Protocol for SARS-CoV-2 post-vaccine surveillance study in Australian adults and children with cancer: an observational study of safety and serological and immunological response to SARS-CoV-2 vaccination (SerOzNET).

BACKGROUND: Cancer is associated with excess morbidity and mortality from coronavirus disease 2019 (COVID-19) following infection by the novel pandemic coronavirus SARS-CoV-2. Vaccinations against SARS-CoV-2 have been rapidly developed and proved highly effective in reducing the incidence of severe COVID-19 in clinical trials of healthy populations. However, patients with cancer were excluded from pivotal clinical trials. Early data suggest that vaccine response is less robust in patients with immunosuppressive conditions or treatments, while toxicity and acceptability of COVID-19 vaccines in the cancer population is unknown. Unanswered questions remain about the impact of various cancer characteristics (such as treatment modality and degree of immunosuppression) on serological response to and safety of COVID-19 vaccinations. Furthermore, as the virus and disease manifestations evolve, ongoing data is required to address the impact of new variants. METHODS: SerOzNET is a prospective observational study of adults and children with cancer undergoing routine SARS-CoV-2 vaccination in Australia. Peripheral blood will be collected and processed at five timepoints (one pre-vaccination and four post-vaccination) for analysis of serologic responses to vaccine and exploration of T-cell immune correlates. Cohorts include: solid organ cancer (SOC) or haematological malignancy (HM) patients currently receiving (1) chemotherapy, (2) immune checkpoint inhibitors (3) hormonal or targeted therapy; (4) patients who completed chemotherapy within 6-12 months of vaccination; (5) HM patients with conditions associated with hypogammaglobulinaemia or immunocompromise; (6) SOC or HM patients with allergy to PEG or polysorbate 80. Data from healthy controls already enrolled on several parallel studies with comparable time points will be used for comparison. For children, patients with current or prior cancer who have not received recent systemic therapy will act as controls. Standardised scales for quality-of-life assessment, patient-reported toxicity and vaccine hesitancy will be obtained. DISCUSSION: The SerOzNET study was commenced in June 2021 to prospectively study immune correlates of vaccination in specific cancer cohorts. The high proportion of the Australian population naïve to COVID-19 infection and vaccination at study commencement has allowed a unique window of opportunity to study vaccine-related immunity. Quality of life and patient-reported adverse events have not yet been reported in detail post-vaccination for cancer patients. Trial registration This trial is registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001004853. Submitted for registration 25 June 2021. Registered 30 July 2021 (Retrospectively registered). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382281&isReview=true.

Use and outcomes of chemotherapy for metastatic pancreatic cancer in Australia.

BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is highly lethal. Combination chemotherapy regimens improve overall survival (OS). Historically, only one-third of mPDAC patients in Victoria received chemotherapy. AIM: To describe current Australian chemotherapy utilisation and outcomes in patients with mPDAC using the multi-site PURPLE (Pancreatic cancer: Understanding Routine Practice and Lifting End Results) registry. METHODS: PURPLE collects longitudinal data on consecutive patients with pancreatic cancer seen since January 2016. Data were collated for patients with mPDAC from six Victorian sites, and analysed descriptively. RESULTS: Three hundred and sixty-three patients with mPDAC were identified. Median age was 70 years (range 20-94 years). First-line chemotherapy was administered in 195 (54%) patients. Prevalent regimens included gemcitabine-nab-paclitaxel (71%), gemcitabine alone (10%) and FOLFIRINOX (6%). Sixty-two of 195 (32%) patients who received first line treatment have proceeded to second-line chemotherapy. Chemotherapy-treated patients were younger (69 versus 73 years; P < 0.01), with better Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1 89 vs 66%; P < 0.01) and lower median Charlson comorbidity index (3 vs 4; P < 0.01) compared with untreated patients. Median OS of the entire cohort from diagnosis of metastases was 5.1 months. Median OS was 9.3 months in the chemotherapy treated patients, and 2.5 months in chemotherapy-untreated patients (P < 0.01). CONCLUSIONS: A substantial proportion of patients with mPDAC still do not receive active treatment, which may in part by explained by age, poor performance status and comorbidity. Gemcitabine-nab-paclitaxel was the preferred first-line chemotherapy regimen. Median OS for treated patients in this cohort was comparable to that of recent published clinical trials.

Rapid Protocol Development, Study Startup and Enrolment of a Prospective Study of COVID-19 Vaccination for Patients with Cancer: A Collaborative Approach.

BACKGROUND: COVID-19 is an unprecedented global health emergency. It has been highly disruptive for patients with cancer, both due to an increased burden of severe illness and due to pressure on healthcare systems. COVID-19 vaccination has been an important public health measure for this patient group. AIM: The aim of this study was to describe the rapid design and startup of a multicentre study of COVID-19 vaccine response for vulnerable patients with cancer. Study startup: We set up a multicentre prospective observational study of COVID-19 vaccination response for Australian patients with cancer. Due to intensive collaboration between health services, the funding body and laboratories, we were able to develop a protocol and enrol the first patient within 52 days of the initial study proposal. Rapid startup was further enabled by prompt availability of funding and by high-level engagement of institutional review boards, allowing expedited review. Study enrolment: We rapidly enroled more than 500 patients, 80% within 4 months of study opening. Engagement and follow-up were maintained throughout the course of up to five serial vaccination doses. CONCLUSION: Our study is an example of intensive collaboration inspired by the COVID-19 pandemic and may serve as an example of an agile research response to real-time public health challenges.

The Role of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer.

Neoadjuvant systemic therapy has many potential advantages over up-front surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. Due to these advantages, neoadjuvant therapy is becoming the standard of care for an increasing number of tumor types. Currently, colon cancer patients are still routinely treated with up-front surgery, and neoadjuvant systemic therapy is not yet standard. Limitations to widespread use of neoadjuvant therapy have included inaccurate radiological staging, concerns about tumor progression while undergoing preoperative treatment rendering a patient incurable, and a lack of randomized data demonstrating benefit. However, there is great interest in neoadjuvant chemotherapy, and a number of trials are under way. Early follow up of the first phase III trial of neoadjuvant chemotherapy for colon cancer demonstrated tumor downstaging and suggested an improvement in disease-free survival with neoadjuvant chemotherapy, and it is hoped that this will translate into longer-term overall survival benefit. Clinicians should closely watch this developing field, consider the option of neoadjuvant chemotherapy for colon cancer patients, and actively seek out opportunities for their patients to participate in ongoing clinical trials to further inform this field in future.

Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges.

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.

A 2020 update of anal cancer: the increasing problem in women and expanding treatment landscape.

INTRODUCTION: Anal cancer is a rare malignancy with increasing incidence, notably in women. This disease is highly associated with HPV infection and its incidence and mortality are currently rising. Most patients present with localized disease which has a high survival after definitive treatment with chemoradiation. For patients who develop metastatic disease or present with this de novo, survival is poor. AREAS COVERED: This review provides a summary of current literature on anal cancer. With a focus on women, this includes current epidemiological trends, role of HPV, and the current and future treatment landscape, including HPV vaccination and immunotherapy. Screening currently focusses on HIV-positive men, missing most female cases. In curative disease, trials are investigating treatment de-intensification in good prognostic groups. Immunotherapy is showing early promise in the advanced disease setting. EXPERT OPINION: Similar to cervical cancer, anal cancer is strongly associated with HPV, and therefore, broader implementation of screening programs may reduce its incidence. HPV vaccination is expected to reduce the development of (pre)malignant anal lesions. The emergence of biomarkers will assist patient treatment selection, allowing optimal balance of treatment efficacy and morbidity. It is hoped that new treatment approaches, including immunotherapy, will improve outcomes. International collaboration is needed.

Incident hepatitis B infection subsequent to the diagnosis of HIV infection in a Melbourne cohort: missed opportunities for prevention.

UNLABELLED: Background The characteristics associated with incident hepatitis B (HBV) infection in HIV-positive individuals are not well described in the Australian setting. The aim of this study is to determine the characteristics of and risk factors for HBV infection within HIV-infected individuals in a Melbourne cohort between 1985 and 2011. METHODS: Individuals susceptible to HBV at their HIV diagnosis were identified using their HBV serology stored within the Victorian HIV database. Within this group, those who had a subsequent positive test for hepatitis B surface antigen or hepatitis B core antibody were identified as infected with HBV after their HIV diagnosis. Incident cases were matched with controls from the initially susceptible group who did not seroconvert for analysis. An incidence rate was calculated from the number of seroconversions and the cumulative time at risk (in 1000 patient-years of follow-up). RESULTS: Of the 4711 patients with HIV seen more than once, 3223 had HBV testing. Of the 174 with positive HBV test results, 39 individuals met the definition of seroconversion after HIV diagnosis, representing the incident cases. The estimated HBV incidence rate was 1.81 (95% confidence interval: 1.28-2.47) per 1000 patient-years at risk. These individuals form the basis of a detailed case series and case-control study. Data collected include demographic details, immunological and virological characteristics, antiretroviral treatment and vaccination history. CONCLUSIONS: HIV-infected individuals should be screened for HBV and monitored for incident infection. Optimal control of HIV and improved vaccination coverage provide the best opportunity for prevention.