Modern multimodality approach to hepatic colorectal metastases: solutions and controversies.

Hepatic resection for colorectal metastases, limited to the liver, has become the standard of care, and currently remains the only potentially curative therapy. Numerous single institutional reports have demonstrated long-term survival and there are no other treatment options that have shown a survival plateau. However, curative resection is possible in less than 25% of those patients with disease limited to the liver, which translates into only 5-10% of the original group developing colorectal cancer. To increase the number of patients who could benefit from hepatic resection, the last decade has seen considerable effort being directed towards novel approaches to permit curative hepatic resection such as: neoadjuvant systemic and regional chemotherapy, pre-operative portal vein embolization for hypertrophy of future liver remnant, staged hepatic resection and radio frequency ablation combined with resection for addressing multiple bilobar metastases. This article reviews development of these innovative multidisciplinary modalities and the aggressive surgical approach that has been adopted to extend the frontiers of surgical therapy for colorectal hepatic metastases.

The AKT inhibitor perifosine in biochemically recurrent prostate cancer: a phase II California/Pittsburgh cancer consortium trial.

BACKGROUND: Perifosine is an oral alkylphospholipid that inhibits cancer cell growth through decreased Akt phosphorylation. We conducted a phase II trial of perifosine in patients with biochemically recurrent, hormone-sensitive prostate cancer. PATIENTS AND METHODS: Eligible patients had histologically confirmed prostate cancer, previous prostatectomy and/or radiation therapy, and rising prostate-specific antigen (PSA) without radiographic evidence of metastasis. Previous androgen deprivation therapy < 9 months in duration (completed >or= 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease by >or= 50% from the pretreatment value. Treatment was composed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later. RESULTS: Of 25 patients, 24 were evaluable for response. After a median follow-up of 8 months, 5 patients (20%) had a reduction in serum PSA levels, but none met criteria for PSA response. Three patients immediately progressed with no response to therapy. Median progression-free survival was 6.64 months (range, 4.53-12.81 months). No change in the PSA doubling time (7 months) was observed before and after treatment initiation. Dose-limiting toxicities (all grade 3) included hyponatremia, arthritis, hyperuricemia, and photophobia. CONCLUSION: Although well tolerated, perifosine did not meet prespecified PSA criteria for response as a single agent in biochemically recurrent prostate cancer. However, 20% of patients had evidence of PSA reduction, suggesting modest single-agent clinical activity. The role of perifosine in combination with androgen deprivation or chemotherapy is currently under investigation.

Positron emission tomography and improved survival in patients with lung cancer: the Will Rogers phenomenon revisited.

BACKGROUND: The Will Rogers phenomenon occurs when newer technology allows for more sensitive detection of tumor spread, resulting in stage migration and an apparent improvement in patient survival. We investigated whether use of highly sensitive positron emission tomography (PET) scanning in non-small cell lung cancer has had this effect. METHODS: We performed a retrospective analysis involving 12,395 patients with non-small cell lung cancer in the pre-PET (1994-1998) and PET (1999-2004) periods. Interperiod differences in staging procedures, clinical variables, and patient survival were evaluated. RESULTS: There was a 5.4% decline in the number of patients with stage III disease and an 8.4% increase in the number of patients with stage IV disease in the PET period, corresponding with an increase in PET use from 6.3% to 20.1% (P < .001). The PET period predicted better survival with a hazard ratio (HR) of 0.95 (95% confidence interval [CI], 0.91-0.99) (P = .02). Use of PET was independently associated with better survival in patients with stage III (HR, 0.77; 95% CI, 0.69-0.85) and stage IV (HR, 0.64; 95% CI, 0.58-0.70) disease, but not those with stage I or II disease. CONCLUSION: These data support the notion that stage migration is responsible at least in part for an apparent improvement in survival for patients with stage III and IV non-small cell lung cancer in the PET scan era.