Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.

Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using IMRT. The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose-volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7-31.2% depending on the alpha/beta ratio of prostate cancer (p<0.001), and a mean increase in rectal NTCP of 3.0% (p<0.001). If only the DIPTN was dose escalated, the TCP was increased by 6.4-27.5% (p<0.003) and the rectal NTCP was increased by 1.8% (p<0.01). In the dose escalated DIPTN IMRT plans, the highest rectal NTCP was seen in patients with IPTNs in the posterior peripheral zone close to the anterior rectal wall, and the lowest NTCP was seen with IPTNs in the lateral peripheral zone. The ratio of increased TCP to NTCP may represent an improvement in the therapeutic ratio, but was dependent on the position of the IPTN relative to the anterior rectal wall. Improvements in prostate imaging and prostate immobilization are required before clinical implementation would be possible. Clinical trials are required to confirm the clinical benefits of these improved dose distributions

Transformation to "high grade" neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma.

Several different acquired resistance mechanisms of EGFR mutant lung adenocarcinoma to EGFR-tyrosine kinase inhibitor (TKI) therapy have been described, most recently transformation to small cell lung carcinoma (SCLC). We describe the case of a 46-year-old female with relapsed EGFR exon 19 deletion lung adenocarcinoma treated with erlotinib, and on resistance, cisplatin-pemetrexed. Liver rebiopsy identified an afatinib-resistant combined SCLC and non-small cell carcinoma with neuroendocrine morphology, retaining the EGFR exon 19 deletion. This case highlights acquired EGFR-TKI resistance through transformation to the high-grade neuroendocrine carcinoma spectrum and that that such transformation may not be evident at time of progression on TKI therapy. (C) 2012 Elsevier Ireland Ltd. All rights reserved

A comparison of conformal and intensity-modulated techniques for oesophageal radiotherapy.

A comparison of conformal and intensity-modulated techniques for oesophageal radiotherapy. AB Background and purpose: To investigate the potential of intensity-modulated radiotherapy (IMRT) to reduce lung irradiation in the treatment of oesophageal carcinoma with radical radiotherapy. Materials and methods: A treatment planning study was performed to compare two-phase conformal radiotherapy (CFRT) with IMRT in five patients. The CFRT plans consisted of anterior, posterior and bilateral posterior oblique fields, while the IMRT plans consisted of either nine equispaced fields (9F), or four fields (4F) with orientations equal to the CFRT plans. IMRT plans with seven, five or three equispaced fields were also investigated in one patient. Treatment plans were compared using dose-volume histograms and normal tissue complication probabilities. Results: The 9F IMRT plan was unable to improve on the homogeneity of dose to the planning target volume (PTV), compared with the CFRT plan (dose range, 16.9 +/- 4.5 (1 SD) vs. 12.4 +/- 3.9%; P = 0.06). Similarly, the 9F IMRT plan was unable to reduce the mean lung dose (11.7 +/- 3.2 vs. 11.0 +/- 2.9 Gy; P = 0.2). Similar results were obtained for seven, five and three equispaced fields in the single patient studied. The 4F IMRT plan provided comparable PTV dose homogeneity with the CFRT plan (11.8 +/- 3.3 vs. 12.4 +/- 3.9%; P = 0.6), with reduced mean lung dose (9.5 +/- 2.3 vs 11.0 +/- 2.9 Gy; P = 0.001). Conclusions: IMRT using nine equispaced fields provided no improvement over CFRT. This was because the larger number of fields in the IMRT plan distributed a low dose over the entire lung. In contrast, IMRT using four fields equal to the CFRT fields offered an improvement in lung sparing. Thus, IMRT with a few carefully chosen field directions may lead to a modest reduction in pneumonitis, or allow tumour dose escalation within the currently accepted lung toxicity

Potential role of intensity-modulated radiotherapy in the treatment of tumors of the maxillary sinus.

Potential role of intensity-modulated radiotherapy in the treatment of tumors of the maxillary sinus. Purpose: To assess 3-dimensional conformal radiotherapy (3D- CRT) and intensity-modulated. radiotherapy (IMRT) techniques to see whether doses to critical structures could be reduced while maintaining planning target volume (PTV) coverage in patients receiving conventional radiotherapy (RT) for carcinoma of the maxillary sinus because of the risk of radiation-induced complications, particularly visual loss. Methods and Materials: Six patients who had recently received conventional RT for carcinoma of the maxillary sinus were studied. Conventional RT, 3D-CRT, and step-and-shoot IMRT plans were prepared using the same 2-field arrangement. The effect of reducing the number of segments in the IMRT beams was investigated. Results: 3D-CRT and IMRT reduced the brain and ipsilateral parotid gland doses compared with the conventional plans. IMRT reduced doses to both optic nerves; for the contralateral optic nerve, 15- segment IMRT plans delivered an average maximal dose of 56.4 Gy (range 53.9-59.3) compared with 65.7 Gy (range 65.3-65.9) and 64.2 Gy (range 61.4-65.6) for conventional RT and 3D-CRT, respectively. IMRT also gave improved PTV homogeneity and improved coverage, with an average of 8.5 % (range 7.0-11.7 %) of the volume receiving < 95 % of the prescription dose (64 Gy) compared with 14.7 % (range 14.1-15.9 %) and 15.1 % (range 14.4-16.1 %) with conventional RT and 3D-CRT, respectively. Little difference was found between the 15 and 7-segment plans, but 5 segments resulted in a reduced minimal PTV dose. Conclusions: IMRT offers significant advantages over conventional RT and 3D-CRT techniques for treatment of maxillary sinus tumors. Good results can be obtained from 7 segments per beam without compromising the PTV coverage. This number of segments is practical for implementation in a busy RT department

Optimisation of radiotherapy for carcinoma of the parotid gland: a comparison of conventional, three-dimensional conformal, and intensity-modulated techniques

Optimisation of radiotherapy for carcinoma of the parotid gland: a comparison of conventional, three-dimensional conformal, and intensity-modulated techniques. AB Background and purpose: To compare external beam radiotherapy techniques for parotid gland tumours using conventional radiotherapy (RT), three-dimensional conformal radiotherapy (3DCRT), and intensity-modulated radiotherapy (IMRT). To optimise the IMRT techniques, and to produce an IMRT class solution. Materials and methods: The planning target volume (PTV), contra-lateral parotid gland, oral cavity, brain-stern, brain and cochlea were outlined on CT planning scans of six patients with parotid gland tumours. Optimised conventional RT and 3DCRT plans were created and compared with inverse-planned IMRT dose distributions using dose-volume histograms. The aim was to reduce the radiation dose to organs at risk and improve the PTV dose distribution. A beam-direction optimisation algorithm was used to improve the dose distribution of the IMRT plans, and a class solution for parotid gland IMRT was investigated. Results: 3DCRT plans produced an equivalent PTV irradiation and reduced the dose to the cochlea, oral cavity, brain, and other normal tissues compared with conventional RT. IMRT further reduced the radiation dose to the cochlea and oral cavity compared with 3DCRT. For nine- and seven-field IMRT techniques, there was an increase in low-dose radiation to non- target tissue and the contra-lateral parotid gland. IMRT plans produced using three to five optimised intensity-modulated beam directions maintained the advantages of the more complex IMRT plans, and reduced the contra-lateral parotid gland dose to acceptable levels. Three- and four-field non-coplanar beam arrangements increased the volume of brain irradiated, and increased PTV dose inhomogeneity. A four-field class solution consisting of paired ipsilateral coplanar anterior and posterior oblique beams (15, 45, 145 and 170 degrees from the anterior plane) was developed which maintained the benefits without the complexity of individual patient optimisation. Conclusions: For patients with parotid gland tumours, reduction in the radiation dose to critical normal tissues was demonstrated with 3DCRT compared with conventional RT. IMRT produced a further reduction in the dose to the cochlea and oral cavity. With nine and seven fields, the dose to the contra-lateral parotid gland was increased, but this was avoided by optimisation of the beam directions. The benefits of IMRT were maintained with three or four fields when the beam angles were optimised, but were also achieved using a four- field class solution. Clinical trials are required to confirm the clinical benefits of these improved dose distributions