Annals of Surgical Oncology

The peritoneal cancer index (PCI) is used to refer gastrointestinal malignancy patients to either palliative or curative management of their peritoneal carcinomatosis. The aim of this retrospective study was to evaluate the prognostic value of the PCI in patients with primary advanced epithelial ovarian cancer (EOC) after complete cytoreductive surgery. PCI quantitatively assesses cancer distribution on the peritoneum by calculating tumor sizes in each of 13 abdominopelvic regions. Correlation between PCI score and clinical factors were analyzed using Kendall's tau b. Univariate and multivariate survival analyses were performed with the Kaplan–Meier method and Cox regression model, respectively. We retrospectively enrolled 80 consecutive patients with primary EOC treated in our gynecology department. All patients underwent complete cytoreductive surgery. Patients whose history included interval tumor debulking and completion cytoreductive surgery were excluded. Most tumors were of a serous histological subtype (96.3 %). Median age at diagnosis was 58.0 years. Their median PCI score was 12.0 (range 3–32). We found statistical correlations between PCI and ascites (p = 0.001), surgery duration (p < 0.001), T status of TNM staging (p = 0.036), and preoperative CA 125 (p = 0.025). In the univariate analysis, higher PCI scores were related to poor overall (OS) and progression-free (PFS) survival rates (p = 0.036 and p < 0.001, respectively). Multivariate analysis showed that the association remained significant only for PFS (p = 0.005), not for OS (p = 0.162). PCI did not portend OS in patients with primary ovarian cancer. Further prospective and multicenter studies are needed to validate these results.

Secondary thyroid cancer is believed to lead to a more aggressive clinical course than primary thyroid cancer. We aim to examine the difference between primary and secondary thyroid cancer in terms of patient characteristics and perioperative outcomes at the national level. A cross-sectional study utilizing the Nationwide Inpatient Sample database for 2003–2010 was merged with County Health Rankings Data. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to identify adult patients with thyroid cancer. A total of 21,581 discharge records were included. Overall, 16,625 (77.0 %) patients had primary cancer, while the rest (23.0 %) had secondary cancer. Younger (<45 years) and older (>65 years) patients, males, and those of White or Hispanic background were more likely to have secondary cancers (p < 0.05 each). The prevalence of secondary cancer was higher in communities of low health risk (24.0 % vs. 21.1 %; p < 0.024). Secondary cancer was more likely to be managed by total thyroidectomy (odds ratio [OR] 2.40, 95 % CI 2.12–2.73) and to require additional radical neck dissection (OR 12.51, 95 % CI 10.98–14.25). Patients with secondary thyroid cancers were at higher risk of postoperative complications (p < 0.01 each). The cost of secondary cancer management was significantly higher than primary cancer (US$12,449.00 ± 302.07 vs. US$7848.12 ± 149.05; p < 0.001). However, compared with intermediate-volume surgeons, the complication risk was lower for high-volume (OR 0.47, 95 % CI 0.24–0.92; p = 0.026). Secondary thyroid cancer is associated with a higher risk of perioperative complications and higher cost and distinct demographic profile. Patients managed by higher-volume surgeons were less likely to experience disadvantageous outcomes.

Ninety-day hospital readmission rates following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) range from 20 to 40%. The aim of this study was to develop and validate a simple score to predict readmissions following CRS/HIPEC. Using a prospectively maintained database, we retrospectively reviewed clinicopathologic, perioperative, and day-of-discharge data for patients undergoing CRS/HIPEC for peritoneal surface malignancies between 2010 and 2018. In-hospital mortalities and discharges to hospice were excluded. Multivariate logistic regression was utilized to identify predictors of unplanned readmission, with three-quarters of the sample randomly selected as the derivation cohort and one-quarter as the validation cohort. Using regression coefficient-based scoring methods, we developed a weighted 7-factor, 10-point predictive score for risk of readmission. Overall, 1068 eligible discharges were analyzed; 379 patients were readmitted within 90 days (35.5%). Seven factors were associated with readmission: stoma creation, Peritoneal Cancer Index score ≥ 15, hyponatremia, in-hospital major complication, preoperative chemotherapy, anemia, and discharge to nursing home. In the validation cohort, 25 patients (9.2%) were categorized as high risk for readmission, with a predicted rate of readmission of 69.3% and an observed rate of 76.0%. The score had fair discrimination (area under the curve 0.70) and good calibration (Hosmer–Lemeshow goodness-of-fit p-value of 0.77). Our proposed risk score, easily obtainable on day of discharge, distinguishes patients at high risk for readmission over 90 days following CRS/HIPEC. This score has the potential to target high-risk individuals for intensive follow-up and other interventions.

The introduction of the epidermal growth factor receptor inhibitors (EGFR-I) has increased the treatment options available for patients with metastatic colorectal cancer (mCRC). Two EGFR-I agents currently approved for the treatment of mCRC are the fully human monoclonal antibody panitumumab and the mouse-human chimeric monoclonal antibody cetuximab. While these agents have demonstrated activity across multiple lines of therapy, early studies suggested that clinical benefit was confined to a subset of patients treated. Mutation of the KRAS oncogene has emerged as a powerful negative predictive biomarker to identify patients with mCRC who do not benefit from EGFR-I therapy. Multiple retrospective analyses have demonstrated that clinical benefit from treatment with EGFR-I is limited to patients with tumors harboring the wild-type KRAS gene. In this review, the KRAS pathway and studies evaluating KRAS as a prognostic marker in CRC are discussed along with advances in KRAS gene mutation testing. Clinical trials evaluating the role of KRAS status in response to EGFR-I monotherapy or in combination with chemotherapy are also highlighted along with ongoing studies evaluating the role of EGFR-I treatment on curative resections rates. Future studies investigating EGFR-I therapy in mCRC should incorporate KRAS mutation testing into the study protocol in order to more accurately determine the patient population that will obtain clinical benefit from these novel agents.

This study was designed to evaluate neoadjuvant intensified chemotherapy in potentially resectable or unresectable liver metastases (LM) from colorectal cancer (CRC). Criteria for potentially resectable LM were complex hepatectomy and/or risky procedure, close contact with major vascular structures, and for unresectable LM, a future liver remnant predicted to be less than 25–30 % of total liver volume. Between October 2004 and August 2007, 125 patients were randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy (FOLFIRI-HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0 surgical resection, best ORR, progression-free survival (PFS), and overall survival (OS). A total of 122 patients were treated; 45 % of patients had less than 30 % of remaining liver tissue, 20 % had major vascular contact, and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24, 19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7, 9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first 4 cycles in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64 operated patients. Median PFS was 9.2 months in control arms versus 11.9 months in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively. FOLFIRINOX showed promising activity in CRC patients with LM compared with standard or intensified bi-chemotherapy regimens.

The optimal cutoffs for carbohydrate antigen 19-9 (CA19-9) response after neoadjuvant therapy (NT) for pancreatic adenocarcinoma (PDAC) are not well characterized. This study aimed to analyze the relationship of serum CA19-9 to other markers of response and to identify thresholds correlating to outcomes. A retrospective review of resected PDAC patients from 2010 to 2017 at an academic tertiary referral center was conducted. The analysis enrolled 250 subjects. Normalization and multiple cutoff points for CA19-9 response were assessed. Normalization was not associated with improved survival (35.17 vs. 29.43 months; p = 0.173). Although a response 45% or higher was associated with longer survival (35 vs. 20 months; p = 0.018), a response of 85% or higher was optimal (55.7 vs. 25.97 months; p < 0.0001). A response of 85% or higher remained a strong independent predictor of survival [hazard ratio (HR), 0.47; p = 0.007]. Subjects with a response of 85% or higher had received more NT cycles [3 (range 2–6) vs. 3 (range 2–4) cycles; p = 0.006] and fewer adjuvant cycles [4 (range 3–6) vs. 5 (range 3–6) cycles; p = 0.027]. Reduction in T-size correlated with a drop in CA19-9 and a size reduction of 25% or higher (56.97 vs. 28.17 months; p = 0.016) improved survival. A serum CA19-9 response of 85% or higher was a strong independent predictor of a reduction in T-size of 25% or higher (HR 2.40; p = 0.007). A CA19-9 response of 85% or higher is the optimal threshold for predicting survival. It is predictive of T-size reduction. Future NT trials should incorporate CA19-9 response as an end point.

Invasive apocrine carcinoma is a rare breast cancer that is frequently triple negative. Little is known about the characteristics of its molecular subtypes. We compared the incidence, demographics, and clinicopathologic features of this cancer with non-apocrine carcinomas stratified by molecular subtype. Women with invasive apocrine cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic and demographic features were compared with non-apocrine carcinomas, both overall using data from 2004 to 2017 and stratified by molecular subtypes using data from 2010 to 2017. The life table method was used to determine the 7-year breast cancer-specific survival. Compared with non-apocrine cancers, apocrine cancers presented at a younger age, with larger, higher-grade tumors that were much more likely to be triple negative (50% vs. 11%) or human epidermal growth factor receptor 2 (HER2)-positive (28% vs. 15%) and less likely to be luminal (22% vs. 74%); however, the 7-year survival was the same at 85%. The characteristics varied dramatically by molecular type. Compared with non-apocrine triple-negative, apocrine triple-negative patients were less likely to be African American and were much older, with smaller, lower-grade tumors and much better survival (86% vs. 74%). In contrast, compared with luminal non-apocrine, apocrine luminal patients had larger, higher-grade tumors and worse survival (79% vs. 89%). Invasive apocrine carcinomas have more aggressive features than non-apocrine carcinomas but the breast cancer-specific survival is the same. Half of these apocrine tumors are triple negative but these have more favorable features and much better survival than non-apocrine triple-negative cancers.

Neoadjuvant chemotherapy is being increasingly used in operable breast cancer. There are limited data on the safety of bevacizumab (bev) in the neoadjuvant setting. We sought to explore the safety of neoadjuvant cisplatin/bev in a protocol for triple negative breast cancer (TNBC). A total of 51 patients with confirmed TNBC were enrolled in a single-arm trial of neoadjuvant cisplatin plus bev. Of the 51 patients, 28 with confirmed TNBC were enrolled in our trial of single-agent neoadjuvant cisplatin. Two-sided Fisher exact test were used for comparing the 2 trials. The 51 patients received neoadjuvant protocol therapy with cisplatin/bev and underwent definitive local therapy. Breast conserving therapy (BCT) was performed in 29 (57%) and mastectomy with or without reconstruction in 22 (43%). Postoperative complications were reported in 22 patients (43%); 4 (8%) required explanation of expanders. Also, 28 patients completed neoadjuvant cisplatin therapy. BCT was performed in 13 (46%) and mastectomy with or without reconstruction in 15 (54%). Postoperative complications were reported in 11 patients (39%). None of the 5 reconstructions were lost. We compared all toxicities between the two trials (P = .81 NS), and wound healing related complications between the two trials (P = .10 NS). Cisplatin/bevacizumab and cisplatin alone neoadjuvant therapy resulted in a significant number of postoperative complications. Specifically, use of expanders/implants may be problematic for patients treated with bev. However, this was a single-arm trial; randomized controlled studies will be needed to determine the optimal use of bevacizumab in the timing of breast cancer surgery.