Crystal S. Denlinger

Colorectal Cancer Survivorship: Movement Matters

Colorectal cancer survivorship begins at diagnosis and continues throughout life. After diagnosis, survivors face the possibility of second cancers, long-term effects of cancer treatment, and comorbid conditions. Interventions that can provide primary, secondary, and tertiary prevention in this population are important. Physical activity has been shown to decrease colon cancer incidence and recurrence risk as well as improve quality of life and noncancer health outcomes including cardiovascular fitness in colon cancer survivors. The data are less robust for rectal cancer incidence and recurrence, although improvements in quality of life and health outcomes in rectal cancer survivors are also seen. Potential mechanisms for this benefit may occur through inflammatory or insulin-like growth factor pathways. The issues of colorectal cancer survivorship and the impact of physical activity on these issues are reviewed, with discussion of possible biologic mechanisms, barriers to physical activity intervention studies, and future research directions for physical activity in this burgeoning survivor population. Cancer Prev Res; 4(4); 502–11. ©2011 AACR.

Impact of the radiation boost on outcomes after breast-conserving surgery and radiation.

PURPOSE We examined the impact of radiation tumor bed boost parameters in early-stage breast cancer on local control and cosmetic outcomes. METHODS AND MATERIALS A total of 3,186 women underwent postlumpectomy whole-breast radiation with a tumor bed boost for Tis to T2 breast cancer from 1970 to 2008. Boost parameters analyzed included size, energy, dose, and technique. Endpoints were local control, cosmesis, and fibrosis. The Kaplan-Meier method was used to estimate actuarial incidence, and a Cox proportional hazard model was used to determine independent predictors of outcomes on multivariate analysis (MVA). The median follow-up was 78 months (range, 1-305 months). RESULTS The crude cosmetic results were excellent in 54%, good in 41%, and fair/poor in 5% of patients. The 10-year estimate of an excellent cosmesis was 66%. On MVA, independent predictors for excellent cosmesis were use of electron boost, lower electron energy, adjuvant systemic therapy, and whole-breast IMRT. Fibrosis was reported in 8.4% of patients. The actuarial incidence of fibrosis was 11% at 5 years and 17% at 10 years. On MVA, independent predictors of fibrosis were larger cup size and higher boost energy. The 10-year actuarial local failure was 6.3%. There was no significant difference in local control by boost method, cut-out size, dose, or energy. CONCLUSIONS Likelihood of excellent cosmesis or fibrosis are associated with boost technique, electron energy, and cup size. However, because of high local control and rare incidence of fair/poor cosmesis with a boost, the anatomy of the patient and tumor cavity should ultimately determine the necessary boost parameters.

Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma.

Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver‐directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349–1369.

Progress in the Development of Prognostic and Predictive Markers for Gastrointestinal Malignancies

Opinion statementGastrointestinal cancers remain a significant cause of morbidity and mortality. While increasing therapeutic options have improved outcomes for many patients, they have also complicated treatment decision-making. Unfortunately, most patients with advanced gastrointestinal malignancies die from their disease. Prognostic and predictive markers could improve treatment significantly by identifying patients who may or may not require a given therapy, and determining those most likely to benefit from a therapy. Candidates for such markers include blood antigens and circulating tumor cells, tumor enzyme and gene expression, and pharmacodynamic endpoints. In this review, we summarize reported and ongoing research to define and validate prognostic and predictive markers in gastrointestinal malignancies, with an emphasis on colorectal cancer and brief overview of pancreatic and neuroendocrine tumors.

Pharmacokinetic analysis of irinotecan plus bevacizumab in patients with advanced solid tumors

PurposeThe purpose of this study was to evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted.MethodsThis was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3.ResultsForty-five subjects were enrolled. No difference in dose-normalized AUC0–last for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected.ConclusionBevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity.

Lifestyle Factors in Cancer Survivorship: Where We Are and Where We Are Headed.

Advances in early detection and curative therapies have led to an increased number of cancer survivors over the last twenty years. With this population comes the need to evaluate the late and long term effects of cancer treatment and develop recommendations about how to optimally care for these survivors. Lifestyle factors (diet, body weight, physical activity, and smoking) have been linked to a higher risk of many medical comorbidities (cardiovascular, metabolic, etc.). There is increasing evidence linking these factors to the risk of developing cancer and likely cancer-related outcomes. This link has been studied extensively in common cancers like breast, colon, prostate, and lung cancers through observational studies and is now being prospectively evaluated in interventional studies. Realizing that survivors are highly motivated to improve their overall health after a diagnosis of cancer, healthy lifestyle recommendations from oncology providers can serve as a strong tool to motivate survivors to adopt health behavior changes. Our article aims to review the evidence that links lifestyle factors to cancer outcomes and provides clinical recommendations for cancer survivors.

Prognostic Significance of MUC-1 in Circulating Tumor Cells in Patients With Metastatic Pancreatic Adenocarcinoma.

Objectives Development of targeted therapies for pancreatic cancer could be enhanced by a reliable method for noninvasive tumor cell assessment. In this pilot study, we isolated and phenotypically characterized circulating tumor cells (CTCs) from patients with metastatic pancreatic cancer and explored their relationship to clinical outcome. Methods Peripheral blood from 50 patients was collected at treatment initiation and first disease evaluation for CTC enumeration and phenotyping by CellSearch® system. Expression of human mucin 1 (MUC-1) was performed. Results Forty-eight and 37 patients had evaluable samples at baseline and first disease evaluation, respectively. The cohort was 62% male, with a median age of 63 years. At least 1 CTC per 7.5 mL was detected in 23 patients (48%) pretreatment and 11 patients (30%) at first disease evaluation. No difference was seen in overall survival between patients with 1 or more CTCs versus no CTC at baseline (P = 0.14). Patients with MUC-1 expressing CTC (n = 10) had shorter median overall survival compared with those with MUC-1 negative CTC (n = 13; 2.7 vs 9.6 m; P = 0.044). Conclusions Circulating tumor cell enumeration and phenotypic characterization from metastatic pancreatic cancer patients are feasible. No correlation was found between CTC isolation and survival. However, the presence of MUC-1 expressing CTC demonstrated a trend toward inferior survival.

Development and Preliminary Testing of PROGRESS: A Web-based Education Program for Prostate Cancer Survivors Transitioning from Active Treatment

PurposeThis formative research study describes the development and preliminary evaluation of a theory-guided, online multimedia psycho-educational program (PROGRESS) designed to facilitate adaptive coping among prostate cancer patients transitioning from treatment into long-term survivorship.MethodsGuided by the Cognitive-Social Health Information Processing Model (C-SHIP) and using health communications best practices, we conducted a two-phase, qualitative formative research study with early stage prostate cancer patients (n = 29) to inform the Web program development. Phase 1 included individual (n = 5) and group (n = 12) interviews to help determine intervention content and interface. Phase 2 employed iterative user/usability testing (n = 12) to finalize the intervention. Interview data were independently coded and collectively analyzed to achieve consensus.ResultsSurvivors expressed interest in action-oriented content on (1) managing treatment side effects, (2) handling body image and comorbidities related to overweight/obesity, (3) coping with emotional and communication issues, (4) tips to reduce disruptions of daily living activities, and (5) health skills training tools. Patients also desired the use of realistic and diverse survivor images.ConclusionsIncorporation of an established theoretical framework, application of multimedia intervention development best practices, and an evidence-based approach to content and format resulted in a psycho-educational tool that comprehensively addresses survivors’ needs in a tailored fashion.Implications for Cancer SurvivorsThe results suggest that an interactive Web-based multimedia program is useful for survivors if it covers the key topics of symptom control, emotional well-being, and coping skills training; this tool has the potential to be disseminated and implemented as an adjunct to routine clinical care.

A phase II trial of the proteasome inhibitor bortezomib in patients with advanced biliary tract cancers

BACKGROUND Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest that proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers. PATIENTS AND METHODS Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0 to 2 previous therapies received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 of a 21-day cycle. The primary end point was objective response rate. A Simon 2-stage design was used (null response rate of < 5% and response rate of ≥ 20% of interest). RESULTS Twenty patients enrolled (bile duct/gallbladder cancer [14/6] and previous treatments 0/1/2 [10/6/3]). The trial was discontinued early because of lack of confirmed partial responses. No unanticipated adverse events were noted. There was 1 unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% confidence interval [CI], 0.7-77.6 months). Median survival was 9 months (95% CI, 4.6-18.5 months). The 6-month and 1-year survival rates were 70% and 38%, respectively. There was no difference in survival based on primary disease site. CONCLUSION Single-agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered.

Survivorship, Version 2.2017: Clinical practice guidelines in oncology

Many cancer survivors experience menopausal symptoms, including female survivors taking aromatase inhibitors or with a history of oophorectomy or chemotherapy, and male survivors who received or are receiving androgen-ablative therapies. Sexual dysfunction is also common in cancer survivors. Sexual dysfunction and menopause-related symptoms can increase distress and have a significant negative impact on quality of life. This portion of the NCCN Guidelines for Survivorship provide recommendations for screening, evaluation, and treatment of sexual dysfunction and menopausal symptoms to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period.