Rectal toxicity for patients treated with proton beam radiation diagnosed with prostate cancer using free rectal water, water filled rectal balloon or interstitial Hydrogel for rectal immobilization Victoria Casablanca B.S.R.T (T), Staff Radiation Therapist Northwestern Medicine Chicago Proton Center Welcome. Thank you for joining me today. This talk is on Rectal toxicity for patients treated with Proton beam radiation. I do not have any disclosures to report today. In this talk I will be covering the method of our research, the background of our research, and the results of our research as well as what is next for this research.

Purpose of this Research Why is this study being done… to improve effectiveness of treatments and procedures Hypothesis of this study…lower grade rectal toxicities in treatments using Hydrogel What was studied…treatments from November 2010 to March 2017 The purpose of this study was to collect and analyze information from individuals with a similar diagnosis. Ultimately, the goal is to improve effectiveness of treatments and procedures and limit side effects and late complications for patients. Multiple techniques are used to decrease the rectal dose and improve internal immobilization for treatment of prostate cancer. We hypothesized that patients with an implanted biodegradable tissue expander would have lower grade rectal toxicities than the alternatives (rectal fill of free water or rectal balloon). In this study we looked at three types of rectal immobilization in comparison with grades of rectal toxicities. This was a retrospective study ranging from treatments in November 2010 to March 2017. Over this time frame the type of rectal immobilization has adapted with newer technologies.

Background Free Rectal Water Rectal Balloon Implanted Tissue Expander (Hydrogel) Photo taken of Radiadyne ImmobiLoc rectal balloon. In 2011 at the proton center we were filling rectums with free water using 100ccs inserted into the rectum prior to treatment. Around 2012 we introduced the rectal balloon, pictured here.

Hydrogel Position Normal Anatomy Implanted Spacer On average 1 cm of Beginning in 2015 Hydrogel Gel spacer injected through the perineal wall to minimize dose to rectum Persistence: lasts about 3 months Absorbs: Within approx 6 months Currently the majority of our patients are treated using an implanted tissue expander called Hydrogel pictured here Hydrogel creates on average, 1cm of space between prostate and rectum www.spaceoar.com

Method of Research 2941 1028 308 309 220 837 Number of patients researched based on time constraints* Total number of patients on Registry Study Free Water Total number of patients diagnosed with Prostate Cancer Balloon Research conditions: Since the submission of the abstract these numbers and results have been updated. Prospective collection of data through the prostate registry from a single institution with Proton Collaborative Group from November 2010 to March 2017. Most were treated with daily fractionated proton radiation therapy to 79.2 Cobalt Gray Equivalents (CGE) in 1.8 CGE fractions. Three consecutive cohorts of patients were treated, first with free rectal water (308 patients), then with rectal balloons (309 patients) and most recently with an interstitial hydrogel (220 patients). We evaluated GI toxicities (proctitis, fecal incontinence, diarrhea, and rectal hemorrhage) for each of the three techniques. 1028 of the 2941 patients on registry study were diagnosed and treated for prostate cancer. We chose a smaller randomized sample size for each rectal fill totally to 837 patients researched. Free water 308 number of patients Rectal balloon 309 number of patients Hydrogel 221 number of patients * As well as time constraints there were a handful of patients whom were removed from the research. These patients were recorded as having no rectal fill for treatment. Toxicities -Grade 1-3 proctitis, fecal incontinence, diarrhea, and rectal hemorrhage Registry Study … Proton Collaborative Group from a single institution November 2010 to March 2017 Hydrogel

Toxicity Defined Gastrointestinal Disorders Diarrhea Adapted from CTCEA v4.0 Gastrointestinal Disorders Diarrhea Grade 1: Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline Grade 2: Increase of 4 - 6 stools per day over baseline; moderate increase in ostomy output compared to baseline Grade 3: Increase of >=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL Fecal Incontinence Grade 1: Occasional use of pads required Grade 2: Daily use of pads required Grade 3: Severe symptoms; elective operative intervention indicated Proctitis Grade 1: Rectal discomfort, intervention not indicated Grade 2: Symptoms (e.g., rectal discomfort, passing blood or mucus); medical intervention indicated; limiting instrumental ADL Grade 3: Severe symptoms; fecal urgency or stool incontinence; limiting self care ADL Rectal Hemorrhage Grade 1: Mild; intervention not indicated Grade 2: Moderate symptoms; medical intervention or minor cauterization indicated Grade 3: Transfusion, radiologic, endoscopic, or elective operative intervention indicated Diarrhea term by CTCAE v4.0: A disorder characterized by frequent and watery bowel movements. Fecal Incontinence term: A disorder characterized by inability to control the escape of stool from the rectum. Proctitis term: A disorder characterized by inflammation of the rectum. Rectal Hemorrgage term: A disorder characterized by bleeding from the retroperitoneal area. Activites of Daily Living: ADL

Results

Results Rectal Fill Total Patients Grade 0 Grade 1 Grade 2 Grade 3 Total Adverse Events Free Water 308 116 143 49 192 Balloon 309 90 156 60 3 219 Hydrogel 220 142 68 11 1 80 Grade 3 GI toxicities were rare, occurring in only 4/837 patients (0.48%). Grade 2 toxicities were more common in patients treated with free water (49/308) or rectal balloon (60/309) than with hydrogel (11/220). A significantly larger portion of hydrogel patients experienced no GI toxicity (Grade 0 – 142/220) compared to free water (116/308) or rectal balloon (90/309). CONCLUSION: The incidence of >Grade 1 rectal toxicity is noticably lower in patients who are treated with an implanted biodegradable hydrogel expander, compared to prior techniques of rectal immobilization.

Results This slide show cases the percentage of patients that reported a toxicity in the respective group based on rectal fill. As denoted with the green color bar for Hydrogel it is noted that when appropriate it is smaller than the other two rectal fills for grade 1-3. In Grade 0 or no reported toxicity it is a larger percentage of patients.

Conclusion Analysis is ongoing at this time. Initial results show improved rectal toxicity for patients treated with a rectal fill of Hydrogel in comparison to those treated with rectal fill of free water or balloon. Continued collection of data through the registry study at a single institution, Northwestern Medicine Chicago Proton Center, through the Proton Collaborative Group. Special thank you I would like to give a special thanks to those that worked diligently on this research study. Rebecca Price, who put in the long hours and nights gathering data. Megan our Clinical research coordinator Dr. William Hartsell Northwestern Medicine and the patients who allowed us the opportunity to analyze their treatment to better understand for the future.

Questions?