Survey of current practices from an international task force for gynecological stereotactic ablative radiotherapy.

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) is an effective treatment that improves local control for many tumours. However, the role of SABR in gynecological cancers (GYN) has not been well-established. We hypothesize that there exists considerable variation in GYN-SABR practice and technique. The goal of this study is to describe clinical and technical factors in utilization of GYN-SABR among 11 experienced radiation oncologists. MATERIALS AND METHODS: A 63 question survey on GYN-SABR was sent to 11 radiation oncologists (5 countries) who have published original research, conducted trials or have an established program at their institutions. Responses were combined and analyzed at a central institution. RESULTS: Most respondents indicated that salvage therapy (non-irradiated or re-irradiated field) for nodal (81%) and primary recurrent disease (91%) could be considered standard options for SABR in the setting of inability to administer brachytherapy. All other indications should be considered on clinical trials. Most would not offer SABR as a boost in primary treatment off-trial without absolute contraindications to brachytherapy. Multi-modality imaging is often (91%) used for planning including PET, CT contrast and MRI. There is a wide variation for OAR tolerances however small bowel is considered the dose-limiting structure for most experts (91%). Fractionation schedules range from 3 to 6 fractions for nodal/primary definitive and boost SABR. CONCLUSIONS: Although SABR has become increasingly standard in other oncology disease sites, there remains a wide variation in both clinical and technical factors when treating GYN cancers. Nodal and recurrent disease is considered a potential indication for SABR whereas other indications should be offered on clinical trials. This study summarizes SABR practices among GYN radiation oncologists while further studies are needed to establish consensus guidelines for GYN-SABR treatment.

Effects of Preparatory Coaching and Home Practice for Deep Inspiration Breath Hold on Cardiac Dose for Left Breast Radiation Therapy.

AIMS: Deep inspiration breath hold (DIBH) reduces cardiac radiation exposure by creating cardiac-chest wall separation in breast cancer radiotherapy. DIBH requires sustaining chest wall expansion for up to 40 s and involves complex co-ordination of thoraco-abdominal muscles, which may not be intuitive to patients. We investigated the effect of in-advance preparatory DIBH coaching and home practice on cardiac doses. MATERIALS AND METHODS: Successive patients from 1 February 2015 to 31 December 2016 with left-sided breast cancer who underwent tangential field radiotherapy utilising the DIBH technique were included. The study cohort consisted of patients treated by a physician who routinely provided DIBH coaching and home practice instructions at least 5 days before simulation. The control group included non-coached patients under another physician's care. Minimum, maximum and mean cardiac doses and V5, V10 and V30 from DIBH and free breathing simulation computed tomography scans were obtained from the planning system. DIBH and free breathing cardiac doses and volume exposures were compared between the coached and non-coached groups using the two-sample t-test, Fisher's exact test and the Mann-Whitney U-test. RESULTS: Twenty-seven coached and 42 non-coached patients were identified. The DIBH maximum cardiac dose was lower in coached patients at 13.1 Gy compared with 19.4 Gy without coaching (P = 0.004). The percentage cardiac volume exposure in DIBH was lower in coached patients; the DIBH V10 was 0.5% without coaching and 0.1% with coaching (P = 0.005). There was also a trend towards lower DIBH V5 in the coached group compared with the non-coached group (1.2% versus 1.9%, P = 0.071). No significant differences in patient cardiopulmonary comorbidity factors that might influence cardiac doses were found between the groups. CONCLUSIONS: Our results suggest that cardiac dose sparing can potentially be further improved with a 5 day regimen of preparatory DIBH coaching and in-advance home practice before simulation. These hypothesis-generating findings should be confirmed in a larger study.

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk.

The clinical applications of stereotactic body radiotherapy or stereotactic ablative radiotherapy (SABR) for the treatment of primary and metastatic tumours of different organ sites have been expanding rapidly in the recent decade. SABR requires advanced technology in radiotherapy planning and image guidance to deliver a highly conformal ablative dose precisely to targets (or tumours) in the body. Although this treatment modality has shown promising results with regard to tumour control, some serious complications have been observed and reported. In order to achieve a favourable therapeutic ratio, strategies to mitigate the risk of complications must be in place. This overview will summarise the reported serious complications caused by SABR and strategies to mitigate the risk will be discussed.

SU-E-T-04: Repair Kinetics of Sublethal Damage in Rat Cervical Spinal Cord - Application of the GLQ Model Incorporating Reciprocal Time Pattern.

PURPOSE: The repair rate conventionally assumed to be constant during the entire radiation course. However, increasing evidences from animal studies show that the repair process may slow down with time and the experimental data does not fit an exponential pattern. To address this enigma, we presented a generalized linear-quadratic (gLQ) model incorporating reciprocal time repair pattern of sublethal damage and fit the model to published experimental data. METHODS: In the gLQ model, the parameter G in the surviving fraction represents the repair process of sublethal damage with Tr as the repair half-time. When a reciprocal time pattern of repair process was adopted, a generalized form of G was derived analytically for arbitrary radiation schemes (I(t) = Ii, ti-1 < t < ti, where i=1 to N, Ii is the dose rate of the ith segment to the voxel in question, and N is the total number of segments for the entire treatment course). The published animal data was used to test the reciprocal formulas. RESULTS: The gLQ model incorporating a reciprocal time pattern to describe the repair process was used to fit the experimental data. The reciprocal model showed better fit to the animal data than the exponential model, particularly for the ED50 data, resulting in the following parameters: the reduced chi-square of 1.52, α/ß=0.9 Gy, Tr =1.0 h for the reciprocal model and reduced chi-square of 3.39, α/ß=1.6 Gy, Tr=3.5 h for the exponential model. CONCLUSIONS: The modeling results suggest that the gLQ model incorporating the reciprocal time pattern of sublethal damage repair facilitates the interpretation of complex experimental designs, especially for irregular dose delivery schedules. These formulas can be used to analyze experimental and clinical data, where a slowing-down of the repair process occurs during the radiation therapy course.

Iterative active deformational methodology for tumor delineation: Evaluation across radiation treatment stage and volume.

PURPOSE: To introduce, implement, and assess an iterative modification to the active deformational image segmentation method as applied to cervical cancer tumors. MATERIALS AND METHODS: A comparison by Jaccard similarity (JS) between this active deformational method and manual segmentation was performed on tumors of various sizes across preradiation, 3 weeks postradiation, and 6 weeks postradiation using a General Linear Mixed Model across 121 studies from 52 patients with Stage IIB-IV cervical cancers. RESULTS: The deformable segmentation method produced promising levels of agreement including JS factors of 0.71+/-0.11 in the preradiation studies. The analysis illustrated a rate of improvement in JS with increasing tumor volume that differed between the preradiation and 6 weeks postradiation stage (P=0.0474). In the large preradiated tumors each additional cm3 of volume was associated with an increase or improvement in JS of 0.0008 (95% confidence interval [CI]: 0.0003, 0.0014). In the smaller postradiation tumors, each additional cm3 of volume was associated with a more robust improvement in JS of 0.0046 (95% CI: 0.0009, 0.0082). CONCLUSION: Agreement was strongly affected by tumor volume, and its performance was most impacted across volume in the later stages of radiation therapy. The deformation-based segmentation method appears to demonstrate utility for delineating cervical cancer tumors, particularly in the earliest stages of radiation treatment, where agreement is greatest.

Dose escalation to combat hypoxia in prostate cancer: a radiobiological study on clinical data.

Earlier studies have demonstrated that hypoxic regions exist in human prostate cancer and the degree of hypoxia correlates with the treatment outcome of radiotherapy. Using the concept of the clinical oxygen enhancement ratio (COER), the linear-quadratic (LQ) model was extended to account for the effect of tumour hypoxia. The clinical data collected at the Fox Chase Cancer Center for prostate cancer were analysed based on the LQ model as well as the tumour control probability (TCP) model. The LQ and TCP parameters (alpha = 0.15 Gy (-1), alpha/beta = 3.1 Gy and the number of clonogens K = 10(6) approximately 10(7) cells) determined in earlier studies were used to derive the COER for prostate cancer: COER = 1.4 with a standard confidence interval (CI) of (1.2, 1.8). The result is consistent with the in vitro OER measurements of human tumour cell lines under chronic hypoxia conditions. This implies that a higher dose is needed to overcome tumour hypoxia. For prostate tumours, the prescription dose required to overcome tumour hypoxia is 165 Gy (CI: 153 approximately 186 Gy) for permanent 125I implants and 88 Gy (CI: 74 approximately 118 Gy) in 2 Gy fractions for external-beam radiotherapy. The impact of LQ parameters on the calculations of COER and dose escalation was discussed. This study provides a preliminary estimate of the dose escalation needed to overcome tumour hypoxia based on clinical data. More clinical data with better statistics and longer follow-up time are required to further tune the radiobiological modelling of hypoxia for prostate cancer.

Dose escalation of three-dimensional conformal radiotherapy for locally recurrent nasopharyngeal carcinoma: a prospective randomised study.

AIMS: To investigate prospectively the feasibility and efficacy of dose escalation using three-dimensional conformal radiotherapy (3D-CRT) boost technique for locally recurrent nasopharyngeal carcinoma (NPC) in a randomised study. MATERIALS AND METHODS: Thirty-six patients with locally recurrent NPC (>6 months interval from previous radical radiotherapy, no cervical lymph-node involvement and no distant metastasis) were enrolled. Treatment included conventional external-beam radiotherapy to 54 Gy, followed by a 3D-CRT boost to the gross tumour region. Patients were randomised to three boost dose levels: 16 Gy, 20 Gy and 24 Gy for groups I, II and III, respectively, with 12 patients in each group. All boost doses were delivered in 4-Gy fractions and 3 fractions per week. Median follow-up was 27 months (range 14-44 months). RESULTS: Three-year, local-recurrence-free survival rate was significantly higher (72%) for the high-dose group III than for groups I and II (37% and 28%, respectively, P = 0.047). No significant difference was found in the 3-year overall survival rate among the three groups (72%, 59% and 82% for groups I, II and III, respectively). Three-year distant metastases rates were 17%, 0% and 18%, respectively. Skull-base invasion (P = 0.017) and pathology (P = 0.0006) correlated with overall survival. Treatment was well tolerated and no significant difference was observed among the three groups in acute and late toxicities (grade III toxicity is minimal: 17%, 17%, 0% of oral mucositis and 25%, 17%, 17% of nasopharyngeal mucositis in groups I, II, III, respectively, and 8% leukocytopenia only in group II; no grade IV toxicity occurred in any of the groups except for a fatal bleeding in group III). CONCLUSIONS: Re-irradiation with high-dose 3D-CRT boost technique results in high local control rate and acceptable toxicity in patients with recurrent NPC. Dose escalation to the boost volume to 78 Gy (54 Gy + 24 Gy boost) results in improved recurrence-free survival compared with lower doses.

Initial clinical experience with frameless stereotactic radiosurgery: analysis of accuracy and feasibility.

PURPOSE: To report on preliminary clinical experience with a novel image-guided frameless stereotactic radiosurgery system. METHODS AND MATERIALS: Fifteen patients ranging in age from 14 to 81 received radiosurgery using a commercially available frameless stereotactic radiosurgery system. Pathologic diagnoses included metastases (12), recurrent primary intracranial sarcoma (1), recurrent central nervous system (CNS) lymphoma (1), and medulloblastoma with supratentorial seeding (1). Treatment accuracy was assessed from image localization of the stereotactic reference array and reproducibility of biteplate reseating. We chose 0.3 mm vector translation error and 0.3 degree rotation about each axis as the maximum tolerated misalignment before treating each arc. RESULTS: The biteplates were found on average to reseat with a reproducibility of 0.24 mm. The mean registration error from CT localization was found to be 0.5 mm, which predicts that the average error at isocenter was 0.82 mm. No patient treatment was delivered beyond the maximum tolerated misalignment. The radiosurgery treatment was delivered in approximately 25 min per patient. CONCLUSION: Our initial clinical experience with stereotactic radiotherapy using the infrared camera guidance system was promising, demonstrating clinical feasibility and accuracy comparable to many frame-based systems.

Factors influencing visualization of vertebral metastases on MR imaging versus bone scintigraphy.

OBJECTIVE: The purpose of this study was to investigate whether the location and size of vertebral body metastases influence the difference in detection rates between MR imaging and bone scintigraphy. MATERIALS AND METHODS: We retrospectively evaluated the vertebral body lesions detected on MR imaging in 74 patients with known widely disseminated metastatic disease. Three radiologists independently reviewed the MR images and bone scintigraphs. MR imaging findings included lesion size and its spatial relationship to the bony cortex (intramedullary, subcortical, and transcortical) and results were correlated with those of planar technetium 99m bone scintigraphy. RESULTS: Findings on bone scans were negative for all intramedullary lesions without cortical involvement shown on MR imaging, regardless of their size. Findings on bone scans (71.3% for transcortical and 33.8% for subcortical) were frequently positive for lesions with cortical involvement (trans- or subcortical), and the probability of positive findings on bone scans was also influenced by the lesion size. Statistical analysis showed a positive correlation among cortical involvement, lesion size, and positive findings on bone scintigraphy (p < 0.0001). CONCLUSION: Location (the presence of cortical bone involvement on MR imaging) and size of the vertebral body metastases appear to be important contributing factors to the difference in detection rates between MR imaging and bone scintigraphy. Cortical involvement is likely the cause of positive findings on bone scans. Early vertebral metastases tend to be small and located in the medullary cavity without cortical involvement, and therefore, findings may be positive on MR images but negative on bone scans.

Esthesioneuroblastoma: the University of Iowa experience 1978-1998.

OBJECTIVE: Esthesioneuroblastoma is rare and the best treatment has yet to be defined. The purpose of this study is to analyze the natural history, treatment, and patterns of failure of esthesioneuroblastoma treated at one institution. METHODS: Between 1978 and 1998, 13 patients with esthesioneuroblastoma were identified using the University of Iowa Tumor Registry. All patients were staged according to Kadish criteria. Mean follow-up was 6.3 years. Six patients had 5 or more years of follow-up and four had follow-up exceeding 9.5 years. One patient was lost to follow-up at 36 months. RESULTS: No patients had Kadish stage A disease, five were stage B, and eight stage C. Overall actuarial 5- and 10-year survival rate was 61% and 24%, respectively. Disease-free survival rate at 5 and 10 years was 56% and 42%, respectively. Seven patients have died, three of intercurrent disease and three of disease progression, one with an unknown disease status. Six patients remain alive, three without evidence of disease and three have experienced a local or regional recurrence. Five patients who were initially controlled developed recurrence, three local only, one locoregional, and one regional and distant. Median time to failure was 96 months. All patients with follow-up exceeding 12 years have experienced either a local or regional recurrence. Survival after salvage therapy in these patients ranged from 3 to 12 years. CONCLUSION: Esthesioneuroblastoma has a long natural history characterized by frequent local or regional recurrence after conventional treatment. Successful retreatment can lead to prolonged survival.

Pixel analysis of MR perfusion imaging in predicting radiation therapy outcome in cervical cancer.

The purpose of this study was to assess heterogeneity of tumor microcirculation determined by dynamic contrast-enhanced magnetic resonance (MR) imaging and its prognostic value for tumor radiosensitivity and long-term tumor control using pixel-by-pixel analysis of the dynamic contrast enhancement. Sixteen patients with advanced cervical cancer were examined with dynamic contrast-enhanced MR imaging at the time of radiation therapy. Pixel-by-pixel statistical analysis of the ratio of post- to precontrast relative signal intensity (RSI) values in the tumor region was performed to generate pixel RSI distributions of dynamic enhancement patterns. Histogram parameters were correlated with subsequent tumor control based on long-term cancer follow-up (median follow-up 4.6 years; range 3.8-5.2 years). The RSI distribution histograms showed a wide spectrum of heterogeneity in the dynamic enhancement pattern within the tumor. The quantity of low-enhancement regions (10th percentile RSI < 2.5) significantly predicted subsequent tumor recurrence (88% vs. 0%, P = 0.0004). Discriminant analysis based on both 10th percentile RSI and pixel number (reflective of tumor size) further improved the prediction rate (100% correct prediction of subsequent tumor control vs. recurrence). These preliminary results suggest that quantification of the extent of poor vascularity regions within the tumor may be useful in predicting long-term tumor control and treatment outcome in cervical cancer. J. Magn. Reson. Imaging 2000;12:1027-1033.

Late effects in children treated with radiation therapy for Wilms' tumor.

PURPOSE: To determine the frequency and types of late effects in children receiving radiation therapy (RT) for Wilms' tumor. MATERIALS AND METHODS: From 1968 to 1994, 55 children received megavoltage RT at our institution as part of treatment for Wilms' tumor. A total of 42 (76.4%) have survived and have a minimum follow-up of 5 years. There were 25 female and 17 male patients with a median age at diagnosis of 48 months (range, 7-126 months). There were 12 Stage I, eight Stage II, 15 Stage III, six Stage IV, and one Stage V patient. RT was delivered to the hemiabdomen in 36 and whole abdomen in six patients. RT dose was 1000-1200 cGy (Group A) in 12, 1201-2399 cGy (Group B) in 11, and 2400-4000 cGy (Group C) in 19. Whole-lung RT was delivered to 13 patients either at diagnosis or pulmonary relapse. All patients received chemotherapy; the most common agents were actinomycin-D/vincristine/adriamycin in 13 and actinomycin-D/vincristine in 18. Median follow-up was 181 months (range, 60-306 months). RESULTS: Of 42 patients, 13 (31.0%) did not have late effects of treatment. The number of patients who developed muscular hypoplasia, limb length inequality, kyphosis, and iliac wing hypoplasia were seven (16.7%), five (11.9%), three (7.1%), and three (7.1%), respectively. Scoliosis was seen in 18 (42.9%) with only one patient requiring orthopedic intervention. Median time to development of scoliosis was 102 months, with a range of 16-146 months. The actuarial incidence of scoliosis at 5, 10, and 15 years after RT was 4.8 +/- 3.3%, 51.8 +/- 9.0%, and 56.7 +/- 9.3%, respectively. Only one of 12 Group A patients developed scoliosis. The 10- and 15-year actuarial incidences of scoliosis for Group A and B patients were 37.7 +/- 12.4% and 37.7 +/- 12.4%, whereas for Group C patients the incidences were 65.8 +/- 12.0% and 74.4 +/- 11. 7% (p = 0.03, log rank test). The actuarial incidence of bowel obstruction at 5, 10, and 15 years was 9.5 +/- 4.5%, 13.0 +/- 5.6%, and 17.0 +/- 6.5%. Of 23 patients, five irradiated within 10 days of surgery and one of 19 irradiated after 10 days developed bowel obstruction (p = 0.09, log rank test). Three patients developed hypertension with normal blood urea nitrogen (BUN) and creatinine levels; another patient had chronic renal insufficiency in a nonirradiated kidney. One patient developed diffuse interstitial pneumonitis. Of the 19 female patients who have reached puberty, three have given birth, and 15 have regular and one has irregular menstrual periods. Four patients developed benign neoplasms; three were in the RT field (two osteochondroma, one lipoma) and one outside (cervical intraepithelial neoplasia II). There were three second malignancies (chronic myelogenous leukemia at 9 years, osteosarcoma at 11 years, and breast cancer at 25 years after initial diagnosis of nephroblastoma); both solid malignancies occurred in the RT field. CONCLUSIONS: Late effects of therapy were seen in more than two thirds of children treated for Wilms' tumor. Children treated with lower doses (<2400 cGy) had a lower incidence of scoliosis compared with those who received more than 2400 cGy. There is also a suggestion that the incidence is lower in patients who received 1000-1200 cGy. Severe physical and functional deformity from RT was uncommon.

Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols.

We describe a standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast-enhanced T(1)-weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd-DTPA). These include a) the volume transfer constant K(trans) (min(-1)); b) the volume of extravascular extracellular space (EES) per unit volume of tissue v(e) (0 < v(e) < 1); and c) the flux rate constant between EES and plasma k(ep) (min(-1)). The rate constant is the ratio of the transfer constant to the EES (k(ep) = K(trans)/v(e)). Under flow-limited conditions K(trans) equals the blood plasma flow per unit volume of tissue; under permeability-limited conditions K(trans) equals the permeability surface area product per unit volume of tissue. We relate these quantities to previously published work from our groups; our future publications will refer to these standardized terms, and we propose that these be adopted as international standards.

MR microcirculation assessment in cervical cancer: correlations with histomorphological tumor markers and clinical outcome.

This article reviews the experience available to date on microcirculation assessment in cancer of the cervix including correlation studies of magnetic resonance (MR) microcirculatory parameters with histo-morphometric predictors and direct correlation with patient outcome. The data suggest that MR microcirculation parameters do not always correlate with histo-morphometric parameters, while there is evidence that MR parameters predict patients' treatment outcome. These observations raise the issue that perhaps the histo-morphometric parameters, accepted gold standards for tumor angiogenesis and prognostic factors, reflect anatomical information at a "static" single time point and may not always provide sufficient information on the "dynamic" microcirculation function of the tumor. MR microcirculation assessment reflects both anatomical and functional information and may provide this additional information on the "dynamic" angiogenic and metabolic status of a tumor. Therefore, assessment of tumor microcirculation may augment the individual risk profile in cervical cancer patients and has the potential to impact on therapy selection and treatment outcome.

Radiation field simulation of gynecologic malignancies: localization of the cervix and vagina with a flexible vaginal localizer contrast tampon.

The authors evaluated a flexible vaginal localizer contrast tampon for radiation therapy simulation. In 51 patients, the degree of cervical or vaginal cuff displacement secondary to the contrast tampon was evaluated by comparing simulation radiographs (with tampon) and initial portal radiographs (without tampon). The same comparisons were made on the radiographs obtained in 25 control subjects who underwent simulation without a tampon. Mean displacement in the group who underwent simulation with a tampon was minimal (< or = 5 mm in each direction) and similar to that in the control group. This technique provides reliable cervical and vaginal cuff localization.

The use of laminarias for osmotic dilation of the cervix in gynecological brachytherapy applications.

PURPOSE: Osmotic dilators (laminarias) have been used for gradual nontraumatic dilation of the cervical canal for various intrauterine procedures; however, this technique has not been well accepted in gynecological brachytherapy. The purpose of this study was to evaluate the efficacy of osmotic cervical dilation for brachytherapy in gynecologic cancer patients, without the use of general/regional anesthesia, and to assess patient tolerance, complications, and outcome. METHODS AND MATERIALS: Thirteen brachytherapy procedures were performed in 6 patients with clinical Stages I and II endometrial (5) and Stage IB cervical cancer (1), who were unable to tolerate general/regional anesthesia because of severe medical problems. An osmotic dilator (synthetic laminaria) was inserted into the cervical os 10-12 h before each brachytherapy procedure and removed just before the procedure. Standard Fletcher-Suit-Delclos tandem insertions with vaginal colpostats or cylinders were then performed. Degree of cervical dilation, patient discomfort, procedure time, intra- and postoperative complications were recorded, and local control and survival were assessed. Median follow-up was 31 months (range: 8-35 months). RESULTS: The diameter of the dilated cervical os after laminaria removal was adequate (> or = 5 mm) for tandem insertion, and no additional mechanical dilation was required in all but one procedure (1 of 13). All procedures were performed without general/regional anesthesia. The mean duration of the procedures was 44 min (range, 20-60 min). Discomfort was minimal in all cases. There were no intra- or postoperative complications. All patients maintained local control until death (1 of metastatic disease, 2 of intercurrent disease) or last follow-up (2 with no evidence of disease, 1 alive with metastatic disease). CONCLUSION: This preliminary study suggests that osmotic cervical dilation with a synthetic laminaria is a useful technique to facilitate intrauterine tandem insertion in patients who cannot tolerate general/regional anesthesia. This technique may reduce treatment-associated morbidity, shorten procedure time, and allow the delivery of adequate radiation therapy in this uncommon but challenging patient population.

Radiation therapy during pregnancy.

Malignant disease requiring radiation therapy during pregnancy presents an enormous challenge for the clinician. The optimal radiotherapeutic management of the patient and the optimal management of the pregnancy involve directly opposing demands. Ionizing radiation should be avoided during pregnancy whenever possible. Doses in excess of 0.1 Gy (10 rad) delivered during gestation have been associated with various detrimental effects, and therapeutic abortion has been recommended. If radiation is unavoidable, such as in the treatment of some gynecologic tumors, lymphomatous diseases, or other advanced solid tumors, it must be performed with extreme caution and maximal effort to reduce the dose to the fetus by special shielding techniques. Decisions regarding the use of radiation therapy during pregnancy, the delay of therapy, or pregnancy termination should be made by a multidisciplinary team and be guided by the prognosis of the disease, the stage of gestation, the risk to the fetus from the expected fetal radiation dose, and the patient's ethical and religious beliefs.

Prediction of tumor control in patients with cervical cancer: analysis of combined volume and dynamic enhancement pattern by MR imaging.

OBJECTIVE: Quantitative analysis of either tumor volume or dynamic enhancement pattern using MR imaging has been reported as useful in the prediction of response to radiation therapy in cancer of the cervix. Because data for both analyses can be obtained in a single MR examination, the purpose of this study was to evaluate whether combining both analyses can further improve the efficacy of using MR imaging to predict tumor control after radiation therapy. MATERIALS AND METHODS: Twenty patients with bulky carcinomas of the cervix, stages bulky IB (n = 2), IIB (n = 6), IIIA (n = 1), IIIB (n = 9), IVA (n = 1), and recurrent (n = 1), were studied. Initial tumor volumes were calculated by outlining the area of tumor in each slice on T2-weighted images and multiplying by the slice profile. Two dynamic contrast-enhanced MR studies were obtained in each patient immediately before the start of radiation therapy and after 20-22 Gy in 2 weeks of radiation therapy. Dynamic enhancement imaging was performed at 3-sec intervals in the sagittal plane for 120 sec after rapid (9 ml/sec) i.v. injection of MR contrast agent (0.1 mmol/kg of gadoteridol) using a power injector. Time and signal intensity curves reflecting the relative signal intensity of contrast enhancement in the tumor region were generated, and the relative signal intensity of the tumor region during the early plateau phase was calculated. Median follow-up was 25 months (range, 11-35 months). RESULTS: The combined analysis did not improve the prediction rate of local recurrence in small-sized tumors, which responded well to radiation therapy regardless of their dynamic enhancement pattern. However, the combined analysis did improve the prediction rate of local recurrence in intermediate- and large-sized tumors (75% and 80%, respectively) over assessment by either volume analysis (33% and 60%, respectively) or dynamic enhancement pattern analysis (64% and 64%, respectively). The combined analysis was most useful in intermediate-sized tumors (40-99 cm3; 33% recurrence), significantly improving differentiation between high-risk (80% recurrence) and low-risk 10% recurrence) patients (p = .010). CONCLUSION: Our preliminary results suggest that the combined data of both tumor morphologic (volume) and microcirculatory (dynamic enhancement pattern) parameters allow more accurate prediction of local failure in patients with advanced cervical cancer than does each individual parameter alone. Combined data appear to have the greatest potential in patients with intermediate-sized tumors, who constitute most patients (60%) and remain a challenge for outcome prediction and management.