Curr. Oncol., Volume 20, Issue 2 (April 2013) – 24 articles

New antitumour immunotherapy strategies for stage IV metastatic melanoma include ipilimumab, a monoclonal antibody against CTLA-4. Patterns of response with cancer immunotherapy differ from those with cytotoxic chemotherapy. We present two cases of long-duration immune-related responses with ipilimumab in a phase II trial. A 66-year-old woman with multiple lung metastases from a scalp primary melanoma received 4 doses of ipilimumab with mixed clinical response. However, after the first maintenance dose, she developed severe ileitis and colitis that responded to steroid therapy. Four months later, she had surgery and radiotherapy for a single brain metastasis. Radiologically, stable disease continued for 36 months after the last ipilimumab dose, and partial response for 5 years after ipilimumab start. A 54-year-old man with cervical lymph node and pulmonary metastases from a scalp primary melanoma received three induction doses of ipilimumab. He developed alopecia universalis and widespread vitiligo, and he discontinued treatment because of hypophysitis. Maintenance ipilimumab was started after a 6-month drug-free interval, with no further adverse events over 15 cycles. At week 12, computed tomography imaging showed no lung metastases and partial response in a supraclavicular lymph node, which was positive on positron-emission tomography. Five years after starting ipilimumab, the supraclavicular lymph node was calcified, and the patient was off steroid therapy and asymptomatic. The foregoing patients demonstrate long responses with ipilimumab (in association with delayed severe colitis in one case, and a constellation of immune events, including alopecia universalis in another). Re-treatment with ipilimumab may be possible even after significant immune adverse events. Full article

Very late recurrence of gastric cancer is rare. Here, we report a dramatic recurrence of gastric cancer, with isolated skeletal metastasis and bone marrow carcinomatosis, 22 years after the patient’s initial presentation. Gastric cancer recurrence involving bone or bone marrow is also uncommon and associated with poor prognosis. Pathology from a bone marrow biopsy showed signet ring cell morphology. The patient in this case demonstrated a surprising response—lasting 11 months—to palliative chemotherapy with cisplatin and capecitabine. This case report and literature review describes the characteristics of late gastric cancer recurrence and an approach to the diagnosis and management of patients with bone metastasis or bone marrow carcinomatosis. Full article

An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4–ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc. Full article

Background: Promising new drugs such as lenalidomide, an immunomodulatory agent, are available for the treatment of multiple myeloma. We describe the process of creating a provincial guideline for the use of lenalidomide, alone or in combination with other drugs, in relapsed, refractory, or newly diagnosed disease (including smoldering and symptomatic patients, and candidates and non-candidates for transplant) and in maintenance treatment (after transplant or non-transplant therapy); and for strategies to manage lenalidomide-related toxicities. Methods: Outcomes of interest included overall survival, event-free survival, progression-free survival, time to progression, time to next treatment, response rate, and incidence of serious toxicity. The MEDLINE, EMBASE, and Cochrane Library databases, as well as meeting abstracts and the Web sites of relevant organizations, were systematically searched for relevant literature. Results: Recommendations were developed using the evidence from published studies and the clinical expertise of the working group and of the Cancer Care Ontario Hematology Disease Site Group. Conclusions: Lenalidomide in combination with dexamethasone can be recommended for both previously untreated and treated patients with multiple myeloma. Guidelines for the management of cytopenias, venous thromboembolism, and second primary malignancies are discussed. Full article

Aims: To provide evidence-based practice guideline recommendations concerning the role of endolaryngeal surgery (with or without laser) compared with radiation therapy for patients with early (T1) glottic cancer, assessing survival, locoregional control, laryngeal preservation rates, and voice outcomes. Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies from 1996 to 2011. Recommendations were formulated based on that evidence and on the expert opinion of Cancer Care Ontario’s Head and Neck Cancer disease site group. The systematic review and practice guideline were externally reviewed by practitioners in Ontario, Canada. Results: The available evidence was of a level insufficient to demonstrate a clear difference between treatment options when considering the likelihood of local control or overall survival. Although the evidence was mainly retrospective, there was a suggestion that, compared with surgery, radiotherapy might be associated with less measureable perturbation of voice without a significant difference in patient perception. The likelihood of laryngeal preservation may be higher when surgery can be offered as initial treatment. Conclusions: For patients with early (T1) glottic cancer, the evidence is insufficient to demonstrate a difference between endolaryngeal surgery (with or without laser) and external-beam radiation therapy. The choice between treatment modalities has been based on patient and clinician preferences and general medical condition. Full article

Purpose: Multidisciplinary cancer clinics may improve patient care. We examined how a single-day multidisciplinary liver clinic (MDLC) affected care recommendations for patients compared with the recommendations provided before presentation to the MDLC. Methods: We analyzed the demographic and clinicopathologic data of 343 patients assessed in the Johns Hopkins Liver Tumor Center from 2009 to 2012, comparing imaging and pathology interpretation, diagnosis, and management plan between the outside provider (OSP) and the MDLC. Results: Most patients were white (n = 259, 76%); median age was 60 years; and 146 were women (43%). Outside providers referred 182 patients (53%); the rest were self-referred. Patients travelled median of 83.4 miles (interquartile range: 42.7–247 miles). Most had already undergone imaging (n = 338, 99%) and biopsy (n = 194, 57%) at the OSP, and a formal management plan had been formulated for about half (n = 168, 49%). Alterations in the interpretation of imaging occurred for 49 patients (18%) and of biopsy for 14 patients (10%). Referral to the MDLC resulted in a change of diagnosis in 26 patients (8%), of management plan in 70 patients (42%), and of tumour resectability in 7 patients (5%). Roughly half the patients (n = 174, 51%) returned for a follow-up, and 154 of the returnees (89%) received treatment, primarily intraarterial therapy (n = 88, 57%), systemic chemotherapy (n = 60, 39%), or liver resection (n = 32, 21%). Enrollment in a clinical trial was proposed to 34 patients (10%), and 21 of the 34 (62%) were accrued. Conclusions: Patient assessment by our multidisciplinary liver clinic had a significant impact on management, resulting in alterations to imaging and pathology interpretation, diagnosis, and management plan. The MDLC is an effective and convenient means of delivering expert opinion about the diagnosis and management of liver tumours. Full article

Background and Methods: Lymphoepithelioma-like carcinoma (LELC) is a rare malignancy in ocular adnexa. Here, we report 4 patients with LELC and review 11 patients reported in the literature. Clinical profiles, association with Epstein–Barr virus (EBC), treatment, and outcomes are analyzed. Results: Lacrimal glands and the lacrimal drainage system, eyelid, and conjunctiva are potential primary sites for LELC. The tumours are characterized histologically by nests of undifferentiated malignant cells surrounded by lymphoid infiltrates. Infection with EBC was confirmed in LELC of ocular adnexa, and that association seemed to be restricted to Asian populations. Results from our centre uniformly showed expression of EBC-encoded small rnas in primary tumour, locally recurrent tumour, and metastatic lymph nodes. This disease had a tendency to relapse regionally. Postoperative radiotherapy seems to improve disease-free survival. Tumours appear to be sensitive to radiotherapy and chemotherapy based on cisplatin and 5-fluorouracil. At our centre, 3 patients were still living at 22, 33, and 76 months after surgery. One patient died of distant metastasis after a survival of 38 months. Conclusions: Lymphoepithelioma-like carcinoma is a heterogenous entity among ocular adnexal malignancies. Multimodality treatment provides a better chance at survival. Further investigation is required to achieve a better understanding of the biologic behavior of this entity and of its optimal treatment. Full article

Background: The burden of axillary disease in patients with locally advanced breast cancer (labc) after neoadjuvant therapy (nat) has not been extensively described in a large modern cohort. Here, we describe the extent of nodal metastases after nat in patients with labc. Methods: All patients with labc treated at a single institution during 2002–2007 were identified. Demographic, radiologic, and pathologic variables were extracted. To assess the extent of lymph node metastases after nat, patients were separated into two groups: those with and without clinical or radiologic evidence of lymph node metastases before nat. Axillary lymph nodes retrieved at surgery that had no evidence of metastases after hematoxylin and eosin (h&e) staining underwent further pathology evaluation. Results: Of the 116 patients identified, 115 were female (median age: 48.5). Before nat, 26 patients were clinically and radiologically node-negative; of those 26, 14 were histologically negative on final pathology. After serial sectioning and immunohistochemistry, 9 of 26 (35%) were node-negative. Of the 90 patients who had clinical or radiologic evidence of lymph node metastases before nat, 23 (26%) had no evidence of lymph node metastases on h&e staining. After serial sectioning and immunohistochemistry, 19 (21%) had no further axillary lymph node metastases. Overall, 76% of patients had pathology evidence of lymph node metastases after nat. Conclusions: Most patients with labc have axillary metastases after nat. Our findings support axillary lymph node dissection and locoregional radiation in most patients with labc after nat. Full article

Background: Panitumumab is a fully human monoclonal antibody, directed against the epidermal growth factor receptor, that was shown to be effective in third-line metastatic colorectal cancer. We performed a retrospective analysis of patients with chemo-refractory non-KRAS-mutated metastatic colorectal cancer, who received panitumumab at the Jewish General Hospital in Montreal, Canada, between 2009 and 2012. Methods: This chart review included 44 patients (median age: 60 years; performance status: 0–3), of whom 50% had already received three lines of treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival and safety. Tumour progression was determined by radiologic assessments performed once every 3 months per clinical guidelines or by clinical deterioration as determined by the clinician–investigator. Results: In our sample, median PFS was 21.86 ± 5.23 weeks (95% confidence interval: 12.9 to 36.9 weeks) and overall survival was 35.14 ± 7.75 weeks (95% confidence interval: 25.6 to 73.4 weeks) with a median of 5 cycles of panitumumab treatment. The most frequently reported toxicities with panitumumab were skin toxicity (16.2% grade 3) and hypomagnesemia (10.8% grade 3). No infusion reactions were reported. Conclusions: Despite a small sample size from a single institution, our survival and efficacy data are encouraging and comparable to results obtained from the registration panitumumab trial. Our findings suggest that panitumumab can be effective and tolerable in a real-world setting. Full article

Purpose: The objective of the present study was to analyze, with relatively high sensitivity and specificity, uptake properties of [¹¹C]-choline in prostate cancer patients by means of positron-emission tomography (pet)/computed tomography (ct) imaging using objectively defined pet parameters to test for statistically significant changes before, during, and after external-beam radiation therapy (ebrt) and to identify the time points at which the changes occur. Methods: The study enrolled 11 patients with intermediate-risk prostate cancer treated with ebrt, who were followed for up to 12 months after ebrt. The [¹¹C]-choline pet scans were performed before treatment (baseline); at weeks 4 and 8 of ebrt; and at 1, 2, 3, 6, and 12 months after ebrt. Results: Analysis of [¹¹C]-choline uptake in prostate tissue before treatment resulted in a maximum standardized uptake value (suv_max) of 4.0 ± 0.4 (n = 11) at 40 minutes after injection. During week 8 of ebrt, the suv_max declined to 2.9 ± 0.1 (n = 10, p < 0.05). At 2 and 12 months after ebrt, suv_max values were 2.3 ± 0.3 (n = 10, p < 0.01) and 2.2 ± 0.2 (n = 11, p < 0.001) respectively, indicating that, after ebrt, maximum radiotracer uptake in the prostate was significantly reduced. Similar effects were observed when analyzing the tumour:muscle ratio (tmr). The tmr declined from 7.4 ± 0.6 (n = 11) before ebrtto 6.1 ± 0.4 (n = 11, nonsignificant) during week 8 of ebrt, to 5.6 ± 0.03 (n = 11, p < 0.05) at 2 months after ebrt, and to 4.4 ± 0.4 (n = 11, p < 0.001) at 12 months after ebrt. Conclusions: Our study demonstrated that intraprostatic [¹¹C]-choline uptake in the 11 analyzed prostate cancer patients significantly declined during and after ebrt. The pet parameters SUV_max and tmr also declined significantly. These effects can be detected during radiation therapy and up to 1 year after therapy. The prognostic value of these early and statistically significant changes in intraprostatic [¹¹C]-choline pet avidity during and after ebrt are not yet established. Future studies are indicated to correlate changes in [¹¹C]-choline uptake parameters with long-term biochemical recurrence to further evaluate [¹¹C]-choline pet changes as a possible, but currently unproven, biomarker of response. Full article

Background: Altered formulations of taxanes may lack cross-resistance with standardly used solvent-based taxanes. The primary objective of the present study was to assess the clinical benefit of nanoparticle albumin-bound (nab)–paclitaxel in women with metastatic breast cancer previously treated with and without adjuvant taxane in British Columbia. Methods: The BC Cancer Agency Pharmacy data repository and Breast Cancer Outcomes Unit database were linked to identify all patients who received nab-paclitaxel in British Columbia since its introduction in 2007. Hormone receptor status, demographic characteristics, number of cycles prescribed, and time to treatment failure were extracted and analyzed. Results: From 2007 to 2011, 138 patients in British Columbia received nab-paclitaxel, with 122 patients available for analysis. Most (70.5%) received adjuvant chemotherapy; about a quarter (24.6%) received an adjuvant taxane. Patients who received adjuvant taxane were more likely to have node-positive (86.7% vs. 48.9%, p = 0.007), estrogen receptor–negative (46.7% vs. 13.0% p < 0.001) disease and to receive initial adjuvant radiotherapy (76.7% vs. 51.1%, p < 0.001). For the entire cohort, the median number of nab-paclitaxel cycles prescribed was 4.4 (range: 0.3–13). The median number of nab-paclitaxel cycles was greater when that agent was given as first- or second-line therapy than as third-line or greater therapy (5.0 cycles vs. 3.7 cycles respectively). The median time to treatment failure was 96 days in the prior adjuvant taxane group (range: 0–361) and 73.5 days in the no prior adjuvant taxane group (range: 0–1176). Conclusions: This retrospective study demonstrates potential clinical activity of nab-paclitaxel in metastatic breast cancer regardless of whether patients had prior exposure to adjuvant taxanes. Full article

Background: Neurocognitive deficits from brain tumours may impair the ability to safely operate a motor vehicle. Although certain jurisdictions in Canada legally require that physicians report patients who are unfit to drive, criteria for determining fitness are not clearly defined for brain tumours. Methods: Patients receiving brain radiotherapy at our institution from January to June 2009 were identified using the Oncology Patient Information System. In addition to descriptive statistics, details of driving assessment were reviewed retrospectively. The Fisher exact test was used to determine factors predictive of reporting a patient to the Ontario Ministry of Transportation (MTO) as unfit to drive. A logistic regression model was constructed to further determine factors predictive of reporting. Results: Of the 158 patients available for analysis, 48 (30%) were reported to the MTO, and 64 (41%) were advised to stop driving. With respect to the 53 patients with seizures, a report was submitted to the MTO for 30 (57%), and a documented discussion about the implications of driving was held with 35 (66%). On univariate analysis, younger age, a central nervous system primary, higher brain radiotherapy dose, unifocal disease, and the presence of seizures were predictive of physician reporting (p < 0.05). On logistic regression modelling, the presence of seizures (odds ratio: 3.9) and a higher radiotherapy dose (odds ratio: 1.3) remained predictive of reporting. Interpretation: Physicians frequently do not discuss the implications of driving with brain tumour patients or are not properly documenting such advice (or both). Clear and concise reporting guidelines need to be drafted given the legal, medical, and ethical concerns surrounding this public health issue. Full article

Purpose: Gemcitabine and capecitabine (gem-cap), gemcitabine and erlotinib (gem-e), and folfirinox (5-fluorouracil–leucovorin–irinotecan–oxaliplatin) are new treatment options for metastatic pancreatic cancer, but they are also more expensive and potentially more toxic than gemcitabine alone (gem). We conducted a cost-effectiveness analysis of these treatment options compared with gem. Methods: A Markov model was constructed to examine costs and outcomes of gem-cap, gem-e, folfirinox, and gem in patients with metastatic pancreatic cancer from the perspective of a government health care plan. Ontario health economic and costing data (2010 Canadian dollars) were used. Efficacy data for the treatments were obtained from the published literature. Resource utilization data were derived from a chart review of consecutive metastatic patients treated for pancreatic cancer at Princess Margaret Hospital, Toronto, Ontario, 2008–2009, and supplemented with data from the literature. Utilities were obtained by surveying medical oncologists across Canada using the EQ-5D. Incremental cost-effectiveness ratios (icers) were calculated. Results: The icers for gem-cap, gem-e, and folfirinox compared with gem were, respectively, CA$84,299, CA$153,631, and CA$133,184 per quality-adjusted life year (qaly). The model was driven mostly by drug acquisition costs. Given a willingness-to-pay (wtp) threshold greater than CA$130,000/qaly, folfirinox was most cost-effective treatment. When the wtp threshold was less than CA$80,000/qaly, gem alone was most cost-effective. The gem-e option was dominated by the other treatments. Conclusions: The most cost-effective treatment for metastatic pancreatic cancer depends on the societal wtp threshold. If the societal wtp threshold were to be relatively high or if drug costs were to be substantially reduced, folfirinox might be cost-effective. Full article

A fascinating article, recently published in Nature and titled “Mosaic PPM1D Mutations Are Associated with Predisposition to Breast and Ovarian Cancer” by Nazneen Rahman and her colleagues, is a rare example of a discovery that causes a re-evaluation of our assumptions about cancer and cancer genes. [...]
Full article

Background and Objectives: To explore the perceptions of South Asian (sa) breast cancer survivors concerning their follow-up care, and to determine the optimal content and format of a survivorship care plan (scp) for this population, according to various life stages. Methods: A survey was mailed to 259 sa women with a diagnosis of nonmetastatic breast cancer who were 18–85 years of age, 3–60 months post-discharge, and not on active treatment. Descriptive statistics and content analysis were applied to the responses. The data were cross-tabulated by age: group A (64 years). Results: We received 64 completed surveys. The compliance rate for adjuvant hormonal therapy was high (86.3%). Most of the respondents (n = 61, 95.4%) had visited their family doctor within several months (0.5–24 months) after discharge. Their main physical effects concern was fatigue, and anxiety concerning health was the main psychosocial impact. Groups A and B were more concerned about physical appearance, depression, and the impact of cancer on family members. Women in the older groups were concerned about family obligations and work issues. Several women (n = 9, 14.1%) described strain on their marriage and on their relationships with family and friends as significant issues. Slightly more than one third (n = 24, 37.5%) experienced a deepening of faith, and almost as many (n = 23, 35.9%) felt that their illness was something that was meant to happen. Conclusions: Many of the impacts of breast cancer treatment are shared by women of all ethnic backgrounds. Others—such as high levels of compliance, little reported strain on spousal and family relationships, and the importance of faith—reflect specific cultural variations. These universal and culture-specific themes should all be kept in mind when developing a scp tailored to sa women. The developmental life stage of a woman affects how she views the cancer diagnosis, especially with respect to family, reproduction, and work issues. Full article

Background and Objectives: As more treatment options become available and supportive care improves, a larger number of people will survive after treatment for breast cancer. In the present study, we explored the experiences and concerns of female South Asian (sa) breast cancer survivors (bcss) from various age groups after treatment to determine their understanding of follow-up care and to better understand their preferences for a survivorship care plan (scp). Methods: Patients were identified by name recognition from BC Cancer Agency records for sa patients who were 3–60 months post treatment, had no evidence of recurrence, and had been discharged from the cancer centre to follow-up. Three focus groups and eleven face-to-face semistructured interviews were audio-recorded, transcribed verbatim, cross-checked for accuracy, and analyzed using thematic and content analysis. Participants were asked about their survivorship experiences and their preferences for the content and format of a scp. Results: Fatigue, cognitive changes, fear of recurrence, and depression were the most universal effects after treatment. “Quiet acceptance” was the major theme unique to sa women, with a unique cross-influence between faith and acceptance. Emphasis on a generalized scp with individualized content echoed the wide variation in breast cancer impacts for sa women. Younger women preferred information on depression and peer support. Conclusions: For sa bcss, many of the psychological and physical impacts of breast cancer diagnosis and treatment may be experienced in common with bcss of other ethnic backgrounds, but the present study also suggests the presence of unique cultural nuances such as spiritual and language-specific support resource needs. The results provide direction for designing key content and format of scps, and information about elements of care that can be customized to individual patient needs. Full article