Joanne F. Chou

Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial

PURPOSE There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. METHODS We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. RESULTS Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts. CONCLUSION Clinical benefits were associated with symptom self-reporting during cancer care.

Pathologic stage is most prognostic of disease‐free survival in locally advanced rectal cancer patients after preoperative chemoradiation

Preoperative chemoradiation is the standard treatment for locally advanced rectal cancer. However, it is uncertain whether pretreatment clinical stage, degree of response to neoadjuvant treatment, or pathologic stage is the most reliable predictor of outcome. This study compared various staging elements and treatment‐related variables to identify which factors or combination of factors reliably prognosticates disease‐free survival in rectal cancer patients receiving neoadjuvant combined modality therapy.

Clinical and pathologic factors that predict lymph node yield from surgical specimens in colorectal cancer: a population-based study.

The National Quality Forum endorses the recommendation of examining at least 12 lymph nodes (LNs) from colorectal cancer (CRC) specimens. However, heterogeneity in LN harvest exists. The objective of this study was to investigate the clinicopathologic factors that influence LN yield.

Five hundred patients with Merkel cell carcinoma evaluated at a single institution.

Objective:To identify factors associated with survival in Merkel cell carcinoma (MCC). Background:Merkel cell carcinoma is a rare cutaneous neoplasm. Staging and treatment are based on studies, which incompletely characterize the disease. Methods:Review of a prospective database was performed. Overall survival (OS) was estimated by the Kaplan-Meier method. Disease-specific death (DSD) was analyzed by the competing risks method. Factors associated with OS and DSD were determined by the log-rank test and Grays test, respectively. Results:A total of 500 patients with MCC treated at our institution from 1969 to 2010 were identified. Eighty-eight patients presented older than 6 months after diagnosis and were excluded from further analysis. Of the remaining 412 patients, the median age at diagnosis was 71 years. Median follow-up was 3 years. Fifty percent of patients died during follow-up: 25% died of disease, 24% died of other causes. Five-year OS and DSD were 56% and 30%, respectively. Pathologic stage and lymphovascular invasion were independent predictors of DSD. Patients with metastatic disease (stage 4) or clinically positive lymph nodes (stage 3b) had increased DSD compared with patients with microscopically positive (stage 3a) or negative lymph nodes (stage 1 and 2). There was no difference in DSD between stage 3a or 2 compared with stage 1. Importantly, only 1 of 132 patients without lymphovascular invasion died of MCC. Conclusions:OS is a poor measure of the influence of MCC on life expectancy. The presence of lymphovascular invasion and clinically, but not microscopically, positive lymph nodes were associated with increased DSD. These factors should be incorporated into MCC staging and treatment recommendations.

Breast Cancer After Chest Radiation Therapy for Childhood Cancer

PURPOSE The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose. PATIENTS AND METHODS We evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). RESULTS Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio [SIR], 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer-specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively. CONCLUSION Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.

BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer

BRAF mutations occur in 5% to 11% of patients with metastatic colorectal cancer (mCRC) and have been associated with poor prognosis. The current study was undertaken to determine the clinicopathologic characteristics, PIK3CA (phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, catalytic subunit alpha) mutation frequency, and outcomes after metastasectomy in patients with BRAF‐mutant mCRC.

The Effect of Posttherapy 131I SPECT/CT on Risk Classification and Management of Patients with Differentiated Thyroid Cancer

The objective of this study was to determine whether posttherapy 131I SPECT/CT changed the need for additional cross-sectional imaging or modified the American Thyroid Association risk of recurrence classification. We performed planar imaging and SPECT/CT in a consecutive series of patients after 131I therapy. Methods: Planar imaging and SPECT/CT were performed on 148 consecutive patients with thyroid carcinoma (125 papillary, 2 follicular, 8 Hürthle cell, and 13 poorly differentiated) approximately 5 d after the therapeutic administration of 1,739–8,066 MBq (47–218 mCi) of 131I. The indication for treatment was postsurgical ablation (n = 109) or recurrent or metastatic disease with rising thyroglobulin levels (n = 39). SPECT/CT scans were obtained for all subjects for 1 bed position (38 cm), which included the neck and upper chest. Additional SPECT/CT scans of the abdomen or pelvis were acquired if suggestive findings were noted on planar images. All patients were treated in real time, according to the standard of care in our practice. At that time, clinical decisions regarding thyroid tumor classification were made by our multidisciplinary group based on all data, including operative findings, pathology, imaging, and thyroglobulin levels. In a retrospective analysis, planar and SPECT/CT images were interpreted independently, and sites of uptake were categorized as likely benign, malignant, or equivocal. An experienced thyroid endocrinologist used a combination of surgical histopathology and scan findings to determine whether additional cross-sectional imaging was required and determined if the imaging findings changed the patients risk category. Results: In 29 patients, 61 additional cross-sectional imaging studies were avoided using SPECT/CT, compared with medical decision making based on the planar images alone. In 7 of 109 postsurgical patients, SPECT/CT findings changed the initial American Thyroid Association risk of recurrence classification. The sensitivity of planar imaging and SPECT/CT for identification of focal 131I uptake in the thyroid bed was similar in the postsurgical and recurrence cohorts. For metastatic disease in the neck, characterization of 131I uptake by SPECT/CT in the postsurgical group was significantly better than that by planar scanning (P < 0.01). Among the 109 postsurgical patients, the characterization of iodine uptake in the lung, liver, and bone was also more accurate using SPECT/CT than planar scanning (P < 0.01). The CT portion of SPECT/CT demonstrated non–iodine-avid lesions in 32 of 148 patients. Conclusion: SPECT/CT data provided information that reduced the need for additional cross-sectional imaging in 29 patients (20%) and significantly altered the initial risk of recurrence estimates in 7 of 109 patients (6.4%), thereby altering patient management recommendations with regard to frequency and intensity of follow-up studies.

Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: Conversion to resection and long-term outcomes

PURPOSE Evaluate conversion rate of patients with unresectable colorectal-liver metastasis to complete resection with hepatic-arterial infusion plus systemic chemotherapy including bevacizumab (Bev). PATIENTS AND METHODS Forty-nine patients with unresectable colorectal liver metastases (CRLM) were included in a single-institution phase II trial. Conversion to resection was the primary outcome. Secondary outcomes included overall survival (OS), progression-free survival, and response rates. Multivariate and landmark analyses were performed to evaluate survival differences between resected and nonresected patients. RESULTS Median number of tumors was 14 and 65% were previously treated patients. A high biliary toxicity rate was found in the first 24 patients whose treatment included Bev. The remaining 25 patients were treated without Bev. Overall response rates were 76% (4 complete responses). Twenty-three patients (47%) achieved conversion to resection at a median of 6 months from treatment initiation. Median OS and progression-free survival for all patients were 38 (95% confidence interval: 28 to not reached) and 13 months (95% confidence interval: 7-16). Bev administration did not impact outcome. Conversion was the only factor associated with prolonged OS and progression-free survival in multivariate analysis. On landmark analysis, patients who had undergone resection had longer OS than those who did not undergo resection (3-year OS: 80% vs 26%). Currently, 10 of 49 (20%) patients have no evidence of disease (NED) at a median follow-up of 39 months (32-65 months). CONCLUSIONS In patients with extensive unresectable CRLM, the majority of whom were previously treated, 47% were able to undergo complete resection after combined HAI and systemic therapy. Conversion to resection is associated with prolonged survival.

Predicting Survival After Curative Colectomy for Cancer: Individualizing Colon Cancer Staging

PURPOSE Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy. METHODS Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves. RESULTS Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T- and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line. CONCLUSION Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer.

KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases.

The validity of the KRAS mutation as a predictor of recurrence‐free survival (RFS) or overall survival (OS) is unclear. The current study investigated whether the presence of the KRAS mutation decreased RFS or OS in patients with colorectal cancer who underwent liver resection.