Curr. Oncol., Volume 15, Issue 6 (December 2008) – 8 articles

Pancreatic malignancies can be subdivided into endocrine and non-endocrine processes. Of the non-endocrine tumours, ductal carcinoma is the most common, and the ductal carcinomas can be further subdivided into adenocarcinomas and squamous cell carcinomas. The adenocarcinomas constitute most of the non-endocrine pancreatic malignancies, and the treatment options for these, although limited in efficacy, are relatively well established. The squamous cell carcinoma pathology is a rare entity, and few reports of it are found in the literature. As a result, treatment options for squamous cell carcinoma of the pancreas are poorly understood. Here, we report the presentation of a 48-year-old woman with metastatic squamous cell carcinoma of the pancreas. The subsequent investigations, treatment, and outcome are described. Full article

Background: The use of fractionated stereotactic radiotherapy (FSRT) has evolved with technical advances in noninvasive immobilization, radiation delivery, and image guidance. The application of FSRT to pituitary tumours is aimed at reducing toxicity through improved dose conformality and reduced treatment margins. The aim of the present paper is to report our own experience and to review the published data on FSRT for pituitary macroadenomas. Methods: Between September 2000 and October 2005, 13 patients with pituitary macroadenoma underwent FSRT at our institution. In 12 patients, radiotherapy treatment followed surgical resection (transsphenoidal resection in 8, frontal craniotomy in 3, and multiple transsphenoidal resections followed by craniotomy in 1). In 4 patients, the tumours were functional (2 adrenocorticotropic hormone–secreting, 1 prolactinoma, and 1 growth hormone–secreting); the tumours in the remaining patients were clinically non-secretory. Before radiation, 3 patients had panhypopituitarism, and 6 patients had visual field defects. All patients were treated with FSRT using non-coplanar micro–multileaf collimation portals. A median dose of 50.4 Gy (range: 45–60 Gy) was prescribed to the 76.9%–95.2% isodose surface and delivered in 1.8-Gy fractions. The median planning target volume (gross tumour plus 3 mm) was 33.5 cm³ (range: 3.2–75 cm³). Results: After a median follow-up of 24 months (range: 6–60 months), local control was 100%. One patient achieved clinical complete response. Treatment was well tolerated acutely for all patients. Neither radiation-induced optic neuropathy nor any radiation-related endocrine dysfunction was observed in our patients. Conclusions: In accordance with published series, we found FSRT to be safe and effective in the management of large pituitary macroadenomas. Full article

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy have both demonstrated efficacy in recurrent metastatic non-small-cell lung cancer (NSCLC) following failure of first-line platinum-based chemotherapy. Although the 3 available therapeutic agents—docetaxel, erlotinib, and pemetrexed—have significantly changed the treatment landscape for recurrent NSCLC, the optimal selection of second- and third-line therapy has not been established. This practice review examines the outcomes in clinical practice of using second-line erlotinib followed by third-line chemotherapy in the treatment of recurrent metastatic NSCLC. Methods: We conducted a retrospective review of NSCLC patient charts at three Canadian institutions. Patients with recurrent NSCLC who had received second-line erlotinib therapy followed by third-line chemotherapy were selected by census. A chart review assessed key outcomes that included time to progression (TTP), response, and change in performance status. Outcomes for specific patient subgroups were also examined. Results: We identified 35 patients for this retrospective practice review. First-line platinum-doublet therapy demonstrated a mean TTP of 6.6 months and a 46% overall response rate (15 partial responses and 1 complete response). Second-line treatment with erlotinib produced the highest mean TTP of all lines of therapy (9.2 months) and an overall response rate of 40% (all being partial responses). In the third-line setting, in which most patients received docetaxel, the mean TTP was 4.3 months and the overall response rate was 18% (all being partial responses). Subgroup analysis showed that all patient subgroups demonstrated benefit from second-line erlotinib treatment; improved benefit was observed in patients who developed rash, in female patients, in never smokers, in Asian patients, in patients with positive egfr status, and in patients with adenocarcinoma histology. Conclusions: For patients with advanced NSCLC who progressed following first-line platinum-based chemotherapy, the data demonstrate that second-line EGFR-TKI treatment is efficacious and well-tolerated and that it does not appear to diminish the benefit of third-line chemotherapy. Full article

Objectives: Locally advanced breast cancer (LABC) poses a difficult clinical challenge with an overall poor long-term prognosis. The strength of the association between tumour characteristics, treatment response, and outcome is not well defined. In the present study, we attempted to gain further insight into LABC by reviewing tumour characteristics of patients treated with neoadjuvant chemotherapy and by studying the association of those characteristics with outcome. We calculated the residual cancer burden (RCB) score obtained at surgery and attempted to study its correlation with event-free survival (EFS) and overall survival (OS). Methods: We studied patients diagnosed primarily with LABC (n = 45). Pathologic and clinical responses were determined. Pathology slides were reviewed. Results: Of the 45 study patients, 9% had stage iib disease; 29%, stage IIIA; 51%, stage IIIB; and 11%, stage IIIC. Inflammatory breast cancer (IBC) was found in 16%. Pathologic complete response (pCR) was achieved in 22% of all patients. None of the patients with IBC achieved pCR. Patients with estrogen receptor–negative (ER−)/progesterone receptor–negative (PR−) tumours were more likely to achieve pCR than were those with ER+/PR+ tumours. Among patients with tumours that overexpressed human epidermal growth factor receptor 2 (HER2/neu), 17% achieved pCR as compared with 25% of patients with non-overexpressing tumours; only 1 patient had received trastuzumab. The RCB scores were calculated in 32 patients and ranged between 0 and 4.6. Conclusions: The present study examined practical issues related to the classification and management of LABC and IBC. The RCB, defined from routine pathology materials, was easily quantifiable. It appears to be a better predictor than pCR of outcome following neoadjuvant chemotherapy in LABC. Higher RCB scores were associated with lower EFS and a lower rate of OS. A continual quest for reliable predictive and correlative prognostic markers, and for better surrogate endpoints for outcome, is essential to advance our understanding of LABC and to improve treatment outcomes. Full article

Dynamic protein–protein interactions between proapoptotic and pro-survival Bcl-2 family members regulate outer-mitochondrial membrane permeabilization and cytochrome c release, key events in the path to apoptosis. Their relative levels often dictate the fate of a cell following an apoptotic stimulus. However, in cancer cells, the pro-survival Bcl-2 family members are frequently upregulated, thereby creating a constitutive block to apoptosis and resulting in continued cell survival under conditions that normally result in cell death. Because many chemotherapeutics used to treat cancer also trigger apoptosis, this upregulation of pro-survival members also contributes to resistance to conventional cancer therapies. Strategies that inactivate pro-survival Bcl-2 family members therefore suggest a means by which this downstream block in apoptosis can be alleviated, resulting in the selective killing of malignant cells. Here, we outline the progress of three small-molecule Bcl-2 antagonists that have advanced into clinical evaluation. Full article

This issue of the journal sees a diverse group of manuscripts that takes us through to the end of 2008 and of our 15th year of publication—an appropriate time to thank all our sponsors and supporters for their contributions and our editorial board and support staff for their many hours of effort. [...] Full article