Geoffrey A. Porter

Evaluating Survivorship Care Plans: Results of a Randomized, Clinical Trial of Patients With Breast Cancer

PURPOSE An Institute of Medicine report recommends that patients with cancer receive a survivorship care plan (SCP). The trial objective was to determine if an SCP for breast cancer survivors improves patient-reported outcomes. PATIENTS AND METHODS Women with early-stage breast cancer who completed primary treatment at least 3 months previously were eligible. Consenting patients were allocated within two strata: less than 24 months and ≥ 24 months since diagnosis. All patients were transferred to their own primary care physician (PCP) for follow-up. In addition to a discharge visit, the intervention group received an SCP, which was reviewed during a 30-minute educational session with a nurse, and their PCP received the SCP and guideline on follow-up. The primary outcome was cancer-related distress at 12 months, assessed by the Impact of Event Scale (IES). Secondary outcomes included quality of life, patient satisfaction, continuity/coordination of care, and health service measures. RESULTS Overall, 408 survivors were enrolled through nine tertiary cancer centers. There were no differences between groups on cancer-related distress or on any of the patient-reported secondary outcomes, and there were no differences when the two strata were analyzed separately. More patients in the intervention than control group correctly identify their PCP as primarily responsible for follow-up (98.7% v 89.1%; difference, 9.6%; 95% CI, 3.9 to 15.9; P = .005). CONCLUSION The results do not support the hypothesis that SCPs are beneficial for improving patient-reported outcomes. Transferring follow-up to PCPs is considered an important strategy to meet the demand for scarce oncology resources. SCPs were no better than a standard discharge visit with the oncologist to facilitate transfer.

Retroperitoneal sarcoma: a population-based analysis of epidemiology, surgery, and radiotherapy.

No population‐based studies of retroperitoneal sarcoma (RPS) have been conducted, and the use and timing of adjuvant radiotherapy for RPS is controversial. The objective of this study was to examine the incidence and treatment of RPS, specifically regarding the use of adjuvant radiotherapy.

Effect of Obesity on Presentation of Breast Cancer

BackgroundObesity has been shown to be associated with reduced survival in patients with invasive breast cancer (IBC), although the mechanisms for this finding are unclear. The objective of this study was to examine the effect of obesity on the presentation and pathologic staging of IBC.MethodsFrom February 15, 2002, to February 15, 2004, all patients undergoing surgery for primary IBC at two institutions were enrolled in a prospective cohort study. National Institutes of Health criteria were used to categorize patients: normal or underweight (NW; body mass index <25 kg/m2), overweight (OW; body mass index 25–29.9 kg/m2), and obese or severely obese (OB; body mass index ≥30 kg/m2). Presentation and pathologic factors were then compared among groups.ResultsThe study cohort consisted of 519 patients; 166 (32%) were NW, 177 (34%) were OW, and 176 (34%) were OB. OW (46%) and OB (39%) patients were more likely to be diagnosed with IBC via screening mammography compared with NW (31%) patients (P = .01), although no differences were found between groups with respect to previous use of screening mammography. Aggressive pathologic features, including lymph node metastases, advanced tumor-node-metastasis stage, and grade were found more commonly among OB patients.ConclusionsOW and OB patients were more likely to receive a diagnosis via screening mammography, thus suggesting that mammography may play a more important role in OW and OB patients. Despite this, OB patients presented with larger, more advanced tumors; this may help to explain obesity-associated survival differences in IBC patients. This is important information given the prevalence of obesity in North America.

Cyclin D1 polymorphism (G870A) and risk for esophageal adenocarcinoma

To investigate individual susceptibility to gastroesophageal reflux disease, Barrett esophagus, and esophageal adenocarcinoma, the authors studied the frequency of the common G870A polymorphism of CCND1, which encodes cyclin D1, a key cell cycle regulatory protein.

Basic Fibroblast Growth Factor (FGF-2) Overexpression Is a Risk Factor for Esophageal Cancer Recurrence and Reduced Survival, which Is Ameliorated by Coexpression of the FGF-2 Antisense Gene

Purpose: The basic fibroblast growth factor (FGF-2) gene is bidirectionally transcribed to generate overlapping sense and antisense (FGF-AS) mRNAs. FGF-AS has been implicated in the post-transcriptional regulation of FGF-2 expression. The aim of this study was to characterize FGF-2 and FGF-AS in esophageal cancer and to correlate their expression with clinicopathologic findings and outcome. Experimental Design: Reverse transcription-PCR was used to study FGF-2 and FGF-AS mRNA expression (normalized to glyceraldehyde-3-phosphate dehydrogenase) in 48 esophageal cancers relative to matched histologically normal esophageal epithelia (internal control). We used Cox proportional hazards analysis to calculate hazard ratios for recurrence and survival of patients with underexpression relative to the overexpression of FGF-2 and/or FGF-AS. Results: Overexpression of FGF-2 mRNA, by comparison with tumors underexpressing FGF-2, was associated with significantly increased risk for tumor recurrence (hazard ratio, 3.80; 95% confidence interval, 1.64-8.76) and reduced overall survival (hazard ratio, 2.11; 95% confidence interval, 1.0-4.58). When the effects of FGF-2 and FGF-AS were considered simultaneously, the association of FGF-2 mRNA overexpression with recurrence and mortality was even more pronounced, whereas FGF-AS mRNA overexpression was associated with reduced risk for recurrence and improved survival. Conclusions: Overexpression of FGF-2 mRNA is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer and that these risks are reduced in tumors coexpressing the FGF-AS mRNA. These data support the hypothesis that FGF-AS is a novel tumor suppressor that modulates the effect of FGF-2 expression and may have potential clinical application to the development of novel therapeutic strategies.

Inducible nitric oxide synthase, nitrotyrosine and p53 mutations in the molecular pathogenesis of Barrett's esophagus and esophageal adenocarcinoma.

Nitric oxide (NO) has been implicated as a potential causative factor for endogenous p53 mutations in gastrointestinal malignancy. To investigate the role of NO in esophageal adenocarcinoma (EADC), we studied patterns of p53 mutations, expression of inducible nitric oxide synthase (iNOS) and the tissue accumulation of nitrotyrosine (NTS), a stable reaction product of NO and a marker for cellular protein damage, in human premalignant and malignant esophageal epithelia. Tissues were obtained from patients with gastroesophageal reflux disease (GERD)‐induced esophagitis (n = 76), Barretts esophagus (BE; n = 119) and primary EADC (n = 54). DNA sequencing was used to characterize p53 mutations, RT‐PCR to study iNOS mRNA expression, and immunohistochemistry to study NTS. Relative to self‐matched normal epithelia, a progressive increase in iNOS mRNA expression was seen in GERD (30%; 23/76), BE (48%; 57/119), and EADC (63%; 34/54) tissues (P < 0.001). Among patients with EADC, elevated levels of NTS immunoreactivity were more frequent in tumors with p53 mutations (11/21; 52%) compared with tumors with wild‐type p53 (9/33; 27%; P = 0.063), and specifically in tumors with p53 mutations at CpG dinucleotides (10/12; 83%) compared with non‐CpG p53 mutations (1/9; 11%; P = 0.008). The increasing frequency of iNOS (mRNA) overexpression in GERD, BE and EADC supports the hypothesis that an active inflammatory process, most likely a consequence of GERD, underlies molecular progression to EADC. The highly significant association between NTS, reflecting chronic NO‐induced cellular protein damage, and endogenous p53 mutations at CpG dinucleotides, provides further evidence for a molecular link between chronic inflammation and esophageal malignancy.

A randomized controlled trial comparing acetaminophen plus ibuprofen versus acetaminophen plus codeine plus caffeine after outpatient general surgery.

BACKGROUND Narcotics are used extensively in outpatient general surgery but are often poorly tolerated with variable efficacy. Acetaminophen combined with NSAIDs is a possible alternative. The objective of this study was to compare the efficacy of acetaminophen, codeine, and caffeine (Tylenol No. 3) with acetaminophen and ibuprofen for management of pain after outpatient general surgery procedures. STUDY DESIGN A double-blind randomized controlled trial was performed in patients undergoing outpatient inguinal/umbilical/ventral hernia repair or laparoscopic cholecystectomy. Patients were randomized to receive acetaminophen plus codeine plus caffeine (Tylenol No. 3) or acetaminophen plus ibuprofen (AcIBU) 4 times daily for 7 days or until pain-free. Pain intensity, measured four times daily by visual analogue scale, was the primary outcome. Secondary end points included incidence of side effects, patient satisfaction, number of days until patient was pain-free, and use of alternative analgesia. RESULTS One hundred forty-six patients were randomized (74 Tylenol No. 3 and 72 AcIBU), and 139 (95%) patients completed the study. No significant differences in mean or maximum daily visual analogue scale scores were identified between the 2 groups, except on postoperative day 2, when pain was improved in AcIBU patients (p = 0.025). During the entire week, mean visual analogue scale score was modestly lower in AcIBU patients (p = 0.018). More patients in the AcIBU group, compared with Tylenol No. 3, were satisfied with their analgesia (83% versus 64%, respectively; p = 0.02). There were more side effects with Tylenol No. 3 (57% versus 41%, p = 0.045), and the discontinuation rate was also higher in Tylenol No. 3-treated patients (11% versus 3%, p = 0.044). CONCLUSIONS When compared with Tylenol No. 3, AcIBU was not an inferior analgesic and was associated with fewer side effects and higher patient satisfaction. AcIBU is an effective, low-cost, and safe alternative to codeine-based narcotic analgesia for outpatient general surgery procedures.

A phase II experience with neoadjuvant irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) for colorectal liver metastases

BackgroundChemotherapy may improve survival in patients undergoing resection of colorectal liver metastases (CLM). Neoadjuvant chemotherapy may help identify patients with occult extrahepatic disease (averting unnecessary metastasectomy), and it provides in vivo chemosensitivity data.MethodsA phase II trial was initiated in which patients with resectable CLM received CPT-11, 5-FU and LV for 12 weeks. Metastasectomy was performed unless extrahepatic disease appeared. Postoperatively, patients with stable or responsive disease received the same regimen for 12 weeks. Patients with progressive disease received either second-line chemotherapy or best supportive care. The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and safety.Results35 patients were accrued. During preoperative chemotherapy, 16 patients (46%) had grade 3/4 toxicities. Resection was not possible in 5 patients. One patient died of arrhythmia following surgery, and 1 patient had transient liver failure. During the postoperative treatment phase, 12 patients (55%) had grade 3/4 toxicities. Deep venous thrombosis (DVT) occurred in 11 patients (34%) at various times during treatment. Of those who underwent resection, median DFS was 23.0 mo. and median OS has not been reached. The overall survival from time of diagnosis of liver metastases was 51.6 mo for the entire cohort.ConclusionA short course of chemotherapy prior to hepatic metastasectomy may serve to select candidates best suited for resection and it may also direct postoperative systemic treatment. Given the significant incidence of DVT, alternative systemic neoadjuvant regimens should be investigated, particularly those that avoid the use of a central venous line.Trial RegistrationClinicalTrials.gov NCT00168155.

A polymorphic variant of the insulin-like growth factor type I receptor gene modifies risk of obesity for esophageal adenocarcinoma

BACKGROUND To investigate potential biologic mechanisms underlying the association between obesity and risk for esophageal adenocarcinoma (EADC), we studied the frequency of a common polymorphism of the insulin-like growth factor I receptor (IGF-IR) gene in patients with either gastroesophageal reflux disease (GERD), premalignant Barrett esophagus (BE) and or invasive EADC. METHODS Using a well characterized series of 431 individuals enrolled in a case-control study, we studied the frequency of the IGF-IR gene polymorphism, G1013A. RESULTS On multivariate analysis controlling for age and gender, in comparison to asymptomatic controls, obese individuals with the polymorphic A-variant (G/A, A/A) were found to have significantly increased risk for EADC (OR 4.81; 95%CI 1.09-21.15), whereas obese individuals with the G/G variant were not at statistically significant increased risk (OR 2.69; 95%CI 0.41-17.62). Similarly, compared to asymptomatic controls, only obese individuals with the A-variant (G/A, A/A) were at increased risk for BE (OR 3.11; 95%CI 1.12-8.63), while obese individuals with the G/G variant were not at increased risk for BE (OR 2.91; 95%CI 0.69-12.15). CONCLUSION We conclude that the common IGF-IR gene polymorphism G1013A modulates the risk of obesity for EADC, an effect most likely mediated by altered the receptor function by influencing gene transcription or mRNA stability. These findings further implicate the insulin-like growth factor axis in the molecular pathogenesis of EADC, and represent a plausible mechanistic link underlying the association between obesity and malignancy.

Access to Care and Satisfaction in Colorectal Cancer Patients

This study described the various components of access to care for resectable colorectal cancer, and correlated the timeliness of these components with patient satisfaction. With a prospective/retrospective cohort design, all patients undergoing surgical resection for primary colorectal cancer from 2/1/01 to 15/12/01, were identified during their admission for surgery. A comprehensive, standardized method of ascertaining specific time intervals, which included a patient interview, was used. A patient satisfaction questionnaire was developed, tested, and used in consenting patients. Over the study period, 118 patients underwent colorectal cancer resection. Of these, 110 (93%) consented to participate and 101 (86%) completed the satisfaction questionnaire, including test–retest. The median time intervals (interquartile range) for the various components of access to care were as follows: symptoms to first physician visit, 32 days (10–75); first physician visit to diagnosis, 88 days (44–218); diagnosis to surgery, 19 days (10–44); surgery to chemotherapy (where applicable), 54 days (47–72). On multivariate analysis, tumor location in the rectum was associated with longer prediagnosis intervals, whereas increasing tumor stage was associated with shorter intervals from diagnosis to surgery. Variation in the time interval from diagnosis to surgery was associated with patient satisfaction (r = 0.49; P < 0.0001). Substantially less correlation was identified between patient satisfaction and the time from first physician visit to diagnosis (r = 0.25, P = 0.04). No significant correlation was identified between patient satisfaction scores and the time interval from symptoms to first physician visit (r = 0.11; P = 0.7). Despite concerns regarding surgical waitlists, the longest time intervals experienced by colorectal cancer patients precede diagnosis. However, variations in the relatively short time period from diagnosis to surgery appeared to have the most impact on patient satisfaction. Interventions which improve the timeliness of specific components of access to care may not necessarily result in improved patient satisfaction.