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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.

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC. [ABSTRACT FROM AUTHOR]

Different strategies based on peptides are available for cancer treatment, in particular to counter-act the progression of tumor growth and disease relapse. In the last decade, in the context of therapeutic strategies against cancer, peptidebased vaccines have been evaluated in different tumor models. The peptides selected for cancer vaccine development can be classified in two main type: tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs), which are captured, internalized, processed and presented by antigen-presenting cells (APCs) to cell-mediated immunity. Peptides loaded onto MHC class I are recognized by a specific TCR of CD8+ T cells, which are activated to exert their cytotoxic activity against tumor cells presenting the same peptide-MHC-I complex. This process is defined as active immunotherapy as the host's immune system is either de novo activated or restimulated to mount an effective, tumorspecific immune reaction that may ultimately lead to tu-mor regression. However, while the preclinical data have frequently shown encouraging results, therapeutic cancer vaccines clinical trials, including those based on peptides have not provided satisfactory data to date. The limited efficacy of peptide-based cancer vaccines is the consequence of several factors, including the identification of specific target tumor antigens, the limited immunogenicity of peptides and the highly immunosuppressive tumor microenvironment (TME). An effective cancer vaccine can be developed only by addressing all such different aspects. The present review describes the state of the art for each of such factors. [ABSTRACT FROM AUTHOR]

The incidence of lung cancer continues to grow globally, contributing to an ever-increasing load on healthcare systems. Emerging evidence has indicated lowered efficacy of conventional treatment strategies, such as chemotherapy, surgical interventions and radiotherapy, prompting the need for exploring alternative interventions. A growing focus on immunotherapy and the development of personalized medicine has paved the way for vaccine-based delivery in lung cancer. With various prominent targets such as CD8 + T cells and PD-L1, immune-targeted, anti-cancer vaccines have been evaluated in both, pre-clinical and clinical settings, to improve therapeutic outcomes. However, there are a number of challenges that must be addressed, including the scalability of such delivery systems, heterogeneity of lung cancers, and long-term safety as well as efficacy. In addition to this, natural compounds, in combination with immunotherapy, have gained considerable research interest in recent times. This makes it necessary to explore their role in synergism with immune-targeted agents. The authors of this review aim to offer an overview of recent advances in our understanding of lung cancer pathogenesis, detection and management strategies, and the emergence of immunotherapy with a special focus on vaccine delivery. This finding is supported with evidence from testing in non-human and human models, showcasing promising results. Prospects for phytotherapy have also been discussed, in order to combat some pitfalls and limitations. Finally, the future perspectives of vaccine usage in lung cancer management have also been discussed, to offer a holistic perspective to readers, and to prompt further research in the domain., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplasm, with surgical resection and adjuvant chemotherapy the only curative treatment. Treatment-related toxicities place a considerable burden on patients although exercise training has shown promise is helping to manage such adversities and facilitate rehabilitation. The feasibility and safety of exercise training as a supportive therapy during adjuvant chemotherapy remains unknown. Methods: Patients with PDAC were screened post-surgical resection and enrolled in a 16-week, progressive, concurrent exercise programme alongside their chemotherapy regimen. Feasibility was the primary objective detailing recruitment, retention and adherence rates throughout as well as the safety and fidelity of the intervention. Secondarily, the impact on functional fitness and patient-reported outcomes was captured at baseline, post-intervention and 3-month follow up. Results: Eight patients consented to participate in this trial, with five proceeding to enrol in exercise training. Concurrent exercise training is feasible and safe during adjuvant chemotherapy and prevented an expected decline in functional fitness and patient-reported outcomes during this time. Discussion: This case series provides preliminary evidence that concurrent exercise training during adjuvant therapy is safe, feasible and well tolerated, preventing an expected decline in functional fitness, muscular strength and health-related quality of life (HRQoL). Given the adverse effects of treatment, these findings are promising and provide further evidence for the inclusion of exercise training as a standard of care for surgical rehabilitation and managing treatment-related toxicities. Future research should explore the impact of exercise training during neoadjuvant chemotherapy, with prehabilitation now standard practice for borderline resectable disease. Trial registration: ClinicalTrials.gov Identifier: NCT04305067, prospectively registered 12/03/2020, https://classic.clinicaltrials.gov/ct2/show/NCT04305067. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of systemic therapy on health-related quality of life (HRQoL) in patients with advanced esophagogastric cancer in daily clinical practice. This study assessed the HRQoL of patients with esophagogastric cancer during first-line systemic therapy, at disease progression, and after progression in a real-world context. Methods: Patients with advanced esophagogastric cancer (2014–2021) receiving first-line systemic therapy registered in the Prospective Observational Cohort Study of Oesophageal-gastric cancer (POCOP) were included (n = 335). HRQoL was measured with the EORTC QLQ-C30 and QLQ-OG25. Outcomes of mixed-effects models were presented as adjusted mean changes. Results: Results of the mixed-effect models showed the largest significant improvements during systemic therapy for odynophagia (− 18.9, p < 0.001), anxiety (− 18.7, p < 0.001), and dysphagia (− 13.8, p < 0.001) compared to baseline. After progression, global health status (− 6.3, p = 0.002) and cognitive (− 6.2, p = 0.001) and social functioning (− 9.7, p < 0.001) significantly worsened. At and after progression, physical (− 9.0, p < 0.001 and − 8.8, p < 0.001) and role functioning (− 15.2, p = 0.003 and − 14.7, p < 0.001) worsened, respectively. Trouble with taste worsened during systemic therapy (11.5, p < 0.001), at progression (12.0, p = 0.004), and after progression (15.3, p < 0.001). Conclusion: In general, HRQoL outcomes in patients with advanced esophagogastric cancer improved during first-line therapy. Deterioration in outcomes was mainly observed at and after progression. Implications for cancer survivors: Identification of HRQoL aspects is important in shared decision-making and to inform patients on the impact of systemic therapy on their HRQoL. [ABSTRACT FROM AUTHOR]

Purpose. Exercise is emerging as an adjunct therapy to cancer treatment; however, its role in older patients with advanced pancreatic cancer undergoing first-line chemotherapy is unclear. The aim of this study was to primarily provide evidence on feasibility with an exploratory examination of the initial efficacy of exercise in this clinical setting. Materials and Methods. Six patients aged 60–75 years with de novo or recurrent advanced pancreatic cancer undergoing first-line chemotherapy consented to participate in twice-weekly exercise that included resistance and aerobic training and boxing-related activities for up to 12 weeks. Patients were monitored for attendance, adherence, and adverse events. Body composition, muscle strength, functional ability, patient-reported outcome measures, and patient-reported experience measures were assessed at baseline and/or postintervention. Results. Of the 6 patients, 1 withdrew after baseline testing and 5 attended 42%–95% of planned sessions and adhered to 28%–83% of the prescribed exercise. There were no serious exercise-emergent adverse events. All 5 patients increased or maintained lean mass (0.1%–4.4%) and 4 reduced fat mass (−0.4%–−8.6%). Improvements were observed in 4 or all 5 patients for muscle strength (7.1%–75%), 5 times sit-to-stand (1.3%–21.4%), 6-m backward walk (16.5%–35.8%), and patient-reported outcomes. Furthermore, all patients perceived exercise as very helpful in managing their cancer and expressed a strong willingness to continue exercise in the future. Conclusion. A multimodal exercise program appears feasible with potential physical and psychological benefits for older patients with advanced pancreatic cancer undergoing first-line chemotherapy. Further research including a larger sample size is warranted. [ABSTRACT FROM AUTHOR]

Introduction: In Pakistan, chronic respiratory conditions contribute a large burden of morbidity and mortality. A major reason for this is the lack of availability of local evidence-based clinical practice guidelines (EBCPGs) in Pakistan, particularly at the primary care level. Thus, we developed EBCPGs and created clinical diagnosis and referral pathways for the primary care management of chronic respiratory conditions in Pakistan. Methods: The source guidelines were selected by two local expert pulmonologists after a thorough literature review on PubMed and Google Scholar from 2010 to December 2021. The source guidelines covered idiopathic pulmonary fibrosis, asthma, chronic obstructive pulmonary disorders, and bronchiectasis. The GRADE-ADOLOPMENT process consists of three key elements: adoption (using recommendations as is or with minor changes), adaptation (effective context-specific changes to recommendations) or additions (including new recommendations to fill a gap in the EBCPG). We employed the GRADE-ADOLOPMENT process to adopt, adapt, adopt with minor changes, or exclude recommendations from a source guideline. Additional recommendations were added to the clinical pathways based on a best-evidence review process. Results: 46 recommendations were excluded mainly due to the unavailability of recommended management in Pakistan and scope beyond the practice of general physicians. Clinical diagnosis and referral pathways were designed for the four chronic respiratory conditions, explicitly delineating the role of primary care practitioners in the diagnosis, basic management, and timely referral of patients. Across the four conditions, 18 recommendations were added (seven for IPF, three for bronchiectasis, four for COPD, and four for asthma). Conclusion: The widespread use of the newly created EBCPGs and clinical pathways in the primary healthcare system of Pakistan can help alleviate the morbidity and mortality related to chronic respiratory conditions disease in the country. [ABSTRACT FROM AUTHOR]

In this article, the results of research of dynamical processes during the first stage of a missile launch from very short-range mobile firing unit (MFU) are presented. The determined laws of motion of the system's components enabled determining characteristic motions that need to be reconstructed by the launcher simulator intended to be developed for personnel training. The half-car approach is applied for modelling the unit which consists of a vehicle and is attached to its missile launcher. The combined system is represented by a lumped-parameter model. The mathematical model is derived by applying the principle of Lagrange differential equations. Motion laws of the components of the system as its response to excitation load generated during missile launch were determined. [ABSTRACT FROM AUTHOR]

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground in the treatment of lung cancer. Recent advances in adoptive cell therapy (CAR T, TCR, TIL), the associated clinical trials on lung cancer, and associated hurdles are discussed in this review. Recent trials on lung cancer patients (without a targetable oncogenic driver alteration) reveal significant and sustained responses when treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that a loss of effective anti-tumor immunity is associated with lung tumor evolution. Therapeutic cancer vaccines combined with immune checkpoint inhibitors (ICI) can achieve better therapeutic effects. To this end, the present article encompasses a detailed overview of the recent developments in the immunotherapeutic landscape in targeting small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Additionally, the review also explores the implication of nanomedicine in lung cancer immunotherapy as well as the combinatorial application of traditional therapy along with immunotherapy regimens. Finally, ongoing clinical trials, significant obstacles, and the future outlook of this treatment strategy are also highlighted to boost further research in the field. [ABSTRACT FROM AUTHOR]

Background: Postoperative complications after perihilar cholangiocarcinoma surgical procedure are still very high. The implementation of a multimodal prehabilitation program could improve these outcomes. Based on our experience and that of the literature in hepatobiliary and pancreatic surgery, we propose a protocol to promote its implementation., Methods: First, we performed a retrospective analysis of the implementation feasibility of a multimodal prehabilitation program in patients' candidates for elective perihilar cholangiocarcinoma surgery in our center. Second, we conducted a literature search of publications in PubMed until December 2022. Relevant data about hepato-pancreato-biliary surgery and prehabilitation programs in features and postoperative outcomes was analyzed., Results: Since October 2020, 11 patients were evaluated for prehabilitation in our hospital. Two of them could not be resected intraoperatively due to disease extension. The median hospital stay was 10 days (iqr, 7-11). There were no major complications and 1 patient died. Of a total of 17 articles related to prehabilitation in hepato-biliary-pancreatic surgery, no reports focusing exclusively on perihilar cholangiocarcinoma were found. Six of the studies had nutritional therapies in addition to physical interventions, and 12 studies used home-based exercise therapy., Conclusions: Based on our experience and the data obtained from other studies, a prehabilitation program could be useful to improve perioperative physical and mental fitness in patients' candidates for elective perihilar cholangiocarcinoma surgery. However, more well-designed studies are needed to allow us to obtain more evidence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose : Lung cancer is the leading cause of cancer mortality worldwide. To improve the therapeutic outcomes, drug delivery systems, and particularly liposomes, have been widely investigated. Therefore, this review analyzed systematically the literature to inquire about the safety and efficacy of liposomal formulations in lung cancer treatment. Methods: Three electronic databases (PubMed, Web of Science and Cochrane CENTRAL) were systematically searched until May 2020. Clinical trials containing information about the effects of liposomal formulations in lung cancer patients were considered eligible. Results: Twenty two selected studies present different treatment options for both small and non-small-cell lung cancers. After compiling and analyzing all the published information, we verified that combination of liposomal cisplatin and paclitaxel led to a statistically significant improvement of the evaluated outcomes. Moreover, tecemotide, a liposome-based immunotherapy, demonstrated lower toxicity compared to control groups. Evidences that other subgroups could benefit from this formulation were also provided. Conclusion: This systematic review (registration number CRD42021246587) demonstrates that liposomal formulations are promising alternatives to overcome limitations of traditional cancer therapy. However, larger, longer, randomized and double-blinded clinical trials, selecting their patients' cohort considering more responsive subgroups would be beneficial to strengthen the scientific and clinical evidence of the results herein reported. [ABSTRACT FROM AUTHOR]

Background: Carboplatin is the backbone cytotoxic agent for many chemotherapy regimens for lung cancer. Dosing of carboplatin is complicated due to its relationship to renal function and narrow therapeutic index. Overestimation of renal function may lead to supratherapeutic dosing and toxicity, while underestimation may lead to underdosing and therapeutic failure. Although the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have higher accuracy in estimating glomerular filtration rate (eGFR), the Cockcroft Gault (CG) formula has been historically used for carboplatin dosing internationally.Methods: We compared these formulae to identify patient profiles that were associated with significant carboplatin dose variation by retrospectively analysing the carboplatin dosing of 96 patients with lung cancer. Carboplatin doses were calculated using eGFR generated by MDRD, CKD-EPI 2009 and CKD-EPI 2021 equations. These three hypothetical doses were compared to actual CG-based doses prescribed.Results: MDRD and CKD-EPI equations resulted in comparable carboplatin doses; however, CG doses diverged markedly with up to 17% of the patients receiving a carboplatin dose that was at least 20% higher than a non-CG formula would have predicted, and 20% received a dose that was at least 20% lower than a non-CG formula would have predicted. Our data suggest CG use overestimates kidney function in patients with a higher bodyweight and body surface area (BSA) while underestimating it in patients with a lower bodyweight and BSA. Importantly, we demonstrate potential real-world benefit as CKD-EPI predicted lower doses for patients whose (CG-derived) carboplatin dose was later reduced following clinical assessment prior to infusion.Conclusions: We have therefore confirmed significant differences in carboplatin dosing depending on the equation used in our modern patient population and suggest that use of CKD-EPI provides the most clinically appropriate carboplatin dosing and should be implemented as the new standard of care internationally. [ABSTRACT FROM AUTHOR]

Background: Patients have significantly lower QoL scores after pancreatic resection due to cancer in the physical and psychological domains compared to healthy controls or other cancer patients. Intensified physiotherapy or physical training can increase QoL by reducing fatigue levels and improving physical functioning. However, data on the long-term effects of intensive or supervised physiotherapy is lacking. The aim of this exploratory study is the assessment of QoL in the intervention group, using various QoL questionnaires in their validated German translations and gather data on its feasibility in the context of chemotherapy with a follow-up of 12 months (and develop concepts to improve QoL after pancreatic cancer resection).Methods: Fifty-six patients (mean age: 66.4 ± 9.9 years) were randomized in this study to intervention (cohort A, n = 28) or control group (cohort B, n = 28). Intervention of intensified physiotherapy program consisted of endurance and muscle force exercises using cycle ergometer. In the control group physiotherapy was limited to the duration of the hospital stay and was scheduled for 20 min on 5 days per week. The clinical visits took place 2 days preoperatively, 1 week, 3 months, 6 months and 12 months postoperatively. Both groups attended the follow-up program. QoL was evaluated using the Short Physical Performance Battery (SPPB), Short Form-8 Health Survey (SF-8) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and pancreatic cancer-specific module QLQ-PAN26 questionnaires. The course of QoL was evaluated using a repeated measures ANOVA and a per protocol design.Results: Of the initial 56 randomized patients, 34 finished the 12 months follow-up period. There were no adverse events due to the intervention and 80% of patients in the intervention group where adherent. There was no significant influence on physical performance as measured by SPPB and SF-8 questionnaire. However, after 6 months patients in the intervention group regained their prior physical condition, whereas the control group did not. Intensive physiotherapy significantly influenced various factors of QoL measured with the C30 questionnaire positively, such as physical functioning (p = 0.018), role functioning (p = 0.036), and appetite loss (p = 0.037), even after 6 months. No negative effects in patients undergoing chemotherapy compared to those without chemotherapy was observed.Conclusion: This first randomized controlled study with a 12-month follow-up shows that supervised physiotherapy or prescribed home-based exercise after pancreatic cancer resection is safe and feasible and should be proposed and started as soon as possible to improve certain aspects of QoL.Trial Registration: German Clinical Trials Register (No: DRKS00006786 ); Date of registration: 01/10/2014. [ABSTRACT FROM AUTHOR]

Background: Surgical resection remains the only curative treatment for pancreatic cancer and is associated with significant post-operative morbidity and mortality. Patients eligible for surgery, increasingly receive neo-adjuvant therapy before surgery or adjuvant therapy afterward, inherently exposing them to toxicity. As such, optimizing physical function through exercise during treatment remains imperative to optimize quality of life either before surgery or during rehabilitation. However, current exercise efficacy and prescription in pancreatic cancer is unknown. Therefore, this study aims to summarise the published literature on exercise studies conducted in patients with pancreatic cancer undergoing treatment with a focus on determining the current prescription and progression patterns being used in this population.Methods: A systematic review of four databases identified studies evaluating the effects of exercise on aerobic fitness, muscle strength, physical function, body composition, fatigue and quality of life in participants with pancreatic cancer undergoing treatment, published up to 24 July 2020. Two reviewers independently reviewed and appraised the methodological quality of each study.Results: Twelve studies with a total of 300 participants were included. Heterogeneity of the literature prevented meta-analysis. Exercise was associated with improvements in outcomes; however, study quality was variable with the majority of studies receiving a weak rating.Conclusions: High quality evidence regarding the efficacy and prescription of exercise in pancreatic cancer is lacking. Well-designed trials, which have received feedback and input from key stakeholders prior to implementation, are required to examine the impact of exercise in pancreatic cancer on key cancer related health outcomes. [ABSTRACT FROM AUTHOR]

Treatments for pancreatic cancer can have debilitating side effects including fatigue, weight loss, and cardiac toxicity, resulting in functional loss and psychological distress. Exercise has been proposed as a therapy to counteract physical and psychological detriments. The case: A 47-year-old male undergoing chemotherapy for stage 3 locally advanced pancreatic cancer. He was cycling during hospital chemotherapy infusions (6 fortnightly cycles of FOLFIRINOX: 5-FU 2, 400 mg/m2, over 48 h: irinotecan 180 mg/m2, oxaliplatin 85 mg/m2, no 5-FU bolus) plus 12 weeks of twice weekly aerobic and resistance exercise. Over 12 weeks, body composition was maintained, and physical function improved, with specific increases in muscular strength of up to 50% and aerobic capacity improving by 9%. Moreover, quality of life, fatigue, psychological distress, and sleep quality improved by 38, 113, 50, and 9%, respectively. Additionally, the participant experienced more severe side effects in week 6, when he did not cycle to a high intensity during hospital infusion and had less total weekly exercise. After cycle 6 (week 11), chemotherapy was halted, and a Whipple resection procedure was successfully performed. It can be concluded that regular aerobic and resistance exercise plus exercise during infusion can attenuate expected decline in physical and mental health with pancreatic cancer treatment and may reduce treatment side effects and have favourable effects on prognosis. [ABSTRACT FROM AUTHOR]

The prevalence of obesity has seen a global increase in the past decades, escalating to one of the major epidemiological challenges today. Global economic growth has caused changes in dietary and physical activity patterns fueling obesity across age, gender, and income groups. The implications are many, as obesity has been associated with numerous serious health conditions, ultimately affecting morbidity and mortality. There is a growing recognition of the risk a high body mass index confers on the development and outcome of several malignancies, including pancreatic cancer. Pancreatic cancer is a highly lethal disease with exceptionally poor outcome, with incidences rising worldwide. Due to vague symptoms and no screening recommendations, a vast majority of patients are diagnosed at late stages, with already advanced disease and no opportunity for surgical intervention. Obesity mediates risk for pancreatic cancer through insufficiently understood mechanisms, possibly including inflammation and hormonal misbalance. As excess abdominal adiposity is among the few modifiable risk factors for pancreatic cancer onset, enduring weight loss could manifest an effective preventive measure. Lifestyle modifications on a population level aimed to reduce obesity could also scale down the grim pancreatic cancer rates. In cases when these measures alone are insufficiently effective, bariatric surgery can be an advantageous alternative. Extremely obese patients exhibit many health benefits following bariatric surgery along with weight loss, consequently reducing the chances of pancreatic cancer, especially if additionally adopting healthy lifestyle habits. [ABSTRACT FROM AUTHOR]

Understanding of the functioning of MUC1 (human mucin) has advanced significantly over 40 years of its investigation. The anti-adhesive properties of the extracellular domain, which were the main focus of early studies initially explaining overexpression of MUC1 in progressing oncological diseases, were gradually put on the back burner. Researchers became more interested in its regulatory and signaling functions in cells rather in its anti-adhesive properties. The found the ability of MUC1 for signal transduction, and its ability to participate in cell metabolism opened new possibilities for improved control over cancer cells in addition to just attracting antigens of the immune system to a target. Nevertheless, there are issues in the functioning of MUC1 that raise doubts about its effectiveness in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are on the rise. Sarcopenia and sarcopenic obesity have proven to be prognostic factors in different types of cancers. In the context of previous findings, we evaluated the impact of body composition in patients undergoing surgery in a national pancreatic center. Methods: Patient’s body composition (n = 133) was analyzed on diagnostic CT scans and defined as follows: Skeletal muscle index ≤38.5 cm2/m2 (women), ≤52.4 cm2/m2 (men); obesity was classified as BMI ≥25kg/m2. Results: Sarcopenia showed a negative impact on overall survival (OS; 14 vs. 20 months, p = 0.016). Sarcopenic patients suffering from obesity showed poorer OS compared to non-sarcopenic obese patients (14 vs. 23 months, p = 0.007). Both sarcopenia and sarcopenic obesity were associated with sex (p<0.001 and p = 0.006; males vs. females 20% vs. 38% and 12% vs. 38%, respectively); sarcopenia was further associated with neoadjuvant treatment (p = 0.025), tumor grade (p = 0.023), weight loss (p = 0.02) and nutritional depletion (albumin, p = 0.011) as well as low BMI (<25 kg/m2, p = 0.038). Sarcopenic obese patients showed higher incidence of major postoperative complications (p<0.001). In addition, sarcopenia proved as an independent prognostic factor for OS (p = 0.031) in the multivariable Cox Regression model. Conclusion: Patients with sarcopenia and sarcopenic obesity undergoing resection for PDAC have a significantly shorter overall survival and a higher complication rate. The assessment of body composition in these patients may provide a broader understanding of patients’ individual condition and guide specific supportive strategies in patients at risk. [ABSTRACT FROM AUTHOR]

Fatigue is one of the most commonly reported sequelae after traumatic brain injury (TBI). This study evaluated the impact of a graduated physical activity programme on fatigue after TBI. Using a prospective randomised single-blind crossover design, 123 individuals with TBI, over the age of 18, were enrolled. Interventions included a home-based walking programme utilising a pedometer to track daily number of steps at increasing increments accompanied by tapered coaching calls over a 12-week period. Nutritional counselling with the same schedule of coaching calls served as the control condition. Main outcome measures included: the Global Fatigue Index (GFI), the Barrow Neurological Institute (BNI) Fatigue Scale Overall Severity Index Score, and the Multidimensional Fatigue Inventory (MFI). Step counts improved over time regardless of group assignment. The walking intervention led to a decrease in GFI, BNI Total, and MFI General scores. Participants reported less fatigue at the end of the active part of the intervention (24 weeks) and after a wash out period (36 weeks) as measured by the BNI Overall. The study suggests that walking can be used as an efficient and cost-effective tool to improve fatigue in persons who have sustained a TBI. [ABSTRACT FROM AUTHOR]

Background. Malignant brain tumors are unpredictable and incurable, with 5-year survival rates less than 30%. The poor prognosis combined with intensive treatment necessitates the inclusion of complementary and supportive therapies that optimize quality of life and reduce treatment-related declines in health. Exercise therapy has been shown to be beneficial in other cancer populations, but no evidence is available for brain cancer survivors. Therefore, we report results from 2 preliminary cases. Methods. Two female patients diagnosed with glioblastoma multiforme and oligodendroglioma participated in a structured and supervised 12-week exercise program. The program consisted of two 1-hour resistance and aerobic exercise sessions per week and additional self-managed aerobic sessions. Outcome measures of strength, cardiovascular fitness, and several psychological indicators (depression, anxiety, and quality of life) were recorded at baseline, after 6 weeks and at the conclusion of the intervention. Results. Exercise was well tolerated; both participants completed all 24 sessions and the home-based component with no adverse effects. Objective outcome measures displayed positive responses relating to reduced morbidity. Similar positive responses were found for psychological outcomes. Scores on the Hospital Anxiety and Depression Scale showed clinically meaningful improvements in depression and total distress. Conclusion. These findings provide initial evidence that, despite the difficulties associated with brain cancer treatment and survivorship, exercise may be safe and beneficial and should be considered in the overall management of patients with brain cancer. [ABSTRACT FROM AUTHOR]

In the present study, two cases of paraneoplastic limbic encephalitis (PLE) associated with small cell lung cancer were reported. Using avidin-biotin immunoperoxidase methods, purified recombinant HuD western blotting and Euroline Neuronal Antigens Profile 2 immunoglobulin G western blotting, it was found that the well-characterized anti-Hu and anti-amphiphysin onconeuronal antibodies were present in the serum/cerebrospinal fluid of the patients. With a review of the literature, it was found that patients with PLE of Chinese Han nationality had two types of clinical manifestations, simple and complex, and that the lesions could also be divided into focal and scalable lesions. Furthermore, the clinical manifestations and lesion scopes were associated with certain types of cancer and antibodies. In addition, it was found that the prognosis for patients with PLE with autoantibodies targeting membrane antigens is improved compared with that for patients with PLE with autoantibodies targeting intracellular antigens, due to an increased sensitivity to immunomodulatory treatments and anti-cancer therapy. [ABSTRACT FROM AUTHOR]

An author index for the November 2, 2013 issue of "Asia-Pacific Journal of Clinical Oncology" is presented.