Emerging biological therapies for the treatment of malignant pleural mesothelioma.

Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occurred to develop immunotherapies and biomarker driven therapy to improve patient outcomes over this period.Areas covered: This review examines current standard of care systemic therapy in the first- and second line setting. The last 12 months has seen 2 significant trials (Checkmate 743 and CONFIRM) which provide evidence supporting the role of immunotherapy in the management of MPM. Further trials are underway to assess the role of combination chemoimmunotherapy and personalized therapy. Additionally, a large number of clinical trials are ongoing to assess the efficacy of oncoviral, dendritic cell, anti-mesothelin and chimeric antigen receptor T cell therapy in the treatment of MPM.Expert opinion: Recent Phase III trial results have established a role for immunotherapy in the management of MPM. The optimal sequencing and combination of chemotherapy and immunotherapy remains to be determined. Novel therapies for MPM are promising however efficacy remains to be determined and issues remain regarding access to and delivery of these therapies.

Survival in borderline resectable and locally advanced pancreatic cancer is determined by the duration and response of neoadjuvant therapy.

BACKGROUND: Pancreatic cancer is the 8th commonest cancer and the 5th commonest cause of cancer-related death in Australia, with a 9% average 5-year survival. This study aims to investigate the effects of neoadjuvant treatment on overall survival (OS) and recurrence-free survival (RFS) in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic adenocarcinoma followed by curative resection. MATERIALS AND METHODS: Prospectively-collected demographic, medical, surgical and pathological data of patients with BRPC and LAPC treated with both neoadjuvant therapy (NAT) and surgery at a single tertiary referral centre in Australia were reviewed and analysed. RESULTS: Between 2012 and 2018, 60 patients, 34 with BRPC and 26 with LAPC, were treated with NAT followed by curative resection. The commonest neoadjuvant chemotherapy regimens were Gemcitabine + Abraxane (51.7%) and FOLFIRINOX (35.0%), with 48.3% of patients additionally receiving neoadjuvant radiotherapy. Median RFS was 30 months and median OS was 35 months. On multivariable analysis, inferior OS was predicted by enlarged loco-regional lymph nodes on initial computed tomography (p = 0.032), larger tumour size post-NAT (p = 0.006) and Common Terminology Criteria for Adverse Events post-NAT toxicity greater than grade 2 (p = 0.015). LAPC patients received more neoadjuvant chemotherapy (p = 0.008) and radiotherapy (p = 0.021) than BRPC and achieved a superior pathological response (p = 0.010). CONCLUSION: Patients who respond to NAT likely have a favourable disease biology and will progress well following resection. It is these patients who should be selected for more aggressive upfront management, and those with resistant disease should be spared from high-risk surgery.

Accreditation Standard Guideline Initiative for Tai Chi and Qigong Instructors and Training Institutions.

Evidence of the health and wellbeing benefits of Tai Chi and Qigong (TQ) have emerged in the past two decades, but TQ is underutilized in modern health care in Western countries due to lack of promotion and the availability of professionally qualified TQ instructors. To date, there are no government regulations for TQ instructors or for training institutions in China and Western countries, even though TQ is considered to be a part of Traditional Chinese medicine that has the potential to manage many chronic diseases. Based on an integrative health care approach, the accreditation standard guideline initiative for TQ instructors and training institutions was developed in collaboration with health professionals, integrative medicine academics, Tai Chi and Qigong master instructors and consumers including public safety officers from several countries, such as Australia, Canada, China, Germany, Italy, Korea, Sweden and USA. In this paper, the rationale for organizing the Medical Tai Chi and Qigong Association (MTQA) is discussed and the accreditation standard guideline for TQ instructors and training institutions developed by the committee members of MTQA is presented. The MTQA acknowledges that the proposed guidelines are broad, so that the diversity of TQ instructors and training institutions can be integrated with recognition that these guidelines can be developed with further refinement. Additionally, these guidelines face challenges in understanding the complexity of TQ associated with different principles, philosophies and schools of thought. Nonetheless, these guidelines represent a necessary first step as primary resource to serve and guide health care professionals and consumers, as well as the TQ community.

Convergent priorities and tensions: a qualitative study of the integration of complementary and alternative therapies with conventional cancer treatment.

PURPOSE: Demand for complementary and alternative medicine (CAM) is high among cancer patients. This, alongside growing evidence for the efficacy of some CAM therapies, is driving change within cancer centres, where evidence-based CAM therapies are increasingly provided alongside standard cancer treatments. In Australia, commitment to equitable access to healthcare is strong, and some cancer centres are now providing integrative services at no cost to the patient. This represents a significant shift in healthcare provision. This study aimed to examine health professional and patient dynamics in an integrated cancer service where CAM is provided at no cost to patients alongside standard cancer treatments. It specifically sought to understand what might drive or hinder further integration of CAM with standard treatment in the cancer context. METHODS: Qualitative interviews were undertaken with twenty key stakeholders-cancer patients, cancer nurses, and oncologists-who were delivering or receiving care in an Australian public hospital where acupuncture services are provided at no cost to patients alongside standard chemotherapy and radiation treatments. RESULTS: Findings point to key areas where the concerns and priorities of cancer patients, cancer nurses, and oncologists converge and diverge in ways that reflect core personal and professional interests regarding patient care needs, the evidence base for CAM efficacy and safety, and rising healthcare costs. CONCLUSIONS: Understanding points of convergence and divergence could assist clinicians and service providers in negotiating ways forward for integrative cancer services.

Acupuncture in Oncology: The Effectiveness of Acupuncture May Not Depend on Needle Retention Duration.

BACKGROUND: Guidelines surrounding optimum needle retention duration in acupuncture have not been established, despite a growing evidence base for acupuncture over recent decades. This retrospective study explored the effect of varying acupuncture needle retention durations in cancer patients. METHOD: Patients received either 2 (n = 35), 10 (n = 53), or 20 minutes (n = 54) of acupuncture once a week for 6 weeks. Outcomes of anxiety and depression, stress, fatigue, and quality of life (QOL), with the Hospital Anxiety and Depression Scale, Perceived Stress Scale, Functional Assessment of Cancer Therapy-Fatigue, and European Organization for Research and Treatment of Cancer Quality of Life, were measured at baseline and at 6 weeks following the intervention. RESULTS: The mean age of participants was 58 years (n = 152). The majority were female, diagnosed with breast cancer. Depression, stress, fatigue, and QOL were significantly improved in all 3 groups at 6 weeks postintervention. No significant differences in all outcomes were found between the 3 groups (≤2 vs 10 minutes vs 20 minutes). There were no differences with the satisfaction of the acupuncture services and perceived efficacy of acupuncture among the 3 groups. More than 95% of participants indicated that they would recommend acupuncture to other cancer patients, friends, and their family members. CONCLUSION: The efficacy of acupuncture may not only depend on needle retention duration, but may also be associated with multiple factors. Considering the limitations of this study design, robust randomized controlled studies are warranted to confirm the findings.

Factors affecting whether or not cancer patients consider using acupuncture.

OBJECTIVE: To explore the factors associated with utilisation of an acupuncture service in a tertiary oncology setting in an Australian public hospital. METHOD: Cancer patients attending oncology clinics at a university teaching hospital were invited to participate in the evaluation of acupuncture services from June 2014 to May 2015. Patients had a prior diagnosis of cancer (albeit at different stages) and were planning to receive, or were already receiving, systemic and/or radiation cancer treatment. RESULTS: The majority (81%) of participants indicated that they would consider the use of acupuncture during their cancer treatment. The most common reasons given for not considering acupuncture included adequate control of symptoms already with medical treatment, inconvenient clinic timing, and needle phobia. The main reasons given for considering acupuncture use included its perceived capability of reducing fatigue, boosting energy levels, improving immune function, and reducing pain and anxiety. Patients considering acupuncture use also demonstrated significantly higher levels of stress (p<0.001), anxiety and depression (p<0.001), fatigue (p<0.001), and lower global quality of life (p<0.01) compared to those who were not considering acupuncture. CONCLUSIONS: The findings show that demand for acupuncture by cancer patients is high. A substantial proportion of cancer patients intend to use acupuncture to manage cancer and/or cancer treatment-related symptoms. Discussion with patients about acupuncture and other complementary therapies during the consultation may improve cancer care.

Does the Chemotherapy Backbone Impact on the Efficacy of Targeted Agents in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis of the Literature.

IMPORTANCE: The EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) bevacizumab and aflibercept have demonstrated varying efficacy in mCRC. OBJECTIVE: To document the overall impact of specific chemotherapy regimens on the efficacy of targeted agents in treating patients with mCRC. DATA SOURCES: MEDLINE, EMBASE and Cochrane databases were searched to 2014, supplemented by hand-searching ASCO/ESMO conference abstracts. STUDY SELECTION: Published RCTs of patients with histologically confirmed mCRC were included if they investigated either 1) chemotherapy with or without a biological agent or 2) different chemotherapy regimens with the same biological agent. EGFR-I trials were restricted to KRAS exon 2 wild-type (WT) populations. DATA EXTRACTION AND SYNTHESIS: Data were independently abstracted by two authors and trial quality assessed according to Cochrane criteria. The primary outcome was overall survival with secondary endpoints progression free survival (PFS), overall response rate (ORR) and toxicity. RESULTS: EGFR-I added to irinotecan-based chemotherapy modestly improved OS with HR 0.90 (95% CI 0.81-1.00, p = 0.04), but more so PFS with HR 0.77 (95% CI 0.69-0.86, p<0.00001). No benefit was evident for EGFR-I added to oxaliplatin-based chemotherapy (OS HR 0.97 (95% CI 0.87-1.09) and PFS HR 0.92 (95% CI 0.83-1.02)). Significant oxaliplatin-irinotecan subgroup interactions were present for PFS with I2 = 82%, p = 0.02. Further analyses of oxaliplatin+EGFR-I trials showed greater efficacy with infusional 5FU regimens (PFS HR 0.82, 95% CI 0.72-0.94) compared to capecitabine (HR 1.09; 95% CI 0.91-1.30) and bolus 5FU (HR 1.07; 95% CI 0.79-1.45); subgroup interaction was present with I2 = 72%, p = 0.03. The oxaliplatin-irinotecan interaction was not evident for infusional 5FU regimens. For AIs, OS benefit was observed with both oxaliplatin-based (HR 0.83) and irinotecan-based (HR 0.77) regimens without significant subgroup interactions. Oxaliplatin+AI trials showed no subgroup interactions by type of FP, whilst an interaction was present for irinotecan+AI trials although aflibercept was only used with infusional FP (I2 = 89.7%, p = 0.002). CONCLUSION AND RELEVANCE: The addition of EGFR-I to irinotecan-based chemotherapy has consistent efficacy, regardless of FP regimen, whereas EGFR-I and oxaliplatin-based regimens were most active with infusional 5FU. No such differential activity was observed with the varying chemotherapy schedules when combined with AIs.

Effect of medical Qigong on cognitive function, quality of life, and a biomarker of inflammation in cancer patients: a randomized controlled trial.

PURPOSE: Cancer patients often experience diminished cognitive function (CF) and quality of life (QOL) due to the side effects of treatment and the disease symptoms. This study evaluates the effects of medical Qigong (MQ; combination of gentle exercise and meditation) on CF, QOL, and inflammation in cancer patients. METHODS: Eighty-one cancer patients recruited between October 2007 and May 2008 were randomly assigned to two groups: a control group (n = 44) who received the usual health care and an intervention group (n = 37) who participated in a 10-week MQ program. Self-reported CF was measured by the European Organization for Research and Treatment of Cancer (EORTC-CF) and the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog). The Functional Assessment of Cancer Therapy-General (FACT-G) was used to measure QOL. C-reactive protein (CRP) was assessed as a biomarker of inflammation. RESULTS: The MQ group self-reported significantly improved CF (mean difference (MD) = 7.78, t (51) = -2.532, p = 0.014) in the EORTC-CF and all the FACT-Cog subscales [perceived cognitive impairment (MD = 4.70, t (43) = -2.254, p = 0.029), impact of perceived cognitive impairment on QOL (MD = 1.64, t (45) = -2.377, p = 0.024), and perceived cognitive abilities (MD = 3.61, t (45) = -2.229, p = 0.031)] compared to controls. The MQ group also reported significantly improved QOL (MD = 12.66, t (45) = -5.715, p < 0.001) and had reduced CRP levels (MD = -0.72, t (45) = 2.092, p = 0.042) compared to controls. CONCLUSIONS: Results suggest that MQ benefits cancer patients' self-reported CF, QOL, and inflammation. A larger randomized controlled trial including an objective assessment of CF is planned.

The use and perceived benefits resulting from the use of complementary and alternative medicine by cancer patients in Australia.

AIM: The use of complementary and alternative medicine (CAM) by cancer patients is growing. However, few studies have examined the perceived benefits and adverse effects resulting from the use of CAM by cancer patients. The aim of this study was to evaluate CAM use by cancer patients and to explore their perceptions of the benefit, safety and efficacy of CAM in general. METHODS: Oncologists from three university teaching hospitals screened patients for eligibility. Eligible patients (N = 1323) were mailed a letter of invitation with a questionnaire between January and May 2008. RESULTS: Overall 381 questionnaires were returned, showing that 65% of cancer patients used at least one form of CAM. Patients considered taking biological CAM before, during and after chemotherapy. Up to 90% of CAM users believed that CAM provided potential health benefits and less than 3% reported adverse effects experienced from the use of CAM. Most respondents (80%) believed CAM can provide health benefits even when efficacy has not been proven. Most patients (90%) believed that doctors should consider learning about CAM to provide appropriate advice to their cancer patients, and most (83%) indicated they would be happier to accept CAM if it was offered by the hospital. CONCLUSION: A substantial portion of Australian cancer patients use CAM. Given the limited data on efficacy and safety for most CAM, it may be reasonable to offer CAM within the hospital environment so its use can be monitored and patients can receive more evidence-based care.

Patient-doctor communication: use of complementary and alternative medicine by adult patients with cancer.

The purpose of this survey was to examine patient-doctor communication about the use of complementary and alternative medicine (CAM) by adult patients with cancer and compare patients' satisfaction with the consultation between patients who had and those who had not discussed the use of CAM with their doctors. Oncologists from three hospitals screened patients for eligibility. Eligible patients were mailed a letter of invitation with a questionnaire (N = 1,323). Three hundred eighty-one questionnaires were returned. Sixty-five percent of cancer patients used at least one form of CAM. Use of CAM was not discussed with the oncologist by 55% of respondents using biologically based CAM and by 80% of those using non-biologically based CAM since the diagnosis of cancer. Patients who discussed the use of biologic CAM with their oncologists were more satisfied with the consultation than those who had not (p = .027), whereas there were no significant differences between patients who discussed or did not discuss use of non-biologically based CAM (p = .102). A substantial proportion of cancer patients do not discuss the use of CAM with their oncologists. It is important to improve patient-doctor communication about the use of CAM to increase patients' satisfaction with the oncology consultation.

Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy.

PURPOSE: Liver metastases are the principal cause of death in patients with advanced colorectal cancer (CRC). Irinotecan is a chemotherapeutic agent used in the treatment of CRC and has demonstrated synergistic potential when used with radiation. Radioembolization with yttrium-90 microspheres has demonstrated increased response and survival rates when given with fluorouracil chemotherapy. This study's goal was to evaluate the maximum-tolerated dose of concomitant irinotecan and radioembolization in fluorouracil-refractory patients with CRC hepatic metastases. PATIENTS AND METHODS: Twenty-five irinotecan-naive patients who had experienced relapse after previous chemotherapy were enrolled onto three dose-escalating groups. Irinotecan was administered at 50, 75, or 100 mg/m(2) on days 1 and 8 of a 3-week cycle for the first two cycles, and full irinotecan doses (ie, 100 mg/m(2)) were administered during cycles 3 to 9. Radioembolization was administered during the first chemotherapy cycle. RESULTS: Most patients experienced acute, self-limiting abdominal pain and nausea. Mild lethargy and anorexia were common. Grades 3 to 4 events were seen in three of six patients at 50 mg/m(2) (obstructive jaundice, thrombocytopenia, diarrhea), in five of 13 patients at 75 mg/m(2) (neutropenia, leukopenia, thrombocytopenia, elevated alkaline phosphatase, abdominal pain, ascites, fatigue) and in four of six patients at 100 mg/m(2) (diarrhea, deep vein thrombosis, constipation, leukopenia). Eleven (48%) of 23 patients had a partial response, and nine patients (39%) had stable disease. The median progression-free survival was 6.0 months; the median survival was 12.2 months. CONCLUSION: Concomitant use of radioembolization plus irinotecan did not reach a maximum-tolerated dose. The recommended dose of irinotecan in this setting is 100 mg/m(2) on days 1 and 8 of a 3-week cycle.