ROCC – Radiomics Of locally advanced Cervical Cancer

ROCC – Radiomics Of locally advanced Cervical CancerThis project is concerned with the application of medical images in radiotherapy of patients with locally advanced cervicx cancer, which affects 300 women yearly in Norway. The survival for this group of patients is about 70 %, and it is important to understand the factors leading to cancer-related death and take measures to increase survival.In 2016, one finalized subproject on local radiotherapy dose escalation by simultaneous integrated boost has been published in an international journal; see "Forskningsprodusjon. Several imaging modalities may provide the image basis for such escalation, where 18-FDG-PET is most relevant for several types of cancers. High 18F-FDG tumor uptake prior to radiotherapy is associated with reduced survival for patients with lung cancer, head and neck cancer and locally advanced cervix cancer, among others. Moreover, in-field tumor recurrences typically occur in regions showing high 18F-FDG uptake prior to radiotherapy. Finally, regions within the tumor with high 18F-FDG uptake appear to be spatially stable. These findings indicate that tumor regions with high 18F-FDG uptake are attractive targets for dose escalation. It has been more than a decade since the introduction of dose painting. In spite of great interest, the approach has not gained widespread use clinically. One possible reason could be that the implementation of dose painting is technically complex, particularly for DPBN. To our knowledge, planning of true DPBN is not offered in standard versions of any commercial treatment planning system (TPS) today. The need for in-house developed planning systems or modifications in TPS research versions may be an obstacle for clinical implementation of DPBN. We have introduced a new method for DPBN planning in a standard TPS. The method is based on 18F-FDG PET images for dose prescription and the treatment plan summation option of standard TPS’ employing intensity modulation. With our method, DBPN can be delivered in accordance with the 18F-FDG dose prescription for different cancer patient cases. In another subproject, we explore a short-course radiotherapy dose escalation strategy for bulky tumors. Standard treatment for patients with locally advanced disease is external beam radiotherapy (EBRT) with concomitant chemotherapy followed by brachytherapy (BT). About one in ten patients suffer from local failure and typically two out of ten experience moderate to severe late side effects. Patients with large tumours at time of brachytherapy remain challenging to treat, particularly without combining intracavitary and interstitial BT implants and with limited imaging capability. The usage of interstitial implants is invasive and many centres worldwide do not offer this technique. It is therefore of interest to explore new EBRT strategies that may facilitate for improved brachytherapy by reducing the complexity and thus potentially improve the outcome for cervical cancer patients that are challenging to treat today. A new treatment concept is investigated for patients with locally advanced cervical cancer exploring both photon and proton intensity modulated radiotherapy. This concept for external beam dose escalation early in the treatment course may improve the subsequent brachytherapy by increasing tumour shrinkage. The treatment concept may have potential to improve outcome for patients with locally advanced cervical cancer. A manuscript was submitted to an international journal on this topic. One final paper on tumor shrinkage for the candidate's degreee was submitted Autumn 2016. The planned date for PhD dissertation is April 21, 2017.

ROCC – Radiomics Of locally advanced Cervical CancerThis project is concerned with the application of medical images in radiotherapy of patients with locally advanced cervicx cancer, which affects 300 women yearly in Norway. The survival for this group of patients is about 70 %, and it is important to understand the factors leading to cancer-related death and take measures to increase survival.One finalized subproject on radiotherapy dose painting "by numbers" (DPBN) has been published in an international journal; see "Forskningsprodusjon. Several imaging modalities may provide the image basis for radiotherapy dose painting, where 18-FDG-PET is most relevant for several types of cancers. High 18F-FDG tumor uptake prior to radiotherapy is associated with reduced survival for patients with lung cancer, head and neck cancer and locally advanced cervix cancer, among others. Moreover, in-field tumor recurrences typically occur in regions showing high 18F-FDG uptake prior to radiotherapy. Finally, regions within the tumor with high 18F-FDG uptake appear to be spatially stable. These findings indicate that tumor regions with high 18F-FDG uptake are attractive targets for dose escalation. It has been more than a decade since the introduction of dose painting. In spite of great interest, the approach has not gained widespread use clinically. One possible reason could be that the implementation of dose painting is technically complex, particularly for DPBN. To our knowledge, planning of true DPBN is not offered in standard versions of any commercial treatment planning system (TPS) today. The need for in-house developed planning systems or modifications in TPS research versions may be an obstacle for clinical implementation of DPBN. We have introduced a new method for DPBN planning in a standard TPS. The method is based on 18F-FDG PET images for dose prescription and the treatment plan summation option of standard TPS’ employing intensity modulation. With our method, DBPN can be delivered in accordance with the 18F-FDG dose prescription for different cancer patient cases. In another subproject, we explore a short-course radiotherapy dose escalation strategy for bulky tumors. Standard treatment for patients with locally advanced disease is external beam radiotherapy (EBRT) with concomitant chemotherapy followed by brachytherapy (BT). About one in ten patients suffer from local failure and typically two out of ten experience moderate to severe late side effects. Patients with large tumours at time of brachytherapy remain challenging to treat, particularly without combining intracavitary and interstitial BT implants and with limited imaging capability. The usage of interstitial implants is invasive and many centres worldwide do not offer this technique. It is therefore of interest to explore new EBRT strategies that may facilitate for improved brachytherapy by reducing the complexity and thus potentially improve the outcome for cervical cancer patients that are challenging to treat today. A new treatment concept is investigated for patients with locally advanced cervical cancer exploring both photon and proton intensity modulated radiotherapy. This concept for external beam dose escalation early in the treatment course may improve the subsequent brachytherapy by increasing tumour shrinkage. The treatment concept may have potential to improve outcome for patients with locally advanced cervical cancer. A manuscript was submitted to an international journal on this topic.

Radiomics of locally advanced cervical cancerThis project is concerned with the application of medical images in radiotherapy of patients with locally advanced cervicx cancer, which affects 300 women yearly in Norway. The survival for this group of patients is about 70 %, and it is important to understand the factors leading to cancer-related death and take measures to increase survival.One finalized subproject has been published in an international journal; see "Forskningsprodusjon". This project is on "Spatial dosimetric sensitivity analysis in 3D-based brachytherapy". In radiotherapy, the tumor and organs at risk are usually manually delineated in medical images (typically MR or CT) of the patients. Therefore, such delineations are prone to inter-observer variability. We have experience with such inter-observer variability issues. If e.g. the tumor is erroneously delineated too small, the periphery of the tumor may receive too low doses and tumor recurrence could be the consequence. In this respect, it is relevant to systematically investigate the consequences of tumor delineation errors with respect to tumor dose. In this project, tumor delineations are to be modified in a computer-based procedure and tumor doses will subsequently be scored based on clinical cases. Thus, a topographical mapping of problematic tumor regions will be achieved; information that may impact future radiotherapy planning procedures. This project was also presented at the ESTRO meeting in Vienna, April 2014. Work is also continued on another subproject, "PET-based simultaneous integrated boost". FDG-PET is a method for identifying hypermetabolic parts of the tumor. It has been shown that patients with high FDG uptake in the tumor have reduced chance of cure following radiotherapy. For other cancer sites, it has also been shown that tumor recurrence occurs in the region of high FDG-uptake. In other words, regions with high FDG-uptake should be given special attention in radiotherapy. In this subproject, we will do radiotherapy planning where the information from FDG-PET will be included. In a simultaneous integrated approach, the high-uptake FDG-PET region will be dose-escalated compared to the rest of the tumor and the elective region. The consequences with respect to normal tissue doses will be recorded and compared to standard approaches. The aim is to present a technique where a higher degree of tumor shrinkage is obtained prior to brachytherapy, leading to both increased probability of local control and reduced probability of normal tissue complications. A paper draft on this project is now in circulation among co-authors and will be submitted within end of february. A continuation of this subproject is currently ongoing.

Bildeveiledet behandling av lokalavansert livmorhalskreftLokalavansert livmorhalskreft er en alvorlig sykdom med 5-års overlevelse på omtrent 70 %. Digital diagnostisk bildeinformasjon skal i dette prosjektet utnyttes til å øke forståelsen av årsakene til kreftrelatert død hos denne pasientgruppen og vurdere nye behandlingsregimer.Lokalavansert livmorhalskreft er en alvorlig sykdom med 5-års overlevelse på omtrent 70 %. Dette skyldes både manglende kontroll på sykdommen lokalt i bekkenet og spredning til andre områder i kroppen (metastasering). Den anbefalte behandlingen av de aktuelle pasientene i dette prosjektet er stråleterapi, i tillegg til kjemoterapi, og behandlingen kan gi betydelige bivirkninger hos så mange som 15 % av pasientene som kureres. Dermed, både på grunn manglende sykdomskontroll og bivirkninger, er det viktig å undersøke de underliggende årsakene og vurdere nye behandlingsstrategier. I dette prosjektet ønsker vi å bruke digital medisinsk avbildning slik som magnetisk resonanstomografi (MRI) og positron emisjonstomograf (PET) til å studere egenskapene til livmorhalskreft, og hvordan disse endres i løpet av behandlingsforløpet. MRI og PET brukes vanligvis til å detektere sykdom i kroppen, men vi skal bruke bildebehandlingsverktøy for å hente ute bildeverdier innenfor svulstene. Dette kan gi oss ‘biomarkører’ som kan fortelle om en gitt pasient har en mer eller mindre aggressiv sykdom. Slike biomarkører kan i fremtiden rettlede oss til å foreta riktige behandlingsvalg for den enkelte pasient. Videre skal vi vurdere å bruke de medisinske bildene brukes til å forme strålefeltene ved strålebehandlingen på en bedre måte. Vi skal også studere hvordan feil i inntegninger av svulster i MR-bilder før strålebehandling potensielt kan gi feil stråledose til tumor. Dette kan gi oss informasjon om hva slags sikkerhetsmarginer vi bør ha ved slik type behandling, og studiet foreligger nå som et utkast til en vitenskapelig rapport.