Executive Summary of the American Radium Society Appropriate Use Criteria for Local Excision in Rectal Cancer.

The goal of treatment for early stage rectal cancer is to optimize oncologic outcome while minimizing effect of treatment on quality of life. The standard of care treatment for most early rectal cancers is radical surgery alone. Given the morbidity associated with radical surgery, local excision for early rectal cancers has been explored as an alternative approach associated with lower rates of morbidity. The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines for the use of local excision in early stage rectal cancer that include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) used by a multidisciplinary expert panel to rate the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. These guidelines are intended for the use of all practitioners and patients who desire information regarding the use of local excision in rectal cancer.

Radiotherapy in the management of pancreatic neuroendocrine tumors (PNET): experience at three institutions.

AIM: Advanced pancreatic neuroendocrine tumor (PNET) presents a therapeutic challenge as many are unresectable and relatively resistant to systemic therapy with a high malignant potential. We share our experience using concurrent capecitabine or infusional 5-fluorouracil with radiation for patients with resected and locally advanced PNET. PATIENTS AND METHODS: Six patients (two females, four males) with PNET were treated with capecitabine or infusional 5-FU and concurrent radiation. RESULTS: The median age was 52 years (range: 38 to 63 years), with ECOG Performance Status (PS) 0-1, grade 0-1 weight loss, and grade 0-1 pain. One patient underwent resection with negative margins, two with positive margins, and three had unresectable locally advanced disease. All six patients demonstrated partial radiographic response and sustained local control. The treatment was tolerable with only grade 2 hand-foot syndrome and grade 1 mucositis observed. CONCLUSION: Prospective studies to further investigate the role of chemoradiation in this setting are warranted.

Locally advanced pancreatic cancer: a review.

It is anticipated that there will be 37,170 new cases of pancreatic cancer diagnosed in the United States this year, resulting in approximately 33,370 deaths from the disease. Approximately 40% of these patients will present with locally advanced, non-metastatic disease. Treatment regimens that incorporate conventional radiation therapy for local tumor control, and chemotherapy to prevent distant failure in this metastasis-prone malignancy, are the current standard of care. A number of clinical studies have been undertaken to establish the optimal definitive chemoradiation treatment in this setting. Other potential treatment strategies include chemoradiation incorporating novel chemotherapeutic agents, intraoperative radiation therapy, brachytherapy, and the integration of combined therapies that utilize targeted molecular agents. This review summarizes the current status, controversies, and future prospects for the treatment of locally advanced pancreatic cancer.

Phase I study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: expression analysis of genes related to outcome.

PURPOSE: To establish the feasibility of capecitabine with concurrent radiotherapy (XRT) in patients with locally advanced (LA) pancreatic cancer and evaluate the effect of XRT on thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and tumor necrosis factor-alpha (TNF-alpha). PATIENTS AND METHODS: Fifteen patients with LA pancreatic cancer received three-dimensional conformal XRT to a dose of 50.4 Gy with capecitabine at escalating doses from 600 to 1,250 mg/m2 bid (Monday through Friday). Following chemo-XRT, stable and responding patients were treated with capecitabine 2,000 mg/m2 orally bid for 14 days every 21 days. Tumor specimens were procured with endoscopic ultrasound-guided fine-needle aspiration 1 week before and 2 weeks after chemo-XRT to evaluate TP, DPD, and TNF-alpha mRNA levels. RESULTS: Dose-limiting grade 3 diarrhea was observed in two of six patients treated at a capecitabine dose of 1,000 mg/m2 with XRT. Three patients (20%) achieved partial response. Mean percent difference in TP pre- and post-XRT was 119.2% (P = .1934). There was no significant differences in mean TNF-alpha, or DPD levels pre- and post-XRT (P = .1934 and .4922, respectively). TP and TNF-alpha levels were not significantly correlated both at pre- and post-XRT (P = .670 and P < .154, respectively). Median value of TP:DPD ratios at baseline was 2.65 (range, 0.36 to 11.08). No association between TP:DPD ratio and efficacy of capecitabine or severity of toxicities was identified. CONCLUSION: The recommended dose for phase II evaluation is capecitabine 800 mg/m2 bid (Monday through Friday) with concurrent XRT. This approach offers an easy alternative to intravenous fluorouracil as a radiosensitizer in these patients. Role of TP and TP:DPD ratio warrants further investigation in a larger clinical trial.

Molecular targets as therapeutic strategies in the management of breast cancer.

Although the molecular and genetic determinants of most sporadic breast cancers remain unknown, increasing understanding of molecular and genetic events affecting breast carcinogenesis has provided information about the potential roles of specific biomarkers in tumour development and spread. It is now recognised that mutations of some tumour suppressor genes appear to play important early roles in the formation of some breast cancers. In addition, alterations in proto-oncogenes may contribute to the development of some breast cancers. The study of breast tumour biology at the molecular level has led to the development of targeted drug design, which provides a variety of agents targeted at specific molecules for the prevention, diagnosis and treatment of breast cancer. This review will describe the recognised molecular targets in breast cancer.