Η ΣΤΟΧΕΥΜΕΝΗ ΑΚΤΙΝΟΘΕΡΑΠΕΙΑ ΣΤΟΝ ΗΠX ΚΑΡΚΙΝΟ Κουλουλίας Ειρ. Βασίλειος Αναπλ. Καθηγητής Ακτινοθεραπευτικής Ογκολογίας Ιατρική Σχολή Παν. Αθηνών B Εργαστηριο Ακτινολογίας Μονάδα Ακτινοθεραπείας ΠΓΝ ATTIKON
3D CRT : Βασικές Αρχές Όγκοι και Στόχοι (Volumes & Targets) Ορισμοί [ICRU 50 and 62] GTV (Gross Tumor Volume) CTV (Clinical Target Volume) PTV (Planning Target Volume) Όρια (Margins)
Όγκοι, Στόχοι, Όρια : Σκοπός Ένας από τους στόχους της ακτινοθεραπείας είναι η μεγιστοποίηση του θεραπευτικού αποτελέσματος, δηλαδή ο καλύτερος έλεγχος του όγκου, σε συνδυασμό με την ελαχιστοποίηση της πιθανότητας επιπλοκών.
Όγκοι, Στόχοι, Όρια : Σκοπός Για να επιτευχθεί είναι απαραίτητο: Η επιλογή των στόχων να γίνεται με ακρίβεια, και Να αποφεύγεται, όσο το δυνατόν περισσότερο, η επιβάρυνση, κρίσιμων φυσιολογικών οργάνων
ICRU (50) Όγκοι (Volumes) Gross Tumor Volume (GTV) Clinical Target Volume (CTV) Planning Target Volume (PTV)
Gross Tumor Volume Δύναται να προσδιοριστεί με κλινική εξέταση και / ή με απεικονιστικές τεχνικές
Clinical Target Volume Gross Tumor Volume ± υποκλινική νόσος Yποκλινική νόσος: παρουσία πιθανών καρκινικών κυττάρων, που δεν μπορούν να ανιχνευτούν με καθιερωμένες τεχνικές. Περιλαμβάνονται επίσης ιστοί με αυξημένο κίνδυνο κλινικής διασποράς (π.χ. λεμφαδένες)
Planning Target Volume Γεωμετρικό μέγεθος που επιβεβαιώνει ότι η δόση τελικώς αποδίδεται στο CTV. Σχεδιάζεται για τις αποκλίσεις της διάστασης, μορφής και θέσης των CTV. Οι αποκλίσεις μπορεί να είναι τυχαίες (φυσικές διαδικασίες, κινήσεις ασθενούς) ή συστηματικές (απώλεια βάρους, τεχνικοί περιορισμοί). Οι αποκλίσεις μπορεί να συμβούν είτε κατά την διάρκεια μίας συνεδρίας (intrafraction), είτε μεταξύ συνεδριών (interfraction)
Όρια Υπολογίζουν την κίνηση των εσωτερικών οργάνων. Internal Target Volume (ITV) Ο γεωμετρικός όγκος που εσωκλείει το CTV και την εσωτερική του κίνηση. Setup Margin (SM): - Υπολογίζει την κίνηση του ασθενούς. - Εξαρτάται από τις μεθόδους ακινητοποίησης και από τον ελέγχου της καθημερινής τοποθέτησης του ασθενούς.
Μέθοδος τεχνικής 3D CRT Ακινητοποίηση Λήψη CT scan Σχεδιασμός Πλάνου Contouring Ορισμός Δεσμών & Υπολογισμός Δόσης Αξιολόγηση Πλάνου Εξομοίωση (Επαλήθευση θέσης Ισοκέντρου) Εκτέλεση Θεραπείας / Επαλήθευση
ΠΑΓΚΡΕΑΣ
ESTRO 33 SOMETHING IS MISSING
Neoadjuvant Gemcitabine Chemotherapy followed by Concurrent IMRT Simultaneous Boost Achieves High R0 Resection in Borderline Resectable Pancreatic Cancer Patients. PLOS one 2016, Huang et al. BACKGROUND:To study the feasibility of down stage the borderline resectable pancreatic cancer (BRPC) to resectable disease, we reported our institutional results using an intensity-modulated radiation therapy (IMRT) simultaneous integrated boost (SIB) dose escalation approach to improve R0 resectability. METHODS:We reviewed our past 7 years of experience of using neoadjuvant induction chemotherapy with Gemcitabine followed by concurrent chemoradiaiton for BRPC. During the concurrent, chemo was 5-FU and radiation were IMRT with SIB technique to target the key areas with dose escalation to 5600 in 28 fractions. The key areas were defined by PET positive area. This was followed by restaging imaging to rule out distant metastases before resection. RESULTS:25 finished dose escalation protocol. 2 of the 25 cases developed distant metastases, 23 (92%) patients without distant metastases underwent pancreatectomy. Among the those received pancreatectomy, 22 (95%) achieved negative margin (R0). The gastrointestinal toxicity > grade 2 was 8% and there was no grade 4 toxicity. CONCLUSION:Neoadjuvant Gemcitabine-based induction chemotherapy followed by 5- FU-based IMRT-SIB is a feasible option in improving the likelihood of R0 resection rate in BRPC without compromising the organs at risk for toxicity.
Chemotherapy and intensity-modulated radiation therapy for locally advanced pancreatic cancer achieves a high rate of R0 resection. Huquet et al. Acta Oncol 2016 BACKGROUND:To assess local control, survival and conversion to resectability among locally advanced pancreatic cancer (LAPC) patients treated with induction chemotherapy (ICT) followed by chemoradiotherapy treatment using intensitymodulated radiation therapy (IMRT). MATERIAL AND METHODS:Between 2007 and 2012, 134 LAPC patients were treated with ICT followed by IMRT. After chemoradiotherapy, 40 patients received maintenance chemotherapy. RESULTS:With a median follow-up of 20 months, median overall survival (OS) was 23 months. One- and two-year OS was 85% and 47%, respectively. On multivariate analysis, progression of disease after IMRT was associated with worse OS. Cumulative incidence of local failure was 10% at one year and 36% at two years. Twenty-six patients (19%) underwent resection after chemoradiotherapy including 22 patients (85%) with negative margins. On multivariate analysis, response to IMRT was associated with surgery (p =.01). Acute grade 3-4 hematologic and nonhematologic toxicity rates were 26% and 4.5%, respectively. CONCLUSION:IMRT is safe in patients with LAPC. Patients with non-progressive LAPC after ICT and who received IMRT had high rates of local control and prolonged survival.
Effect of chemoradiotherapy and neoadjuvant chemoradiotherapy in resectable pancreatic cancer: a systematic review and meta-analysis Xu et al. J Cancer Res Clin Oncol RESULTS:A total of 28 studies were identified as relevant, but only 17 studies with a total of 3,088 patients were included in the comparison between CRT versus non-crt, and a total number of three studies with 189 patients included in the comparison between neoadjuvant CRT versus postoperative CRT. The comparison between CRT and non-crt showed that the overall pooled HR for death was 0.96 (95% CI 0.89-1.03; P = 0.28). The HR for progress was 0.83 (95% CI 0.68-1.03, P = 0.09). Comparison between neoadjuvant CRT and adjuvant CRT revealed a pooled HR of 0.93 (95% CI 0.69-1.25; P = 0.62). CONCLUSIONS:This meta-analysis showed that CRT showed no significant effect on OS and PFS when compared to non-crt. Neoadjuvant CRT showed no significant effect over postoperative adjuvant CRT.
More trials are needed with IMRT-SBRT. Xu et al.
ΤΑ ΠΑΛΙΑ ΧΡΟΝΙΑ
HCC
GALL BLADDER
Is external palliative radiotherapy for gallbladder carcinoma effective? Onkologie 2001 Eleftheriadis N, Pistevou-Gombaki K, Plataniotis G, Sofroniadis I, Kouloulias V. CONCLUSIONS: External conformal radiotherapy with 30Gy in 10 fractions seems to be a safe and effective method of palliative management of gallbladder carcinoma. However, further studies are necessary to determine the role of radiotherapy in palliative or adjuvant treatment of gallbladder carcinoma.
Therapeutic Potential of Adjuvant Stereotactic Body Radiotherapy for Gallbladder Cancer Cureus 2015 Surgical treatment remains the only curative treatment for gallbladder cancer. However, even after liver resection, locoregional failure seems to be a significant problem. While there is no Level I evidence, multiple studies have shown benefit for adjuvant radiation in high-risk patients. After extensive liver resection, tolerance to conventional chemoradiation may be limited by potential liver toxicity. Stereotactic body radiotherapy has been used safely and effectively in hepatobiliary malignancies. We present a case report, highlighting the potential therapeutic role of adjuvant stereotactic body radiotherapy (SBRT) for gallbladder cancer.
Έχει θέση η ΑΚΘ? GUIDELINES
Integration of Radiation Oncology with Surgery as Combined-Modality Treatment. Guderson et al. 2013 Int J Radiat Oncol Biol Phys. The ultimate in contemporary integration of radiation and surgery is found in patients who are candidates for surgery plus both EBRT and IORT. Orthovoltage IORT following tumor reductive surgery is reasonably well tolerated and seems to confer in-field control in carefully selected patients. Distant metastases remain the major problem for patients with pancreatic adenocarcinoma. Adjuvant EBRT after surgery+iort seems a potentially beneficial modality, however further studies are needed.
Cytoreductive surgery combined with intraoperative chemo-hyperthermia and postoperative radiotherapy in the management of advanced pancreatic adenocarcinoma: feasibility aspects and efficacy. Kouloulias et al. J Hepatobiliary Pancreat Surg. 2001 BACKGROUND/PURPOSE:The aim of our study was to evaluate the feasibility and the efficacy of cytoreductive surgery (CS) with intraoperative chemo-hyperthermia in the management of advanced stage IVA (T4N0M0) pancreatic cancer. METHODS:From August 1995 through March 1996, seven patients with unresectable adenocarcinoma of the pancreas underwent CS, with preoperative chemotherapy (5-fluorouracil [FU] for 96 h), plus 45-Gy external beam postoperative irradiation with a 6-MeV linear accelerator (1.8 Gy per fraction, 5 days per week). A single session of intraoperative hyperthermia was performed with a waveguide-type applicator operating at 433 MHz, and temperature was measured by inserting a flexiguide needle catheter carrying a thermometry probe with three measuring points into the tumor. The tumor region was heated to 43 degrees C-45 degrees C for up to 60 min, while 5-FU 500 mg was injected simultaneously through the gastroduodenal artery into the splenic artery (intraoperative regional chemotherapy). RESULTS:Postoperative recovery was uneventful for all patients. After the combined treatment, there was a significant decrease in the values of both serum carcinoembryonic antigen (CEA; P = 0.017, Wilcoxon test) and carbohydrate antigen (CA)19-9 ( P = 0.016; Wilcoxon test), from 7.6 +/- 1.5 ng/ml CEA and 869.6 +/- 126.9 U/ml CA to 3.5 +/- 0.8 ng/ml CEA and 104.7 +/- 35.4 U/ml CA19-9. Moreover, there was a significant improvement ( P = 0.016; Wilcoxon test) in Eastern Cooperative Oncology Group performance status, pain score, and body mass index. The median overall survival was 18.5 (SE, 1.8) months. CONCLUSIONS: Our preliminary clinical results suggest the tolerability and the considerable potential advantage of using cytoreductive resection with preoperative chemotherapy, intraoperative chemohyperthermia, and external beam postoperative radiotherapy for the management of advanced adenocarcinoma of the pancreas.
Γενικά συμπεράσματα Για τον καρκίνο παγκρέατος φαίνεται ότι η εντοπισμένη ΑΚΘ σαν προεγχειρητική συνδυασμένη με ΧΜΘ κερδίζει ολοένα έδαφος ειδικά αν είναι IMRT ή SBRT. H IORT μόνο σε επιλεγμένους ασθενείς +EBRT Για τον χολαγγειοκαρκίνο φαίνεται ότι η εντοπισμένη ΑΚΘ (IMRT ή SBRT) θα παίξει ρόλο στο μέλλον ενώ επί του παρόντος μόνο στα πλαίσια ανακουφιστικής ή κλινικής μελέτης Για τον ΗΚΚ η ΑΚΘ παίζει ρόλο στα πλαίσια IMRT ή SBRT και ειδικά επί θρομβωτικής συνδρομής Η υπερθερμία μπαίνει όλο και πιο ενεργά στην κλινική πράξη αναφορικά με το πάγκρεας. Θέλουμε και άλλες μελέτες!!!
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