Muto, Matteo (2020) Dose Intensification of Radiotherapy in neoadjuvant rectal cancer treatment Personalized Therapy with the use of Magnetic Resonance Imaging . Preliminary Results. [Tesi di dottorato]

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Colorectal cancer is one of the most common types of cancer. Staging of rectal cancer differs from colon cancer in that it is important to assess for locally advanced disease, which is an indication for treatment with chemotherapy and/or radiation prior to surgical intervention. Magnetic resonance imaging (MRI) of the pelvis with specific rectal cancer protocol is the current standard of care to assess for local tumor advancement and lymph node involvement . Surgery is the primary treatment modality for patients with Rectal Cancer . Preoperative chemoradiation is now considered standards of care for local advance rectal cancer patients. The usual dose in chemoradiation protocol given to initial pelvic fields is 45 Gy in 25 fractions of 1.8 Gy each , an additional tumor boost may be administered, should include the tumor with a 2- to 5-cm margin, to an additional 5.4 Gy , the concomitant usual chemotherapy is capecitabine 825 mg/mq/bid per os . In this study was decided to use the Diffusion weighted (DW) magnetic resonance (MR) imaging and the ADC maps as a tool for evaluating patients and dividing them into two categories good e bad responder. After obtaining for each patient images of MR pre (baseline) and MR during (treatment) , variation in ADC in percentage (Δ ADC% ) for each patient have been calculated , and then the data obtained were compared and matched with the histological exams . At this point was calculated the receiver operating characteristic (ROC) curves and the area under the curve (AUC) to investigate the discriminatory capacity of the Δ ADC . With this analysis it was possible , to divide the patients between bad and good responder . This study has two steps . Starting from the data analysis of step 1 , hence the first group of 39 patients , we observed that pathologic examination of the entire surgical specimen showed 14 patients considered as good responder (TRG 0-1) 36% of the patients , and 25 patients considered as bad responder (TRG 2-3) 64% . Using the ∆ ADC formula , we found a significantly higher value in good responder patients than in bad responder patients. In step 2, the decision to perform an additional radiotherapy dose 2 boost (5.4 Gy in 3 fractions) was introduced with respect to step 1 for patients who were considered bad responders at MRI during treatment . In the second phase of the project , 15 patients have been enrolled , 10 of which received an additional radiotherapy dose boost (5.4 Gy in 3 fractions) , but to date it has not been possible to recover the data of the histological examination for all patients undergoing the boost. This study is one of the first studies that aims to change the therapeutic approach of rectal cancer based on MR results during radiotherapy. What is expected for the future in the treatment of rectal cancer is to perform increasingly personalized treatments aimed at improving the complete response to neoadjuvant treatment, without increasing the treatments related toxicity. For this reason studies such as this may play a role in defining which patients may be eligible for a dose intensification protocol . The trend in oncology today is to perform therapies more and more personalized taking into account the multiple characteristics of each case.

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