Outcomes of stereotactic ablative radiotherapy following a clinical diagnosis of stage I NSCLC: Comparison with a contemporaneous cohort with pathologically proven disease

Introduction

As a finding of benign disease is uncommon in Dutch patients undergoing surgery after a clinical diagnosis of stage I NSCLC, patients are also accepted for stereotactic ablative radiotherapy (SABR) without pathology. We studied outcomes in patients who underwent SABR after either a pathological (n = 209) or clinical diagnosis (N = 382).

Materials and methods

Five hundred and ninety-one patients with a single pulmonary lesion underwent SABR after either a pathological- or a clinical diagnosis of stage I NSCLC based on a ¹⁸FDG-PET positive lesion with CT features of malignancy. SABR was delivered to a total dose of 60 Gy in 3, 5 or 8 fractions, and outcomes were compared between groups with and without pathological diagnosis.

Results

Patients with pathology had significantly larger tumor diameters (p < .001) and higher predicted FEV1% values (p = .025). No significant differences were observed between both groups in overall survival (p = .99) or local control (p = .98). Regional and distant recurrence rates were also similar.

Conclusions

In a population with a low incidence of benign ¹⁸FDG-PET positive lung nodules, clinical SABR outcomes were similar in large groups of patients with or without pathology. The survival benefits reported after the introduction of SABR are unlikely to be biased by inclusion of benign lesions.     

Diagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation

Purpose

To prospectively assess diagnostic performance of response assessment fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with HNSCC treated with high-precision definitive (chemo)radiation.

Methods

Fifty-seven patients treated on a prospective clinical trial having post-treatment response assessment FDG-PET/CT scans were included. Clinico-pathologic findings and follow-up information was considered as reference standard.

Results

First response assessment FDG-PET/CT was done at a median of 9 weeks (inter-quartile range 8-10 weeks) from completion of treatment. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of first response assessment FDG-PET/CT for identifying residual disease at primary site was 50%, 91.8%, 50%, 91.8%, and 86%. The corresponding figures for the neck were 62.5%, 98%, 83.3%, 94.1%, and 93%. With a median follow-up of 26 months (range 7-45 months), the 3-year loco-regional control (83.9% vs 58.3%, p = 0.001) and overall survival (68.8% vs 58.3%, p = 0.063) was significantly better in patients with negative response assessment scans.

Conclusion

The overall diagnostic accuracy of response assessment FDG-PET/CT is good, but its sensitivity and PPV is somewhat low, particularly for primary site. A negative response assessment FDG-PET/CT scan is highly suggestive of absence of viable disease that could be used to guide decision-making.     

Analysis of acute radiation-induced esophagitis in non-small-cell lung cancer patients using the Lyman NTCP model

Purpose

To analyze acute esophagitis (AE) in a Chinese population receiving 3D conformal radiotherapy (3DCRT) for non-small cell lung cancer (NSCLC), combined or not with chemotherapy (CT), using the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model.

Materials and methods

157 Chinese patients (pts) presented with NSCLC received 3DCRT: alone (34 pts) or combined with sequential CT (59 pts) (group 1) or with concomitant CT (64 pts) (group 2). Parameters (TD₅₀, n, and m) of the LKB NTCP model predicting for > grade 2 AE (RTOG grading) were identified using maximum likelihood analysis. Univariate and multivariate analyses using a binary regression logistic model were performed to identify patient, tumor and dosimetric predictors of AE.

Results

Grade 2 or 3 AE occurred in 24% and 52% of pts in group 1 and 2, respectively (p < 0.001). For the 93 group 1 pts, the fitted LKB model parameters were: m = 0.15, n = 0.29 and TD₅₀ = 46 Gy. For the 64 group 2 pts, the parameters were: m = 0.42, n = 0.09 and TD₅₀ = 36 Gy. In multivariate analysis, the only significant predictors of AE were: NTCP (p < 0.001) and V₅₀, as continuous variable (RR = 1.03, p = 0.03) or being more than a threshold value of 11% (RR = 3.6, p = 0.009).

Conclusions

A LKB NTCP model has been established to predict AE in a Chinese population, receiving thoracic RT, alone or combined with CT. The parameters of the models appear slightly different than the previous one described in Western countries, with a lower volume effect for Chinese patients.     

Tumor volume discrepancies between FDG-PET and MRI for cervical cancer

Purpose

To compare the MRI-defined gross tumor volume (MR-GTV) to the metabolic tumor volume (Metabolic GTV) defined by FDG-PET in patients with cervical cancer.

Materials and methods

Forty seven patients with cervical cancer underwent FDG-PET/CT and MRI simulations. FDG-PET images were acquired with a spatial resolution of 5 mm. MR imaging was performed on a 1.5 Tesla scanner. MR-GTV was contoured on the T2 axial images while Metabolic GTV was auto-contoured using a 40% SUV threshold. Tumor volumes were compared.

Results

Eighteen patients (38.3%) had tumors ?62 cc on MRI. Seventeen patients (36.2%) had tumors ?14 and <62 cc, while 12 patients (25.5%) had tumors <14 cc. 83% of patients in the ?62 cc, 23.5% in the 14-62 cc, and 16.7% in the <14 cc cohort had Grade 3 images as defined by Dimopoulos et al. In the ?62 cc cohort, MR-GTV and Metabolic GTV had a lesion coverage factor of 0.68 (mean MR-GTV_vol 124.1, mean Metabolic GTV_vol 119.9 cc). This fell to 0.51 (32.4, 33.1 cc) for the 14-62 cc, and 0.28 (8.4, 8.7 cc) for the <14 cc cohort. These differences were statistically significant on ANOVA testing (p < 0.001).

Conclusions

MRI provided better visualization of larger tumors than smaller tumors in reference to FDG-PET/CT. FDG-PET/CT visualized tumor volumes different from T2-weighted MRI, especially in tumors <14 cc in regard to location.     

Is pre-therapeutical FDG-PET/CT capable to detect high risk tumor subvolumes responsible for local failure in non-small cell lung cancer?

Background and purpose

Local failure is a significant issue following radiotherapy (RT) for patients with non-small cell lung cancer (NSCLC). The aim of this study was to find out whether FDG-PET/CT is capable to predict tumor relapse location in patients with NSCLC, in particular to determine high risk tumors’ subvolumes responsible for local failure.

Material and methods

Ten patients with locoregional relapse of NSCLC underwent FDG-PET/CT before, during, and in the 4-12 months following curative chemoradiotherapy (ChRT, 66 Gy) using a combined PET/CT scanner. Morphologic and metabolic tumor volumetry and an evaluation of FDG-uptake dynamics were performed.

Results

CT showed partial reduction of tumor volume after RT in all patients. PET-revealed partial in eight patients and complete metabolic response in two patients during RT. Six to nine months after RT, local failure was diagnosed in all patients with both methods. Tumor recurrences were localized mostly in the most active ones of pre-therapeutically metabolic regions of the primary tumor.

Conclusions

Local failure in NSCLC appears most common at the primary site and within the irradiated target volume with the highest FDG uptake. This observation may be useful for further optimization of radiotherapy of NSCLC, for example, by the application of additional radiation dose to subvolumes of primary tumors with higher FDG uptake.     

Anal cancer maximum F-18 fluorodeoxyglucose uptake on positron emission tomography is correlated with prognosis

Purpose

To evaluate anal cancer uptake of F-18 fluorodeoxyglucose (FDG) measured as the maximum standardized uptake value (SUV_max) by positron emission tomography (PET) and its correlation with prognostic factors.

Patients and methods

The study population consisted of 77 patients with stages 0-IIIB anal cancer who underwent pre-treatment FDG-PET. Tumor histology included 65 squamous cell, 11 basaloid, and 1 small cell cancers. SUV_max and sites of lymph node metastasis were recorded. We analyzed the association between SUV_max and prognostic factors.

Results

The mean SUV_max was 10.0 (range 1.0-43.1). The stage distribution included: 2 stage 0, 7 stage I, 49 stage II, 10 stage IIIA, 9 stage IIIB. SUV_max and clinical tumor size were not associated (R² = 0.338). Histology did not significantly influence SUV_max (mean SUV_max 10.0 for squamous versus 9.90 for basaloid). Higher SUV_max was associated with an increased risk of nodal metastasis at diagnosis (p < 0.0001). Higher SUV_max was associated with worse disease-free survival (p = 0.05). Patients with high anal tumor SUV_max at diagnosis were at an increased risk of persistent or recurrent disease on post-therapy FDG-PET performed less than 4 months after completing therapy (p = 0.0402).

Conclusions

SUV_max is a valuable biomarker of anal cancer prognosis, predicting increased risk of lymph node metastasis and worse disease-free survival.     

Limited prognostic value of dual time point F-18 FDG PET/CT in patients with early stage (stage I & II) non-small cell lung cancer (NSCLC)

Objective

The aim of the current study was to investigate the prognostic value of dual time point F-18 FDG PET/CT in patients with early stage (stage I & II) NSCLC.

Methods

A retrospective review identified 66 patients with surgically resected early (stage I & II) NSCLC who received dual time point F-18 FDG PET/CT at diagnosis of cancer. Survival analysis was conducted using Kaplan-Meier analysis, and survival curves stratified by age, sex, mediastinal lymph node involvement, TNM staging, SUV_maxE, SUV_maxD, and %ΔSUV_max were generated for estimation of overall survival and disease-free survival (DFS). Independent predictive factors for survival were determined using Cox proportional hazard model.

Results

The overall survival and DFS were better in patients with tumor SUV_maxE ? 5.75 than the patients with tumor SUV_maxE ? 5.75. Seventeen patients (18.2%) with a tumor SUV_maxD ? 6.8 and 4 of 33 patients with tumor SUV_maxD ? 6.8 recurred during follow-up period. The median disease-free survival of the patients with tumor SUV_maxD ? 6.8 was 31.7 months and was significantly worse than the patients with tumor SUV_maxD ? 6.8 (Log rank test, Χ² = 10.45, p = 0.0012). The %ΔSUV_max did not have prognostic values for overall survival and disease-free survival. The SUV_maxE and SUV_maxD were the potent predictors for overall survival. Also, the potent predictor of DFS was the SUV_maxE.

Conclusion

In conclusion, %ΔSUV_max measured by dual time point F-18 FDG PET/CT might not have a prognostic value for overall survival and DFS in surgically resected early stage (stage I & II) NSCLC.     

The metabolic response using F-fluorodeoxyglucose-positron emission tomography/computed tomography and the change in the carcinoembryonic antigen level for predicting response to pre-operative chemoradiotherapy in patients with rectal cancer

Background and purpose

To predict tumor regression in pre-operative chemoradiotherapy (CRT) using ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and serum carcinoembryonic antigen (CEA) in patients with rectal cancer.

Materials and methods

The metabolic response of the tumor was assessed by determining the maximal standardized uptake value (SUV_max), absolute difference (ΔSUV_max), and SUV reduction ratio (SRR) on pre- and post-CRT PET/CT scans. The serum CEA, absolute difference (ΔCEA), and the CEA reduction ratio (CRR) were also determined. A receiver-operating characteristic (ROC) curve was generated.

Results

Of all seventy two patients, mean pre- and post-CRT SUV_max was 14.9 and 5.8, respectively. The mean pre- and post-CRT CEA level was 15.5 ng/ml and 5.4 ng/ml, respectively. Forty-three patients (59.8%) were classified as responders (Dworak’s tumor regression grade 3-4) and 36 patients (50%) achieved tumor down-staging. ROC analysis showed that both post-CRT SUV_max and SRR were predictive factors for responders (p = 0.03 and p = 0.02, respectively). A threshold of post-CRT SUV_max was 5.4 and that of SRR was 53.1%. Pre-CRT SUV_max, ΔSUV_max, and all parameters in regard to CEA were not significant in ROC analysis.

Conclusions

The post-CRT SUV_max and SRR are potential factors for predicting tumor response in pre-operative CRT. The patients with lower post-CRT SUV_max and higher SRR could be expected to achieve maximum tumor regression after pre-operative CRT in this study.     

Coexisting pulmonary nodules in operable lung cancer: prevalence and probability of malignancy

Introduction

Coexistence of pulmonary nodules in operable non small cell lung cancer (NSCLC) may influence the therapeutic indication. The aim of this study was to evaluate prospectively the prevalence and the probability of malignancy of pulmonary nodules in operable lung cancer.

Methods

From a prospective database, all surgically treated patients diagnosed with NSCLC from 1998 to 2003 were retrospectively reviewed. Patients presenting pulmonary nodule(s) were identified.

Results

Two hundred thirty nine patients had a complete resection for a NSCLC and 56 patients (24%) presented altogether 88 nodules on thoracic CT. Twenty-four of these nodules (27%) were malignant, 28 (32%) benign and 36 (41%) of undetermined nature. Five factors associated with nodule's malignancy were identified: tumour histology (non-squamous (non-SCC) 44% vs. SCC 7%, p = 0.001), localization of the nodules in an upper lobe (vs. other lobe, p = 0.004), co localization in the same lobe as the NSCLC (vs. another lobe, p = 0.03), nodule size (p = 0.05) and shape (speculated vs. non spiculated, p = 0.02). From these factors, a probability score was assessed with a malignancy rate in SCC of 0% in nodules presenting ≤1 feature, 33% with 2 features and 100% with ≥3 features and in non-SCC of 40% with 1 feature, 82% with 2 features and 100% with 3 ≥ features.

Conclusion

Diagnosis of satellite nodules associated with early stage NSCLC is common. We developed a predictive score to estimate the probability of malignancy which may be a precious aid in the management of pulmonary nodules associated to a NSCLC.     

Gradient-based delineation of the primary GTV on FDG-PET in non-small cell lung cancer: A comparison with threshold-based approaches, CT and surgical specimens

Purpose

The aim of this study was to validate a gradient-based segmentation method for GTV delineation on FDG-PET in NSCLC through surgical specimen, in comparison with threshold-based approaches and CT.

Materials and methods

Ten patients with stage I-II NSCLC were prospectively enrolled. Before lobectomy, all patients underwent contrast enhanced CT and gated FDG-PET. Next, the surgical specimen was removed, inflated with gelatin, frozen and sliced. The digitized slices were used to reconstruct the 3D macroscopic specimen. GTVs were manually delineated on the macroscopic specimen and on CT images. GTVs were automatically segmented on PET images using a gradient-based method, a source to background ratio method and fixed threshold values at 40% and 50% of SUV_max. All images were finally registered. Analyses of raw volumes and logarithmic differences between GTVs and GTV_macro were performed on all patients and on a subgroup excluding the poorly defined tumors. A matching analysis between the different GTVs was also conducted using Dice’s similarity index.

Results

Considering all patients, both lung and mediastinal windowed CT overestimated the macroscopy, while FDG-PET provided closer values. Among various PET segmentation methods, the gradient-based technique best estimated the true tumor volume. When analysis was restricted to well defined tumors without lung fibrosis or atelectasis, the mediastinal windowed CT accurately assessed the macroscopic specimen. Finally, the matching analysis did not reveal significant difference between the different imaging modalities.

Conclusions

FDG-PET improved the GTV definition in NSCLC including when the primary tumor was surrounded by modifications of the lung parenchyma. In this context, the gradient-based method outperformed the threshold-based ones in terms of accuracy and robustness. In other cases, the conventional mediastinal windowed CT remained appropriate.     

Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy

Background

The aim of this study was to assess the predictive value of tumor expression of nine genes on clinical outcome in patients with advanced NSCLC receiving platinum-gemcitabine chemotherapy.

Methods

Quantitative PCR or immunohistochemistry were used to analyze the expression of β-tubuline IIA (TUBB2A), β-tubuline III (TUBB3), BRCA1, ERCC1, Abraxas (ABRX) and RAP80 in mRNA isolated from paraffin-embedded tumor biopsies of 45 NSCLC patients treated as part of a larger observational trial. All patients received first-line platinum-gemcitabine chemotherapy for stage IIIB or IV NSCLC.

Results

Median progression-free survival (PFS) was 7 months, overall survival (OS) 12 months. A partial treatment response was found in 14 patients (33%). Patients with low ERCC1 or ABRX expression had a significantly better response to chemotherapy (R = −0.45, p < 0.01 for ERCC1; R = −0.40, p = 0.016 for ABRX). A significant correlation was found between the individual time for PFS and the expression of both ERCC1 (R = −0.36, p = 0.015) and ABRX (R = −0.46, p = 0.001). Patients with low ERCC1 expression had a longer OS as compared to patients with high ERCC1 expression (HR = 0.26, log-rank p = 0.02).

Conclusions

The study confirms tumor expression of ERCC1 as a predictor for clinical outcome in patients with advanced NSCLC receiving platinum-based chemotherapy, and found ABRX expression to be similarly predictive of clinical outcome. Prospective validation is warranted and - if confirmed - non platinum-containing chemotherapy should be explored as the preferred treatment in patients with high ERCC1 or ABRX expression and no activating mutations of EGFR.     

Promoter methylation of BRMS1 correlates with smoking history and poor survival in non-small cell lung cancer patients

Purpose

To investigate whether methylation of BRMS1 is associated with clinical outcomes in patients with NSCLC.

Methods

Methylation status of BRMS1 was examined in 325 NSCLC patients who were treated with surgery. We analyzed associations between the methylation of BRMS1 genes separately and available epidemiologic and clinical information including smoking status, gender, age, and histological type, or the stage of the tumor.

Results

In the cohort of 325 NSCLC cases, 152 samples were identified as methylated (46.77%). Promoter methylation of BRMS1 was present only in 6 specimens (8.42%) in adjacent non-cancerous tissues (P = 2.257 × 10⁻¹⁴). Patient smoking history had a positive correlation with methylation rate of BRMS1 (OR = 2.508, 95%CI(1.516, 4.151)). Compared with unmethylated group, methylated group showed the lower level of BRMS1 mRNA (P = 0.013). And patients with a high level of BRMS1 mRNA expression had significantly better overall survival than those with low expression (P = 0.002). Multivariate Cox proportional hazard regression analysis also showed that promoter methylation of BRMS1 was significantly unfavorable prognostic factors (hazard ratio, 1.912; 95% CI, and 1.341-2.726).

Conclusions

These results provide clinical evidence to support the notion that BRMS1 is a NSCLC metastasis suppressor gene. Measuring methylation status of BRMS1 promotor is a useful marker for identifying NSCLC patients with worse disease-free survival.     

Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer solitary metastases: systematic review and analysis of reported cases

Back ground

Although patients with stage IV non-small cell lung cancer (NSCLC) have a poor prognosis, a subset of patients with solitary brain or adrenal metastasis have more favorable outcome following surgical resection. Nevertheless, the outcome and predictive factors for survival following metastatectomy for patients with other metastatic sites are not well defined.

Methods

We performed a systematic review using PUBMED database for all articles which included patients with NSCLC and solitary metastasis to sites other than the adrenal gland or the brain who had undergone resection of their metastasis and definitive treatment of the primary lung cancer. Potential prognostic factors on survival including age, sex, histology, T and N stage of the primary tumor, synchronous vs. metachronous presentation, visceral vs. non-visceral metastasis and the use of perioperative chemotherapy were analyzed using multi-variable Cox proportional hazard model.

Results

62 cases were eligible for the analysis. The 5-year survival rate was 50% for the entire cohort. Mediastinal lymph node involvement was independently predictive of inferior outcome; 5-year survival rate 0% vs. 64% in favor of no involvement, p < 0.001. Similarly, patients with intra-thoracic stage III disease had an inferior outcome compared to patients with stage II and stage I disease: 5-year survival rate 0% vs. 77% and 63%, respectively, p < 0.001. Other factors have no effect on outcome.

Conclusion

Selected patients with distant metastatic NSCLC can achieve long term survival following metastatectomy and definitive treatment of the primary tumor. Mediastinal lymph node involvement is associated with poor prognosis.     

Volumetric response analysis during chemoradiation as predictive tool for optimizing treatment strategy in locally advanced unresectable NSCLC

Purpose

To study the feasibility of measuring volumetric changes in the primary tumor on megavoltage-computed tomography (MVCT) during chemoradiation and to examine the correlation with local response.

Patients and methods

Fifteen consecutive patients with stage III, inoperable, locally advanced non-small cell lung cancer (NSCLC) were treated in a prospective dose escalation study protocol of concurrent chemoradiation. They were monitored for acute toxicity and evaluated with daily MVCT imaging. The volumetric changes were fitted to a negative exponential resulting in a regression coefficient (RC). Local response evaluation was done with positron emission tomography using the radio-labeled glucose analogue F18 fluorodeoxyglucose (FDG-PET).

Results

The mean volume decrease (±standard deviation) was 73% (±18%). With a mean treatment time of 42 days this treatment schedule resulted in a mean decrease of 1.74%/day. Of the 13 evaluable patients seven developed a metabolic complete remission (MCR). The mean RC of the patients with MCR is 0.050 versus a mean RC of 0.023 in non-responders (p = 0.0074). Using a proposed cut-off value for the RC of 0.03 80% of the non-responders will be detected correctly while misclassifying 16.4% of patients who will eventually achieve an MCR. The total cumulative percentage of esophageal grade 3 or more toxicity was 46.7%.

Conclusion

The RC derived from volumetric analysis of daily MVCT is prognostic and predictive for local response in patients treated with chemoradiation for a locally advanced NSCLC. Because this treatment schedule is toxic in nearly half of the patient population, MVCT is a tool in the implementation of patient-individualized treatment strategies.     

The maximum standardized uptake value (SUVmax) on FDG-PET is a strong predictor of local recurrence for localized non-small-cell lung cancer after stereotactic body radiotherapy (SBRT)

Background

The maximum standardized uptake value (SUVmax) of FDG-PET may predict local recurrence for localized non-small-cell lung cancer (NSCLC) after stereotactic body radiotherapy (SBRT).

Methods

Among 195 localized NSCLCs that were treated with total doses of either 40 Gy or 50 Gy in 5 SBRT fractions, we reviewed those patients who underwent pre-treatment FDG-PET using a single scanner for staging. Local control rates (LCRs) were obtained by the Kaplan-Meier method and a log-rank test. Prognostic significance was assessed by univariate and multivariate analyses.

Results

A total of 95 patients with 97 lesions were eligible. Median follow-up was 16.0 months (range: 6.0-46.3 months). Local recurrences occurred in 9 lesions. By multivariate analysis, only the SUVmax of a primary tumor was a significant predictor (p = 0.002). Two years LCRs for lower SUVmax (<6.0; n = 78) and higher SUVmax (?6; n = 19) were 93% and 42%, respectively. In subgroups with T1b and T2, LCRs were significantly better for lower SUVmax than for higher SUVmax (p < 0.0005 and p < 0.01). In both subgroups that received 40 Gy and 50 Gy, LCRs were also significantly better for lower SUVmax than for higher SUVmax (p < 0.001 and p < 0.01).

Conclusions

SUVmax was the strongest predictor for local recurrence. A high SUVmax may be considered for dose escalation to improve local control. Additional follow-up is needed to determine if SUVmax is correlated with regional recurrence, distant metastasis, and survival.     

Histopathological and immunohistochemical features associated with clinical response to neoadjuvant gefitinib therapy in early stage non-small cell lung cancer

Background

Matrix metalloproteinases (MMPs) are considered important players in angiogenesis and cancer progression. Several drugs developed for targeting MMPs have until now been without clinical efficacy. As both malignant cells and cells of the surrounding stroma contribute to tumor growth, we have explored the impact of MMP-2, -7 and -9 expression in both the tumor and stromal compartment of non-small-cell lung cancers (NSCLC).

Patients and methods

From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). Immunohistochemistry was used to detect the expression of MMP-2, -7 and -9 in tumor and stromal cells.

Results

In univariate analyses, high tumor cell MMP-7 expression (P = 0.029) and high stromal MMP-9 expression (P = 0.001) were positive prognostic factors. In the multivariate analysis, high tumor cell MMP-7 expression (HR 1.58, CI 1.08-2.32, P = 0.020) and high stromal MMP-9 expression (HR 1.92, CI 1.25-2.96, P = 0.003) were independent positive prognostic factors for disease-specific survival.

Conclusion

High levels of MMP-7 in tumor cells and high levels of MMP-9 in tumor associated stroma were independent positive prognostic factors in NSCLC patients.     

The outcome differences of CT screening for lung cancer pre and post following an algorithm in Zhuhai, China

Purpose

To evaluate the change in outcomes from CT screening for lung cancer before and after collaboration with the International Early Lung Cancer Action Program (I-ELCAP) as well as changing from a single-row detector to a multi-row detector CT scanner (MDCT).

Methods and materials

All participants in the screening program were 40 years of age and older. From 1994 to 2002, a single slice spiral CT was used, the screening protocol was established empirically at our institution. From 2003 to 2009 a 16 slice MDCT was used and our institute became the first I-ELCAP site in China. Collaboration included use of the I-ELCAP protocol, image reading training, teaching files training and attendance at international conferences. The clinical and CT characteristics of participants and diagnosed lung cancers pre and post-collaboration were summarized. The outcomes before and after collaboration were compared, including nodule positive rate, lung cancer frequency, stage distribution, pathology, intervals between last routine screening and surgery, the rate of surgery for benign disease and survival rate.

Results

3348 participants were enrolled during 1994-2002 and 3582 participants during 2003-2009. Their age, gender, smoking and family cancer histories were comparable. The screening detection rate of lung cancer was 1.1% (36/3348) vs. 1.0% (34/3582) (P = 0.6), mean size was 18.6 mm vs. 15.6 mm (P = 0.04), stage I lung cancer was 67% vs. 91% (P = 0.38), median intervals between last routine screening and surgery was 213 days vs. 96 days (P < 0.001), 5-year survival rate due to lung cancer was 75% vs. 95% (P = 0.032) in pre- and post collaboration group respectively. The nodule positive rate was 6.2% (208/3348) vs. 9.8% (351/3582) (P < 0.001), the rate of surgery for benign disease was 18% (8/44) vs. 8% (3/37) (P = 0.4) in pre- and post collaboration group respectively.

Conclusion

Smaller lung cancer were detected, interval between last routine screening and surgery was shorter, surgery for benign disease decreased, and survival rate increased in CT screening for lung cancer in Zhuhai after the collaboration with I-ELCAP and with MDCT. Technology improvements along with a well defined protocol improved outcomes of CT screening for lung cancer in Zhuhai, China.     

Precise correlation between MRI and histopathology - Exploring treatment margins for MRI-guided localized breast cancer therapy

Background

Magnetic resonance imaging (MRI) is more often considered to guide, evaluate or select patients for partial breast irradiation (PBI) or minimally invasive therapy. Safe treatment margins around the MRI-visible lesion (MRI-GTV) are needed to account for surrounding subclinical occult disease.

Purpose

To precisely compare MRI findings with histopathology, and to obtain detailed knowledge about type, rate, quantity and distance of occult disease around the MRI-GTV.

Methods and materials

Patients undergoing MRI and breast-conserving therapy were prospectively included. The wide local excision specimens were subjected to detailed microscopic examination. The size of the invasive (index) tumor was compared with the MRI-GTV. The gross tumor volume (GTV) was defined as the pre-treatment visible lesion. Subclinical tumor foci were reconstructed at various distances to the MRI-GTV.

Results

Sixty-two patients (64 breasts) were included. The mean size difference between MRI-GTV and the index tumor was 1.3 mm. Subclinical disease occurred in 52% and 25% of the specimens at distances ?10 mm and ?20 mm, respectively, from the MRI-GTV.

Conclusions

For MRI-guided minimally invasive therapy, typical treatment margins of 10 mm around the MRI-GTV may include occult disease in 52% of patients. When surgery achieves a 10 mm tumor-free margin around the MRI-GTV, radiotherapy to the tumor bed may require clinical target volume margins >10 mm in up to one-fourth of the patients.     

Diagnostic and staging impact of radiotherapy planning FDG-PET-CT in non-small-cell lung cancer

Background and purpose

To evaluate whether FDG-PET performed for radiotherapy (RT) planning can detect disease progression, compared with staging PET.

Materials and methods

Twenty-six patients with newly-diagnosed non-small-cell lung cancer underwent planning PET-CT for curative RT within 8 weeks (mean: 33 ± 14 days) of staging PET-CT. Progressive disease (PD) was defined as >25% increase in tumour size (transaxial) or volume, as delineated by SUV threshold of 2.5, or new sites (SUV > 2.5).

Results

The planning PET detected PD in 16 patients (61%), compared to four patients (15%) by CT component of PET-CT. The mean scan interval was longer in patients with progression: 40 ± 12 days, compared to 22 ± 11 days without progression. Planning PET detected PD in 13/17 (76%), 12/14 (86%) and 7/7 patients if the interval was ?4, 5 and 6 weeks, respectively, compared with 3/9 patients if interval <4 weeks. Planning PET detected PD in primary metabolic volume in seven patients, 20 new nodal sites in 12 new nodal stations and nine patients, five extra-nodal sites in five patients. This resulted in upstaging in nine patients (35%): stage IIIA in three, IIIB in three and IV in three.

Conclusions

RT-planning FDG-PET can provide incremental diagnostic information and may impact on staging in a significant number of patients.     

Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume in patients with thoracic esophageal squamous cell carcinoma: A report of 1077 cases

Purpose

To study the pattern of lymph node metastases after esophagectomy and clarify the clinical target volume (CTV) delineation of thoracic esophageal squamous cell carcinoma (ESCC).

Methods and materials

Total 1077 thoracic ESCC patients who had undergone esophagectomy and lymphadenectomy were retrospectively examined. The clinicopathologic factors related to lymph node metastasis were analyzed using logistic regression analysis.

Results

The rates of lymph node metastases in patients with upper thoracic tumors were 16.7% (9/54) cervical, 38.9% (18/54) upper mediastinal, 11.1% (6/54) middle mediastinal, 5.6% (3/54) lower mediastinal, and 5.6% (3/54) abdominal, respectively. The rates of lymph node metastases in patients with middle thoracic tumors were 4.0% (27/680), 3.8% (26/680), 32.9% (224/680), 7.1% (48/680), and 17.1% (116/680), respectively. The rates of lymph node metastases in patients with lower thoracic tumors were 1.0% (5/343), 3.0% (10/343), 22.7% (78/343), 37.0% (127/343), and 33.2% (114/343), respectively. T stage, the length of tumor and the histological differentiation emerged as statistically significant risk factors of lymph node metastases of thoracic ESCC (P < 0.001).

Conclusions

T stage, the length of tumor and the histologic differentiation influence the pattern of lymph node metastases in thoracic ESCC. These factors should be considered comprehensively to design the CTV for radiotherapy (RT) of thoracic ESCC. Selective regional irradiation including the correlated lymphatic drainage regions should be performed as well.