Pearly Khaw

F-18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with nonsmall cell lung carcinoma

Successful treatment of nonsmall cell lung carcinoma (NSCLC) with radical radiotherapy (RT) requires accurate delineation of tumor extent. Conventional computed tomography–based noninvasive staging often estimates intrathoracic thoracic tumor extent incorrectly and fails to detect distant metastasis. High sensitivity and specificity are reported for F‐18 fluorodeoxyglucose (FDG) positron emission tomography (PET) staging in potentially resectable NSCLC. The authors investigated FDG‐PET staging in radical RT candidates with unresectable NSCLC.

Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial

BACKGROUND About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer. METHODS PORTEC-3 was a multicentre, open-label, randomised, international trial. Women with high-risk endometrial cancer were randomly allocated (1:1) to radiotherapy alone (48·6 Gy) in 1·8 Gy fractions five times a week or chemoradiotherapy (two cycles concurrent cisplatin 50 mg/m(2) and four adjuvant cycles of carboplatin area under the curve [AUC] 5 and paclitaxel 175 mg/m(2)) using a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The primary endpoints of the PORTEC-3 trial were overall survival and failure-free survival analysed in the intention-to-treat population. This analysis focuses on 2-year toxicity and health-related quality of life as secondary endpoints; analysis was done according to treatment received. Health-related quality of life was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) the cervix cancer module and chemotherapy and neuropathy subscales of the ovarian cancer module at baseline, after radiotherapy and at 6, 12, 24, 36, and 60 months after randomisation. Adverse events were graded with Common Terminology Criteria for Adverse Events version 3.0. The study was closed on Dec 20, 2013, after achieving complete accrual, and follow-up remains ongoing for the primary outcomes analysis. This trial is registered with ISRCTN.com, number ISRCTN14387080, and with ClinicalTrials.gov, number NCT00411138. FINDINGS Between Sept 15, 2006, and Dec 20, 2013, 686 women were randomly allocated in the PORTEC-3 trial. Of these, 660 met eligibility criteria, and 570 (86%) were evaluable for health-related quality of life. Median follow-up was 42·3 months (IQR 25·8-55·1). At completion of radiotherapy and at 6 months, EORTC QLQ-C30 functioning scales were significantly lower (worse functioning) and health-related quality of life symptom scores higher (worse symptoms) for the chemoradiotherapy group compared with radiotherapy alone, improving with time. At 12 and 24 months, global health or quality of life was similar between groups, whereas physical functioning scores remained slightly lower in patients who received chemoradiotherapy compared with patients who received radiotherapy alone. At 24 months, 48 (25%) of 194 patients in the chemoradiotherapy group reported severe tingling or numbness compared with 11 (6%) of 170 patients in the radiotherapy alone group (p<0·0001). Grade 2 or worse adverse events were found during treatment in 309 (94%) of 327 patients in the chemoradiotherapy group versus 145 (44%) of 326 patients in the radiotherapy alone group, and grade 3 or worse events were found in 198 (61%) of 327 patients in the chemoradiotherapy group versus 42 (13%) of 326 patients in the radiotherapy alone group (p<0·0001), with most of the grade 3 adverse events being haematological (45%). At 12 and 24 months, no significant differences in grade 3 or worse adverse events were found between groups; only grade 2 or higher sensory neuropathy adverse events persisted at 24 months (25 [10%] of 240 patients in the chemoradiotherapy group vs one [<1%] of 247 patients in the radiotherapy alone group; p<0·0001). INTERPRETATION Despite the increased physician and patient-reported toxicities, this schedule of adjuvant chemotherapy given during and after radiotherapy in patients with high-risk endometrial cancer is feasible, with rapid recovery after treatment, but with persistence of patient-reported sensory neurological symptoms in 25% of patients. We await the analysis of primary endpoints before final conclusions are made. FUNDING Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Project Grant, Cancer Australia Grant, Italian Medicines Agency, and Canadian Cancer Society Research Institute.

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.

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.

Smokers with cervix cancer have more uterine corpus invasive disease and an increased risk of recurrence after treatment with chemoradiation.

Background Smoking is a risk factor for cervix cancer and causes hypoxemia, which promotes tumor infiltration and potentially impacts on treatment outcome. We performed a retrospective study to determine if smokers had an increased risk of uterine corpus infiltration, which is associated with more advanced disease and/or treatment failure after primary chemoradiation. Methods Results from a prospective database of patients treated with primary chemoradiation for locally advanced cervix cancer with a pretreatment MRI were analyzed. Smoking status was assessed by self-report at presentation. Results Smoking status was recorded for 346 of the 362 patients with 98 current smokers (28%), 56 ex-smokers (16%), and 192 nonsmokers (55%). Median age was 58 years with ever-smokers having a younger age at diagnosis than nonsmokers. Histologic type, International Federation of Gynecology and Obstetrics stage, tumor volume, and nodal involvement were similar across groups, as were toxicities of treatment. Ever-smokers were more likely to have corpus uterine invasion than nonsmokers. Ever-smokers had more recurrences than nonsmokers, with nonsmokers having a longer median overall survival (50.1 vs 38.7 months, P = 0.004) and relapse-free survival (46.8 vs 28.5 months, P = 0.003). In multifactor analysis, ever-smoking status was a significant predictor of developing corpus invasive disease and of inferior relapse-free and overall survival after treatment. Conclusions Smokers have a greater risk for developing corpus invasive cervix cancer. Although nonsmokers have an older age at diagnosis, they live longer and have fewer recurrences after a diagnosis of locally advanced carcinoma of the cervix.

Relief of non-metastatic shoulder pain with mediastinal radiotherapy in patients with lung cancer

Three patients with lung cancer and shoulder pain for which no local cause could be found are described. All three benefited from a course of palliative radiotherapy to ipsilateral mediastinal disease remote from the site of the pain. It is suggested that the pain is referred from intrathoracic involvement of the phrenic nerve by cancer, and that palliative irradiation of the mediastinum should be considered if investigations fail to reveal a local cause for ipsilateral shoulder pain.

Patients' and clinicians' preferences for adjuvant chemotherapy in endometrial cancer: an ANZGOG substudy of the PORTEC-3 intergroup randomised trial.

Background:To determine the minimum survival benefits that patients, and their clinicians, judged sufficient to make adjuvant chemotherapy (ACT) worthwhile, in addition to pelvic radiotherapy, for women with high risk and advanced stage endometrial cancer.Methods:Eighty-three participants in the PORTEC-3 trial completed a time trade-off questionnaire before and after adjuvant therapy; 44 of their clinicians completed it once only. The questionnaire used four hypothetical scenarios including baseline survival times without ACT of 5 and 8 years, and baseline survival rates at 5 years without ACT of 50 and 65%.Results:Over 50% of patients judged an extra 1 year of survival time or an extra 5% in survival rate sufficient to make ACT worthwhile. Over 50% of clinicians judged an extra 1 year of survival time, or an extra 10% in survival rate, sufficient to make ACT worthwhile. Compared with patients, clinicians required similar survival time benefits (medians both 1 year, P=0.4), but larger survival rate benefits (medians 8.5% vs 5%, P=0.03), and clinicians’ preferences varied less (IQR 0.5–1.5 years vs 0.4–2 years, P=0.0007; 5–10% vs 1–13%, P=0.004). Patients’ preferences changed over time for the survival rate scenarios depending on whether they had ACT or not (change in median benefit - 3 months vs 2.5 months respectively, P=0.028). There were no strong predictors of patients’ or clinicians’ preferences.Conclusions:Patients and clinicians judged moderate survival benefits sufficient to make ACT worthwhile after pelvic radiotherapy for endometrial cancer. These benefits are larger than those judged sufficient by patients with breast or colon cancers, but similar to those judged sufficient by patients with lung or ovarian cancers.

Stage IB cervix cancer with nodal involvement treated with primary surgery or primary radiotherapy: Patterns of failure and outcomes in a contemporary population.

The purpose of this study is to evaluate patterns of failure, overall survival (OS), disease‐free survival (DFS), prognostic factors and late toxicities in node positive International Federation of Gynaecology and Obstetrics (FIGO) stage IB cervix cancer treated with curative intent.

Carcinoma of the cervix in elderly patients treated with radiotherapy: patterns of care and treatment outcomes

Objective The aim of this analysis was to examine the management of cervix cancer in elderly patients referred for radiotherapy and the results of treatment in terms of overall survival (OS), relapse-free survival (RFS), and treatment-related toxicities. Methods Patients were eligible if they were aged ≥75 years, newly diagnosed with cervix cancer and referred for radiotherapy as part of their treatment. Patient details were retrieved from the gynaecology service database where clinical, histopathological treatment and follow-up data were prospectively collected. Results From 1998 to 2010, 126 patients aged ≥75 years, met selection criteria. Median age was 81.5 years. Eighty-one patients had definitive radiotherapy, 10 received adjuvant radiotherapy and 35 had palliative radiotherapy. Seventy-one percent of patients had the International Federation of Gynecology and Obstetrics stage 1b–2b disease. Median follow-up was 37 months. OS and RFS at 3 years among those treated with curative intent were 66.6% and 75.9% respectively with majority of patients dying without any evidence of cervix cancer. Grade 2 or more late toxicities were: bladder 5%, bowel 11%, and vagina 27%. Eastern Cooperative Oncology Group (ECOG) status was a significant predictor of OS and RFS with each unit increment in ECOG score increased the risk of death by 1.69 times (p<0.001). Conclusion Following appropriate patient selection, elderly patients treated curatively with radiotherapy for cervix cancer have good disease control. Palliative hypofractionated regimens are well tolerated in patients unsuitable for radical treatment.

Results of the Australasian (Trans-Tasman Oncology Group) radiotherapy benchmarking exercise in preparation for participation in the PORTEC-3 trial

Protocol deviations in Randomised Controlled Trials have been found to result in a significant decrease in survival and local control. In some cases, the magnitude of the detrimental effect can be larger than the anticipated benefits of the interventions involved. The implementation of appropriate quality assurance of radiotherapy measures for clinical trials has been found to result in fewer deviations from protocol. This paper reports on a benchmarking study conducted in preparation for the PORTEC‐3 trial in Australasia.