology Criteria for Adverse Events (CTCAE) and the Royal Marsden Hospital (RMH) DILD score. Clinical and radiological features of DILD were analyzed. Sixty patients overall (2.4%) developed DILD. Median time to onset of DILD was 63 days (range, 14–336 days). A total of 45% of patients who developed DILD were clinically asymptomatic. Incidence was highest in patients receiving drug conjugates (7.4%), followed by inhibitors of the PI3K/AKT/mTOR pathway (3.9%). The most common pattern seen was hypersensitivity pneumonitis (33.3%), followed by nonspecific interstitial pneumonia (30%), and cryptogenic organizing pneumonia (26.7%). A higher DILD score [OR, 1.47, 95% confidence interval (CI), 1.19–1.81 P & 0.001] and the pattern of DILD (OR, 5.83 for acute interstitial pneumonia 95% CI, 0.38–90.26 P = 0.002) were significantly associated with a higher CTCAE grading. The only predictive factor for an improvement in DILD was an interruption of treatment (OR, 0.05 95% CI, 0.01–0.35 P = 0.01). DILD in early-phase clinical trials is a toxicity of variable onset, with erse clinical and radiological findings. Radiological findings precede clinical symptoms. The extent of the affected lung parenchyma, scored by the RMH DILD score, correlates with clinical presentation. Most events are low grade, and improve with treatment interruption, which should be considered early.
Publisher: Wiley
Date: 03-2018
DOI: 10.1111/AJCO.12867
Abstract: To characterize the outcomes of patients with nonmelanoma solid tumors receiving anti-PD-1 immunotherapy not funded by the Australian Pharmaceutical Benefits Scheme. Medical records of patients with metastatic nonmelanoma tumor diagnoses treated with anti-PD-1 (self-funded pembrolizumab or nivolumab through an access program) from January 1, 2014, to December 31, 2016, at Peter MacCallum Cancer Centre, were retrospectively reviewed. Events after December 31, 2016, were censored. Of 47 patients identified, 27 (57%) had lung cancer. Twenty-six had compassionate access to nivolumab (24 lung, one renal, one gastroesophageal with possible new lung primary). Median overall survival was 5.7 months. Eleven (23%) achieved a partial response none had complete response. Twenty (43%) had disease progression on first imaging 16 (48%) of these continued treatment beyond radiological progression, with three achieving subsequent partial responses. Ten (21%) were not re-staged mostly due to rapid deterioration or death. At 6 and 12 months, nine (20%) and two (4%) remained on treatment, respectively. Five (12%) discontinued treatment due to immune-related toxicities. Of 34 patients who died, 71% received treatment within the last month of life 38% died in an acute hospital. None of 25 patients with poor Eastern Cooperative Oncology Group performance scores of 2-4 responded. The response rates and overall survival of patients with NSCLC, renal carcinoma and triple negative breast cancer of good performance status receiving anti-PD-1 therapy outside of a clinical trial are consistent with clinical trial data. However, patients with poor ECOG performance status are unlikely to respond. Careful patient selection and counseling about the potential outcomes of self-funding treatment in this setting is needed.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475018.V1
Abstract: Table S1. Frequency of DILD as per category
Publisher: Elsevier BV
Date: 07-2020
Publisher: Wiley
Date: 09-04-2015
DOI: 10.1111/AJCO.12348
Abstract: Ipilimumab is a human anti-CTLA-4 monoclonal antibody recently approved for the treatment of advanced melanoma. Stimulation of T-cell activity unmasks antitumor activity, but can cause immune-related adverse events. Autoimmune hypophysitis is of particular importance because its presentation can be subtle but life threatening. We present two cases where early recognition of ipilimumab-related autoimmune hypophysitis led to timely intervention and low subsequent morbidity, without compromise of antitumor effects. We provide recommendations for detection and management of this potentially life-threatening complication of ipilimumab.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475015.V1
Abstract: Table S2. DILD Characteristics
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.CTARC.2021.100309
Abstract: Early-phase cancer clinical trials are becoming increasingly accessible for patients with advanced cancer who have exhausted standard treatment options and later phase trial options. Many of these trials mandate research tissue biopsies. Research biopsies have been perceived as ethically fraught due to the perception of potential coercion of vulnerable human subjects. We performed an audit of two years of practice to assess the safety of ultrasound (US)-guided research biopsies, and to look at the yield of a simultaneous tumour next-generation sequencing (NGS) and immunohistochemistry (IHC) molecular characterisation programme. We show that in our institution, US-guided research biopsies were safe, produced adequate tumour content and in a selected subset who underwent in-house NGS sequencing, showed a high rate of actionable mutations with 30% having a Tier 1 variant. Nevertheless, these research biopsies may only provide direct benefit for a minority of patients and we conclude with a reflection on the importance of obtaining truly informed consent.
Publisher: Springer Science and Business Media LLC
Date: 16-10-2023
Publisher: S. Karger AG
Date: 2019
DOI: 10.1159/000501211
Abstract: b i Introduction: /i /b The cancer research community increasingly question the rigidity of eligibility criteria in clinical trials. Common reasons for “screen failure” (RFSF) are well documented however, their effect on subsequent standard therapy (SST) and outcomes is unclear. b i Methods: /i /b This retrospective study evaluated patients aged ≥18 years with solid malignancy who were listed as ineligible on a screening log between February 2011 and March 2018. Patients screen-failed for biomarker results or incorrect cancer stage rior treatment profile were excluded. Data were collected from electronic hospital records, including demographics, cancer history, RFSF, subsequent therapy, and outcomes. b i Results: /i /b Overall, 217 patients were eligible. The most common histologies were lung (28%), melanoma, colon, and pancreatic (all 11%) 90% were metastatic. The most common RFSF were rapid disease progression (PD 16%), performance status (PS) ≥2 (12%), and abnormal liver function tests (aLFT 12%). After screen failure, 129/217 (59%) had SST 9 were dose-reduced. Treatment-naïve or phase III trial-ineligible patients were more likely to receive SST than those pre-treated or phase I trial-ineligible (72/104 vs. 52/113, i /i = 0.0006 71/109 vs. 15/42, i /i = 0.00013), respectively. RFSF stabilised/improved in 104/217 (48%) the main RFSF was co-morbidity (19/104). The most common RFSF to deteriorate were rapid PD (27/72), PS ≥2 (20/72), and aLFT with liver metastases (LM 13/72). b i Conclusions: /i /b RFSF related to organ function rarely deteriorate unless directly involved with underlying malignancy. Most RFSF do not prevent patients from having SST, nor increase dose reductions, especially in treatment-naïve hase III trial-ineligible patients. Those with RFSF of poor PS, rapid PD, and aLFT from LM are less suitable for SST. Careful broadening of trial eligibility is warranted.
Publisher: Innovative Healthcare Institute
Date: 07-09-2021
DOI: 10.36401/JIPO-21-9
Abstract: Immune checkpoint inhibitors (ICIs) are increasingly a standard of care for many cancers these agents can result in immune-related adverse events (irAEs) including fever, which is common but can rarely be associated with systemic immune activation (SIA or acquired HLH). All consecutive patients receiving ICIs in the Drug Development Unit of the Royal Marsden Hospital between May 2014 and November 2019 were retrospectively reviewed. Patients with fever ≥ 38°C or chills/rigors (without fever) ≤ 6 weeks of commencing ICIs were identified for clinical data collection. Three patients met diagnostic criteria for SIA/HLH with median time to onset of symptoms of 10 days. We describe the clinical evolution, treatment used, and outcomes for these patients. High-dose steroids are used first-line with other treatments, such as tocilizumab, immunoglobulin and therapeutic plasmapheresis can be considered for steroid-refractory SIA/HLH. SIA/HLH post ICI is a rare but a potentially fatal irAE that presents with fever and a constellation of nonspecific symptoms. Early recognition and timely treatment are key to improving outcomes.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475021
Abstract: Figure S1A. Correlation of patterns of DILD as per ATS/ERS classification and clinical severity. AIP correlated significantly with worse severity (P=0.002). NSIP, non-specific interstitial pneumonia COP, cryptogenic organizing pneumonia AIP, acute interstitial pneumonia HP, hypersensitivity pneumonitis. Figure S1B. A higher RMH DILD score predicts for increasing clinical severity of DILD as per CTCAE grading. Shown are CTCAE grading and RMH DILD Score at the time of DILD detection. Box plot mapping RMH DILD Scores against CTCAE grading showing statistically significant worsening of CTCAE grading and symptoms with higher RMH DILD score (P=0.004) DILD was confirmed to be the cause of death in one patient who had an initial RMH DILD score of 5 and was asymptomatic with an excellent partial response to therapy and so was continued on therapy. This patient then developed symptomatic DILD with a worsening RMH DILD score of 8, deteriorated and died. RMH DILD score, Royal Marsden Hospital Score for drug induced interstitial lung disease CTCAE, Common Terminology Criteria for Adverse Events Version 5.0. Figure S2. Continuation of IMP following radiological detection of asymptomatic DILD resulting in clinical deterioration. Images from a patient with breast cancer treated with an investigational drug-conjugate. Patient had no prior lung disease and no lung metastases at baseline. Cartoons (left) show RMH DILD scoring of matched sagittal radiographic images (right). The first row shows initial development of radiographic changes after 2 cycles of treatment when patient was asymptomatic (RMH DILD score of 5) and otherwise had a remarkable RECIST PR. With a further cycle of treatment, the changes had significantly worsened (RMH DILD score of 8), with development of rapidly progressive clinical symptoms which was ultimately fatal despite treatment with antibiotics, steroids, and respiratory support.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475027.V1
Abstract: Figure S1A. Correlation of patterns of DILD as per ATS/ERS classification and clinical severity. Figure S1B. A higher RMH DILD score predicts for increasing clinical severity of DILD as per CTCAE grading.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475024
Abstract: Figure S2. Continuation of IMP following radiological detection of asymptomatic DILD resulting in clinical deterioration.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475015
Abstract: Table S2. DILD Characteristics
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475027
Abstract: Figure S1A. Correlation of patterns of DILD as per ATS/ERS classification and clinical severity. Figure S1B. A higher RMH DILD score predicts for increasing clinical severity of DILD as per CTCAE grading.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475021.V1
Abstract: Figure S1A. Correlation of patterns of DILD as per ATS/ERS classification and clinical severity. AIP correlated significantly with worse severity (P=0.002). NSIP, non-specific interstitial pneumonia COP, cryptogenic organizing pneumonia AIP, acute interstitial pneumonia HP, hypersensitivity pneumonitis. Figure S1B. A higher RMH DILD score predicts for increasing clinical severity of DILD as per CTCAE grading. Shown are CTCAE grading and RMH DILD Score at the time of DILD detection. Box plot mapping RMH DILD Scores against CTCAE grading showing statistically significant worsening of CTCAE grading and symptoms with higher RMH DILD score (P=0.004) DILD was confirmed to be the cause of death in one patient who had an initial RMH DILD score of 5 and was asymptomatic with an excellent partial response to therapy and so was continued on therapy. This patient then developed symptomatic DILD with a worsening RMH DILD score of 8, deteriorated and died. RMH DILD score, Royal Marsden Hospital Score for drug induced interstitial lung disease CTCAE, Common Terminology Criteria for Adverse Events Version 5.0. Figure S2. Continuation of IMP following radiological detection of asymptomatic DILD resulting in clinical deterioration. Images from a patient with breast cancer treated with an investigational drug-conjugate. Patient had no prior lung disease and no lung metastases at baseline. Cartoons (left) show RMH DILD scoring of matched sagittal radiographic images (right). The first row shows initial development of radiographic changes after 2 cycles of treatment when patient was asymptomatic (RMH DILD score of 5) and otherwise had a remarkable RECIST PR. With a further cycle of treatment, the changes had significantly worsened (RMH DILD score of 8), with development of rapidly progressive clinical symptoms which was ultimately fatal despite treatment with antibiotics, steroids, and respiratory support.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6528971
Abstract: AbstractPurpose: Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. Patients and Methods: A total of 2,499 consecutive patients with advanced cancer on phase I clinical trials were included. DILD was identified by a dedicated radiologist and investigators, categorized per internationally recognized radiological patterns, and graded per Common Terminology Criteria for Adverse Events (CTCAE) and the Royal Marsden Hospital (RMH) DILD score. Clinical and radiological features of DILD were analyzed. Results: Sixty patients overall (2.4%) developed DILD. Median time to onset of DILD was 63 days (range, 14–336 days). A total of 45% of patients who developed DILD were clinically asymptomatic. Incidence was highest in patients receiving drug conjugates (7.4%), followed by inhibitors of the PI3K/AKT/mTOR pathway (3.9%). The most common pattern seen was hypersensitivity pneumonitis (33.3%), followed by nonspecific interstitial pneumonia (30%), and cryptogenic organizing pneumonia (26.7%). A higher DILD score [OR, 1.47, 95% confidence interval (CI), 1.19–1.81 i P /i 0.001] and the pattern of DILD (OR, 5.83 for acute interstitial pneumonia 95% CI, 0.38–90.26 i P /i = 0.002) were significantly associated with a higher CTCAE grading. The only predictive factor for an improvement in DILD was an interruption of treatment (OR, 0.05 95% CI, 0.01–0.35 i P /i = 0.01). Conclusions: DILD in early-phase clinical trials is a toxicity of variable onset, with erse clinical and radiological findings. Radiological findings precede clinical symptoms. The extent of the affected lung parenchyma, scored by the RMH DILD score, correlates with clinical presentation. Most events are low grade, and improve with treatment interruption, which should be considered early. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22475024.V1
Abstract: Figure S2. Continuation of IMP following radiological detection of asymptomatic DILD resulting in clinical deterioration.
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Crescens Diane Tiu.