Who should receive single-fraction palliative radiotherapy for gastric cancer bleeding?: An exploratory analysis of a multicenter prospective observational study (JROSG 17-3).

Purpose: Although the Palliative Prognostic Index (PPI) has been used to predict survival in various cancers, to our knowledge, no study has examined its applicability in gastric cancer. This study aimed to determine the baseline PPI cutoff value for recommending single-fraction radiotherapy in patients with bleeding gastric cancer. Materials and methods: This was a secondary analysis of the Japanese Radiation Oncology Study Group (JROSG) 17-3, a multicenter prospective study of palliative radiotherapy for bleeding gastric cancer. Discrimination was evaluated using a time-dependent receiver operating characteristic curve, and the optimal cutoff value was determined using the Youden index. A calibration plot was used to assess the agreement between predicted and observed survival. Results: We enrolled 55 patients in JROSG 17-3. The respective median survival times were 6.7, 2.8, and 1.0 months (p = 0.021) for patients with baseline PPI scores of ≤ 2, 2 < PPI ≤ 4, and PPI > 4. The areas under the curve for predicting death within 2, 3, 4, and 5 months were 0.813, 0.787, 0.775, and 0.721, respectively. The negative predictive value was highest when survival < 2 months was predicted and the Youden index was highest when the cutoff PPI value was 2. The calibration curve showed a reasonable agreement between the predicted and observed survival. Conclusion: Baseline PPI is useful for estimating short-term prognosis in patients treated with palliative radiotherapy for gastric cancer bleeding. A cutoff PPI value of 2 for estimating survival ≤ 2 months should be used to recommend single-fraction radiotherapy.

Relationship between changes in quality of life and genitourinary toxicity grade after brachytherapy with I-125 alone for localised prostate cancer.

Background: The relationship between the grading of toxicities based on toxicity criteria and longitudinal changes in quality of life (QOL) scores after permanent prostate brachytherapy (PPB) for localized prostate cancer remains unclear. This study aimed to evaluate these relationships. Materials and methods: We assessed 107 patients treated with PPB using Iodine-125 alone from May 2007 to April 2010. Disease-specific QOL scores before PPB and at 1, 3, 6, 12, and 24 months after PPB were retrospectively evaluated with the Expanded Prostate Cancer Index Composite (EPIC), focusing on urinary domains. Toxicities were graded using the Radiation therapy oncology group and the European organization for research and treatment of cancer toxicity criteria. Results: The median follow-up duration was 116 (range 18-148) months. Thirty-four patients (31.8%) developed grade ≥ 2 acute genitourinary (GU) toxicities; six (5.6%) developed grade ≥ 2 late GU toxicities. The general urinary domain score dropped significantly at 1 month (77.1 ± 14.1) post-PPB compared to the baseline score (92.2 ± 8.2), and then gradually returned to the baseline level by 12 months (93.7 ± 8.3) post-PPB. Reductions in the general urinary domain scores, including its subscale scores at 1, 3, and 6-months post-PPB were significantly greater among patients with grade ≥ 2 GU toxicity than among those with grade 0-1 GU toxicity. Changes in urinary domain scores demonstrated a close relationship with acute GU toxicity grades after PPB. Conclusions: Longitudinal assessments of the EPIC QOL scores provided additional information regarding time-course changes in GU toxicities after PPB.

Treatment response after palliative radiotherapy for bleeding gastric cancer: a multicenter prospective observational study (JROSG 17-3).

BACKGROUND: Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. METHODS: Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) bleeding response rate at 4 weeks. Response entailed all of the following criteria: (i) hemoglobin levels ≥ 8.0 g/dL; (ii) 7 consecutive days without blood transfusion anytime between enrollment and blood sampling; and (iii) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or re-irradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. RESULTS: We enrolled 55 patients from 15 institutions. The ITT response rates were 47%, 53%, and 49% at 2, 4, and 8 weeks, respectively. The per-protocol response rates were 56%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Neither response nor BED (α/ß = 10) predicted overall survival. Multivariable Fine-Gray model showed that BED was not a significant predictor of response. Univariable Cox model showed that BED was not significantly associated with re-bleeding. Grades 1, 2, 3, and, ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSIONS: The per-protocol response rate increased to 90% during the 8-week follow-up. The frequent occurrence of death starting shortly after enrollment lowered the ITT response rate. BED was not associated with survival, bleeding response, or re-bleeding.

Hemostatic Effect of Palliative Radiation Therapy in Preventing Blood Transfusions from Bleeding Occurring within Advanced Gastric Cancer.

Purpose: To report the hemostatic effects of palliative radiation therapy (RT) for the prevention of blood transfusions (BT) in patients with advanced gastric cancer (AGC). Methods and Materials: Twenty-eight patients who received palliative three-dimensional conformal RT for hemostasis of gastric bleeding were retrospectively assessed in a study conducted in Japan. The median follow-up was 143.5 days. Changes in hemoglobin (Hb) levels were compared at the beginning of RT and four weeks later. Blood transfusion-free survival (BTFS) and overall survival (OS) were measured from the beginning of RT. Treatment toxicity was evaluated within 60 days of RT initiation. Results: No statistically significant decrease in Hb level was observed four weeks after RT. Twenty-eight patients did not receive BT within a month after RT, of whom three died within a month; 6/28 patients (21%) received BT at a median interval of 99.5 days following RT. The one-year BTFS and OS rates for all patients were 69% and 12%, respectively. The one-year BTFS was statistically significantly higher in 17 patients treated with a biologically effective dose (BED)10 of 39 Gy (30 Gy in 10 fractions) (78%) compared with six patients treated with a BED10 of 48 Gy (40 Gy in 20 fractions) (25%). Grade 1 and 2 nausea (n = 11) and a Grade 2 increase in alanine aminotransferase (n = 1) were observed. One patient died of Grade 5 hemorrhage. Conclusions: Palliative RT is an effective treatment to prevent BT for bleeding occurring within AGC. Specifically, a fractionation regimen of 30 Gy in 10 fractions (a BED10 of 39 Gy) has a more durable hemostatic effect and thus should be considered for better prognosis.

The 5-year outcomes of moderately hypofractionated radiotherapy (66 Gy in 22 fractions, 3 fractions per week) for localized prostate cancer: a retrospective study.

BACKGROUND: Hypofractionated radiotherapy using fewer and larger fractional doses may be more beneficial than conventional external-beam radiotherapy for localized prostate cancer. We evaluated the 5-year outcomes of moderately hypofractionated radiotherapy for localized prostate cancer. METHODS: We retrospectively evaluated 195 patients with localized prostate cancer (T1-3N0M0) who underwent intensity-modulated radiotherapy (IMRT) (66 Gy delivered in fractions of 3 Gy every other weekday) between May 2005 and December 2011. Patients received androgen deprivation therapy depending on the perceived intermediate or high risk of their disease. A prostate-specific antigen nadir +2.0 ng/ml indicated biochemical failure. We assessed toxicity using the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and patient-reported outcomes using the Expanded Prostate Cancer Index Composite (EPIC). RESULTS: The risk classifications (proportion) were low risk (13.8%), intermediate risk (35.9%), and high risk (50.3%). The median follow-up was 69 months. Thirteen (6.66%) patients experienced biochemical failure within a median of 40 months (interquartile range, 25-72 months). The 5-year overall survival rate and no biological evidence of disease rate were 97.7% and 92.4%, respectively. Based on the RTOG/EORTC criteria, no patient experienced acute or late toxicity of grade 3 or higher. The EPIC scores revealed significant differences in the average value of all domains (p < 0.01). At 1 month postradiotherapy completion, the general urinary and bowel domain scores had decreased, but these scores returned to baseline level by 3 months post radiotherapy. CONCLUSIONS: The moderately hypofractionated radiotherapy protocol yielded short-term satisfactory clinical outcomes with acceptable toxicity.

Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403.

PURPOSE: To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients. RESULTS: Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed. CONCLUSIONS: Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.

Correlation between the changes in the EPIC QOL scores and the dose-volume histogram parameters in high-dose-rate brachytherapy combined with hypofractionated external beam radiation therapy for prostate cancer.

OBJECTIVE: To evaluate the correlations between the changes in the quality-of-life scores and the dose-volume histogram parameters in patients receiving high-dose-rate brachytherapy combined with hypofractionated external beam radiation therapy for localized prostate cancer. METHODS: Among the patients who were treated with high-dose-rate brachytherapy (18 Gy in two fractions) combined with hypofractionated external beam radiation therapy (45 Gy in 15 fractions), the data of 118 consecutive patients followed up for >24 months were prospectively analyzed. The disease-specific quality of life was assessed using the expanded prostate cancer index composite, and the acute genitourinary toxicities were graded based on the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Toxicity criteria. RESULTS: The median follow-up duration was 58 months (42-84 months). Thirteen patients (11%) developed Grade 2 or more severe acute genitourinary toxicities. The score for the general urinary domain of the expanded prostate cancer index composite quality-of-life scores dropped significantly at 1 month after high-dose-rate brachytherapy, and then returned to the baseline level by 3 months. Among the dose-volume histogram parameters, the reduction of the expanded prostate cancer index composite quality-of-life scores for the general urinary domain and its subscales at 12 months after high-dose-rate brachytherapy was significantly greater in the patients for whom the V150 or urethral D10 was within the upper 20% of the range than in those in whom the values of these dosimetric parameters were within the lower 20% of the range. CONCLUSION: The high-dose area of the prostate gland (V150) or urethra (D10) might influence the quality-of-life scores for the urinary domain and its subscales over the long term.

Radiation-induced dimer formation of EGFR: implications for the radiosensitizing effect of cetuximab.

AIM: The purpose of this study was to investigate whether radiation induces ligand-independent dimerization of epidermal growth factor receptor (EGFR) and explore the possible role of radiation-induced receptor dimerization in the radiosensitizing effect of cetuximab. MATERIALS AND METHODS: The human vulvar squamous cell carcinoma cell line A431 was used. The dimerization and activation of EGFR were quantified using immunoprecipitation, a western blotting analysis, and a chemical cross-linking analysis with dithiobis-sulfosuccinimidyl propionate. RESULTS: Irradiation at a dose of 2 Gy induced the autophosphorylation of EGFR. Consistent with autophosphorylation, a 360-kDa polypeptide, corresponding to the size of the EGFR dimer, was detected in addition to an EGFR monomer. Radiation also induced hetero-dimerization between EGFR and HER2/neu. Cetuximab combined with radiation inhibited radiation-induced autophosphorylation of EGFR, and inhibited radiation-induced homo-dimerization of EGFR. However, cetuximab incompletely inhibited radiation-induced hetero-dimerization between EGFR and HER2. CONCLUSION: The results of this investigation suggest that radiation-induced homo- and/or hetero-dimerization between EGFR and/or HER2 might be involved in the radioresponse of cancer cells.

Updated therapeutic strategy for adult low-grade glioma stratified by resection and tumor subtype.

The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ≥90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy.

The role of chemoradiotherapy in patients with unresectable T4 breast tumors.

PURPOSE: Unresectable T4 tumors of the breast are usually treated with systemic therapies, while the role of local therapies remains debatable. This study aims to evaluate the effectiveness of chemoradiotherapy as a part of T4 breast cancer treatment, and to assess the role of local radiotherapies in patients with unresectable T4 breast tumors. MATERIALS/METHODS: Between February 1998 and June 2010, 39 unresectable T4 breast tumors were treated with chemoradiotherapy at our institutes. Clinical stages included stage IIIB (n = 15), stage IIIC (n = 3), and stage IV (n = 21). Twenty-one cases had undergone previous systemic therapies, whereas the remaining 18 cases reported no history of previous treatment. Radiation doses of 59-66 Gy (median 60 Gy) were administered to the breast in addition to concurrent chemotherapies. Acute adverse effects were assessed on a weekly basis during treatment to 2 weeks after completion of treatment, and were scored by the Common Terminology Criteria for Adverse Events v3.0. Treatment response was assessed at 1 month after completion of chemoradiotherapy. Statistical analysis of survival was calculated using the Kaplan-Meier method. RESULTS: Chemoradiotherapy was completed in all cases. Greater than grade 3 hematological toxicities were observed with regard to lymphocytes (33%), platelets (8%), neutrophils (3%), and hemoglobin (3%). Greater than grade 3 nonhematologic toxicities included chemoradiation dermatitis (23%) and pneumonitis (5%). Sixteen T4 tumors (41%) achieved complete response, whereas 23 (59%) achieved partial response. All patients were treated with chemotherapy and/or endocrine therapy following chemoradiotherapy. The median follow-up period was 20 months (range 3-96 months). Nineteen patients died because of progressive breast cancer. Infield recurrence or relapse was observed in 11 cases during the course of treatment, but only 3 cases were symptomatic. The 2-year overall local control rate was 73.6%, and the survival rate was 65.9%. CONCLUSION: Chemoradiotherapy represents a viable option for local treatment of unresectable T4 breast tumors.

Patterns of intracranial glioblastoma recurrence after aggressive surgical resection and adjuvant management: retrospective analysis of 43 cases.

The present retrospective study evaluated the recurrence patterns after aggressive surgical removal of intracranial glioblastomas in 43 consecutive adult patients. The resection rate of the enhanced lesion on magnetic resonance imaging was 100% and 95-99% in 22 and 21 cases, respectively. All patients received postoperative fractionated radiotherapy (60 Gy in 30 fractions) with additional chemotherapy (25 cases) or vaccine therapy (18 cases). During follow-up (median 17 months), tumor recurrence was identified in 33 patients, most frequently regional within the wall of the resection cavity (20 cases). No clinical factor differed significantly between the groups of patients with regional or marginal tumor progression (N = 22) and patients with distant or multiple recurrences (N = 8). Progression-free survival did not differ significantly between these two groups (p = 0.27). However, overall survival was significantly longer (p = 0.04) in patients with regional or marginal tumor progression, and constituted 90% and 54% at 1 and 2 years after surgery, respectively, compared to 75% and 0% in patients with distant or multiple recurrences. Aggressive surgical resection and adjuvant management of intracranial glioblastoma may change its recurrence pattern. Tumor progression appears in the wall of the resection cavity or within 2 cm from its margin in approximately half of patients.

Dropped head syndrome induced by chemoradiotherapy for nasopharyngeal carcinoma: a case report.

'Dropped head syndrome' (DHS) is characterized by severe weakness of the muscles of the back of the neck, resulting in chin-on-chest deformity. Dropped head syndrome induced by radiotherapy is very rare. We report a case of DHS following chemoradiotherapy with a total of 64.8 Gy in 36 fractions for nasopharyngeal carcinoma.

Long-term follow-up of a randomized Phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021).

OBJECTIVE: Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed. METHODS: Eligible patients were <75 years old and performance status 0-2, and had Stages II-IVA esophageal cancer. For arm A (short-term infusion), cisplatin 70 mg/m(2) Days 1 and 29 and 5-fluorouracil 700 mg/m(2) Days 1-5 and 29-33 were given concurrently with radiotherapy of 60 Gy/30 fr/7 weeks (1 week split). For arm B (protracted infusion), cisplatin 7 mg/m(2) Days 1-5, 8-12, 29-33 and 36-40, and 5-fluorouracil 250 mg/m(2) Days 1-14 and 29-42 were given with the same radiotherapy. Two cycles of consolidation cisplatin/5-fluorouracil chemotherapy were given to both arms. RESULTS: Between 2001 and 2006, 91 patients were enrolled; 46 were randomized to arm A, and 45 to arm B. The 2- and 5-year overall survival rates for arm A were 46 and 35% (95% confidence interval: 22-48%), while those for arm B were 44 and 22% (11-35%), respectively. Excluding four patients with early death, seven (17%) patients in arm A and eight (18%) in arm B showed late toxicities of Grade 3 or more. Most of the toxicities were cardiac or pleural toxicities. Patients with severe late toxicities often had coexistent hypothyroidism. There were three patients with a secondary malignancy possibly related to treatment. CONCLUSIONS: Low-dose protracted infusion chemotherapy with radiotherapy is not superior to full-dose short-term infusion chemotherapy with radiotherapy for esophageal cancer. Late toxicities, including cardiac and pleural toxicities, hypothyroidism and secondary malignancy, should be carefully monitored.

Insufficiency fractures after pelvic radiation therapy for uterine cervical cancer: an analysis of subjects in a prospective multi-institutional trial, and cooperative study of the Japan Radiation Oncology Group (JAROG) and Japanese Radiation Oncology Study Group (JROSG).

PURPOSE: To investigate pelvic insufficiency fractures (IF) after definitive pelvic radiation therapy for early-stage uterine cervical cancer, by analyzing subjects of a prospective, multi-institutional study. MATERIALS AND METHODS: Between September 2004 and July 2007, 59 eligible patients were analyzed. The median age was 73 years (range, 37-84 years). The International Federation of Gynecologic Oncology and Obstetrics stages were Ib1 in 35, IIa in 12, and IIb in 12 patients. Patients were treated with the constant method, which consisted of whole-pelvic external-beam radiation therapy of 50 Gy/25 fractions and high-dose-rate intracavitary brachytherapy of 24 Gy/4 fractions without chemotherapy. After radiation therapy the patients were evaluated by both pelvic CT and pelvic MRI at 3, 6, 12, 18, and 24 months. Diagnosis of IF was made when the patients had both CT and MRI findings, neither recurrent tumor lesions nor traumatic histories. The CT findings of IF were defined as fracture lines or sclerotic linear changes in the bones, and MRI findings of IF were defined as signal intensity changes in the bones, both on T1- and T2-weighted images. RESULTS: The median follow-up was 24 months. The 2-year pelvic IF cumulative occurrence rate was 36.9% (21 patients). Using Common Terminology Criteria for Adverse Events version 3.0, grade 1, 2, and 3 IF were seen in 12 (21%), 6 (10%), and 3 patients (5%), respectively. Sixteen patients had multiple fractures, so IF were identified at 44 sites. The pelvic IF were frequently seen at the sacroileal joints (32 sites, 72%). Nine patients complained of pain. All patients' pains were palliated by rest or non-narcotic analgesic drugs. Higher age (>70 years) and low body weight (<50 kg) were thought to be risk factors for pelvic IF (P=.007 and P=.013, Cox hazard test). CONCLUSIONS: Cervical cancer patients with higher age and low body weight may be at some risk for the development of pelvic IF after pelvic radiation therapy.

Treatment outcome of medium-dose-rate intracavitary brachytherapy for carcinoma of the uterine cervix: comparison with low-dose-rate intracavitary brachytherapy.

PURPOSE: To evaluate and compare the efficacy of medium-dose-rate (MDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for uterine cervical cancer. METHODS AND MATERIALS: We evaluated 419 patients with squamous cell carcinoma of the cervix who were treated by radical radiotherapy with curative intent at Tokyo Women's Medical University from 1969 to 1999. LDR was used from 1969 to 1986, and MDR has been used since July 1987. When compared with LDR, fraction dose was decreased and fraction size was increased (1 or 2 fractions) for MDR to make the total dose of MDR equal to that of LDR. In general, the patients received a total dose of 60 to 70 Gy at Point A with external beam radiotherapy combined with brachytherapy according to the International Federation of Gynecology and Obstetrics stage. In the LDR group, 32 patients had Stage I disease, 81 had Stage II, 182 had Stage III, and 29 had Stage IVA; in the MDR group, 9 patients had Stage I disease, 19 had Stage II, 55 had Stage III, and 12 had Stage IVA. RESULTS: The 5-year overall survival rates for Stages I, II, III, and IVA in the LDR group were 78%, 72%, 55%, and 34%, respectively. In the MDR group, the 5-year overall survival rates were 100%, 68%, 52%, and 42%, respectively. No significant statistical differences were seen between the two groups. The actuarial rates of late complications Grade 2 or greater at 5 years for the rectum, bladder, and small intestine in the LDR group were 11.1%, 5.8%, and 2.0%, respectively. The rates for the MDR group were 11.7%, 4.2%, and 2.6%, respectively, all of which were without statistical differences. CONCLUSION: These data suggest that MDR ICBT is effective, useful, and equally as good as LDR ICBT in daytime (about 5 hours) treatments of patients with cervical cancer.

Prospective multi-institutional study of definitive radiotherapy with high-dose-rate intracavitary brachytherapy in patients with nonbulky (<4-cm) stage I and II uterine cervical cancer (JAROG0401/JROSG04-2).

PURPOSE: To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study. METHODS AND MATERIALS: Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBT of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy(10) (α/ß = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review. RESULTS: Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6-39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7-72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%-100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%-98%) and 95% (95% CI, 89%-100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade ≥ 1) were 18% (95% CI, 8%-28%) for large intestine/rectum, 4% (95% CI, 0%-8%) for small intestine, and 0% for bladder. No Grade ≥ 3 cases were observed for genitourinary/gastrointestinal late complications. CONCLUSIONS: These results suggest that definitive radiotherapy using HDR-ICBT with a low cumulative dose schedule (BED, 62 Gy(10) at point A) can provide excellent local control without severe toxicity in nonbulky (<4-cm) early-stage cervical cancer.

[A case of malignant peritoneal mesothelioma successfully treated with concurrent chemoradiotherapy].

Malignant peritoneal mesothelioma is extremely rare, and its prognosis is poor. The median survival period is said to be approximately one year after diagnosis. We report a case of recurrent malignant peritoneal mesothelioma treated with concurrent chemoradiotherapy (CCRT). The patient has been alive for six years without recurrence. This report seems to be the first that indicates CCRT to be useful for peritoneal mesothelioma. The patient was a 21-year-old woman who underwent emergency surgery of the in acute abdomen at another hospital. The resected tumor was 18 cm in size and pathological examination revealed that it was a malignant mesothelioma of the epithelioid type. CAP therapy (cyclophosphamide+adriamycine+cisplatin)+CPT-11 administration was given only one course, and the patient was then transferred to our hospital. She underwent resection of the residual disease and six courses of TC therapy (paclitaxel+carboplatin) as adjuvant chemotherapy. Twelve months after chemotherapy, pelvic recurrence occurred. We attempted surgery but only biopsy could be performed because of a pelvic wall invasion. The patient underwent CCRT with weekly cisplatin. The tumor was reduced by irradiation of 50. 4 Gy and disappeared after 6 months. No recurrence has been found six years since the last treatment. CCRT might be effective against malignant peritoneal mesothelioma of the epithelioid type.

Evaluation of anxiety and salivary chromogranin a secretion in women receiving breast conserving surgery followed by radiation therapy.

We conducted a prospective study to assess the anxiety and salivary Chromogranin A (CgA), which is considered to be a biomarker of the stress response, in outpatients receiving breast conserving surgery followed by radiation therapy (RT) to the whole breast. Fifty consecutive patients who received whole-breast RT were enrolled in this study. The anxiety levels were measured by the State-Trait Anxiety Inventory (STAI) at the beginning of RT (baseline), 30 Gy, completion of RT, and 1 and 3 months after RT. Salivary CgA levels were also measured at the same time. The mean state anxiety score for all patients was 46.16 with a standard error (SE) of 1.57 at the beginning of RT (baseline) which continued to decline during and after RT. It reached its lowest score with 36.34 ± 1.56 at 3 months after RT (p < 0.0001). The mean trait anxiety score for all patients was 43.10 ± 1.54 at baseline and remained constant during RT but began to decline after completion of RT and reached a low level at 3 months after RT (p = 0.0021). The mean salivary CgA concentration for all patients demonstrated no consistent trends over time, but at 30 Gy the concentration showed a significant decreasing pattern (p = 0.0473). Salivary CgA concentrations and state anxiety and trait anxiety scores at all time points showed no correlation. The mean anxiety scores measured by STAI showed no positive correlation with salivary CgA concentration for breast cancer patients undergoing radiation therapy following breast conserving surgery.

Biliary anatomy on 3D MRCP: Comparison of volume-rendering and maximum-intensity-projection algorithms.

PURPOSE: To compare volume-rendering (VR) and maximum-intensity-projection (MIP) of three-dimensional T2-weighted turbo spin-echo magnetic resonance cholangiopancreatography using a free-breathing navigator-triggered prospective acquisition correction (3D-TSE-PACE-MRCP) to define biliary anatomies. MATERIALS AND METHODS: VR and MIP images of 3D-TSE-PACE-MRCP for 102 patients were retrospectively evaluated. Interpretation of cystic duct variation and biliary branching patterns of each image were recorded independently by two radiologists in a blinded fashion. Interpretation confidence on a five-point scale was compared using the Wilcoxon signed-rank test. The McNemar test was used to compare the accuracies of each reformation with the reference standard obtained by consensus interpretation of both the images and source images. RESULTS: The reference standard identified all biliary bifurcations and 95 of 102 cystic duct confluences (93.1%). VR findings agreed with the reference standard findings more often than MIP with regard to cystic duct variation (94 [92.2%] vs. 76 [74.5%], P<0.01) while there was no significant difference for biliary branching patterns (99 [97.1%] vs. 92 [90.2%], P=0.092). The mean confidence score was significantly higher with VR than MIP with regard to both cystic duct variation and biliary branching patterns (3.7 vs. 2.4; P<0.01; 4.1 vs. 3.3; P<0.01). CONCLUSION: VR reformation of 3D-TSE-PACE-MRCP defines biliary anatomies more accurately than MIP.