Curr. Oncol., Volume 26, Issue 1 (February 2019) – 29 articles

Nivolumab, an anti–PD-1 antibody, is now considered an important therapeutic agent in several advanced malignancies. However, immune-related adverse events such as endocrinopathies have been reported with its use. Thyroid disorder and isolated adrenocorticotropic hormone deficiency have frequently been reported as nivolumab-induced immune-related adverse events. Another endocrinopathy is nivolumab-induced type 1 diabetes mellitus (T1DM), described as diabetes mellitus with rapid onset and complete insulin insufficiency, at times leading to fulminant T1DM. We report the case of a 68-year-old woman who developed pancreatic islet–related autoantibody-negative T1DM, possibly induced by nivolumab, under continuous glucocorticoid administration. She was treated with nivolumab for advanced malignant melanoma, concomitant with 10 mg prednisolone daily for thrombophlebitis tapered to 5 mg after 13 courses of nivolumab therapy. At approximately the 27th course of nivolumab therapy, she showed elevated plasma glucose levels despite preserved insulin secretion. A month later, she developed diabetic ketoacidosis. Her insulin secretion decreased and finally was exhausted. She was diagnosed with acute-onset rather than fulminant T1DM because of a rapidly progressive course to diabetic ketoacidosis during just more than 1 week. She is currently receiving insulin replacement. There has been no recurrence of the melanoma. Thus, nivolumab might induce autoimmune diabetes mellitus, with patients having T1DM-sensitive human leucocyte antigen being more susceptible even when receiving glucocorticoids. Physicians should be aware that nivolumab could potentially induce T1DM as a critical immune-related adverse event. Full article

Cancer immunotherapy has been one of the highlights in the advancement of cancer care. Certain immune checkpoint inhibitors bind to PD-1 on T cells and mediate an antitumour immune response. Given that immune checkpoint inhibitors are becoming part of standard care, a new class of adverse events—immune-related adverse events—has emerged. Among them is endocrine toxicity, most commonly targeting the thyroid, pituitary, or adrenal glands. New-onset diabetes mellitus has been reported in fewer than 1% of patients. We present a patient with type 1 diabetes mellitus secondary to immunotherapy, together with an overview of the associated literature. Patients who develop type 1 diabetes mellitus experience a rapid course, and diabetic ketoacidosis is commonly the presenting symptom. Insulin is currently the treatment of choice; oral antidiabetics or corticosteroids do not assist in management. Several predictive factors are under investigation, but physician awareness and prompt management are key to a positive outcome. Full article

Objective: Extended prophylaxis against venous thromboembolism (vte) after abdominal or pelvic cancer surgery with low molecular weight heparin (lmwh) is recommended by multiple guidelines. The primary objective of the present study was to assess adherence to that guideline recommendation at tertiary care centres within Hamilton Health Sciences (hhs). Methods: Given that an estimated 70% of the study population would be expected to receive extended prophylaxis, a sample size of 105 patients was calculated. Patients who had undergone abdominal or pelvic surgery for cancer from March 2012 to December 2015 were identified, and data were collected from electronic health records. The primary outcome was prescription of extended vte prophylaxis. Results: Of 105 patients, only 3 received extended vte prophylaxis. Those 3 patients had serous carcinoma of the uterus, transitional cell carcinoma of the bladder, and cecal cancer. Of the 3 patients, 2 were followed by the thrombosis service while in hospital; none of the other 102 patients received any form of extended vte prophylaxis. Conclusions: Based on multiple randomized controlled trials, guidelines suggest lmwh prophylaxis for up to 4 weeks after major abdominal or pelvic cancer surgery. Despite those recommendations, postoperative extended vte prophylaxis is not commonly prescribed at hhs facilities. Next steps will include identification of barriers and an examination of how those barriers could be addressed. Failure to use prophylaxis is not consistent with evidencebased guidelines and is placing patients at risk of vte. Full article

Background: We examined how conditional market approval of cancer pharmaceuticals by Health Canada (hc) affects public funding recommendations by the pan-Canadian Oncology Review (pcodr). We were also interested to see how often hc conditions are enforced. Methods: Health Canada and pcodr databases for 2010–2017 were analyzed for patterns in hc conditional authorization and post-authorization reviews of cancer drugs and for correlation with pcodr reimbursement recommendations. Results: Between 2010 and 2017, pcodr reviewed 105 unique drug–indication pairings; 21% (n = 22) had conditional hc authorization. In all cases, conditional authorization was given on the basis of preliminary data in a surrogate endpoint and was contingent on further data showing benefit in more robust outcome measures (for example, overall survival). Of those 22 drugs, 36% did not have updated data, 36% had updated data that met hc conditions, and 27% had data that met some, but not all, conditions. During the period considered, hc never revoked conditional authorization for failure to meet conditions. None of the 22 drugs was given an unconditional positive recommendation for public reimbursement by pcodr. A conditional recommendation was given to 11 of the drugs (50%), and reimbursement was not recommended for 6 drugs (27%) because of insufficient evidence. Conclusions: One fifth of the cancer drugs reviewed for public reimbursement in Canada were conditionally authorized by hc based on preliminary data. Conditional authorization was associated with a recommendation against public funding by pcodr. No drugs had their conditional market authorization revoked for failure to meet conditions, suggesting that a more robust hc reappraisal framework is needed. Full article

Objective: The purpose of the present work was to develop evidence-based indications for Mohs micrographic surgery in patients with a diagnosis of skin cancer. Methods: The guideline was developed by Cancer Care Ontario’s Program in Evidence-Based Care, together with the Melanoma Disease Site Group and the Surgical Oncology Program, through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews. Recommendation 1: Given a lack of high-quality, comparative evidence, surgery (with postoperative or intraoperative margin assessment) or radiation (for those who are ineligible for surgery) should remain the standard of care for patients with skin cancer. Recommendation 2: Mohs micrographic surgery is recommended for patients with histologically confirmed recurrent basal cell carcinoma of the face and is appropriate for primary basal cell carcinomas of the face that are larger than 1 cm, have aggressive histology, or are located on the H zone of the face. Recommendation 3: Mohs micrographic surgery should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada Specialist Certificate or equivalent, and have received advanced training in Mohs micrographic surgery. Full article

Background: Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (NSCLS) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment. Methods: An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions. Results: Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified. Conclusions: In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged. Full article

Trastuzumab is the standard treatment in Canada for patients with breast cancer positive for HER2 (human epidermal growth factor receptor 2), dramatically improving outcomes in that patient group. However, its current intravenous (IV) administration is associated with long infusion times that place a significant burden on health care resources and patient quality of life. In an effort to provide a faster and easier administration method, a subcutaneous (SC) formulation of trastuzumab has been developed. Data from comparative trials demonstrate that the two formulations are comparable with respect to pharmacokinetics and efficacy. They also have similar safety profiles, with the exception of mild local and administration reactions with the SC formulation. Furthermore, the SC formulation is preferred by patients and health care professionals, and greatly reduces administration and chair time. Additional advantages include easier preparation and dosing, reduced drug wastage, and reduced discomfort at the injection site. By using well-thought-out administration procedures, the SC formulation can be given safely and effectively, potentially reducing the burden on health care resources and improving quality of life for patients. Full article

Background: Stereotactic radiosurgery (SRS) for patients with 5 or more brain metastases (BMets) is a matter of debate. We report our results with that approach and the factors influencing outcome. Methods: In the 103 patients who underwent SRS for the treatment of 5 or more BMets, primary histology was non-small-cell lung cancer (57% of patients). All patients were grouped by Karnofsky performance status and recursive partitioning analysis (RPA) classification. In our cohort, 72% of patients had uncontrolled extracranial disease, and 28% had stable or responding systemic disease. Previous irradiation for 1–4 BMets had been given to 56 patients (54%). The mean number of treated BMets was 7 (range: 5–19), and the median cumulative BMets volume was 2 cm³ (range: 0.06–28 cm³). Results: Multivariate analyses showed that stable extracranial disease (p < 0.001) and RPA (p = 0.022) were independent prognostic factors for overall survival (OS). Moreover, a cumulative treated BMets volume of less than 6 cm³ (adjusted hazard ratio: 2.54; p = 0.006; 95% confidence interval: 1.30 to 4.99) was associated with better OS. The total number of BMets had no effect on survival (p = 0.206). No variable was found to be predictive of local control. The RPA was significant (p = 0.027) in terms of distant recurrence. Conclusions: Our study suggests that SRS is a reasonable option for the management of patients with 5 or more BMets, especially with a cumulative treatment volume of less than 6 cm³. Full article

Introduction: Stereotactic ablative radiotherapy (SABR) is a relatively new technique for the curative-intent treatment of patients with inoperable early-stage non-small-cell lung cancer (NSCLC). Previous studies have demonstrated a prognostic value for positron emission tomography–computed tomography (PET/CT) parameters, including maximal standardized uptake value (SUV_max), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) in lung cancer patients. We aimed to determine which pet/ct parameter is most prognostic of local control (LC) and overall survival (OS) in patients treated with SABR for NSCLC. Methods: We conducted a retrospective review of patients treated with SABR for stage i inoperable NSCLC at BC Cancer between 2009 and 2013. The Akaike information criterion was used to compare the prognostic value of the various PET/CT parameters. Results: The study included 134 patients with a median age of 76 years. Median tumour diameter was 2.2 cm, gross tumour volume was 8.1 mL, SUV_max was 7.9, MTV was 2.4 mL, and tlg was 10.9 SUV•mL. The 2-year LC was 92%, and os was 66%. On univariate and multivariate analysis, imaging variables including tumour size, gross tumour volume, SUV_max, MTV, and tlg were all associated with worse LC. Tumour size was not associated with significantly worse OS, but other imaging variables were. The PET/CT parameter most prognostic of LC was MTV. Compared with SUV_max, TLG and MTV were more prognostic of OS. Conclusions: In patients with early-stage NSCLC treated with SABR, MTV appears to be prognostic of LC and OS. Full article

Background: Radiation therapists play an important role in helping patients to safely manage and triage potentially life-threatening symptoms. The purpose of the present study was to assess factors influencing the use by radiation therapists of evidence-informed symptom practice guides for patients experiencing cancer treatment–related symptoms. Methods: In a mixed-methods descriptive study guided by the Knowledge-to-Action framework, interviews and a barriers survey were conducted. Two independent reviewers conducted a content analysis of interview transcripts. Barriers survey data were analyzed using frequency distributions and univariate descriptive statistics. Open-ended data from the surveys underwent content analysis and were triangulated with interview findings. Results: Of 90 radiation therapists approached, 58 completed the survey (64%), and 14 were interviewed. Of the 98% who reported providing symptom management to patients undergoing radiation treatment, 53% used evidence-informed practice guidelines. Radiation therapists had moderate moral norms (4.6 of 7) and beliefs about the consequences of using costars (pan-Canadian Oncology Symptom Triage and Remote Support) practice guides (4.8), but neutral intention (3.4) and beliefs about their own capabilities (3.9). Environmental barriers included lack of time (2.0), lack of access (2.5), and neutral organizational support (3.0). Radiation therapists identified a need for training (5.5). Common unique barriers to practice guide use were lack of time during radiation treatments, unclear fit with scope of practice, disparate focus on site-specific symptoms, and lack of medication knowledge. Conclusions: The symptom practice guides were perceived by the radiation therapists to benefit patients, enhance their own knowledge of symptom management, and promote consistent practice. Additional work is required to identify the scope of practice of radiation therapists within the interprofessional team. Full article

Traditionally, the role of primary care providers (pcps) across the cancer care trajectory has focused on prevention and early detection. In combination with screening initiatives, new and evolving treatment approaches have contributed to significant improvements in survival in a number of cancer types. For Canadian cancer survivors, the 5-year survival rate is now better than it was a decade ago, and the survivor population is expected to reach 2 million by 2031. Notwithstanding those improvements, many cancer survivors experience late and long-term effects, and comorbid conditions have been noted to be increasing in prevalence for this vulnerable population. In view of those observations, and considering the anticipated shortage of oncology providers, increasing reliance is being placed on the primary care workforce for the provision of survivorship care. Despite the willingness of pcps to engage in that role, further substantial efforts to elucidate the landscape of high-quality, sustainable, and comprehensive survivorship care delivery within primary care are required. The present article offers an overview of the integration of pcps into survivorship care provision. More specifically, it outlines known barriers and potential solutions in five categories: (1) Survivorship care coordination; (2) Knowledge of survivorship; (3) pcp-led clinical environments; (4) Models of survivorship care; (5) Health policy and organizational advocacy. Full article

Objectives: We examined the effects of magnanimous therapy on psychological coping, adjustment, living function, and survival rate in patients with advanced lung cancer. Methods: Patients with advanced lung cancer (n = 145) matched by demographics and medical variables were randomly assigned to an individual computer magnanimous therapy group (IC-MT), a group computer magnanimous therapy group (GC-MT), or a control group (CTRL). Over 2 weeks, the IC-MT and GC-MT groups received eight 40-minute sessions of IC-MT or GC-MT respectively, plus usual care; the CTRL group received only usual care. The Cancer Coping Modes Questionnaire (CCMQ), the Psychological Adjustment Scale for Cancer Patients (PASCP), and the Functional Living Index–Cancer (FLIC) were assessed at baseline and 2 weeks later. The relationships of changes in those indicators were analyzed, and survival rates were compared. Results: The psychological coping style, adjustment, and living function of the IC-MT and GC-MT groups improved significantly after the intervention (p < 0.01). After 2 weeks, significant (p < 0.01) differences between the treatment groups and the CTRL group in coping style, adjustment, and living function suggested successful therapy. The changes in living function were correlated with changes in psychological coping and adjustment. No difference in efficacy between IC-MT and GC-MT was observed. The survival rate was 31.84% in the IC-MT group and 9.375% in the CTRL group at 2 years after the intervention. Conclusions: In patients with advanced lung cancer, IC-MT and GC-MT were associated with positive short-term effects on psychological coping style, adjustment, and living function, although the magnitude of the effect did not differ significantly between the intervention approaches. The effects on living function are partly mediated by improvements in psychological coping and adjustment. Full article

Hospitals play an important role in the care of patients with advanced cancer: nearly half of all cancer deaths occur in acute-care settings. The need for increasing access to palliative care and related support services for patients with cancer in acute-care hospitals is therefore growing. Here, we examine how often and how early in their illness patients with cancer might be receiving palliative care services in the 2 years before their death in an acute-care hospital in Canada. The palliative care code from inpatient administrative databases was used as a proxy for receiving, or being referred for, palliative care. Currently, the palliative care code is the only data element routinely collected from patient charts that allows for the tracking of palliative care activity at a pan-Canadian level. Our findings suggest that most patients with cancer who die in an acute-care hospital receive a palliative designation; however, many of those patients are identified as palliative only in their final admission before death. Of the patients who received a palliative designation before their final admission, nearly half were identified as palliative less than 2 months before death. Findings signal that delivery of services within and between jurisdictions is not consistent, that the palliative care needs of some patients are being missed by physicians, and that palliative care is still largely seen as end-of-life care and is not recognized as an integral component of cancer care. Measuring the provision of system-wide palliative care remains a challenge because comprehensive national data about palliative care are not currently reported from all sectors. To advance measurement and reporting of palliative care in Canada, attention should be focused on collecting comparable data from regional and provincial palliative care programs that individually capture data about palliative care delivery in all health care sectors. Full article

For more than a decade, there has been no improvement in outcomes for patients with unresectable locally advanced (LA) non-small-cell lung cancer (NSCLC). The standard treatment in that setting is definitive concurrent chemotherapy and radiation (CCRT). Although the intent of treatment is curative, most patients rapidly progress, and their prognosis is poor, with a 5-year overall survival (OS) rate in the 15%–25% range. Those patients therefore represent a critical unmet need, warranting expedited approval of, and access to, new treatments that can improve outcomes. The PACIFIC trial, which evaluated durvalumab consolidation therapy after CCRT in unresectable LA NSCLC, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and a significant improvement in OS. Durvalumab thus fills a critical unmet need in the setting of unresectable LA NSCLC and provides a new option for patients treated with curative intent. Here, we review the treatment of unresectable LA NSCLC, with a focus on the effect of the clinical data for durvalumab. Full article

Background: Palliative care (pc) consultation has been associated with less aggressive care at end of life in a number of malignancies, but the effect of the consultation timing has not yet been fully characterized. For patients with unresectable pancreatic cancer (upcc), aggressive and resource-intensive treatment at the end of life can be costly, but not necessarily of better quality. In the present study, we investigated the association, if any, between the timing of specialist pc consultation and indicators of aggressive care at end of life in patients with upcc. Methods: This retrospective cohort study examined the potential effect of the timing of specialist pc consultation on key indicators of aggressive care at end of life in all patients diagnosed with upcc in Nova Scotia between 1 January 2010 and 31 December 2015. Statistical analysis included univariable and multivariable logistic regression. Results: In the 365 patients identified for inclusion in the study, specialist pc consultation was found to be associated with decreased odds of experiencing an indicator of aggressive care at end of life; however, the timing of the consultation was not significant. Residency in an urban area was associated with decreased odds of experiencing an indicator of aggressive care at end of life. We observed no association between experiencing an indicator of aggressive care at end of life and consultation with medical oncology or radiation oncology. Conclusions: Regardless of timing, specialist pc consultation was associated with decreased odds of experiencing an indicator of aggressive care at end of life. That finding provides further evidence to support the integral role of pc in managing patients with a life-limiting malignancy. Full article

Background: Randomized controlled trials (rcts) provide limited evidence to support the use of survivorship care plans (scps), but they provide strong evidence for patient decision aids (ptdas). Despite that evidence, the uptake of ptdas has been limited, but scps are being endorsed and implemented in many cancer programs across Canada. The objective of the present study was to illuminate the decision-making processes involved in the adoption of scps and ptdas. Methods: Informed by the principles of grounded theory, in-depth semi-structured interviews were conducted with clinicians, managers, and administrators who work in cancer care programs across Canada (n = 21). Data were collected and analyzed concurrently, using a constant comparative analysis approach. Data collection ended when theoretical saturation was reached. Results: For these types of patient-centred tools, participants noted that high-quality research evidence is often unnecessary for adoption decisions. Six key factors contribute to adoption or non-adoption decisions for scps and ptdas: (1) Alignment of research evidence with other evidence; (2) Perceived clinician benefit; (3) Endorsement by organizations and professional bodies; (4) Existence of local champions; (5) Adaptability to local contexts; (6) Ability to routinize and reach a large patient population. Conclusions: High-level evidence is not always the main consideration when adopting new tools into practice. And yet, understanding how clinicians and health system decision-makers decide whether and how to adopt new tools is important to optimizing the use of new tools and practices that are supported by research evidence. Full article

Background: We examined the uptake of risk-reducing interventions, including bilateral mastectomy, risk-reducing salpingo-oophorectomy, oral contraceptive pills, tamoxifen, and raloxifene, for the entire population of women with a deleterious BRCA1 or BRCA2 mutation in the Canadian province of British Columbia. Methods: This retrospective population-based study used data available in British Columbia for all women who, between 1996 and 2014, were tested and found to have a BRCA mutation. Rates of risk-reducing interventions stratified according to the type of BRCA mutation and prior history of breast or gynecologic cancer (ovary, fallopian tube, peritoneal) are presented. Cancers diagnosed in women with a BRCA mutation after disclosure of their mutation status are also presented. Results: The final study cohort consisted of 885 patients with a deleterious BRCA1 (n = 474) or BRCA2 (n = 411) mutation. Of the women with no prior breast cancer, 30.8% carrying a BRCA1 mutation and 28.3% carrying a BRCA2 mutation underwent bilateral mastectomy. Of women with no prior gynecologic cancer, 64.7% carrying a BRCA1 mutation and 62.2% carrying a BRCA2 mutation underwent risk-reducing bilateral salpingo-oophorectomy. Rates of chemoprevention with oral contraceptive pills and tamoxifen or raloxifene were low in all groups. In this cohort, 23 gynecologic and 70 breast cancers were diagnosed after disclosure of BRCA mutation status. Conclusions: Our results suggest reasonable uptake of risk-reducing interventions in high-risk women. To minimize the occurrence of breast and ovarian cancer in women with a BRCA1 or BRCA2 mutation, more attention could be paid to ensuring that affected women receive proper counselling and follow-up. Full article

Patient use of integrative oncology (the inclusion of nonconventional treatments alongside the conventional standard of care) continues to grow, with some studies showing its use in cancer patients to be as high as 91%. Naturopathic physicians are primary care providers who use integrative therapies to deliver patient-centred care. The Oncology Association of Naturopathic Physicians (oncanp) was formed in 2004 as a specialty association for naturopathic physicians providing integrative cancer care (nd oncs). Currently, the membership encompasses more than 400 naturopathic physicians and students, 115 of whom are board-certified Fellows of the American Board of Naturopathic Oncology. In 2016, oncanp established a committee comprising recognized experts in the field of naturopathic oncology to develop a Principles of Care (poc) guideline. The committee first undertook a review of existing standard-of-care and best-practice guidelines in the field of oncology and then adapted those concepts into a draft document. The draft document was then reviewed by naturopathic physicians, medical and radiation oncologists, naturopathic policy experts, and finally the oncanp membership at large. The poc document presented here provides clear guidelines for nd oncs on how best to deliver patient-centred care in the areas of assessment, treatment planning, care management, interprofessional collaboration, and survivorship care. This naturopathic oncology poc document can be a valuable resource for nd oncs and other oncology care providers to further an understanding of the naturopathic and integrative oncology care model and its potential for collaboration. Full article

Purpose: Patient-reported symptom data are collected prospectively by a provincial cancer agency to mitigate the significant symptom burden that patients with cancer experience. However, an assessment of whether such symptom screening occurs uniformly for those patients has yet to be performed. In the present study, we investigated patient, disease, and health system factors associated with receipt of symptom screening in the year after a cancer diagnosis. Methods: Patients diagnosed with cancer between 2007 and 2014 were identified. We measured whether 1 or more symptom screenings were recorded in the year after diagnosis. A multivariable modified Poisson regression with robust error variance was used to identify predictors [age, comorbidity, rurality, socioeconomic status, immigration status, cancer site, registration at a regional cancer centre (CC), and year of diagnosis] of being screened for symptoms. Results: Of 425,905 patients diagnosed with cancer, 163,610 (38%) had 1 or more symptom screening records in the year after diagnosis, and 75% survived at least 1 year. We identified variability in symptom screening by primary cancer site, regional CC, age, sex, comorbidity, material deprivation, rurality of residence, and immigration status. Patients who had been diagnosed with melanoma or endocrine cancers, who were not registered at a regional CC, who lived in the most urban areas, who were elderly, and who were immigrants were least likely to undergo symptom screening after diagnosis. Conclusions: Our evaluation of the implementation of a population-based symptom screening program in a universal health care system identified populations who are at risk for not receiving screening and who are therefore future targets for improvements in population symptom screening and better management of cancer-related symptoms at diagnosis. Full article

Cediranib, a potent inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor subunit B, and the c-Kit receptor tyrosine kinase, has shown antitumour activity as an antiangiogenic agent in preclinical models. Initial clinical trials with cediranib in a variety of tumour types, including glioblastoma multiforme, non-small-cell lung cancer, renal cell cancer, colorectal cancer, and prostate cancer, showed activity comparable to that for other vascular endothelial growth factor (vegf) inhibitors, but with significant toxicities, resulting in abandonment of the drug’s development in 2011. [...] Full article

Background: Exposing patients with metastatic colorectal cancer (MCRC) to all three active chemotherapeutic agents (oxaliplatin, irinotecan, fluorouracil) has improved survival. The benefit of second-line chemotherapy after a first-line triplet is not clearly defined. We evaluated the efficacy of second-line chemotherapy in patients who had received first-line triplet therapy. Methods: The medical records of patients treated on a prospective trial of first-line triplet therapy were reviewed for second-line treatment. Univariate and multivariate analyses were performed to establish factors of prognostic significance. Results: Of the 53 patients who received first-line triplet therapy, 28 (53%) received second-line chemotherapy [13 men; 8 with a colon primary; mutant KRAS in 10, wild-type in 15, and unknown status in 3; Eastern Cooperative Oncology Group performance status (PS) of 1 in 16 patients, PS 2 in 3, PS 3 in 2, and unknown in 7; involved organs: liver in 17 patients, lung in 16, and peritoneum in 8]. Second-line chemotherapy consisted of XELOX or FOLFOX in 13 patients, XELIRI or FOLFIRI in 12, and single-agent irinotecan in 3. Concurrent bevacizumab was given in 16 patients (57%), and cetuximab, in 2 (7%). Median survival was 28.0 months [95% confidence interval (CI): 22.8 months to 33.2 months] for patients receiving second-line therapy and 23.0 months (95% CI: 13.2 months to 32.8 months) for those not receiving it. Best response was partial in 6 patients (21%), stable disease in 11 (39%), and progressive disease in 11 (39%). Median progression-free survival was 4.8 months (95% CI: 2.4 months to 9.6 months), and overall survival was 15 months (95% CI: 9.6 months to 20.4 months). Conclusions: Second-line chemotherapy after first-line triplet therapy in MCRC is feasible and suggests efficacy comparable to that reported for second-line therapy after a doublet, regardless of the agent used. Full article

Background: Combined androgen blockade (CAB) is a promising treatment modality for prostate cancer (PCA). In the present meta-analysis, we compared the efficacy and safety of first-line CAB using an antiandrogen (AA) with castration monotherapy in patients with advanced PCA. Methods: PubMed, embase, Cochrane, and Google Scholar were searched for randomized controlled trials (RCTS) published through 12 December 2016. Hazard ratios (HRS) with 95% confidence intervals (CIS) were determined for primary outcomes: overall survival (OS) and progression-free survival (PFS). Subgroup analyses were performed for Western compared with Eastern patients and use of a nonsteroidal AA (NSAA) compared with a steroidal AA (SAA). Results: Compared with castration monotherapy, CAB using an AA was associated with significantly improved OS (n = 14; HR: 0.90; 95% CI: 0.84 to 0.97; p = 0.003) and PFS (n = 13; HR: 0.89; 95% CI: 0.80 to 1.00; p = 0.04). No significant difference in OS (p = 0.71) and PFS (p = 0.49) was observed between the Western and Eastern patients. Compared with castration monotherapy, CAB using a NSAA was associated with significantly improved OS (HR: 0.88; 95% CI: 0.82 to 0.95; p = 0.0009) and PFS (HR: 0.85; 95% CI: 0.73 to 0.98; p = 0.007)—a result that was not achieved with CAB using a SAA. The safety profiles of CAB and monotherapy were similar in terms of adverse events, including hot flushes, impotence, and grade 3 or 4 events, with the exception of risk of diarrhea and liver dysfunction or elevation in liver enzymes, which were statistically greater with CAB using an AA. Conclusions: Compared with castration monotherapy, first-line CAB therapy with an AA, especially a NSAA, resulted in significantly improved OS and PFS, and had an acceptable safety profile in patients with advanced PCA. Full article

Background: The role of systemic inflammation–based markers remains uncertain in advanced or metastatic neuroendocrine tumours (NETS). Methods: Systemic inflammatory factors, such as levels of circulating white blood cells and other blood components, were combined to yield inflammation-based prognostic scores [high-sensitivity inflammation-based Glasgow prognostic score (hSGPS), neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR), high-sensitivity inflammation-based prognostic index (hSPI), and prognostic nutritional index (PNI)], whose individual values as prognostic markers were retrospectively determined. Univariate and multivariate analyses were used to examine the association of inflammatory markers with overall survival (OS). Results: The study included 135 patients. Univariate analysis revealed that elevated white blood cell count, elevated neutrophil count, low serum albumin, elevated high-sensitivity C-reactive protein, and elevated hSPI, hSGPS, and NLR scores were significantly associated with worse OS. Multivariate analyses demonstrated that, apart from pathology grade and original site of the tumour, elevated hSPI (p = 0.004) was an independent prognostic factor for worse OS. Conclusions: In the present study, elevated pretreatment hSPI was observed to be an independent predictor of shorter OS in patients with inoperable advanced or metastatic NET. The hSPI might thus provide additional guidance for therapeutic decision-making in such patients. Full article