SummaryBackgroundIndications for chemotherapy in gestational trophoblastic disease include raised human chorionic gonadotropin (hCG) concentrations 6 months after uterine evacuation of hydatidiform mole, even when values are falling. We aimed to establish whether chemotherapy is always necessary in these patients.MethodsWe retrospectively identified women registered between January, 1993, and May, 2008, at Charing Cross Hospital, London, UK, who had persistently high hCG concentrations 6 months after evacuation of hydatidiform mole. Rates of hCG normalisation, relapse, and death were assessed in patients continued under surveillance and those who received chemotherapy after 6 months. We postulated that a surveillance policy would be clinically acceptable if hCG values returned to normal in 75% of patients or more.Findings76 (<1%) of 13 960 patients with hydatidiform moles had persistently high hCG concentrations of more than 5 IU/L 6 months after evacuation. 66 (87%) patients continued under surveillance and hCG values spontaneously returned to normal without chemotherapy in 65 (98%) of these patients. Values in one patient did not become normal because of chronic renal failure, but she remains healthy. Ten patients received chemotherapy, and hCG concentrations returned to normal in eight (80%) of these individuals (surveillance vs chemotherapy groups p=0·044) and remained slightly high (6–11 IU/L) in two without any associated clinical problems off treatment. We noted no significant differences between individuals in the surveillance and chemotherapy groups, apart from lower median hCG concentrations 6 months after evacuation in those under surveillance than in those given chemotherapy (13 IU/L, range 5–887, vs 157 IU/L, range 6–6438; p=0·004). Overall, there were no deaths in this series.InterpretationA surveillance policy seems to be clinically acceptable in patients with low and declining concentrations of hCG 6 months after evacuation of hydatidiform mole.FundingNational Commissioning Group, Imperial Experimental Cancer Medicine Centre, Imperial Biomedical Research Centre, and Cancer Research UK.
To use a model-based approach to identify a subgroup of patients with locally advanced lung cancer who would benefit from proton therapy compared to photon therapy for reduction of cardiac toxicity. Material/methods: Volumetric modulated arc photon therapy (VMAT) and robust-optimised intensity modulated proton therapy (IMPT) plans were generated for twenty patients with locally advanced lung cancer to give a dose of 70 Gy (relative biological effectiveness (RBE)) in 35 fractions. Cases were selected to represent a range of anatomical locations of disease. Contouring, treatment planning and organs-atrisk constraints followed RTOG-1308 protocol. Whole heart and ub-structure doses were compared. Risk estimates of gradeP3 cardiac toxicity were calculated based on normal tissue complication probability (NTCP) models which incorporated dose metrics and patients baseline risk-factors (pre-existing heart disease (HD)). Results: There was no statistically significant difference in target coverage between VMAT and IMPT. IMPT delivered lower doses to the heart and cardiac substructures (mean, heart V5 and V30, P < .05). In VMAT plans, there were statistically significant positive correlations between heart dose and the thoracic vertebral level that corresponded to the most inferior limit of the disease. The median level at which the superior aspect of the heart contour began was the T7 vertebrae. There was a statistically significant difference in dose (mean, V5 and V30) to the heart and all substructures (except mean dose to left coronary artery and V30 to sino-atrial node) when disease overlapped with or was inferior to the T7 vertebrae. In the presence of pre-existing HD and disease overlapping with or inferior to the T7 vertebrae, the mean estimated relative risk reduction of gradeP3 toxicities was 24-59%. Conclusion: IMPT is expected to reduce cardiac toxicity compared to VMAT by reducing dose to the heart and substructures. Patients with both pre-existing heart disease and tumour and nodal spread overlapping with or inferior to the T7 vertebrae are likely to benefit most from proton over photon therapy.
Aims Evidence has emerged that internal mammary chain (IMC) radiotherapy reduces breast cancer mortality, leading to changes in treatment guidelines. This study investigated current IMC radiotherapy criteria and the percentages of patients irradiated for breast cancer in England who fulfilled them. Materials and methods A systematic search was undertaken for national guidelines published in English during 2013–2018 presenting criteria for ‘consideration of’ or ‘recommendation for’ IMC radiotherapy. Patient and tumour variables were collected for patients who received breast cancer radiotherapy in England during 2012–2016. The percentages of patients fulfilling criteria stipulated in each set of guidelines were calculated. Results In total, 111 729 women were recorded as receiving adjuvant breast cancer radiotherapy in England during 2012–2016 and full data were available on 48 095 of them. Percentages of patients fulfilling IMC radiotherapy criteria in various national guidelines were: UK Royal College of Radiologists 13% (6035/48 095), UK National Institute for Health and Care Excellence 18% (8816/48 095), Germany 32% (15 646/48 095), Ireland 56% (26 846/48 095) and USA 59% (28 373/48 095). Differences between countries occurred because in Ireland and the USA, treatment may be considered in some node-negative patients, whereas in the UK, treatment is considered if at least four axillary nodes are involved or for high-risk patients with one to three positive nodes. In Germany, treatment may be considered for all node-positive patients. Conclusions There is substantial variability between countries in criteria for consideration of IMC radiotherapy, despite guidelines being based on the same evidence. This will probably lead to large variations in practice and resource needs worldwide.
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