Utilization of surgery in trimodality-eligible patients with locally advanced esophageal adenocarcinoma in a nonprotocol setting.

Trimodality therapy with neoadjuvant chemoradiation followed by surgery significantly improves the survival of locally advanced (clinical stage IIA-III) esophageal cancer patients compared to treatment with surgery alone. This has resulted in an increased use of neoadjuvant therapy in recent years, yet little is known regarding how this increase has impacted the utilization of surgery in the treatment of locally advanced disease. Although previous reports of experimental protocols suggest that 90-95% of patients complete trimodality therapy including a surgical resection, trimodality therapy completion among adenocarcinoma patients eligible for curative resection has not been evaluated in a nonprotocol setting. We sought to (i) assess the completion of trimodality therapy among locally advanced esophageal adenocarcinoma patients; (ii) characterize the reasons for avoiding surgery; and (iii) identify factors associated with failure to complete trimodality therapy. We identified 296 patients with locally advanced esophageal adenocarcinoma eligible for trimodality therapy at our institution. All patients were evaluated in a multidisciplinary setting and considered eligible for curative resection after initial staging and physiologic assessment. Multivariable logistic regression was used to identify factors associated with failure to complete trimodality therapy. Of 296 trimodality-eligible patients, 33% (97/296) did not complete trimodality therapy. Reasons for not undergoing surgery included patient choice (27.8%, 27/97), distant progression of disease during chemoradiation (23.7%, 23/97), and physician preference for surveillance (23.7%, 23/97). In addition, 17.5% (17/97) of patients had physical deterioration in performance status, and treatment-related deaths occurred in 7.2% (7/97) prior to surgery. In the total study population (n = 296), multivariable logistic regression identified older age (≥70 years: odds ratio [OR] = 6.611, 95% confidence interval [CI]: 2.900-15.071), pretreatment standard uptake value (6.8-10.1: OR = 2.393, 95% CI: 1.050-5.455; ≥15.8: OR = 3.623, 95% CI: 1.604-8.186), and a radiation dose of 50.4 Gy (OR = 5.312, 95% CI: 2.365-11.929) as being significantly associated with failure to complete trimodality therapy. Among the subgroup of patients that successfully completed chemoradiation (n = 266), older patients (≥70 years: OR = 9.606, 95% CI: 3.637-25.372), those with a comorbidity score of 2 or higher (OR = 4.059, 95% CI: 1.257-13.103), and those that received a radiation dose of 50.4 Gy (OR = 4.878, 95% CI: 1.974-12.054) were at a significantly higher risk of not completing trimodality therapy. Trimodality therapy completion among patients with locally advanced esophageal adenocarcinoma in a nonprotocol setting is considerably lower than what has previously been reported in clinical trials. Our findings suggest that a selective approach to surgery is commonly utilized in clinical practice. Trimodality-eligible patients that are older and have a higher comorbidity score are at risk for not completing trimodality therapy.

Accelerated fractionation radiation therapy for liver metastases: selection of an optimal patient population for the evaluation of late hepatic injury in RTOG studies.

The palliation of hepatic metastases represents a major therapeutic problem in oncology. The generally unfavorable prognosis of patients with liver metastasis may complicate the evaluation of the efficacy and toxicity of various therapeutic modalities. The Radiation Therapy Oncology Group (RTOG) is evaluating new accelerated fractionation schemes for hepatic irradiation. In designing this study it became necessary to identify a favorable subpopulation of patients with an expected median survival of 6 months in whom the late effects of treatment could be evaluated. Data from two RTOG liver metastases studies (7605 and 8003) were analyzed using multi-variate techniques. Cases with a serum bilirubin level of greater than 1.5 mg%, performance score of less than 50, and gastric or pancreatic primary carcinomas were initially excluded because of the adverse influence of these factors on survival. One hundred and ninety cases met the criteria for inclusion in this analysis. A loglinear model was used to identify the patient characteristics associated with a favorable prognosis for survival. These included a performance score of 80-100, colorectal carcinoma primary, and no extrahepatic metastases. A logistic regression equation was derived and confirmed that the probability of surviving at least 6 months depended on the effects of performance score, primary site and the presence or absence of extra-hepatic metastases. Patients with all three favorable factors constituted 30% of the evaluable study population and had a predicted survival of 50% at 6 months. A patient population with these characteristics will be used to study the late effects of accelerated fractionated radiation therapy on the liver.

A comparison of misonidazole sensitized radiation therapy to radiation therapy alone for the palliation of hepatic metastases: results of a Radiation Therapy Oncology Group randomized prospective trial.

Between May 1980 and July 1983, the RTOG conducted a randomized prospective study comparing external radiation therapy and misonidazole to radiation therapy alone for patients with hepatic metastases. Two hundred fourteen patients were accessioned to this study of whom 187 were evaluable. Radiation therapy was delivered to the whole liver to a dose of 21.0 Gy in 7 fractions. Misonidazole was administered orally, 1.5 gm/m2 daily 4-6 hr before each treatment. Patients in the two treatment groups were evenly distributed with respect to stratification variables including primary site, extent of metastatic disease, and Karnofsky Performance Score (KPS). End points examined included amelioration of hepatic pain, improvement of KPS and alkaline phosphatase, decrease in liver and tumor size, and survival. The addition of misonidazole did not significantly improve the therapeutic response to radiation therapy in any of the parameters studied. Hepatic irradiation was effective in relieving abdominal pain with 80% of the symptomatic patients achieving improvement following therapy. Pain was completely relieved in 54% of these patients. Patients with liver metastases from colon carcinoma improved more frequently than those with metastases from other primary tumor sites (p = 0.02). Relief of pain occurred more frequently in patients treated with radiation therapy and misonidazole (87%) compared with radiation therapy alone (74%) (p = 0.08). Palliation of pain was prompt, occurring within a median of 1.7 weeks from the initiation of treatment, and 94% of patients who improved did so within 6 weeks of treatment. The median duration of response was 13.0 weeks in the symptomatic patients; 52% of those surviving 3 months remained improved. KPS improved in 28% of patients. Serial CT scans revealed a partial response in 7% and a marginal response in 13% of patients. One patient had a complete response to treatment. The median survival of patients treated in this series was 4.2 months with no difference between the two treatment groups. Patients with metastases from colon carcinoma and an initial KPS of 80 or more (48% of the patient population) had a median survival of 5.8 months with radiation therapy alone compared with 6.6 months with radiation therapy and misonidazole (p = 0.36). There was no significant treatment related morbidity. Radiation therapy remains an excellent palliative tool for the management of patients with symptomatic hepatic metastases. Further research must continue to identify new methods of selectivity enhancing the tumor response to radiation therapy.