In-cetuximab-F(ab’)2 SPECT imaging for quantification of accessible epidermal growth factor receptors (EGFR) in HNSCC xenografts

Background and purpose

Immunohistochemical epidermal growth factor receptor (EGFR) expression does not correlate with treatment response in head and neck squamous cell carcinomas (HNSCC). Aim was to apply the tracer ¹¹¹In-cetuximab-F(ab’)₂ for EGFR microSPECT imaging and to investigate if tracer uptake correlated with response to EGFR-inhibition by cetuximab in HNSCC xenografts. Usage of F(ab)₂ fragments allows for shorter interval between tracer injection and imaging.

Materials and methods

Mice with HNSCC xenografts, SCCNij202, 153, 185 and 167 were imaged with microSPECT using ¹¹¹In-cetuximab-F(ab’)₂. Subsequently, tumors were analyzed by autoradiography and immunohistochemistry and tracer concentration was determined. Tumor uptake was correlated with previously assessed response to cetuximab treatment.

Results

MicroSPECT imaging showed preferential uptake in HNSCC xenografts. Tumor-to-liver ratios were 3.1 ± 0.2 (SCCNij202), 2.8 ± 0.4 (SCCNij153), 2.0 ± 0.8 (SCCNij185), 2.0 ± 0.4 (SCCNij167). Immunohistochemical EGFR fractions (fEGFR) differed significantly between xenografts; 0.77 ± 0.07 (SCCNij202), 0.66 ± 0.11 (SCCNij153), 0.57 ± 0.19 (SCCNij185), 0.16 ± 0.10 (SCCNij167) (p < 0.001). Tumor fEGFR correlated with ¹¹¹In-cetuximab-F(ab’)₂ tumor uptake (r = 0.6, p < 0.01) and tracer autoradiography (r = 0.7, p < 0.0001). Tumor uptake of ¹¹¹In-cetuximab-F(ab’)₂ was proportionally associated with cetuximab treatment response in three out of four xenograft models.

Conclusion

¹¹¹In-cetuximab-F(ab’)₂ showed good tumor-to-background contrast on microSPECT imaging, allowing noninvasive assessment of EGFR expression in vivo, and possibly evaluation of treatment response to EGFR-inhibition.     

Dynamic contrast enhanced CT aiding gross tumor volume delineation of liver tumors: An interobserver variability study

Purpose

To evaluate the application of perfusion CT for gross tumor volume (GTV) delineation for radiotherapy of intrahepatic tumors.

Materials and methods

15 radiotherapy patients with confirmed liver tumors underwent contrast enhanced 4D-CT (Philips Brilliance Big-bore) as well as dynamic contrast enhanced (DCE) CT (GE 750HD). Perfusion maps were generated with CT perfusion v5 from GE. Five observers delineated GTVs of all intrahepatic foci on the 4D-CT, time-averaged DCE-CT and perfusion CT for every patient. STAPLE consensus contours were generated. Dice’s coefficients were compared between GTVs generated by observers on each image set and the corresponding consensus GTVs. Comparisons were also performed with patients stratified by hepatocellular carcinoma (HCC) metastatic tumors, and by tumor volume.

Results

Overall, mean Dice’s coefficients were 0.81 ± 0.14, 0.84 ± 0.10, and 0.81 ± 0.14 for 4D-CT, DCECT and perfusion. DCE-CT performed significantly better than 4D-CT and perfusion (p = 0.005 and p = 0.01 respectively). For patients with HCC, DCE-CT reduced interobserver variability significantly compared to 4D-CT (Dice’s coefficients 0.87 vs. 0.84, p < 0.05). For patients with metastatic disease time-averaged DCE-CT images decreased variability compared to 4D-CT (Dice’s coefficient 0.81 vs. 0.76, p < 0.05), especially true for tumors < 100 cc. The smaller tumors results are important to be included here.

Conclusions

DCE-CT imaging of liver perfusion reduced interobserver variability in GTV delineation for both HCC and metastatic liver tumors.     

Atherosclerotic lesions in lymphoma survivors treated with radiotherapy

Background and purpose

Radiotherapy causes premature atherosclerosis in Hodgkin’s lymphoma survivors (HLSs). We determined whether atherosclerosis within the radiation field was predicted by traditional risk factors independent of radiation and compared the extent of atherosclerosis in HLSs treated with mantle field radiotherapy with non-irradiated patients.

Material and methods

Forty-three HLSs (median age 50 years, range 38–63) treated with mantle field radiotherapy were included. Cardiovascular risk factors were registered at first follow-up (FU-1) 5–13 years after treatment. A second follow-up (FU-2) occurred 18–27 years after treatment. At FU-2, in-field atherosclerosis was assessed by computed tomography with calculation of coronary artery calcium volume score (CACS) and pre-cranial artery atherosclerosis score (PAS). Peripheral endothelial dysfunction was assessed by ante-brachial strain-gauge plethysmography. CT angiography of pre-cranial vessels was also performed in 43 non-irradiated patients.

Results

Multiple linear regression analyses showed that cholesterol at FU-1 was a predictor of CACS (β 308 (95% CI 213–403), p < 0.001), PAS (β 3.67 (95% CI 2.29–5.04), p < 0.001) and peripheral endothelial dysfunction (β 2.74 (95% CI 0.47–5.01), p = 0.02). There were more atherosclerotic lesions in HLSs (n = 141) than in non-irradiated patients (n = 73, p = 0.001).

Conclusion

Irradiated arteries are characterized by widespread atherosclerotic lesions aggravated by elevated levels of cholesterol.     

Hypofractionated whole breast irradiation for patients with large breasts: A randomized trial comparing prone and supine positions

Background and purpose

Comparison of acute toxicity of whole-breast irradiation (WBI) in prone and supine positions.

Materials and methods

This non-blinded, randomized, prospective, mono-centric trial was undertaken between December 29, 2010, and December 12, 2012. One hundred patients with large breasts were randomized between supine multi beam (MB) and prone tangential field (TF) intensity modulated radiotherapy (IMRT). Dose–volume parameters were assessed for the breast, heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast. The primary endpoint was acute moist skin desquamation. Secondary endpoints were dermatitis, edema, pruritus and pain.

Results

Prone treatment resulted in: improved dose coverage (p < 0.001); better homogeneity (p < 0.001); less volumes of over-dosage (p = 0.001); reduced acute skin desquamation (p < 0.001); a 3-fold decrease of moist desquamation p = 0.04 (chi-square), p = 0.07 (Fisher’s exact test)); lower incidence of dermatitis (p < 0.001), edema (p = 0.005), pruritus (p = 0.06) and pain (p = 0.06); 2- to 4-fold reduction of grades 2–3 toxicity; lower ipsilateral lung (p < 0.001) and mean LAD (p = 0.007) dose; lower, though statistically non-significant heart and maximum LAD.

Conclusions

This study provides level I evidence for replacing the supine standard treatment by prone IMRT for whole-breast irradiation in patients with large breasts. A confirmatory trial in a multi-institutional setting is warranted.     

A quality control model that uses PTV-rectal distances to predict the lowest achievable rectum dose,improves IMRT planning for patients with prostate cancer

Background and purpose

To predict the lowest achievable rectum D35 for quality assurance of IMRT plans of prostate cancer patients.

Materials and methods

For each of 24 patients from a database of 47 previously treated patients, the anatomy was compared to the anatomies of the other 46 to predict the minimal achievable rectum D35. The 24 patients were then replanned to obtain maximally reduced rectum D35. Next, the newly derived plans were added to the database to replace the original clinical plans, and new predictions of the lowest achievable rectum D35 were made.

Results

After replanning, the rectum D35 reduced by 9.3 Gy ± 6.1 (average ± 1 SD; p < 0.001) compared to the original plan. The first predictions of the rectum D35 were 4.8 Gy ± 4.2 (average ± 1 SD; p < 0.001) too high when evaluated with the new plans. After updating the database, the replanned and newly predicted rectum D35 agreed within 0.1 Gy ± 2.8 (average ± 1 SD; p = 0.89). The doses to the bladder, anus and femoral heads did not increase compared to the original plans.

Conclusions

For individual prostate patients, the lowest achievable rectum D35 in IMRT planning can be accurately predicted from dose distributions of previously treated patients by quantitative comparison of patient anatomies. These predictions can be used to quantitatively assess the quality of IMRT plans.     

Procedure volume of gastric cancer resections versus 5-year survival

Aim

We used nationwide, population-based data to examine associations between hospital and surgeon volumes of gastric cancer resections and their patients’ short-term and long-term survival likelihood.

Methods

The study uses 1997–1999 inpatient claims data from Taiwan's National Health Insurance linked to “cause of death” data for 1997–2004. The total cohort of 6909 gastric cancer resection patients were categorized by their surgeon's/hospital's procedure volume, and examined for differences in 6-month mortality and 5-year mortality (post 6 months), by procedure volume, using Cox proportional hazard regressions, adjusting for surgeon, hospital and patient characteristics. We hypothesized that surgeons’ case volume and age but not hospital volume will predict short-term and long-term survival.

Results

Adjusted estimates show that increasing surgeon volume predicts better 6-month survival (adjusted mortality hazard ratio = 1.3 for low-volume surgeons relative to very high-volume surgeons; p < 0.01) and 5-year survival (adjusted mortality hazard ratios = 1.3; p < 0.001 for low-volume; 1.2 with p < 0.01 for medium volume) and increasing surgeon's age (adjusted hazards ratio = 1.4 for age < 41 years relative to 41–50 years; p ≤ 0.001; 0.8 for ≥51 years relative to 41–50 years; p < 0.05). In hospital volume regressions, surgeon's age is a consistent and significant predictor, not hospital volume. Findings suggest a key role of experience in surgical skill and sensitivity for early stage diagnosis in gastric cancer survival.

Conclusions

Although a key study limitation is the lack of cancer stage data, the pattern of findings suggests that experienced surgeons have relatively better survival outcomes among gastric cancer patients.     

Faecal incontinence after chemoradiotherapy in anal cancer survivors: Long-term results of a national cohort

Purpose

To examine the prevalence and severity of faecal incontinence amongst anal cancer survivors after chemoradiotherapy.

Material and methods

Anal cancer survivors from a complete, unselected, national cohort, minimum 2-years follow-up, were invited to a cross-sectional study. The St. Mark’s incontinence score was used to evaluate occurrence and degree of faecal incontinence the last four weeks. The results were compared to age- and sex-matched volunteers from the general population.

Results

Of 199 invited survivors and 1211volunteers, 66% and 21%, respectively, signed informed consent. The survivors had significantly higher St. Mark’s score than the volunteers (mean 9.7 vs. 1.1, p < 0.001). Incontinence of stool of any degree was reported by 43% vs. 5% (OR 4.0, CI 2.73–6.01), and urgency was reported by 64% vs. 6% (OR 6.6, CI 4.38–9.90) of the survivors and volunteers, respectively. Only 29% of those with leakage of liquid stool used constipating drugs. Survivors of locally advanced tumours had a higher incontinence score (p < 0.01).

Conclusions

Moderate to severe faecal incontinence is common amongst anal cancer survivors. Post-treatment follow-up should include the evaluation of continence, and incontinent survivors should be offered better symptom management and multidisciplinary approach if simple measures are insufficient.     

A dosimetric study of polyethylene glycol hydrogel in 200 prostate cancer patients treated with high-dose rate brachytherapy ± intensity modulated radiation therapy

Background and purpose

We sought to analyze the effect of polyethylene glycol (PEG) hydrogel on rectal doses in prostate cancer patients undergoing radiotherapy.

Materials and methods

Between July 2009 and April 2013, we treated 200 clinically localized prostate cancer patients with high-dose rate (HDR) brachytherapy ± intensity modulated radiation therapy. Half of the patients received a transrectal ultrasound (TRUS)-guided transperineal injection of 10 mL PEG hydrogel (DuraSeal™ Spinal Sealant System; Covidien, Mansfield, MA) in their anterior perirectal fat immediately prior to the first HDR brachytherapy treatment and 5 mL PEG hydrogel prior to the second HDR brachytherapy treatment. Prostate, rectal, and bladder doses and prostate–rectal distances were calculated based upon treatment planning CT scans.

Results

There was a success rate of 100% (100/100) with PEG hydrogel implantation. PEG hydrogel significantly increased the prostate–rectal separation (mean ± SD, 12 ± 4 mm with gel vs. 4 ± 2 mm without gel, p < 0.001) and significantly decreased the mean rectal D_{2 mL} (47 ± 9% with gel vs. 60 ± 8% without gel, p < 0.001). Gel decreased rectal doses regardless of body mass index (BMI).

Conclusions

PEG hydrogel temporarily displaced the rectum away from the prostate by an average of 12 mm and led to a significant reduction in rectal radiation doses, regardless of BMI.     

The influence of smoking intensity on the clinicopathologic features and survival of patients with surgically treated non-small cell lung cancer

Background

Smoking is a well-known carcinogen for lung cancer. However, whether smoking affects the biological behavior of lung cancer remains uncertain. This study aimed to investigate the influences of smoking intensity on the clinicopathologic characteristics of and survival in non-small cell lung cancer (NSCLC).

Methods

We retrospectively reviewed 2238 consecutive patients who underwent surgical resection for NSCLC between 1990 and 2010. Smoking intensity was defined as pack-years (PY). The patients were divided into three groups according to the median value of smoking intensity (40 PY): group A (never smokers), group B (smoking intensity less than 40 PY) and group C (smoking intensity more than 40 PY).

Results

There were 1629 (72.8%) male patients, and the mean age was 61.71 ± 13.17 years. Adenocarcinoma was reported in 1058 (47.3%) patients. The median follow-up period was 30.7 months (range: 0.0–261.7 months). The 5-year overall survivals for groups A, B and C were 60.1%, 51.6% and 43.2%, respectively (p < 0.001). In subset analysis by histology, the 5-year overall survival was significantly different according to smoking intensity in adenocarcinoma (p < 0.001), but there was no difference in the non-adenocarcinoma. In adenocarcinoma, the incidences of vascular invasion (p = 0.028), pleural invasion (p = 0.013) and poor differentiation (p < 0.001) were higher and tumor sizes (p < 0.001) were greater in group C than others. On multivariate analysis, smoking intensity was an adverse risk factor for overall survival in surgically treated adenocarcinoma patients (hazard ratio = 1.008, p = 0.028).

Conclusion

Smoking intensity was an adverse prognostic factor after surgical resection of adenocarcinoma. Heavy smoking was correlated with poor pathologic characteristics in adenocarcinoma.     

Pulsed low-dose irradiation of orthotopic glioblastoma multiforme (GBM) in a pre-clinical model: Effects on vascularization and tumor control

Background and purpose

To compare dose-escalated pulsed low-dose radiation therapy (PLRT) and standard radiation therapy (SRT).

Methods and materials

Intracranial U87MG GBM tumors were established in nude mice. Animals received whole brain irradiation with daily 2-Gy fractions given continuously (SRT) or in ten 0.2-Gy pulses separated by 3-min intervals (PLRT). Tumor response was evaluated using weekly CT and [¹⁸F]-FDG-PET scans. Brain tissue was subjected to immunohistochemistry and cytokine bead array to assess tumor and normal tissue effects.

Results

Median survival for untreated animals was 18 (SE ± 0.5) days. A significant difference in median survival was seen between SRT (29 ± 1.8 days) and PLRT (34.2 ± 1.9 days). Compared to SRT, PLRT resulted in a 31% (p < 0.01), 38% (p < 0.01), and 53% (p = 0.01) reduction in normalized tumor volume and a 48% (p < 0.01), 51% (p < 0.01), and 70% (p < 0.01) reduction in tumor growth rate following the administration of 10 Gy, 20 Gy, and 30 Gy, respectively. Compared to untreated tumors, PLRT resulted in similar tumor vascular density, while SRT produced a 40% reduction in tumor vascular density (p = 0.05). Compared to SRT, PLRT was associated with a 28% reduction in degenerating neurons in the surrounding brain parenchyma (p = 0.05).

Conclusions

Compared to SRT, PLRT resulted in greater inhibition of tumor growth and improved survival, which may be attributable to preservation of vascular density.     

Redefining the target early during treatment. Can we visualize regional differences within the target volume using sequential diffusion weighted MRI?

Purpose

In head and neck cancer, diffusion weighted MRI (DWI) can predict response early during treatment. Treatment-induced changes and DWI-specific artifacts hinder an accurate registration between apparent diffusion coefficient (ADC) maps. The aim of the study was to develop a registration tool which calculates and visualizes regional changes in ADC.

Methods

Twenty patients with stage IV HNC treated with primary radiotherapy received an MRI including DWI before and early during treatment. Markers were manually placed at anatomical landmarks on the different modalities at both time points. A registration method, consisting of a fully automatic rigid and nonrigid registration and two semi-automatic thin-plate spline (TPS) warps was developed and applied to the image sets. After each registration step the mean registration errors were calculated and ΔADC was compared between good and poor responders.

Results

Adding the TPS warps significantly reduced the registration error (in mm, 6.3 ± 6.2 vs 3.2 ± 3.3 mm, p < 0.001). After the marker based registration the median ΔADC in poor responders was significantly lower than in good responders (7% vs. 21%; p < 0.001).

Conclusions

This registration method allowed for a significant reduction of the mean registration error. Furthermore the voxel-wise calculation of the ΔADC early during radiotherapy allowed for a visualization of the regional differences of ΔADC within the tumor.     

Does enhanced CT influence the biological GTV measurement on FDG-PET images?

Objectives

To test the influence of media injection in PET/CT on the functional or gross tumour volume measurement.

Patients and methods

Thirty-three patients (56 ± 19 years) with non-Hodgkin’s lymphoma (n = 22) or Hodgkin’s disease (n = 11) were prospectively studied at staging. PET/CTs were performed 60 min after injection of FDG. Iopamiron 300 (Iopamidol, 1.5 cc/kg) was injected immediately after, followed 50 s later by a second craniocaudal CT (CT+). PET images were successively reconstructed using the unenhanced CT (PET−) and the CT+ (PET+) for attenuation correction using iterative reconstruction (4 iterations, 8 subsets, 5 mm post-filtering). The SUV_max, SUV_mean, SUV_peak and functional tumoural volume were measured in tumoural lymphadenopathies or malignant tissues (n = 56 VOIs) using 5 3D-thresholding methods on PET− and PET+ images: absolute SUV value of 2.5; 40% of SUV_max, and 3 adaptative thresholding methods (Vauclin, Black and Schaefer methods).

Results

The SUV_mean and the volume measurement were significantly different (p < 0.001) for the five segmentation methods for PET− (p < 0.001) and PET+ (p < 0.001). The SUV_max, SUV_mean and SUV_peak increased significantly in PET+ compared to PET− (2–5%). The SUV_peak was not significantly different for the five segmentation methods. The functional volume measurements were significantly different between PET− and PET+ only for the 2.5 segmentation method (+3%; p = 0.001), but not for the 40%, Vauclin, Black and Schaefer methods.

Conclusion

The functional volume could be measured in PET/CT when CT was performed with enhanced media. Caution should be taken when using the volume delineation method. Volume delineation methods using absolute threshold may artefactually increase the functional volume when enhanced CT is used for attenuation correction. The delineation volume using the relative or adaptative method should be preferred when contrast media are used for PET/CT.     

EGFR mutated non-small cell lung cancer patients: More prone to development of bone and brain metastases?

Objectives

Both bone and brain are frequent sites of metastasis in non-small cell lung cancer (NSCLC). Conflicting data exist whether EGFR mutant (+) patients are more prone to develop brain metastases or have a better outcome with brain metastases compared to EGFR/KRAS wildtype (WT) or KRAS+ patients. For bone metastases this has not been studied.

Methods

In this retrospective case-control study all EGFR+ (exons 19 and 21) patients diagnosed at two pathology departments were selected (2004/2008 to 2012). For every EGFR+ patient a consecutive KRAS+ and WT patient with metastatic NSCLC (mNSCLC) was identified. Patients with another malignancy within 2 years of mNSCLC diagnosis were excluded. Data regarding age, gender, performance score, histology, treatment, bone/brain metastases diagnosis, skeletal related events (SRE) and subsequent survival were collected.

Results

189 patients were included: 62 EGFR+, 65 KRAS+, 62 WT. 32%, 35% and 40%, respectively, had brain metastases (p = 0.645). Mean time to brain metastases was 20.8 [±12.0], 10.8 [±9.8], 16.4 [±10.2] months (EGFR+–KRAS+, p = 0.020, EGFR+–WT, p = 0.321). Median post brain metastases survival was 12.1 [5.0–19.1], 7.6 [1.2–14.0], 10.7 [1.5–19.8] months (p = 0.674). 60%, 52% and 50% had metastatic bone disease (p = 0.528). Mean time to development of metastatic bone disease was 13.4 [±10.6], 23.3 [±19.4], 16.4 [±9.6] months (p = 0.201). Median post metastatic bone disease survival was 15.0 [10.6–20.3], 9.0 [5.2–12.9], 3.2 [0.0–6.9] months (p = 0.010). Time to 1st SRE was not significantly different.

Conclusions

Incidence of brain and bone metastases was not different between EGFR+, KRAS+ and WT patients. Post brain metastases survival, time from mNSCLC diagnosis to metastatic bone disease and 1st SRE did not differ either. Post metastatic bone disease survival was significantly longer in EGFR+ patients. Although prevention of SRE's is important for all patients, the latter finding calls for a separate study for SRE preventing agents in EGFR+ patients.     

A new survival score for patients with brain metastases who received whole-brain radiotherapy (WBRT) alone

Background and purpose

Survival scores for patients with brain metastasis exist. However, the treatment regimens used to create these scores were heterogeneous. This study aimed to develop and validate a survival score in homogeneously treated patients.

Materials and methods

Eight-hundred-and-eighty-two patients receiving 10 × 3 Gy of WBRT alone were randomly assigned to a test group (N = 441) or a validation group (N = 441). In the multivariate analysis of the test group, age, performance status, extracranial metastasis, and systemic treatment prior to WBRT were independent predictors of survival. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. Scores were summed and total scores ranged from 6 to 19 points. Patients were divided into four prognostic groups.

Results

The 6-month survival rates were 4% for 6–9 points, 29% for 10–14 points, 62% for 15–17 points, and 93% for 17–18 points (p < 0.001) in the test group. The survival rates were 3%, 28%, 54% and 96%, respectively (p < 0.001) in the validation group.

Conclusions

Since the 6-month survival rates in the validation group were very similar to the test group, this new score (WBRT-30) appears valid and reproducible. It can help making treatment choices and stratifying patients in future trials.     

Association of GSTP1 expression with resistance to docetaxel and paclitaxel in human breast cancers

Aims

It has been reported that glutathione S-transferase P1 (GSTP1) expression is implicated in resistance to taxanes (docetaxel and paclitaxel) in human breast cancer cells in vitro. In the study presented here, we examine whether GSTP1 expression is associated with resistance to docetaxel or paclitaxel in human breast cancers. We also investigated the relationship between GSTP1 methylation status and response to these taxanes.

Material and methods

Sixty two primary breast cancer patients were treated with docetaxel or paclitaxel as primary systemic treatment (PST). GSTP1 expression was detected immunohistochemically and the hypermethylation status GSTP1 gene was identified with a methylation specific primer assay.

Results

The mean tumor reduction rate for all patients (n = 62) was significantly (p < 0.001) higher in GSTP1 negative (0.73 ± 0.04; mean ± standard error) than GSTP1 positive (0.31 ± 0.09) tumors. The subset analysis showed that the mean reduction rate was significantly (p = 0.005) higher in GSTP1 negative (0.59 ± 0.06) than GSTP1 positive (0.11 ± 0.13) tumors in the docetaxel group as well as in the paclitaxel group (p = 0.006; GSTP1 negative tumors: 0.84 ± 0.05; GSTP1 positive tumors: 0.56 ± 0.08). On the other hand, GSTP1 methylation showed no significant association with the reduction rate.

Conclusion

Our present study has suggested that GSTP1 protein expression, but not GSTP1 methylation status, might be associated with response to docetaxel and paclitaxel. This suggests that GSTP1 immunohistochemical expression might be a potentially clinically useful predictive factor for response to docetaxel and paclitaxel.     

Frequency of EGFR and KRAS mutations in patients with non small cell lung cancer by racial background: Do disparities exist?

Introduction

Mutations in EGFR and KRAS can impact treatment decisions for patients with NSCLC. The incidence of these mutations varies, and it is unclear whether there is a decreased frequency among African Americans (AfAs).

Methods

We performed a retrospective chart review of 513 NSCLC patients undergoing EGFR and KRAS mutational analysis at the Hospital of the University of Pennsylvania between May 2008 and November 2011. Clinical and pathologic data were abstracted from the patients’ electronic medical record.

Results

Of 497 patients with informative EGFR mutation analyses, the frequency of EGFR mutation was 13.9%. The frequency of EGFR mutations was associated with race (p < 0.001) and was lower in AfA patients compared to Caucasian (C) patients but did not reach statistical significance (4.8% vs. 13.7%, p = 0.06). Mean Charlson Comorbidity Index and number of cigarette pack years were significantly lower in patients with EGFR mutations (p = 0.01 and p < 0.001, respectively). Multivariable logistic regression analysis showed a significant association between race and EGFR mutation (p = 0.01), even after adjusting for smoking status (p < 0.001) and gender (p = 0.03). KRAS mutation (study frequency 28.1%) was not associated with race (p = 0.08; p = 0.51 for Afa vs. C patients), but was more common among smokers (p < 0.001) and females (p = 0.01).

Conclusions

Based on multivariable analysis, even after adjusting for smoking status and gender, we found that race was statistically significantly associated with EGFR mutation, but not KRAS mutational status. To the best of our knowledge, this is the largest single institution series to date evaluating racial differences in EGFR and KRAS mutational status among patients with NSCLC.