David Bernshaw

Patterns of failure and prognostic factor analyses in locally advanced cervical cancer patients staged by positron emission tomography and treated with curative intent.

Purpose: The aim of this retrospective analysis was to assess whether parameters derived from magnetic resonance imaging (MRI) and positron emission tomography (PET) provide incremental prognostic value compared with International Federation of Gynecology and Obstetrics (FIGO) stage in cervix cancer patients treated with curative intent using concurrent chemoradiotherapy. Materials and Methods: This was a retrospective study of patients with locoregionally advanced cervical cancer staged by examination under anesthesia and pretreatment MRI and PET. Potential prognostic factors examined were derived from either clinical evaluation (age, FIGO stage, clinical diameter, histology), MRI (corpus invasion, tumor volume), or PET (lymph node metastasis). Outcome measures examined were overall survival, relapse-free survival, time to failure, local failure, nodal failure, and distant failure. Results: There were 206 eligible patients. The mean potential follow-up was 4.4 years. At 5 years, for all patients, overall survival rate was 59%. For all outcome measures apart from local failure, for which adenocarcinoma histology was the most powerful adverse prognostic factor (HR, 4.29; P < 0.0001), lymph node status on PET was the dominant unifactor and multifactor prognostic factor. Corpus involvement on MRI was significantly associated with nodal involvement on PET but of MRI-derived parameters only tumor volume has prognostic value, limited to time to failure and nodal failure. Conclusions: Nodal status on PET was the major predictor of outcome in locally advanced cervix cancer treated with chemoradiation and was superior to FIGO staging. Tumor volume measured from MRI appears to be an important predictor of loco-regional relapse.

Conformal Brachytherapy Planning for Cervical Cancer Using Transabdominal Ultrasound

PURPOSE To determine if transabdominal ultrasound (US) can be used for conformal brachytherapy in cervical cancer patients. MATERIALS AND METHODS Seventy-one patients with locoregionally advanced cervix cancer treated with chemoradiation and brachytherapy were included in this study. The protocol consisted of US-assisted tandem insertion and conformal US-based planning. Orthogonal films for applicator reconstruction were also taken. A standard plan was modified to suit the US-based volume and treatment was delivered. The patient then underwent a magnetic resonance imaging (MRI) scan with the applicators in situ. Retrospectively, individual standard (STD), US, and MRI plans were extrapolated for five fractions and superimposed onto the two-dimensional sagittal MRI images for comparison. Doses to Point A, target volume, International Commission on Radiation Units and Measurements (ICRU) 38 bladder and rectal points, and individualized bowel points were calculated on original implant geometry on Plato for each planning method. RESULTS STD (high-dose-rate) plans reported higher doses to Point A, target volume, ICRU 38 bladder and rectal points, and individualized bowel point compared with US and MRI plans. There was a statistically significant difference between standard plans and image-based plans-STD vs. US, STD vs. MRI, and STD vs. Final-having consistent (p <or= 0.001) respectively for target volume, Point A, ICRU 38 bladder, and bowel point. US plan assessed on two-dimensional MRI image was comparable for target volume (p = 0.11), rectal point (p = 0.8), and vaginal mucosa (p = 0.19). Local control was 90%. Late bowel morbidity (G3, G4) was <2%. CONCLUSIONS Transabdominal ultrasound offers an accurate, quick, accessible, and cost-effective method of conformal brachytherapy planning.

Estimation of tumor volume in cervical cancer by magnetic resonance imaging.

In 32 patients with stage 1 or 2 cervical cancer, preoperative magnetic resonance imaging (MRI) images were compared with corresponding linear measurements made on fresh histopathology specimens. Their clinical tumor diameters recorded as a part of Federation of International Gynecologists and Obstetricians (FIGO) staging were also correlated with the MRI-derived tumor volumes. The locations of neoplastic lesions within the cervix and uterus were identified accurately by MRI as verified in subsequent histopathology examinations. The examination under anesthesia (EUA) diameter (tumor size) was not related to the MRI-derived tumor diameter. Pathologic tumor diameter correlated well with the corresponding diameter in T2-weighted MRI. Tumor volume as measured by MRI was an accurate representation of the local extent of the disease and can be used as an objective measure of cervical cancer at the primary site. Substituting MRI-derived volume in place of clinical tumor diameter in the FIGO staging system will help refine its prognostic significance in patients with both operable and nonoperable cervical cancer.

A role for radiotherapy in neuropathic bone pain : Preliminary response rates from a prospective trial (Trans-Tasman Radiation Oncology Group, Trog 96.05)

PURPOSE Radiotherapy (RT) has a proven role in palliation of pain from bone metastases with numerous randomized trials obtaining response rates (RRs) of typically 70-80% regardless of the fractionation employed. However RT for neuropathic bone pain (NBP), i.e., pain with a radiating cutaneous component due to compression/irritation of nerves by tumor has not previously been studied, and its role is thus uncertain. METHODS AND MATERIALS In February 1996, the Trans-Tasman Radiation Oncology Group (TROG) initiated a multicenter randomized trial comparing a single 8 Gy fraction with 20 Gy in 5 fractions for NBP with an accrual target of 270. Formal interim analyses were planned at 90 and 180 patients. The 90th patient was accrued in June 1998, and data from the first interim analysis with both arms combined form the basis of this report. RESULTS Forty-four patients were randomized to a single 8 Gy, 46 to 20 Gy in 5 fractions. The commonest primary sites were prostate (34%), lung (28%) and breast (10%). Median age was 68 years (range 37-89). The index site was spine (86%), rib (13%), base of skull (1%). On an intention-to-treat basis, the overall RR was 53/90 = 59% (95% CI = 48-69%), with 27% achieving a complete response and 32% a partial response. The overall RR for eligible patients was 49/81 = 60% (95% CI = 49-71%) with 27% and 33% achieving complete and partial responses respectively. Estimated median time to treatment failure was 3.2 months (95% CI = 2.1-5.1 months), with estimated median survival of 5.1 months (95% CI = 4.2-7.2 months). To date, six spinal cord/cauda equina compressions and four new or progressive pathological fractures have been detected at the index site after randomization, although one cord compression occurred before radiotherapy was planned to commence. In February 1999, the Independent Data Monitoring Committee strongly recommended continuation of the trial. CONCLUSION Although these results are preliminary, it seems clear that there is indeed a role for RT in the treatment of NBP. Analysis of outcome by treatment arm awaits completion of the randomized trial.

Impact of post-therapy positron emission tomography on prognostic stratification and surveillance after chemoradiotherapy for cervical cancer

A study was undertaken to investigate the detection of relapse and survival outcomes in patients with cervical cancer treated with curative intent chemoradiotherapy, and evaluated with a post‐therapy 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scan.

Comparative Study of LDR (Manchester System) and HDR Image-guided Conformal Brachytherapy of Cervical Cancer: Patterns of Failure, Late Complications, and Survival

PURPOSE To compare patterns of failure, late toxicities, and survival in locally advanced cervical cancer patients treated by either low-dose-rate (LDR) or conformal high-dose-rate (HDRc) brachytherapy as a part of curative radiotherapy. MATERIALS AND METHODS A retrospective comparative study of 217 advanced cervix cancer patients was conducted; 90 of these patients received LDR and 127 received HDRc brachytherapy. All patients were staged using International Federation of Gynecology and Obstetrics (FIGO) rules, had pretreatment magnetic resonance imaging (MRI), and were treated with concurrent cisplatin chemoradiotherapy. Both groups matched for FIGO stage, MRI tumor volume, and uterine invasion status. RESULTS Local and pelvic failures were similar 12-13% and 14% both in both groups. Abdominal and systemic failures in LDR group were 21% and 24%, whereas corresponding failures in HDRc group were 20% and 24%. Sixty-eight percent (87/127) of patients treated by HDRc remained asymptomatic, whereas 42% (38/90) of patients were asymptomatic from the bowel and bladder symptoms after treatment with LDR. The 5-year OS rate was 60% (SE = 4%). The 5-year failure-free survival rate was 55% (SE = 3%). There was no significant difference between the groups. CONCLUSIONS Image-guided HDRc planning led to a large decrease in late radiation effects in patients treated by HDRc. Patterns of failure and survival were similar in patients treated either by LDR or HDRc.

Ultrasound guided conformal brachytherapy of cervix cancer: survival, patterns of failure, and late complications

Objective The aim of this study was to report on the long-term results of transabdominal ultrasound guided conformal brachytherapy in patients with cervical cancer with respect to patterns of failures, treatment related toxicities and survival. Methods Three hundred and nine patients with cervical cancer who presented to Institute between January 1999 and December 2008 were staged with magnetic resonance imaging and positron emission tomography and treated with external beam radiotherapy and high dose rate conformal image guided brachytherapy with curative intent. Follow-up data relating to sites of failure and toxicity was recorded prospectively. Results Two hundred and ninety-two patients were available for analyses. The median (interquantile range) follow-up time was 4.1 years (range, 2.4 to 6.1 years). Five-year failure free survival and overall survival (OS) were 66% and 65%, respectively. Primary, pelvic, para-aortic, and distant failure were observed in 12.5%, 16.4%, 22%, and 23% of patients, respectively. In multivariate analysis, tumor volume and nodal disease related to survival, whereas local disease control and point A dose did not. Conclusion Ultrasound guided conformal brachytherapy of cervix cancer has led to optimal local control and OS. The Melbourne protocol compares favorably to the more technically elaborate and expensive GEC-ESTRO recommendations. The Melbourne protocols technical simplicity with real-time imaging and treatment planning makes this a method of choice for treating patients with cervical cancer.

Comparison of Measurements of the Uterus and Cervix Obtained by Magnetic Resonance and Transabdominal Ultrasound Imaging to Identify the Brachytherapy Target in Patients With Cervix Cancer

PURPOSE To compare measurements of the uterus and cervix obtained with magnetic resonance imaging (MRI) and transabdominal ultrasound to determine whether ultrasound can identify the brachytherapy target and be used to guide conformal brachytherapy planning and treatment for cervix cancer. METHODS AND MATERIALS Consecutive patients undergoing curative treatment with radiation therapy between January 2007 and March 2012 were included in the study. Intrauterine applicators were inserted into the uterine canal while patients were anesthetized. Images were obtained by MRI and transabdominal ultrasound in the longitudinal axis of the uterus with the applicator in treatment position. Measurements were taken at the anterior and posterior surface of the uterus at 2.0-cm intervals along the applicator, from the external os to the tip of the applicator. Data were analyzed using Bland Altman plots examining bias and 95% limits of agreement. RESULTS A total of 192 patients contributed 1668 measurements of the cervix and uterus. Mean (± SD) differences of measurements between imaging modalities at the anterior and posterior uterine surface ranged from 1.5 (± 3.353) mm to 3.7 (± 3.856) mm, and -1.46 (± 3.308) mm to 0.47 (± 3.502) mm, respectively. The mean differences were less than 3 mm in the cervix. The mean differences were less than 1.5 mm at all measurement points on the posterior surface. CONCLUSION Differences in the measurements of the cervix and uterus obtained by MRI and ultrasound were within clinically acceptable limits. Transabdominal ultrasound can be substituted for MRI in defining the target volume for conformal brachytherapy treatment of cervix cancer.

Prognostic significance of lymphovascular space invasion and nodal involvement in intermediate- and high-risk endometrial cancer patients treated with curative intent using surgery and adjuvant radiotherapy

Objective The aim of this study was to assess whether lymphovascular space invasion (LVSI) and nodal status provide adequate prognostic information in comparison with the entire set of traditional prognostic factors in intermediate- and high-risk endometrial cancer patients treated and staged with primary surgery and adjuvant radiotherapy. Methods Three hundred twenty-four previously untreated high-intermediate- and high-risk endometrial cancer patients with FIGO (International Federation of Gynecology and Obstetrics) stage I to IIIC; endometrioid, serous, or clear cell histology; diagnosed between November 1995 and December 2006; who presented to Peter MacCallum Cancer Centre for adjuvant radiotherapy were included in these analyses. All traditionally recognized prognostic factors and newly created 4 pairs of combination of LVSI and nodal status were studied with respect to survival and patterns of failure. Results The median follow-up time was 4.8 years. Five-year failure-free survival for all patients according to FIGO stage I, II, and III were 87.4%, 89.0%, and 62.4 %, respectively. In multivariable analysis for relapse, positive LVSI had a hazard ratio of 4.9 (P = 0.000), which increased to 8.8 (P = 0.004) in the presence of positive nodes. For overall survival, only LVSI was significant, with a hazard ratio of 3.02 (P = 0.003). In particular, in the presence of LVSI and nodes, histological type, grade, and myometrial invasion were not significant prognosticators for relapse or overall survival. Conclusions This model enables the separation of good prognosis patients even among poorly differentiated endometrioid, serous, and clear cell carcinoma patients and can be used in simplifying the staging of endometrial cancer and for selecting patients for high-risk endometrial cancer studies.

Patterns of failure and prognostic factor analyses in locally advanced cervical cancer patients staged by magnetic resonance imaging and treated with curative intent

Earlier we had shown that tumor volume and corpus invasion were important prognostic factors in cervical cancer and that corpus invasion was associated with nodal metastases. In view of these findings, we wanted to examine the factors associated with the patterns of relapse in cervical cancer patients who were staged by magnetic resonance imaging (MRI) and treated with curative intent. This was a retrospective study of locoregionally advanced cervical cancer patients treated with curative intent. All patients had examination under anesthesia and pretreatment MRI. Potential prognostics examined were FIGO stage, clinical diameter, histology, corpus invasion, tumor volume, and age. Outcome measures examined were times to failure, local failure, nodal failure, and distant failure. There were 249 eligible patients. The median age of the patients was 58 years, 85% had squamous histology, and 63% of tumors exhibited corpus invasion. Median tumor volume was 33.5 mL (range 1–628). The mean follow-up was 4.5 years. Eighty-five patients had relapsed and 89 died (70 following failure and 19 otherwise). At 5 years, for all patients, the failure-free rate was 62%, the local failure–free rate 88%, the nodal failure–free rate 69%, and the distant failure–free rate 74%. Corpus invasion, tumor volume, and age were all highly significantly and independently related to risk of failure at local, nodal, and distant (except tumor volume) sites. In the presence of these factors, clinical tumor diameter and FIGO stage were not significantly related to risk of any type of failure