Advanced imaging applications for locally advanced cervical cancer.

Advanced imaging approaches (computed tomography, CT; magnetic resonance imaging, MRI; 18F-fluorodeoxyglucose positron emission tomography, FDG PET) have increased roles in cervical cancer staging and management. The recent FIGO (International Federation of Gynecology and Obstetrics) recommendations encouraged applications to assess the clinical extension of tumors rather than relying on clinical examinations and traditional non-cross sectional investigations. MRI appears to be better than CT for primary tumors and adjacent soft tissue involvement in the pelvis. FDG-PET/CT has increased in usage with a particular benefit for whole body evaluation of tumor metabolic activity. The potential benefits of advanced imaging are assisting selection of treatment based upon actual disease extent, to adequately treat a tumor with minimal normal tissue complications, and to predict the treatment outcomes. Furthermore, sophisticated external radiation treatment and brachytherapy absolutely require advanced imaging for target localization and radiation dose calculation.

CT appearances of post-radiation livers in patients with unresectable cholangiocarcinoma.

OBJECTIVE: To characterize the computed tomographic (CT) findings of post-radiation livers and the interval changes in patients with unresectable cholangiocarcinoma. MATERIAL AND METHOD: Thirteen patients with unresectable cholangiocarcinoma who received concurrent chemoradiation with conformal radiotherapy technique (50 to 66 Gy, 2 Gy/fraction) were included in the present study. CT at pre-radiation and sequential follow-up at 1, 3, 6, 9 and 12 months were retrospectively reviewed by two abdominal radiologists to identify CT characteristics of post-radiation liver and the interval changes. RESULTS: CT at pre-radiation and sequential follow-up at 1, 3, 6, 9 and 12 months were available in 92.3%, 100%, 76.9%, 53.8%, 30.8% and 23.1%, respectively. Post-radiation livers showed sharply-delineated, hypodense radiation areas, which were well related with the isodose line of 35 to 56 Gy (mean = 44.4 +/- 6.55 Gy). These radiation areas were mostly appreciated on portal venous phase at 1-month follow-up study in 12 of 13 (92.3%) patients and these were gradually less defined in subsequent studies. Progressive decrease size of radiation areas with persistent enhancement on delayed phase images were recognized. Progression of hepatic cortical irregularity was seen in four (30.8%) patients, as well as pulmonary fibrosis of lung bases. CONCLUSION: Post-radiation liver in patients with unresectable cholangiocarcinoma showed a sharply-defined, hypodense radiation area, which was mostly appreciated in 1-month follow-up CT and was gradually less defined in subsequent studies with evidence of progressive atrophic change.

Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix.

PURPOSE: To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer. PATIENTS AND METHODS: Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2) weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m(2) on day 1, plus gemcitabine, 1,000 mg/m(2) on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A). RESULTS: Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A. CONCLUSION: Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients.

BACKGROUND: Sensorineural hearing loss (SNHL) is one of the major long term side effects from radiation therapy (RT) in nasopharyngeal cancer (NPC) patients. This study aims to review the incidences of SNHL when treating with different radiation techniques. The additional objective is to determine the relationship of the SNHL with the radiation doses delivered to the inner ear. METHODS: A retrospective cohort study of 134 individual ears from 68 NPC patients, treated with conventional RT and IMRT in combination with chemotherapy from 2004-2008 was performed. Dosimetric data of the cochlea were analyzed. Significant SNHL was defined as >15 dB increase in bone conduction threshold at 4 kHz and PTA (pure tone average of 0.5, 1, 2 kHz). Relative risk (RR) was used to determine the associated factors with the hearing threshold changes at 4 kHz and PTA. RESULTS: Median audiological follow up time was 14 months. The incidence of high frequency (4 kHz) SNHL was 44% for the whole group (48.75% in the conventional RT, 37% with IMRT). Internal auditory canal mean dose of >50 Gy had shown a trend to increase the risk of high frequency SNHL (RR 2.02 with 95% CI 1.01-4.03, p=0.047). CONCLUSION: IMRT and radiation dose limitation to the inner ear appeared to decrease SNHL.

l-[METHYL-(11)C] methionine positron emission tomography for target delineation in malignant gliomas: impact on results of carbon ion radiotherapy.

PURPOSE: To assess the importance of (11)C-methionine (MET)-positron emission tomography (PET) for clinical target volume (CTV) delineation. METHODS AND MATERIALS: This retrospective study analyzed 16 patients with malignant glioma (4 patients, anaplastic astrocytoma; 12 patients, glioblastoma multiforme) treated with surgery and carbon ion radiotherapy from April 2002 to Nov 2005. The MET-PET target volume was compared with gross tumor volume and CTV, defined by using computed tomography/magnetic resonance imaging (MRI). Correlations with treatment results were evaluated between positive and negative extended volumes (EVs) of the MET-PET target for CTV. RESULTS: Mean volumes of the MET-PET targets, CTV1 (defined by means of high-intensity volume on T2-weighted MRI), and CTV2 (defined by means of contrast-enhancement volume on T1-weighted MRI) were 6.35, 264.7, and 117.7 cm(3), respectively. Mean EVs of MET-PET targets for CTV1 and CTV2 were 0.6 and 2.2 cm(3), respectively. The MET-PET target volumes were included in CTV1 and CTV2 in 13 (81.3%) and 11 patients (68.8%), respectively. Patients with a negative EV for CTV1 had significantly greater survival rate (p = 0.0069), regional control (p = 0.0047), and distant control time (p = 0.0267) than those with a positive EV. Distant control time also was better in patients with a negative EV for CTV2 than those with a positive EV (p = 0.0401). CONCLUSIONS: For patients with malignant gliomas, MET-PET has a possibility to be a predictor of outcome in carbon ion radiotherapy. Direct use of MET-PET fused to planning computed tomography will be useful and yield favorable results for the therapy.

Accelerated hyperfractionated radiotherapy for cervical cancer: multi-institutional prospective study of forum for nuclear cooperation in Asia among eight Asian countries.

PURPOSE: To evaluate the toxicity and efficacy of accelerated hyperfractionated radiotherapy (RT) for locally advanced cervical cancer. METHODS AND MATERIALS: A multi-institutional prospective single-arm study was conducted among eight Asian countries. Between 1999 and 2002, 120 patients (64 with Stage IIB and 56 with Stage IIIB) with squamous cell carcinoma of the cervix were treated with accelerated hyperfractionated RT. External beam RT consisted of 30 Gy to the whole pelvis, 1.5 Gy/fraction twice daily, followed by 20 Gy of pelvic RT with central shielding at a dose of 2-Gy fractions daily. A small bowel displacement device was used with the patient in the prone position. In addition to central shielding RT, intracavitary brachytherapy was started. Acute and late morbidities were graded according to the Radiation Therapy Oncology Group and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: The median overall treatment time was 35 days. The median follow-up time for surviving patients was 4.7 years. The 5-year pelvic control and overall survival rate for all patients was 84% and 70%, respectively. The 5-year pelvic control and overall survival rate was 78% and 69% for tumors > or = 6 cm in diameter, respectively. No treatment-related death occurred. Grade 3-4 late toxicities of the small intestine, large intestine, and bladder were observed in 1, 1, and 2 patients, respectively. The 5-year actuarial rate of Grade 3-4 late toxicity at any site was 5%. CONCLUSION: The results of our study have shown that accelerated hyperfractionated RT achieved sufficient pelvic control and survival without increasing severe toxicity. This treatment could be feasible in those Asian countries where chemoradiotherapy is not available.

Angiogenesis in stage IIIB squamous cell carcinoma of uterine cervix: reproducibility of measurement and preliminary outcome as a prognostic factor.

This study was performed to determine the reliability and replicability of IMD analysis using the Factor VIII immunohistochemical method. The following purpose was determining the relationship between IMD and clinical outcome in individual cervical cancer patient treated with radical radiotherapy. Twenty nine patients with stage IIIB cervical cancer were enrolled. Phase one was performed by using two pieces of tissue biopsy from different locations in the tumor from each patient. The IMD value was counted by the two pathologists after counterstaining by Factor VIII immunohistochemical method. No interobserver disagreement between the two pathologists was found (correlation coefficient = 0.92, 95% CI 0.82-0.96 for the first piece of tissue and 0.85, 95% CI 0.67-0.93 for the second piece). There was no variability in the IMD between the 2 pieces of tissue specimens from different locations of the tumor Phase two followed to evaluate the relationship between IMD and clinical outcome in individual cervical cancer patients. Because of the small sample size, different patients' characteristics, different treatment protocol and short term follow up, there is no statistically significant conclusion.

Hyperthermia in combination with radiation therapy for treatment of advanced inoperable breast cancer.

Twelve breast cancer patients with locally advanced inoperable lesions were studied. Six cases had received chemotherapy, 6 had not. Most of the tumors were ulcerative lesions with an average size of 11.5 cm. The patients were treated with 43 degrees C hyperthermia once or twice a week together with radiation at a dose of 20-70 Gy. Six of them were also treated with concurrent chemotherapy. Two cases responded completely (17%) and 10 cases responded partially (83%). The result indicates that the combination of hyperthermia and radiation, with or without chemotherapy, might be a good treatment option for locally advanced inoperable breast cancer, especially for patients who have had failure or contraindication to chemotherapy. It is an effective treatment for palliation of local symptoms, showing a tendency to achieve local control of large, ulcerative advanced breast lesions especially when such treatment is followed by salvage surgery.

Concurrent radiation therapy and irinotecan in stage IIIB cervical cancer.

UNLABELLED: The present study was to evaluate the efficacy and toxicity of concurrent radiation therapy and irinotecan in patients with stage IIIB cervical cancer. Fifteen patients with no prior radiation therapy and chemotherapy were enrolled in the study. These patients received 50 Gy of external radiation to whole the pelvis, 50 Gy with an additional dose of 6-10 Gy to the parametrium and 1 or 2 sessions of intracavitary Cesium-137. Weekly intravenous infusion of 40 mg/m2 irinotecan was given for 5 cycles during the course of radiation therapy. Of 14 evaluable patients, 4 (28.6%) achieved complete response and 7 (50.0%) achieved partial response. Treatment-related toxicity included grade 1 & 2 anemia, grade 1 & 2 leucopenia, grade 1 & 2 neutropenia and 7.1 per cent grade 3 diarrhea. No grade 4 toxicity or treatment-related death occurred in the present study. CONCLUSION: Irinotecan is a promising new cytotoxic agent in treatment concurrently with radiation therapy in newly diagnosed locally advanced cervical cancer. This modality of treatment appeared to be effective with acceptable toxicity.