Background
Adjuvant radiation is generally not recommended for colon cancer but may be considered in certain clinical scenarios advanced local disease (pT4) and/or positive margins. Guidelines in ...this area are lacking; thus we analyzed the National Cancer Database (NCDB) for patterns of care in this regard and any predictors for outcome.
Methods
We queried the NCDB from 2004 to 2016 for patients with resected adenocarcinoma of the colon having pT4 and/or had positive margins on final pathology and who received adjuvant multiagent chemotherapy. Multivariable logistic regression was used to identify predictors of adjuvant radiation. A propensity score was used to perform matched Kaplan–Meier analysis. Propensity-adjusted Cox regression was used to identify predictors of overall survival.
Results
We identified 23,325 patients meeting criteria, of whom 1711 (7%) received adjuvant radiation. Median follow-up was 36 months. The majority of patients were pT4 alone (65%). Predictors of adjuvant radiation were lower comorbidity score, younger age, more remote year of treatment, and both pT4 and positive margins. Kaplan–Meier analysis revealed improved overall survival (OS) in patients with both pT4 and positive margins treated with radiation (median OS: 66 versus 47 months,
p
= 0.02). Receipt of adjuvant radiation was associated with improved OS hazard ratio (HR): 0.86 (0.80–0.93)
p
= 0.0002 on Cox regression analysis. Increased age, higher comorbidity score, lower income, government insurance, and combined pT4/positive margins were indicative of worse survival.
Conclusions
Expectedly, adjuvant radiation use was relatively low but was associated with improved OS in patients with both pT4 and positive margins.
Superparamagnetic iron oxide nanoparticles (SPION) have attracted great attention not only for therapeutic applications but also as an alternative magnetic resonance imaging (MRI) contrast agent that ...helps visualize liver tumors during MRI-guided stereotactic body radiotherapy (SBRT). SPION can provide functional imaging of liver parenchyma based upon its uptake by the hepatic resident macrophages or Kupffer cells with a relative enhancement of malignant tumors that lack Kupffer cells. However, the radiomodulating properties of SPION on liver macrophages are not known. Utilizing human monocytic THP-1 undifferentiated and differentiated cells, we characterized the effect of ferumoxytol (Feraheme
), a carbohydrate-coated ultrasmall SPION agent at clinically relevant concentration and therapeutically relevant doses of gamma radiation on cultured cells in vitro. We showed that ferumoxytol affected both monocytes and macrophages, increased the resistance of monocytes to radiation-induced cell death and inhibition of cell activity, and supported the anti-inflammatory phenotype of human macrophages under radiation. Its effect on human cells depended on the duration of SPION uptake and was radiation dose-dependent. The results of this pilot study support a strong mechanism-based optimization of SPION-enhanced MRI-guided liver SBRT for primary and metastatic liver tumors, especially in patients with liver cirrhosis awaiting a liver transplant.
Background
The prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation ...as a prognostic marker in patients with locally advanced rectal cancer (LARC).
Methods
We identified LARC patients treated with neoadjuvant chemoradiation from 2004–2015 excluding those with stage I/IV disease and unknown KRAS status. Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival.
Results
Of the 784 eligible patients, 506 were KRAS-negative (KRAS −) and 278 were KRAS-positive (KRAS +). Median survival was 63.6 months and 76.3 months for KRAS + and KRAS − patients respectively, with propensity adjusted 3 and 5-year survival of 79.9% vs. 83.6% and 56.7% vs. 61.9% respectively (HR 1.56,
p
1.074–2.272). Male sex, no insurance, and KRAS + disease were associated with poorer survival on unadjusted and propensity adjusted multivariable analyses.
Conclusions
Our analysis of KRAS + LARC suggest that KRAS + disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted.
The appropriate timing of chemotherapy following surgery for resectable pancreatic adenocarcinoma is controversial. Using the National Cancer Database we evaluated time to initiation of chemotherapy ...postresection and correlated with outcome.
We identified stage I-III pancreatic adenocarcinoma treated surgically with adjuvant chemoradiotherapy. Receiver operator curve analysis identified an interval of 66 days as the a priori value for largest discrepancy in outcome. Multivariable logistic regression analysis identified variables associated with increased time to chemotherapy postoperatively (>66 days). Propensity matching was performed to account for indication bias.
In total, 6873 and 3348 patients received chemotherapy before and after the 66-day cutoff, respectively. Predictors of expedited chemotherapy included lower comorbidity, treatment outside a community program in an urban location, having insurance, white race, and treatment after 2009. Propensity-matched median survival was 21.8 months for all patients, and of these, 6462 were stage 1. Five-year survival was 20% in patients receiving chemotherapy within 66 days and 18% in those not (P = 0.0266). In stage 1 patients, 5-year survival was 23% versus 21% (P = 0.0116) in favor of expedited chemotherapy.
The present propensity-matched analysis showed a significant association with survival for earlier delivery of chemotherapy in the adjuvant setting.
The use of super-paramagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent (SPION-CA) can safely label hepatic macrophages and be localized within hepatic parenchyma for T2*- and ...R2*-MRI of the liver. To date, no study has utilized the R2*-MRI with SPIONs for quantifying liver heterogeneity to characterize functional liver parenchyma (FLP) and hepatic tumors. This study investigates whether SPIONs enhance liver heterogeneity for an auto-contouring tool to identify the voxel-wise functional liver parenchyma volume (FLPV). This was the first study to directly evaluate the impact of SPIONs on the FLPV in R2*-MRI for 12 liver cancer patients. By using SPIONs, liver heterogeneity was improved across pre- and post-SPION MRI sessions. On average, 60% of the liver range 40–78% was identified as the FLPV in our auto-contouring tool with a pre-determined threshold of the mean R2* of the tumor and liver. This method performed well in 10 out of 12 liver cancer patients; the remaining 2 needed a longer echo time. These results demonstrate that our contouring tool with SPIONs can facilitate the heterogeneous R2* of the liver to automatically characterize FLP. This is a desirable technique for achieving more accurate FLPV contouring during liver radiation treatment planning.
Background
Trans-arterial chemoembolization and radiofrequency ablation are commonly used for control of hepatocellular carcinoma (HCC) on liver transplant (LTx) waiting list. Stereotactic body ...radiation therapy (SBRT) was introduced to our institution for HCC as a bridging or downsizing therapy to LTx.
Patients and methods
Twenty-five HCC lesions in 22 patients were treated with SBRT while waiting for LTx from January 2010 to December 2015. Nineteen of these patients received deceased donor LTx. SBRT was defined as 40–50 Gy delivered in 4–6 fractions. Pre- and post-liver transplant outcome were analyzed in addition to the dropout rate and tumor response to SBRT.
Results
Median size of original tumors was 3.2 cm (2.0–8.9), and median size of tumor after SBRT was significantly smaller at 0.9 cm (0–3.2) in the explanted livers (
p
< 0.01). The dropout rate was 9%, and they were only downsized patients outside of Milan criteria. Liver disease did not progress between pre- and post-SBRT except one patient. Twenty-eight percent of treated HCCs showed complete pathologic response, and 22% had extensive partial response with some residual tumor. No HCC recurrence was experienced after LTx.
Conclusion
SBRT is indicated to be safe, effective treatment for HCC on LTx waiting list, and it leads to satisfactory post-liver transplant outcomes.
The only potentially curative approach for pancreatic cancer is surgical resection, but this technically challenging procedure carries risks for postoperative morbidities and mortality. This study of ...a large, contemporary national database illustrates incidences of, and risk factors for, post-procedural mortality, prolonged hospital stay, and 30-day readmission.
From the National Cancer Database (NCDB), stage I-III pancreatic adenocarcinomas were identified 2004-2015. Surgical techniques included pancreaticoduodenectomy, partial pancreatectomy (selective removal of the pancreatic body/tail), total pancreatectomy (removal of the entire pancreas) with or without subtotal resection of the duodenum and/or stomach, and extended pancreatectomy. Predictors of 30/90-day post-operative mortality, 30-day readmission rates, and prolonged hospital stay (>17 days per receiver operating curve analysis) were identified via multivariable logistic regression.
Overall, 24,798 patients were analyzed (median age of 66). The majority of cases were T3 (47%), N0 (65%), pancreatic head lesions (83%), and treated with pancreaticoduodenectomy (57%). Only 16% received neoadjuvant therapy. Overall unadjusted risk of 30- and 90-day mortality ranged from 1.3-2.5% and 4.1-7.1%, respectively, depending on extent of surgery. Independent predictors of 30-/90-day mortality included preoperative therapy, increasing age, higher comorbidity score, lower income, case volume, and more extensive surgery. Similar findings were demonstrated regarding prolonged hospital stay and 30-day readmission. Age ≥70 was most associated with 30-day mortality, whereas age ≥60 was most associated with 90-day mortality and prolonged hospital stay.
Quantitation of incidences and risk factors for postoperative outcomes following resection for pancreatic cancer is essential for judicious patient selection and shared decision-making between providers and patients.
Importance
Primary Adenocarcinoma of the anus is a rare disease with a poor prognosis and thus tends to have a more aggressive treatment algorithm, typically involving a surgical approach. Prior to ...2001, a few retrospective studies outlined improved outcomes with the incorporation of surgery with chemoradiation. However, since the publication of these studies, advancement in radiotherapy modalities and imaging have left the question of improved outcomes while reserving surgery for salvage.
Objective
We conducted this National Cancer Database (NCDB)‐driven retrospective study to analyze treatment trends and outcomes in the current time from 2004 to 2015 with respect to chemoradiation and surgery.
Design
Retrospective NCDB tumor registry data review—using propensity score‐adjusted multivariable analyses for survival.
Setting
Database review.
Participants
We selected for patients listed in the NCDB with AJCC stage 1‐3 anal adenocarcinoma diagnosed between 2004 and 2015 and selected out patients with undocumented/stage 4 disease, those with radiation outside the pelvis, not treated with systemic therapy and patients lost to follow‐up.
Exposure(s)
None.
Main outcomes and measures
Overall survival and use of surgery in the up‐front management of anal adenocarcinoma.
Results
Of the 1729 patients eligible in this study, 1028 were treated with surgery as up‐front management and 701 had definitive chemoradiation. Median overall survival for all patients was 55 months with a 5‐year survival rate of 55%. Patients treated without surgery had worse overall survival, median survival of 45 months compared to 87 months (P < 0.0001) with 5‐year survival rates of 42% and 55% in favor of incorporation of surgery. Analysis across patients treated with surgery alone, surgery followed by adjuvant chemoradiation, neoadjuvant chemoradiation followed by surgery, and chemoradiation alone had median survival rates of 78, 83, 92, and 46 months, respectively. Propensity score‐adjusted multivariable analysis identified older age, grade 3, high comorbidity score, and lack of surgery as predictive of worse outcome.
Conclusions and Relevance
The results of the NCDB analysis indicate improved overall survival with the incorporation of surgery into the initial management of anal adenocarcinoma when compared to chemoradiation alone, despite the omission of surgery in up to 50% of the cases logged. Our results corroborate earlier studies published prior to the year 2000 for surgery to be included in the definitive management of anal adenocarcinoma.
This analysis used the National Cancer Database to look at treatment trends in the rare adenocarcinoma of the anal canal. Surprisingly, almost half of all cases were managed nonoperatively, with resultant inferior outcome compared to those patients who underwent surgery as part of their management.
The application of automated segmentation methods for tumor delineation on
F
18
-fluorodeoxyglucose positron emission tomography (FDG-PET) images presents an opportunity to reduce the interobserver ...variability in radiotherapy (RT) treatment planning. In this work, three segmentation methods were evaluated and compared for rectal and anal cancer patients: (i) Percentage of the maximum standardized uptake value
(
SUV
%
max
)
, (ii) fixed SUV cutoff of 2.5
(
SUV
2.5
)
, and (iii) mathematical technique based on a confidence connected region growing (CCRG) method. A phantom study was performed to determine the
SUV
%
max
threshold value and found to be 43%,
SUV
43
%
max
. The CCRG method is an iterative scheme that relies on the use of statistics from a specified region in the tumor. The scheme is initialized by a subregion of pixels surrounding the maximum intensity pixel. The mean and standard deviation of this region are measured and the pixels connected to the region are included or not based on the criterion that they are greater than a value derived from the mean and standard deviation. The mean and standard deviation of this new region are then measured and the process repeats. FDG-PET-CT imaging studies for 18 patients who received RT were used to evaluate the segmentation methods. A PET avid
(
PET
avid
)
region was manually segmented for each patient and the volume was then used to compare the calculated volumes along with the absolute mean difference and range for all methods. For the
SUV
43
%
max
method, the volumes were always smaller than the
PET
avid
volume by a mean of 56% and a range of 21%–79%. The volumes from the
SUV
2.5
method were either smaller or larger than the
PET
avid
volume by a mean of 37% and a range of 2%–130%. The CCRG approach provided the best results with a mean difference of 9% and a range of 1%–27%. Results show that the CCRG technique can be used in the segmentation of tumor volumes on FDG-PET images, thus providing treatment planners with a clinically viable starting point for tumor delineation and minimizing the interobserver variability in radiotherapy planning.
Background
Standard of care for locally advanced rectal cancer (LARC) (stage II/III) includes preoperative chemoradiation (CRT) followed by resection and adjuvant chemotherapy. Total neoadjuvant ...therapy (TNT) is a new treatment paradigm that delivers systemic therapy prior to CRT aimed at improving outcomes for high-risk patients. Here we analyzed the national cancer database (NCDB) comparing short-term post-operative outcomes between patients receiving TNT and CRT.
Methods
The NCDB was queried to identify patients with LARC between the 2004 and 2014 treated with TNT or CRT. Primary outcomes included post-operative 30-day mortality and readmissions between TNT and CRT which were analyzed via logistic regression. Secondary outcomes included post-operative length of stay (LOS) and OS which were compared with two-tailed
t
-test and Kaplan-Meier with log rank testing, respectively.
Results
A total of 9066 patients met inclusion criteria with a median age at diagnosis that was 57 years (IQR, 19–65); 62.3% were male and 87.8% white. Neoadjuvant therapy consisted of either standard CRT (97.2%) or TNT (2.8%). Patients treated at academic programs and those with N1
p
< 0.001, OR 2.34, 95%CI 1.71–3.19 or N2
p
< 0.001, OR 3.29, 95%CI 2.19–4.94 disease were associated with increased utilization of TNT. TNT was not significantly associated with either 30-day mortality (
p
= 1.0) or readmissions (
p
= 0.82). Further, there was no significant difference identified between CRT and TNT for hospital LOS or OS (
p
= 0.18).
Conclusion
This large-scale analysis of patients with LARC demonstrates increased utilization of TNT in patients harboring node-positive disease. Further, TNT does not appear to increase 30-day post-operative mortality, readmissions, or hospital LOS.
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