Curr. Oncol., Volume 22, Issue 3 (June 2015) – 26 articles

Background: The endpoints of progression-free survival (pfs) and time-to-progression (ttp) are frequently used to evaluate the clinical benefit of anticancer drugs. However, the surrogacy of those endpoints for overall survival (os) is not validated in all cancer settings. In the present study, we used a trial-based approach to assess the relationship between median pfs or ttp and median os in chronic lymphocytic leukemia (cll). Methods: The pico (population, interventions, comparators, outcomes) method was used to conduct a systematic review of the literature. The population consisted of patients with cll; the interventions and comparators were standard therapies for cll; and the outcomes were median pfs, ttp, and os. Two independent reviewers screened titles, abstracts, and full papers for eligibility and then extracted data from selected studies. Correlation coefficients were calculated to assess the relationship between median pfs or ttp and median os. Subgroup correlation analyses were also conducted according to the characteristics of the selected studies (such as line of treatment and type of treatment under investigation). Results: Of the 1263 potentially relevant articles identified during the literature search, twenty-three were included. On average, median pfs or ttp was 16.0 months (standard deviation: 12.4 months) and median os was 43.5 months (standard deviation: 31.2 months). Results of the correlation analysis indicated that median pfs or ttp is highly correlated with median os (Spearman correlation coefficient: 0.813; p ≤ 0.001). A significant correlation between median pfs or ttp and median os was observed in second- and subsequent-line therapies, but not in the first-line setting. Conclusions: Our study demonstrates a strong correlation between median pfs or ttp and median os in previously treated cll, which reinforce the hypothesis that pfs and ttp could be adequate surrogate endpoints for os in this cancer setting. Full article

Therapeutic Revolution: The History of Medical Oncology From Early Days to the Creation of the Subspecialty is a book about the history of medical oncology, the extraordinary turbulence that permeated the early years of the field, and the events that led to this subspecialty of internal medicine [...] Full article

Dr. Pierre Band’s book on The History of Medical Oncology from Early Days does matter—particularly nowadays, in the era of fast developments and a rising number of subspecialties with language at times too specialized to follow. From that perspective, the book’s largely educational and detailed portrayal of medical oncology is hugely refreshing [...] Full article

After some decades of contention, one can almost despair and conclude that (paraphrasing) “the mammography debate you will have with you always.” Against that sentiment, in this review I argue, after reflecting on some of the major themes of this long-standing debate, that we must begin to move beyond the narrow borders of claim and counterclaim to seek consensus on what the balance of methodologically sound and critically appraised evidence demonstrates, and also to find overlooked underlying convergences; after acknowledging the reality of some residual and non-trivial harms from mammography, to promote effective strategies for harm mitigation; and to encourage deployment of new screening modalities that will render many of the issues and concerns in the debate obsolete. To these ends, I provide a sketch of what this looking forward and beyond the current debate might look like, leveraging advantages from abbreviated breast magnetic resonance imaging technologies (such as the ultrafast and twist protocols) and from digital breast tomosynthesis—also known as three-dimensional mammography. I also locate the debate within the broader context of mammography in the real world as it plays out not for the disputants, but for the stakeholders themselves: the screening-eligible patients and the physicians in the front lines who are charged with enabling both the acts of screening and the facts of screening at their maximally objective and patientaccessible levels to facilitate informed decisions. Full article

Malignant pheochromocytoma is a tumour with a very low incidence that occurs sporadically or in the presence of multiple endocrine neoplasia. We present the case of a woman with a sporadic occurrence of pheochromocytoma diagnosed in the phase of multiple dissemination in the abdominal cavity and overexpressing adrenaline, noradrenaline, and dopamine. Local transarterial chemoembolization and systemic treatment with lanreotide resulted in a very good response, a decrease in the production of catecholamines for 12 months and a partial decrease for another 8 months, with stabilization of disease determined by imaging. Systemic treatment with tegafur resulted in disease stabilization lasting 50 months, after which the drug was discontinued because of adverse effects. Maintenance therapy with lanreotide continues, and no disease progression has been observed for 4 months. The treatment algorithm for such patients is multidisciplinary and must always take into account the current scope of the disease, intercurrence, and the general condition of the patient. Full article

Background: Systemic therapy options are needed for women with recurrent, metastatic, or persistent cervical cancer. This systematic review and clinical practice guideline were developed to address that need, and to update a 2007 guideline from Cancer Care Ontario’s Program in Evidence-Based Care. Methods: The literature between 2006 and April 2014 in the medline and embase databases, the Cochrane Database of Systematic Reviews (Issue 4, 2014), the Cochrane Central Register of Controlled Trials (Issue 3, 2014), relevant guideline databases, and conference proceedings of the American Society of Clinical Oncology (2007–2013) was searched. A working group developed draft guidelines and incorporated comments and feedback from internal and external reviewers. Results: Four phase iii randomized controlled trials met the inclusion criteria for the review and provided the basis for draft recommendations. Feedback was obtained from Ontario practitioners and others abroad, which led to modifications to the draft recommendations. Three key recommendations were developed. Conclusions: The working group concluded that all patients should be offered the opportunity to participate in appropriate randomized clinical trials. Cisplatin–paclitaxel, cisplatin–vinorelbine, cisplatin–gemcitabine, and cisplatin–topotecan are recommended combinations for this patient population. The substitution of carboplatin for cisplatin in the foregoing combinations can also be recommended because carboplatin is associated with fewer adverse effects and greater ease of administration. Selection of combination chemotherapy will depend on the toxicity profile, patient preference, and other factors. Finally, bevacizumab in combination with cisplatin–paclitaxel or carboplatin–paclitaxel is recommended for a specific subset of the target population as outlined in Gynecologic Oncology Group study 0240. Full article

Introduction: The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (RDF) in the prophylaxis of radiation-induced nausea and vomiting (RINV). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. Methods: Patients undergoing palliative radiotherapy at risk for RINV were prescribed ondansetron RDF 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting–specific daily diary, the Functional Living Index–Emesis (FLIE), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–C15 Palliative (QLQ-C15-PAL). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. “Overall control” was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. “Acute phase” was defined as the days during radiation until the first day after radiation; “delayed phase” was defined as days 2–10 after radiation. Results: The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and QLQ-C15-PAL questionnaires. Conclusions: Ondansetron rdf is effective for the prophylaxis of RINV. Full article

Background: Proliferative scoring of breast tumours can guide treatment recommendations, particularly for estrogen receptor (ER)–positive, HER2-negative, T1–2, N0 disease. Our objectives were to (1) estimate the proportion of such patients for whom proliferative indices [mitotic count (MC), Ki-67 immunostain, and Oncotype DX (Genomic Health, Redwood City, CA, U.S.A.) recurrence score (RS)] were obtained; (2) compare the indices preferred by oncologists with the indices available to them; (3) correlate Nottingham grade (NG) and its subcomponents with Oncotype DX; (4) assess interobserver variation. Methods: All of the ER-positive, HER2-negative, T1–2, N0 breast cancers diagnosed from 2007 to 2011 (n = 5110) were linked to a dataset of all provincial breast cancers with a RS. A 5% random sample of the 5110 cancers was reviewed to estimate the proportion that had a MC, Ki-67 index, and RS. Correlation coefficients were calculated for the RS with NG subcomponent scores. Interobserver variation in histologic grading between outside and central review pathology reports was assessed using a weighted kappa test. Results: During 2007–2011, most cancers were histologically graded and assigned a MC; few had a Ki-67 index or RS. The NG and MC were significantly positively correlated with RS. The level of agreement in histologic scoring between outside and central pathology reports was good or very good. Very few cases with a low MC had a high RS (1.8%). Conclusions: Patients with low NG and MC scores are unlikely to have a high RS, and thus are less likely to benefit from chemotherapy. In the context of limited resources, that finding can guide clinicians about when a RS adds the most value. Full article

Introduction: Randomized controlled trials (RCTS) are the “gold standard” for establishing treatment efficacy; however, efficacy does not automatically translate to a comparable level of effectiveness in routine practice. Our objectives were to (1) describe outcomes of palliative platinum-doublet chemotherapy (PPDC) in non-small-cell lung cancer (NSCLC) in routine practice, in terms of survival and well-being; and (2) compare the effectiveness of PPDC in routine practice with its efficacy in RCTS. Methods: Electronic treatment records were linked to the Ontario Cancer Registry to identify patients who underwent PPDC for NSCLC at Ontario’s regional cancer centres between April 2008 and December 2011. At each visit to the cancer centre, a patient’s symptoms are recorded using the Edmonton Symptom Assessment System (ESAS). Score on the esas “well-being” item was used here as a proxy for quality of life (QOL). Survival in the cohort was compared with survival in RCTS, adjusting for differences in case mix. Changes in the ESAS score were measured 2 months after treatment start. The proportion of patients having improved or stable well-being was compared with the proportion having improved or stable QOL in relevant RCTS. Results: We identified 906 patients with pre-PPDC ESAS records. Median survival was 31 weeks compared with 28–48 weeks in RCTS. After accounting for deaths and cases lost to follow-up, we estimated that, at 2 months, 62% of the cohort had improved or stable well-being compared with 55%–63% who had improved or stable QOL in RCTS. Conclusions: The effectiveness of PPDC for NSCLC in routine practice in Ontario is consistent with its efficacy in RCTS, both in terms of survival and improvement in well-being. Full article

Introduction: This systematic review addresses the use of epidermal growth factor receptor (egfr) inhibitors in three populations of advanced non-small-cell lung cancer (nsclc) patients—unselected, selected, and molecularly selected—in three treatment settings: first line, second line, and maintenance. Methods: Ninety-six randomized controlled trials found using the medline and embase databases form the basis of this review. Results: In the first-line setting, data about the efficacy of egfr tyrosine kinase inhibitors (tkis) compared with platinum-based chemotherapy are inconsistent. Results from studies that selected patients based on clinical characteristics are also mixed. There is high-quality evidence that an egfr tki is preferred over a platinum doublet as initial therapy for patients with an activating mutation of the EGFR gene. The egfr tkis are associated with a higher likelihood of response, longer progression-free survival, and improved quality of life. Multiple trials of second-line therapy have compared an egfr tki with chemotherapy. Meta-analysis of those data demonstrates similar progression-free and overall survival. There is consequently no preferred sequence for second-line egfr tki or second-line chemotherapy. The egfr tkis have also been evaluated as switch-maintenance therapy. No molecular marker could identify patients in whom a survival benefit was not observed; however, the magnitude of the benefit was modest. Conclusions: Determination of EGFR mutation status is essential to making appropriate treatment decisions in patients with nsclc. Patients who are EGFR mutation–positive should be treated with an egfr tki as first-line therapy. An egfr tki is still appropriate therapy in patients who are EGFR wild-type, but the selected agent should be administered as second- or third-line therapy. Full article

Background: Delineating the nodal clinical target volume (CTVn) remains a challenging task in patients with cervical or upper thoracic esophageal carcinoma (EC). In particular, the extent of the lymph area that should be included in the irradiation field remains controversial. In the present study, the extent of the CTVn was determined based on the incidence of lymph node involvement mapped by computed tomography (CT) imaging. Methods: Our study included 468 patients who were diagnosed with cervical and upper thoracic ec and who received staging information between June 2005 and April 2011. The anatomic distribution of metastatic regional lymph nodes was mapped using CT images and grouped using the levels established by the Radiation Therapy Oncology Group. The probability of the various groups being involved was examined. If a lymph node group had a probability of 10% or more of being involved, it was considered at high risk for metastasis, and elective treatment as part of the CTVn was recommended. Results: Lymph node involvement was mapped by CT in 256 patients (54.7%). Not all lymph node groups should be included in the CTVn. For cervical lesions, the involved lymph nodes were located mainly between the hyoid bone and the arcus aortae; the recommended CTVn should consist of the neck lymph nodes at levels iii and iv (supraclavicular group) and thoracic groups 2 and 3P. In upper thoracic ec patients, most of the involved lymph nodes were distributed between the cricoid cartilage and the subcarinal area; the CTVn should cover the supraclavicular group and thoracic nodal groups 2, 3P, 4, 5, and 7. Conclusions: Our CT-based study indicates a specific distribution and incidence of metastatic lymph node groups in patients with cervical and upper thoracic EC. The results suggest that regional lymph node groups should be electively included in the CTVn for precise radiation administration. Full article

In the Canadian National Breast Screening Study, the hazard ratio for breast cancer–specific death was 1.47 for women with cancers detected in the prevalence screening round, 0.9 for women with cancers detected in the subsequent four screening rounds, and 1.05 for women with cancers detected in all screening rounds [...] Full article

About the ongoing breast cancer screening mammography debate (less a controversy, because many points of consensus and convergence are present if not always apparent), we can make these points as prelude: that it is complex; that it is naïvely implausible to expect any decisive final resolution to the residual issues that will be convincing to the principle contending parties; and that behind it all, the devil is in the methodology [...] Full article

Background: For cancer patients, information about their disease and its treatment is often delivered within a short time period, potentially leading to patient misunderstanding, which can impede optimal patient care. In this 3-part clinical study, we investigated the utility of an individualized care plan for patients with gastrointestinal (gi) cancer starting a new treatment. Methods: In part 1, a comprehensive literature search identified items for potential inclusion in the care plan. Those items were formatted into a questionnaire. The questionnaire was then administered to patients as a structured interview. In part 2, health care professionals involved in the care of patients with gi cancer evaluated the resulting care plan for content and relevancy. In part 3, a 20-week prospective cohort study (10 weeks using standard of care, 10 weeks using individualized care plans) was conducted. Outcomes were assessed at baseline and at 2–4 weeks after administration of the care plan. Results: In part 1, a 73-item questionnaire was developed and completed by 20 patients in semi-structured interviews. In part 2, long and short versions of the care plan were created. Most health care professionals preferred the long version. Based on their comments, a final version of the care plan was created. The part 3 study enrolled 104 patients. Overall satisfaction scores were significantly higher in the intervention group at baseline (p = 0.010) and follow-up (p = 0.005). Compared with control patients, the intervention cohort also reported significantly higher overall quality of life (p = 0.044) and fewer symptoms of anxiety (p = 0.048) at follow-up. Conclusions: Provision of an individualized care plan resulted in improvements in outcome measures at both baseline and follow-up. Future studies are needed to confirm these findings. Full article

Background: The importance of histologic classification in selecting the appropriate systemic therapy for non-small-cell lung cancer (NSCLC) came to attention in 2007. In British Columbia, that information was communicated through international and national meetings, our centralized cancer care program, and to the medical community at large in multidisciplinary forums. We examined the effects of those education programs on the categorization of NSCLC and associated systemic treatment practices. Methods: The BC Cancer Agency provides cancer care to 4.6 million residents of British Columbia. A retrospective review of all stage IIIB and IV NSCLC patients referred in 2007 and 2011 collected baseline characteristics, treatment, and outcomes. Histology was classified using the International Classification of Diseases for Oncology, 3rd edition, for the Canadian Cancer Registry. Results: In 2007, 671 patients were referred, and 170 received chemotherapy; in 2011, the relevant figures were 680 and 197 respectively. Baseline characteristics in the cohorts were not statistically significantly different in 2007 and 2011. Histologic classifications in 2007 were 41% nonsquamous, 13% squamous, and 46% not otherwise specified (NOS); in 2011, they were 63%, 17%, and 20% respectively. Exposure to pemetrexed in any line of therapy in 2007 was 22% for nonsquamous, 17% for squamous, and 10% for NOS; in 2011, exposure was 39%, 3%, and 37% respectively. Exposure to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) in 2007 was 36%, 22%, and 33%; in 2011, it was 64%, 60%, and 63%. Median overall survival duration, 2007 versus 2011, was 3.25 months versus 3.57 months with best supportive care, and 11.31 months versus 11.54 months with chemotherapy. Conclusions: The specificity of NSCLC histologic categorization improved in 2011 compared with 2007, with a reduction of 26 percentage points in the rate of NOS disease. The proportion of patients treated with chemotherapy over time remained the same, but the use of pemetrexed and egfr tki increased. The increased accuracy in histologic classification resulted in more appropriate utilization of systemic drugs. Full article

Background Treatment for advanced non-small-cell lung cancer (NSCLC), especially in patients with wild-type EGFR, remains limited. Recently, erlotinib, a tyrosine kinase inhibitor (TKI) targeting EGFR mutation, was approved as second-line treatment in EGFR wild-type NSCLC. Despite evidence of better overall survival (OS) with chemotherapy than with TKI in second-line treatment, data on the use of TKI in the real-life clinical setting remain limited. The present practice review of TKI use for second- and third-line treatment in EGFR wild-type NSCLC also compares clinical outcomes for TKI and single-agent docetaxel as second-line treatment. Methods Our retrospective cohort study included patients with EGFR wild-type NSCLC treated at the Jewish General Hospital (Montreal, QC) between 2003 and 2013. Patients received a TKI (erlotinib or gefitinib) in the second and third line or docetaxel in the second line. For each group, we determined OS, disease control rate, progression-free survival (PFS), and event-free survival (EFS). Results The TKI group included 145 patients, with 92 receiving second-line treatment. In the control group, 53 patients received docetaxel as second-line therapy. In the TKI group, OS was 6.0 months; PFS, 2.7 months; and EFS, 3.0 months. Comparing second-line treatments, OS was 5.3 and 5.0 months respectively (p = 0.88), PFS was 2.5 and 1.8 months respectively (p = 0.041), and EFS was 3.0 and 1.7 months respectively (p = 0.009). Conclusions In our study cohort, second-line therapy for EGFR wild-type NSCLC with TKI (compared with docetaxel) was associated with statistically better PFS and EFS and noninferior OS. Those findings raise the question of whether EFS should also be considered when choosing second-line treatment in this patient population. Full article

Purpose: We assessed the quality of life (qol) of nasopharyngeal carcinoma (npc) survivors with a survival time of more than 2 years in Fujian, China, and we analyzed factors influencing qol. Method: We calculated the prevalence of psychological distress and radiotherapy (rt)–induced symptoms in 216 npc survivors who participated in a cross-sectional survey. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (version 3.0) was used to assess the qol of npc survivors. Multiple linear regression was applied to analyze the factors influencing qol. Results: The prevalence rates of rt-induced symptoms and psychological problems were 11.58% (95% ci: 7.21% to 15.58%) for difficulty in swallowing, 17.59% (95% ci: 12.51% to 22.67%) for mouth dryness or sores, 13.89% (95% ci: 9.28% to 18.50%) for nasal dryness or congestion, 18.52% (95% ci: 13.34% to 23.70%) for fatigue, 11.11% (95% ci: 6.92% to 15.30%) for frequent dizziness, 18.06% (95% ci: 12.93% to 23.19%) for decline in hearing, 14.81% (95% ci: 10.07% to 19.55%) for poor sleep quality, 18.52% (95% ci: 13.34% to 23.70%) for worry about disease recurrence, 18.98% (95% ci: 13.75% to 24.21%) for anxiety, and 25.00% (95% ci: 19.23% to 30.77%) for depression. Mean survival times were 4.32 ± 2.63 years in patients with mouth dryness or sores, 4.26 ± 2.90 years in patients with fatigue, and 5.60 ± 2.94 years in patients with a decline in hearing. The mean global qol score was 74.21 (95% ci: 72.22 to 76.20). At a significance level of α = 0.05, the factors influencing qol were age (p = 0.032), education level (p = 0.001), anxiety score (p < 0.001), depression score (p < 0.001), mouth dryness or sores (p < 0.001), fatigue (p = 0.027), and disease stage (p = 0.044). Conclusions: The prevalence rates of mouth dryness or sores, fatigue, decline in hearing, depression, and anxiety were high in npc survivors with a survival time of more than 2 years. These rt-induced symptoms and psychological problems can last for many years after rt. The qol of the npc survivors was good. Factors influencing qol were age, education level, anxiety, depression, mouth dryness or sores, fatigue, and disease stage. Our results suggest that during clinical treatment, doctors should minimize the radiation dose to the ears of patients. In addition, our results emphasize the importance of providing oral and ear nursing and psychological care to npc survivors. Full article