Clinical Factors Affecting Bevacizumab Efficacy With and Without Conventional Chemotherapy in Metastatic Colon Cancer.

PURPOSE: Bevacizumab (BZ) combined with first line chemotherapy (CC) has shown good clinical outcomes in metastatic colorectal cancer (mCRC). Overall survival (OS) and/or progression free survival in mCRC patients receiving BZ with or without 5FU-based CC is thought to be affected by clinical and morphological factor(s). PATIENTS AND METHODS: We reviewed retrospective medical records of all consecutive mCRC patients treated with BZ with or without CC at tertiary care center between 2003 and 2009 out of which149 patients (m = 77, f = 72) were eligible. RESULTS: Our study population had a mean age at diagnosis of 63.5 years (SD = 11) with median follow-up period of 19.4 months. On initial radiological evaluation following BZ therapy, 56 patients (m = 31, f = 25) had complete or partial response categorized as "early responders." Remaining patients (m = 46, f = 47) who were either stable or showed progressive disease were categorized as "non-responders." Fifty percent among early responders and 60% among non-responders [relative risk (RR) 0.67 (95% confidence interval (CI), 0.43-1.06)] demonstrated disease progression on follow up. There was a slightly better OS among early responders compared to non-responders (median 21.5 months days versus 16.8 months, P = 0.07). Cox regression analysis suggested male sex (RR 0.65, 95% CI, 0.43-0.98), hematochezia (RR 0.63, 95% CI, 0.4-0.98), resectable primary tumor (RR 0.42, 95% CI, 0.24-0.72) and resectable metastatic mass (RR 0.32, 95% CI, 0.14-0.74) were found to be associated with longer OS. Abdominal pain (RR 1.76, 95% CI, 1.1-2.8), accompanying diabetes (RR 1.76, 95% CI, 1.09-2.85), and unexplained weight loss (RR 2.73, 95% CI, 1.73-4.29) were associated with poor OS. CONCLUSIONS: Better OS among mCRC patients with resectable primary and metastatic tumors was seen. This is the first study to demonstrate slightly better outcome in males and negative influence of diabetes on outcome in mCRC treated with BZ.

Duodenal Perforation Secondary to Erlotinib Therapy in a Patient With Non-Small Cell Lung Cancer.

Lung cancer is a lethal disease with high mortality, and treatment modality varies with type of tumor and stage of the disease. Targeted molecular therapies have been developed for patients with advanced non-small cell lung cancer. The presence of epidermal growth factor receptor (EGFR) mutation qualifies the patient for EGFR-TKI (tyrosine kinase inhibitor) therapy such as erlotinib, which is not without risk. We report an interesting case of duodenal perforation secondary to erlotinib therapy. This is the second reported case of bowel perforation after erlotinib therapy in a patient with advanced non-small cell lung cancer.

Gelatinous bone marrow transformation secondary to unusual eating habits and drastic weight loss.

Gelatinous bone marrow transformation (GMT), also known as starvation bone marrow, has been reported in a number of chronic illnesses, eating disorders (anorexia nervosa) and malignancies. We report the case of a 37-year-old man with a history of bipolar disorder and obesity (weighing >300 pounds) who presented due to recently developing a deep yellow colour to his skin. Over the past 2 years, through diet and exercise, he lost over 150 pounds. He reported running 6-8 miles per day and eating 'lots of squash'. We made the diagnosis of starvation hepatitis and bone marrow degeneration, and referred the patient to a dietician and haematologist/oncologist, where improvements were observed at 4 weeks follow-up.

Modeling efficacy of bevacizumab treatment for metastatic colon cancer.

PURPOSE: Bevacizumab, an FDA-approved adjuvant treatment for metastatic colon cancer, has extended survival for many patients. However, factors predicting response to treatment remain undefined. PATIENTS AND METHODS: Relevant clinical and environmental data were abstracted from medical records of 149 evaluable patients treated with bevacizumab for metastatic colon cancer at a multi-specialty clinic. Tumor response was calculated from radiologic reports using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and verified by oncologist review. Patients with at least one occurrence of complete or partial response or stable disease were classified as responders; those exhibiting progressive disease were classified as non-responders. RESULTS: Univariate analysis demonstrated that blood in stool (P<0.05), unexplained weight loss (P<0.05), primary colon cancer site (P<0.05), chemotherapy treatment of primary tumor site (P<0.05), and adenocarcinoma versus adenoma subtype (P<0.05) was associated with tumor responsiveness. Factors remaining statistically significant following multivariate modeling included adenocarcinoma as tumor cell type versus other adenocarcinoma subtypes (OR=6.35, 95% CI: 1.08-37.18), chemotherapy treatment applied to primary tumor (OR= 0.07, 95% CI: 0.0-0.76,), tumor localization to cecal/ascending colon (OR=0.061, 95% CI: 0.006-0.588,), and unexplained weight loss (OR=0.1, 95% CI: 0.02-0.56,). Chemotherapy treatment of primary tumor, unexplained weight loss, and cecal/ascending localization of the tumor were associated with poorer outcomes. Adenocarcinoma as cell type compared to other adenocarcinoma subtypes was associated with better response to bevacizumab treatment. CONCLUSION: RESULTS suggest that response to bevacizumab therapy may be predicted by modeling clinical factors including symptomology on presentation, tumor location and type, and initial response to chemotherapy.

Low-dose ruxolitinib for improving leukopaenia and reducing recurrent infections associated with myelofibrosis.

Myelofibrosis, either primary or resulting from essential thrombocythemia or polycythemia vera, may present with highly variable white blood cell counts, including progressive leukopaenia with its associated risk of infections. Medications have been developed to reduce splenomegaly and other symptoms, but there are no reports of improved white blood cell counts. We report a case of primary myelofibrosis with marked improvement in leukopaenia and reduced recurrent infections, in addition to reduction in spleen size and improvement in disease-associated symptoms, within 20 weeks after using low-dose ruxolitinib. Although reduction of splenomegaly in myelofibrosis patients is the anticipated benefit of ruxolitinib, the drug may also have the potential to improve leukopaenia if used at a low dose.

Silent thyroiditis, isolated corticotropin deficiency, and alopecia universalis in a patient with ulcerative colitis and elevated levels of plasma factor VIII: an unusual case of autoimmune polyglandular syndrome type 3.

OBJECTIVE: To describe an unusual case of autoimmune polyglandular syndrome (APS) type 3 and provide a brief review of the literature. METHODS: We present the clinical course and laboratory data of a patient with silent thyroiditis, isolated corticotropin (adrenocorticotropic hormone or ACTH) deficiency, alopecia universalis, and ulcerative colitis with an associated hypercoagulable state. The related literature is also reviewed briefly. RESULTS: A 43-year-old man who had a history of ulcerative colitis with an associated hypercoagulable state and alopecia universalis was referred to the endocrinology department for evaluation of fatigue and a mildly elevated level of thyrotropin (thyroid-stimulating hormone or TSH). He previously had mildly increased TSH levels, for which low-dose levothyroxine therapy had been prescribed. During use of this therapy, a suppressed TSH level developed, necessitating discontinuation of thyroid hormone therapy; a subsequent increase in TSH value was followed by a spontaneous return to euthyroidism. An ACTH stimulation test revealed adrenal insufficiency. His ACTH level was low, 21-hydroxylase antibodies were not present, and further testing demonstrated otherwise intact pituitary function. Magnetic resonance imaging of his pituitary gland showed normal findings. Treatment with hydrocortisone promptly decreased his fatigue. He was found to have an elevated factor VIII level as the cause of his hypercoagulable state. The patient continues to feel well with use of hydrocortisone therapy and has normal thyroid function. CONCLUSION: This patient's components of APS type 3 have not been previously reported; thus, the complex nature of the APS variants is supported.

Urethral 'recurrence' found 14 years after radical cystectomy.

We report a case of transitional cell urethral cancer diagnosed 14 years after radical cystectomy. Traditionally, in the postcystectomy setting, these cancers have been referred to as 'recurrences'. We review the biological models for the oncogenesis of these cancers and propose that they are typically a result of a field cancerization effect, rather than being derived from the same clone responsible for the original urothelial tumor.

Hemorrhagic cystitis as an unexpected adverse reaction to temozolomide: case report.

A case is reported in which temozolomide, a promising new DNA alkylating agent, was successfully used to treat radiation refractory metastatic brain tumors arising from primary breast cancer. However, the treatment had to be terminated after the second round of treatment due to the development of hemorrhagic cystitis. This side effect was totally unexpected. Another class of alkylating agents (cyclophosphamide and related compounds) exhibits this side effect caused by a prevalent acrolein metabolite. Temozolomide and its sister compounds, dacarbazine and 5-(3-methyltriazen-1-yl)imidazole-4-caroxamide, have never been reported to have this adverse reaction. This case serves to alert physicians to the existence of a possible subpopulation of patients who may experience hemorrhagic cystitis on treatment with imidazotetrazines by a mechanism that is yet to be established.