Planning analysis for locally advanced lung cancer: dosimetric and efficiency comparisons between intensity-modulated radiotherapy (IMRT), single-arc/partial-arc volumetric modulated arc therapy (SA/PA-VMAT)

<p>Abstract</p> <p>Purpose</p> <p>To analyze the differences between the intensity-modulated radiotherapy (IMRT), single/partial-arc volumetric modulated arc therapy (SA/PA-VMAT) techniques in treatment planning for locally advanced lung cancer.</p> <p>Materials and methods</p> <p>12 patients were retrospectively studied. In each patient's case, several parameters were analyzed based on the dose-volume histograms (DVH) of the IMRT, SA/PA-VMAT plans respectively. Also, each plan was delivered to a phantom for time comparison.</p> <p>Results</p> <p>The SA-VMAT plans showed the superior target dose coverage, although the minimum/mean/maximum doses to the target were similar. For the total and contralateral lungs, the higher V_5/10, lower V_20/30and mean lung dose (MLD) were observed in the SA/PA-VMAT plans (<it>p </it>< 0.05, respectively). The PA-VMAT technique improves the dose sparing (V₂₀, V₃₀and MLD) of the controlateral lung more notably, comparing to those parameters of the IMRT and SA-VMAT plans respectively. The delivered monitor units (MUs) and treatment times were reduced significantly with VMAT plans, especially PA-VMAT plans (for MUs: mean 458.3 <it>vs</it>. 439.2 <it>vs</it>. 435.7 MUs, <it>p </it>< 0.05 and for treatment time: mean 13.7 <it>vs</it>. 10.6 <it>vs</it>. 6.4 minutes, <it>p </it>< 0.01).</p> <p>Conclusions</p> <p>The SA-VMAT technique achieves highly conformal dose distribution to the target. Comparing to the IMRT plans, the higher V_5/10, lower V_20/30and MLD were observed in the total and contralateral lungs in the VMAT plans, especially in the PA-VMAT plans. The SA/PA-VMAT plans also reduced treatment time with more efficient dose delivering. But the clinical benefit of the VMAT technique for locally advanced lung cancer needs further investigations.</p

Whole brain radiotherapy plus simultaneous in-field boost with image guided intensity-modulated radiotherapy for brain metastases of non-small cell lung cancer

BACKGROUND: Whole brain radiotherapy (WBRT) plus sequential focal radiation boost is a commonly used therapeutic strategy for patients with brain metastases. However, recent reports on WBRT plus simultaneous in-field boost (SIB) also showed promising outcomes. The objective of present study is to retrospectively evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity-modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC. METHODS: Twenty-nine NSCLC patients with 87 inoperable brain metastases were included in this retrospective study. All patients received WBRT at a dose of 40 Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning verification and correction were used to ensure that the set-up errors were within 2 mm by cone beam computed tomography in all patients. RESULTS: The one-year intracranial control rate, local brain failure rate, and distant brain failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year intracranial control rate, local brain failure rate, and distant brain failure rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial progression-free survival and median survival were 10 months. Six-month, one-year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to 62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of intracranial lesions <3, and history of EGFR-TKI treatment had better survival. Three lesions (3.45%) demonstrated radiation necrosis after radiotherapy. Grades 2 and 3 cognitive impairment with grade 2 radiation leukoencephalopathy were observed in 4 (13.8%) and 4 (13.8%) patients. No dosimetric parameters were found to be associated with these late toxicities. Patients received EGFR-TKI treatment had higher incidence of grades 2–3 cognitive impairment with grade 2 leukoencephalopathy. CONCLUSIONS: WBRT plus SIB with IG-IMRT is a tolerable and effective treatment for NSCLC patients with inoperable brain metastases. However, the results of present study need to be examined by the prospective investigations

Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left atrium was performed in 41 cases; Double sleeve lobectomy combined with resection and reconstruction of super vena cava was carried out in 90 cases; Lobectomy combined with resection and reconstruction of diaphragm was performed in 3 cases; Double sleeve lobectomy combined with resection and reconstruction of partial left atrium was performed in 30 cases; Bronchoplastic procedures and pulmonary artery reconstruction combined with reconstruction of aorta sheath was carried out in 10 cases; Right pneumonectomy combined with resection and reconstruction partial left atrium, total right diaphragm with Dacron, and post cava and right liver vein was performed in one case; Lobectomy combined with resection and reconstruction of carina was carried out in 10 cases; Bronchoplastic procedures and pulmonary artery reconstruction combined with resection and reconstruction of carina and superior vane cava, or combined with superior vena cava and left atrium, or with carina and left atrium was performed in 55 cases in this series. Five patients died of operative complications and the operative mortality was 0.97%. CK19 mRNA expression was found in 141 patients. The positive rate of CK19 mRNA expression was 27.3% in peripheral blood samples in the 516 cases. The positive rates of micrometastasis in peripheral blood was significantly related to histological classification, P-TNM staging and N staging of the cancer (P &lt; 0.05), but not to age, sex, smoking status of the patients, and size of primary tumor, and locations of the tumor (P &gt; 0.05). The median survival time was 43.74 months. The 1, 3, 5 and 10 year survival rates of the 516 cases was 89.1%, 39.3%, 19.8% and 10.4%, respectively. The postoperative survival rate was remarkably correlated with micrometastasis in peripheral blood, histological classification of the tumor, size of primary cancer and lymph mode involvement (P &lt; 0.05). The results of multivariable Cox model analysis showed that "personalizedmolecular P-TNM staging", micrometastasis in peripheral blood, pathological types of the tumor and mediastinal lymph node metastasis of the cancer were the most significant factors for predicting prognosis in the patients with locally advanced nonsmall lung cancer. Conclusion (1) Micrometastasis was existed in peripheral blood of patients with lung cancer, which can not be detected with conventional methods. (2) Detecting of CK19 mRNA expression in peripheral blood in lung cancer patients can be used for diagnosis of micrometastasis of lung cancer and “molecular staging” and “molecular P-TNM staging” for lung cancer patients. It will be helpful for selection of surgical treatment indication, the beneficiary of neoadjuvant chemotherapy and postopertive adjuvant therapy in the patients with locally advanced non-small cell lung cancer. (3) Personalized surgical treatment can significantly improve prognosis and increase curative rate and long-term survival rate of locally advanced nonsmall cell lung cancer based on personalized molecular staging

Involved-field irradiation or elective-nodal irradiation in neoadjuvant chemo-radiotherapy for locally-advanced esophageal cancer: comprehensive analysis for dosimetry, treatment-related complications, impact on lymphocyte, patterns of failure and survival

PurposeTo compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).Materials and methodsWe retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups.ResultsThe median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p&lt;0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p=0.004) and pericardial effusion (26.7% vs. 11.8%, p=0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively (p=0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN- patients, especially in the first year of follow-up (6.67% vs. 0.56%, p=0.003).ConclusionThe ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted

A Genome-Wide Linkage and Association Scan Reveals Novel Loci for Hypertension and Blood Pressure Traits

Hypertension is caused by the interaction of environmental and genetic factors. The condition which is very common, with about 18% of the adult Hong Kong Chinese population and over 50% of older individuals affected, is responsible for considerable morbidity and mortality. To identify genes influencing hypertension and blood pressure, we conducted a combined linkage and association study using over 500,000 single nucleotide polymorphisms (SNPs) genotyped in 328 individuals comprising 111 hypertensive probands and their siblings. Using a family-based association test, we found an association with SNPs on chromosome 5q31.1 (rs6596140; P<9×10−8) for hypertension. One candidate gene, PDC, was replicated, with rs3817586 on 1q31.1 attaining P = 2.5×10−4 and 2.9×10−5 in the within-family tests for DBP and MAP, respectively. We also identified regions of significant linkage for systolic and diastolic blood pressure on chromosomes 2q22 and 5p13, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P<7×10−5) for DBP. This is the first combined linkage and association study of hypertension and its related quantitative traits with Chinese ancestry. The associations reported here account for the action of common variants whereas the discovery of linkage regions may point to novel targets for rare variant screening

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Conventionally-fractionated image-guided intensity modulated radiotherapy (IG-IMRT): a safe and effective treatment for cancer spinal metastasis

Abstract Background Treatments for cancer spinal metastasis were always palliative. This study was conducted to investigate the safety and effectiveness of IG-IMRT for these patients. Methods 10 metastatic lesions were treated with conventionally-fractionated IG-IMRT. Daily kilovoltage cone-beam computed tomography (kV-CBCT) scan was applied to ensure accurate positioning. Plans were evaluated by the dose-volume histogram (DVH) analysis. Results Before set-up correction, the positioning errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) axes were 0.3 ± 3.2, 0.4 ± 4.5 and -0.2 ± 3.9 mm, respectively. After repositioning, those errors were 0.1 ± 0.7, 0 ± 0.8 and 0 ± 0.7 mm, respectively. The systematic/random uncertainties ranged 1.4–2.3/3.0–4.1 before and 0.1–0.2/0.7–0.8 mm after online set-up correction. In the original IMRT plans, the average dose of the planning target volume (PTV) was 61.9 Gy, with the spinal cord dose less than 49 Gy. Compared to the simulated PTVs based on the pre-correction CBCT, the average volume reduction of PTVs was 42.3% after online correction. Also, organ at risk (OAR) all benefited from CBCT-based set-up correction and had significant dose reduction with IGRT technique. Clinically, most patients had prompt pain relief within one month of treatment. There was no radiation-induced toxicity detected clinically during a median follow-up of 15.6 months. Conclusion IG-IMRT provides a new approach to treat cancer spinal metastasis. The precise positioning ensures the implementation of optimal IMRT plan, satisfying both the dose escalation of tumor targets and the radiation tolerance of spinal cord. It might benefit the cancer patient with spinal metastasis.</p