Management for locally advanced cervical cancer: new trends and controversial issues

This article reviewed new trends and controversial issues, including the intensification of chemotherapy and recent brachytherapy (BT) advances, and also reviewed recent consensuses from different societies on the management of locally advanced cervical cancer (LACC). Intensive chemotherapy during and after radiation therapy (RT) was not recommended as a standard treatment due to severe toxicities reported by several studies. The use of positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for pelvic RT planning has increased the clinical utilization of intensity-modulated radiation therapy (IMRT) for the evaluation of pelvic lymph node metastasis and pelvic bone marrow. Recent RT techniques for LACC patients mainly aim to minimize toxicities by sparing the normal bladder and rectum tissues and shortening the overall treatment time by administering a simultaneous integrated boost for metastatic pelvic lymph node in pelvic IMRT followed by MRI-based image guided adaptive BT.

Comparison of concurrent chemoradiotherapy versus sequential radiochemotherapy in patients with completely resected non-small cell lung cancer

PURPOSE: Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols. MATERIALS AND METHODS: From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4–60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals. RESULTS: Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229). CONCLUSION: CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy.

Sustaining Blood Lymphocyte Count during Preoperative Chemoradiotherapy as a Predictive Marker for Pathologic Complete Response in Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The objective of this study was to explore the relationship between the circulating lymphocyte level during preoperative chemoradiotherapy (CRT) and pathologic complete response (pCR) in locally advanced rectal cancer. MATERIALS AND METHODS: From May 2010 to May 2013, 52 patients treated with preoperative CRT followed by surgery, were analysed. Patients received conventional fractionated radiotherapy (50-54 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. Absolute blood lymphocyte counts and their relative percentage in total white blood cell counts were obtained from complete blood count tests performed prior to and after 4, 8, and 12 weeks of CRT. We analysed the association between achieving pCR and change in blood lymphocyte level during CRT, as well as clinical parameters. RESULTS: Among 52 patients, 14 (26.9%) had evidence of pCR. Sustaining the blood lymphocyte count during CRT (lymphocyte count at 4 weeks/baseline lymphocyte count > 0.35; odds ratio, 8.33; p=0.02) and initial carcinoembryonic antigen < 4.4 ng/mL (odds ratio, 6.71; p=0.03) were significantly associated with pCR in multivariate analyses. CONCLUSION: Sustaining blood lymphocyte count during preoperative CRT was predictive for pCR in rectal cancer. Further studies are warranted to investigate the association between pathologic responses and circulating lymphocyte count with its subpopulation during preoperative CRT.

Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

PURPOSE: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. MATERIALS AND METHODS: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). RESULTS: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. CONCLUSION: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.

CT-based quantitative evaluation of radiation-induced lung fibrosis: a study of interobserver and intraobserver variations

PURPOSE: The degree of radiation-induced lung fibrosis (RILF) can be measured quantitatively by fibrosis volume (VF) on chest computed tomography (CT) scan. The purpose of this study was to investigate the interobserver and intraobserver variability in CT-based measurement of VF. MATERIALS AND METHODS: We selected 10 non-small cell lung cancer patients developed with RILF after postoperative radiation therapy (PORT) and delineated VF on the follow-up chest CT scanned at more than 6 months after radiotherapy. Three radiation oncologists independently delineated VF to investigate the interobserver variability. Three times of delineation of VF was performed by two radiation oncologists for the analysis of intraobserver variability. We analysed the concordance index (CI) and inter/intraclass correlation coefficient (ICC). RESULTS: The median CI was 0.61 (range, 0.44 to 0.68) for interobserver variability and the median CIs for intraobserver variability were 0.69 (range, 0.65 to 0.79) and 0.61(range, 0.55 to 0.65) by two observers. The ICC for interobserver variability was 0.974 (p < 0.001) and ICCs for intraobserver variability were 0.996 (p < 0.001) and 0.991 (p < 0.001), respectively. CONCLUSION: CT-based measurement of VF with patients who received PORT was a highly consistent and reproducible quantitative method between and within observers.

Parotid gland sparing effect by computed tomography-based modified lower field margin in whole brain radiotherapy

PURPOSE: Parotid gland can be considered as a risk organ in whole brain radiotherapy (WBRT). The purpose of this study is to evaluate the parotid gland sparing effect of computed tomography (CT)-based WBRT compared to 2-dimensional plan with conventional field margin. MATERIALS AND METHODS: From January 2008 to April 2011, 53 patients underwent WBRT using CT-based simulation. Bilateral two-field arrangement was used and the prescribed dose was 30 Gy in 10 fractions. We compared the parotid dose between 2 radiotherapy plans using different lower field margins: conventional field to the lower level of the atlas (CF) and modified field fitted to the brain tissue (MF). RESULTS: Averages of mean parotid dose of the 2 protocols with CF and MF were 17.4 Gy and 8.7 Gy, respectively (p or =20 Gy were observed in 15 (28.3%) for CF and in 0 (0.0%) for MF. The whole brain percentage volumes receiving >98% of prescribed dose were 99.7% for CF and 99.5% for MF. CONCLUSION: Compared to WBRT with CF, CT-based lower field margin modification is a simple and effective technique for sparing the parotid gland, while providing similar dose coverage of the whole brain.

Prognostic factors and treatment outcome after radiotherapy in cervical cancer patients with isolated para-aortic lymph node metastases / 부인종양

OBJECTIVE: The purpose of the present study was to evaluate treatment outcomes and prognostic factors in cervical cancer patients with isolated para-aortic lymph node (PALN) metastases. We especially tried to evaluate PALN factors such as size, site and number. METHODS: From August 1994 to December 2009, 40 cervical cancer patients with isolated PALN node metastases at initial diagnosis were selected for analysis. Patients underwent both extended field external beam and intracavitary brachytherapy. Fourteen patients received 5-fluorouracil and cisplatin (FP) and 16 patients received weekly concurrent cisplatin. Information of PALN, such as size, site, and number, was founded before PALN radiotherapy. RESULTS: The median follow-up time after primary treatment was 28.5 months (range, 2 to 213 months). The 3-year overall and progression-free survival rate after primary treatment was 44.3% and 31.3%, respectively. In multivariate analysis including tumor stage, performance status, and chemotherapy, FP regimen concurrent chemoradiotherapy was more effective than radiotherapy alone (p=0.030). The 3-year progression-free survival rate was 41.9% and 11.1% in patients with PALN numbers of or =2, respectively (p=0.008). The 3-year progression-free survival rate was 42.1% and 19.2% in patients with PALN size of or =1.5 cm, respectively (p=0.031). CONCLUSION: The radiologic features of PALN, such as number or size, can be used to determine prognosis in PALN metastatic cervical cancer patients. Furthermore, FP regimen concurrent chemoradiotherapy was associated with better patient survival than radiotherapy alone. However, more studies are required to confirm possible different treatment outcomes between FP and weekly cisplatin regimens.