PET/CT Staging Followed by Intensity-Modulated Radiotherapy (IMRT) Improves Treatment Outcome of Locally Advanced Pharyngeal Carcinoma: a matched-pair comparison

BACKGROUND: Impact of non-pharmacological innovations on cancer cure rates is difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]-fluoro-2-deoxyglucose-positron emission tomography and integrated computer tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative treatment of advanced pharyngeal carcinoma. PATIENTS AND METHODS: Forty five patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002 until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control analysis on all patients with PET/CT and IMRT was done after matching with eighty six patients treated between 1991 and 2001 without PET/CT and 3D-conformal radiotherapy with respect to gender, age, stage, grade, and tumor location with a ratio of 1:2. Median follow-up was eighteen months (range, 6-49 months) for the PET/CT-IMRT group and twenty eight months (range, 1-168 months) for the controls. RESULTS: PET/CT and treatment with IMRT improved cure rates compared to patients without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was 97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in the control group (p = 0.005). CONCLUSION: PET/CT in combination with IMRT and chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal carcinomas. Long-term follow-up is needed to confirm these findings

Comparison of CT and integrated PET-CT based radiation therapy planning in patients with malignant pleural mesothelioma

<p>Abstract</p> <p>Background</p> <p>When combined with adequate tumoricidal doses, accurate target volume delineation remains to be the one of the most important predictive factors for radiotherapy (RT) success in locally advanced or medically inoperable malignant pleural mesothelioma (MPM) patients. Recently, 18-fluorodeoxyglucose positron emission tomography (PET) has demonstrated significant improvements in diagnosis and accurate staging of MPM. However, role of additional PET data has not been studied in RT planning (RTP) of patients with inoperable MPM or in those who refuse surgery. Therefore, we planned to compare CT with co-registered PET-CT as the basis for delineating target volumes in these patients group.</p> <p>Methods</p> <p>Retrospectively, the CT and co-registered PET-CT data of 13 patients with histologically proven MPM were utilized to delineate target volumes separately. For each patient, target volumes (gross tumor volume [GTV], clinical target volume [CTV], and planning target volume [PTV]) were defined using the CT and PET-CT fusion data sets. The PTV was measured in two ways: PTV1 was CTV plus a 1-cm margin, and PTV2 was GTV plus a 1-cm margin. We analyzed differences in target volumes.</p> <p>Results</p> <p>In 12 of 13 patients, compared to CT-based delineation, PET-CT-based delineation resulted in a statistically significant decrease in the mean GTV, CTV, PTV1, and PTV2. In these 12 patients, mean GTV decreased by 47.1% ± 28.4%, mean CTV decreased by 38.7% ± 24.7%, mean PTV1 decreased by 31.1% ± 23.1%, and mean PTV2 decreased by 40.0% ± 24.0%. In 4 of 13 patients, hilar lymph nodes were identified by PET-CT that was not identified by CT alone, changing the nodal status of tumor staging in those patients.</p> <p>Conclusion</p> <p>This study demonstrated the usefulness of PET-CT-based target volume delineation in patients with MPM. Co-registration of PET and CT information reduces the likelihood of geographic misses, and additionally, significant reductions observed in target volumes may potentially allow escalation of RT dose beyond conventional limits potential clinical benefits in tumor control rates, which needs to be tested in future studies.</p

Cardiovascular Radiation Therapy: a New Standard

The treatment for cardiovascular disease, especially the treatment of coronary stenosis, has been continously improving during the last decades. Routine use of angioplasty was improved by the use of coronary stenting further reducing cardiac morbidity. However, the incidence of restenosis after cardiovascular angioplasty remains high. The restenosis process is mainly explained by neo-intimal proliferation. Therefore, the utility of ionizing radiation has been systematically investigated in order to reduce proliferation of the neointimal tissue. Radiation therapy turns out to be a very efficient approach in reducing the rate of both de novo lesions as well as of instant restenosis. Recent clinical data from randomized trials confirm the utility of intracoronary radiation therapy and change the treatment standards in interventional cardiology.Le traitement des maladies cardiovasculaires et plus spécifiquement la prise en charge des patients avec des sténoses vasculaires, qu’elles soient cardiaques ou périphériques, est en train d’être modifié de façon radicale. Avec l’introduction des techniques d’angioplastie par voie transcutanée (PTCA) et la mise en place de «stents», on a certainement amélioré le devenir de ces malades. Toutefois, l’incidence de resténose après ces interventions endovasculaires reste élevée. Ce phénomène d’oblitération vasculaire après angioplastie ou stent s’explique en partie par des mécanismes de prolifération néo-intimale. On s’est donc logiquement tourné vers les radiations ionisantes com me alternative thérapeutique possible, vu leur efficacité sur les processus de prolifération cellulaire. Autant pour les lésions de novo que les resténoses instent, on observe l’efficacité des radiations ionisantes. Les résultats des premiers essais randomisés ont été rendus publics et ceci va certainement changer les standards de prise en charge en cardiologie interventionnelle

Clinical outcome of postoperative highly conformal versus 3D conformal radiotherapy in patients with malignant pleural mesothelioma

BACKGROUND: Radiotherapy (RT) is currently under investigation as part of a trimodality treatment of malignant pleural mesothelioma (MPM). The introduction of highly conformal radiotherapy (HCRT) technique improved dose delivery and target coverage in comparison to 3-dimensional conformal radiotherapy (3DCRT). The following study was undertaken to investigate the clinical outcome of both radiation techniques. METHODS: Thirty-nine MPM patients were treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant RT. Twenty-five patients were treated with 3DCRT, and 14 with HCRT (Intensity modulated radiotherapy or volumetric modulated arc therapy). Overall survival, disease free survival, locoregional recurrence and pattern of recurrence were assessed. A matched pair analysis was performed including 11 patients of each group. RESULTS: After matching for gender, age, histology, tumor stage and resection status, HCRT seemed superior to 3DCRT with a local relapse rate of 27.3% compared to 72.7% after 3DCRT (p = 0.06). The median time to local relapse was increased by 49% with HCRT in comparison to 3DCRT from 10.9 ± 5.4 months to 16.2 ± 3.1 months (p = 0.06). The median overall survival was 22.3 ± 15.3 months for HCRT and 21.2 ± 9.2 months for 3DCRT (p = 0.57). Recurrence analysis showed that in-field local relapses occurred in previously underdosed regions of the tumor bed in 16% of patients treated with 3DCRT and in 0% of HCRT patients. CONCLUSIONS: The use of HCRT increases the probability of local control as compared to 3DCRT by improving target volume coverage. HCRT did not improve overall survival in this patient series due to the high rate of distant recurrences

Combined photon and electron three-dimensional conformal versus Intensity-Modulated Radiotherapy with integrated boost for adjuvant treatment of malignant pleural mesothelioma after pleuropneumonectomy

PURPOSE: The optimal technique for postoperative radiotherapy (RT) after extrapleural pleuropneumonectomy (EPP) of malignant pleural mesothelioma (MPM) remains debated. METHODS AND MATERIALS: The data from 8 right-sided and 9 left-sided consecutive cases of MPM treated with RT after radical EPP were reviewed. Of the 17 patients, 8 had been treated with three-dimensional (3D) conformal RT (3D-CRT) and 9 with intensity-modulated RT (IMRT) with 6-MV photons. The clinical outcome and adverse events were assessed. For comparative planning, each case was replanned with 3D-CRT using photons and electrons or with IMRT. Homogeneity, doses to the organs at risk, and target volume coverage were analyzed. RESULTS: Both techniques yielded acceptable plans. The dose coverage and homogeneity of IMRT increased by 7.7% for the first planning target volume and 9.7% for the second planning target volume, ensuring >or=95% of the prescribed dose compared with 3D-CRT (p < 0.01). Compared with 3D-CRT, IMRT increased the dose to the contralateral lung, with an increase in the mean lung dose of 7.8 Gy and an increase in the volume receiving 13 Gy and 20 Gy by 20.5% and 7.2%, respectively (p < 0.01). A negligible dose increase to the contralateral kidney and liver was observed. No differences were seen for the spinal cord and ipsilateral kidney. Two adverse events of clinical relevant lung toxicity were observed with IMRT. CONCLUSION: Intensity-modulated RT and 3D-CRT are both suitable for adjuvant RT. IMRT improves the planning target volume coverage but delivered greater doses to the organs at risk. Rigid dose constraints for the lung should be respected

Nasenbluten, Sehstorungen. [Nosebleed, vision disorders]

A 79-year-old man had repeated episodes of nose bleeding, disturbances of vision and anemia. Elevated WBC and lymphocytosis suggested chronic lymphatic leukemia. Serum electrophoresis revealed IgM paraproteinemia. The disease progressed rapidly under appropriate therapy. An autopsy revealed NHL of the lymphoplasmocytoid type (IWF: A--LP-immunocytoma), a NHL carrying a slightly poorer prognosis than classical chronic lymphatic leukemia

Intensity-modulated radiotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy

Radiotherapy reduces the local relapse rate after pleuropneumonectomy of malignant pleural mesothelioma (MPM). The optimal treatment technique with photons remains undefined. Comparative planning for intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) was performed. Six MPM patients with significant postoperative intrathoracic air cavities were planned with IMRT and VMAT. A dose comparison for the targets and organ at risks (OAR) was performed. Robustness was assessed in respect to the variation of target dose with change in volume of air cavities. VMAT reduced the dose to the contralateral lung by reducing the volume covered by 13 Gy and 20 Gy by a factor 1.8 and 2.8, in respect to IMRT (p = 0.02). Dose distribution with VMAT was the most stable technique in regard to postsurgical air cavity variation. For IMRT, V90, V95, and the minimal target dose decreased by 40%, 64%, and 12% compared to 29%, 47%, and 7% with VMAT when air cavity decreased. Two arcs compared to one arc decreased the dose to all the organs at risk (OAR) while leaving PTV dose coverage unchanged. Increasing the number of arcs from two to three did not reduce the dose to the OAR further, but increased the beam-on time by 50%. Using partial arcs decreased the beam-on time by 43%. VMAT allows a lower lung dose and is less affected by the air cavity variation than IMRT. The best VMAT plans were obtained with two partial arcs. VMAT seems currently the most suitable technique for the treatment of MPM patients when air cavities are remaining and no adaptive radiotherapy is performed

Dendritic cells transduced with wild-type p53 gene elicit potent anti-tumour immune responses

In this study we have tested the concept of using wild-type p53 gene for immunotherapy of cancer. Dendritic cells (DC) were transduced with a human wild-type p53 containing recombinant adenovirus (Ad-p53). About a half of DC transduced with this virus expressed p53 protein by FACS analysis 48 h after infection. Mice immunized twice with Ad-p53 DC developed substantial cytotoxic T lymphocyte (CTL) responses against tumour cells expressing wild-type and different mutant human and murine p53 genes. Very low CTL responses were observed against target cells infected with control adenovirus (Ad-c). Immunization with Ad-p53 provided complete tumour protection in 85% of mice challenged with tumour cells expressing human mutant p53 and in 72.7% of mice challenged with tumour cells with murine mutant p53. Treatment with Ad-p53-transduced DC significantly slowed the growth of established tumours. Thus, DC transduced with wild-type p53 may be a promising new tool for the immunotherapy of cancer