• Radiation Oncology Journal
• /
• v.34 no.2
• /
• pp.96-105
• /
• 2016

Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45-50 Gy in 25-28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer.

• Progress in Medical Physics
• /
• v.29 no.4
• /
• pp.143-149
• /
• 2018

To verify the correlations between the clinical outcomes and physical factors of short-course chemoradiotherapy (SCRT) and long-course chemoradiotherapy (LCRT) with delayed surgery in patients with rectal cancer. Seventy-two patients with rectal cancer were enrolled in this study. Nineteen patients were treated with SCRT (25 Gy, 5 fractions) by intensity-modulated radiation therapy (IMRT), and 53 patients were treated with LCRT (50.4 Gy, 28 fractions) by three-dimensional conformal radiation therapy (3DCRT). Various physical factors for the target and organs at risk (OARs) were calculated to compare the clinical outcomes. The organ equivalent dose (OED) and lifetime attributable risk (LAR) of bowels and bladders were similar between the SCRT and LCRT groups, whereas the values of femurs were higher in the LCRT group. The equivalent uniform dose and normal tissue complication probability were higher in the LCRT than the SCRT group for most organs. Treatment complications, including anastomotic leakage, bowel adhesion, and hematologic toxicity, were not significantly different between SCRT and LCRT groups. CIs were $0.84{\pm}0.2$ and $0.61{\pm}0.1$ for SCRT and LCRT, respectively. The CVIs were $1.07{\pm}0.0$ and $1.10{\pm}0.1$, and the HIs were $0.09{\pm}0.0$ and $0.11{\pm}0.1$ for SCRT and LCRT, respectively. The sphincter-saving rates were 89.5% and 94.3% for SCRT and LCRT, respectively. The complete pathologic remission rates were 21.1% and 13.2%, and the down-staging rates were 47.4% and 26.4% for SCRT and LCRT, respectively. SCRT with IMRT is comparable to conventional LCRT in both physical indexes and clinical outcome. The preoperative SCRT, compensated by IMRT, is an effective and safe modality.

• Mass Spectrometry Letters
• /
• v.13 no.3
• /
• pp.84-94
• /
• 2022

Neoadjuvant chemoradiotherapy (nCRT) is a standard therapy used for locally advanced rectal cancer prior to surgery, which can more effectively reduce the locoregional recurrence rate and radiation toxicity compared to postoperative chemoradiotherapy. The response of patients to nCRT varies, and thus, robust biomarkers for predicting a pathological complete response are necessary. This study aimed to identify possible biomarkers involved in the complete response/non-response of rectal cancer patients to nCRT. Comparative proteomic analysis was performed on rectal tissue samples before and after nCRT. Proteins were extracted for label-free proteomic analysis. Western blot and real-time PCR were performed using rectal cancer cell line SNU-503 and radiation-resistant rectal cancer cell line SNU-503R80Gy. A total of 135 up- and 93 down-regulated proteins were identified in the complete response group. Six possible biomarkers were selected to evaluate the expression of proteins and mRNA in SNU-503 and SNU-503R80Gy cell lines. Lyso-phosphatidylcholine acyltransferase 2, annexin A13, aldo-ketose reductase family 1 member B1, and cathelicidin antimicrobial peptide appeared to be potential biomarkers for predicting a pathological complete response to nCRT. This study identified differentially expressed proteins and some potential biomarkers in the complete response group, which would be further validated in future studies.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.19
• /
• pp.8475-8478
• /
• 2014

Purpose: This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed-based chemoradiotherapy in treating patients with locally advanced or metastatic esophageal cancer. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for relevant patients were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: For pemetrexed-based regimens, 4 clinical studies including 47 patients with locally advanced or metastatic esophageal cancer were considered eligible for inclusion. Systematic analysis showed that, in all patients, the pooled RR was 51% (24/47). Major adverse effects of grade III/IV were esophagitis, neutropenia, thrombocytopenia, anemia anorexia, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusion: This systematic analysis suggests that pemetrexed based radiotherapy is associated with reasonable activity and good tolerability in treating patients with locally advanced or metastatic esophageal cancer.

• Radiation Oncology Journal
• /
• v.30 no.3
• /
• pp.99-107
• /
• 2012

Purpose: The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. Materials and Methods: The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used (5-fluorouracil and leucovorin, capecitabine, or tegafur/uracil). Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Results: Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Conclusion: Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

• Journal of Yeungnam Medical Science
• /
• v.36 no.2
• /
• pp.124-135
• /
• 2019

Background: We aimed to establish robust histoprognostic predictors on residual rectal cancer after preoperative chemoradiotherapy (CRT). Methods: Analyzing known histoprognostic factors in 146 patients with residual disease allows associations with patient outcome to be evaluated. Results: The median follow-up time was 77.8 months, during which 59 patients (40.4%) experienced recurrence and 41 (28.1%) died of rectal cancer. On univariate analysis, residual tumor size, ypT category, ypN category, ypTNM stage, downstage, tumor regression grade, lymphatic invasion, perineural invasion, venous invasion, and circumferential resection margin (CRM) were significantly associated with recurrence free survival (RFS) or/and cancer-specific survival (CSS) (all p<0.005). On multivariate analysis, higher ypTNM stage and CRM positivity were identified as independent prognostic factors for RFS (ypTNM stage, p=0.024; CRM positivity, p<0.001) and CSS (p=0.022, p=0.017, respectively). Furthermore, CRM positivity was an independent predictor of reduced RFS and CSS, irrespective of subgrouping according to downstage (non-downstage, p<0.001 and p<0.001; downstage, p=0.002 and p=0.002) or lymph node metastasis (non-metastasis, p<0.001 and p=0.001; metastasis, p<0.001 and p<0.001). Conclusion: CRM status may be as powerful as ypTNM stage as a prognostic indicator for patient outcome in patients with residual rectal cancer after preoperative CRT.

• Radiation Oncology Journal
• /
• v.31 no.4
• /
• pp.185-190
• /
• 2013

Purpose: We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods: Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. Results: The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. Conclusion: We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.10
• /
• pp.4285-4289
• /
• 2015

Purpose: Blood hemoglobin levels are known to influence response to radiotherapy. This retrospective analysis compared the effect of hemoglobin levels upon response to radiation among patients treated with radiation alone (by accelerated hyperfractionated radiotherapy) versus those treated with concurrent cisplatin chemoradiotherapy. Materials and Methods: Among patients treated for locally advanced carcinoma of the cervix (LACC) during 2009-10, a total of 60 fulfilled the eligibility criteria. In this time frame, external beam radiotherapy was delivered with either concurrent chemoradiotherapy (CRT, n=31) (45Gy over 25 fractions, with weekly cisplatin at 40mg/m2), or with accelerated hyperfractionated radiotherapy (AHRT, n=29) (20Gy over 10 daily fractions over the first two weeks, followed by 30Gy over 20 fractions over the next two weeks, with two fractions of 1.5Gy per day, without the use of chemotherapy). Mean weekly hemoglobin (MWH) levels of all patients were calculated as the arithmetic means of weekly recorded blood hemoglobin levels. As per MWH, patients in both of the AHRT or the CRT groups were classified into two subgroups-those with MWH between 10-10.9g/dL, or with MWH>11g/dL. Complete response (CR) to external beam RT phase (prior to brachytherapy) was declared after clinical examinations and computed tomography. The CR rate was noted for both MWH sub-groups within each of the AHRT and CRT groups. Results: Within the AHRT group, patients with MWH>11g/dL had a much better CR rate in comparison to those with MWH:10-10.9g/dL (80% vs. 21.1%) which was statistically significant (p 0.0045). Within the CRT group, there was no significant difference in the outcomes within the MWH>11g/dL and MWH:10-10.9g/dL sub-groups (CR rates of 80% vs. 61.9%, p=0.4285). Conclusions: The importance of maintaining a minimum hemoglobin level of 11g/dL during RT is much greater for patients treated with RT alone, than for patients treated with concurrent chemoradiotherapy. Enhanced haemoglobin levels during RT may to an extent negate the ill-effects that may otherwise arise due to non-use of concurrent chemotherapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5237-5242
• /
• 2013

Background: Inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an essential participant in the neoplastic process, promoting proliferation, survival and migration. Platelets can release some growth factors such as platelet-derived growth factor, platelet factor 4, and thrombospondin. Such factors have been shown to promote hematogenous tumour spread, tumor cell adhesion and invasion, and angiogenesis and to play an important role in tumor progression. In this study, we aimed to investigate effects of the pretreatment neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on survival and response to chemoradiotherapy in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: Ninety-four patients with non-metastatic NSCLC were included and separated into two groups according to median valuse of NLR and PLR (low:<3.44 or high:${\geq}3.44$ and low:<194 or high${\geq}194$, respectively). Results: Pretreatment high NLR and PLR were associated with significantly shorter disease-free and overall survival rates. Multivariate analysis revealed that the overall survival rates were significantly linked with PLR (OR: 1.87, CI: 1.20-2.91, p: 0.006) and response to chemoradiotherapy (OR: 1.80, CI: 1.14-2.81, p: 0.012) and the disease-free survival rates were significantly associated with NLR (OR: 1.81, CI: 1.16-2.82, p: 0.009) and response to chemoradiotherapy (OR: 2.30, CI: 1.45-3.66, p: 0.001). There was no significant difference between patients with high and low NLR in terms of response to chemoradiotherapy. Similarly, there was no significant influence of the PLR. Conclusions: Pretreatment NLR and PLR measurements can provide important prognostic results in patients with NSCLC and assessment of the two parameters together appears to better predict the prognosis in patients with NSCLC. The effect of inflammation, indicators of NLR and PLR, on survival seems independent of the response to chemoradiotherapy.

• Journal of Gastric Cancer
• /
• v.16 no.2
• /
• pp.105-110
• /
• 2016

Purpose: In the Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial, we investigated whether chemoradiotherapy after D2 gastrectomy reduces the rate of recurrence. Recently, the ratio of metastatic lymph nodes to examined lymph nodes (N ratio) has been proposed as an independent prognostic factor in gastric cancer (GC). The aim of this study was to investigate the relationship between the metastatic N ratio and prognosis of GC after curative D2 surgery. Materials and Methods: We retrospectively reviewed the data of 458 ARTIST patients who underwent D2 gastrectomy followed by adjuvant chemotherapy (XP, n=228) or chemoradiotherapy (XPRT, n=230). The disease-free survival (DFS) rates of patients were used to evaluate the influence of N ratio on the treatment outcome. To achieve this, 4 different N ratio categories (0%, 1%~9%, 10%~25%, and >25%) were compared on the basis of their influence on the treatment outcome. Results: On multivariate analysis, the N ratio remained an independent prognostic factor for DFS. The hazard ratios (HRs) for the N ratio categories of 0%, 1%~9%, 10%~25%, and >25% were 1, 1.061, 1.202, and 3.571, respectively. In patients having N ratio >25%, the 5-year DFS rates were 55% and 28% for the XPRT and XP arms, respectively (HR, 0.527; 95% confidence interval, 0.307~0.904; P=0.020). Conclusions: In patients with curatively resected GC, the N ratio was independently associated with DFS. Although this finding warrants further investigation in future prospective studies, the benefit of chemoradiotherapy for D2 resected GC appears to be more beneficial in cancers having N ratios >25%.