MR-based follow-up after brachytherapy and proton beam therapy in uveal melanoma

PurposeMRI is increasingly used in the diagnosis and therapy planning of uveal melanoma (UM). In this prospective cohort study, we assessed the radiological characteristics, in terms of anatomical and functional imaging, of UM after ruthenium-106 plaque brachytherapy or proton beam therapy (PBT) and compared them to conventional ultrasound.MethodsTwenty-six UM patients were evaluated before and 3, 6 and 12 months after brachytherapy (n = 13) or PBT (n = 13). Tumour prominences were compared between ultrasound and MRI. On diffusion-weighted imaging, the apparent diffusion value (ADC), and on perfusion-weighted imaging (PWI), the time-intensity curves (TIC), relative peak intensity and outflow percentages were determined. Values were compared between treatments and with baseline.ResultsPre-treatment prominences were comparable between MRI and ultrasound (mean absolute difference 0.51 mm, p = 0.46), but larger differences were observed post-treatment (e.g. 3 months: 0.9 mm (p = 0.02)). Pre-treatment PWI metrics were comparable between treatment groups. After treatment, brachytherapy patients showed favourable changes on PWI (e.g. 67% outflow reduction at 3 months, p < 0.01). After PBT, significant perfusion changes were observed at a later timepoint (e.g. 38% outflow reduction at 6 months, p = 0.01). No consistent ADC changes were observed after either treatment, e.g. a 0.11 x 10(-3)mm(2)/s increase 12 months after treatment (p = 0.15).ConclusionMR-based follow-up is valuable for PBT-treated patients as favourable perfusion changes, including a reduction in outflow, can be detected before a reduction in size is apparent on ultrasound. For brachytherapy, a follow-up MRI is of less value as already 3 months post-treatment a significant size reduction can be measured on ultrasound.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Comparison of magnetic resonance imaging-based and conventional measurements for proton beam therapy of uveal melanoma

Objective: Conventionally, ocular proton therapy (PT) is planned using measurements obtained by an ophthalmologist using ultrasound, fundoscopy, biometry, and intraoperative assessments. Owing to the recent advances in magnetic resonance imaging (MRI) of uveal melanoma (UM), it is possible to acquire high-resolution 3-dimensional images of the eye, providing the opportunity to incorporate MRI in ocular PT planning. In this study, we described how these measurements can be obtained using MRI, compared the MRI-based measurements with conventional ophthalmic measurements, and identified potential pitfalls for both modalities. Design: Cross-sectional study. Subjects: Data from 23 consecutive patients with UM treated with PT were retrospectively evaluated. Methods: Magnetic resonance imaging-based measurements of axial length, tumor height and basal diameter, and marker-tumor distances were compared with the conventional ophthalmic measurements, and discrepancies were evaluated in a multidisciplinary setting. Main Outcome Measures: Tumor prominence and basal diameters on MRI and ultrasound, axial length on MRI and biometry, tumor-marker distances on MRI and measured intraoperatively. Results: The mean absolute differences of the tumor height and basal diameter measurements between ultrasound and MRI were 0.57 mm and 1.44 mm, respectively. Larger absolute differences in height and basal diameter were observed when the full tumor extent was not visible on ultrasound (0.92 mm and 1.67 mm, respectively) compared with when the full tumor extent was visible (0.44 mm and 1.15 mm, respectively). When the full tumor was not visible on ultrasound, MRI was considered more reliable. Tumor-marker distances measured using MRI and intraoperative techniques differed Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Peritoneal carcinomatosis from colorectal cancer. Preclinical and clinical studies into surgical and medical treatment

Contains fulltext : 93554.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 13 april 2012Promotor : Bleichrodt, R.P. Co-promotores : Hendriks, T., Hingh, I.H.J.T. de, Lemmens, V.E.208 p

Peritoneal carcinomatosis of colorectal origin: Incidence, prognosis and treatment options

Contains fulltext : 109022.pdf (publisher's version ) (Open Access)Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitating levels of ascites, which profoundly affect the quality of life for affected patients. PC appears resistant to traditional 5-fluorouracil-based chemotherapy, and surgery was formerly reserved for palliative purposes only. In the absence of effective treatment, the historical prognosis for these patients was extremely poor, with an invariably fatal outcome. These poor outcomes likely explain why PC secondary to CRC has received little attention from oncologic researchers. Thus, data are lacking regarding incidence, clinical disease course, and accurate treatment evaluation for patients with PC. Recently, population-based studies have revealed that PC occurs relatively frequently among patients with CRC. Risk factors for developing PC have been identified: right-sided tumor, advanced T-stage, advanced N-stage, poor differentiation grade, and younger age at diagnosis. During the past decade, both chemotherapeutical and surgical treatments have achieved promising results in these patients. A chance for long-term survival or even cure may now be offered to selected patients by combining radical surgical resection with intraperitoneal instillation of heated chemotherapy. This combined procedure has become known as hyperthermic intraperitoneal chemotherapy. This editorial outlines recent advancements in the medical and surgical treatment of PC and reviews the most recent information on incidence and prognosis of this disease. Given recent progress, treatment should now be considered in every patient presenting with PC

Hyperthermia and intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis: an experimental study

OBJECTIVE: Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C can improve survival if used as an adjunct to cytoreductive surgery (CS) for treatment of peritoneal carcinomatosis (PC). It remains unclear if both hyperthermia and chemotherapy are essential for the reported survival benefit. METHODS: Eighty WAG/Rij rats were inoculated intraperitoneally with the rat colon carcinoma cell line CC-531. Animals were randomly assigned to 1 of the 4 treatment groups (n = 20): CS only, CS followed by HIPEC (mitomycin 35 mg/m(2) at 41 degrees C), CS followed by intraperitoneal mitomycin perfusion at 37 degrees C, CS followed by intraperitoneal saline perfusion at 41 degrees C. Survival was the primary outcome with a maximum follow up of 126 days. RESULTS: Median survival was 62 days in rats treated with CS only and 57 days in rats treated with CS followed by hyperthermic saline perfusion. Rats receiving HIPEC had a median survival of 121 days (P = 0.022 when compared with CS only). In the group treated with chemotherapy at 37 degrees C, 13 of 20 animals were still alive at the end of the experiment so median survival was not reached. (CS vs. IPEC: P = 0.002, hazard ratio 0.36, 95% CI 0.19-0.69) Rats treated with hyperthermic saline perfusion did not have an increased survival as compared with CS only. CONCLUSIONS: The effectiveness of intraoperative intraperitoneal perfusion after CS is highly dependent on the presence of chemotherapeutic agents in the perfusate but not on hyperthermia. The need to include hyperthermia in the adjuvant intraoperative treatment after CS for PC should be further investigated

Intraoperative versus Early Postoperative Intraperitoneal Chemotherapy after Cytoreduction for Colorectal Peritoneal Carcinomatosis: an Experimental Study.

Item does not contain fulltextBACKGROUND: Perioperative intraperitoneal chemotherapy is used as an adjunct to cytoreductive surgery (CS) for peritoneal carcinomatosis (PC) in order to prolong survival. Worldwide, hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and combinations of the two are used. It remains unclear which regimen is most beneficial. METHODS: The rat colon carcinoma cell line CC-531 was injected into the peritoneal cavity of 80 WAG/Rij rats to induce PC. Animals were randomized into four treatment groups (n = 20): CS only, CS followed by HIPEC (mitomycin 35 mg/m(2) at 41.5 degrees C), CS followed by EPIC during 5 days (i.p. injection of mitomycin on day 1 and 5-fluorouracil on days 2-5), and CS followed by HIPEC plus EPIC. Primary outcome was survival. RESULTS: In rats treated with CS only, median survival was 53 days (95% confidence interval (CI) 49-57 days). In rats treated with CS followed by HIPEC, survival was significantly (P = 0.001) increased (median survival 94 days, 95% CI 51-137 days). In the group treated with EPIC after CS, 12 out of 20 rats were still alive at the end of the experiment (P < 0.001 as compared with CS only). In the group receiving both treatments, 11 rats died of toxicity, and therefore this group was not included in the survival analysis. CONCLUSIONS: Both EPIC and HIPEC were effective in prolonging survival. The beneficial effect of EPIC on survival seemed to be more pronounced than that of HIPEC. Further research is indicated to evaluate and compare the possible benefits and adverse effects associated with both treatments.1 juli 201

Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy.

Item does not contain fulltextBACKGROUND: Although systemic therapies have shown to result in survival benefit in patients with metastatic colorectal cancer (mCRC), outcomes in patients with peritoneal carcinomatosis (PC) are poor. No data are available on outcomes of current chemotherapy schedules plus targeted agents in mCRC patients with PC. METHODS: Previously untreated mCRC patients treated with chemotherapy in the CAIRO study and with chemotherapy and targeted therapy in the CAIRO2 study were included and retrospectively analysed according to presence or absence of PC at randomisation. Patient demographics, primary tumour characteristics, progression-free survival (PFS), overall survival (OS), and occurrence of toxicity were evaluated. RESULTS: Thirty-four patients with PC were identified in the CAIRO study and 47 patients in the CAIRO2 study. Median OS was decreased for patients with PC compared with patients without PC (CAIRO: 10.4 versus 17.3 months, respectively (p </= 0.001); CAIRO2: 15.2 versus 20.7 months, respectively (p < 0.001)). Median number of treatment cycles did not differ between patients with or without PC in both studies. Occurrence of major toxicity was more frequent in patients with PC treated with sequential chemotherapy in the CAIRO study as compared to patients without PC. This was not reflected in reasons to discontinue treatment. In the CAIRO2 study, no differences in major toxicity were observed. CONCLUSION: Our data demonstrate decreased efficacy of current standard chemotherapy with and without targeted agents in mCRC patients with PC. This suggests that the poor outcome cannot be explained by undertreatment or increased susceptibility to toxicity, but rather by relative resistance to treatment.1 juli 201

The ROCOCO performance scoring system translates dosimetric differences into clinically relevant endpoints: Comparing IMPT to VMAT in an example pilocytic astrocytoma dataset

Contains fulltext : 232798.pdf (Publisher’s version ) (Open Access)BACKGROUND AND PURPOSE: Proton therapy is expected to outperform photon-based treatment regarding organs at risk (OAR) sparing but to date there is no method to practically measure clinical benefit. Here, we introduce the novel ROCOCO Performance Scoring System (RPSS) translating dose differences into clinically relevant endpoints and apply this to a treatment plan comparison of volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in 20 pilocytic astrocytoma patients. MATERIAL AND METHODS: The RPSS was developed on the basis of expert-based weighting factors and toxicity scores per OAR. The imaging datasets of 20 pilocytic astrocytoma patients having undergone radiotherapy were included in this in silico dosimetric comparison trial as proof of principle. For each of these patients, treatment plans to a total dose of 54 Gy (RBE) were generated for VMAT and IMPT and these were compared regarding radiation dose to the clinical target volume (CTV) and OARs. The RPSS was calculated for each treatment plan comparing VMAT and IMPT. RESULTS: In 40 analysed treatment plans, the average and low dose volumes to various OARs were significantly reduced when using IMPT compared to VMAT (p < 0.05). Using the RPSS, a significant difference between both treatment modalities was found, with 85% of the patients having a lower RPSS in favour of the IMPT plan. CONCLUSION: There are dosimetric differences between IMPT and VMAT in pilocytic astrocytoma patients. In absence of clinically validated NTCP models we introduce the RPSS model in order to objectively compare treatment modalities by translating dosimetric differences in potential clinical differences

Proton therapy for selected low grade glioma patients in the Netherlands

Proton therapy offers an attractive alternative to conventional photon-based radiotherapy in low grade glioma patients, delivering radiotherapy with equivalent efficacy to the tumour with less radiation exposure to the brain. In the Netherlands, patients with favourable prognosis based on tumour and patient characteristics can be offered proton therapy. Radiation-induced neurocognitive function decline is a major concern in these long surviving patients. Although level 1 evidence of superior clinical outcome with proton therapy is lacking, the Dutch National Health Care Institute concluded that there is scientific evidence to assume that proton therapy can have clinical benefit by reducing radiation-induced brain damage. Based on this decision, proton therapy is standard insured care for selected low grade glioma patients. Patients with other intracranial tumours can also qualify for proton therapy, based on the same criteria. In this paper, the evidence and considerations that led to this decision are summarised. Additionally, the eligibility criteria for proton therapy and the steps taken to obtain high-quality data on treatment outcome are discussed

Proton therapy for selected low grade glioma patients in the Netherlands

Proton therapy offers an attractive alternative to conventional photon-based radiotherapy in low grade glioma patients, delivering radiotherapy with equivalent efficacy to the tumour with less radiation exposure to the brain. In the Netherlands, patients with favourable prognosis based on tumour and patient characteristics can be offered proton therapy. Radiation-induced neurocognitive function decline is a major concern in these long surviving patients. Although level 1 evidence of superior clinical outcome with proton therapy is lacking, the Dutch National Health Care Institute concluded that there is scientific evidence to assume that proton therapy can have clinical benefit by reducing radiation-induced brain damage. Based on this decision, proton therapy is standard insured care for selected low grade glioma patients. Patients with other intracranial tumours can also qualify for proton therapy, based on the same criteria. In this paper, the evidence and considerations that led to this decision are summarised. Additionally, the eligibility criteria for proton therapy and the steps taken to obtain high-quality data on treatment outcome are discussed. (C) 2020 The Author(s). Published by Elsevier B.V.Biological, physical and clinical aspects of cancer treatment with ionising radiatio