Background
Recurrence in glioblastoma patients often occur close to the original tumour and indicates that the current treatment is inadequate for local tumour control. In this study, we explored the ...feasibility of using multi-modality imaging at the time of radiotherapy planning. Specifically, we aimed to identify parameters from pre-treatment PET and MRI with potential to predict tumour recurrence.
Materials and methods
Sixteen patients were prospectively recruited and treated according to established guidelines. Multi-parametric imaging with
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F-FET PET/CT and
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F-FDG PET/MR including diffusion and dynamic contrast enhanced perfusion MRI were performed before radiotherapy. Correlations between imaging parameters were calculated. Imaging was related to the voxel-wise outcome at the time of tumour recurrence. Within the radiotherapy target, median differences of imaging parameters in recurring and non-recurring voxels were calculated for contrast-enhancing lesion (CEL), non-enhancing lesion (NEL), and normal appearing grey and white matter. Logistic regression models were created to predict the patient-specific probability of recurrence. The most important parameters were identified using standardized model coefficients.
Results
Significant median differences between recurring and non-recurring voxels were observed for FDG, FET, fractional anisotropy, mean diffusivity, mean transit time, extra-vascular, extra-cellular blood volume and permeability derived from scans prior to chemo-radiotherapy. Tissue-specific patterns of voxel-wise correlations were observed. The most pronounced correlations were observed for
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F-FDG- and
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F-FET-uptake in CEL and NEL. Voxel-wise modelling of recurrence probability resulted in area under the receiver operating characteristic curve of 0.77 from scans prior to therapy. Overall, FET proved to be the most important parameter for recurrence prediction.
Conclusion
Multi-parametric imaging before radiotherapy is feasible and significant differences in imaging parameters between recurring and non-recurring voxels were observed. Combining parameters in a logistic regression model enabled patient-specific maps of recurrence probability, where
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F-FET proved to be most important. This strategy could enable risk-adapted radiotherapy planning.
This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian ...tube, or primary peritoneal cancer.
Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks).
A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm.
Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.
Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated ...with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa).
A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT.
The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 CI: 6.67-20.14). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT.The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT.
The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.
Surgical resection provides long term survival in approximately 30% of patients with colorectal carcinoma (CRC) liver metastases. However, only a limited number of patients with CRC-metastases are ...amendable for surgery. We have tested the effect of stereotactic body radiotherapy (SBRT) in the treatment of inoperable patients with CRC-metastases. Sixty-four patients with a total number of 141 CRC-metastases in the liver (n = 44), lung (n = 12), lymph nodes (n = 3), suprarenal gland (n = 1) or two organs (n = 4) were treated with SBRT with a central dose of 15 Gy×3 within 5-8 days. Median follow-up was 4.3 years. After 2 years, actuarial local control was 86% and 63% in tumor and patient based analysis, respectively. Nineteen percent were without local or distant progression after 2 years and overall survival was 67, 38, 22, 13, and 13% after 1, 2, 3, 4 and 5 years, respectively. One patient died due to hepatic failure, one patient was operated for a colonic perforation and two patients were conservatively treated for duodenal ulcerations. Beside these, only moderate toxicities such as nausea, diarrhoea and skin reactions were observed. SBRT in patients with inoperable CRC-metastases resulted in high probability of local control and promising survival rate. One toxic death and few severe reactions were observed. For the majority of patients, the treatment related toxicity was moderate.
Abstract 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.
This study was intended to determine the role of PET/CT in the staging of anal cancer as a supplement to three-dimensional transanal ultrasound (TAUS) and inguinal ultrasound (US). The impact of the ...PET/CT on the initial stage and treatment plan proposed by TAUS/US was assessed.
Ninety-five (95) patients referred to our clinic between July 1, 2005, and December 31, 2009, were retrospectively reviewed. All patients had biopsy-proven primary squamous cell cancer of the anal canal. There were 65 females (68%) and 30 males (32%), and the median age was 58 years (range, 35-88 years). Six (6%) of the patients were HIV positive. All patients were staged with TAUS/US and PET/CT.
Twenty-eight (28) patients were diagnosed with suspicious perirectal node metastases. TAUS visualized 24 of these, whereas PET/CT detected 15. Suspicious inguinal nodes were visualized on either US or PET/CT in 41 patients. Seventeen (17) of these had confirmed malignant disease on biopsy, and 15 had confirmed benign disease. All 17 patients (100%) with malignant inguinal nodes were diagnosed by PET/CT, whereas US identified 16 (94%). Ten patients were diagnosed with suspicious inguinal nodes on PET/CT that had not been seen on US. One of these was malignant, three were benign, and six were not biopsied. PET/CT diagnosed eight metastatic sites, whereas TAUS/US diagnosed three. PET/CT discovered three of the five synchronous cancers seen in this study. PET/CT upstaged the disease in 14% of the cases and changed the treatment plan proposed by TAUS/US in 17%.
PET/CT has great potential influence on the staging and treatment of anal cancer. TAUS is important in the staging of the primary tumor and N1-stage, whereas PET/CT seems necessary for the N2/3-stage, the M-stage and synchronous cancers.
To determine visual outcome including the occurrence of radiation induced optic neuropathy (RION) as well as tumor control after fractionated stereotactic radiation therapy (FSRT) of benign anterior ...skull base meningiomas or pituitary adenomas. Thirty-nine patients treated with FSRT for anterior skull base meningiomas and 55 patients treated with FSRT for pituitary adenomas between January 1999 and December 2009 with at least 2 years follow-up were included. Patients were followed up prospectively with magnetic resonance imaging scans, visual acuity and visual field examinations. RION was found in four (10 %) patients with anterior skull base meningiomas and seven patients (13 %) with pituitary adenomas. The five-year actuarial freedom from 25 % RION visual field loss was 94 % following FSRT. Actuarial 2-, 5- and 10-year tumor control rates were 100, 88.4 and 64.5 % for anterior skull base meningiomas and 100, 98.2 and 94.9 % for pituitary adenomas, respectively. Patients with an impaired visual field function pre-FSRT were more likely to experience worsened function (
p
= 0.016). We found that RION, was a relatively uncommon event, in a large prospective cohort of patients that were systematically monitored following FSRT of benign anterior skull base tumors. Long term tumor control was favorable, especially for pituitary adenomas.
•Correlation between known risk factors and spinal toxicity could not be established in this cohort.•Diabetes was related to increased toxicity.•The risk of radiation induced fracture should be ...considered before reirradiation.
In this study we investigate the risk of radiation-induced serious adverse event of the spine in a large cohort of consecutive retreated patients with palliative radiotherapy (RT) for metastatic cancer in the spine.
From 2010 to 2014, 2387 patients received spinal irradiation with a palliative intent for metastatic spinal cord compression at our institution. The patients were reviewed for prior RT and 220 patients had received re-irradiation of the spine. Clinical and treatment data were obtained from the patients’ records and the RT planning system.
Patients had metastatic disease from breast, prostate, lung, hematological or other cancers (22.7%, 21.8%, 21.4%, 3.2% and 30.9%, respectively). Median follow-up was 99 days. Median cumulative EQD2 was 57.6 Gy2; range: 20.0–90.0 Gy. Spinal events related to re-irradiation were observed in fourteen patients; six patients were diagnosed with radiation-induced myelopathy (RIM) and nine patients with radiation-induced vertebral fracture (RIF). In a multivariate analysis, diabetes was related to increased risk of toxicity (HR = 7.9; P = 0.003).
The incidence of RIM and RIF (6 and 9 out of 220 patients, respectively) was low in our cohort of re-irradiated patients. Patients with diabetes had a higher risk of adverse events which should be considered before re-irradiation of the spine.
The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for ...patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial.
Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15Gy×3 within 5–10 days.
Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach.
SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma.
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