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Cancer

Digestive system diseases Consensus statement 20 May 2019 Free

Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement

Testing for hepatitis B in all patients with haematological and solid tumour malignancies, and prophylactic treatment in for people with chronic HBV or past exposure to HBV, is recommended to avoid HBV reactivation during cancer therapy

Joseph Doyle · Michelle Raggatt · Monica Slavin · Sue‐Anne McLachlan · Simone I Strasser · Joseph J Sasadeusz · Jessica Howell · Krispin Hajkowicz · Harshal Nandurkar · Anna Johnston · Narin Bak · Alexander J Thompson

Mja2 50160
Digestive system diseases Research 11 March 2019 Free

The burden of pancreatic cancer in Australia attributable to smoking

The knownThe future pancreatic cancer burden attributable to tobacco smoking has not been estimated in Australia. The newNearly 22% of the future burden of pancreatic cancer is attributable to current and former smoking, 15% (5500 cases over the next 10 years) to current smoking alone. The smoking‐related burden of pancreatic cancer is markedly higher for men and for people under 65. The implicationsReducing smoking rates among men and people under 65 would have the greatest impact on reducing the future burden of pancreatic cancer in Australia.

Maria E Arriaga · Claire M Vajdic · Robert J MacInnis · Karen Canfell · Dianna J Magliano · Jonathan E Shaw · Julie E Byles · Graham G Giles · Anne W Taylor · Tiffany K Gill · Vasant Hirani · Robert G Cumming · R Paul Mitchell · Emily Banks · Julie Marker · Barbara‐Ann Adelstein · Maarit A Laaksonen

Mja2 12108
Cancer Narrative review 14 January 2019 Free

Radiotherapy and immunotherapy: a synergistic effect in cancer care

At present, high level evidence for the safety and efficacy of radiotherapy and immunotherapy still need to be demonstrated clinically; therefore, the combination cannot be recommended outside of clinical trials. It is also currently unclear which patients will benefit from the combination. However, due to the increased number of clinical trials investigating radiotherapy as a mean to antitumour immunity, it is likely that the evidence will emerge shortly.40,41 In 2016, a study presented a list of 93 active trials combining radiotherapy with an antibody inhibiting CTLA‐4, PD‐1 and PD‐L1, transforming growth factor β‐cytokine, or other immune molecules.40 ClinicalTrials.gov now reports at least 200 completed or recruiting trials evaluating the new combination. Box 1 lists investigator‐initiated clinical trials combining radiotherapy and immunotherapy in Australia. If positive, the results of these trials are likely to lead to a paradigm shift in the use of radiotherapy, which would certainly be a cost‐effective and low toxicity mean to enhance the response to immune agents in addition to its well established role of killing tumour cells. 3 Trial name (trial registration no.) Phase Disease (stage) Radiotherapy dose Immunotherapy Question SABRSeq (NCT03307759) 1b (randomised) NSCLC (IV) 18–20 Gy/1 fraction to 1–3 metastases, 7 days before ICIs 18–20 Gy/1 fraction to 1–3 metastases, 7 days after ICIs Pembrolizumab Safety profile of SABR with ICIs when given before or after SABR RAPPORT (NCT02855203) 1b/2 (single arm) RCC (oligometastatic IV) 18–20 Gy/1 fraction to 1–5 metastases, 5 days before ICIs Pembrolizumab Safety profile of SABR with pembrolizumab BOSTON‐II (closed) (NCT02303366) 1b (single arm) Breast (oligometastatic IV) 20 Gy/1 fraction to 1–5 metastases Pembrolizumab Safety profile of SABR with pembrolizumab AZTEC (TROG 17.05) 2 (randomised) Breast triple negative (IV with ≥ 2 metastases) 20 Gy/1 fraction to 1–4 metastases 24 Gy/3 fractions to 1–4 metastases Delivered before ICIs Atezolizumab Efficacy and safety of two SABR fractionation with atezolizumab ICE‐PAC (ACTRN12618000954224) 2 (single arm) Prostate (mCRPC) (IV) 18–20 Gy/1 fraction to 2–3 metastases, 5 days before ICIs Avelumab rPFS at 24 weeks NIVORAD (TROG 16.01) 2 (randomised) NSCLC (IV) 18–20 Gy/1 fraction to ≥ 1 metastases 14 days after ICIs No radiotherapy Nivolumab PFS at 6 months SABR‐IMPACT I (ACTRN12616001064493) (U1111‐1185‐5624) 1 (multilevel) Melanoma (non‐oligometastatic IV) 10–30 Gy/1 fraction to single metastasis, before or during ICIs Ipilimumab, nivolumab or pembrolizumab Maximum tolerated dose of SABR with ICIs PCR‐MIB (NCT02662062) 2 (single arm) Bladder (II–III post‐TURBT) 64 Gy/32 fractions + concurrent cisplatin + ICIs Pembrolizumab Grade 3 or 4 acute toxicities (excluding urinary) ABC‐X Study (NCT03340129) 2 (single arm) Melanoma (brain metastasis IV) SRS: 16–22 Gy/1 fraction or 30 Gy/10 fractions whole brain Ipilimumab and nivolumab Intracranial response to immunotherapy Ave‐Rec (NCT03299660) 2 (single arm) Rectal carcinoma (III) 50.4 Gy/28 fractions + 5FU, before ICIs Avelumab Pathological response rate ICIs = immune checkpoint inhibitors. 5FU = fluorouracil. mCRPC = metastatic castration‐resistant prostate cancer. NSCLC = non‐small cell lung cancer. PFS = progression‐free‐survival. RCC = renal cell carcinoma. rPFS = radiological progression‐free survival. SABR = stereotactic ablative radiotherapy. TURBT = transurethral resection of bladder tumour. ◆ Much needs to be understood to optimise the complex immunological effect of radiotherapy and its interaction with ICIs. Histological subtype, target organ (bone, visceral, brain), immunotherapy molecule, volume of irradiation, radiotherapy dose and sequence are hypothesised to have different effects. Radiotherapy pulsing, in which doses of radiation are delivered regularly (eg, monthly) throughout the ICI therapy, has also been proposed.64In conclusion, ICIs result in impressive clinical responses in select groups of patients, but optimal results in larger populations will require combination with other therapies. Radiotherapy will certainly be part of this arsenal, but fundamental questions about mechanisms of treatment non‐redundancy, tumour resistance and patients’ tolerance are to be answered. Preclinical studies to direct informed clinical trial design are needed to determine how best to integrate these modalities and optimise their synergistic effect.

Guy‐Anne Turgeon · Andrew Weickhardt · Arun A Azad · Benjamin Solomon · Shankar Siva

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Cancer Letter 14 January 2019 Free

Clinical Oncology Society of Australia position statement on exercise in cancer care

To the Editor: We write to express our concerns regarding the Clinical Oncology Society of Australia (COSA) position statement on exercise in cancer care published in the MJA1 and promoted in media outlets as a “world‐first” position statement that calls for exercise to be prescribed for all patients with cancer.2 The guideline replicates those first published in Australia in 20093 and in the United States in 20104 as well as by other organisations,5 and are the same as public health recommendations for healthy adults.6 Given the array of cancers, disease stages and treatments and their combinations, it is somewhat surprising that the same general guideline is being prescribed for all patients with cancer and is not differentiated from that for healthy adults — especially, given patient health and comorbidity status and the challenges that a cancer diagnosis and treatment entail. Research in exercise oncology has progressed over the past 9 years, and more targeted and tailored guidelines reflecting the developing evidence base are now required for implementation in this population. Moreover, the majority of patients with cancer are unable to meet the COSA recommendation of at least 150 minutes of aerobic exercise and two to three resistance exercise sessions due to time availability and physical, psychological and financial capacity as well as access, let alone the level of care required for those with advanced disease. It is significant that the COSA recommendation has not been refined through clinical trials in patients with cancer and has the potential to create considerable angst for the patient and raise concerns for clinicians, who know that their patients may not be able to achieve such goals. Moreover, we highlight that there is minimal financial support for patients with cancer to undertake ongoing exercise, making the COSA recommendation somewhat superfluous. When exercise is prescribed, it must be evidenced‐based and tailored to specifically ameliorate adverse health problems, while recognising that certain modes and dosages of exercise may be detrimental. We agree that there is considerable potential for exercise medicine in the management of cancer; however, a more considered approach needs to be implemented rather than the generic exercise recommendations of the COSA statement.

Robert U Newton · Dennis R Taaffe · Daniel A Galvao

Cancer Guideline Summary 2 December 2018 Free

Methods of melanoma detection and of skin monitoring for individuals at high risk of melanoma: new Australian clinical practice guidelines

Early detection of primary melanoma remains an effective strategy to reduce melanoma‐related mortality. This article presents multiple methods of monitoring the skin in patients at high risk of developing melanoma. Determining the relative indications for each method and how each method should be introduced into the surveillance of a patient requires careful consideration and an individualised approach.TBP and SDDI provide different methods for the detection of change in the context of melanoma surveillance and, therefore, these methods should be applied to different, but overlapping (ie, non‐mutually exclusive), settings. TBP permits identification of most new or changed lesions on the skin surface. TBP is particularly suited to patients at elevated risk with high naevus counts and multiple dysplastic naevi. SDDI fulfils a different need for monitoring one or many individual flat lesions of concern that lack diagnostic clinical or dermoscopic features of melanoma. Of note, both TBP and SDDI rely on patient adherence to follow‐up appointments, and poor compliance would thus compromise the benefits that these methods confer. It is therefore crucial to emphasise to patients the importance of regular follow‐up.Much of the existing literature has been conducted in high risk patient cohorts; however, these techniques, particularly TBP, are less tested in lower risk populations and may not have the same value. To undertake a randomised controlled trial evaluating these methods in high risk patients would present ethical difficulties; nevertheless, a randomised controlled trial of TBP and SDDI in a large cohort of lower risk individuals might be justifiable. Further research is needed to elucidate the optimal risk thresholds for the introduction of both TBP and SDDI to surveillance programs. Research regarding cost‐effectiveness for the above‐mentioned diagnostic aids in different risk cohorts is also required. Specialised surveillance with TBP and SDDI has been shown to be a cost‐effective strategy for the management of individuals at high risk of melanoma. Notwithstanding the demonstrated cost‐effectiveness in high risk patients, these modalities are not currently reimbursed by the Australian Medicare system.Furthermore, RCM may be used to assist with the identification of melanoma for suspicious lesions located on the head and neck, lesions in areas that are subject to chronic sun exposure, lesions dermoscopically typified by regression and amelanotic tumours. At present, there is insufficient evidence to recommend the routine use of automated instruments for the clinical diagnosis of melanoma. Nonetheless, the use of both automatic instruments and of artificial intelligence for the clinical diagnosis of melanoma represents an exciting area for future research. Further research should also be directed at assessing the performance of new methods of skin imaging, such as three dimensional imaging, the role of teledermatology using TBP, dermoscopy and SDDI, and skin self‐assessment of suspicious lesions using smartphone applications. Of note, TBP also has the potential to aid skin self‐examination; yet, evidence to date would appear to indicate limited uptake by consumers. An important area for future research might also be to explore barriers to and determinants of skin self‐examination, and to investigate appropriate methods of educating consumers with respect to melanoma surveillance.

Nikki R Adler · John W Kelly · Pascale Guitera · Scott W Menzies · Alex J Chamberlain · Paul Fishburn · Alison E Button‐Sloan · Clinton Heal · H Peter Soyer · John F Thompson

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Cancer Letters 19 November 2018 Free

Retention of medical records of patients with high-risk medical devices

To the Editor:Legislation mandates that all adult medical records be retained for a minimum of 7 years from the time of last patient contact, after which they can be destroyed. Exceptions to this requirement exist for young patients, and there are state-by-state variations, but there is no legislative requirement to retain records of patients who have implantable, high-risk devices. This is disturbing because many of these devices have an in vivo lifespan that exceeds 7 years. Of particular concern are patients with breast implants whose records may have been destroyed before a diagnosis of breast implant-associated anaplastic large cell lymphoma, which has an average latency period from implant to diagnosis of 9 years.1 Later presentations of this lymphoma are not uncommon, with latency intervals up to 23 years;2 therefore, it is imperative that implant details are retained to enable us to better understand the pathophysiology of this potentially fatal disease, which has been strongly associated with deeply textured surface implants. While the Australian Breast Device Registry (ABDR) is a safe repository for secure information on patients who are registered, those patients who are not may be at risk of losing important information about their implants. Furthermore, the expected lifespan of in vivo breast implants is at least a decade,3 so records may have been discarded at the time of patients presenting with serious implant-related problems. In our efforts to improve the safety of patients with breast implants, 30% of whom are breast reconstruction cases for cancer or congenital deformities, we encourage all practitioners to ensure that their patients are registered with the ABDR so their implant details are securely stored.4 In an effort to preserve the details of all Australian patients with breast implants, the ABDR can also store patient implant details retrospectively and will accept information from Australian patients having cosmetic tourism surgery overseas, after which significant complications can arise.5 It may be time, however, for legislation to be enacted to lengthen the mandatory retention period for patients with high-risk devices or to make it legally compulsory for practitioners inserting high-risk devices to enrol all patients into a clinical quality registry such as the ABDR.

Rodney D Cooter · Ingrid Hopper · John J McNeil

Cancer Letters 19 November 2018 Free

Hypertrophic lichen planus mistaken for squamous cell carcinoma

To the Editor:Lichen planus is an autoimmune mucocutaneous inflammatory disorder. Diagnosis is often made clinically and confirmed on biopsy.1 Hypertrophic lichen planus is a distinct subtype characterised by pruritic, hyperkeratotic plaques. Histopathological findings may not have the typical features of lichen planus and can mimic squamous cell carcinoma (SCC).2 Distinguishing between hypertrophic lichen planus and SCC can be difficult for clinicians and pathologists. In our dermatology practice, we encountered three patients initially diagnosed with SCC, but on review, the cases were consistent with lichen planus. One patient was a 52-year-old woman presenting with asymmetrical, raised and violaceous lesions to her lower legs. She was referred to a skin cancer clinic that performed biopsies of these lesions, which were reported as well differentiated SCC. These lesions were excised, but they were recurrent and were excised again. The second patient was a 54-year-old man who presented with a one-year history of eruptive raised, violaceous lesions to his chest and legs. Biopsies were reported as SCC and multiple lesions were excised by a general surgeon. The third patient was a 77-year-old woman with a 2-year history of pruritic lesions to the lower legs (Box). Biopsies were reported as well differentiated SCC. Each of these patients underwent numerous excisions before being referred to our practice. The patients were reassessed and new biopsies taken, and the clinical picture was discussed with a dermatopathologist. Hypertrophic lichen planus was confirmed as the diagnosis in each of these patients, and they responded well to prednisone, acitretin and topical steroid treatment. SCC may arise in long-standing hypertrophic lichen planus, but it should be emphasised that cases of supposed SCC with atypical history should not be treated without consideration of the many mimics of SCC, including pseudoepitheliomatous hyperplasia, irritated seborrhoeic keratosis, coral reef granuloma, hypertrophic lupus erythematosus and hypertrophic lichen planus. Clinicians should provide clinical description and a list of potential differentials when referring to a pathologist. Adequate biopsy depth is important, as lichenoid activity may only be present at the tips of the rete ridges, which may be missed on a superficial biopsy. These cases highlight the difficulties in distinguishing hypertrophic lichen planus from SCC. In the cases we described, correct diagnosis was made after re-evaluation and clinicopathological correlation. Box – Figure showing violaceous hyperkeratotic patches on the patient’s lower leg, with original biopsies reported as squamous cell carcinoma (A). Histopathology showed a lichenoid inflammatory infiltrate confined to the tips of the rete processes (B)* * Infiltrate is composed of predominantly lymphocytes with few eosinophils and plasma cells. While these features are typical of hypertrophic lichen planus, superficial shave biopsies may not capture the lichenoid infiltrate at the rete processes.

Emily X Shao · Benjamin Carew · James Muir

Cancer Research 24 September 2018 Free

Surveillance improves survival of patients with hepatocellular carcinoma: a prospective population-based study

Survival may be improved by surveillance, as it enables curative therapies to be initiated

Thai P Hong · Paul J Gow · Michael Fink · Anouk Dev · Stuart K Roberts · Amanda Nicoll · John S Lubel · Ian Kronborg · Niranjan Arachchi · Marno Ryan · William W Kemp · Virginia Knight · Vijaya Sundararajan · Paul Desmond · Alexander JV Thompson · Sally J Bell

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