Definitive Pelvic Radiotherapy Research Articles

A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers

ObjectiveWee1 kinase is a crucial regulator of the G2/M checkpoint which prevents entry of damaged DNA into mitosis. Adavosertib (AZD1775), a selective inhibitor of Wee1, induces G2 escape and increases...

Dynamic Nomogram Based on the Metastatic Number and Sites and Therapy Strategies Predicting the Prognosis of Patients with Metastatic Cervical Cancer.

Individual survival prediction is of vital importance to optimize the individualized treatment of metastatic cervical cancer (mCC) patients. The goal of this study was to identify the potential risk factors for the survival of mCC patients and construct a nomogram for their prognosis. Medical records of patients with newly diagnosed mCC at the First Affiliated Hospital of Xi'an Jiaotong University were reviewed retrospectively. Risk factors were identified using Cox proportional hazards analysis and Kaplan-Meier curves. Random forest was used to identify factors associated with therapy strategy. Nomogram and dynamic nomogram were established using 'rms' and "DynNom" R package. A total of 98 patients with mCC were finally identified. In Cox analyses, multiple metastases and concurrent chemoradiotherapy (CCRT) were identified as independent predictors for overall survival (OS). We further explored the prognostic value of metastatic number and sites and therapy strategies for mCC patients by Kaplan-Meier curves. A dynamic nomogram including metastases number and sites (multiple metastases, liver and lymph node (LN) above diaphragm metastases) and chemoradiotherapy strategies (CCRT, postradiotherapy chemotherapy, and radiotherapy to metastatic sites) was constructed for predicting the prognosis of mCC patients. For newly diagnosed patients, we strongly recommended the combination of chemotherapy and definitive pelvic radiotherapy and, if possible, radiation to metastatic site, but CCRT should be implemented with caution. We constructed a dynamic nomogram indicating that patients with younger age, shorter symptom duration, and better laboratory test results are suitable for CCRT. Survival analyses showed that the metastatic number and sites and therapy strategies are associated with the prognosis of mCC patients. The CCRT and prognostic nomograms may help clinicians to make better clinical decisions and effectively predict the prognosis for newly diagnosed mCC patients.

A machine learning model for grade 4 lymphopenia prediction during pelvic radiotherapy in patients with cervical cancer.

Background/purposeSevere lymphopenia during pelvic radiotherapy (RT) predicts poor survival in patients with cervical cancer. However, the risk of severe lymphopenia has not been well predicted. We developed a machine learning model using clinical and dosimetric information to predict grade 4 (G4) lymphopenia during pelvic RT in patients with cervical cancer.MethodsThis retrospective study included cervical cancer patients treated with definitive pelvic RT ± induction/concurrent chemotherapy. Clinical information and a set of dosimetric parameters of external beam radiotherapy plan were collected. G4 lymphopenia during RT, which was also referred to as G4 absolute lymphocyte count (ALC) nadir, was defined as ALC nadir <0.2 × 109 cells/L during RT according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Elastic-net logistic regression models were constructed for the prediction of G4 lymphopenia during pelvic RT using a repeated cross-validation methodology.ResultsA total of 130 patients were eligible, and 43 (33.1%) patients had G4 lymphopenia during RT. On multivariable analysis, G4 ALC nadir was associated with poor overall survival (OS) [hazard ratio (HR), 3.91; 95% confidence interval (CI), 1.34–11.38, p = 0.01]. Seven significant factors [Eastern Cooperative Oncology Group (ECOG) performance score, pre-RT hemoglobin, pre-RT lymphocytes, concurrent chemotherapy, gross tumor volume of regional lymphadenopathy (GTV_N volume), body volume, and maximum dose of planning target volume receiving at least 55 Gy (PTV_5500 Dmax)] were obtained by elastic-net logistic regression models and were included in the final prediction model for G4 ALC nadir. The model’s predicting ability in test set was area under the curve (AUC) = 0.77 and accuracy = 0.76. A nomogram of the final predicting model was constructed.ConclusionsThis study developed and validated a comprehensive model integrating clinical and dosimetric parameters by machine learning method, which performed well in predicting G4 lymphopenia during pelvic RT for cervical cancer and will facilitate physicians to identify patients at high risk of G4 lymphopenia who might benefit from modified treatment approaches.

Implications for pelvic lymph node irradiation in definitive chemoradiotherapy of node negative muscle invasive bladder cancer based on predictive factors of clinicopathologic discrepancy.

To identify pre-surgical imaging predictive value and factors associated with the clinicopathologic discrepancy for implication of definitive pelvic radiotherapy in clinically node-negative bladder cancer. The documented data of bladder cancer patients who underwent radical cystectomy plus pelvic lymphadenectomy were collected retrospectively. Patients' characteristics, last imaging, pathology reports, disease-specific survival and overall survival were retrieved. From 142 patients, pre-surgical imaging had a sensitivity of 76.4%, specificity of 73.7%, positive predictive value (PPV) of 94.9%, and negative predictive value (NPV) of 32.6% (p value < 0.0001) for detection of muscle invasion. Also, for detection of positive lymph nodes, imaging had a sensitivity of 31.8%, specificity of 85.7%, PPV of 50%, and NPV of 73.7% (p value: 0.022). 44.4% of study population were upstaged after surgery (24.6% associated with N-upstaging) and 18.3% were downstaged (12% associated with N-downstaging). Receipt of neoadjuvant chemotherapy and T-stage were not correlated with N-upstaging. On multivariate analysis, lymphovascular invasion (LVI) maintained its significance for independent prediction of upstaging (OR 3.3, 95% CI 1.5-7.5, p value: 0.004) and inversely with downstaging (OR 0.34, 95% CI 0.12-0.96, p value: 0.04). Older age (OR 1.03, 95% CI 1.0-1.05, p value 0.047), positive margins (OR 2.1, 95% CI 1.2-3.8, p value 0.011), presence of LVI (OR 2.5, 95% CI 1.4-4.7, p value 0.003), perineural invasion (OR 2.0, 95% CI 1.2-3.4, p value 0.013), and lymph node ratio (OR 1.011, 95% CI 1.001-1.021, p value 0.03) were associated with worse survival. Also, N-upstaging independently predicted a worse survival after controlling for surgical pathology stage (OR 2.3, 95% CI 1.2-4.5, p value 0.011). The optimal target volume in definitive chemoradiotherapy of node-negative bladder cancer patients remains to be established. Since then, customizing the treatment is considered especially for positive LVI in TURBT specimen.

Machine Learning of Dose-Volume Histogram Parameters Predicting Overall Survival in Patients with Cervical Cancer Treated with Definitive Radiotherapy.

Purpose To analyze the effects of dosimetric parameters and clinical characteristics on overall survival (OS) by machine learning algorithms. Methods and Materials 128 patients with cervical cancer were treated with definitive pelvic radiotherapy with or without chemotherapy followed by image-guided brachytherapy. The elastic-net models with integrating DVH parameters and baseline clinical factors, only DVH parameters and only baseline clinical factors were constructed in 5-folds cross-validations for 100 iteration bootstrapping, and then were compared using concordance index (C-index) criteria. Finally, the selected important factors were used to build multivariable Cox-pH models for OS and also shown in nomograms for clinical usage. Results The median OS occurred was 25.78 months with 25 (19.53%) deaths. The elastic-net models integrating clinical and DVH factors had the best prediction performances (C-index 0.76 in the train set and C-index 0.74 in the test set). Three important factors were selected, including baseline hemoglobin level as the protective factor, primary tumor volume (GTV_P) volume, and body V5 as the risk factors. The final multivariable Cox-pH models were constructed using these important factors and had prediction performance (C-index: 0.78, 95%CI: 0.73–0.81). Conclusions This is the first attempt to establish elastic-net models to study the contributions of DVH parameters for predicting OS in patients with cervical cancer. These results can facilitate individualized tailoring of radiation treatment in cervical cancer patients.

PD-0321 Comparison of synthetic CT generation methods for MRI-only definitive pelvic radiotherapy

PD-0321 Comparison of synthetic CT generation methods for MRI-only definitive pelvic radiotherapy

Validation of an MRI-only planning workflow for definitive pelvic radiotherapy

PurposePrevious work on Magnetic Resonance Imaging (MRI) only planning has been applied to limited treatment regions with a focus on male anatomy. This research aimed to validate the use of a hybrid multi-atlas synthetic computed tomography (sCT) generation technique from a MRI, using a female and male atlas, for MRI only radiation therapy treatment planning of rectum, anal canal, cervix and endometrial malignancies.Patients and methodsForty patients receiving radiation treatment for a range of pelvic malignancies, were separated into male (n = 20) and female (n = 20) cohorts for the creation of gender specific atlases. A multi-atlas local weighted voting method was used to generate a sCT from a T1-weighted VIBE DIXON MRI sequence. The original treatment plans were copied from the CT scan to the corresponding sCT for dosimetric validation.ResultsThe median percentage dose difference between the treatment plan on the CT and sCT at the ICRU reference point for the male cohort was − 0.4% (IQR of 0 to − 0.6), and − 0.3% (IQR of 0 to − 0.6) for the female cohort. The mean gamma agreement for both cohorts was > 99% for criteria of 3%/2 mm and 2%/2 mm. With dose criteria of 1%/1 mm, the pass rate was higher for the male cohort at 96.3% than the female cohort at 93.4%. MRI to sCT anatomical agreement for bone and body delineated contours was assessed, with a resulting Dice score of 0.91 ± 0.2 (mean ± 1 SD) and 0.97 ± 0.0 for the male cohort respectively; and 0.96 ± 0.0 and 0.98 ± 0.0 for the female cohort respectively. The mean absolute error in Hounsfield units (HUs) within the entire body for the male and female cohorts was 59.1 HU ± 7.2 HU and 53.3 HU ± 8.9 HU respectively.ConclusionsA multi-atlas based method for sCT generation can be applied to a standard T1-weighted MRI sequence for male and female pelvic patients. The implications of this study support MRI only planning being applied more broadly for both male and female pelvic sites.Trial registration This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (www.anzctr.org.au) on 04/10/2017. Trial identifier ACTRN12617001406392.

Comparison of Synthetic Computed Tomography Generation Methods, Incorporating Male and Female Anatomical Differences, for Magnetic Resonance Imaging-Only Definitive Pelvic Radiotherapy

PurposeThere are several means of synthetic computed tomography (sCT) generation for magnetic resonance imaging (MRI)-only planning; however, much of the research omits large pelvic treatment regions and female anatomical specific methods. This research aimed to apply four of the most popular methods of sCT creation to facilitate MRI-only radiotherapy treatment planning for male and female anorectal and gynecological neoplasms. sCT methods were validated against conventional computed tomography (CT), with regard to Hounsfield unit (HU) estimation and plan dosimetry.Methods and MaterialsPaired MRI and CT scans of 40 patients were used for sCT generation and validation. Bulk density assignment, tissue class density assignment, hybrid atlas, and deep learning sCT generation methods were applied to all 40 patients. Dosimetric accuracy was assessed by dose difference at reference point, dose volume histogram (DVH) parameters, and 3D gamma dose comparison. HU estimation was assessed by mean error and mean absolute error in HU value between each sCT and CT.ResultsThe median percentage dose difference between the CT and sCT was <1.0% for all sCT methods. The deep learning method resulted in the lowest median percentage dose difference to CT at −0.03% (IQR 0.13, −0.31) and bulk density assignment resulted in the greatest difference at −0.73% (IQR −0.10, −1.01). The mean 3D gamma dose agreement at 3%/2 mm among all sCT methods was 99.8%. The highest agreement at 1%/1 mm was 97.3% for the deep learning method and the lowest was 93.6% for the bulk density method. Deep learning and hybrid atlas techniques gave the lowest difference to CT in mean error and mean absolute error in HU estimation.ConclusionsAll methods of sCT generation used in this study resulted in similarly high dosimetric agreement for MRI-only planning of male and female cancer pelvic regions. The choice of the sCT generation technique can be guided by department resources available and image guidance considerations, with minimal impact on dosimetric accuracy.

Long-term satisfaction with curative treatment and follow-up in prostate cancer survivors

Purpose In a cross-sectional observational study to explore long-term satisfaction with treatment among men who had undergone radical prostatectomy (RP) or definitive pelvic radiotherapy (RT) for prostate cancer (PCa). Methods After mean 7 years from therapy (range: 6–8), 431 PCa-survivors (RP: n = 313, RT: n = 118) completed a mailed questionnaire assessing persistent treatment-related adverse effects (AEs) (Expanded Prostate cancer Index Composite [EPIC-26]) and seven Quality indicators describing satisfaction with the health care service following a most often general practitioner (GP)-led follow-up plan. A logistic regression model evaluated the associations between long-term satisfaction and treatment modality, age, the seven satisfaction-related Quality indicators, and persistent AEs. The significance level was set at p< .05. Results Four of five (81%) PCa-survivors reported long-term satisfaction with their treatment. In a multivariable model, satisfaction was positively associated with sufficient information about treatment and AEs, patient-perceived sufficient cooperation between the hospital and the GP and sufficient follow-up of AEs (ref.: insufficient). Age ≥70 years (ref.: <70) and a rising summary score within the EPIC-26 sexual domain additionally increased long-term satisfaction. The treatment modality itself (RP versus RT) did not significantly impact on satisfaction. Conclusions The majority of curatively treated PCa-survivors are satisfied with their treatment more than 5 years after primary therapy. Sufficient information, improved cooperation between the hospital specialists and the responsible GP and optimized follow-up of AEs may further increase long-term satisfaction among prostatectomized and irradiated PCa-survivors.

A Novel Risk Factor for Para-Aortic Lymph Node Recurrence After Definite Pelvic Radiotherapy in Stage IIIB Cervical Cancer.

Background: Studies determining which patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB disease benefit from prophylactic extended-field irradiation (EFRT), which can reduce para-aortic lymph node (PALN) failure rates, are limited. The study was designed to evaluate the value of the controlling nutritional status (CONUT) score as a risk factor for predicting PALN recurrence and identifying potential indications of prophylactic EFRT. Methods: From 2010 to 2015, a retrospective review was conducted among patients with FIGO stage IIIB cervical cancer who were treated with definitive pelvic radiotherapy or concurrent chemoradiotherapy. We analyzed para-aortic lymph node metastasis-free survival (PALNMFS) using Kaplan-Meier curves. Multivariate analyses were performed using Cox regression models. Results: A total of 116 patients with FIGO stage IIIB cervical cancer were included in the study and the median follow-up was 42.2 months (range: 3.5-104.2 months). Multivariate analysis revealed that the CONUT score (HR: 3.141; 95% CI: 2.321-5.436; P < .001) and ≥3 pelvic lymph node metastases (HR: 2.235; 95% CI: 1.428-11.242; P < .001) were independent risk predictors of PALNMFS. Compared with the low CONUT group (score<3), the high CONUT group (score≥3) was associated with a significantly worse 3-year disease-free survival rate (46.9 vs 69.5%, P = .001), a significantly lower 3-year overall survival rate (68.5 vs 79.7%, P = .016) and a significantly lower PALNMFS rate (74.8 vs 96.4%, P < .001). Conclusions: A high CONUT score (score≥3) and ≥3 pelvic metastatic lymph nodes were significant predictors of PALNMFS after pelvic radiation in FIGO stage IIIB cervical cancer patients. Patients with these risk factors might benefit from prophylactic EFRT.

Retrospective analysis of para-aortic lymph node recurrence in locally advanced cervix cancers treated with “pelvic-only field” radiotherapy

INTRODUCTION: Previous studies suggested that treating para-aortic lymph node micro-metastases with extended-field radiotherapy could result in higher rate of tumor control in high-risk locally advanced cervical cancers. Our study aimed to assess the patterns of recurrences following pelvic-only irradiation, with an emphasis on recurrence in para-aortic lymph node. MATERIALS AND METHODS: We retrospectively evaluated patterns of recurrences in patients with cervical cancers who were treated with definitive pelvic radiotherapy at our institution from 2013 to 2016. Univariate and multivariate analyses were performed to identify risk factors associated with para-aortic lymph node recurrence. RESULTS: We enrolled 463 patients in the study. The median of follow-up was 63.5 months. Five-years overall survival, recurrence-free survival, and para-aortic lymph node recurrence rates were respectively 78.9%, 76.2% and 6.5%. During follow-up, 23.33% experienced recurrences. Most often tumors recurred locally (42.60%). Para-aortic recurrences were found in 26 patients. Patients’ age (≤57 years) (HR=4.9, p=0.002), histological subtype (adenocarcinoma) (HR=2.7, p=0.035), presence of pelvic lymph node metastasis (HR=0.3, p=0.037) and absence of brachytherapy (HR=6.5, p&lt;0.0001) were significantly associated with para-aortic lymph node (PALN) recurrence in multivariate analysis. CONCLUSION: Recurrences following pelvic-only irradiation were frequently observed in the pelvis. Clinical characteristics associated with a high risk of PALN recurrence were young age, absence of brachytherapy, presence of pelvic lymph node metastases, and the adenocarcinoma subtype. However, further studies with a greater number of patients need to be undertaken.

Risk factors associated with Para-Aortic Lymph Node Failure after pelvic irradiation in patients with Cervical Cancer.

Objective: Previous studies have shown that prophylactic extended-field irradiation can reduce para-aortic lymph node failure (PALNF) rates in patients with cervical cancer. As such, this type of irradiation may particularly benefit patients with a high risk of PALNF. In the present study, we analyzed the risk factors for PALNF in patients with cervical cancer treated with pelvic irradiation in order to identify potential indications of prophylactic extended-field irradiation.Methods: We evaluated patients with 2018 FIGO stage IB3-IIIC1 cervical cancer who were treated with definitive pelvic radiotherapy or concurrent chemoradiotherapy at our institution between 2011 and 2014. Univariate and multivariate analyses were performed to identify risk factors for PALNF.Results: We included 572 patients in the study. The median follow-up period was 37.9 months. Eighteen patients (3.1%) first site of tumor relapse was the para-aortic lymph nodes, and thus showed PALNF. Using multivariate Cox regression analysis, we identified two significant risk factors for PALNF: tumor extension to the pelvic wall (hazard ratio, HR 3.60, p=0.026) and ≥ 2 pelvic MLNs (HR 5.30, p=0.005). For patients with and without risk factors, the 3-year overall survival, disease-free survival, and PALNF rates were 77.3% and 90.1% (p<0.001), 56.4% and 83.1% (p<0.001), and 12.0% and 2.3% (p<0.001), respectively.Conclusion: Tumor extension to the pelvic wall and ≥ 2 pelvic MLNs are positively associated with PALNF after pelvic irradiation in patients with cervical cancer. Further trials will be required to validate whether patients with these two risk factors may benefit from prophylactic extended-field irradiation.

Efficacy of radical doses of pelvic radiotherapy for primary tumor treatment in patients with newly diagnosed organ metastatic cervical cancer

BackgroundThe clinical efficacy of definitive pelvic radiotherapy for primary tumors in patients with newly diagnosed organ metastatic cervical cancer is unclear. Therefore, we conducted a retrospective study to evaluate the efficacy of definitive pelvic radiotherapy combined with systemic chemotherapy in patients with organ metastatic cervical cancer.MethodsWe retrospectively analysed medical records from patients with newly diagnosed organ metastatic cervical cancer, all treated with chemotherapy at the Zhejiang Cancer Hospital between October 2006 and December 2016. Survival times were compared using the Kaplan-Meier method. The univariate log-rank method and multivariate Cox proportional hazard models were used to identify associated variables with survival.ResultsA total of 48 patients were identified from 11,982 primary cervical cancer patients and divided into two groups according to treatment mode: 36 patients received chemotherapy combined with definitive pelvic radiotherapy (group A), 12 patients underwent chemotherapy with/without palliative pelvic radiotherapy (group B). Median follow-up was 14.4 months (range, 4.6–114.7 months). Median overall survival (OS) for group A and group B was 17.3 and 10 months, respectively. Using the univariate analysis, group A was found to have a better OS than group B (p = 0.002). In multivariate analysis, group A (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15–0.67, p = 0.003) was associated with lower risk of death compared with group B. The main reason for treatment failure was found to be due to the progression of distant metastatic lesions in 36 patients (75%) from the whole cohort.ConclusionIn this cohort of organ metastatic cervical cancer patients in good performance status, chemotherapy combined with definitive pelvic radiotherapy was associated with improved survival outcomes when compared with chemotherapy with/without palliative pelvic radiotherapy. Prospective trials evaluating definitive pelvic radiotherapy for newly diagnosed organ metastatic cervical cancer, therefore, are warranted.

Association of total hysterectomy with survival among newly diagnosed uterine cancer patients with distant organ metastasis.

5583 Background: There is growing evidence that definitive local therapies (surgery or radiotherapy) may increase patient’s survival for some types of metastatic cancers. However, the role of total abdominal hysterectomy (TAH) for newly diagnosed uterine cancer with distant organ metastasis has not been established. The objective of this study is to determine the potential overall survival (OS) benefit associated with TAH for distant metastatic uterine cancer. Methods: The National Cancer Database was analyzed to evaluate OS for newly diagnosed uterine cancer patients with metastasis to brain, lung, liver, bone or distant lymph node, treated with chemotherapy with or without TAH. Those without treatment, treated with definitive pelvic radiotherapy, or without baseline variables were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. In order to control the selection biases, we performed Landmark analysis, and survival analysis by the sequence of chemotherapy and TAH. Separate survival analysis was performed for patients who received chemotherapy plus definitive pelvic radiotherapy (RT) or chemotherapy plus TAH and definitive pelvic RT. Results: From 2010 to 2014, 1,809 uterine cancer patients with distant organ metastasis received chemotherapy alone and 1,388 patients received chemotherapy plus TAH. At a median follow-up of 13.4 months, addition of TAH to chemotherapy was associated with improved survival on univariate (HR 0.57; P &lt; 0.001) and multivariate analysis (HR 0.59; P &lt; 0.001) compared to chemotherapy alone. Propensity score-matched analysis demonstrated superior median survival (19.8 vs 11.0 months) and 2-year OS (44% vs 28%) with TAH (multivariate HR 0.59; P &lt; 0.001). Landmark analyses limited to long-term survivors of ≥0.5, ≥1, and ≥2 years showed improved OS with TAH in all subsets (all P &lt; 0.05). The benefit of TAH was present among not only those involving one metastatic site (HR 0.59; P &lt; 0.001), but also those involving multiple metastatic sites (HR 0.60; P &lt; 0.001). Separate survival analyses showed chemotherapy plus definitive pelvic RT or chemotherapy plus TAH and RT were both superior to chemotherapy alone. Conclusions: In this large contemporary analysis, uterine cancer patients with distant organ metastasis receiving TAH and chemotherapy had substantial longer survival than patients treated with chemotherapy alone. Prospective trials evaluating TAH for metastatic uterine cancer are warranted.

Tumor-specific outcome of metachronous uterine malignancy after pelvic irradiation for cervical cancer

ObjectiveTo examine survival of women who develop metachronous uterine malignancy after definitive pelvic radiotherapy for cervical cancer. MethodsThis retrospective observational study examined the Surveillance, Epidemiology, End Results Program between 1973 and 2013. Women with cervical cancer who received definitive radiotherapy without hysterectomy were examined for the diagnosis of metachronous uterine malignancy (n = 5277). Survival was compared between metachronous and non-metachronous uterine malignancies according to tumor factors. ResultsThe 10- and 20-year cumulative incidences of metachronous uterine malignancy were 0.6% and 1.2%, respectively. When compared to non-metachronous uterine malignancy, metachronous tumor were more likely to be non-endometrioid and advanced-stage (both, P < 0.001). As a whole cohort, metachronous uterine malignancy was significantly associated with decreased overall survival (OS) compared to non-metachronous tumors (hazard ratio [HR] 4.22, P < 0.001). OS was significantly worse in metachronous compared to non-metachronous malignancies, although the magnitude of statistical significance was greater for endometrioid tumors (HRs for endometrioid versus non-endometrioid: 6.17 versus 1.92). For grade 1–2 endometrial cancer, metachronous cases had significantly decreased OS compared to non-metachronous cases, a larger difference than that seen in higher grade tumors (HRs for grade 1–2 versus 3: 7.79 versus 2.15). Similarly, in early-stage endometrial cancer, metachronous cases had significantly decreased OS, with a greater HR compared to advanced-stage disease (HRs for stage I–II versus III–IV: 5.29 versus 2.29). ConclusionRadiotherapy-associated metachronous uterine malignancy after cervical cancer is rare but commonly presents with aggressive tumor characteristics. The impact on survival is considerably high when metachronous uterine malignancy is endometrioid, low-grade, and early-stage.

Insufficiency Fractures after Pelvic Radiotherapy for Uterine Cervical Cancer: An Analysis of Subjects in a Prospective Multi-institutional Trial, and Cooperative Study of Japan Radiation Oncology Group (JAROG) and Japanese Radiation Oncology Study Group (JROSG)

To investigate the pelvic insufficiency fractures (IF) post definitive pelvic radiotherapy for early stage uterine cervical cancer, we analyzed the subject in a prospective multi-institutional study (JAROG0401/ JROSG04-2).

Recent Achievements and Future Developments in Advanced and Recurrent Cervical Cancer: Trials of the Gynecologic Oncology Group

Following publication of five pivotal randomized trials of concurrent chemo-irradiation for patients with locally advanced cervical cancer (ie, International Federation of Gynecology and Oncology (FIGO] stages IB2-IVA) in 1999 and 2000, the National Cancer Institute issued a Clinical Alert advising that concurrent chemotherapy (typically, single-agent cisplatin) be incorporated into the treatment program of women scheduled to receive definitive pelvic radiotherapy. Although the adoption of this new standard has improved overall survival and decreased the recurrence rate by 50%, for those patients who do relapse, the prognosis is very poor and, ultimately, therapy in this setting is palliative in nature. The Gynecologic Oncology Group (GOG) has now completed eight randomized trials for metastatic and recurrent cervical cancer, all of which have studied cisplatin-based regimens. The eighth trial (protocol 204) compared four cisplatin-based doublets containing paclitaxel, topotecan, vinorelbine, or gemcitabine. Because the vast majority of patients are now expected to receive cisplatin "up front" as part of primary therapy with pelvic radiation, there are concerns for the development of drug-resistant clones in recurrences both inside and outside of the radiation field. The GOG has recently reported the results from a phase II trial evaluating the anti-vascular agent, bevacizumab, in women who were eligible for second-line or third-line therapy for metastatic and/or recurrent disease (protocol 227C). It becomes imperative that we continue to evaluate novel regimens for this disease.

Prognostic factors in muscle-invasive bladder cancer treated with radiotherapy: an immunohistochemical study.

To determine the prognostic role of p53, Ki-67 and p21 for patients with muscle-invasive bladder cancer treated with curative intent by radiotherapy. The study included 131 patients (24 women and 107 men, median age 72 years, range 40-86) with transitional cell carcinoma (T2-T4) treated with external definitive pelvic radiotherapy between 1985 and 1994. Paraffin-embedded pretreatment biopsies from the patients were examined for the presence of p53, p21 and Ki-67, detected by immunohistochemistry, and related to tumour stage, grade and patient survival. The expression of p53 protein correlated positively with the detection of Ki-67 (P < 0.05) but did not correlate with p21. None of the immunohistochemical variables (p53, p21 or Ki-67) correlated with T category and only Ki-67 correlated with histological grade. Patients with > 5% p21 expression tended to live longer than those with < 5% (P = 0.09). In a multivariate analysis, the T category (T2/T3 vs. T4), histological grade (2 vs. 3) and p21 expression (< or = 5% vs. > 5%) were independent prognostic factors for overall survival. Further investigation is warranted in patients with muscle-invasive bladder cancer undergoing different types of treatment p21 seems to play an independent prognostic role in these patients, in addition to T category and grade.