Today we'll be talking about best papers in cancer rehabilitation. My name is Evgenia Dvorkin-Wininger and I'm from the Department of Physical Medicine Rehabilitation at Metro Health Medical Center. I will be followed by Dr. Riley and then by Dr. Smith. The objectives of our presentation are to identify some of the top papers in the last year published in the Human Ornithology Journals, summarize results and conclusions, describe weaknesses and strengths, and also identify some ways we can implement some of these practices in our own clinical practice. The first paper is called Longitudinal Effects of a Novel and Advanced Mnemonic Compression Device on Patient-Reported Outcomes in the Management of Cancer-Related Head and Neck Lymphedema. The goal of the study was to assess changes in patient-reported symptoms, function and treatment satisfaction with extended at-home use of the pneumatic compression device. It was an observational study with retrospective analysis. A little bit of background, as many of us know, head and neck cancer survivors have multiple issues in survivorship. For example, dysphagia, dysarthria, difficulty with breathing, decrease in cervical range of motion and shoulder range of motion, dehydration, malnutrition, impaired body image, as well as social isolation. One of the issues they also experience is head and neck lymphedema, often due to the cancer itself, surgery, and or radiation. There's a disruption of lymphatic structures as well as lymphatic transport. This is due to the tumor burden or due to surgery and radiation. There have been previous studies that have found that patients have prevalence of lymphedema up to 75 to 90%. More specifically, this is soft tissue swelling in the region of the head and neck cancer and or the treatment. It's high protein fluid that progresses or causes inflammatory response, subsequently tissue fibrosis, pain, disfigurement, decrease in range of motion, and restriction and high risk of infections. Fibrosis forms early, even in the beginning of treatment, compared to some of the other lymphedema that we see in the extremities. In addition to the external lymphedema that we can all appreciate, some patients experience internal lymphedema in the larynx and pharynx. One of the gold standards of lymphedema is manual lymph drainage, specifically in the extremity lymphedema, but this is the same in the head and neck cancer patient preparation as well. MLDs perform starting at the supraclavicular nodes with the direction of fluid to the trunk, the neck, and the face. With regards to advanced pneumatic compression device, generally there are three types of pumps. There's a single chamber or non-segmental type with uniform pressure. There's a multi-chamber or segmental type of device that has pressure gradient that you can't manually adjust. And then third, there's a multi-chamber programmable pump with multiple chambers as well as the ability to change manually the pressure for the treatment. The way it works is there's an inflatable garment for the arm, the leg, the trunk, or the chest, and electrical pneumatic pump that fills the garment with compressed air. It is inflated and deflated with a cycle times pressure in between the devices. This is just a picture representing the variety of devices from type 1 to type 3. Again, type 3 is more advanced with multiple chambers and the ability to change the pressure gradient. So one of these more advanced devices is called Flexi-Touch system and it's under the Tactile Medical Company. The Flexi-Touch system is an only FDA approved available pneumatic compression device for head and neck survivors. It was approved by the FDA in 2016. It's something that can be applied during lymphedema therapy as well as at home. And it's generally meant to augment lymphedema therapy and manual lymph drainage as well as compression garments. Again, this is a multi-chambered system. There's adjustable gradient pressure to specific anatomical sites and overall there's 14 chambers that cover the head, the neck, the upper torso. So this particular study occurred over about one year. There was a post and a pre-device survey after consistent home use. The requirement was that the patient had to use it at least for 25 days. The patients often use it at least 30 minutes once a day. And the patients were instructed by a representative from Tactile Medical or from one of the therapists to make sure that they use it correctly. Some of the general demographics of this patient population, it was that the average number of patients were over the age of 70. It was screened with cell carcinoma. Most of the patients were male. In addition, most of the patients were at least six months after treatment. The next group was anywhere between six months to 12 months after treatment. So the pre-treatment survey was done during home device training visits. And it was repeated one month after the treatment. Generally the pre-treatment survey asked questions about the effect of lymphedema, the quality of life of the patients that have after lymphedema. And the post-treatment survey addressed questions such as satisfaction with using the device, the ease of using the device, and any improvement patients felt with pain, range of motion, breathing, et cetera. So there were 449 patients that were surveyed. 90% of these patients used the pump for at least four weeks. 74%, as we discussed, were male. 67% of the patients had cancer of the oral pharynx or oral cavity. And most of these patients have tried complete decongestant therapy or MLD and a compression garment prior. So again, the survey had five questions. So these questions included, how would you describe the ability to control your lymphedema throughout treatment? How often has lymphedema prevented the ability to perform ADLs? State level of head and neck pain. How much difficulty does lymphedema cause when swallowing and breathing? And then the post-lymphedema questions included, again, it was the survey about the satisfaction of using the device. So the pre-survey and post-survey questionnaire showed that there was statistically significant improvement in all five of the questions. There was improvement in ability to control lymphedema symptoms, decrease in how often lymphedema prevented patients from doing their ADLs, improvement in head and neck pain, as well as improvement in range of motion and swallowing. Now, this is the results from the survey looking specifically at satisfaction. So over 87% of patients were satisfied or very satisfied, over 80% felt comfortable with the device, 90% felt better after using or doing this therapy, and overall 78% found that it was very easy or easy to use. So in conclusion, there was statistically significant decrease in symptom burden of lymphedema, there was improvement in ADLs, decrease in pain and difficulties with swallowing and breathing, and overall there is high satisfaction with using the device that ultimately leads to improved compliance and symptom management. Some future directions, for example, would include determining what is the optimal duration of use, how frequently and for how long. In addition, there was no control group, so having a study with a control group or a randomized control style would be the next step. In conclusion, pre- and post-device use survey showed statistically significant improvement in swallowing, breathing, and ADLs. These improvements in quality of life can lead to a potential randomized control study in the future. Again, some limitations included there was no control group, relatively this was a small sample size. Some of the other issues include insurance coverage, there was no discussion about payment in the study. And then the data that was collected used the tactile medical survey, did not focus on patient-reported outcomes. So some ways that we can integrate this into clinical practice, I think we can confidently say that this could be another adjunct for a patient or another thing they can use in addition to MLD and compression garments. We know compression garments are difficult to tolerate for some patients, so this could be another modality the patient can use. One of the, again, issues is insurance coverage, not all insurances cover this, so that would be another potential limitation for certain patient populations. However, overall, the gains outweigh the potential limited losses. So the second study we're going to talk about is exercise-based rehabilitation for cancer survivors with chemotherapy-induced peripheral neuropathy. So as many of us know, chemotherapy-induced peripheral neuropathy, or CIPN, persists in many patients right after treatment and for years to come. At least up to 68% of patients have these symptoms who have been treated with neurotoxic chemotherapies. Symptoms include numbness, tingling, burning, can cause pain, decreased quality of life, as well as balance and gait impairments leading to increased risk of falls. There's been some previous studies looking at exercise programs that have been promising. This particular study specifically looks at patient-related outcomes. The goal is to investigate the impact of exercise as rehabilitation for cancer survivors with persistent CIPN symptoms using comprehensive assessment of patient function as well as CIPN symptoms. This was a prospective study done in Australia. It was in patients who had CIPN and completed chemotherapy. So there was one group of patients and three time periods of assessment. First, we would call the control group. It was preceding intervention, also known as the baseline. Then there was assessment done with the same group of people pre the eight-week exercise intervention. And then there was another assessment done eight weeks after the exercise intervention. The reason to have the control period was to assess changes in outcome without formal exercise. So these patients were recruited over about two and a half years. Most of them were three months post-treatment with one of neurotoxic chemotherapies such as cisplatin and dasytaxel. Patients have to have a grade equal to or greater than two CIPN on the National Cancer Institute Common Tumor Analogy Criteria. Exclusion criteria included patients with MSK impairments. Ultimately, there were 29 patients in this study. This is just a quick review of this grading system for CIPN that they used, so grade two or greater. Grade two is moderate symptoms with respect to motor neuropathy, sensory, or prosthesis. Grade three, severe symptoms. Grade four, life-threatening. Grade five, death. So the exercise intervention included a personalized exercise prescription, including resistance, balance, and cardiovascular training. It was a one-hour session three times a week for an eight-week period. Half of the therapy was completed with an exercise physiologist, and half was completed in the house. There was an initial comprehensive assessment, and the goal of the therapy was for the patients to be rating of perceived exertion, or RPE, between 13 and 15, and that falls in this green category here. So again, the exercise prescription, and this is one example, it included resistance training, balance training, and cardiovascular exercise. So some of the outcome measures that were included in this study are the following. So first, there was the total neuropathy score clinical version, or TNSC, looking specifically at muscle weakness, numbness, and tingling. The second that was used is the EORTC CIPN-20 questionnaire, specifically looking at sensory, motor, and autonomic symptoms. Then we had the functional assessments, looking at mobility, such as the six-minute walk test, the standing balance, as well as the balance strength, or the five-time sit-to-stand test. The other outcomes looked at disability and quality of life. One was the CIPN-RODS, focusing on disability and function limitation, SF-36 focused on the quality of life questionnaire. And lastly, there were neurophysiologic tests, such as nerve conduction studies, specifically of the tibial, sterile, and median nerves. So there were 29 patients, as we discussed. At least, almost 83% had numbness and tingling. 83% could tolerate the exercise program. Again, this is a little bit of a busy slide. So in summary, the results showed that there was exercise, that exercise improved symptoms of CIPN, both in patient-reported outcomes, as well as objective symptoms, and they did not see any change in the control group. There was a decrease in patient-reported disability, improved quality of life, again, specifically in the quality of life questionnaire, there was no change in the control period. And there was significantly improved distance walked on the six-minute walk test, improvement in balance as well, as well as standing balance. One of the things, however, that did not see or show any changes was on the nerve conduction studies. So more research is needed to evaluate specific mechanisms, clinical and long-term impact of improvement. This study did show the rehabilitation impact of exercise on function, impairments and symptoms. And as we expected, there was no significant change in control period versus clear benefit in the intervention time period. In the past, there have been some other studies that looked at improvements in patients reported CIPN symptoms with balanced training and exercise. One of the difference with this study is that it also looked at resistance and aerobic training. There was an idea that maybe exercise-induced neurophysiologic changes occurred, but this study did not see any differences in the nerve conduction studies. Symptom improvement is due to general recovery of quality of life deficits that are associated with CIPN. This affects likely reason for improvements from baseline to pre-exercise and most in the unstable surface with eyes closed, balanced condition. In conclusion, evidence of rehabilitation potential for persistent CIP and symptoms in cancer survivors. In this eight-week period of exercise, there was significant reduction in symptom burden and disability, improvement of standing and dynamic balance, mobility, and quality of life. Some limitations is that this was small cohort, single group design, no follow-up, and there could be some selection recruitment bias. Future directions would include a randomized controls trial with a larger sample size, evaluate the persistence of these interventions long-term, and maybe determine the mechanism of exercise benefit, optimize frequency, timing, intensity of intervention. In terms of integration to clinical practice, again the importance of counseling, educating our patients about the importance of exercise, empowering our patients, as well as helping our patients that are not interested in pharmacological management of symptoms. Thank you, and we will move on to Dr. Riley to discuss the next two papers. Thank you, Jenny. I have no financial disclosures. The first paper that I'll be presenting is Making Patients Fit for Surgery, Introducing a Four-Pillar Multimodal Prehab Program in Colorectal Cancer. This was published in AJP Menar in 2019 through the Department of Surgical Oncology from this group in the Netherlands. No talk on prehabilitation would be complete without a slide that looks something like this, and so this is just to say that there's a big increase in publications in prehabilitation and a lot of interest in prehabilitation, and so these authors were specifically looking at the colorectal cancer population. We know that this is the second most prevalent cancer worldwide and that surgery is a big component to care, but unfortunately has a lot of significant post-operative morbidity and mortality, and so these authors were looking at the colorectal cancer population to see does a multimodal program that involves an exercise component of higher intensity interval training, as well as smoking cessation, psychological counseling, and nutrition support, is that program feasible, is it safe, and is it effective, and so that's what these authors set out to look at. So they designed the study to be a four-week program in which patients were involved in prehab or control and the exercise was performed under a supervised setting, as they mentioned that the home-based programs typically have low compliance and small. And so the objective here was to test the feasibility, safety, and effectiveness of a multimodal prehab program intended to be studied in an RCT in the future. So this was a non-randomized prospective observational cohort study. The control in the study was the group of patients that were on the waitlist to enter the study, and in terms of the inclusion criteria, patients had to be older than 18 with a scheduled elective colorectal cancer surgery without having any prior new adjuvant treatment and the ability to give informed consent. The exclusion criteria included patients with metastatic disease, chronic renal failure, an ASA score of 4 or 5, and conditions that interfere with exercise such as paraplegia and orthopedic impairment. So they placed these patients into this study. The prehab group contained 20 patients and the control had 30. And so in the prehab group, these patients were enrolled in this exercise program that had components of both endurance and resistant exercises. And so they had three sessions a week of this program in a supervised setting, and on their days off, they were encouraged to do 60 minutes of walking or cycling on their own time. So the high-intensity interval training component was three blocks of moderate intensity and three blocks of high-intensity exercise performed on a stationary bike. They had baseline testing of their VO2 max, anaerobic threshold, respiratory quotient, and an EKG was performed as well. These patients for the high-intensity blocks began at the 65% VO2 peak, working up to 85 to 100% for the moderate intensity blocks. They were starting at 75% of their anaerobic threshold or 20% of their VO2 peak. With regards to the resistance exercises, their one rep max was calculated, and then they were asked to do two sets of 10 repetitions per exercise of the five exercises that you see on the screen. Within the first week, they were working at 65% of the one rep max. In the second week, they did 70% of the one rep max. And in weeks three to four, they were doing 75% of the one rep max. The other components of this program were nutrition, so they had protein supplements twice daily. They received dietary advice and vitamin supplementation. And in terms of psychological support, they all met with a trained psychologist to talk about anxiety, coping, relaxation, and expectations. They could have additional sessions as they wanted, and they also were phoned weekly during the period of the trial for adherence to the program and a review of the prehab program. The primary outcomes of the study were feasibility as measured by adherence to training sessions and dropouts, as well as safety measured by adverse events. They also administered a qualitative survey on program satisfaction. The secondary components were functional measures, so the six-minute walk test after prehabilitation and four weeks post-operatively, as well as the muscle strength as measured by the one rep max. The statistics, so this was an intention to treat analysis, functional capacity and strength. The means and standard deviation were calculated for normally distributed and medians for non-normally distributed. T-tests and Mann-Whitney U were conducted for continuous parameters, and then the categorical data was reported as qualitative measures. The demographics of this trial were very similar between those who were in the prehab and the control group, although the authors do mention that patients in the prehab group had lower six-minute walk tests, VO2 peak, and one rep max as compared to the control group. And in terms of the primary outcomes, so there were zero adverse events. Three out of 20 patients in the prehab group dropped out, two because they had their surgeries scheduled earlier than anticipated, and one dropped out to be a caregiver for her husband. There was 85% of patients who completed the program, 88% of the training sessions were completed as well, 90% of patients felt less tired because of the program, and there was a high level of satisfaction with the mean score of 4.6 out of 5. With the functional measures, 88% of patients in the prehab group improved their functional capacity, 100% improved their one rep max, and 64% had a clinically relevant improvement in their six-minute walk test. And this is really the money slide from this presentation. So in the dark dashed lines, you see the prehab group, and in the control, you see the light dotted circles. You see that from baseline to after prehab, these patients improved their six-minute walk test in the prehab group, and although that value dropped slightly at four weeks post-operatively, it's still higher than their baseline as compared to the control group in which, you know, we don't have measures for their right before surgery values, but at the same time, that measure drops from baseline to after surgery in this group. And so ultimately, these authors found that 86% of patients in the prehab group were able to return to their functional baseline at four weeks after the operation as compared to 40% of the control group, and that was found to be statistically significant. These are charts from the qualitative data. So the first one showing main reasons for participation, these being they wanted to become more fit, they wanted to contribute to the usefulness of the program, these patients felt like they were fitter, and that their support team, or they felt a lot of support from the team through this program, and then the last one shows the variables that they consider challenges in the program, and these are pretty equally distributed. And so ultimately, this program had high attendance and high completion rate. Although it added 17 appointments for these patients, many of these patients felt that this was feasible and were satisfied with this program. There were no adverse events. These patients had improved functional capacity, the limitations being that there was no preoperative assessment or right before surgery assessment for the control group as compared to the prehab group. This study by nature of it wasn't designed to prove effectiveness. And just how generalizable this study is to other patient populations outside of the colorectal cancer group remains to be seen. And so future directions, prehab may improve functional capacity in the colorectal cancer patient population undergoing elective surgery, high intensity interval training in the study was found to be a safe intervention in a supervised setting. This program was feasible and well tolerated by patients and hopefully future studies will be able to better elucidate the effects of prehab with the potential to reduce complications and hospital lengths of stay. The second paper that I'm going to be presenting is the cost effectiveness of the collaborative care to preserve performance in cancer COPE trial telerehabilitation interventions for patients with advanced cancer. This was published in Cancer Medicine in 2020. And we presented the COPE trial last year in best papers. And so this essentially was a trial looking at the effect of administering telerehabilitation to patients with advanced cancer with functional impairments and pain. And this trial found that there were significant improvements in hospital length of stay and post acute care needs for patients who receive telerehabilitation, as well as improvement in pain and function. And so the goal of this particular study was to look at the cost effectiveness of the interventions from this trial. And so just as I mentioned, that was the objective cost effectiveness. You can see in this diagram below the design of the COPE trial. So 516 patients with advanced cancer were randomized to three arms. So arm A being the enhanced usual care group, arm B being telerehab, arm C being telerehab plus pain care manager. And the telerehab was administered by a fitness care manager, aka a physical therapist, the pain care manager in arm C. The trial looked, or this trial is looking at the direct intervention. So the costs associated with administering the rehab intervention. And then the second part of the analysis was looking at the downstream effects in hospitalization costs in those who had telerehab. So does getting telerehab then reduce your hospital length of stay? And does it reduce the costs associated with hospitalization? And this data had to kind of be estimated based on literature available from the Kaiser Family Foundation. So these authors determined the length of stay for these patients and then use this value from the literature to estimate the cost of hospitalization for these patients. However, they also had access to the Rochester Epidemiology Project group. So this was essentially rather than guessing what the estimates of costs were for these patients, they had access to the total comprehensive care costs for this one group. And so that was the secondary analysis that was performed in this trial. And so on this slide, you'll see the patient quality of life in this study was measured by the EQ5D3L. And so the effectiveness or the incremental utility gain was incremental change in the EQ5D3L per arm over the six month course of the trial. And so the incremental utility gain was then converted to quality adjusted life years for cost effectiveness. And then when you look at the white portion of the table, you get to see all the different costs that they considered. And so for the direct intervention itself, they considered fixed costs, such as the costs of the DVDs, the pedometers, the resistance bands, variable costs being the amount of time these patients spent on the phone with the physical therapists and the nursing. And then later on, you take a look and you see the hospitalization costs and utilization costs. And so, like I mentioned, these were kind of estimates. So they were determining the probability of hospitalization and the hospital length of stay. And then they use data from the literature from the Kaiser Family Foundation to calculate the cost of the inpatient hospitalization per day. It's important to note that these values don't include the cancer treatment themselves or any procedures that the patients had within the hospitalization. So the cost effectiveness measures, the incremental cost effectiveness ratio was the measure of additional cost per unit of health gain. And then the probabilistic sensitivity analysis, this essentially is conducting 100,000 simulations to take a look and determine the cost effectiveness acceptability curve, which would then tell you at various willingness to pay thresholds, which strategy is the most cost effective strategy. The demographics in this study are similar. The only significant difference was that more patients in the RAP group were treated with chemotherapy at baseline as compared to the non-RAP group. And the RAP group, again, being that subset of patients for whom we have their total cost of care. And then the only other thing on this slide is that you'll notice that there is a very large percentage of patients who are white and a very large percentage of patients who have access to an in-home caregiver. So this shows the results of the direct intervention itself. So on the left-hand side in the table, you see arm A was the enhanced usual care. So that was the control group. So no associated costs with this, no quality adjusted life year gain. Below that you see arm C, which was the tele-rehab and pain management group. So to deliver this intervention, the additional cost or mean cost was $270.18 with a quality adjusted life year of 0.0075. This strategy is considered dominated. So more costly and less effective than arm B, which is below it. So arm B, the tele-rehab alone, the mean cost of administering this per patient was $154.94 with mean effectiveness of 0.01 and an incremental cost effectiveness ratio of $15,494. If you take a look at the curve on the right, you see that at a willingness to pay threshold at $100,000, that 95.4% of these simulations were cost effective. So at a willingness to pay threshold of $15,494, arm B was the more cost effective strategy. So what happens when you take a look at the downstream costs of hospitalization? You see similar results. So for enhanced usual care, the mean cost of this was about $3,400. Again, no mean effectiveness gain calculated. Arm C, the cost of this per patient was about $3,000. This was considered dominated again by arm B, the tele-rehab alone, which had a mean cost of $2,018.54. The mean effectiveness was the same as the prior slide, 0.01. This was the cost saving strategy. And so, like I mentioned, this analysis was based on estimates from the literature. What happens when you have access to all the information? You see the exact same results. So arm A being the more expensive strategy, arm C second most, and then arm B being the most cost effective strategy. So arm B was 25% more cost effective than arm C. This was not found to be statistically significant. Although you will note that when you look at the inpatient hospitalization costs across the group, that this was statistically significant. So in conclusion, at a willingness to pay threshold as low as $15,494, tele-rehab was found to be a cost effective strategy. And this was also cost saving when they considered the hospitalization and utilization costs for the patients during this six month time period. These authors also mentioned that this was probably a conservative estimate of the cost savings associated with tele-rehab. So, for example, in the COPE trial, they found that patients in arm A had more ICU admissions, which we would guess would be more expensive than a general floor admission. And so they didn't account for that difference in this analysis. Also, patients in arm B were found to have less post-acute care needs than the other two arms. And so that also is likely another place that these cost savings were underestimated. And then finally, this study only really looked at the six month period during the trial. And so we don't really know what happens after six months and are there additional cost savings that occur after six months. Limitations in this trial, although it was great to see the Rochester Epidemiology Project subset, it was a small sample size. And just as I mentioned, this was only a six month period of intervention that we looked at. The other considerations are that this is a patient population that's largely white and largely has access to an in-home caregiver without a disability. So hard to say how applicable this is to various other populations. So in conclusion, tele-rehab was found to be effective in improving quality of life function and pain in the COPE trial, and in this trial, was also found to be a low-cost intervention and hopefully future studies will be able to be helpful in examining the effects of tele-rehab over a longer period of time. Thank you, and I'll pass it off to Dr. Smith. All right, thank you, Dr. Riley, that was really informative, let me center myself. So I'm going to be talking about two trials, one of which kind of feeds off of what Dr. Riley was talking about, and that's what I'm going to be talking about first, with no disclosure. So this is another tele-rehabilitation, tele-medicine intervention for cancer rehabilitation, based off of a previous trial called Emerging from the Haze that was out of Cedars-Sinai for management of cancer-related cognitive impairment, or CRCI, and this is a sort of the offshoot where it's multi-centered and it's, like I said, tele-rehabilitation, it's not in-person. And so what that is, is they want to see if a group-based intervention can improve cancer-related cognitive impairment-related symptoms, and they had a prospective weightless control design. I think this is a really interesting topic, a bit of background, CRCI is ubiquitous, there's some studies that show over three-fourths of patients at some point after chemotherapy will self-report cognitive impairment, and that can be associated with a whole bunch of symptoms, short-term memory loss, trouble multitasking or staying on track with a conversation, or just subjective difficulty in kind of doing their activities of daily living or managing a checkbook, that sort of thing. And it makes people feel isolated, helpless, and it kind of enhances and is enhanced by post-traumatic stress disorder from their actual diagnosis. And the prior results that I alluded to are that when patients get in a group and they learn more about what CRCI is and what some self-management techniques are, they do better. The challenge, though, is that the cognitive testing for CRCI doesn't match up with patient symptoms, meaning you could go in for a six-hour neuropsychological battery and come out maybe saying normal or mildly impaired, but patients are really impacted by their life. There's a few reasons for this. One might be that the testing just isn't good enough. Another might be that it's not taking into consideration covariates, you know, meaning how well are you sleeping, what's your stress, et cetera. Or the most likely is that patients are, you know, up here doing really well functionally, then they get chemotherapy and they do a little bit worse, but they need to reach a much lower threshold before our neuropsychological tests show anything. So this study looks at if we can just kind of help patients cope better and better understand what's going on, including those covariates, do they get better? This was a telehealth class-based group intervention, and Cedars-Sinai in L.A. was one site, Kansas, University of Kansas in Kansas City was the other. And so it's nice that there are two geographical and disparate regions. It's a six-week course. There's education, like a didactic PowerPoint. There's homework. And like I said, you're in a group of about six people. It's led by a cancer rehabilitation physiatrist, a neuropsychologist, and in some cases an advanced practice nurse. The patients included were non-metastatic breast cancer survivors, either two months or five years post-chemotherapy, and they were excluded if they had a neurocognitive deficit unrelated to their cancer. The maximum wait time, although this wasn't typically reached, was four months, and again, this was a weightless control trial. So this is a busy slide, and it might be hard to see. It essentially walks through what the coursework was for these patients, and so it's six weeks. The first is an introduction, and it talks about how the brain learns and how it can be affected by chemotherapy. And then it goes into the second week of stress and management, like mindfulness. The third week talks about mood and negative thoughts, as well as cognitive exercises patients can do. The fourth week talks about strategies to improve attention span that don't involve necessarily medication, although that's discussed, and it also talks about sleep hygiene. The fifth week talks about strategies to enhance memory, and it talks about the importance of nutrition. And then finally it talks about, in week six, sort of putting this all together and balancing your lifestyle and making it so you're not overexerting yourself and overstressing yourself. And so the outcome measures that were used for this were adherence to the program, a perceived cognitive impairment based on the Functional Assessment of Cancer Therapy, or FACT-COG tool, a battery called the PROMIS-29, which looks at some cognitive issues, but also fatigue, pain, anxiety, depression, that type of thing, to sort of get to these covariates, an applied cognition form of PROMIS, and a loneliness scale, UCLA loneliness scale. And these are the results. There wasn't a statistically significant difference in terms of age, in terms of stage of cancer, menopausal status, race, ethnicity. About 70% of that cohort was white, so it's predominantly white, and around 10% black for the next highest racial group. And the treatment history, like I said, was pretty much the same. So on the right, in this kind of smaller-to-see slide, and I'll go into this a bit more detail, are the results. And so short-term, the time one was immediately after the intervention, and then time two was one month after the intervention, post-haze, as they call it, because it's emerging from the haze. So immediately after, there was a lot of benefit in terms of improvement on the perceived cognition, and a significant benefit in terms of loneliness. Those benefits were less marked after a month after the haze, but they still sustained in terms of cognition. However, loneliness kind of reverted back, which is telling to me in that being in this group class and feeling validated was very important to these patients. So the intervention improved essentially across the board, all of the patient-reported outcomes. And I'm sorry, I said a month, but it's a year after. The waitlist control group patients did not get better until they did the intervention, so we have some data to show that it works. Interestingly, the higher the perceived loneliness, the worse perceived cognition, which kind of makes sense. You know, if you are feeling really lonely, I think it'd be tougher to have clear thoughts than if you have people like a caregiver or, you know, a spouse or somebody to talk these issues out with. Satisfaction with the overall survey was quite high. And so, you know, what do we kind of make of this? So I think this is a really important topic to be addressing, and I think that this type of intervention has a lot of potential. This is the second study to suggest that it's effective, and this is the first multi-center and tele-rehabilitation study to suggest that this is effective, which is really important. Because CRCI is so difficult to diagnose, you know, our neuropsychological tests don't help us a whole lot, so we can say, okay, this is a working memory issue, this is an executive functioning issue, here are some strategies. Instead of trying to drill down into that, what this group did, which I like a lot, was just to say, you know what, you're reporting a lot of distress and these symptoms, let's validate that and try to still improve what you're feeling. So I think it's really analogous to a lot of chronic post-concussive patients, chronic pain patients, that sort of thing, where it's more about accepting and sort of dealing with these deficits, even if we can't drill down and diagnose these. The group class environment seemed to really empower the patients. Some of the limitations, and forgive me for not having the header here, are this is, it's relatively racially homogenous, you know, like I said, 70% were white. I think, you know, perhaps more telling was that it occurs during the day, meaning that it's biased towards people who are unemployed. They might have more severe impairment, that might be why they're unemployed, or they might be older. There might be some folks working and struggling through that are suffering but can't get into this test. It also wasn't randomized, so there's a bit of an expectancy effect, meaning, you know, patients who are doing this might have a higher perceived impairment and might be expecting to improve. So we have to, I think, I don't know how you can completely blind this, but I think you could randomize it into usual care, and that would be sort of the more gold standard. And I think it had a limited evaluation of comorbidities. So the PROMIS-29 is okay, but it doesn't really drill down into sleep and other issues that patients are having. And so if you really wanted to see it as PTSD, as anxiety, does physical activity have a big impact on CRCI, then I think you need to have more thorough outcome assessments. The advantages to this was that there was a clear improvement following the intervention. Patients really liked it. It was feasible. They adhered to a high rate, which is consistent with what we know about patients and this perceived cognitive impairment, that this is a very disabling or at least psychologically distressing condition, and patients want treatment for this more than most other post-cancer survivorship symptoms. I also think it's really promising that telehealth was an effective vehicle for this, given that this is sort of going to be the trend in rehabilitation medicine in general for a while. It was multidisciplinary, physiatrists and neuropsychologists led. Their future directions are going to be a prerecorded version of this, which will make it easier to implement in your clinics. I can speak anecdotally saying that we are going to adopt something like this very soon, the same type of emerging from the HACE program to be another site for this. So it's definitely feasible, and if you're interested in this, I think email the authors. So my second paper I'm going to discuss in the last of our presentation switches gears a little bit. It has to do with aromatase inhibitor-induced musculoskeletal symptoms, or AIMS, and a follow-up to a study in 2019 that showed that duloxetine improved stiffness and pain in these patients. And what it looks at is, is there a difference between the effect on obese and non-obese patients when it comes to duloxetine and AIMS? So brief background, I'm not going to belabor this because it's, you know, this is a whole hour-long talk, but aromatase inhibitors, for those who don't know, are used to treat estrogen-receptor-positive cancer, either active metastatic cancer, or patients who have no evidence of disease and have circulating microscopic tumor cells that we can't pick up on tests, and they want to deprive them of estrogen of their food so they die off. This improves survival anywhere from a few percentage points to, you know, 20 or 30 percent, depending on risk factors. Unfortunately, AI use, aromatase inhibitor use, is associated with a lot of musculoskeletal symptoms that can be distressing, pain, stiffness, carpal tunnel syndrome, trigger finger, tinnitus, cerebritis, et cetera. And like I said, in the previous phase three trial, which is a, phase three is a multi-centered placebo-controlled trial, they found a modest effect of duloxetine reducing stiffness and pain in these patients. So this is the aromatase inhibitors, anastrozole, letrozole, and exemestane are pretty common, and they inhibit the aromatization of testosterone to estrogen to deprive the cells and, unfortunately, your body's normal tissues of estrogen. So a lot of patients present with upper extremity, especially hand stiffness in the morning. It feels like an arthritis, but x-rays are often negative, and autoimmune serology should be negative if it's true aims. Usually these set in around six weeks and almost always around six months. We don't quite know the entire mechanism, and I'll get to this, you know, in a little bit, but it might be that estrogen is chondroprotective. So without that, the joints feel stiffer, but we also know that our tendon sheets and our finger and our carpal ligament have estrogen receptors. So if all of a sudden you slam the brakes on estrogen production, those local sites may go haywire and be inflamed. So this is important. About a third of women might discontinue treatment due to these arthralgias, and very few, you know, relative to how much would be ideal, are adhering at three years, and this leads to an increase in mortality. So there are some real opportunities for rehabilitation to reduce mortality by improving compliance with these medications. Risk factors for AIMS are obesity, which is the heart of this study, prior taxing, chemotherapy, previous arthralgias, genetic phenotypes, and I didn't write this on the slide, but more distress prior to starting aromatase inhibitors also causes that. So obesity is interesting because it's linked to more severe symptoms, too. There was a trial, and this sort of was the impetus for this paper that looked at anti-inflammatory omega-3 fatty acid supplementation in obese women with AIMS, and it reduced pain and stiffness. And so the authors hypothesized, does duloxetine, which is not anti-inflammatory by nature, also have a similar effect on obese women compared to non-obese? And so in this trial, post-menopausal women, non-metastatic, who were on an aromatase inhibitor for at least three weeks, after one week, they jumped from 30 milligrams to 60 milligrams, and they took this for 12 weeks, so three months, were assigned, and again, compared to placebo. And not at the time of the trial, but post hoc, a secondary analysis, divided these patients into obese and non-obese, and they were given patient-reported outcomes at two weeks, six weeks, and then three months for the final. These patient-reported outcomes were a brief pain index was the primary outcome. They also had a few looking at stiffness, like an arthritis type of score, a FACT endocrine systems score, and a global rating of change questionnaire, meaning I'm better, I'm worse, and this is by how much. So the results are, I'm sorry, this is the demographics. There was no significant difference, except that for the obese cohort, a higher proportion were likely to be black. The results, though, were, I think, pretty telling, in that there was a reduction in the brief pain index that was significant in the obese cohort at all time points, two, six, and 12 weeks, but in the non-obese cohort, duloxetine was no better than the placebo for these patients, which I think tells us a little bit about what may be the underlying mechanism for AIMS in these patients. So this is a diagram that shows the drop, and I should note that even though there was a slight difference in race in the cohorts when controlled in an analysis, duloxetine had no effect regardless of race. On the left is the non-obese patients. The reduction is seen in both the placebo, the gray, and the duloxetine blue. However, in the obese patients, placebo did not reduce symptoms nearly as much as duloxetine, and you can see a statistically significant difference at all time points, although the longer this went on, more of the placebo effect went in. That's on the right side is the obese patients. The blue is the intervention. So the results are that obese women got actually a benefit from this, whereas non-obese was no better than placebo. We don't know why. It could be that there's an anti-inflammatory component to SNRIs, and we know that adipose tissue raises inflammation. Also possible is that there's a different mechanism of AIMS if you're obese versus non-obese. Non-obese may be more physically active, and so to still develop AIMS, there might be some underlying issue. Maybe there's a genetic polymorphism, for example. Importantly, it's been studied, and there's no difference in absorption of duloxetine if you have increased adipose tissue. So this, you know, to me, is a pretty strong study, and to me, it's a bit of a game changer, and it helps me at least understand these patients a bit better. Would I still prescribe duloxetine for a non-obese patient with stiffness? Probably if it's a generalized arthrology, because we don't have a ton of other options, although I think medications like agabapentinoid are worth studying, because the mechanism of this is an upregulation of activity of calcium channel blockers. Gabapentinoids block calcium channels in the dorsal root ganglion. In this study, though, you know, I would, for me, it drives home that for refractory generalized stiffness in obese patients with AIMS, this is definitely a very good option. It's a very strong study. It was large and multi-centered, like I said. It's very generalizable. The pain was often mild to moderate in these patients. These aren't severely disabled patients, and that's most of our cohort is mild to moderate stiffness, and the inclusion criteria was very broad. There wasn't much in terms of exclusion. You know, like I said, in terms of weaknesses, it doesn't necessarily drill to the mechanism of, you know, does physical activity matter? You know, are non-obese patients more physically active, and that's why the placebo was, you know, just as effective, because they didn't need the duloxetine. It also didn't look at diet, and it didn't look at mood, which I thought was important if you're prescribing a medication with antidepressant properties. So it's an interesting jumping-off point for future studies to look at mood and duloxetine and the effect of it. So this is very translatable to clinical practice. It's a medication we prescribe commonly, or at least I do. You know, it's a once-a-day med that's fairly well-tolerated. So I would consider it in any patient with generalizable arthralgias and stiffness because you might improve compliance with aromatase inhibitors. So that's our presentation of the six best papers of the year. You know, I encourage you to read these further. You can rewatch this, and hopefully this generated some good discussion, you know, or good kind of thoughts and questions for you. And if you're like me, I have more questions than answers after listening to these really good presentations by my colleagues, and so I'm really excited to dive deep into this and see what the next year brings. So thank you for listening, and have a great day.

mnemonic compression device

cancer-related lymphedema

patient-reported symptoms

treatment satisfaction

at-home use

pain reduction

swallowing improvement

device satisfaction

exercise-based rehabilitation