Outcomes and Prognosis of Non-Elderly Patients with Brain Metastases-A Prospective Cohort Incorporating Individualized Assessment of Heart Rate Variability.

Outcomes and prognostic factors among patients with brain metastases (BM) have been widely studied, but seldom for the non-elderly. Heart rate variability (HRV) is a physiological phenomenon and has been shown as a survival prognostic factor in cancer patients. This study aimed to evaluate the outcomes and prognosis among non-elderly BM patients with the incorporation of HRV analysis. Forty non-elderly BM patients treated using whole brain radiotherapy (WBRT) were studied from January 2010 prospectively with 5-min electrocardiography (ECG) recordings. Individualized HRV was generated by the ECG, and the time domain HRV index SDNN was chosen for survival analysis. The median overall survival (OS) for the entire group was 6.21 months. Univariate analysis revealed that a KPS < 80 (p = 0.019) and an SDNN < 10 ms (p = 0.007) demonstrated statistical significance for OS; multivariate analysis confirmed that a KPS < 80 (p = 0.004; HR = 3.060, CI = 1.437-6.517) and an SDNN < 10 ms (p = 0.010; HR = 2.664, CI = 1.262-5.624) were independent prognostic factors. Prospective studies for risk stratification among non-elderly BM patients based on our results are warranted to validate our findings.

Developing a multivariable normal tissue complication probability model to predict late rectal bleeding following intensity-modulated radiation therapy.

Purpose: To develop a multivariable normal tissue complication probability (NTCP) model to predict moderate to severe late rectal bleeding following intensity-modulated radiation therapy (IMRT). Methods and materials: Sixty-eight patients with localized prostate cancer treated by IMRT from 2008 to 2011 were enrolled. The median follow-up time was 56 months. According to the criteria of D'Amico risk classifications, there were 9, 20 and 39 patients in low, intermediate and high-risk groups, respectively. Forty-two patients were combined with androgen deprivation therapy. Fifteen patients had suffered from grade 2 or more (grade 2+) late rectal bleeding. The numbers of predictors for a multivariable logistic regression NTCP model were determined by the least absolute shrinkage and selection operator (LASSO). Results: The most important predictors for late rectal bleeding ranked by LASSO were platelet count, risk group and the relative volume of rectum receiving at least 65 Gy (V65). The NTCP model of grade 2+ rectal bleeding was as follows: S = -17.49 + Platelets (1000/µL) * (-0.025) + Risk group * Corresponding coefficient (low-risk group = 0; intermediate-risk group = 19.07; high-risk group = 20.41) + V65 * 0.045. Conclusions: A LASSO-based multivariable NTCP model comprising three important predictors (platelet count, risk group and V65) was established to predict the incidence of grade 2+ late rectal bleeding after IMRT.

Analysis of prognostic factors and clinical outcomes in uterine cervical carcinoma with isolated para-aortic lymph node recurrence.

To evaluate clinical outcomes and to identify prognostic factors in isolated para-aortic lymph node (PALN) recurrence, we retrospectively reviewed 65 patients who developed PALN recurrence as the first site of tumor progression from a total of 1521 patients who were treated with curative pelvic radiation therapy (RT) for uterine cervical carcinoma between May 1993 and January 2017. Forty-five of the 65 patients received salvage therapy. The median salvage PALN radiation dose was 54 Gy (range: 18 to 62 Gy). Prognostic factors for overall survival (OS) and distant metastases (DMs) were analyzed with univariate and multivariate Cox regression. The median follow-up period for surviving patients was 61 months (4-202 months). The median OS was 27.7 months (0.3-202 months). The highest level of PALN metastases at or above the L1 spinal level (hazard ratio [HR] 9.88, 95% confidence interval [CI] 3.44-28.38, P<0.001) and the presence of leg edema and/or back pain at recurrence (HR 3.25, 95% CI 1.57-6.75, P=0.002) were significantly associated with worse OS. A significantly higher incidence of DMs (HR 5.97, 95% CI 2.05-17.35, P=0.001) was found in the patients with a high level (≥L1) of PALN metastases. Salvage RT (HR 0.35, 95% CI 0.17-0.71, P=0.004) and restaging with positron emission tomography/computed tomography (PET/CT) (HR 0.2, 95% CI 0.04-0.93, P=0.039) were independent predictors of a better OS. In conclusion, a high level (≥L1) of PALN metastases predicts poor survival and a high rate of DMs. Periodic surveillance for early detection and restaging by PET/CT imaging to identify the optimal treatment at recurrence is recommended.

Pretreatment prognostic factors of survival and late toxicities for patients with nasopharyngeal carcinoma treated by simultaneous integrated boost intensity-modulated radiotherapy.

BACKGROUND: To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). METHODS: A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS). RESULTS: Statistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2-3 vs. N0-1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3-4 (HR: 3.5, 95% CI: 1.0-12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001-1.011, p = 0.027) were associated with higher incidence of radiation neuropathy. CONCLUSION: N classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.

Differences in the outcomes and complications between elderly and younger uterine cervical cancer patients treated by definitive radiotherapy - A propensity score-matched study.

PURPOSE: To evaluate the differences in the treatment outcomes and complications between elderly patients and younger patients with uterine cervical cancer (CxCa). METHODS AND MATERIALS: From April 1993 to December 2007, 138 CxCa patients aged ≥75years (Elderly group) and 334 CxCa patients aged <60years (Young group) who underwent definitive radiotherapy/chemoradiotherapy at our institution were reviewed. Two propensity score-matched cohorts of patients were selected from both age groups to evaluate the differences in the outcomes and complications. The overall survival (OS), cancer-specific survival (CSS), local failure (LF), distant failure (DF), late proctitis, and cystitis were compared between the age groups. RESULTS: The median follow-up time for survivors was 60.6months. A cohort of 99 pairs of patients was selected for the outcome comparison; there was a significant difference in the 5-year OS between the Elderly and Young groups (49.2% and 71.5%, respectively; p<0.001) but no differences in CSS, LF, and DF. Another cohort of 79 pairs of patients was selected for complication analysis. Significant differences between the Elderly and Young groups were observed in the 5-year cumulative grade 2 proctitis (39.7% and 17.2%, respectively; p=0.015) and grade 3 proctitis (18.1% and 6.2%, respectively; p=0.040). CONCLUSIONS: Although OS was worse in the elderly patients, no differences were observed in CSS, LF, and DF. Meanwhile, elderly patients tended to have higher radiation-related proctitis than younger patients. A more conservative treatment strategy for elderly CxCa patients is reasonable in our future practice.

Simultaneous integrated boost (SIB) of the parametrium and cervix in radiotherapy for uterine cervical carcinoma: a dosimetric study using a new alternative approach.

OBJECTIVE: To compare the dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) using the simultaneous integrated boost (SIB) technique with that of the traditional midline block (MB) technique for boosting the parametrium in patients with cervical cancer. METHODS: Treatment plans using VMAT or IMRT with the SIB technique (VMAT-SIB and IMRT-SIB) and IMRT followed by the MB technique (IMRT-MB) were generated for each of the 10 patients with cervical cancer. For the SIB plans, 45-Gy and 50-Gy dose levels in 25 equal fractions were set for the pelvis planning target volume 45 (PTV45) and the parametrial boost volume (PTV50), respectively. For the IMRT-MB plans, the parametrium was sequentially boosted with the MB technique (5.4 Gy in three fractions) after pelvic IMRT (PTV45). RESULTS: Volume receiving 100% of the prescribed dose or more coverage of the PTV50 was significantly better for VMAT-SIB and IMRT-SIB than that for IMRT-MB (99.08 and 99.31% compared with 91.79%, respectively; p < 0.05). VMAT-SIB and IMRT-SIB both generated significantly greater doses to the organs at risk (OARs) except for the volume receiving 50 Gy or more doses, which were significantly lower for the bladder and bowel. Comparable results were achieved with VMAT-SIB and IMRT-SIB. CONCLUSION: The VMAT-SIB and IMRT-SIB techniques are promising in terms of dose distributions and tumour coverage, although these approaches might result in slightly higher doses of radiation to the OARs. Advances in knowledge: This is the first study to examine the feasibility of the SIB technique using IMRT or VMAT to boost the parametrium. The techniques dosimetrically produced better target coverage but resulted in slightly higher doses to the OARs.

The Therapeutic Benefit of Radical Resection for T4b Oral Cavity Squamous Cell Carcinoma with Partial or Complete Response After Radical Chemo-Intensity-Modulated Radiotherapy (IMRT).

BACKGROUND: This study investigated the therapeutic benefit of radical resection (SRR) for clinical T4b oral cavity squamous cell carcinoma (OSCC) with partial or complete response after radical chemoradiotherapy (CRT). METHODS: At the authors' institution, 79 patients with newly diagnosed non-metastatic T4b OSCC were treated with CRT from January 2009 to December 2014. All of them were irradiated using intensity-modulated radiotherapy (IMRT), with a radical dose (median 70 Gy; range 66-76 Gy) in the gross tumor area. Of the 65 cases achieving partial or complete response after CRT, 33 were treated further with SRR and 32 with adjuvant chemotherapy or observation. The locoregional control (LRC), overall survival (OS), and cancer-free survival (CFS) rates were compared between the two groups. RESULTS: The 3-year LRC, OS, and CFS rates were respectively 72.3, 75.1, and 72.6 % in the SRR group compared with 32.8, 47.7, and 44.3 % in the non-SRR group (p < 0.05). Multivariate analysis showed that SRR was the only statistically significant prognostic factor related to LRC, OS, and CFS. For those with SRR, pathologic downstaging was observed in 27 cases (81.8 %). Perioperative flap failure was observed in three cases (9.2 %) and neck wound necrosis in four cases (12.1 %). CONCLUSIONS: For T4b OSCC, incorporating SRR in the therapy is technically safe and has survival benefit, with a significant response after CRT applied by IMRT, with a radical dose in the gross tumor area.

Impact of treatment time-related factors on prognoses and radiation proctitis after definitive chemoradiotherapy for cervical cancer.

This study aimed to investigate the impact of treatment time-related factors on outcomes and radiation proctitis in patients undergoing concurrent chemoradiotherapy (CCRT) for cervical cancer. From September 2001 to December 2012, 146 patients with stage IIB cervical squamous cell carcinoma treated with CCRT were reviewed from a prospective cohort. Patients who received the same dose (45 Gy) of external beam radiation therapy (EBRT) were included in the analysis (n = 125). The same equivalent dose of 2 Gy (EQD2) of high-dose-rate intracavitary brachytherapy (HDR-ICBT) was delivered at either 4 fractions of 6 Gy or 6 fractions of 4.5 Gy. The effects of the overall treatment time (OTT) and interval between EBRT and HDR-ICBT on the cancer-specific survival (CSS), local recurrence (LR), and incidence of proctitis were compared. The treatment time-related factors did not adversely affect the CSS and LR rates. The multivariate analyses did not identify the OTT as an independent factor of CSS (P = 0.839) and LR (P = 0.856). However, OTT ≤56 days (P = 0.026) was identified as the only independent factor of overall proctitis. The 5-year Grade 2 or greater proctitis rates were 14.9% and 0% (P = 0.001) in patients with the EBRT to ICBT interval ≤5 days and >5 days, respectively. To reduce rectal damage without compromising prognosis, the gap between EBRT and HDR-ICBT should exceed 5 days in cervical cancer patients undergoing CCRT. Strictly limiting the OTT to 56 days may result in radiation proctitis without improvements in prognosis.

Pretreatment Factors Associated with Recurrence for Patients with Cervical Cancer International Federation of Gynecology and Obstetrics Stage IB1 Disease.

BACKGROUND: Pretreatment prognostic information is lacking for patients with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IB1 disease. Thus, we attempted to identify a high-risk subgroup among them prior to treatment. METHODS: Cervical cancer FIGO stage IB1 patients who had received curative treatment with various modalities in our institute between January 2004 and December 2010 were enrolled. Pretreatment clinical parameters including age, squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen, hemoglobin (Hb) level, platelet count, histological type, and treatment modality were analyzed for treatment outcomes. RESULTS: One hundred ninety-seven patients were included with a median follow-up of 66 months (range 6-119 months). In Cox regression analysis, only SCC histology (HR 0.457, 95% CI 0.241-0.967, p = 0.017) was an independent factor predicting better disease-free survival (DFS). Among SCC histology, patients with an Hb level less than 12 g/dl and a SCC-Ag level more than 3 ng/ml had worse treatment outcomes. The 5-year DFS rates were 89.2, 69.3, and 44.4% for the patients at low-risk (SCC, Hb >12 g/dl, SCC-Ag ≤3 ng/ml), intermediate-risk (non-SCC), and high-risk (SCC, Hb ≤12 g/dl, SCC-Ag >3 ng/ml), respectively (p < 0.001). CONCLUSION: Non-SCC and SCC histology with both anemia and high pretreatment SCC-Ag level were associated with recurrence. Further validation studies are warranted for clarification.

Prognostic factors associated with radiotherapy for cervical cancer with computed tomography-detected para-aortic lymph node metastasis.

Patients with cervical cancer diagnosed with a para-aortic lymph node (PALN) metastasis by computed tomography (CT) scan were analyzed to identify associated prognostic factors. A total of 55 patients were reviewed, and 27 of these patients underwent extended-field radiotherapy (EFRT). The median PALN dose in patients receiving EFRT was 45 Gy (range, 27-57.6 Gy). Of the 55 patients, 28 underwent pelvic radiotherapy (RT); concurrent chemoradiotherapy (CCRT) was administered to 41 patients. The Kaplan-Meier method was used to calculate the actuarial rate. Multivariate analysis was performed using the Cox proportional hazards model. Five-year overall survival (OS) rates were 41% and 17.9% in patients undergoing EFRT and pelvic RT (P = 0.030), respectively. Age < 53 years (P = 0.023), FIGO Stage I-II (P = 0.002), and treatment with EFRT (P = 0.003) were independent predictors of better OS. The use of CCRT (P = 0.014), Stage I-II (P = 0.002), and treatment using EFRT (P = 0.036) were independent predictors of distant metastasis. In patients undergoing EFRT plus CCRT, the 5-year OS was 50%. Three-year PALN disease-free rates were 8.8%, 57.9% and 100% (P < 0.001) in CCRT patients who received PALN doses of 0 Gy, ≤45 Gy and ≥50.4 Gy, respectively. Although PALN metastasis is thought to be distant metastasis in cervical cancer, EFRT plus CCRT shows a good outcome, particularly in younger patients in an early FIGO stage. Cervical cancer with a PALN metastasis should not be considered incurable. Doses ≥50.4 Gy for treating PALN may result in better disease control.

Galectin-1 is an independent prognostic factor for local recurrence and survival after definitive radiation therapy for patients with squamous cell carcinoma of the uterine cervix.

PURPOSE: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. METHODS AND MATERIALS: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. RESULTS: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. CONCLUSION: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

A prospective cohort study to compare treatment results between 2 fractionation schedules of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer.

PURPOSE: To compare the treatment results of 2 fractionation schedules for high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. METHODS AND MATERIALS: From June 2001 through January 2008, 267 patients with stage IB-IVA cervical cancer were enrolled in the study. All patients underwent 4-field pelvic irradiation and HDR-ICBT. The median central and parametrial doses were 39.6 Gy and 45 Gy, respectively. Patient underwent either 6 Gy×4 (HDR-4) (n=144) or 4.5 Gy×6 (HDR-6) (n=123) to point A of ICBT using 192Ir isotope twice weekly. The rates of overall survival, locoregional failure, distant metastasis, proctitis, cystitis, and enterocolitis were compared between HDR-4 and HDR-6. RESULTS: There were no significant differences in the demographic data between HDR-4 and HDR-6 except for total treatment time. The 5-year proctitis rates were 23.0% and 21.5% in HDR-4 and HDR-6 (P=.399), respectively. The corresponding rates of grade 2-4 proctitis were 18.7% and 9.6% (P=.060). The corresponding rates of grades 3-4 proctitis were 5.2% and 1.3% (P=.231). Subgroup analysis revealed that HDR-4 significantly increased grade 2-4 proctitis in patients aged≥62 years old (P=.012) but not in patients aged<62 years (P=.976). The rates of overall survival, locoregional failure, distant metastasis, cystitis, and enterocolitis were not significantly different between HDR-4 and HDR-6 schedules. CONCLUSION: The small fraction size of HDR-ICBT is associated with grade 2 proctitis without compromise of prognosis in elderly patients. This schedule is suggested for patients who tolerate an additional 2 applications of HDR-ICBT.

Pretreatment carcinoembryonic antigen level is a risk factor for para-aortic lymph node recurrence in addition to squamous cell carcinoma antigen following definitive concurrent chemoradiotherapy for squamous cell carcinoma of the uterine cervix.

BACKGROUND: To identify pretreatment carcinoembryonic antigen (CEA) levels as a risk factor for para-aortic lymph node (PALN) recurrence following concurrent chemoradiotherapy (CCRT) for cervical cancer. METHODS: From March 1995 to January 2008, 188 patients with squamous cell carcinoma (SCC) of the uterine cervix were analyzed retrospectively. No patient received PALN irradiation as the initial treatment. CEA and squamous cell carcinoma antigen (SCC-Ag) were measured before and after radiotherapy. PALN recurrence was detected by computer tomography (CT) scans. We analyzed the actuarial rates of PALN recurrence by using Kaplan-Meier curves. Multivariate analyses were carried out with Cox regression models. We stratified the risk groups based on the hazard ratios (HR). RESULTS: Both pretreatment CEA levels ≥ 10 ng/mL and SCC-Ag levels < 10 ng/mL (p < 0.001, HR = 8.838), SCC-Ag levels ≥ 40 ng/mL (p < 0.001, HR = 12.551), and SCC-Ag levels of 10-40 ng/mL (p < 0.001, HR = 4.2464) were significant factors for PALN recurrence. The corresponding 5-year PALN recurrence rates were 51.5%, 84.8%, and 27.5%, respectively. The 5-year PALN recurrence rate for patients with both low (< 10 ng/mL) SCC and CEA was only 9.6%. CEA levels ≥ 10 ng/mL or SCC-Ag levels ≥ 10 ng/mL at PALN recurrence were associated with overall survival after an isolated PALN recurrence. Pretreatment CEA levels ≥ 10 ng/mL were also associated with survival after an isolated PALN recurrence. CONCLUSIONS: Pretreatment CEA ≥ 10 ng/mL is an additional risk factor of PALN relapse following definitive CCRT for SCC of the uterine cervix in patients with pretreatment SCC-Ag levels < 10 ng/mL. More comprehensive examinations before CCRT and intensive follow-up schedules are suggested for early detection and salvage in patients with SCC-Ag or CEA levels ≥ 10 ng/mL.

Postoperative low pelvic radiotherapy and chemotherapy for stage II and III rectal cancer.

OBJECTIVES: To evaluate whether postoperative low pelvic radiotherapy (RT) combined with chemotherapy is an appropriate treatment for stage II and III rectal cancer. METHODS: Between November 1997 and May 2006, 104 patients with stage II and III rectal cancer underwent surgery as the primary treatment followed by postoperative RT combined with chemotherapy in our institute and were reviewed retrospectively. Sixty-nine patients received low pelvic RT only (upper margin at 1 cm above the low end of the sacroiliac joint; median dose 54 Gy) (low pelvic RT group) and the other 35 patients received whole pelvic RT (upper margin at the mid L5; median dose 43.2 Gy) and subsequently received a boost to the low pelvis (total median dose 54 Gy) (whole pelvic RT group). RESULTS: The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 72% versus 63%, 86% versus 84%, and 66% versus 62% for low pelvic versus whole pelvic RT group. There were no statistical differences in these 2 groups. Two patients (2.9%) of the low pelvic RT group and 2 patients (5.7%) of the whole pelvic RT group developed upper pelvis relapse, which was out of the low pelvic field. The incidence of Grade 3 to 5 small bowel late complications of the low pelvic RT group was significantly less than that of the whole pelvic RT group (4.3% vs. 20%) (P=0.029). CONCLUSIONS: Low pelvic RT significantly reduces small bowel late complications and does not compromise the overall survival rate, local control rate, and distant metastasis-free rate.

Prognostic value of pretreatment carcinoembryonic antigen after definitive radiotherapy with or without concurrent chemotherapy for squamous cell carcinoma of the uterine cervix.

PURPOSE: To evaluate whether pretreatment carcinoembryonic antigen (CEA) levels have a prognostic role in patients after definitive radiotherapy for squamous cell carcinoma (SCC) of the uterine cervix. METHODS AND MATERIALS: A retrospective study of 550 patients was performed. The SCC antigen (SCC-Ag) and CEA levels were regarded as elevated when they were ≥2 and ≥5 ng/mL, respectively. A total of 208 patients underwent concurrent chemoradiotherapy (CCRT). The Kaplan-Meier method was used to calculate the distant metastasis (DM), local failure (LF), disease-free survival (DFS), and overall survival (OS) rates. Multivariate analysis was performed using the Cox proportional hazards model. The hazard ratio (HR) with 95% confidence interval (CI) was evaluated for the risk of a poor prognosis. RESULTS: Compared with the patients with normal CEA/SCC-Ag levels, CEA levels ≥10 ng/mL but without elevated SCC-Ag levels was an independent factor for LF (HR, 51.81; 95% CI, 11.51-233.23; p < .001), DM (HR, 6.04; 95% CI, 1.58-23.01; p = .008), DFS (HR, 10.17; 95% CI, 3.18-32.56; p < .001), and OS (HR, 5.75; 95% CI, 1.82-18.18; p = .003) after RT alone. However, no significant role for CEA was noted in patients with SCC-Ag levels ≥2 ng/mL. In patients undergoing CCRT, a CEA level ≥10 ng/mL was an independent factor for LF (HR, 2.50; 95% CI, 1.01-6.21; p = .047), DM (HR, 3.41; 95% CI, 1.56-7.46; p = .002), DFS (HR, 2.73; 95% CI, 1.39-5.36; p = .003), and OS (HR, 3.93; 95% CI 1.99-7.75; p < .001). A SCC-Ag level of ≥40 ng/mL was another prognostic factor for DM, DFS, and OS in patients undergoing not only CCRT, but also RT alone. The 5-year OS rate for CCRT patients with CEA <10 ng/mL and ≥10 ng/mL was 75.3% and 35.8%, respectively (p < .001). CCRT was an independent factor for better OS (HR, 0.69; 95% CI, 0.50-0.97; p = .034). CONCLUSION: Pretreatment CEA levels in patients with SCC of the uterine cervix provide complementary information for predicting LF, DM, DFS, and OS, except for in patients with abnormal SCC-Ag levels before RT alone. More aggressive therapy might be advisable for patients with CEA levels of ≥10 ng/mL.

Factors for predicting rectal dose of high-dose-rate intracavitary brachytherapy after pelvic irradiation in patients with cervical cancer: a retrospective study with radiography-based dosimetry.

PURPOSE: To evaluate the predictive factors for rectal dose of the first fraction of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. METHODS AND MATERIALS: From March 1993 through February 2008, 946 patients undergoing pelvic irradiation and HDR-ICBT were analyzed. Examination under anesthesia (EUA) at the first implantation of the applicator was usually performed in the early period. Rectal point was determined radiographically according to the 38th Report of the International Commission of Radiation Units and Measurements (ICRU). The ICRU rectal dose (PRD) as a percentage of point A dose was calculated; multiple linear regression models were used to predict PRD. RESULTS: Factors influencing successful rectal dose calculation were EUA (p < 0.001) and absence of diabetes (p = 0.047). Age (p < 0.001), body weight (p = 0.002), diabetes (p = 0.020), and EUA (p < 0.001) were independent factors for the PRD. The predictive equation derived from the regression model was PRD (%) = 57.002 + 0.443 x age (years) - 0.257 x body weight (kg) + 6.028 x diabetes (no: 0; yes: 1) - 8.325 x EUA (no: 0; yes: 1) CONCLUSION: Rectal dose at the first fraction of HDR-ICBT is positively influenced by age and diabetes, and negatively correlated with EUA and body weight. A small fraction size at point A may be considered in patients with a potentially high rectal dose to reduce the biologically effective dose if the ICRU rectal dose has not been immediately obtained in the first fraction of HDR-ICBT.

The treatment responses in cases of radiation therapy to portal vein thrombosis in advanced hepatocellular carcinoma.

PURPOSE: To review the response to radiation therapy for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) and determine the factors favoring its efficacy. METHODS AND MATERIALS: Patients with HCC and PVT referred for radiation therapy between 1997 and 2005 were retrospectively reviewed. Patients who had undergone treatment to primary HCC before radiation or had extrahepatic metastasis were excluded. A radiation dose of 60 Gy with 2 to 3Gy per fraction was prescribed. Clinical features before therapy were investigated, and the most significant imaging change after radiotherapy was regarded as the treatment response. Survival times were compared and the hazard ratios of independent variables were determined. RESULTS: The treatment response rate of the 326 patients included in the study was 25.2% (n = 82). The median survival times were 13.3, 11.6, 9.0, 4.5, and 2.1 months for complete response, partial response, vascular transformation, no response, and the lost follow-up patients, respectively. Statistically significant differences in survival were not found among responder groups (p = 0.224-0.916) but were found between responders and nonresponders (p = 0.002). The most significant independent variables associated with survival (p < 0.001) were performance status and radiation dose. Minor independent factors were ascites, alfa-fetoprotein, albumin, and HBsAg (p = 0.009-0.038). In patients with favorable performance status, those with no more than one minor risk factor had a superior prognosis after radiation therapy (p = 0.013). This result was verified by a review of similar patients in 2006. CONCLUSION: Radiation therapy is the treatment of choice for selected HCC patients with PVT.

Comparison of the outcome and morbidity for localized or locally advanced prostate cancer treated by high-dose-rate brachytherapy plus external beam radiotherapy (EBRT) versus EBRT alone.

OBJECTIVE: To compare the survival, gastrointestinal (GI) and genitourinary (GU) toxicity for localized or locally advanced prostate cancer treated by high-dose-rate-brachytherapy (HDR-BT) plus external beam radiotherapy (EBRT) versus EBRT alone at a single institute in Taiwan. METHODS: Eighty-eight patients with T1c-T3b prostate cancer consecutively treated by EBRT alone (33 patients) or HDR-BT+EBRT (55 patients) were studied. The median dose of EBRT was 70.2 Gy in the EBRT group and 50.4 Gy in the HDR-BT group. HDR-BT was performed 2-3 weeks before EBRT, with 12.6 Gy in three fractions over 24 h. RESULTS: Five patients (15.2%) in the EBRT group and seven (12.7%) in the HDR-BT group developed a biochemical relapse. The 5-year actuarial biochemical relapse-free survival rates were 65.0% in the EBRT group and 66.7% in the HDR-BT group (P = 0.76). The 5-year actuarial likelihood of late > or =Grade 2 and > or =Grade 3 GI toxicity in the EBRT versus HDR-BT group was 62.8 versus 7.7% (P < 0.001) and 19.6 versus 0% (P = 0.001), respectively. In a multivariate analysis, the only predictor for late GI toxicity was the mode of RT. The 5-year actuarial likelihood of late > or =Grade 2 and > or =Grade 3 GU toxicity in the EBRT versus HDR-BT group was 14.8 versus 15.9% (P = 0.86) and 3.6 versus 8.5% (P = 0.40), respectively. CONCLUSIONS: The addition of HDR-BT before EBRT with a reduced dose from the EBRT produces a comparable survival outcome and GU toxicity but a significantly less GI toxicity for prostate cancer patients.

Multivariate analysis of para-aortic lymph node recurrence after definitive radiotherapy for stage IB-IVA squamous cell carcinoma of uterine cervix.

PURPOSE: To evaluate the pretreatment risk factors of para-aortic lymph node (PALN) recurrence after primary radiotherapy for cervical cancer. METHODS AND MATERIALS: Between May 1992 and January 2006, the data from 758 patients with squamous cell carcinoma of the uterine cervix were retrospectively analyzed. No patient had undergone PALN radiotherapy as their initial treatment. PALN recurrence was diagnosed by computed tomography. PALN relapse-free status was determined clinically or radiographically. We analyzed the actuarial rates of PALN recurrence using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. RESULTS: Of the 758 patients, 38 (5%) and 42 (6%) had isolated and nonisolated PALN recurrences after a median follow-up of 50 months (range, 2-159 months), respectively. The 3-year and 5-year overall survival rate after PALN recurrence was 35% and 28%, respectively. A squamous cell carcinoma antigen (SCC-Ag) level >40 ng/mL (p <0.001), advanced parametrial involvement (score 4-6; p = 0.002), and the presence of pelvic lymphadenopathy (p = 0.007) were independent factors associated with PALN relapse on multivariate analysis. The 5-year PALN recurrence rate in patients with a SCC-Ag level >40 ng/mL, SCC-Ag level of 20-40 ng/mL, parametrial score of 4-6, pelvic lymphadenopathy, and no risk factors was 57%, 22%, 34%, 37%, and 9%, respectively. CONCLUSIONS: Patients with squamous cell carcinoma of the uterine cervix and a high SCC-Ag level, pelvic lymphadenopathy, or advanced PM involvement were predisposed to PALN recurrence after definitive radiotherapy. More intensive follow-up schedules are suggested for early detection and salvage in high-risk patients.

Exacerbated radiodermatitis and bilateral subdural hemorrhage after whole brain irradiation combined with epidermal growth factor receptor tyrosine kinase inhibitors for brain metastases in lung cancer.

A 57-year-old male developed an adenocarcinoma lung cancer in November 2003. He received the full course chemotherapy but without a significant regression. The targeted therapy gefitinib was prescribed 2 years after diagnosis, producing a very good partial response. However, brain metastasis was diagnosed. A whole brain irradiation was performed for 37.5Gy with a fraction size of 2.5Gy and gefitinib was replaced with erlotinib on the 5th day after radiation therapy commenced for disease progressing. Unexpectedly, the patient developed a severe skin reaction in the region exposed to the radiation field, and a bilateral subdural hemorrhage, following radiation therapy. The reaction was thought to be triggered by the combination of radiation and epidermal growth factor receptor tyrosine kinase inhibitors, which may be responsible for hypersensitizing the radiation response in normal tissue in the unique individual.