S.A. Engelholm

Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignant pleural mesothelioma

BACKGROUND AND PURPOSE The combination of chemotherapy, surgery, and radiotherapy has improved the prognosis for patients with malignant pleural mesothelioma (MPM). Intensity-modulated radiotherapy (IMRT) has allowed for an increase in dose to the pleural cavity and a reduction in radiation doses to organs at risk. The present study reports and analyses the incidence of fatal pulmonary toxicity in patients treated at Rigshospitalet, Copenhagen. MATERIALS AND METHODS Twenty-six patients were treated with induction chemotherapy followed by extrapleural pneumonectomy and IMRT between April 2003 and April 2006. The entire preoperative pleural surface area was treated to 50 Gy and areas with residual disease or close surgical margins were treated to 60 Gy in 30 fractions. RESULTS The main toxicities were nausea, vomiting, esophagitis, dyspnea, and thrombocytopenia. One patient died from an intracranial hemorrhage during severe thrombocytopenia. Four patients (15%) experienced grade 5 lung toxicity, i.e. pneumonitis 19-40 days after the completion of radiotherapy. Patients with pneumonitis had a significantly larger lung volume fraction receiving 10 Gy or more (V10) (median: 60.3%, range 56.4-83.2%) compared to patients without pneumonitis (median: 52.6%, range: 25.6-80.3%) (p=0.02). Mean lung dose (MLD) was also significantly higher in patients who developed pneumonitis (median 13.9 Gy, range: 13.6-14.2 Gy) than in patients who did not (median=12.4 Gy, range: 8.4-15.4 Gy) (p=0.04). CONCLUSIONS Significant differences in MLD and V10 for patients with fatal pulmonary toxicity compared to patients without fatal lung toxicity have been demonstrated. Based on the presented data local lung dose constraints have been modified in order to avoid unacceptable toxicity.

Does the use of diagnostic PET/CT cause stage migration in patients with primary advanced ovarian cancer?

OBJECTIVE To investigate if the use of diagnostic FDG-PET/CT leads to stage migration in patients with advanced ovarian cancer and to evaluate the prognostic significance of FDG-PET/CT. METHODS From September 2004 to August 2007, 201 patients with a Risk of Malignancy Index (RMI) >150 based on serum CA-125, ultrasound examinations and menopausal state, underwent PET/CT within 2 weeks prior to standard surgery/debulking of a pelvic tumor. On 15 August, 2009 overall survival and prognostic variables were analysed in 66 ovarian cancer patients (64 stage III and 2 stage IV). RESULTS Median follow-up was 30.2 months; median age was 62.5 years (range 35-85 years); 97% (64/66) had a performance status <or=2; 38% (25/66) underwent complete debulking (no macroscopic residual tumor); 51% (39/66) was diagnosed with PET/CT stage III and 41% (27/66) was diagnosed with PET/CT stage IV. Survival was significantly longer for patients with PET/CT stage III than for patients with PET/CT stage IV (P=0.03). Using univariate analysis, PET/CT stage III (P=0.03), complete debulking (no macroscopic residual tumor) (P=0.002), and GOG performance status <or=2 (P=0.04) were statistically significant prognostic variables. Using multivariate Cox regression analysis, complete debulking was the only statistically significant independent prognostic variable (P=0.02). CONCLUSION In primary advanced ovarian cancer the use of diagnostic FDG-PET/CT leads to stage migration. Adequate staging is the foundation for ovarian cancer treatment and advanced imaging for optimal evaluation of metastases should be promoted in clinical trials. The strongest determinant of patient outcome is residual abdominal tumor after primary surgery.

A treatment planning study of the potential of geometrical tracking for intensity modulated proton therapy of lung cancer

Abstract Background. Proton therapy of lung cancer holds the potential for a reduction of the volume of irradiated normal lung tissue. In this work we investigate the robustness of intensity modulated proton therapy (IMPT) plans to motion, and evaluate a geometrical tumour tracking method to compensate for tumour motion. Material and methods. Seven patients with a nine targets with 4DCT scans were selected. IMPT plans were made on the midventilation phase using a 3-field technique. The plans were transferred and calculated on the remaining nine phases of the 4DCT, and the combined dose distribution was summed using deformable image registration (DIR). An additional set of plans were made in which the proton beam was simply geometrically shifted to the centre of the gross tumour volume (GTV), i.e. simulating tracking of the tumour motion but without on-line adjustment of the proton energies. A possible interplay effect between the dynamics of the spot scanning delivery and the tumour motion has not been considered in this work. Results. Around 97–100% of the GTV was covered by 95% of the prescribed dose (V95) for a tumour displacement of less than about 1 cm with a static beam. For the remaining three of nine targets with a larger motion the tracking method studied provided a marked improvement over static beam; raising the GTV V95 from 95 to 100%, 82 to 98% and 51 to 97%, respectively. Conclusion. The possibility of performing DIR and summing the dose on the 4DCT data set was shown to be feasible. The fairly simplistic tracking method suggested here resulted in a marked improvement in GTV coverage for tumours with large intra-fractional motion (>1 cm displacement), indicating that on-line adjustment of the proton energies may be redundant.

PO-0651: Pattern of failure in glioblastoma patients after FET-PET and MRI-guided chemo-radiotherapy

Results: The median overall DBMFS was 12.9 months. A significant difference in median DBMFS was observed for patients with squamous cell vs. adenocarcinoma primary histology (4.57 months vs. 15.9 months, respectively, p <0.015). The initial number of metastases, total initial metastasis volume, ECD status, KPS scores, EGFR mutation status, or ALK gene rearrangement status, made no significant difference on DBMFS. None of the analyzed parameters displayed significant impact on ODBF. WBRT had no significant effect on DBMFS or ODBF in the study population, but patients with history of WBRT prior to SRS had an increased DBFR (0.396 vs. 0.089) which was borderline significant (p=0.05). There was an insufficient number of patients receiving combined WBRT with SRS to determine an effect on distant brain failure vs. SRS alone.

Hilgh Sensitivity and Specificity of PET/CT and Laparoscopic Diagnostic Lymph Node Excision for Lymph Node Metastases in Cervical Cancer Patients

Purpose/Objectives: In cancer of the uterine cervix, lymph node (LN) metastases are associated with poor prognosis. The purpose of this study was to evaluate the efficacy of PET/CT to guide and verify laparoscopic diagnostic lymph node excision in cervical cancer patients. Materials/Methods: A single institution retrospective analysis of procedure efficacy and survival in cervical cancer patients with PET/ CT positive LN as well as identifying possible sources of error. Patient inclusion criteria: Histopathological diagnosis of cervical cancer, LN metastases at PET/CT prior to staging, laparoscopic diagnostic lymph node excision, control PET/CT after surgery. Missed Lesion (ML) was a lesion seen on the staging PET/CT with no sign of tumor tissue at histological analysis and a subsequent planning PET/CT revealing the same lesion as before laparoscopy. False Positive Lesion (FPL) was a lesion seen on the staging PET/CT with no sign of tumor tissue at histological analysis and verified by the planning PET/CT. Kaplan Meier plots and log-rank tests were performed. Histopathology of removed LN number of FPL over time was registered. Results: Sixty-five patients were included. Laparoscopy confirmed metastatic spread to LN in 39 patients. In 4 of 26 patients with negative laparoscopic results, post-operative PET/CT showed ML. Of these, three patients were re-operated of which two had LN metastases confirmed, and one continued having no evidence of metastatic disease. Of the total 23 patients with twice verified negative LN pathology, one patient died of metastatic breast cancer. Of the 42 patients with metastatic disease, 15 died. For the entire staging procedure sensitivity and specificity were calculated to 0.98 and 1.00 respectively. Positive and negative predictive values were 1.00 and 0.96. Of the 23 patients with FPL, histopathology of removed LN showed nonspecific changes of reactive originin65%(C.I.43-84%),fibrosisin17%(5-39%),calcificationsin13% (3-34%), histiocytosis in 35% (16-57%), follicular hyperplasia in 9% (128%) and necrosis in 4% (0-21%) (some showed more than one type). Completely normal architecture was observed in 17% (5-39%) of the patients. No change in frequency of FPL was observed over time. Conclusions: PET/CT as control of laparoscopic diagnostic lymph node excision provides high sensitivity and specificity as well as high positive and negative predictive values, for lymph node staging in cervical cancer patients. However, a high number of FPL was observed at PET/CT, mainly due to inflammation. Although no change in frequency

PD-0212 SURVIVAL AFTER PET/CT PLANNED CONCOMITANT BOOST (IMRT) TO LYMPH NODE METASTASIS IN PATIENTS WITH CERVICAL CANCER

Purpose/Objective: In cancer of the uterine cervix, lymph node metastasis (LN) has been associated with a poor prognosis. The purpose of the current study was to evaluate the effect of the introduction of PET/CT-planned Intensity Modulated Radiotherapy (IMRT) on survival in patients with cervical cancer with LN Materials and Methods: A single institution retrospective analysis of survival and characteristics in cervical cancer patients with LN Inclusion criteria: Histopatological diagnose of cervical cancer, approved curative intended IMRT plan for patients with pelvic and/or para aortic fields, lymph node metastasis verified by CT, PET/CT and/or lymph node biopsy. Cisplatin based chemotherapy concomitant to IMRT. Consecutive patients from 1. January 2000 to 15. September 2011 with primary pelvicor para aortic LN, or recurrence of para aortic LN after primary treatment were included. IMRT was given as a sliding window technique and PET/CT planed on an Eclipse (Varian) doseplanning system. Doses to CTV: 50 Gy and a concomitant boost to LN: 60-64 Gy. Furthermore, patients with primary tumors received PDR brachytherapy 17.5 Gy x 2 Survival statistics and Kaplan Meier plots were calculated using SPSS. The distribution of patient characteristics was also tested. Results: Eighty-three patients were included. Patient characteristics are listed in Table 1. The statistical analysis indicated significant differences in the distributions of histopathology between the three groups. For both age and stage, no significant differences was found.