Curr. Oncol., Volume 24, Issue 4 (August 2017) – 21 articles

The 2017 Canadian Lung Cancer Conference was held 9–10 February in Vancouver, British Columbia. Each year at this prestigious event, hundreds of professionals involved in lung cancer care come together to discuss new research, to learn about recent developments, and to collaborate and network with colleagues from across the country. This year’s meeting featured highly anticipated sessions, including resident education, multidisciplinary breakout sessions, debates, and an immuno-oncology symposium. Full article

Hepatocellular carcinoma (HCC) arising from a hepatic adenoma is a rare phenomenon accounting for fewer than 5% of HCC cases; it seldom recurs after resection of the primary tumour. We report a case of extrahepatic metastasis of HCC arising from a hepatic adenoma that presented as a solitary sternal metastasis without any evidence of intrahepatic recurrence. Our patient was initially treated with radiation therapy and bland embolization, without response. Subsequently, the patient developed progressive disease while taking sorafenib. He later received chemotherapy with docetaxel and gemcitabine, with the development of multiple pulmonary and splenic nodules. However, he remained free of intrahepatic recurrence. To the best of our knowledge, this is the first case of extrahepatic metastasis of HCC arising from a hepatic adenoma without evidence of intrahepatic recurrence. Full article

Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (IMiDS), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (HSR) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the IMiDS are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed HSR when receiving previous lines of IMiDS. As a patient’s advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (RDP) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient’s safety will ensure a smooth transition into pomalidomide treatment. A HSR can be either related or non-related to immunoglobulin E. As IMiDS become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo RDP safely. Patients enjoy a good quality of life and clinical response after the RDP procedure. Full article

Introduction: Regional lymph node dissection (RLND) for melanoma with nodal metastasis is a specialized procedure that is associated with improved disease-specific survival in selected patients. Furthermore, there is evidence that a higher lymph node retrieval rate (LNRR) is associated with improved local control. Currently, no consensus has been reached on the definition of an adequate LNRR. A minimum LNRR has been proposed as a quality assessment parameter that has to be validated. Methods: We conducted a retrospective cohort analysis at the Princess Margaret Cancer Centre (University Health Network, Toronto, ON). The LNRRS for all patients who underwent RLND for malignant cutaneous melanoma during 2000–2010 were recorded. Indications for RLND were a positive sentinel lymph node biopsy or clinical lymphadenopathy (palpable or radiologically detected). Results: Of the 207 identified RLNDS, 146 (70.5%) were subsequent to a positive sentinel lymph node biopsy, and 61 (29.5%) were performed for clinical lymphadenopathy. The median LNRR was 24 nodes (range: 9–47 nodes; 10th percentile: 14 nodes) for axillary RLND, 12 nodes (range: 5–30 nodes; 10th percentile: 8 nodes) for inguinal RLND, and 16 nodes (range: 10–21 nodes; 10th percentile: 11 nodes) for ilioinguinal RLND. The results were similar when comparing patients with positive sentinel lymph nodes and those with clinical lymphadenopathy, and the same surgical techniques were used in both groups. Conclusions: The LNRRS at our institution are similar to rates reported at other tertiary-care melanoma centres. A minimum acceptable LNRR can be considered a quality assessment parameter in the surgical management of melanoma with nodal metastasis. Full article

Purpose: We reviewed the experience of a tertiary cancer centre in the management of adrenocortical carcinoma (ACC) treated over 40 years. We also searched the literature for guidelines related to the treatment of ACC and for evidence for adjuvant radiation therapy (RT). Methods: In a retrospective chart review, ACC patients treated between January 1974 and December 2013 were identified, and patient demographics and tumour characteristics were extracted. Outcomes data, including dates and sites of failure, vital status, and cause of death, were collected. Overall survival was estimated using the Kaplan– Meier method. A MEDLINE search using PubMed, Ovid, and embase was used to review the literature about the role of RT and any available management guidelines for ACC. Results: Of 81 patients identified during the chart review, 39 had confirmed ACC. In 32 patients, surgical resection was performed, including in 2 patients with M1 disease. Of those 32 patients, 16 received adjuvant systemic treatment (mitotane or concurrent chemoradiation). Only 6 patients received adjuvant RT, of whom 3 are still alive (2 living with distant failure). At a median follow-up of 3.8 years, 28 patients had died (72%), 10 were living (26%), and 1 had been lost to follow-up. Of the 22 patients for whom failure data were available, 2 experienced local failure, and the rest, distant failure. Conclusions: The current data are insufficient to make treatment recommendations. Use of collaborative databases and consensus about diagnostic and therapeutic guidelines are warranted for better identification of optimum management. Adjuvant RT could be a reasonable option for R1 disease, but further research is needed. Full article

Background: This systematic review was completed by the Exercise for People with Cancer Guideline Development Group, a group organized by Cancer Care Ontario’s Program in Evidence-Based Care (PEBC). It provides background and guidance for clinicians with respect to exercise for people living with cancer in active and post treatment. It focuses on the benefits of specific types of exercise, pre-screening requirements for new referrals, safety concerns, and delivery models. Methods: Using the PEBC’s standardized approach, MEDLINE and EMBASE were systematically searched for existing guidelines, systematic reviews, and primary literature. Results: The search identified two guidelines, eighteen systematic reviews, and twenty-nine randomized controlled trials with relevance to the topic. The present review provides conclusions about the duration, frequency, and intensity of exercise appropriate for people living with cancer. Conclusions: The evidence shows that exercise is safe and provides benefit in quality of life and in muscular and aerobic fitness for people with cancer both during and after treatment. The evidence is sufficient to support the promotion of exercise for adults with cancer, and some evidence supports the promotion of exercise in group or supervised settings and for a long period of time to improve quality of life and muscular and aerobic fitness. Exercise at moderate intensities could also be sustainable for longer periods and could encourage exercise to be continued over an individual’s lifetime. It is important that a pre-screening assessment be conducted to evaluate the effects of disease, treatments, and comorbidities. Full article

Purpose: We evaluated the efficacy and toxicity of accelerated hypofractionated radiotherapy (AHYPOF-RT) for central-type small lung tumours. Methods: Between November 2006 and January 2015, 40 patients with central-type small lung tumours underwent AHYPOF-RT delivered using 10 MV X-rays and a coplanar 3-field technique. The number of fractions ranged from 24 to 28, with a fraction size of 2.5–3 Gy. A total dose of 69–75 Gy to the isocentre of the planning target volume was administered to each patient. Cumulative survival and local control rates were calculated using the Kaplan–Meier method. Results: The 27 men and 13 women enrolled in the study had a median age of 79 years (range: 60−87 years). The tumour stage was T1a in 9 patients, T1b in 17 patients, and T2a in 14 patients, with a median size of 26.5 cm (range: 11–49 cm). The median follow-up period was 23 months. A complete response was achieved in 3 patients (7.5%), and a partial response, in 17 patients (42.5%). The overall 2-year and 3-year local control rates were 87.3% and 81.8% respectively; the 2-year and 3-year overall survival rates were 78.9% and 66.7% respectively. Grade 3 pneumonitis occurred in 3 patients; no other severe adverse events (≥grade 3) were observed in any patient. Conclusions: Accelerated hypofractionated radiotherapy using a fraction size of 2.5–3 Gy was highly safe and can be a more effective treatment option than conventional radiotherapy for patients with central-type small lung tumours. Full article

Objectives: We aimed to explore and identify what makes patient death more emotionally difficult for oncologists and how oncologists cope with patient death. Methods: A convenience sample of 98 Canadian oncologists (50 men, 48 women) completed an online survey that included a demographics section and a section about patient death. Results: More than 80% of oncologists reported that patient age, long-term management of a patient, and unexpected disease outcomes contributed to difficult patient loss. Other factors included the doctor–patient relationship, identification with the patient, caregiver-related factors, oncologist-related factors, and “bad deaths.” Oncologists reported varying strategies to cope with patient death. Most prevalent was peer support from colleagues, including nurses and other oncologists. Additional strategies included social support, exercise and meditation, faith, vacations, and use of alcohol and medications. Conclusions: Oncologists listed a number of interpersonal and structural factors that make patient death challenging for them to cope with. Oncologists reported a number of coping strategies in responding to patient death, including peer support, particularly from nursing colleagues. No single intervention will be suitable for all oncologists, and institutions wishing to help their staff cope with the emotional difficulty of patient loss should offer a variety of interventions to maximize the likelihood of oncologist participation. Full article

Background: The concept of maintenance therapy in cancer treatment is currently under debate because of modest survival benefits, added toxicity, economic considerations, and quality-of-life concerns. Traditional Chinese Medicine (TCM) is widely used in China for cancer patients, offering the advantages of low toxicity and enhancement of quality of life. However, no systematic reviews or meta-analyses have assessed the role of TCM as maintenance treatment for non-small-cell lung carcinoma. Methods: We searched the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, PubMed, EMBASE, and the Cochrane Library databases for all eligible studies. The endpoints were overall survival (OS), progression-free survival (PFS), the 1-year and 2-year survival rates, and performance status. Our meta-analysis used a fixed-effects model and a random-effects model for heterogeneity in the Stata software application (version 11.0: StataCorp LP, College Station, TX, U.S.A.), with the results expressed as hazard ratios (HRS) or risk ratios (RRS), with their corresponding 95% confidence intervals (95% CIS). Results: Sixteen randomized studies representing 1150 patients met the inclusion criteria. Compared with best supportive care, observation, or placebo, TCM as maintenance treatment was associated with a significant increase in OS (HR: 0.49; 95% CI: 0.35 to 0.68; p < 0.001), PFS (HR: 0.66; 95% CI: 0.51 to 0.84; p = 0.001), and 2-year survival rate (RR: 0.63; 95% CI: 0.44 to 0.92, p = 0.017), and a significant improvement in performance status (RR: 0.68; 95% CI: 0.61 to 0.75; p < 0.001). Conclusions: For patients who show non-progression—including stable disease, partial response, or complete response—after first-line chemotherapy, including those with poor quality of life, oral Chinese herbal medicine can be considered an efficient and safe maintenance therapy strategy. Full article

The 2017 annual meeting of the American Society of Clinical Oncology took place in Chicago, Illinois, 2–6 June. At the meeting, results from key studies in the first-line treatment of indolent non-Hodgkin lymphoma (iNHL) were presented. Of those studies, two were selected for oral presentations: 9-year follow-up data from the STiL NHL1 trial, which compared the efficacy and safety of bendamustine plus rituximab (BR) with those of rituximab plus cyclophosphamide–vincristine–prednisone–doxorubicin (R-CHOP); and 5-year follow-up data from the bright study, which compared BR with R-CHOP and R-CVP (rituximab plus cyclophosphamide–vincristine–prednisone) combined. Our meeting report describes the foregoing studies and includes interviews with key investigators, plus commentaries from three Quebec hematologists on the potential effects for Canadian practice. Full article

Background: Combination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (aCRC). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial. Methods: A multicentre phase I/II trial of reduced-dose capecitabine (2000 mg/m², days 1–14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ECOG) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (LDH) (n = 105), or prior pelvic radiation (n = 54). Based on phase I results, patients with prior pelvic radiation received capecitabine 750 mg/m² twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity. Results: Median age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0–50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand–foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (PFS) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ECOG performance status of 0 (compared with 1 or more) and normal LDH (compared with elevated LDH). Conclusions: Toxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and PFS appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m², or even 750 mg/m², twice daily is an appropriate dose in elderly or frail patients with aCRC. Full article

Acute care hospitals have a role in managing the health care needs of people affected by cancer when they are at the end of life. However, there is a need to provide end-of-life care in other settings, including at home or in hospice, when such settings are more appropriate. Using data from 9 provinces, we examined indicators that describe the current landscape of acute care hospital use at the end of life for patients who died of cancer in hospital in Canada. Interprovincial variation was observed in acute care hospital deaths, length of stay in hospital, readmission to hospital, and intensive care unit use at the end of life. High rates of acute care hospital use near the end of life might suggest that community and home-based end-of-life care might not be suiting patient needs. Full article

Purpose: The purpose of the present review was to determine which antineoplastic systemic therapy is most effective in improving clinical outcomes for patients with incurable gastroenteropancreatic neuroendocrine tumours (NETS). Methods: A systematic search (2008–2016) of the literature in the medline and embase databases and the Cochrane Database of Systematic Reviews was conducted; abstracts from the American Society of Clinical Oncology, the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, the European Society for Medical Oncology, the European Cancer Congress, the European Neuroendocrine Tumor Society, and the North American Neuroendocrine Tumor Society were reviewed. Draft recommendations were created, and a comprehensive review process was undertaken. Outcomes—including progression-free survival (PFS), overall survival, objective response rate, adverse events, and quality of life—were extracted from each of the studies. Results: Eleven randomized controlled trials (RCTS), sixteen nonrandomized prospective studies, and thirteen retrospective studies met the inclusion criteria. Conclusions: Patients with well- or moderately-differentiated pancreatic NETS (PNETS) should receive targeted therapy (that is, everolimus or sunitinib), and patients with non-PNETS should be offered either targeted therapy (that is, everolimus) or somatostatin analogues (SSAS—that is, octreotide long-acting release or lanreotide). Evidence from two phase iii trials demonstrated a significant PFS benefit for patients with PNETS. For patients with non-PNETS, the evidence comes from subgroup analyses of RCTS, as well as from a planned interim analysis. Although the evidence has limitations, the rarity of the disease, coupled with the difficulty of conducting methodologically sound trials in the affected population, means that treatment decisions have to make use of the best available evidence. Because of insufficient evidence for both PNETS and non-PNETS, no evidence-based recommendation can be made for or against other types of targeted therapy, other SSAS, chemotherapy, or combination therapy. Full article

Introduction: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mCRPC) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mCRPC management patterns and therapy utilization trends in Quebec. Methods: The study cohort consisted of patients dying of prostate cancer (PCA) between January 2001 and December 2013, selected from Quebec public health care insurance databases. Patient selection was based on death from a PCA-related cause or therapy used according to the Canadian Urological Association guidelines on mCRPC management. Treatments included chemotherapy (mitoxantrone before 2005 and docetaxel after 2005), abiraterone, bone-targeted therapy (zoledronic acid or denosumab, or both), and palliative radiation therapy (RT). During the study period, neither enzalutamide nor cabazitaxel was publicly reimbursed in Quebec, and as a result, no capture of their use was possible for this study. Multivariate logistic regression was used to identify factors associated with the probability of receiving chemotherapy, bone-targeted therapies, and palliative RT before death from PCA. Results: Overall, the database search identified 3106 patients who died of PCA between January 2001 and December 2013. Median age of death was 78 years. Of those 3106 patients, just 2568 (83%) received mCRPC-specific treatments: chemotherapy, abiraterone, palliative RT, or bone-targeted therapy; the other 17% of the patients were managed solely with maximum androgen blockade (androgen deprivation therapy plus anti-androgens) despite a record of PCA-related death. Logistic regression analyses indicate that patients dying after 2005 were more likely to have received chemotherapy [odds ratio (OR): 1.51; 95% CI: 1.22 to 1.85] and bone-targeted therapy (OR: 1.97; 95% CI: 1.64 to 2.37). Age was a significant predictor for the use of chemotherapy, bone-targeted therapy, and palliative RT (ORS in the range 0.96–0.98, p < 0.05). Conclusions: Patient age seems to be a strong determinant in the of selection mCRPC therapy, affecting the probability of the use of chemotherapy, bone-targeted therapy, or palliative RT. Although chemotherapy is still used only in a small percentage of patients, the introduction of new therapies—such as bone-targeted therapy, docetaxel, and abiraterone—affected treatment selection over time. The availability of enzalutamide since February 2014 will likely produce additional changes in mCRPC management. Full article

Background: Various tyrosine kinase signalling pathways affect the development and progression of colorectal cancer (crc). In clinical trials, regorafenib has been associated with a survival benefit in metastatic crc (mcrc). We assessed the safety and efficacy of regorafenib in real-world patients. Methods: In a retrospective review of patients with mcrc treated with regorafenib at our institution from 2013 to 2015, patient demographics, treatment, and survival data were collected. Progression-free survival (pfs) and overall survival (os) were estimated using the Kaplan–Meier method. Results: In total, 48 patients were offered regorafenib, and 35 (73%) started treatment. Of the patients who started regorafenib, 57% were men. Median age in the cohort was 61 years, and all patients had a performance status in the range 0–2. Time from diagnosis of mcrc to regorafenib treatment was more than 18 months in 71% of patients. Starting dose was 160 mg in 54% of the patients, 120 mg in 40%, and 80 mg in 6%. Dose reductions occurred in 34% of the patients, and interruptions, in 29%. Best response was progressive disease (60%) and stable disease (17%); response in the rest of the patients was unknown. The most common adverse events on regorafenib (any grade) were fatigue (57%), hyperbilirubinemia (43%), thrombocytopenia (37%), anorexia (31%), and hypertension (31%). The most common grade 3 or 4 adverse events were fatigue (29%), hypophosphatemia (17%), weight loss (11%), and hyperbilirubinemia (9%). Common reasons for discontinuing regorafenib included progressive disease (51%) and toxicity (26%). In patients treated with regorafenib, pfs was 2.4 months (95% confidence interval: 1.8 to 3.3 months) and os was 5.6 months (95% confidence interval: 3.7 to 8.9 months). No factors were associated with survival in univariate or multivariate analysis. Conclusions: In a real-world setting, regorafenib is associated with survival similar to that reported in the randomized controlled trials, but at the expense of toxicity leading to discontinuation in many patients. Future studies of regorafenib should focus on identifying the patients most likely to benefit and on minimizing toxicity. Full article

Background: In the present study, we examined the pattern of metastatic spread in patients with advanced non-small-cell lung cancer (NSCLC) and the effect of EGFR mutations. Methods: Patients were identified from a provincial cancer registry, and individual medical records were reviewed. Patients were included if they had stage IV NSCLC and underwent diagnostic EGFR mutation testing. Patients were divided into EGFR mutation-positive (EGFR+) and EGFR wild type (WT) cohorts. The primary endpoint was the cumulative incidence for each metastatic site: lung, bone, brain, liver, adrenal glands, distant nodes, and other. Cumulative incidence curves were estimated using a competing-risks method. The secondary outcome was survival. Results: Of the 543 identified patients, 121 (22.3%) tested as EGFR+, and 422 (77.7%) tested as EGFR WT. The incidence of brain (39.2% vs. 28.2%, p = 0.038) and lung (61.2% vs. 51.0%, p = 0.048) metastasis was higher in the EGFR+ cohort than in the EGFR WT cohort. In the EGFR+ cohort, a higher incidence of liver metastasis was associated with the exon 21 mutation subtype than with the exon 19 deletion subtype [23% vs. 7%, p < 0.01; hazard ratio (HR): 3.47]. Median survival was significantly longer for the EGFR+ cohort than for the EGFR WT cohort (22.4 months vs. 7.9 months, p < 0.001). In multivariable analysis, brain (HR: 1.73), liver (HR: 1.69), and bone (HR: 1.89) metastases were associated with worse survival. Conclusions: Rates of lung and brain metastases are higher in EGFR mutation carriers, even when adjusted for differences in survival. Brain, liver, and bone metastases are independent negative prognostic factors for survival. Full article

Purpose: The purpose of the present study was to determine user satisfaction with Nanny Angel Network (NAN), a free childcare service for mothers undergoing cancer treatment. Methods: All 243 living mothers who had used the nan service were invited by telephone to participate in an online research survey; 197 mothers (81%) consented to participate. The survey, sent by e-mail, consisted of 39 items divided into these categories: demographics, supports, use, satisfaction, and general comments. Results: Of the 197 mothers who consented to receive the e-mailed survey, 104 (53%) completed it. More than 90% of the mothers were very satisfied with the help and support from their Nanny Angel. Many mothers mentioned that the Nanny Angel was most helpful during treatment and medical appointments, with 75% also mentioning that their Nanny Angel helped them to adhere to their scheduled medical appointments. However, 64% felt that they had not received enough visits from their Nanny Angel. Conclusions: Satisfaction with the nan childcare provider was high, but mothers wished the service had been available to them more often. Our study highlights the importance of providing childcare to mothers with inadequate support systems, so as to allow for greater adherence to treatment and medical appointments, and for more time to recover. Full article

In the 1 November issue of The Lancet in 2016, three papers and three accompanying editorials reviewed the descriptive epidemiology of breast and cervical cancer in low-income countries, highlighting the shortcomings of current efforts at cancer control and the need for improvement [...] Full article