Machine learning-based normal tissue complication probability model for predicting albumin-bilirubin (ALBI) grade increase in hepatocellular carcinoma patients.

PURPOSE: The aim of this study was to develop a normal tissue complication probability model using a machine learning approach (ML-based NTCP) to predict the risk of radiation-induced liver disease in hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: The study population included 201 HCC patients treated with radiotherapy. The patients' medical records were retrospectively reviewed to obtain the clinical and radiotherapy data. Toxicity was defined by albumin-bilirubin (ALBI) grade increase. The normal liver dose-volume histogram was reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose (2 Gy/fraction and α/ß = 2). Three types of ML-based classification models were used, a penalized logistic regression (PLR), random forest (RF), and gradient-boosted tree (GBT) model. Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Internal validation was performed by 5-fold cross validation and external validation was done in 44 new patients. RESULTS: Liver toxicity occurred in 87 patients (43.1%). The best individual model was the GBT model using baseline liver function, liver volume, and MLD as inputs and the best overall model was an ensemble of the PLR and GBT models. An AUROC of 0.82 with a standard deviation of 0.06 was achieved for the internal validation. An AUROC of 0.78 with a standard deviation of 0.03 was achieved for the external validation. The behaviors of the best GBT model were also in good agreement with the domain knowledge on NTCP. CONCLUSION: We propose the methodology to develop an ML-based NTCP model to estimate the risk of ALBI grade increase.

Evaluation and external validation of minor lymphatic pelvic pathway for distant metastases in cervical cancer patients treated with concurrent chemoradiotherapy.

To evaluate and validate the minor lymphatic pathway for distant metastases in cervical cancer. This is a retrospective cohort of cervical cancer patients underwent curative concurrent chemoradiotherapy. We used original dataset from 1 university hospital and validation dataset from 3 university hospitals. Lymphadenopathy status in CT imaging was reviewed by radiologist in either the obturator and external iliac nodes (major pathway) or the internal iliac and presacral nodes (minor pathway). We then used Cox regression to adjust for all potential confounders, including paraaortic nodes, T stage, histology, age, total treatment time, total number of nodes, total short axis of nodes. 397 and 384 patients were in the original and validation datasets (median follow-up period, 59.5 month's). The minor pathway was independent prognostic factor in multivariable analysis [HR=2.64; 95%CI=1.07-6.55; P = 0.036] and [HR=14.84; 95%CI=3.15-70.01; P= 0.001] in original and validation datasets, respectively. Whereas, the major pathway was statistically non-significant. Further validation showed that the minor pathway had the highest HR for distant metastases with both the EMBRACE (HR=6.05; 95% CI=1.30-28.08; P = 0.022) and the FIGO 2018 (HR=7.43; 95% CI=2.94-18.78; P<0.001) in the original dataset. A similar result was found with the validation dataset: EMBRACE, HR=30.91; 95% CI=2.78-343.62; P = 0.005; and FIGO 2018, HR=42.41; 95% CI=8.83-203.60; P<0.001.This is the first clinical study to validate that the minor lymphatic pathway was predominantly associated with distant metastases in cervical cancer. This finding should be validated in larger cohort to further integrate in standard staging for prediction of distant metastases.

Development and validation of a prognostic prediction model including the minor lymphatic pathway for distant metastases in cervical cancer patients.

To develop and validate a prognostic model, including the minor lymphatic pathway (internal iliac and presacral nodes). STUDY DESIGN: Retrospective cohort. PARTICIPANTS: Locally advanced cervical cancer underwent concurrent chemoradiotherapy. SAMPLE SIZE: 397 and 384 patients in the development and validation data set. PREDICTORS: Our new nodal staging system with the minor lymphatic pathway. OUTCOME: Distant metastases. STATISTICAL ANALYSIS: Cox regression; net reclassification improvement (NRI) and decision curve analysis (DCA). Our new nodal system was the strongest predictor. The predictors in the final model were new nodal system, tumor stage, adenocarcinoma, initial hemoglobin, tumor size and age. The nodal system and the pretreatment model had concordance indices of 0.661 and 0.708, respectively, with good calibration curves. Compared to the OUTBACK eligibility criteria, the nodal system showed NRI for both cases (22%) and controls (16%). The pretreatment model showed NRI for cases (31%) and controls (18%). DCA in both models showed threshold probability of 15% and 12%, respectively, when compared with 24% in OUTBACK eligibility criteria. Our new nodal staging system and the pretreatment model could differentiate between high-risk and low-risk patients, thus facilitating decisions to provide more aggressive treatment to prevent distant metastases.

Advanced radiotherapy technique in hepatocellular carcinoma with portal vein thrombosis: Feasibility and clinical outcomes.

BACKGROUND: In Thailand, individuals with hepatocellular carcinoma (HCC) who develop portal vein tumor thrombosis (PVTT) have a restricted treatment option because to the extent of the disease, poor underlying liver function, and non-coverage of immuno/targeted therapy. Radiotherapy (RT) plays an increasingly important function in these patients. To investigate the feasibility, efficacy, and adverse event rates, we performed a retrospective analysis of patients with HCC with PVTT who underwent 3-dimensional conformal radiation (3DCRT), intensity-modulated radiation (IMRT), volumetric-modulated radiotherapy (VMAT), and stereotactic body radiotherapy (SBRT) in a single-institution. OBJECTIVES: To examine clinical results in terms of overall survival (OS), local control (LC), response of primary tumor and PVTT, hepatic and gastrointestinal adverse reaction, and prognosis variables for OS and LC. MATERIALS AND METHODS: Between July 2007 and August 2019, non-metastatic HCC with PVTT patients treated with RT were retrospectively reviewed and evaluated. RESULTS: The analysis included data from 160 patients. The mean age of the patients was 60.8 years ((95% CI 58.2-62.0). The median diameter of the tumor was 7.7 cm (range: 1-24.5). 85 (54.5%) individuals had PVTT in the main or first branch. At 1.8-10 Gy per fraction, the mean biologically effective dose (BED) as α/ß ratio of 10 was 49.6 (95% CI 46.7-52.5) Gy10. The median survival time was 8.3 (95% CI 6.1-10.3) months. Survival rates at one and two years were 39.6% and 17.1%, respectively. Estimated incidence of local failure using competing risk analysis were 24% and 60% at 1 and 2 years, respectively. The overall response rate was 74%, with an 18.5 percent complete response rate. In multivariate analysis, tumor size, overall response, and radiation dose were all significant prognostic variables for OS. Hepatic unfavorable events of grade 3 and 4 were for 14.1% of the total. There was no occurrences of grade 3-4 gastrointestinal toxicity, either acute or late. Additionally, there were no treatment-related mortality. CONCLUSIONS: Advanced RT is regarded as a safe and effective therapeutic option for HCC with PVTT. Overall survival was clearly related to tumor size, radiation dose, and tumor/PVTT response. Individuals with BED 56 Gy10 had significantly better overall survival than patients with BED 56 Gy10. A prospective randomized trial is required to validate these outcomes in order to corroborate these findings.

Assessment of the confidence interval in the multivariable normal tissue complication probability model for predicting radiation-induced liver disease in primary liver cancer.

We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose-volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance-covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child-Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74-0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.

Flattening filter free stereotactic body radiation therapy for lung tumors: outcomes and predictive factors.

BACKGROUND: Stereotactic body radiation therapy (SBRT) using flattening filter free (FFF) has been commonly used, however, its outcomes and predictive factors in lung tumors are limiting. Thus, we aim to assess the clinical outcomes of this approach and identify factors associated with outcomes in patients with early stage non-small cell lung cancer (NSCLC) and oligometastatic/oligoprogressive lung tumor (OLT). METHODS: Patients who underwent lung SBRT with FFF were retrospectively reviewed. All patients were delivered using volumetric modulated arc therapy (VMAT) technique. The primary outcome was local control (LC). The secondary outcomes were overall survival (OS) and toxicities. We assessed the association between LC and various factors in OLT. RESULTS: From February 2014 to July 2019, ninety-four patients and 129 lesions with median follow-up time of 30 months were included in the analysis. Twenty-six patients with 26 lesions were early NSCLC, while 68 patients with 103 lesions were OLT, 41.7% of which were from colorectal cancers (CRC) and 18.5% were from primary lung cancers. Two-year LC was 88.9% and 85.7% for early NSCLC and OLT, respectively. Two-year OS was significantly higher for early NSCLC than OLT (83.3% vs. 68.7%, P=0.035). In the multivariate analysis for OLT, CRC origin (hazard ratio, HR 10.59, 95% CI: 2.29-48.95, P=0.003) and gross tumor volume (GTV) mean BED10 ≤147 Gy (HR 5.16, 95% CI: 1.13-23.59, P=0.034) were significantly associated with higher local failure (LF). Most of the acute grade 1-2 toxicities were radiation pneumonitis (26.5%). No grade 3-5 event was observed. CONCLUSIONS: This study confirmed the clinical efficacy and safety of lung SBRT using FFF-technique. Our findings support the role of using a high BED10 regimen to achieve good LC for OLT and the potential role for dose escalation for primary CRC.

The normal tissue complication probability model-based approach considering uncertainties for the selective use of radiation modality in primary liver cancer patients.

PURPOSE: To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancer patients. METHODS AND MATERIALS: Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/ß ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method. RESULTS: Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-A patients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision. CONCLUSIONS: Patients with CP-A and viral hepatitis infection or CP-B/C cirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach.

Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2).

PURPOSE: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade ≥3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life. RESULTS: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (P=.012). The incidence of grade ≥3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (n=48), those treated with IG-IMRT (n=35) had a significantly lower incidence of grade ≥3 neutropenia (8.6% vs 27.1%; 2-sided χ2P=.035) and nonsignificantly lower incidence of grade ≥3 leukopenia (25.7% vs 41.7%; P=.13) and any grade ≥3 hematologic toxicity (31.4% vs 43.8%; P=.25). CONCLUSIONS: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia.

Management of intracranial germ cell tumors at the King Chulalongkorn Memorial Hospital.

OBJECTIVE: To study the outcome of less aggressive radiotherapy combined with surgery and chemotherapy to reduce radiation complication in the treatment of intracranial germ cell tumor (ICGCT) at the King Chulalongkorn Memorial Hospital. MATERIAL AND METHOD: A descriptive study was established by reviewing patients' records from the Division of Therapeutic Radiology and Oncology admitted between 2001 and 2008. Median follow-up time was 65 months. Patient characteristics, investigations, and treatment modalities were presented in proportion. Survival analysis was evaluated by Kaplan-Meier method. The results were compared with the previous study in done in 1990 to 2000. RESULTS: Forty-two records were reviewed and 71% were male. The median age was 16 years. Pineal region was the most common site in 55%. Interestingly, 12% had synchronous lesions at both pineal and suprasellar regions. Out of 41 patients who had histopathological confirmation, 71% were germinoma. Out of 37 patients who had MRI spine or CSF cytology, 43% had CNS dissemination. Less aggressive radiotherapy combined with surgery and chemotherapy was increasingly utilized; however five-year overall survival rate in all patients was 83%, comparable to 82% from the previous study. Survival rates of patients without CNS dissemination were 88% in the present study and 83% in the previous study. Survival rates adjusted for histopathology were 86% for germinoma and 76% for non-germinoma. CONCLUSION: Less aggressive radiotherapy combined with surgery and chemotherapy to reduce radiation complication is an effective treatment for ICGCT.

Cost and effectiveness evaluation of prophylactic HPV vaccine in developing countries.

BACKGROUND: Approximately 80% of cervical cancer cases occur in developing countries. In Thailand, cervical cancer has been the leading cancer in females, with an incidence of 24.7 cases per 100,000 individuals per year. OBJECTIVES: We constructed a decision model to simulate the lifetime economic impact for women in the context of human papillomavirus (HPV) infection prevention. HPV-related diseases were of interest: cervical cancer, cervical intraepithelial neoplasia, and genital warts. The two strategies used were 1) current practice and 2) prophylactic quadrivalent vaccine against HPV types 6, 11, 16, and 18. METHODS: We developed a Markov simulation model to evaluate the incremental cost-effectiveness ratio of prophylactic HPV vaccine. Women transition through a model either healthy or developing HPV or its related diseases, or die from cervical cancer or from other causes according to transitional probabilities under the Thai health-care context. Costs from a provider perspective were obtained from King Chulalongkorn Memorial Hospital. Costs and benefits were discounted at 3% annually. RESULTS: Compared with no prophylactic HPV vaccine, the incremental cost-effectiveness ratio was 160,649.50 baht per quality-adjusted life-year. The mortality rate was reduced by 54.8%. The incidence of cervical cancer, cervical intraepithelial neoplasia grade 1, cervical intraepithelial neoplasia grade 2/3, and genital warts was reduced by up to 55.1%. CONCLUSION: Compared with commonly accepted standard thresholds recommended by the World Health Organization Commission on Macroeconomics and Health, the nationwide coverage of HPV vaccination in girls is likely to be cost-effective in Thailand.

Quality of life among Thai women diagnosed with cervical cancer and cervical intraepithelial neoplasia at King Chulalongkorn Memorial Hospital.

OBJECTIVE: To determine health related quality of life (QoL) of patients diagnosed with cervical intraepithelial neoplasia (CIN) and cervical cancer compared QoL among stages of cancer and to study the association between QoL and patients' characteristics. MATERIAL AND METHOD: The questionnaire elicited information and QoL using Functional Assessment of Cancer Therapy General (FACT-G) questionnaire. The study population was patients with a diagnosis of one of the four FIGO stages of cervical cancer RESULTS: One hundred seventy two patients completed the present study. The adjusted mean scores QoL was 78.76. There were no significant differences between FIGO stages on the global QoL and subscale. The authors found negative association between age and physical wellbeing scores (p = 0.049) and a positive association between age and emotional wellbeing scores (p = 0.004). Lower educational attainment was associated with higher emotional wellbeing scores (p = 0.004). CONCLUSION: For many patients, family, religion, or psycho-social support may be considered a necessity. The younger and better-educated groups may require more information and psycho-emotional support.

Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected].

PURPOSE: To compare survival in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with gefitinib 250 or 500 mg/day or standard methotrexate. PATIENTS AND METHODS: Four hundred eighty-six patients with recurrent SCCHN were randomly assigned to oral gefitinib 250 mg/day, gefitinib 500 mg/day, or methotrexate 40 mg/m(2) intravenously weekly. Primary end point was overall survival, secondary end points were objective response rate (ORR), safety, symptom improvement, and quality of life (QOL). Exploratory end points included association of efficacy with epidermal growth factor receptor gene copy number and other biomarkers. RESULTS: Neither gefitinib 250 nor 500 mg/day improved overall survival compared with methotrexate (hazard ratio [HR], 1.22; 95% CI, 0.95 to 1.57; P = .12; and HR, 1.12; 95% CI, 0.87 to 1.43; P = .39, respectively). In the gefitinib 250 mg/day, 500 mg/day, and methotrexate groups, respectively, median overall survival was 5.6, 6.0, and 6.7 months; ORRs (Response Evaluation Criteria in Solid Tumors) were 2.7%, 7.6% and 3.9%, with no statistically significant difference between either gefitinib arm and methotrexate. No unexpected adverse events were observed, except for tumor hemorrhage-type events with gefitinib (8.9%, gefitinib 250 mg/day; 11.4%, gefitinib 500 mg/day; 1.9%, methotrexate). QOL improvement rates (Functional Assessment of Cancer Therapy-Head & Neck total score) were 13.4%, 18.0%, and 6.0% for gefitinib 250 mg/day, 500 mg/day, and methotrexate, respectively. CONCLUSION: In patients with recurrent or metastatic SCCHN, while responses with gefitinib were seen, neither gefitinib 250 nor 500 mg/day improved overall survival compared with methotrexate. With the exception of tumor hemorrhage-type events with gefitinib, the adverse event profiles were generally consistent with those previously observed.

A two-year experience of implementing 3 dimensional radiation therapy and intensity-modulated radiation therapy for 925 patients in King Chulalongkorn Memorial Hospital.

BACKGROUND AND OBJECTIVE: Three dimensional conformal radiation therapy (3D CRT) and intensity-modulated radiation therapy (IMRT) have been implemented at Department of Therapeutic Radiation and Oncology, King Chulalongkorn Memorial Hospital (KCMH) since July 2005. This is the first study in Thailand to evaluate the pattern of care and utilization of 3D CRT and IMRT for treatment in each individual cancer. MATERIAL AND METHOD: Between July 2005 and July 2007, 925 newly diagnosed cancer patients underwent IMRT or 3D CRT at KCMH. The authors retrospectively reviewed the experience and utilization of 3D CRT and IMRT for each disease site and region. RESULTS: There were 471 males and 454 females. There were 332 patients (35.9%) treated with IMRT. Among the 332 IMRT patients, there were 100, 32 and 27 nasopharyngeal, lung and prostate cancers, respectively. On the contrary, 593 patients (64.1%) were treated with 3D CRT. Among these, breast, cervix and lung cancers were the most common diseases. Except for head and neck as well as genitourinary cancer 3D CRT was still the main technique used in more than 60% of the patients at KCMH. CONCLUSION: 3D CRT and IMRT have been successfully implemented at KCMH for 2 years. Three dimensional conformal radiation therapy was still the main technique used in more than 60% of the patients at KCMH. Prospective studies evaluating tumor control and treatment sequelae are expected.

A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results.

OBJECTIVE: Concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. This study was a preliminary result of a randomized two arms, prospective, open-label phase III trial comparing the activity and safety of the concurrent chemoradiation of Tegafur-Uracil and carboplatin or carboplatin alone in locally advanced cervical cancer. MATERIALS AND METHODS: The stage IIB-IIIB cervical cancer patients were randomized to have Tegafur-Uracil 225 mg/m(2)/day orally, 5 days a week and carboplatin 100 mg/m(2) IV over 30-60 min, weekly on day 1 concurrent with standard radiotherapy (Group A) or carboplatin alone concurrent with standard radiotherapy (Group B). RESULTS: Four hundred and sixty-nine patients were randomized to Group A (n=234) or Group B (n=235). The tumor response at 3-month follow-up time showed no significant difference. The only prognostic factor to improve the complete response rate was the hemoglobin level. The patients in Group A, who had Hb <10 gm/dL had the relatively better change to complete response of 1.48 compared to that in Group B (P 0.025, 95% CI 1.07, 2.04). No severe toxicity or adverse event had been reported. The median follow-up time for Group A and Group B was 12.6 and 11.8 months, respectively. There was no statistical difference in PFS and OS. CONCLUSION: Concurrent chemoradiation by Tegafur-Uracil and carboplatin showed no difference in tumor response rate or treatment toxicity compared to carboplatin alone. The combination drugs might have benefit in poor prognostic patients such as the baseline Hb <10 gm/dL.

Intensity-modulated radiation therapy in head-and-neck cancer, first report in Thailand.

OBJECTIVE: This is the first report in Thailand to evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of head-and-neck cancer. MATERIAL AND METHOD: From July 2005 to March 2006, eighteen patients with head and neck cancer were treated with IMRT, fourteen of which were nasopharyngeal cancer. The median age at diagnosis was 52 years (range 23-58 years). The treatment plan composed of two sequential plans for PTV-low risk (50Gy in 25 fractions) and PTV-high risk (20Gy in 10 fractions). Chemotherapy was given to 13 patients with locoregionally advanced disease (stage T3/T4 and N2/3) using cisplatin (n = 3) or carboplatin (n = 10) every 3 weeks during the course of radiation therapy. RESULTS: The median overall treatment time was 49 days (range, 43-57 days), and 77.8 percent of the patients completed 35 fractions within 50 days. The clinical complete response and partial response rates at 3 months after complete radiation were 71.4% and 28.6%, respectively. However at the median follow-up of 5.6 months, the complete response rate increased to 89%. Treatment break during RT range from 3 to 7 days, was observed in three patients. All of them received concurrent chemoradiation. No distant metastasis was noted. CONCLUSION: The authors' experience of using concurrent chemotherapy with IMRT for a cohort of patients with head and neck carcinoma showed a very high rate response rate at early follow-up. Long-term clinical outcome is expected.

Reducing radiation dose to pelvic small bowel in cervical cancer patients treated with Ir-192 intracavitary brachytherapy by using urinary bladder distension.

OBJECTIVES: Several techniques and devices have been used in an attempt to minimize radiation dose to gastrointestinal tract while giving pelvic radiation. We evaluated the effect of urinary bladder distension to displace pelvic small bowel out of intracavitary brachytherapy field to minimize radiation dose to small bowel in cervical cancer patients. MATERIAL AND METHOD: Eleven cervical cancer patients who received Ir-192 intracavitary brachytherapy with tandem and transverse ovoids were included in this study. Oral contrast material was used to visualize pelvic small bowel. Urinary bladder was distended by injection 125-200 ml. normal saline solution. Pelvic radiograph, anteroposterior and lateral view, was performed before and after bladder distention for brachytherapy treatment planning and comparing radiation dose at small bowel. RESULTS: The average maximum radiation dose at small bowel before and after bladder distension were 3123 cGy and 1998 cGy respectively. The summation of small bowel dose was reduced 54.17% (p = 0.002). CONCLUSION: Urinary bladder distension could effectively displace pelvic small bowel and reduce the radiation dose to small bowel from Ir-192 intracavitary brachytherapy in cervical cancer patients.

Reduced recurrence of late hemorrhagic radiation cystitis by WF10 therapy in cervical cancer patients: a multicenter, randomized, two-arm, open-label trial.

BACKGROUND AND PURPOSE: To evaluate the efficacy and the safety of WF10 as adjunct to standard treatment in the management of late hemorrhagic radiation cystitis compared to standard treatment alone. PATIENTS AND METHODS: Cervical cancer patients with Grade 2 or 3 late hemorrhagic radiation cystitis, were randomized and treated with WF10 0.5 ml/kg body weight, diluted in physiological saline or 5% dextrose water 250 ml, intravenous infusions over 2 h on 5 consecutive days, every 3 weeks for 2 cycles plus standard treatment (WF10 group) or standard treatment alone (control group). Fifty patients in each group were evaluated by questioning; urinalysis and cystoscopy during a 1 year follow up. RESULTS: At week 7, 37 patients (74%) in the WF10 group and 32 patients (64%) in the control group showed complete resolution in objective hematuria (P = 0.28). Significantly lower use of antibiotics (P = 0.002) and antispasmodics (P < 0.001) was found in the WF10 group. Among the responders, 24 patients (77%) in the control group experienced recurrent objective hematuria, whereas in the WF10 group only 17 patients (47%) experienced a recurrence (P = 0.01). Recurrence of objective hematuria occurred significantly faster in the control group as evidenced by Kaplan-Meier and log-rank statistics (P = 0.004), suggesting a long-term effect of WF10. Cystoscopy, at the end of the treatment period and after the one year follow up showed overall improvement without significant difference between two groups. No severe toxicity was monitored. CONCLUSIONS: WF10 therapy is a safe, non-invasive and convenient method in the management of late hemorrhagic radiation cystitis. WF10 therapy, as adjunct to standard treatment, has significantly reduced recurrence of objective hematuria, compared to standard treatment alone, during a one year follow up.

Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma.

PURPOSE: Intracavitary brachytherapy plays an important role in the treatment of cervical carcinoma. Previous results have shown controversy between the effect of dose rate on tumor control and the occurrence of complications. We performed a prospective randomized clinical trial to compare the clinical outcomes between low-dose-rate (LDR) and high-dose-rate (HDR) intracavitary brachytherapy for treatment of invasive uterine cervical carcinoma. METHODS AND MATERIALS: A total of 237 patients with previously untreated invasive carcinoma of the uterine cervix treated at King Chulalongkorn Memorial Hospital were randomized between June 1995 and December 2001. Excluding ineligible, incomplete treatment, and incomplete data patients, 109 and 112 patients were in the LDR and HDR groups, respectively. All patients were treated with external beam radiotherapy and LDR or HDR intracavitary brachytherapy using the Chulalongkorn treatment schedule. RESULTS: The median follow-up for the LDR and HDR groups was 40.2 and 37.2 months, respectively. The actuarial 3-year overall and relapse-free survival rate for all patients was 69.6% and 70%, respectively. The 3-year overall survival rate in the LDR and HDR groups was 70.9% and 68.4% (p = 0.75) and the 3-year pelvic control rate was 89.1% and 86.4% (p = 0.51), respectively. The 3-year relapse-free survival rate in both groups was 69.9% (p = 0.35). Most recurrences were distant metastases, especially in Stage IIB and IIIB patients. Grade 3 and 4 complications were found in 2.8% and 7.1% of the LDR and HDR groups (p = 0.23). CONCLUSION: Comparable outcomes were demonstrated between LDR and HDR intracavitary brachytherapy. Concerning patient convenience, the lower number of medical personnel needed, and decreased radiation to health care workers, HDR intracavitary brachytherapy is an alternative to conventional LDR brachytherapy. The high number of distant failure suggests that other modalities such as systemic concurrent or adjuvant chemotherapy might lower this high recurrence, especially in Stage IIB and IIIB.

Pattern of local-regional recurrence in patient with early breast cancer after mastectomy: an analysis of 357 cases at King Chulalongkorn Memorial Hospital.

A retrospective review was performed on 357 patients with early stage I-IIIA operable breast cancer who were treated with mastectomy and referred to the clinic at the Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between Jan 1991 and Dec 2001. Patients characteristics, treatment modalities and pattern of local and regional failure were evaluated. The median and mean age in the present study were 49 and 50.2 years, respectively. Stage I, II and IIIA were 10.9%, 79.6% and 9.5%, respectively. One hundred and ninety-seven patients (55.2%) received postoperative radiation therapy (RT). Adjuvant chemotherapy was given in 247 patients (69.2%) while 122 patients (34.2%) received adjuvant hormonal therapy. Sixty one patients (17.1%) received both adjuvant chemotherapy and hormonal therapy. However, 12.6% (45/357) did not receive any adjuvant treatment. Median follow up time was 42.6 months (range 6-136 months). Ipsilateral supraclavicular node and chest wall were the most common sites of local-regional recurrence. The chest wall recurrence rate was 10.4% (37/357), which was 16.9% (27/160) in the non postoperative radiation (No RT) group and 5.1% (10/197) in the postoperative radiation (RT) group. For ispilateral supraclavicular node, the recurrence rate was 10.6% (38/357), which was 15.6% (25/160) and 6.6% (13/197) for non RT and RT groups, respectively. The incidence of ipsilateral axilla, ipsilateral internal mammary node and ipsilateral infraclavicular node recurrence rate were 4.2%, 3.6% and 0.8%, respectively. Overall, chest wall and ipsilateral supraclavicular node were the most common sites of local-regional recurrence in early stage operable breast cancer who underwent mastectomy Postoperative adjuvant radiation therapy decreased the risk of local-regional recurrence.