Michael Chao

Pretreatment Transcriptional Profiling for Predicting Response to Neoadjuvant Chemoradiotherapy in Rectal Adenocarcinoma

Purpose: Patients presenting with locally advanced rectal cancer currently receive preoperative radiotherapy with or without chemotherapy. Although pathologic complete response is achieved for approximately 10% to 30% of patients, a proportion of patients derive no benefit from this therapy while being exposed to toxic side effects of treatment. Therefore, there is a strong need to identify patients who are unlikely to benefit from neoadjuvant therapy to help direct them toward alternate and ultimately more successful treatment options. Experimental Design: In this study, we obtained expression profiles from pretreatment biopsies for 51 rectal cancer patients. All patients underwent preoperative chemoradiotherapy, followed by resection of the tumor 6 to 8 weeks posttreatment. Gene expression and response to treatment were correlated, and a supervised learning algorithm was used to generate an original predictive classifier and validate previously published classifiers. Results: Novel predictive classifiers based on Mandards tumor regression grade, metabolic response, TNM (tumor node metastasis) downstaging, and normal tissue expression profiles were generated. Because there were only 7 patients who had minimal treatment response (>80% residual tumor), expression profiles were used to predict good tumor response and outcome. These classifiers peaked at 82% sensitivity and 89% specificity; however, classifiers with the highest sensitivity had poor specificity, and vice versa. Validation of predictive classifiers from previously published reports was attempted using this cohort; however, sensitivity and specificity ranged from 21% to 70%. Conclusions: These results show that the clinical utility of microarrays in predictive medicine is not yet within reach for rectal cancer and alternatives to microarrays should be considered for predictive studies in rectal adenocarcinoma. Clin Cancer Res; 17(9); 3039–47. ©2011 AACR.

RADIATION CHANGES DO NOT INTERFERE WITH POSTCHEMORADIATION RESTAGING OF PATIENTS WITH RECTAL CANCER BY FDG PET/CT BEFORE CURATIVE SURGICAL THERAPY

PURPOSE Changes in F-18 fluorodeoxyglucose (FDG) uptake in normal tissues after chemoradiation therapy (CRT) potentially limit the ability of positron emission tomography (PET) to provide early assessment of therapeutic response. This study evaluated whether such changes negatively impact interpretation of posttherapy PET performed within 6 weeks of CRT completion and before definitive surgery in patients with locally advanced rectal cancer. The positive predictive value (PPV) and specificity of post-CRT PET, read clinically, was determined in 63 consecutive rectal cancer patients who had undergone preoperative CRT. METHODS AND MATERIALS A schema for identifying and scoring postradiation effects on PET was prospectively defined and applied in a blinded manner. This was compared with initial clinical reporting of response. Histologic assessment of the operative specimens was used as the reference standard. Correlation between clinical proctitis during CRT and radiation changes on subsequent PET was also assessed. RESULTS Clinical reporting of post-CRT PET yielded a high PPV (94%; 95% confidence interval, 89--100%) but may have been exaggerated by the low prevalence of complete tumor clearance (16%). The specificity was 80% with only two false-positive results. On blinded reading, significant post-CRT effects on PET were recorded in 4 of 63 patients (6% 95% confidence interval, 0-13%), but pattern recognition converted both false-positive PET results to a complete metabolic response. Clinical CRT proctitis was not correlated with PET findings. CONCLUSION Postradiation effects do not appear to significantly compromise the interpretation of PET for therapeutic response assessment. The proposed PET pattern of response may further improve the specificity of PET.

The use of PET in assessing tumor response after neoadjuvant chemoradiation for rectal cancer

PURPOSE To assess the correlation of 18F-FDG-PET (PET) response to pathological response after neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer. METHODS AND MATERIALS Twenty patients with locally advanced rectal cancer were identified between 2001 and 2005. The median age was 57 years (range 37-72) with 14 males and 6 females. All patients were staged with endorectal ultrasound and/or MRI, CT, and PET. The clinical staging was T3N0M0 (16), T3N1M0 (2), and T3N0M1 (2). Restaging PET was performed after CRT, and prior to definitive surgery. The response on PET and pathology was assessed and correlated. Patient outcome according to PET response was also assessed. RESULTS Following CRT, a complete PET response occurred in 7 patients, incomplete response in 10, and no response in 3 patients. At surgery, complete pathological response was recorded in 7 patients, incomplete response in 10 and no response in 3. There was a good correlation of PET and pathological responses in complete responders (5/7 cases) and non-responders (3/3 cases). After a median follow-up of 62 months (range 7-73), twelve patients were alive with no evidence of disease. All patients achieving complete metabolic response were alive with no evidence of disease, while as those who had no metabolic response, all died as a result of metastatic disease. CONCLUSIONS PET is a promising complementary assessment tool for assessing tumor response after CRT if there is a complete or no response. PET response may also predict for outcome.

Carcinoma of the anal canal: A local experience and review of the literature

Background:  Through the 1970s patients presenting with anal canal carcinoma were managed with a surgical approach − abdomino‐perineal resection. Since then, the pioneering work of Nigro et al. and a series of large clinical trials have clearly demonstrated that combined chemotherapy and radiotherapy result in greater local control, colostomy‐free survival and increase in overall patient survival. The aim of the present study is to determine how widely the combined modality approach has been adopted in routine clinical practice and what outcomes are achieved in this setting.

Fiducial markers and spacers in prostate radiotherapy: current applications

To review the use of fiducial markers and spacers in prostate radiotherapy (RT).

MRI scans significantly change target coverage decisions in radical radiotherapy for prostate cancer

Conventional clinical staging for prostate cancer has many limitations. This study evaluates the impact of adding MRI scans to conventional clinical staging for guiding decisions about radiotherapy target coverage.

Audit of postoperative chemoradiotherapy as adjuvant therapy for resected gastroesophageal adenocarcinoma: An Australian multicentre experience

Background:  Improved disease free and overall survivals were seen in curatively resected patients with gastric and gastroesophageal adenocarcinoma treated with the Intergroup 0116 (INT 0116) protocol of postoperative adjuvant chemoradiotherapy compared to surgery alone. This protocol has not been widely adopted in Australian centres because of perceived risks of toxicity.

Preoperative chemotherapy and radiotherapy for locally advanced rectal cancer.

Background:  The adjuvant treatment of rectal cancer is a rapidly evolving field. The standard approach is a combination of chemotherapy and radiotherapy, with the optimal treatment combination and sequencing yet to be determined. Here, we report our early experience of preoperative chemotherapy and radiotherapy (CRT) in locally advanced rectal cancer at Radiation Oncology Victoria to determine its efficacy and the rate of sphincter preservation.

The influence of language spoken on colorectal cancer diagnosis and management

Multiple studies have reported clearly inferior cancer-related outcomes in minority populations.1 Stage at diagnosis and differences in treatment have been cited as the most important explanatory factors. Some research has evaluated the psychosocial elements of this association; however, the influence of language has not previously been evaluated.1 Patients who do not have English as a preferred language make up a significant minority in Australian public hospitals and although interpreters are available, or family members may act in this capacity, the effect on patient outcomes has not been reported. To assess the influence of language spoken, we queried a prospective colorectal cancer database at Western Hospital, established in 1998 and matched this with data from the hospitals central information system, which records patient preferred language. Of the 1114 patients on our database, 215 (19%) described a language other than English as their preferred language. ANZ J. Surg. 2006; 76: 671–673

OPTIMIZING THE APPROACH TO PATIENTS WITH POTENTIALLY RESECTABLE LIVER METASTASES FROM COLORECTAL CANCER

Liver metastases are a common event in colorectal carcinoma. Significant advances have been made in managing these patients in the last decade, including improvements in staging and surgical techniques, an increasing armamentarium of chemotherapeutics and multiple local ablative techniques. While combination chemotherapy significantly improves median patient survival, surgical resection provides the only prospect of cure and is the focus of this review. Interpretation of published work in this field is challenging, particularly as there is no consensus to what is resectable disease. Of particular interest recently has been the use of neoadjuvant treatment for downstaging and downsizing disease in patients with initially unresectable liver metastases, in the hope of response leading to potentially curative surgery. This review summarizes the recent developments and consensus guidelines in the areas of staging, chemotherapy, local ablative techniques, radiation therapy and surgery, emphasizing the multidisciplinary approach to this disease and ongoing controversies in this field and examines the changing paradigms in the management of colorectal hepatic metastases.