Curr. Oncol., Volume 19, Issue 4 (August 2012) – 19 articles

Paraneoplastic acanthosis nigricans (pan ) is an infrequently encountered cutaneous manifestation of internal malignancy. Here, we describe a case of pan in the setting of a known breast ductal carcinoma in situ, which, to our knowledge, had not been described in association with pan. As a result, thorough investigation was undertaken to search for another concurrent neoplasm that would better explain the development of pan. In so doing, we identified a coexisting metastatic cholangiocarcinoma. We thus conclude that when pan is observed in an uncommon association with a known malignancy, further investigation should be undertaken to explore whether a more likely occult culprit exists. Full article

Enlarging or new lesions frequently appear on magnetic resonance imaging (mri) after concurrent administration of radiation therapy and temozolomide in glioblastoma multiforme (gbm) patients. However, in nearly half such cases, the observed radiologic changes are not due to true disease progression, but instead are a result of a post-radiation inflammatory state called “pseudoprogression.” Retrospective studies have reported that neurologic deterioration at the time of the post-chemoradiotherapy mri is found more commonly in patients with true disease progression. We report a gbm patient with both radiologic progression on the post-chemoradiotherapy mri and concomitant neurologic deterioration, and we caution against incorporating clinical deterioration into the management schema of patients with possible pseudoprogression. Full article

Uterine leiomyosarcomas are rare tumours, and secondary cardiac metastases are even rarer. We present the case of a 56-year-old ethnic Chinese woman who was being treated with adjuvant pelvic radiation for uterine leiomyosarcoma when she presented with signs of right heart failure and shock. She was rapidly diagnosed with a solid mass attached to the tricuspid valve. Subsequent surgical resection revealed leiomyosarcoma metastasis. Metastases of uterine leiomyosarcoma to the heart are extremely rare, but clinicians should be aware of this phenomenon. Surgical resection, when feasible, can be associated with longer survival. Full article

Histiocytic sarcoma is diagnosed according to established criteria. However, treatment is controversial: although lymphoma chemotherapy regimens are often used, their impact on the natural history of the disease is unclear. Here, we report a disease-free survival of 2 years after autologous stem-cell transplantation in a patient with relapsed histiocytic sarcoma. Full article

Objective: Bicalutamide is approved as an adjuvant to primary treatments (radical prostatectomy or radiotherapy) or as monotherapy in men with locally advanced, nonmetastatic prostate cancer (pca). However, this treatment induces gynecomastia in most patients, which often results in treatment discontinuation. Optimal therapy for these breast events is not known so far. We undertook a meta-analysis to assess the efficacy of various treatment options for bicalutamide-induced gynecomastia. Methods: The medline, cancerlit, and Cochrane library databases were searched and the Google search engine was used to identify prospective and retrospective controlled studies published in English from January 2000 to December 2010 comparing prophylactic or curative treatment options with a control group (no treatment) for pca patients who developed bicalutamide-induced gynecomastia. Radiotherapy-induced cardiotoxicity was also evaluated. Results: The search identified nine controlled trials with a total patient population of 1573. Pooled results from prophylactic trials showed a significant reduction of gynecomastia in pca patients treated with prophylactic tamoxifen 20 mg daily (odds ratio: 0.06; 95% confidence interval: 0.05 to 0.09; p = 0.09), and pooled results from treatment trials showed a significant response of gynecomastia to definitive radiotherapy (odds ratio: 0.06; 95% confidence interval: 0.01 to 0.24; p < 0.0001). Aromatase inhibitors and weekly tamoxifen were not found to be effective as prophylactic and curative options. For the radiotherapy, skin-to-heart distance was found to be an important risk factor for cardiotoxicity (p = 0.006). A funnel plot of the meta-analysis showed significant heterogeneity (Egger test p < 0.00001) because of low sample size. Conclusions: Our meta-analysis suggests using prophylactic tamoxifen 20 mg daily as the first-line preventive measure and radiotherapy as the first-line treatment option for bicalutamide-induced gynecomastia. Aromatase inhibitors and weekly tamoxifen are not recommended. Full article

Background: Approximately 10% of new breast cancer patients will present with overt synchronous metastatic disease. The optimal local management of those patients is controversial. Several series suggest that removal of the primary tumour is associated with a survival benefit, but the retrospective nature of those studies raises considerable methodologic challenges. We evaluated our clinical experience with the management of such patients and, more specifically, the impact of surgery in patients with synchronous metastasis. Methods: We reviewed patients with primary breast cancer and concurrent distant metastases seen at our centre between 2005 and 2007. Demographic and treatment data were collected. Study endpoints included overall survival and symptomatic local progression rates. Results: The 111 patients identified had a median follow-up of 40 months (range: 0.6–71 months). We allocated the patients to one ot two groups: a nonsurgical group (those who did not have breast surgery, n = 63) and a surgical group (those who did have surgery, n = 48, 29 of whom had surgery before the metastatic diagnosis). When compared with patients in the nonsurgical group, patients in the surgical group were less likely to present with T4 tumours (23% vs. 35%), N3 nodal disease (8% vs. 19%), and visceral metastasis (67% vs. 73%). Patients in the surgical group experienced longer overall survival (49 months vs. 33 months, p = 0.01) and lower rates of symptomatic local progression (14% vs. 44%, p < 0.001). Conclusions: In our study, improved overall survival and symptomatic local control were demonstrated in the surgically treated patients; however, this group had less aggressive disease at presentation. The optimal local management of patients with metastatic breast cancer remains unknown. An ongoing phase iii trial, E2108, has been designed to assess the effect of breast surgery in metastatic patients responding to first-line systemic therapy. If excision of the primary tumour is associated with a survival benefit, then the preselected subgroup of patients who have responded to initial systemic therapy is the desired population in which to put this hypothesis to the test. Full article

Purpose: Outcomes after treatment with accelerated hypofractionated radiotherapy in stage i medically inoperable non-small-cell lung cancer (nsclc) patients were determined. Methods: Our single-institution retrospective review looked at medically inoperable patients with T1–2N0M0 nsclc treated with accelerated hypofractionated curative-intent radiotherapy between 1999 and 2009. Patients were staged mainly by computed tomography imaging of chest and abdomen, bone scan, and computed tomography/magnetic resonance imaging of brain. Positron-emission tomography (pet) staging was performed in 6 patients. Medical charts were reviewed to determine demographics, radiotherapy details, sites of failure, toxicity (as defined by the Common Terminology Criteria for Adverse Events, version 3.0) and vital status. The cumulative incidence of local and distant failure was calculated. Overall (os) and cause-specific (css) survival were estimated by the Kaplan–Meier method. Result: In the 60 patients treated during the study period, the dose regimens were 50 Gy in 20 fractions (n = 6), 55 Gy in 20 fractions (n = 8), 60 Gy in 20 fractions (n = 42), and 60 Gy in 25 fractions (n = 4). All patients were treated once daily. The median follow-up was 27 months (range: 4–94 months). The os rates at 2 and 5 years were 61% [95% confidence interval (ci): 50% to 75%] and 19% (95% ci: 10% to 34%) respectively. The css rates at 2 and 5 years were 79% (95% ci: 68% to 91%) and 39% (95% ci: 24% to 63%) respectively. The cumulative incidence of local failure was 20% at 5 years. The cumulative incidence of distant failure was 28% at 5 years. No patients experienced grade 3 or greater pneumonitis or esophagitis. Conclusions: Accelerated hypofractionated regimens are well tolerated and provide good local control in medically inoperable patients with stage i nsclc. Such regimens may be a reasonable treatment alternative when stereotactic body radiation therapy is not feasible. Full article

Objective: The objective of the present study was to evaluate the incidence, time of onset, and extent of hemoglobin, testosterone, and erythropoietin changes in patients with localized prostate cancer receiving either radiation alone or radiation combined with total androgen blockade (tab). Methods: The study enrolled 35 patients (median age: 69 years) with clinically localized prostate cancer who received 3-dimensional conformal radiation with or without tab. Patients were generally treated with radiation alone (group 1), radiation plus short-term (≤6 months) tab (group 2), or radiation plus long-term (≥2 years) tab (group 3). Serum hemoglobin, testosterone, and erythropoietin in these patients were prospectively evaluated. Results: The mean baseline serum hemoglobin for group 1 (n = 20), group 2 (n = 6), and group 3 (n = 9) was 149 g/L, 153 g/L, and 143 g/L respectively. We observed no significant decline in serum hemoglobin, testosterone, or erythropoietin among patients treated with radiotherapy alone. A significant drop in serum testosterone was noted in the group 2 and 3 patients within 1 month (p < 0.001), reaching a plateau at approximately 6 months. That change was followed by a significant decline (p < 0.001) in serum hemoglobin at 3–6 months (137 g/L in group 2 and 129 g/L in group 3). We observed a small but statistically significant increase in serum erythropoietin (p < 0.001) of 8 U/L in group 2 and 4 U/L in group 3 after 6 months of tab. No immediate recovery in serum hemoglobin, testosterone, or erythropoietin was observed upon completion of tab. Conclusions: Although conformal radiotherapy alone for localized prostate cancer had no effect on serum hemoglobin, testosterone, or erythropoietin, tab led to a significant decline in testosterone, which was followed by decline in hemoglobin that was not a result of a deficiency of erythropoietin. Full article

Questions: What is the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer? What is the most appropriate surgical procedure for a woman who presents with an adnexal mass suspicious for malignancy? Perspectives: In Canada in 2010, 2600 new cases of ovarian cancer were estimated to have been diagnosed, and of those patients, 1750 were estimated to have died, making ovarian cancer the 7th most prevalent form of cancer and the 5th leading cause of cancer death in Canadian women. Women with ovarian cancer typically have subtle, nonspecific symptoms such as abdominal pain, bloating, changes in bowel frequency, and urinary or pelvic symptoms, making early detection difficult. Thus, most ovarian cancer cases are diagnosed at an advanced stage, when the cancer has spread outside the pelvis. Because of late diagnosis, the 5-year relative survival ratio for ovarian cancer in Canada is only 40%. Unfortunately, because of the low positive predictive value of potential screening tests (cancer antigen 125 and ultrasonography), there is currently no screening strategy for ovarian cancer. The purpose of this document is to identify evidence that would inform optimal recommended protocols for the identification and surgical management of adnexal masses suspicious for malignancy. Outcomes: Outcomes of interest for the identification question included sensitivity and specificity. Outcomes of interest for the surgical question included optimal surgery, overall survival, progression-free or disease-free survival, reduction in the number of surgeries, morbidity, adverse events, and quality of life. Methodology: After a systematic review, a practice guideline containing clinical recommendations relevant to patients in Ontario was drafted. The practice guideline was reviewed and approved by the Gynecology Disease Site Group and the Report Approval Panel of the Program in Evidence-based Care. External review by Ontario practitioners was obtained through a survey, the results of which were incorporated into the practice guideline. Practice Guideline: These recommendations apply to adult women presenting with a suspicious adnexal mass, either symptomatic or asymptomatic. Identification of an Adnexal Mass Suspicious for Ovarian Cancer: Sonography (particularly 3-dimensional sonography), magnetic resonance imaging (mri), and computed tomography (ct) imaging are each recommended for differentiating malignant from benign ovarian masses. However, the working group offers the following further recommendations, based on their expert consensus opinion and a consideration of availability, access, and harm: (1) Where technically feasible, transvaginal sonography should be the modality of first choice in patients with a suspicious isolated ovarian mass. (2) To help clarify malignant potential in patients in whom ultrasonography may be unreliable, mri is the most appropriate test. (3) In cases in which extra-ovarian disease is suspected or needs to be ruled out, ct is the most useful technique. (4) Evaluation of an adnexal mass by Doppler technology alone is not recommended. Doppler technology should be combined with a morphology assessment. (5) Ultrasonography-based morphology scoring systems can be used to differentiate benign from malignant adnexal masses. These scoring systems are based on specific ultrasound parameters, each with several scores base on determined features. All evaluated scoring systems were found to have an acceptable level of sensitivity and specificity; the choice of scoring system may therefore be made based on clinician preference. (6) As a standalone modality, serum cancer antigen 125 is not recommended for distinguishing between benign and malignant adnexal masses. (7) Frozen sections for the intraoperative diagnosis of a suspicious adnexal mass is recommended in settings in which availability and patient preference allow. Surgical Procedures for an Adnexal Mass Suspicious for Malignancy: To improve survival, comprehensive surgical staging with lymphadenectomy is recommended for the surgical management of patients with early-stage ovarian cancer. Laparoscopy is a reasonable alternative to laparotomy, provided that appropriate surgery and staging can be done. The choice between laparoscopy and laparotomy should be based on patient and clinician preference. Discussion with a gynecologic oncologist is recommended. Fertility-preserving surgery is an acceptable alternative to more extensive surgery in patients with low-malignant-potential tumours and those with well-differentiated surgical stage i ovarian cancer. Discussion with a gynecologic oncologist is recommended. Full article

Background: Use of granulocyte colony-stimulating factor (g-csf) as primary prophylaxis against chemotherapy-induced neutropenia has significant cost implications. We examined use of g-csf for early-stage breast cancer patients at our centre. The study also examined the pattern of nurse-led patient teaching with respect to drug self-administration. Methods: Patients who received g-csf between November 2009 and October 2010 were identified from pharmacy records. After consent had been obtained, electronic charts were examined to extract data on chemotherapy and use of g-csf. Patients were contacted by telephone to obtain information on the utilization of home-care nursing visits for g-csf administration. Results: The study analyzed 36 patients. Median age was 58 years (range: 31–78 years). Of the 36 patients, 30 (83%) had received adjuvant treatment, and 6 (17%), neoadjuvant treatment. Most patients (71%) received 10 days (range: 7–10 days) of filgrastim. Of the 36 patients, 29 (81%) received g-csf as primary prophylaxis. In 90% of those patients, primary prophylaxis commenced with the taxane component of treatment. Of the 36 patients, 7 (19%) received g-csf after neutropenia, including 2 who had febrile neutropenia. In 96% of the patients, injections were received at home with the help of a nurse; those patients were subsequently taught self-injection techniques. The median number of nursing visits was 2 (range: 1–3 visits). Most patients were satisfied with the home care and g-csf teaching they received. Conclusions: Most of the g-csf used in breast cancer treatment during the study period was given for primary prophylaxis. A major reason for the decision to use g-csf appears to have been physician-perceived risk of febrile neutropenia. Delivery of g-csf by home-care nurses was well received by patients. Full article

Purpose: Multidisciplinary cancer conferences (mccs) are designed to optimize patient outcomes. It appears intuitive that mccs are essential to clinical decision-making and patient management; however, it is unclear whether that belief is supported by evidence. Our objectives were to assess the currently published literature addressing the impact of mccs on clinical decision-making and patient outcomes. Methods: Ovid medline was searched from 1950 to June 2010 using these keywords: “multidisciplinary/interdisciplinary/clinical meeting$/conference$/round$/team$,” “decision making,” “neoplasms$/cancer$/oncology/tumo(u)r conference$/board$/meeting$,” “multidisciplinary/interdisciplinary cancer conference$/meeting$.” All trials, guidelines, metaanalyses, reviews, and prospective and retrospective studies were included. Results: The keywords retrieved 595 abstracts, and 30 manuscripts were obtained. Most of the studies assessed the impact of mccs on clinical decision-making rather than on patient outcomes. Conclusions: Available evidence supports the belief that mccs significantly influence clinical decision-making and treatment recommendations. In contrast, scant evidence suggests that mccs improve patient outcomes. Unfortunately, the current literature is substantially heterogeneous and therefore does not allow for firm conclusions. Full article

Tobacco, derived from flu-cured leaves of Nicotiana tabacum, a herb native to South America, was introduced by Sir Walter Raleigh to Europe from the Americas in the 17th century. From about 1680, tobacco use became a global, common, and legal habit, with smoking, chewing, or snuffing all assumed to be innocent for more than 200 years. Full article

Numerous reports have demonstrated that liver transplantation for neuroendocrine tumour metastasis is feasible. However, perioperative risks and long-term recurrences remain significant concerns. When liver transplantation is combined with extensive intestinal or pancreatic resection, the risk is particularly high. We report our institutional experience of liver transplantations performed for liver metastases secondary to neuroendocrine tumours, and in combination with a review of the literature, we propose a set of selection criteria. The key points include unresectable hepatic metastases of neuroendocrine origin, absence of extrahepatic metastases, symptomatic disease that is refractory to medical therapy, a Ki-67 level less than 2%, previous resection of the primary disease, and previous therapy for metastatic neuroendocrine tumour. In our experience, the patient in the first case had, post-transplantation, rapid disease progression because of an unidentified primary, and patient in the second case had primary non-function of the liver graft, requiring urgent re-transplantation. More recently, two liver transplantations were successfully performed. The indications were, in the first case, refractory hormonal secretion and, in the other, secondary biliary cirrhosis attributable to hepatic artery therapy with tumour in situ. Subclinical and stable recurrent disease has been detected by scintigraphy in the mesentery and lumbar spine in the former patient. A mesenteric recurrence developed in the latter patient 2 years post transplantation and was subsequently completely resected. At 4 and 5 years post transplantation, both patients are symptom-free. Recurrence after transplantation remains a significant concern, even with careful patient selection, but recurrences may remain indolent. If recurrences are progressive, they may still be amenable to additional medical or surgical therapy. A national or international consensus between oncologists and transplant specialists regarding the indications for liver transplantation is vital, because future progress will depend on careful patient selection and prospective study. Full article

Objectives: We set out to create a psychosocial oncology care framework and a set of relevant recommendations that can be used to (1) improve the quality of comprehensive cancer care for Ontario patients and their families. (2) meet the psychosocial health care needs of cancer patients and their families at both the provider and system levels. Data Sources and Methods: The adapte process and the practice guideline development cycle were used to adapt the 10 recommendations from the 2008 U.S. Institute of Medicine standard Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs into the psychosocial oncology care framework. In addition, the evidence contained in the original document was used, in combination with the expertise of the working group, to create a set of actionable recommendations. Refinement after formal external review was conducted. Data Extraction and Synthesis: The new framework consists of 8 defining domains. Of those 8 domains, 7 were adapted from recommendations in the source document; 1 new domain, to raise awareness about the need for psychosocial support of cancer patients and their families, was added. To ensure high-quality psychosocial care and services, 31 actionable recommendations were created. The document was submitted to an external review process. More than 70% of practitioners rated the quality of the advice document as high and reported that they would recommend its use. Conclusions: This advice document advocates for a multidisciplinary approach to cancer care in response to the distress experienced by cancer patients and their families. The recommendations will be useful in future to measure performance, quality of practice, and access to psychosocial services. Full article

Inhibitors of the vascular endothelial growth factor (vegf-is) signalling pathway have fundamentally changed the treatment of metastatic renal cell carcinoma (mrcc). Hypertension is one of the most common side effects of vegf-is and has been reported with almost every vegf-i used for treatment to date. The exact mechanism of vegf-i–induced hypertension appears complex and multifactorial, and it remains to be fully explained. No randomized clinical trials are available to guide the management of hypertension during vegf-i treatment in mrcc patients. The guiding principles suggested here summarize the consensus of opinions on the diagnosis and management of vegf-i–induced hypertension during treatment of mrcc obtained from an expert working group composed of 4 Canadian medical oncologists and 5 Canadian hypertension specialists. The Canadian Hypertension Education Program guidelines, available literature, and expert opinion were used to develop the guiding principles. Full article

Introduction: Large randomized trials assessing the benefit of adjuvant trastuzumab in early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2) have demonstrated a significant improvement in survival. The objective of the present study was to describe the outcomes of women who received adjuvant trastuzumab for her2-positive breast cancer in British Columbia since publicly funded population-based use was initiated in July 2005. Methods: Women from British Columbia, newly diagnosed with stage i–iii breast cancer between July 2004 and December 2006, who were positive for her2 overexpression by immunohistochemistry (3+) or amplification by fluorescence in situ hybridization (ratio ≥ 2.0) were included in the study. Data were collected from the prospectively assembled BC Cancer Agency Outcomes Unit, with cases linked to the provincial pharmacy data repository to determine the proportion of women who received adjuvant trastuzumab. Results: Our retrospective study identified 703 her2-positive patients, of whom 480 (68%) received trastuzumab. In patients receiving trastuzumab, the 2-year relapse-free survival was 96.1% [95% confidence interval (CI): 93.6% to 97.7%] and the overall survival was 99.3% (95% CI: 97.9% to 99.8%). Among node-negative and -positive patients, the 2-year relapse-free survival was 97.8% and 94.8% respectively (p = 0.09) for the trastuzumab-treated group and 90.9% and 77.3% (p = 0.01) for the group not receiving trastuzumab (n = 223). Site of first distant metastasis was the central nervous system in 19.5% of the entire cohort and in 37.5% of patients treated with trastuzumab. Discussion: This population-based analysis of adjuvant trastuzumab use among Canadian women demonstrates highly favorable outcomes at the 2-year follow-up. Full article

The stages of breast cancer range from 0 to IV. In proper usage, “stage” describes the cancer at diagno-sis, although “stage” is also loosely used to describe cancer progression. For example, a stage II cancer is sometimes said to have progressed to become stage IV (but not stage III). [...] Full article