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In this phase II, single arm trial (ACTRN12617000720314), we investigate if alternating osimertinib and gefitinib would delay the development of resistance to osimertinib in advanced, non-small cell lung cancer (NSCLC) with the epidermal growth factor receptor (EGFR) T790M mutation (n = 47) by modulating selective pressure on resistant clones. The primary endpoint is progression free-survival (PFS) rate at 12 months, and secondary endpoints include: feasibility of alternating therapy, overall response rate (ORR), overall survival (OS), and safety. The 12-month PFS rate is 38% (95% CI 27.5-55), not meeting the pre-specified primary endpoint. Serial circulating tumor DNA (ctDNA) analysis reveals decrease and clearance of the original activating EGFR and EGFR-T790M mutations which are prognostic of clinical outcomes. In 73% of participants, loss of T790M ctDNA is observed at progression and no participants have evidence of the EGFR C797S resistance mutation following the alternating regimen. These findings highlight the challenges of treatment strategies designed to modulate clonal evolution and the clinical importance of resistance mechanisms beyond suppression of selected genetic mutations in driving therapeutic escape to highly potent targeted therapies., (© 2024. The Author(s).)

Introduction: Evidence regarding the role of exercise in pancreatic cancer (PanCa) is limited and is derived exclusively under tightly controlled research conditions. This study aimed to quantify adherence, adverse events, and changes in physical and psychological outcomes in any patients with PanCa referred to undertake exercise during nonsurgical treatment., Methods: The study involved 22 patients with localized or metastatic PanCa undertaking a clinic-based exercise program during chemotherapy or chemoradiotherapy. The program included supervised aerobic and resistance exercise undertaken twice weekly for 12 wk and a 12-wk follow-up with supervised exercise optional dependent on patient preference and condition. Patients were monitored for adherence and adverse events. Objective and patient-reported outcomes were assessed at baseline, 12 wk, and 24 wk., Results: A total of 251 sessions were attended by 19 patients over the first 12 wk (attendance rate, 55%). Complete case analyses indicated significant ( P < 0.05) improvements in functional ability (5.2%-17.2%), muscle strength (16.9%-25.1%), and static balance (6.8%). There were no significant changes in body composition or patient-reported outcomes except for sleep quality, which deteriorated; however, at an individual level, several patients had clinically relevant improvements in cancer-related fatigue and quality of life. Patients who continued with supervised exercise to week 24 largely preserved improvements in functional ability, muscle strength, and static balance. No serious adverse events resulted from the exercise program., Conclusions: Individualized, supervised aerobic and resistance exercise in a clinic-based setting appears to be safe and may improve or maintain physical and psychological health in patients with PanCa undergoing nonsurgical treatment., (Copyright © 2022 by the American College of Sports Medicine.)

Introduction: Exercise is emerging as a therapy in oncology for its physical and psychosocial benefits and potential effects on chemotherapy tolerability and efficacy. However, evidence from randomised controlled trials (RCTs) supporting exercise in patients with borderline resectable or locally advanced pancreatic cancer (PanCa) undergoing neoadjuvant therapy (NAT) are lacking., Methods and Analysis: The EXPAN trial is a dual-centre, two-armed, phase I RCT. Forty patients with borderline resectable or locally advanced PanCa undergoing NAT will be randomised equally to an exercise intervention group (individualised exercise+standard NAT) or a usual care control group (standard NAT). The exercise intervention will be supervised and consist of moderate to vigorous intensity resistance and aerobic-based training undertaken two times a week for 45-60 min per session for a maximum period of 6 months. The primary outcome is feasibility. Secondary outcomes are patient-related and treatment-related endpoints, objectively measured physical function, body composition, psychological health and quality of life. Assessments will be conducted at baseline, prior to potential alteration of treatment (~4 months postbaseline), at completion of the intervention (maximum 6 months postbaseline) and 3-month and 6-month postintervention (maximum 9 and 12 months postbaseline)., Ethics and Dissemination: The EXPAN trial has been approved by Edith Cowan University (reference no.: 2020-02011-LUO), Sir Charles Gairdner Hospital (reference no.: RGS 03956) and St John of God Subiaco Hospital (reference no.: 1726). The study results will be presented at national/international conferences and submitted for publications in peer-reviewed journals., Trial Registration Number: ACTRN12620001081909., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Stage III non-small cell lung cancer (NSCLC) makes up a third of all NSCLC cases and is potentially curable. Despite this 5-year survival rates remain between 15% and 20% with chemoradiation treatment alone given with curative intent. With the recent exciting breakthroughs in immunotherapy use (durvalumab) for stage III NSCLC, further improvements in patient survival can be expected. Most patients with stage III NSCLC present initially to their general practitioner (GP). The recommended time from GP referral to first specialist appointment is less than 14 days with treatment initiated within 42 days. Our review found that there is a shortfall in meeting these recommendations, however a number of initiatives have been established in Australia to improve timely and accurate diagnosis and treatment patterns. The lung cancer multidisciplinary team (MDT) is critical to consistency of evidence-based diagnosis and treatment and can improve patient survival. We aimed to review current patterns of care and clinical practice recommendations for stage III NSCLC across Australia and identify opportunities to improve practice in referral, diagnosis and treatment pathways., (© 2019 John Wiley & Sons Australia, Ltd.)

Introduction: Given the poor prognosis for patients diagnosed with pancreatic cancer, therapies that enhance the ability to tolerate adjuvant treatments, reduce the loss of physical functioning and optimize quality of life are critically important. Exercise may represent such a therapy; however, no previous research has investigated the potential impact of exercise on outcomes in pancreatic cancer patients., Purpose: This study aimed to determine the safety and efficacy of a 6-month supervised exercise program in a pancreatic cancer patient undergoing adjuvant treatment., Methods: A case study was performed on a 49-yr-old male diagnosed with stage IIb pancreatic cancer. The patient had surgery (Whipple resection) followed by adjuvant chemotherapy (gemcitabine and fluorouracil) and radiotherapy (45 Gy). The patient initiated a supervised exercise program involving twice weekly resistance and aerobic exercise sessions during adjuvant therapy. Outcomes were assessed at baseline and after 3 and 6 months of exercise., Results: The exercise program was well tolerated with 73% attendance throughout the 6 months. No treatment toxicities prevented the patient from complying with adjuvant treatment plans. Considerable improvements were observed at both 3- and 6-month assessment points for all measures of physical capacity and functional ability, lean mass, physical activity levels, general health and disease-specific quality of life, cancer-related fatigue, sleep quality, and psychological distress., Conclusions: In this first reported clinical case, exercise led to improvements in a variety of patient outcomes during adjuvant therapy for pancreatic cancer. This initial evidence has important clinical implications, indicating that exercise may be an effective adjunct therapy for the management of pancreatic cancer. Future trials are needed to confirm and expand our initial findings.

We report two cases of the rare neurological paraneoplastic syndrome, limbic encephalitis, as the initial presentation of small cell lung cancer. The first case responded to treatment of the underlying malignancy, while the second required more acute treatment in the intensive care setting. In this case, initial treatment was with immunosuppression to achieve a degree of stability before the underlying malignancy could be treated. Both cases had significant improvement in neurological function. These cases highlight the importance of directed investigation to try and identify an underlying malignancy in patients in whom a diagnosis of limbic encephalitis is made, and the difficulty in managing such patients., (© 2011 Blackwell Publishing Asia Pty Ltd.)

Introduction: BLP25 liposome vaccine (L-BLP25) is an innovative therapeutic cancer vaccine designed to induce an immune response resulting in elimination of tumor cells expressing the MUC1 antigen, which is overexpressed in non-small-cell lung cancer (NSCLC). Manufacturing modifications have produced subtle changes to the lipid A acyl chain composition of L-BLP25. This open-label phase II study was conducted to evaluate the safety of the new formulation in patients with unresectable stage IIIA/IIIB NSCLC., Patients and Methods: Twenty-two patients received L-BLP25 1000 µg every week for 8 weeks plus best supportive care. Maintenance vaccinations were given every 6 weeks, commencing at week 13, until disease progression., Results: Median treatment duration was 9.9 months (range, 1-30 months), 9 patients remain on treatment, and 8 have received treatment for > 2 years. Fifteen patients (68%) had adverse events considered to be related to L-BLP25: these were all grade 1/2, except for 1 grade 3 event (pneumonia). The most common adverse events were injection-site reactions (bruising [23%], erythema [18%], pain [14%], fatigue [18%], and influenza-like illness [14%]). After a median follow-up of 26.7 months, the 1-year survival rate was 82% (95% CI, 66%-98%), and the 2-year survival rate was 64% (95% CI, 44%-84%)., Conclusion: The results suggest that the new formulation of L-BLP25 has a safety profile similar to the original formulation and is safe to use in the phase III clinical development program.