Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer.

BACKGROUND: Signal Transducer and Activator of Transcription-3 (STAT3) mediates cellular functions. We assessed the IHC expression of phosphorylated STAT3 (pSTAT3) in paired primary tumors and liver metastases in patients with advanced stage colorectal cancer (CRC). METHODS: We included patients with tissue blocks available from both the primary CRC and a surgically resected liver metastasis. The IHC pSTAT3 expression agreement was measured using Cohen's kappa statistic. RESULTS: The study included 103 patients, 55% male, median age was 64. 43% tumors originated in rectum, and 63% of the primary tumors were synchronous. Expression of pSTAT3 was 76% in liver metastases and 71% in primary tumors. A difference in pSTAT3 staining between the primary tumor and liver metastases was noted in 64%. There was lost expression of pSTAT3 in the liver metastases in 28% and gained expression in 36% of cases compared to the primary. The kappa statistic comparing agreement between staining patterns of the primary tumors and liver metastases was a "less-than-chance", at -0.02. Median survival was 4.9 years, with no difference in survival outcomes by pSTAT3 expression in the primary tumor or liver metastases. DISCUSSION: STAT3 is not a prognostic marker in the selective setting of metastatic CRC to liver, but it may remain a potential therapeutic target given most liver metastases expressed pSTAT3. Discordant pSTAT3 expression in between primary tumors and paired liver metastases suggests that use of this class of drug to treat liver predominant metastatic colorectal cancer in a biomarker-driven approach may require confirmatory liver tumor biopsy.

Prognostic and predictive clinical factors in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel.

INTRODUCTION: Cabazitaxel is one of several treatment options available for patients with metastatic castration-resistant prostate cancer who have progressed on docetaxel. Little is known about clinical factors that influence prognosis or treatment response for patients receiving cabazitaxel. Identifying prognostic and predictive factors could contribute to the optimal selection of patients for treatment after docetaxel. METHODS: A retrospective review of patients enrolled on the cabazitaxel Canadian Early Access Program (C-EAP) was performed. Clinical factors were analyzed by univariable and multivariable Cox proportional hazards and logistic regression analysis to identify independent predictors of prognosis and response. RESULTS: Forty-five patients from five centres in Canada were included in this study. On multivariable analysis, lower hemoglobin was associated with shorter survival. No other factors were independently associated with survival, prostate-specific antigen (PSA) response, or primary PSA progression. CONCLUSIONS: Clinical factors predicting survival or treatment response were not identified for men with castration-resistant prostate cancer receiving cabazitaxel. Larger studies may be necessary to identify clinical factors and biomarkers that identify whether patients should or should not receive cabazitaxel.

Beyond the black box of geriatric assessment: Understanding enhancements to care by the geriatric oncology clinic.

OBJECTIVE: Comprehensive geriatric assessment (CGA) of older adults with cancer aids treatment decision-making and prognostication. Much less is known about the supportive care elements or enhancements to care afforded by the CGA. We characterized the enhancements to care provided by a geriatric oncology clinic and determined how these vary by indication for referral. MATERIALS AND METHODS: All patients age 65 or older referred to a single academic geriatric oncology clinic between July 2015 (clinic opening) and June 2017 were included. Treatment enhancements were prospectively recorded in 5 categories: educational support, comorbidity management, symptom management, oncologic treatment delivery, and peri-operative management recommendations. Indications for referral were categorized into 3 groups: pre-treatment (n = 97, 44%), on active treatment (n = 89, 41%), and survivorship phase (n = 33, 15%). Data were analyzed using descriptive statistics and multivariable logistic regression. RESULTS: 219 patients were seen during the study period (mean age 79.7 years, 69% male). Overall, educational support (96%) and comorbidity management (95%) were the most common enhancements, whereas peri-operative management (10%) was the least common and provided only to pre-treatment patients. Enhancements to cancer treatment delivery were offered more often to patients pre-treatment than on active treatment (61% versus 41%, p < 0.001). Other enhancements to care did not vary by indication for referral. CONCLUSION: Educational support and comorbidity management are nearly universally offered. Most enhancements to care do not vary by indication for referral. Understanding the enhancements to care provided by geriatric oncology clinics can help with resource planning and program design.

Geriatric oncology screening tools for CGA-based interventions: results from a phase II study of geriatric assessment and management for older adults with cancer.

INTRODUCTION: Screening tools in geriatric oncology have traditionally been studied for their ability to identify patients who have abnormal domains on a comprehensive geriatric assessment (CGA). However, an alternative outcome of identifying patients who would receive CGA-based interventions could improve selection of patients whose management will be altered by a CGA. The objective of this study was to assess the performance of three geriatric oncology screening tools for their ability to predict for CGA-based interventions. MATERIALS AND METHODS: G8, Vulnerable Elders Survey (VES-13) and a modified frailty phenotype (mFP) screening tools were collected prospectively for patients enrolled in a phase II trial of geriatric evaluation and management. Interventions were defined as a new clinical diagnosis, change in management of a comorbidity, or referral to an allied health professional. Performance characteristics were calculated for each screening tool based on the outcomes of ≥2 abnormal CGA-domains and ≥1 CGA-based interventions. RESULTS: Discordance between the outcomes was seen in 31.9% of patients. Using the outcome of ≥2 abnormal CGA-domains, the G8 was most sensitive at 0.73 while VES-13 and mFP were both 1.0 specific. Using the outcome of CGA-based interventions the most sensitive tool was still the G8 at 0.64 and the most specific was the mFP at 0.80. DISCUSSION: All screening tests' performance characteristics for the G8, VES-13 and mFP were lower for the outcome of CGA-based interventions than for the traditional outcome of abnormal CGA-domains. Significant discordance between the outcomes highlights the difficulty with trying to predict which patients will truly benefit from a CGA.

Radical Treatment of Stage II Non-small-cell Lung Cancer With Nonsurgical Approaches: A Multi-institution Report of Outcomes.

INTRODUCTION: Standard management of stage II non-small-cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. We examined outcomes in this defined patient group. METHODS: We reviewed the records of patients with stage II NSCLC treated nonsurgically with curative intent from 2002 to 2012 across 3 academic cancer centers. Data collected included demographics, comorbidities, staging, treatments, and survival. The primary endpoint was overall survival (OS). We assessed factors associated with treatment choice and OS. RESULTS: A total of 158 patients were included: the median age was 74 years (range, 50-91 years), 44% were female, and 68% had a performance status of 0 to 1. The stage II groupings of the patients were T2b-T3 N0 in 55% and N1 in 45%. The most common reasons for inoperability were inadequate pulmonary reserve (27%) and medical comorbidities (24%). All patients received radical radiotherapy (RT) (median, 60 Gy [range, 48-75 Gy]). Seventy-three percent received RT alone; 24% received concurrent and 3% sequential chemoradiotherapy (CRT). In multivariate analyses, CRT was less likely in older patients (≥ 70 years) (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.70; P = .006) and in patients with higher (> 5) Charlson comorbidity scores (OR, 0.34; 95% CI, 0.13-0.90; P = .03) or normal (< 10 × 109/L) white blood cell counts (OR, 0.26; 95% CI, 0.09-0.73; P = .01). At the time of our analysis, 74% have died. The median OS was 22.9 months (range, 17.1-26.6 months). Patients who had undergone CRT had a significantly longer median OS than those receiving RT alone (39.1 vs. 20.5 months; P = .0019), confirmed in multivariate analysis (hazard ratio, 0.38; 95% CI, 0.21-0.69; P = .001). CONCLUSION: Nonsurgical approaches to management of stage II NSCLC are varied. Treatment with CRT was associated with significantly longer survival compared with RT alone. A randomized trial may be warranted.