Stereotactic Body Radiation Therapy for Pulmonary Metastasis from Colorectal Adenocarcinoma: Biologically Effective Dose 150 Gy is Preferred for Tumour Control.

AIMS: To compare the local control rate of pulmonary metastatic lesions in colorectal adenocarcinoma treated with stereotactic body radiation therapy (SBRT) using a biologically effective dose with an α/ß ratio of 10 (BED10) of 150 Gy. MATERIALS AND METHODS: We analysed 231 pulmonary metastatic lesions from colorectal adenocarcinoma treated with SBRT in 135 patients. The patients were referred for the control of oligometastatic or oligoprogressive disease in the lungs. A dose of 40-60 Gy in three to eight fractions was delivered. The local control per tumour (LCpT) by BED10 was evaluated. The local control per patient (LCpP), pulmonary progression-free survival (PPFS), any progression-free survival (APFS) and overall survival were also reported as clinical outcomes. RESULTS: A significant difference was observed in the LCpT between the BED10 groups (P < 0.001). The 1-, 2- and 3-year LCpT were 38.9%, 25.9% and 25.9% in BED10 < 100 group; 84.1%, 62.6% and 60.4% in 100 ≤ BED10 < 150 Gy group; and 97.3%, 94.9% and 85.2% in BED10 ≥ 150 Gy group, respectively. BED10 ≥ 150 Gy remained significant in the multivariate analysis of LCpT. The 3-year LCpP, PPFS, APFS and overall survival rates were 62.7%, 26.5%, 24.8% and 67.7%, respectively. Oligoprogression (versus oligometastasis), multiple pulmonary nodules and extrapulmonary metastasis were associated with a poor prognosis. CONCLUSION: A BED10 ≥ 150 Gy may be required to achieve sufficient local control. The indications for SBRT and the extent of metastatic disease should be assessed for proper estimation of the clinical outcomes.

Prognostic relevance of lymph node status for patients with ampullary adenocarcinoma after radical resection followed by adjuvant treatment.

PURPOSE: Attempts have been made to revise the nodal stage due to simplicity of current N staging system in ampullary adenocarcinoma. However, because of the disease rarity, there have only been a few studies assessing the prognostic impact of lymph node (LN) parameters. METHODS: We retrospectively analyzed 120 patients who underwent radical resection followed by adjuvant chemoradiotherapy for ampullary adenocarcinoma. The effect of LN parameters (number of total harvest LNs, number of metastatic LN (MLN), lymph node ratio (LNR), and log odds of positive LNs (LODDS)) on overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival were evaluated. Cutoff points of MLN, LNR and LODDs were determined using maximal χ2 method. RESULTS: Fifty-seven patients (48%) were staged as pN1 and their survival was not significantly decreased compared with pN0 patients. There was also no significant difference between patients with MLN 0 vs. 1. In univariate analyses, MLN (0-1 vs. ≥2), LNR (≤17% vs. >17%) and perineural invasion were common prognosticators for OS and LRFS. Distant metastasis-free survival was not influenced by LN status. In addition, multivariate analysis revealed that among the LN parameters, LNR was able to independently predict both OS and LRFS. CONCLUSIONS: LNR performs better than other LN related parameters for predicting survival. After radical resection followed by adjuvant treatment, survival of patients with one positive LN does not seem to differ from patients without LN metastasis.

Is c-Met oncoprotein expression an adverse prognosticator in extrahepatic bile duct cancer treated with curative resection followed by adjuvant chemoradiotherapy?

PURPOSE: To analyze the expression of c-Met, and to investigate correlations between the expression of c-Met, clinicopathologic variables, and survival in patients undergoing curative surgery followed by adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Ninety EHBD cancer patients who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled. Expression of c-Met was assessed with immunohistochemical staining on tissue microarray. The correlation between clinicopathologic variables and survival outcomes was evaluated using Kaplan-Meier method and Cox proportional hazard model. RESULTS: On univariate analysis, 66 patients (76.7 %) showed c-Met expression. c-Met expression had a significant impact on 5-year overall survival (OS) (43.0 % in c-Met(+) vs. 25.0 % in c-Met(-), p = 0.0324), but not on loco-regional relapse-free survival or distant metastasis-free survival (DMFS). However, on multivariate analysis incorporating tumor location and nodal involvement, survival difference was not maintained (p = 0.2940). Tumor location was the only independent prognostic factor predicting OS (p = 0.0089). Hilar location tumors, nodal involvement, and poorly differentiated tumors were all identified as independent prognostic factors predicting inferior DMFS (p = 0.0030, 0.0013, and 0.0037, respectively). CONCLUSIONS: This study showed that c-Met expression was not associated with survival outcomes in EHBD cancer patients undergoing curative resection followed by adjuvant chemoradiotherapy. Further studies are needed to fully elucidate the prognostic value of c-Met expression in these patients.

Association between information provision and decisional conflict in cancer patients.

BACKGROUND: In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). PATIENTS AND METHODS: We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. RESULTS: More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30-0.97] and support (aOR, 0.53; 95% CI 0.33-0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26-0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27-0.77). CONCLUSION: This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.

Locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma: implications for adjuvant radiotherapy.

BACKGROUNDS: As for intrahepatic cholangiocarcinoma, the most frequent site of failure after curative intent resection is the liver. We identified the risk factors for locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma. METHODS: Medical records of 115 patients treated with surgical resection alone for intrahepatic cholangiocarcinoma from November 2000 to December 2010 were retrospectively reviewed. Locoregional failure was defined as recurrence within 20 mm from resection margin or regional lymph node. Overall survival and locoregional recurrence rates were analyzed using Kaplan-Meier methods, and the prognostic factors were analyzed using Cox proportional hazards model. RESULTS: Median follow-up duration of surviving patients was 61 months (range 8-139). Sixty-six patients had recurrence, and 45 of 66 patients (68 %) had locoregional recurrence. The 5-year overall survival and locoregional control rates were 49.1 and 51.6 %, respectively. ≥ T2b disease and R1 resection were associated with locoregional recurrence in multivariate analysis. Patients were divided into two groups whether these risk factors exist or not. The 5-year locoregional control rates of low (no risk factor n = 64) and high (1 or 2 risk factors n = 51) risk groups were 62.5 and 34.7 %, respectively (P = 0.001). CONCLUSIONS: After curative intent resection, locoregional control and survival of patients with intrahepatic cholangiocarcinoma were far from satisfactory. Further studies are needed to evaluate the potential benefit of adjuvant locoregional treatment such as radiotherapy for patients with high-risk factors (≥ T2b disease or R1 resection).

Pilot study on interfractional and intrafractional movements using surface infrared markers and EPID for patients with rectal cancer treated in the prone position.

OBJECTIVE: To evaluate interfractional and intrafractional movement of patients with rectal cancer during radiotherapy with electronic portal imaging device (EPID) and surface infrared (IR) markers. METHODS: 20 patients undergoing radiotherapy for rectal cancer with body mass index ranging from 18.5 to 30 were enrolled. Patients were placed in the prone position on a couch with a leg pillow. Three IR markers were put on the surface of each patient and traced by two stereo cameras during radiotherapy on a twice-weekly basis. Interfractional isocentre movement was obtained with EPID images on a weekly basis. Movement of the IR markers was analysed in correlation with the isocentre movement obtained from the EPID images. RESULTS: The maximum right-to-left (R-L) movement of the laterally located markers in the horizontal isocentre plane was correlated with isocentre translocation with statistical significance (p = 0.018 and 0.015, respectively). Movement of the surface markers was cyclical. For centrally located markers, the 95% confidence intervals for the average amplitude in the R-L, cranial-to-caudal (C-C) and anterior-to-posterior (A-P) directions were 0.86, 2.25 and 3.48 mm, respectively. In 10 patients, intrafractional movement exceeding 5 mm in at least one direction was observed. Time-dependent systematic movement of surface markers during treatment, which consisted of continuous movement towards the cranial direction and a sail back motion in the A-P direction, was also observed. CONCLUSION: Intrafractional movement of surface markers has both cyclic components and time-dependent systematic components. Marker deviations exceeding 5 mm were mainly seen in the A-P direction. Pre- or post-treatment EPID images may not provide adequate information regarding intrafractional movement because of systematic movement in the A-P direction during radiotherapy. ADVANCES IN KNOWLEDGE: This work uncovered a sail back motion of patients in the A-P direction during radiotherapy. Pre- or post-treatment EPID images may not provide accurate positioning of patients in the A-P direction because of this time-dependent intrafractional motion.

Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

BACKGROUND: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). METHODS: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. RESULTS: After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. CONCLUSIONS: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

Exclusive radiotherapy for gliomatosis cerebri: long-term follow-up at a single institution.

PURPOSE: To evaluate the efficacy of radiotherapy and factors affecting the prognosis of gliomatosis cerebri. METHODS: Twenty-eight patients with pathologically confirmed gliomatosis cerebri underwent radiotherapy between August 1988 and September 2003. The median age of the patients was 39 years (range 18-67). Performance status was good (ECOG score ≤2) in 23 patients (82 %). The extent of radiotherapy was partial brain in 17 patients, whole brain in 2 patients, and whole brain followed by partial brain in 9 patients. The median radiation dose was 55.8 Gy (range 46.8-70.4). The median duration of follow-up was 136 months for survivors (range 39-191). RESULTS: The median overall and progression-free survival times of all patients were 20 and 11 months, respectively. When initial response to radiotherapy was grouped as improved, stationary, and aggravated, the median overall survival times in patients with improved, stationary, and aggravated responses were 76, 20, and 7 months, respectively (p = 0.0129). However, radiation parameters such as dose and irradiation volume had no impact on overall survival. On multivariate analysis, both performance status and initial response to radiotherapy were significant prognostic factors affecting overall survival (p = 0.0249 and 0.0065, respectively). CONCLUSIONS: This study showed that gliomatosis cerebri could be effectively treated with radiotherapy and that initial response to radiotherapy was a significant prognostic factor affecting the survival.

Postoperative chemoradiotherapy following pancreaticoduodenectomy. Impact of dose-volumetric parameters on the development of diabetes mellitus.

PURPOSE: The purpose of this research was to analyze the relationship between dose-volumetric parameters and the development of diabetes mellitus (DM) in patients treated with chemoradiotherapy (CRT) following curative resection for upper gastrointestinal (GI) cancers. PATIENTS AND METHODS: Medical records of patients who underwent postoperative CRT following curative resection, either pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD) for upper GI cancers including pancreas, biliary, ampullary, and duodenal cancers, between January 2006 and December 2008 were retrospectively reviewed. A total of 42 patients who were regularly followed for at least 2 years were included for analysis. Dose-volumetric parameters such as remnant pancreatic volume, mean dose, maximum dose (Dmax), and percentage of volume receiving specific dose or more were obtained from pre- and postoperative CT scan images and treatment plan. RESULTS: Dmax and V50 (percentage of volume receiving at least 50 Gy) were statistically significant factors for the development of DM (p = 0.013, p = 0.031, respectively). The sensitivity and specificity of Dmax was 0.875 and 0.559, with cut-off value of 51.1 Gy, respectively. V50 had sensitivity of 0.875 and specificity of 0.618 for cut-off value of 16 %. No patient-related factor other than pretreatment cerebrovascular events was associated with the development of DM. On multivariate analysis, V50 was the only factor with statistical significance (p = 0.028), whereas Dmax showed borderline significance (p = 0.079). CONCLUSION: V50 was the only independent factor associated with the development of diabetes and may function as guideline to predict the development of DM in patients receiving CRT following curative resection.

The beneficial effect of palliative resection in metastatic colorectal cancer.

BACKGROUND: We aimed to determine the role of palliative resection in metastatic colorectal cancer (mCRC) and ascertain which patient populations would benefit most from this treatment. METHODS: A total of 1015 patients diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009 were retrospectively studied. RESULTS: Of the 1015 patients, 168 patients with only liver and/or lung metastasis received curative resection. The remaining 847 patients were treated with palliative chemotherapy and/or palliative resection combined with best supportive care. Palliative resection was performed in 527 (62.2%) cases (complete resection with negative margin (R0) in 93, R1/2 in 434). Resected patients had a more prolonged median overall survival (OS) than unresected patients (21.3 vs 14.1 months; P<0.001). In multivariate analysis, R0 resection was found to be associated with a superior OS compared with R1/2 resection (51.3 vs 19.1 months; P<0.001) and no resection (51.3 vs 14.1 months; P<0.001). When we performed propensity score matching, palliative resection was found to be related to prolonged OS (hazard ratio=0.72, 95% confidence interval=0.59-0.89; P=0.003). CONCLUSION: Palliative resection without residual disease and chemotherapy confers a longer-term survival outcome than palliative chemotherapy alone in mCRC patient subset.

RapidArc vs intensity-modulated radiation therapy for hepatocellular carcinoma: a comparative planning study.

OBJECTIVE: The purpose of this study is to compare the dose-volumetric results of RapidArc (RA Varian Medical Systems, Palo Alto, CA) with those of intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma. METHODS: 20 patients previously treated for hepatocellular carcinoma were the subjects of this planning study. 10 patients were treated for portal vein tumour thrombosis (Group A), and 10 patients for primary liver tumour (Group B). Prescription dose to the planning target volume was 54 Gy in 30 fractions, and the planning goal was to deliver more than 95% of prescribed dose to at least 95% of planning target volume. RESULTS: In Group A, mean doses to liver were increased with RA vs IMRT (22.9 Gy vs 22.2 Gy, p=0.0275). However, V(30 Gy) of liver was lower in RA vs IMRT (31.1% vs 32.1%, p=0.0283). In Group B, in contrast, neither mean doses nor V(30 Gy) of liver significantly differed between the two plans. V(35 Gy) of duodenum and V(20 Gy) of kidney were decreased with RA in Groups A and B, respectively (p=0.0058 and 0.0124, respectively). Both maximal doses to spinal cord and monitor unit were significantly lower in the RA plan, regardless of the group. CONCLUSION: The dose-volumetric results of RA vs IMRT were different according to the different target location within the liver. In general, RA tended to be more effective in the sparing of non-liver organs at risk such as duodenum, kidney, and/or spinal cord. Moreover, RA was more efficient in the treatment delivery than IMRT in terms of total monitor unit used.

Postoperative chemoradiotherapy for gallbladder cancer.

PURPOSE: The goal of this work was to analyze the outcome of adjuvant chemoradiotherapy for patients with gallbladder cancer who underwent surgical resection and to identify the prognostic factors for these patients. PATIENTS AND METHODS: Between August 1989 and November 2006, 47 patients with gallbladder cancer underwent surgical resection followed by adjuvant radiotherapy. There were 21 males and 26 females, and median age was 60 years (range 44-75 years). Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to 40-50 Gy at 2 Gy/fraction; 41 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 48 months for survivors. RESULTS: There were 2 isolated locoregional recurrences, 14 isolated distant metastases, and 7 combined locoregional and distant relapses. The 5-year overall survival rate was 43.7%. According to the extent of resection, the 5-year overall survival rates were 52.8%, 20.0%, and 0% in R0-, R1-, and R2-resected patients, respectively (p = 0.0038). On multivariate analysis incorporating extent of resection, T stage, N stage, performance of lymph node dissection, and histologic differentiation, extent of resection was the only prognostic factor associated with overall survival (p = 0.0075). Among the 37 patients with R0 resection, there was no difference of 5-year overall survival rates in patients with N0, N1, and Nx diseases (46.2%, 60.0%, and 44.4%, respectively, p = 0.6246). As for significant treatment-related morbidity, there was only 1 patient with grade 4 gastric ulcer. CONCLUSION: Adjuvant chemoradiotherapy after R0 resection can achieve a good long-term survival rate in gallbladder cancer patients, even in those with lymph node metastases, and may play a role for patients who underwent R0 resection of primary tumor without lymph node dissection.

Neoadjuvant chemotherapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma.

PURPOSE: To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. METHODS AND MATERIALS: We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. RESULTS: The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group (p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group (p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group (p = 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) CONCLUSION: While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma.

Analysis of correlation between rectal complications and rectal dose following high dose rate intracavitary radiotherapy in patients with uterine cervix cancer: in vivo dosimetric analysis.

PURPOSE: To investigate the correlation between late rectal complications and rectal dose in uterine cervix cancer patients treated with high dose rate intracavitary radiotherapy (HDR ICR) and to analyze dose factors reducing complications. METHODS: A retrospective analysis was done of 74 patients treated with external beam RT and HDR ICR between 1995 and 1997. Radiotherapy (RT) consisted of a median 50.4 Gy external beam plus six fractions of HDR ICR given two times per week, concurrent with the last three weeks of external beam therapy, to a total dose of median 24 Gy to point A or the reference point. Rectal doses were calculated at rectal reference points using barium contrast criteria. In vivo measurement of rectal dose was performed with thermoluminescent dosimeters (TLD) immediately prior to the first fraction of HDR ICR. RESULTS: Eight patients developed rectal complications (11%). There was a significant difference between measured rectal doses for patients with rectal complications and those without (p < 0.05), and the doses were higher in complicated patients. A significant increase in the probability of development of complications was found for patients receiving measured rectal doses of ICR fractional dose 320 cGy or more, ICR total dose 2000 cGy or more, and ICR% to point A 80% or more. CONCLUSIONS: This study showed that in vivo dosimetry using TLD during HDR ICR could have a useful role as a predictor of late rectal complications. Dose limitation to the rectum could possibly be achieved by thorough vaginal packing or use of an applicator with proper shielding while maintaining a high dose to the tumor.