Access to care and outcomes for neuroendocrine tumours: does socioeconomic status matter?

Introduction: Neuroendocrine tumours (nets) are a poorly understood malignancy lacking standardized care. Differences in socioeconomic status (ses) might worsen the effect of non-standardized care. We examined the effect of ses on net peri-diagnostic care patterns and outcomes. Methods: In this population-based cohort study, net cases identified from a provincial cancer registry (1994-2009) were divided into low (1st and 2nd income quintiles) and high (3rd, 4th, and 5th quintiles) ses groups. We compared peri-diagnostic health care utilization (-2 years to +6 months), metastatic recurrence, and overall survival (os) between the groups. Results: Of 4966 net patients, 38.3% had a low ses. Neither the primary net sites (p = 0.15), nor the metastatic presentation (p = 0.31) differed. Patients with low ses had a higher mean number of physician visits (20.1 ± 19.9 vs. 18.1 ± 16.5, p = 0.001) and imaging studies (56 ± 50 vs. 52 ± 44, p = 0.009) leading to the net diagnosis. Rates of primary tumour resection (p = 0.14), hepatectomy (p = 0.45), systemic therapy (p = 0.38), and liver embolization (p = 0.13) did not differ with ses. In the low-ses group, metastatic recurrence was more likely (41.1% vs. 37.6%, p = 0.01) during a median follow-up of 61.7 months, and the 10-year os was inferior (47.1% vs. 52.2%, p < 0.01). Low ses was associated with worse os (hazard ratio: 1.16; 95% confidence interval: 1.06 to 1.26) after adjustment for age, sex, comorbidity burden, primary net site, and rural living. Conclusions: Low ses was associated with more physician visits and imaging before a net diagnosis, but not with more advanced stage at presentation nor with an effect on the pattern of therapy. Long-term outcomes were inferior in the low-ses group. These data can help to inform the design of health care delivery for nets.

Patterns and Drivers of Costs for Neuroendocrine Tumor Care: A Comparative Population-Based Analysis.

BACKGROUND: Little is known about resource use in the care of neuroendocrine tumors (NETs). This study defined patterns of costs in NET management and compared them with those of a more common malignancy, colon cancer (CC). METHODS: Using a provincial cancer registry (2004-2012), NET patients were identified and matched at a ratio of 1-3 with CC patients. Four phases of care were examined: pre-diagnostic (PreDx: -2 years to -181 days), diagnostic (Dx: -180 days to +180 days), postdiagnostic (PostDx: +181 days to +3 years), and prolonged post-diagnostic (PPostDx: +181 days to +9 years). The mean costs per patient were compared, and cost predictors were analyzed with quintile regression. RESULTS: Of 3827 NETs, 3355 were matched with 9320 CCs. The PreDx mean NET costs were higher than the CC costs ($5877 vs $5368; p = 0.06), driven by nondrug costs. They were lower in the Dx and PostDx phases (both p < 0.01). For PPostDx, the drug costs were higher for NETs ($26,788 vs $7827; p < 0.01), representing 41% of the costs versus 16% of the costs for CC. Older age and comorbidities predicted higher NET costs in all phases. Lower socioeconomic status (SES) predicted higher costs in the initial phases and higher SES costs in the PPost-Dx phase. Gastroenteric NETs were associated with lower costs in the Dx phase [parameter estimate (PE), -$13,644] and pancreatic NETs with higher costs in PostDx phase (PE, $3348). CONCLUSION: Currently, NETs represent a potential important health care burden. The NET cost patterns differed from those for CC, with the highest costs during the PPostDx phase. The SES and primary NET site affected costs differently at different time points. These data can inform resource allocation tailored to the needs for NETs.

Three-point transfusion risk score in hepatectomy.

BACKGROUND: Perioperative red blood cell transfusions are required in up to 23 per cent of patients undergoing hepatectomy. Previous research has developed three transfusion risk scores to assess risk of perioperative red blood cell transfusion. Here, the performance of these transfusion risk scores was evaluated in a multicentre cohort of patients who underwent hepatectomy and compared with that of a simplified transfusion risk score. METHODS: A database of patients undergoing hepatectomy at four specialized centres between 2008 and 2012 was developed. External validity was assessed by discrimination and calibration. Discrimination was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Calibration was evaluated by the degree of agreement between predicted and actual red blood cell transfusion probabilities. A simplified transfusion risk score using variables common to the three models was created, and discrimination and calibration were evaluated. RESULTS: There were 1287 patients included in this study, with 341 (26·5 per cent) receiving a red blood cell transfusion. Discriminative ability was similar between the three transfusion risk scores, with AUCs of 0·66-0·68 and good calibration. A new three-point risk score was developed based on factors present in all models: haemoglobin 12·5 g/dl or less, primary liver malignancy and major resection (at least 4 segments). Discriminative ability and calibration of the three-point model were similar to those of the three existing models, with an AUC of 0·66. CONCLUSION: The three-point transfusion risk score simplifies assessment of perioperative transfusion risk in hepatectomy without sacrificing predictive ability.

Variability of Ki67 labeling index in multiple neuroendocrine tumors specimens over the course of the disease.

BACKGROUND: The Ki67-LI is a valid surrogate for biologic behavior of neuroendocrine tumors (NETs), with higher levels associated with aggressive behavior. The World Health Organization (WHO) classifies NETs according to Ki67-LI (G1: <3%; G2 : 3-20%; G3: >20%). Little is known about the evolution of NETs histologic characteristics over the disease course. We sought to evaluate variations in Ki67-LI throughout NETs disease course. METHODS: We retrospectively reviewed the Sunnybrook Odette Cancer Center NET database for patients with multiple pathology specimens. Primary outcome was the WHO NET class based on Ki67-LI for each specimen. We assessed change in WHO class between specimens. RESULTS: Forty-three patients were retrieved, of which 39 had specimens from the primary tumor and a metastatic focus, and 4 had specimens from multiple metastatic foci. Sixteen (37.0%) were identified with Ki67-LI falling in different WHO classes on distinct biopsies. For 12 (75.0%) of those 16 patients, Ki67-LI showed enough variability for WHO class to be upstaged: 5 (31%) from G1 to G2, 2 (13%) from G2 to G3, and 5 (31%) from G1 to G3. CONCLUSION: When multiple pathology specimens were available, Ki67-LI varied throughout NETs disease course, with a majority of cases upgraded to a higher WHO class. If confirmed, this finding may have implications in how neuroendocrine tumors are monitored and treated. Further research is warranted to confirm these findings, understand better the underlying mechanisms of Ki67 variability, and define its relationship to prognosis.

Qualitative assessment of patient experiences related to extended pelvic resection for rectal cancer.

BACKGROUND: Patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) represent a complex management challenge. While there is potential for cure in a subset of patients, the cost in terms of morbidity can be high. Few descriptions of the physical, psychological, social, and emotional experiences of these patients exist. METHODS: Face-to-face interviews were completed with ten LARC and LRRC patients treated with multimodal therapy that included surgery. Patient opinions and experiences were explored in depth until information redundancy and common themes were delineated using qualitative research methods. Clinical information was obtained from the database. RESULTS: Nine of the ten patients were male, seven had LARC, and the median age was 71. Six themes were identified from the patient interviews. Themes reflected patients' highly focused desire to seek wellness and cure, but also revealed misunderstanding of their disease biology, probability of cure, therapeutic options, and treatment morbidity. CONCLUSIONS: Patient experiences confirm that this is challenging treatment to complete, and that patient understanding of pre-operative information is incomplete. Our findings underscore the need for a multidisciplinary approach when managing this patient population, with emphasis on both supportive care needs and the technically skilled delivery of surgery, chemotherapy, and radiotherapy.

Use of a collagen-sealing device in hepatic resection: a comparative analysis to standard resection technique.

BACKGROUND: Blood transfusion has been reported as an independent risk factor for poor outcome after liver resection in spite of its well known benefits. Refinements in parenchymal dissection have been pursued to reduce blood loss and transfusion. A collagen-sealing device (CSD) has recently been touted as an alternative technique that aids in blood conservation. We report the results of our initial series of patients undergoing a CSD-assisted resection and present a historical comparison. PATIENTS AND METHODS: Consecutive patients who were undergoing liver resection at a single tertiary cancer centre were enrolled in this study. The Ligasure Atlas device (Valleylab Inc., Division of Tyco Healthcare) was used for parenchymal division in the CSD group. Known blood conservation techniques (i.e. low central venous pressure, ultrasonic dissection, Pringle clamp) were standardized in both groups. Clinical and outcome variables including operative time, estimated blood loss and transfusion requirements were collected. All statistical analyses were performed with SAS version 8.2e. RESULTS: In all, 28 consecutive patients underwent CSD-assisted hepatic resection between October 2003 and September 2004. The control group included 188 patients treated between January 1991 and September 2003. In the CSD group, we observed a reduction in mean estimated blood loss (930 vs 1450 ml, p=0.002) and mean transfusion requirements (0.46 vs 1.19 units, p=0.002). There was no increase in operative time with the new instrument (326 vs 363 min, p=0.167). DISCUSSION: Use of a CSD has the potential to further reduce blood loss and transfusion requirements without increasing operative time.

Outcomes after localized axillary node recurrence in breast cancer.

BACKGROUND: Localized axillary recurrence (LAR) is an uncommon event. It is estimated to occur in 0.5% to 3% of patients when adequate axillary surgery has been performed. Although relatively sparse data exist on the outcome of patients with LAR, in the era of sentinel node biopsy (SNB) these data may have increased relevance. This study assesses the survival outcomes in these patients. METHODS: A retrospective chart review was completed. Patient age, tumor size, pathology, receptor status, and treatment of the primary breast carcinoma were reviewed. Axillary recurrence, treatment, and overall survival data were collected. RESULTS: Fifteen patients were identified with LAR that developed at a median of 77 months after their initial dissection. At the time of treatment for their LAR, all patients had completion axillary clearance and six also had a concurrent completion mastectomy. Further adjuvant treatment was individualized. Five patients (33%) have died, including all patients (3) who developed a LAR within 2 years of their initial breast cancer presentation. Ten-year overall survival is 56%. CONCLUSION: Our experience suggests early (<24 months) LAR is indicative of a poor prognosis. With multimodal treatment, ten-year overall survival is 56%.

Lymph node retrieval and assessment in stage II colorectal cancer: a population-based study.

BACKGROUND: Adjuvant chemotherapy for patients with stage III (node-positive) colorectal cancer (CRC) reduces mortality by one third. Retrieval of an inadequate number of lymph nodes in the surgical specimen may result in incorrectly designating some patients as stage II (node negative), and consequently, such patients may not be offered appropriate chemotherapy. Recent National Cancer Institute guidelines suggest that a minimum of 12 nodes should be examined to ensure accurate staging. METHODS: This population-based study identified stage II (T3N0 and T4N0) CRC cases by using CRC pathology reports (1997-2000) from the Ontario Cancer Registry. Patients aged 19 to 75 years were identified, and demographic, surgical, pathologic, and hospital data were extracted. Factors relating to the number of lymph nodes assessed were examined. RESULTS: A total of 8848 CRC cases were reviewed, and 1789 stage II cases were identified. Seventy-three percent of cases were designated as node negative on the basis of assessment of <12 lymph nodes. Multivariate analysis showed that age, tumor size, specimen length, use of a pathology template, and academic status of the hospital were significant predictors of the number of lymph nodes assessed. CONCLUSIONS: A subset of patients with CRC in Ontario were assigned stage II disease on the basis of examination of relatively few lymph nodes.

Ex vivo sentinel lymph node biopsy in colorectal cancer: a feasibility study.

BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy may improve staging of colorectal cancer. We tested the feasibility of ex vivo SLN dissection. MATERIALS AND METHODS: Patients undergoing resection of a primary colorectal cancer were included in this study. SLN identification involved ex vivo injection of 1 cc isosulfan blue dye subserosally in the colon or submucosally in the rectum on a separate field. SLNs were cut at 2 mm intervals. Three hematoxylin and eosin-stained (HE) sections were prepared in addition to a middle level for cytokeratin immunostaining. RESULTS: Twenty-six patients with varying tumor location and stage were enrolled and the SLN was identified in 88% (23/26) cases. Three failures occurred in patients with rectal cancer. The average number of SLN harvested was 2.5. The status of the nodal basin was accurately predicted in 91% (21/23) of patients. Two false negative sentinel lymph nodes were harvested in 2 of 3 patients with stage III/IV colorectal cancer. The SLN upstaged 2 patients as a result of HE stained step sections (n = 1) and immunostaining (n = 1). CONCLUSIONS: This data suggests that ex vivo SLN biopsy is feasible in colorectal cancer. Although ex vivo SLN biopsy does not alter the lymphatic dissection, it may upstage a subset of patients. The ex vivo technique may be less applicable in rectal cancer and false negative results may occur.