This prospective, randomized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was designed to test the effectiveness and ...safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer.
Patients with locally advanced cervix cancer were randomly assigned to CIS chemoradiotherapy versus CIS/TPZ chemoradiotherapy. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and tolerability.
PFS was evaluable in 387 of 402 patients randomly assigned over 36 months, with enrollment ending in September 2009. Because of the lack of TPZ supply, the study did not reach its original target accrual goal. At median follow-up of 28.3 months, PFS and OS were similar in both arms. Three-year PFS for the TPZ/CIS/RT and CIS/RT arms were 63.0% and 64.4%, respectively (log-rank P = .7869). Three-year OS for the TPZ/CIS/RT and CIS/RT arms were 70.5% and 70.6%, respectively (log-rank P = .8333). A scheduled interim safety analysis led to a reduction in the starting dose for the TPZ/CIS arm, with resulting tolerance in both treatment arms.
TPZ/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose.
To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), ...Australia/New Zealand (ANZ), Europe (E), and North America (NAm).
A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey.
A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation SD 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4.96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05; p = 0.02 for Asia vs. other regions).The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002).
Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials.
The expansion of cancer services closer to home has become a major focus of publicly funded healthcare, with cancer organizations attempting to invest in smaller centers by integrating radiotherapy ...into these facilities. In Canada this has resulted in Ontario, British Columbia and Alberta investing in 12 expanded regional centers over the past 20 years. Quebec, Manitoba and Nova Scotia have made similar investments. Alberta's three new centers opened in 2010, 2013 and 2021 (projected). This study examined improvements in wait times and patient throughput between 2010 and 2020, and highlighted strategies that will support the sustainability and growth of clinical activity through to 2030. Significant improvement in ready to treat wait times for radiotherapy have resulted from opening two centers, and the provincial throughput for patients requiring systemic or radiotherapy has gone up by 16%. A patient satisfaction survey demonstrated that rural patients are happy with their care and desire the provision of more of their cancer treatment closer to home. An expert panel provided recommendations on what needs to be done to stabilize recruitment and retention.
Abstract Objective Mutational activation of PIK3CA is associated with poor prognosis in patients with solid tumors, and may predict favorable response to PI3K/AKT/mTOR pathway inhibitors. However, ...PIK3CA mutational status has not previously been evaluated in patients with cervical carcinoma treated with radical chemoradiotherapy (CRT). The aims of this study were (1) to evaluate the frequency of PIK3CA mutations in patients with cervical cancer treated with radical CRT and (2) to examine the effect of tumor PIK3CA mutational status in pre-treatment biopsies on overall survival (OS) and progression-free survival (PFS). Methods Patients with cervical cancer, treated at a single institution with radical CRT, from 1999 to 2008, were eligible for this retrospective study. Pre-treatment tumor biopsies ( n = 157) were retrieved. Genomic DNA was extracted from tumor blocks, and exons 9 and 20 of the PIK3CA gene were sequenced for mutations. Results Eighty-two tumors were sequenced for both exon 9 and exon 20. 19/82 (23%) tumors were PIK3CA mutation positive; of these 84% were squamous cell carcinomas. 79% of mutations were in exon 9. PIK3CA mutation status was strongly associated with overall survival (OS) in FIGO stage IB/II patients, unadjusted HR 6.0 (95% CI 2.1–17.5), p = 0.0002, but not stage III/IVA patients, unadjusted HR 1.0 (95% CI 0.32–3.1), p = 0.98. Conclusions In cervical cancer patients treated with CRT, tumor PIK3CA mutation status was associated with overall survival in FIGO stage IB/II cervix cancers. Further evaluation with a larger dataset will be required to validate these findings to inform potential clinical trials designs involving PI3K/AKT/mTOR pathway inhibitors.
Aims
Treatment of brain metastases patients has included whole brain radiotherapy (WBRT) for over 50 years, and there is much data showing this to be associated with short-term gains. The integration ...of resection and radiosurgery to these patients allows some better prognostic groups to experience long-term local control and improvement in quality of life. The recursive partitioning analysis of the Radiation Therapy Oncology Group (RTOG) has been used as a predictive model for over a decade to identify three classes of patients. Number of lesions has been used to define treatment for a good prognostic subgroup that is eligible for surgery or radiosurgery, but there are few prospective studies of poorer prognosis brain metastases patients to evaluate the influence of number of lesions on the prediction of outcome. We examined patient, treatment and outcome parameters of all brain metastases patients in a 5-year period so that we could measure outcome and evaluate various factors on survival.
Methods and results
This was a population-based study of all brain metastases patients in Southern Alberta between 2000 and 2005. It used an Excel spreadsheet database and STATA 8 software to analyze outcomes. The study included 568 patients representing 4.4% of our radiotherapy population. Median age, performance status and distribution of primary disease sites were comparable with other large series. Overall survival for the whole group was 3.05 months. Independent factors predicting for improved overall survival included younger age, KPS <70, less than four lesions and the use of stereotactic radiosurgery. Presence of extracranial disease or persistence of primary disease did not adversely impact survival outcome.
Conclusions
This series shows that the number of lesions is a strong predictor of outcome. Integration of this factor into a decision-making model allows for identification of not only good prognosis patients who will benefit from aggressive treatment but it also facilitates decision making for poorer prognosis patients who are less likely to benefit from WBRT. Recursive partitioning RTOG class 2 and 3 patients with more than three lesions did particularly poor and had an overall survival of 3 months with WBRT. We question the value of WBRT in this subgroup and wonder if best supportive care would be more justifiable given the low survival figures achieved.
ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer ...patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters.
A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years.
The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 1.05-5.18, P=.038) and OS (HR 3.13 1.27-7.71, P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 0.61-3.6, P=.38); for OS (HR 2.42 0.94-6.24 P=.067).
In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis.
Although vaginal dilation is often recommended to minimize or prevent vaginal scarring after pelvic radiotherapy, compliance with this recommendation has historically been very low. Therefore, ...effective intervention strategies are needed to enhance compliance with vaginal dilation after radiotherapy for gynecologic cancer.
This study was a randomized controlled clinical trial of a psychoeducational intervention specifically designed to increase compliance with vaginal dilation. The information-motivation-behavioral skills model of enhancing compliance with behavioral change was the basis for the intervention design. Forty-two sexually active women, 21 to 65 years of age, diagnosed with Stages Ic-III cervical or endometrial cancer, who received pelvic radiotherapy, were randomized to either the experimental psychoeducational group or the information-only control group. Assessment via questionnaire occurred before treatment and at 6-week, 6-month, 12-month, 18-month, and 24-month follow-up. Assessment via interview also occurred at 6-month, 12-month, 18-month, and 24-month follow-up.
The psychoeducational intervention was successful in increasing compliance with vaginal dilation.
This study is the first randomized controlled study to demonstrate the effectiveness of an intervention in increasing compliance with the use of vaginal dilators.
Abstract Background and purpose This survey aimed to document practices of Canadian radiation oncologists performing gynecologic brachytherapy for carcinoma of the cervix and to determine what the ...effect of the phasing-out of LDR after-loading systems from the commercial market is having on practice. Materials and methods A 26-item questionnaire was developed to survey various aspects of brachytherapy practice to include: number of patients treated, prescription points/volume, dose and fractionation, timing, critical structure delineation, expected changes due to the phasing-out of support for low dose rate systems, and support for the development of national guidelines. A link to a web-based survey collection instrument was emailed to each radiation oncologist in Canada practicing gynecologic brachytherapy. Results A 67% response rate was achieved in this web-based survey. Radiation oncologists currently using HDR brachytherapy are most commonly delivering 5 fractions of 6 Gy in addition to an EBRT dose of 45 Gy in 25 fractions. The median total dose equivalents to Point A was 82.9 Gy for both early and advanced disease. In response to the announcement by a major vendor that they would be phasing-out service for a popular LDR after-loader, 49% of Canadian radiation oncologists who practice brachytherapy for cervix cancer are changing to an HDR technique with a further 9% changing to a PDR technique. Eighty-six percent of respondents would support the development of national guidelines for cervix brachytherapy in Canada. Conclusions Variation in practice exists in Canada in brachytherapy for cervix cancer. Many centers are in the process of phasing-out LDR techniques in response to the withdrawal of commercial support for these systems. Support for the development of Canadian national guidelines is high.
To survey the current use and future plans for image-guided brachytherapy (BT) for cervical cancer by radiation oncologists in Canada.
Canadian radiation oncologists treating gynecologic malignancies ...were identified in January 2009. A 29-item questionnaire (English and French) querying the current practice in the use of imaging in BT planning, and plans for transition to three-dimensional (3D) image guidance for BT for cervical cancer (curative intent, intact cervix), was electronically circulated. Questionnaire responses were tabulated and analyzed by respondent and by center.
Response rate was 62% (36 of 58 radiation oncologists), representing 71% (22 of 31) of Canadian radiation oncology centers with a gynecologic BT facility. Most of the centers were using high-dose-rate BT (68%), followed by low-dose-rate BT (23%) and pulsed dose-rate BT (10%). Main imaging used for treatment planning by center was plain X-ray (50%), computerized tomography (CT) (45%), and magnetic resonance imaging (MRI) (5%). For respondents using CT or MRI for planning, point A was the most common dose prescription point (50%), followed by gross tumor volume/clinical target volume as per Groupe Européen de Curiethérapie and the European Society for Therapeutic Radiology and Oncology guidelines (44%). For centers using plain X-rays for planning, 73% planned to transition to a 3D image-based approach, with the majority to adopt CT imaging. Eighty percent of respondents agreed that 3D image-guided BT should become standard of care for treatment of cervical cancer in Canada, and additionally support the development of national guidelines.
Most of the Canadian radiation oncologists surveyed and Canadian cancer centers are either using 3D imaging and planning or transitioning to a 3D image-based approach within the next year. Point A remained a commonly documented prescription point. Access to MRI was very low. These results may lead to national treatment guidelines.
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