Patient Reported Outcomes in Penile Cancer

Patient Reported Outcomes in Penile Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Patient Reported Outcomes in Penile Cancer Irini Youssef, Aasha Hoogland, Jad Chahoud, Philippe Spiess, Heather Jim, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-958776/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: Patient reports of their symptom burden (i.e., patient-reported outcomes or PROs) have been shown to direct clinicians’ ability to personalize care and improve outcomes. A disciplined assessment of PRO in the population of patients with penile cancer (PeCa) has not previously been undertaken. Our center has both a significant cadre of patients with PeCa and a significant experience with a well-established PRO: the Edmonton Symptom Assessment Scale (ESAS). Methods: After IRB approval, we screened ESAS surveys of 14,781 patients completed between 2/2017 and 2/2021. Of these, those with PeCa were divided into three cohorts: (A) Those after any partial penectomy procedure without lymph node dissection (LND); (B) Those after partial penectomy procedure with LND; and (C) Those after total penectomy and LND. Patients with recurrent disease were analyzed separately. ESAS scores were collated and compared both by individual symptom and cumulatively. Results: 22 PeCa patients completed 122 ESAS surveys in this time and are included in this analysis: a median of 4 ESAS surveys (mean=5, range=1-19) were completed by each patient. The symptom with the highest median ESAS score was Tiredness (3.00). Patients with recurrent disease had the highest cumulative symptom score (median score = 30). Patients after total penectomy with LND had a higher cumulative symptom score (14.4) than those with partial penectomy and LND (7.9). Conclusions: PROs provide an insight into the morbidity of therapies for PeCa, and the most symptoms are reported by patients with recurrent disease. Cancer Biology Symptom management Patient-reported outcomes Penile cancer ESAS Figures Figure 1 Figure 2 Introduction Patient-centered care mandates the knowledge of patient perspectives and concerns and their subsequent inclusion in any multidisciplinary therapeutic regimen. Modern patient-reported outcomes (PROs) serve a critical role informing the patient perspective as we assess objective clinical data; they correlate with diagnosis [ 1 , 2 ], treatment response [ 3 ], and disease recurrence [ 4 ]. Assessment of PROs has become an important component of comprehensive oncological care since data reported by Basch and colleagues revealed improved survival and quality of life and fewer emergency room visits [ 5 ]. Our center has used PRO data specifically in the form of the Edmonton Symptom Assessment Scale (ESAS). Patients in our Radiation Oncology, Supportive Care and Head & Neck clinics fill these surveys out at each visit and results are transferred to the electronic medical record. Prior publications have analyzed ESAS data in patients with esophageal cancer [ 6 ], retroperitoneal sarcoma[ 7 ] and multiple myeloma [ 8 ], and in ruling out anemia [ 9 ]. Squamous cell carcinoma of the penis (PeCa) is a rare but highly aggressive tumor with the potential for early locoregional recurrence and distant metastasis even after multidisciplinary therapy [ 10 ]. There are no randomized data supporting post-operative radiotherapy routinely in PeCa [ 11 , 12 ], although some recent data support its use in pathological N3 disease [ 13 , 14 ]. Neoadjuvant chemotherapy is recommended for patients with multiple, fixed, or bulky inguinal lymph nodes [ 11 , 15 ]. Most of these patients with bulky or advanced disease will have disease recurrence. Unfortunately, patients with disease recurrence after cisplatin-based chemotherapy and surgical consolidation, have few treatment options with limited survival [ 16 ]. This manuscript attempts to define the role of PRO, specifically ESAS, in PeCa. The subject has not previously been investigated. Our clinical perspective is that penile sparing procedures will be better tolerated by patients, and that lymph node dissection, while crucially necessary, may be quite morbid. Patients And Methods Survey This study was approved by the appropriate Scientific and Institutional Review Boards (Study MCC20731). The scale used for symptom burden assessment was a modified Edmonton Symptom Assessment Scale (ESAS-r-CSS) [ 16 ]. The ESAS-r-CSS surveys 12 symptoms (i.e., anxiety, constipation, depression, difficulty sleeping, drowsiness, lack of appetite, nausea, overall well-being, pain, shortness of breath, spiritual well-being, tiredness). An 11-point Likert-type scale from 0 (none) to 10 (worst possible) was used and symptom burden was collated in two ways: The sum of all scores (range 0-120) reflect total symptom burden, and values were also considered individually (range 0-10). All patients attending the Radiation Oncology and Supportive Care Clinics complete this survey at every visit except daily radiation treatments. Because of the potential bias inherent in patients filling out multiple forms, results were grouped by patient (Table 2 ). This means we averaged survey scores of each patient and used the mean as that patient’s value, rather than counting all the individual surveys by each patient as different surveys. Mean values between each cohort for each ESAS category were compared. Scores for each category were also compared between patients who were previously or never on radiation or chemotherapy and those currently on radiation (Table 3 ) or chemotherapy (Table 4 ). Population: At our center, PRO data are integrated with other patient and clinical data within the enterprise data warehouse: Health and Research Informatics (HRI). After Institutional Review Board approval, we queried HRI for all patients who completed an ESAS survey between February, 2017 and February 2021; 61,189 surveys from 14,781 patients were collected. Table 1 collates data for the 22 PeCa patients who completed surveys during this period. A total of 122 surveys were collected for a median of 4 completed surveys per patient (mean=5, range=1-19). Patients were then divided into four cohorts: (A) Those after any partial penectomy procedure without lymph node dissection (LND); (B) Those after any partial penectomy procedure with LND; and (C) Those after total penectomy and LND. Cohort D included patients with recurrent disease. Complications were quantified using the Clavien–Dindo (CD) classification system for surgical complications [ 17 ]. Results Table 2 - 4 and Figures 1 and 2 summarize the ESAS survey data by patient cohort. Three patients were represented in two cohorts. Patient 3 was in cohort B until recurrence, subsequently his survey values were included in cohort D, as patient 20 was included in cohort C until recurrence, when his surveys were moved to cohort D. Similarly, Patient 9 was first evaluated in cohort A, then C, based on surgical history at the time of visit. In cohort A, of 4 patients, half were currently on chemotherapy, and three were on RT. In cohort B, of 6 patients, four were currently on chemotherapy, and two were on RT. In cohort C, half were receiving both chemotherapy and radiation currently. In cohort D, half were currently on chemotherapy, and one was receiving palliative RT. In the entire patient cohort, the most common individual symptom was Tiredness, mirroring other work [ 18 ]. Cohort D had the highest cumulative symptom score (median 30; Figure 2 ), which is consistent with expectations for a cadre of patients with recurrent disease. Similarly, patients after total penectomy with LND had a higher median score (21) than those with partial penectomy and LND (5), in keeping with our theory that extent of surgery was a consideration in cumulative symptoms score. In Table 2 , significant differences were noted across cohorts in mean scores for pain, tiredness, and overall wellness, with patients in cohort D having the highest scores. When analyzed across all surveys without grouping by patients who took multiple surveys, results revealed a statistically significant difference across all cohorts for each category except nausea, and appetite. Notably, patients in cohort C and D had the first and second highest depression scores, respectively, compared to cohort A and B (mean scores 3.3 and 2.3 compared to 0.91 and 0.3, p<.0005). As noted above, this interpretation is subject to confounding by some patients contributing multiple scores. Table 3 reveals that mean scores statistically differed between patients who had never received radiation compared to patients who previously or were currently receiving radiation for anxiety, depression, sleep, overall wellness and spirituality. In Table 4 , mean scores were statistically significantly higher for anxiety, nausea, depression and spirituality in those who had previously received chemotherapy. Patients currently receiving chemotherapy had the highest mean score for nausea. Discussion Patients with penile cancer are a challenging group to treat, both oncologically and psychologically. This malignancy can be highly aggressive, with high mortality rates once advanced, and local treatment is unfortunately mutilating and devastating [ 11 ]. Due to the rarity of this cancer, there is scarce level one data on organ preservation, so men requiring penectomies are ultimately impacted both functionally and psychologically. The high median symptom score for cohort A patients may be explained by the fact that 3 of the 4 were treated pre-operatively on the International Penile Advanced Cancer Trial (InPACT) trial [ 19 ], with known inguinal disease in these cases. InPACT is co-sponsored by the US National Cancer Institute and the UK Institute of Cancer Research. InPACT has a two-part construct: the first deals with the role of therapy prior to ILND and the second with management of the pelvis. The trial is well designed and to date has accrued over a quarter of the patient goal. In our study, men who had undergone total penectomy (Cohort C) had the highest scores for anxiety and depression. While treatment varies significantly by stage at presentation, PeCa therapy has been shown to cause psychiatric symptoms in 50% of patients [ 20 ]. Ficarra and associates demonstrated that patients having more significant treatments were more likely to have impaired well-being [ 21 ], with rates of anxiety and depression as high as 58% and 39% respectively [ 22 , 23 ]. Often men are confronted with the psychologic impact of a penectomy only after the intervention, which can lead to body image disorders, and negative changes in male identity, sexuality and partnerships [ 24 ]. The high risk of psychological trauma stemming from genital surgery leads to a need for more organ-preserving treatment when appropriate. Men who have undergone partial penectomy have reported normal to slightly reduced sexual satisfaction, and no significant levels of anxiety or depression [ 25 ]. Our patients who had undergone partial penectomy (Cohorts A and B) had lower rates of anxiety and depression combined, and better overall wellness scores. However, penile cancer of any extent is not without its own risk. One SEER analysis of 6155 patients with penile cancer found a suicide risk of 0.2%, all in men who had undergone a surgical intervention [ 26 ]. Early referral to a Supportive Care service is crucial for this patient population. Several studies show that early supportive/palliative care improves both quality and quantity of life in advanced cancer patients [ 27 , 28 ] particularly in men [ 28 ]. Conclusion Penile cancer is a disease with great psychologic implications. Management of this malignancy can be highly disfiguring, causing psychological trauma. Patients undergoing partial penectomy with LND have the fewest overall symptoms, and those with recurrent disease report the highest symptoms. Comprehensive care and support groups are critical in these patients. Declarations Conflict of interest: There are no conflicts of interest to disclose. Funding: No funding was received for conducting this study. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Moffitt Cancer Center. Consent: Informed consent was obtained from all individual participants included in the study. Authors contribution statement: Irini Youssef, MD: Writing, Methodology, Formal Analysis, Aasha I. Hoogland, Ph.D.: Resources, Data Curation, Jad Chahoud, MD, MPH: Writing Philippe E. Spiess, MD: Writing, Supervision Heather Jim, Ph.D.: Investigation, Validation, Writing, Supervision Peter A. S. Johnstone, MD: Conceptualization, Investigation, Validation, Writing, Supervision References Paparrizos, J., R.W. White, and E. Horvitz, Screening for Pancreatic Adenocarcinoma Using Signals From Web Search Logs: Feasibility Study and Results. J Oncol Pract, 2016. 12 (8): p. 737-44. White, R.W. and E. Horvitz, Evaluation of the Feasibility of Screening Patients for Early Signs of Lung Carcinoma in Web Search Logs. JAMA Oncol, 2017. 3 (3): p. 398-401. Victorson, D., M. Soni, and D. Cella, Metaanalysis of the correlation between radiographic tumor response and patient-reported outcomes. Cancer, 2006. 106 (3): p. 494-504. Denis, F., et al., Randomized Trial Comparing a Web-Mediated Follow-up With Routine Surveillance in Lung Cancer Patients. J Natl Cancer Inst, 2017. 109 (9). Basch, E., et al., Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial. J Clin Oncol, 2016. 34 (6): p. 557-65. McDonald, J., et al., The Role of Patient Reported Outcomes (PRO) in Esophageal Cancer (ESOCA) Patients Receiving Radiotherapy (RT). International Journal of Radiation Oncology*Biology*Physics, 2020. 108 : p. E64-E65. Palm, R.F., et al., Using the revised Edmonton symptom assessment scale during neoadjuvant radiotherapy for retroperitoneal sarcoma. Clin Transl Radiat Oncol, 2020. 22 : p. 22-28. Nanda, R., et al., Patient-reported outcomes regarding radiation therapy in patients with multiple myeloma. Acta Oncol, 2020. 59 (8): p. 983-987. Johnstone, P.A.S., et al., Patient-reported outcomes: using ESAS to screen for anemia. Support Care Cancer, 2020. 28 (9): p. 4141-4145. Sonpavde, G., et al., Penile cancer: current therapy and future directions. Ann Oncol, 2013. 24 (5): p. 1179-89. Hakenberg, O.W., et al., EAU guidelines on penile cancer: 2014 update. Eur Urol, 2015. 67 (1): p. 142-150. Robinson, R., et al., Risks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer: A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel. Eur Urol, 2018. 74 (1): p. 76-83. Yuan, Z., et al., The relationship between HPV status and chemoradiotherapy in the locoregional control of penile cancer. World J Urol, 2018. 36 (9): p. 1431-1440. Johnstone, P.A.S., et al., Primary Penile Cancer: The Role of Adjuvant Radiation Therapy in the Management of Extranodal Extension in Lymph Nodes. Eur Urol Focus, 2019. 5 (5): p. 737-741. Bandini, M., F. Pederzoli, and A. Necchi, Neoadjuvant chemotherapy for lymph node-positive penile cancer: current evidence and knowledge. Curr Opin Urol, 2020. 30 (2): p. 218-222. Hakenberg, O.W. and C. Protzel, Chemotherapy in penile cancer. Ther Adv Urol, 2012. 4 (3): p. 133-8. Dindo, D., N. Demartines, and P.A. Clavien, Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg, 2004. 240 (2): p. 205-13. Johnstone, P.A.S., et al., A modified Edmonton Symptom Assessment Scale for symptom clusters in radiation oncology patients. Cancer Med, 2017. 6 (9): p. 2034-2041. Canter, D.J., et al., The International Penile Advanced Cancer Trial (InPACT): Rationale and Current Status. Eur Urol Focus, 2019. 5 (5): p. 706-709. Maddineni, S.B., M.M. Lau, and V.K. Sangar, Identifying the needs of penile cancer sufferers: a systematic review of the quality of life, psychosexual and psychosocial literature in penile cancer. BMC Urol, 2009. 9 : p. 8. Ficarra, V., et al., Local treatment of penile squamous cell carcinoma. Urol Int, 2002. 69 (3): p. 169-73. Yu, C., et al., Sexual Function after Partial Penectomy: A Prospectively Study From China. Sci Rep, 2016. 6 : p. 21862. Romero, F.R., et al., Sexual function after partial penectomy for penile cancer. Urology, 2005. 66 (6): p. 1292-5. Draeger, D.L., K.D. Sievert, and O.W. Hakenberg, Cross-Sectional Patient-Reported Outcome Measuring of Health-Related Quality of Life With Establishment of Cancer- and Treatment-Specific Functional and Symptom Scales in Patients With Penile Cancer. Clin Genitourin Cancer, 2018. 16 (6): p. e1215-e1220. D'Ancona, C.A., et al., Quality of life after partial penectomy for penile carcinoma. Urology, 1997. 50 (4): p. 593-6. Simpson, W.G., et al., Analysis of Suicide Risk in Patients with Penile Cancer and Review of the Literature. Clin Genitourin Cancer, 2018. 16 (2): p. e257-e261. Temel, J.S., et al., Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer. New England Journal of Medicine, 2010. 363 (8): p. 733-742. Nipp, R.D., et al., Differential effects of early palliative care based on the age and sex of patients with advanced cancer from a randomized controlled trial. Palliat Med, 2018. 32 (4): p. 757-766. tables Table 1: Demographics Pt # Cohort Age Surveys completed Complications? (C-D grade) 1 A 46.2 3 Y (I) 2 C 74 1 N 3 B -> D 69.6 10 Y (IIIa) 4 D 68.7 1 N 5 D 71.7 6 N 6 C 43.5 19 N 7 D 88 3 N 8 A 62.9 1 N 9 A -> C 78 4 Y (IIIb) 10 B 73.1 4 N 11 D 61.6 4 Y (I) 12 B 51.7 5 Y (I) 13 D 34.1 11 N 14 B 79.8 1 N 15 B 47.5 8 Y (I) 16 D 73.3 1 N 17 C 59.1 1 N 18 D 67.8 11 N 19 D 74.7 1 N 20 C -> D 75.8 6 N 21 A 46.9 4 N 22 B 49.2 7 N Pt = patient; C-D= Clavien-Dindo Table 2: Comparing grouped means between cohorts. In this analysis, surveys of each patient were averaged, and the mean value was used, rather than counting each individual survey by each patient as unique data. Significant values are bolded . Cohort A Cohort B Cohort C Cohort D P-value Breath 0.90 0.21 0.86 1.28 0.63 Pain 0.94 1.32 1.97 4.82 0.00 Tired 3.58 0.86 1.20 4.35 0.01 Anxiety 1.27 0.68 1.14 1.57 0.75 Nausea 2.17 0.47 0.25 1.94 0.46 Depression 0.73 0.18 2.22 1.35 0.20 Sleep 4.06 1.22 1.97 3.09 0.31 Drowsy 3.40 0.54 1.84 1.93 0.28 Appetite 1.85 1.29 0.36 3.62 0.12 Constipation 1.67 0.07 1.15 1.05 0.52 Overall Wellness 1.29 0.90 0.65 4.00 0.05 Spirituality 0.06 0.13 0.75 0.68 0.50 Sum 21.85 7.86 14.35 29.68 0.02 Table 3: Mean symptom score by timing of radiotherapy. Significant values are bolded . N C P P-value Breath 1.2 0.8 1.1 .716 Pain 3.1 1.6 2.6 .065 Tired 2.9 2.9 3.5 .638 Anxiety 1.4 1.6 4.7 .000 Nausea 1.1 1.3 0.7 .647 Depression 1.5 1.2 4.4 .000 Sleep 2.4 2.3 4.6 .015 Drowsy 1.7 1.8 3.3 .065 Appetite 1.6 2.8 1.6 .094 Constipation 1.2 1.5 0.5 .307 Overall Wellness 2.0 1.5 3.5 .031 Spiritual Score 0.8 0.7 3.7 .000 Sum 20.8 20.0 34.3 .016 Table 4: Mean symptom score by timing of chemotherapy. Significant values are bolded . N C P P-value Breath 1.48 0.43 0.94 .100 Pain 2.40 2.10 2.86 .58 Tired 2.81 3.62 2.86 .498 Anxiety 1.52 1.10 2.86 .019 Nausea 1.38 2.14 0.45 .019 Depression 1.36 0.95 2.80 .006 Sleep 2.14 2.90 3.24 .218 Drowsy 1.90 2.00 2.06 .961 Appetite 1.64 2.33 2.12 .586 Constipation 1.24 2.00 0.71 .073 Overall Wellness 1.79 1.67 2.55 .280 Spiritual Score 0.71 0.52 2.00 .006 Sum 20.4 21.76 25.45 .437 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-958776","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":61675812,"identity":"4d9b4e89-8019-4a97-9f76-38adeaa4e4d0","order_by":0,"name":"Irini Youssef","email":"","orcid":"https://orcid.org/0000-0001-5589-0782","institution":"SUNY Downstate: SUNY Downstate Health Sciences University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Irini","middleName":"","lastName":"Youssef","suffix":""},{"id":61675813,"identity":"e807f772-0a44-4e76-9ae6-9715a9677b32","order_by":1,"name":"Aasha Hoogland","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Aasha","middleName":"","lastName":"Hoogland","suffix":""},{"id":61675814,"identity":"c20bd1f4-05b1-416a-98cf-b7d533de1318","order_by":2,"name":"Jad Chahoud","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jad","middleName":"","lastName":"Chahoud","suffix":""},{"id":61675815,"identity":"48668b24-dd33-4820-9658-5426df406759","order_by":3,"name":"Philippe Spiess","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Philippe","middleName":"","lastName":"Spiess","suffix":""},{"id":61675816,"identity":"a81236d3-9166-4224-96a8-fea68995f28a","order_by":4,"name":"Heather Jim","email":"","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Heather","middleName":"","lastName":"Jim","suffix":""},{"id":61675817,"identity":"5273b3e0-ade7-4b53-af5f-82c10f0764db","order_by":5,"name":"Peter Johnstone","email":"data:image/png;base64,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","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Johnstone","suffix":""}],"badges":[],"createdAt":"2021-10-07 09:00:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-958776/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-958776/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":15371076,"identity":"71217424-8b5e-4a46-8516-68e373c2fccd","added_by":"auto","created_at":"2021-11-09 17:29:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":55508,"visible":true,"origin":"","legend":"Average ESAS Scores by Cohort and Category","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-958776/v1/c435b30601bc35a1be85d833.jpg"},{"id":15371075,"identity":"bcea1318-f4f8-4990-8fc3-da95c43b3743","added_by":"auto","created_at":"2021-11-09 17:29:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":19597,"visible":true,"origin":"","legend":"Sum Score by Cohort","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-958776/v1/6a50731f40465b7346fc0714.jpg"},{"id":16512396,"identity":"c9f4a964-0fb6-4707-a994-c07f91b7db5f","added_by":"auto","created_at":"2021-12-16 13:04:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":402277,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-958776/v1/06e64d2a-b91c-4b34-b93f-4e63379a90d3.pdf"}],"financialInterests":"","formattedTitle":"Patient Reported Outcomes in Penile Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePatient-centered care mandates the knowledge of patient perspectives and concerns and their subsequent inclusion in any multidisciplinary therapeutic regimen. Modern patient-reported outcomes (PROs) serve a critical role informing the patient perspective as we assess objective clinical data; they correlate with diagnosis [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e], treatment response [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], and disease recurrence [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. Assessment of PROs has become an important component of comprehensive oncological care since data reported by Basch and colleagues revealed improved survival and quality of life and fewer emergency room visits [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eOur center has used PRO data specifically in the form of the Edmonton Symptom Assessment Scale (ESAS). Patients in our Radiation Oncology, Supportive Care and Head \u0026amp; Neck clinics fill these surveys out at each visit and results are transferred to the electronic medical record. Prior publications have analyzed ESAS data in patients with esophageal cancer [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e], retroperitoneal sarcoma[\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e] and multiple myeloma [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e], and in ruling out anemia [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eSquamous cell carcinoma of the penis (PeCa) is a rare but highly aggressive tumor with the potential for early locoregional recurrence and distant metastasis even after multidisciplinary therapy [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. There are no randomized data supporting post-operative radiotherapy routinely in PeCa [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e], although some recent data support its use in pathological N3 disease [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Neoadjuvant chemotherapy is recommended for patients with multiple, fixed, or bulky inguinal lymph nodes [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. Most of these patients with bulky or advanced disease will have disease recurrence. Unfortunately, patients with disease recurrence after cisplatin-based chemotherapy and surgical consolidation, have few treatment options with limited survival [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThis manuscript attempts to define the role of PRO, specifically ESAS, in PeCa. The subject has not previously been investigated. Our clinical perspective is that penile sparing procedures will be better tolerated by patients, and that lymph node dissection, while crucially necessary, may be quite morbid.\u003c/p\u003e"},{"header":"Patients And Methods","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\n\u003ch2\u003eSurvey\u003c/h2\u003e\n\u003cp\u003eThis study was approved by the appropriate Scientific and Institutional Review Boards (Study MCC20731). The scale used for symptom burden assessment was a modified Edmonton Symptom Assessment Scale (ESAS-r-CSS) [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. The ESAS-r-CSS surveys 12 symptoms (i.e., anxiety, constipation, depression, difficulty sleeping, drowsiness, lack of appetite, nausea, overall well-being, pain, shortness of breath, spiritual well-being, tiredness). An 11-point Likert-type scale from 0 (none) to 10 (worst possible) was used and symptom burden was collated in two ways: The sum of all scores (range 0-120) reflect total symptom burden, and values were also considered individually (range 0-10). All patients attending the Radiation Oncology and Supportive Care Clinics complete this survey at every visit except daily radiation treatments.\u003c/p\u003e\n\u003cp\u003eBecause of the potential bias inherent in patients filling out multiple forms, results were grouped by patient (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). This means we averaged survey scores of each patient and used the mean as that patient\u0026rsquo;s value, rather than counting all the individual surveys by each patient as different surveys. Mean values between each cohort for each ESAS category were compared. Scores for each category were also compared between patients who were previously or never on radiation or chemotherapy and those currently on radiation (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e) or chemotherapy (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003ePopulation:\u003c/h2\u003e\n\u003cp\u003eAt our center, PRO data are integrated with other patient and clinical data within the enterprise data warehouse: Health and Research Informatics (HRI). After Institutional Review Board approval, we queried HRI for all patients who completed an ESAS survey between February, 2017 and February 2021; 61,189 surveys from 14,781 patients were collected. Table 1 collates data for the 22 PeCa patients who completed surveys during this period. A total of 122 surveys were collected for a median of 4 completed surveys per patient (mean=5, range=1-19).\u003c/p\u003e\n\u003cp\u003ePatients were then divided into four cohorts: (A) Those after any partial penectomy procedure without lymph node dissection (LND); (B) Those after any partial penectomy procedure with LND; and (C) Those after total penectomy and LND. Cohort D included patients with recurrent disease. Complications were quantified using the Clavien\u0026ndash;Dindo (CD) classification system for surgical complications [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e-\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Figures \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e summarize the ESAS survey data by patient cohort. Three patients were represented in two cohorts. Patient 3 was in cohort B until recurrence, subsequently his survey values were included in cohort D, as patient 20 was included in cohort C until recurrence, when his surveys were moved to cohort D. Similarly, Patient 9 was first evaluated in cohort A, then C, based on surgical history at the time of visit. In cohort A, of 4 patients, half were currently on chemotherapy, and three were on RT. In cohort B, of 6 patients, four were currently on chemotherapy, and two were on RT. In cohort C, half were receiving both chemotherapy and radiation currently. In cohort D, half were currently on chemotherapy, and one was receiving palliative RT.\u003c/p\u003e\n\u003cp\u003eIn the entire patient cohort, the most common individual symptom was Tiredness, mirroring other work [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]. Cohort D had the highest cumulative symptom score (median 30; Figure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e), which is consistent with expectations for a cadre of patients with recurrent disease. Similarly, patients after total penectomy with LND had a higher median score (21) than those with partial penectomy and LND (5), in keeping with our theory that extent of surgery was a consideration in cumulative symptoms score. In Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, significant differences were noted across cohorts in mean scores for pain, tiredness, and overall wellness, with patients in cohort D having the highest scores.\u003c/p\u003e\n\u003cp\u003eWhen analyzed across all surveys \u003cspan class=\"Underline\"\u003ewithout\u003c/span\u003e grouping by patients who took multiple surveys, results revealed a statistically significant difference across all cohorts for each category except nausea, and appetite. Notably, patients in cohort C and D had the first and second highest depression scores, respectively, compared to cohort A and B (mean scores 3.3 and 2.3 compared to 0.91 and 0.3, p\u0026lt;.0005). As noted above, this interpretation is subject to confounding by some patients contributing multiple scores.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e reveals that mean scores statistically differed between patients who had never received radiation compared to patients who previously or were currently receiving radiation for anxiety, depression, sleep, overall wellness and spirituality.\u003c/p\u003e\n\u003cp\u003eIn Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, mean scores were statistically significantly higher for anxiety, nausea, depression and spirituality in those who had previously received chemotherapy. Patients currently receiving chemotherapy had the highest mean score for nausea.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePatients with penile cancer are a challenging group to treat, both oncologically and psychologically. This malignancy can be highly aggressive, with high mortality rates once advanced, and local treatment is unfortunately mutilating and devastating [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Due to the rarity of this cancer, there is scarce level one data on organ preservation, so men requiring penectomies are ultimately impacted both functionally and psychologically.\u003c/p\u003e \u003cp\u003eThe high median symptom score for cohort A patients may be explained by the fact that 3 of the 4 were treated pre-operatively on the International Penile Advanced Cancer Trial (InPACT) trial [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], with known inguinal disease in these cases. InPACT is co-sponsored by the US National Cancer Institute and the UK Institute of Cancer Research. InPACT has a two-part construct: the first deals with the role of therapy prior to ILND and the second with management of the pelvis. The trial is well designed and to date has accrued over a quarter of the patient goal.\u003c/p\u003e \u003cp\u003eIn our study, men who had undergone total penectomy (Cohort C) had the highest scores for anxiety and depression. While treatment varies significantly by stage at presentation, PeCa therapy has been shown to cause psychiatric symptoms in 50% of patients [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Ficarra and associates demonstrated that patients having more significant treatments were more likely to have impaired well-being [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], with rates of anxiety and depression as high as 58% and 39% respectively [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Often men are confronted with the psychologic impact of a penectomy only after the intervention, which can lead to body image disorders, and negative changes in male identity, sexuality and partnerships [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe high risk of psychological trauma stemming from genital surgery leads to a need for more organ-preserving treatment when appropriate. Men who have undergone partial penectomy have reported normal to slightly reduced sexual satisfaction, and no significant levels of anxiety or depression [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Our patients who had undergone partial penectomy (Cohorts A and B) had lower rates of anxiety and depression combined, and better overall wellness scores. However, penile cancer of any extent is not without its own risk. One SEER analysis of 6155 patients with penile cancer found a suicide risk of 0.2%, all in men who had undergone a surgical intervention [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Early referral to a Supportive Care service is crucial for this patient population. Several studies show that early supportive/palliative care improves both quality and quantity of life in advanced cancer patients [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] particularly in men [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePenile cancer is a disease with great psychologic implications. Management of this malignancy can be highly disfiguring, causing psychological trauma. Patients undergoing partial penectomy with LND have the fewest overall symptoms, and those with recurrent disease report the highest symptoms. Comprehensive care and support groups are critical in these patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Moffitt Cancer Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIrini Youssef, MD: Writing, Methodology, Formal Analysis,\u003c/p\u003e\n\u003cp\u003eAasha I. Hoogland, Ph.D.: Resources, Data Curation,\u003c/p\u003e\n\u003cp\u003eJad Chahoud, MD, MPH: Writing\u003c/p\u003e\n\u003cp\u003ePhilippe E. Spiess, MD: Writing, Supervision\u003c/p\u003e\n\u003cp\u003eHeather Jim, Ph.D.: Investigation, Validation, Writing, Supervision\u003c/p\u003e\n\u003cp\u003ePeter A. S. Johnstone, MD: Conceptualization, Investigation, Validation, Writing, Supervision\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003ePaparrizos, J., R.W. White, and E. Horvitz, \u003cem\u003eScreening for Pancreatic Adenocarcinoma Using Signals From Web Search Logs: Feasibility Study and Results.\u003c/em\u003e J Oncol Pract, 2016. \u003cstrong\u003e12\u003c/strong\u003e(8): p. 737-44.\u003c/li\u003e\n \u003cli\u003eWhite, R.W. and E. Horvitz, \u003cem\u003eEvaluation of the Feasibility of Screening Patients for Early Signs of Lung Carcinoma in Web Search Logs.\u003c/em\u003e JAMA Oncol, 2017. \u003cstrong\u003e3\u003c/strong\u003e(3): p. 398-401.\u003c/li\u003e\n \u003cli\u003eVictorson, D., M. Soni, and D. 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E64-E65.\u003c/li\u003e\n \u003cli\u003ePalm, R.F., et al., \u003cem\u003eUsing the revised Edmonton symptom assessment scale during neoadjuvant radiotherapy for retroperitoneal sarcoma.\u003c/em\u003e Clin Transl Radiat Oncol, 2020. \u003cstrong\u003e22\u003c/strong\u003e: p. 22-28.\u003c/li\u003e\n \u003cli\u003eNanda, R., et al., \u003cem\u003ePatient-reported outcomes regarding radiation therapy in patients with multiple myeloma.\u003c/em\u003e Acta Oncol, 2020. \u003cstrong\u003e59\u003c/strong\u003e(8): p. 983-987.\u003c/li\u003e\n \u003cli\u003eJohnstone, P.A.S., et al., \u003cem\u003ePatient-reported outcomes: using ESAS to screen for anemia.\u003c/em\u003e Support Care Cancer, 2020. \u003cstrong\u003e28\u003c/strong\u003e(9): p. 4141-4145.\u003c/li\u003e\n \u003cli\u003eSonpavde, G., et al., \u003cem\u003ePenile cancer: current therapy and future directions.\u003c/em\u003e Ann Oncol, 2013. \u003cstrong\u003e24\u003c/strong\u003e(5): p. 1179-89.\u003c/li\u003e\n \u003cli\u003eHakenberg, O.W., et al., \u003cem\u003eEAU guidelines on penile cancer: 2014 update.\u003c/em\u003e Eur Urol, 2015. \u003cstrong\u003e67\u003c/strong\u003e(1): p. 142-150.\u003c/li\u003e\n \u003cli\u003eRobinson, R., et al., \u003cem\u003eRisks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer: A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel.\u003c/em\u003e Eur Urol, 2018. \u003cstrong\u003e74\u003c/strong\u003e(1): p. 76-83.\u003c/li\u003e\n \u003cli\u003eYuan, Z., et al., \u003cem\u003eThe relationship between HPV status and chemoradiotherapy in the locoregional control of penile cancer.\u003c/em\u003e World J Urol, 2018. \u003cstrong\u003e36\u003c/strong\u003e(9): p. 1431-1440.\u003c/li\u003e\n \u003cli\u003eJohnstone, P.A.S., et al., \u003cem\u003ePrimary Penile Cancer: The Role of Adjuvant Radiation Therapy in the Management of Extranodal Extension in Lymph Nodes.\u003c/em\u003e Eur Urol Focus, 2019. \u003cstrong\u003e5\u003c/strong\u003e(5): p. 737-741.\u003c/li\u003e\n \u003cli\u003eBandini, M., F. Pederzoli, and A. Necchi, \u003cem\u003eNeoadjuvant chemotherapy for lymph node-positive penile cancer: current evidence and knowledge.\u003c/em\u003e Curr Opin Urol, 2020. \u003cstrong\u003e30\u003c/strong\u003e(2): p. 218-222.\u003c/li\u003e\n \u003cli\u003eHakenberg, O.W. and C. Protzel, \u003cem\u003eChemotherapy in penile cancer.\u003c/em\u003e Ther Adv Urol, 2012. \u003cstrong\u003e4\u003c/strong\u003e(3): p. 133-8.\u003c/li\u003e\n \u003cli\u003eDindo, D., N. Demartines, and P.A. Clavien, \u003cem\u003eClassification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.\u003c/em\u003e Ann Surg, 2004. \u003cstrong\u003e240\u003c/strong\u003e(2): p. 205-13.\u003c/li\u003e\n \u003cli\u003eJohnstone, P.A.S., et al., \u003cem\u003eA modified Edmonton Symptom Assessment Scale for symptom clusters in radiation oncology patients.\u003c/em\u003e Cancer Med, 2017. \u003cstrong\u003e6\u003c/strong\u003e(9): p. 2034-2041.\u003c/li\u003e\n \u003cli\u003eCanter, D.J., et al., \u003cem\u003eThe International Penile Advanced Cancer Trial (InPACT): Rationale and Current Status.\u003c/em\u003e Eur Urol Focus, 2019. \u003cstrong\u003e5\u003c/strong\u003e(5): p. 706-709.\u003c/li\u003e\n \u003cli\u003eMaddineni, S.B., M.M. Lau, and V.K. Sangar, \u003cem\u003eIdentifying the needs of penile cancer sufferers: a systematic review of the quality of life, psychosexual and psychosocial literature in penile cancer.\u003c/em\u003e BMC Urol, 2009. \u003cstrong\u003e9\u003c/strong\u003e: p. 8.\u003c/li\u003e\n \u003cli\u003eFicarra, V., et al., \u003cem\u003eLocal treatment of penile squamous cell carcinoma.\u003c/em\u003e Urol Int, 2002. \u003cstrong\u003e69\u003c/strong\u003e(3): p. 169-73.\u003c/li\u003e\n \u003cli\u003eYu, C., et al., \u003cem\u003eSexual Function after Partial Penectomy: A Prospectively Study From China.\u003c/em\u003e Sci Rep, 2016. \u003cstrong\u003e6\u003c/strong\u003e: p. 21862.\u003c/li\u003e\n \u003cli\u003eRomero, F.R., et al., \u003cem\u003eSexual function after partial penectomy for penile cancer.\u003c/em\u003e Urology, 2005. \u003cstrong\u003e66\u003c/strong\u003e(6): p. 1292-5.\u003c/li\u003e\n \u003cli\u003eDraeger, D.L., K.D. Sievert, and O.W. Hakenberg, \u003cem\u003eCross-Sectional Patient-Reported Outcome Measuring of Health-Related Quality of Life With Establishment of Cancer- and Treatment-Specific Functional and Symptom Scales in Patients With Penile Cancer.\u003c/em\u003e Clin Genitourin Cancer, 2018. \u003cstrong\u003e16\u003c/strong\u003e(6): p. e1215-e1220.\u003c/li\u003e\n \u003cli\u003eD\u0026apos;Ancona, C.A., et al., \u003cem\u003eQuality of life after partial penectomy for penile carcinoma.\u003c/em\u003e Urology, 1997. \u003cstrong\u003e50\u003c/strong\u003e(4): p. 593-6.\u003c/li\u003e\n \u003cli\u003eSimpson, W.G., et al., \u003cem\u003eAnalysis of Suicide Risk in Patients with Penile Cancer and Review of the Literature.\u003c/em\u003e Clin Genitourin Cancer, 2018. \u003cstrong\u003e16\u003c/strong\u003e(2): p. e257-e261.\u003c/li\u003e\n \u003cli\u003eTemel, J.S., et al., \u003cem\u003eEarly Palliative Care for Patients with Metastatic Non\u0026ndash;Small-Cell Lung Cancer.\u003c/em\u003e New England Journal of Medicine, 2010. \u003cstrong\u003e363\u003c/strong\u003e(8): p. 733-742.\u003c/li\u003e\n \u003cli\u003eNipp, R.D., et al., \u003cem\u003eDifferential effects of early palliative care based on the age and sex of patients with advanced cancer from a randomized controlled trial.\u003c/em\u003e Palliat Med, 2018. \u003cstrong\u003e32\u003c/strong\u003e(4): p. 757-766.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eDemographics\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePt #\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCohort\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurveys completed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003e\u003cstrong\u003eComplications? (C-D grade)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e46.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eY (I)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eB -\u0026gt; D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e69.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eY (IIIa)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e68.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e71.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e43.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e62.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eA -\u0026gt; C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eY (IIIb)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e73.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e61.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eY (I)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e51.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eY (I)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e34.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e79.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e47.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eY (I)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e73.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e17\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e59.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e67.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e74.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eC -\u0026gt; D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e75.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e46.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e\u003cstrong\u003e22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e49.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePt = patient; C-D= Clavien-Dindo\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u003c/strong\u003e Comparing grouped means between cohorts. In this analysis, surveys of each patient were averaged, and the mean value was used, rather than counting each individual survey by each patient as unique data. Significant values are \u003cstrong\u003ebolded\u003c/strong\u003e.\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCohort A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCohort B\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCohort C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCohort D\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBreath\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e4.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTired\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e3.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e4.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnxiety\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNausea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e2.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDepression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e2.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSleep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e4.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e3.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrowsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e3.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAppetite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e3.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eConstipation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall Wellness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e1.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpirituality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSum\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e21.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e7.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e14.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15%\"\u003e\n \u003cp\u003e29.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3:\u003c/strong\u003e Mean symptom score by timing of radiotherapy. Significant values are \u003cstrong\u003ebolded\u003c/strong\u003e.\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBreath\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e.716\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTired\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e.638\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnxiety\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNausea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e.647\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDepression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSleep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrowsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAppetite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e.094\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eConstipation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall Wellness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.031\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpiritual Score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSum\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e20.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13%\"\u003e\n \u003cp\u003e34.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4:\u003c/strong\u003e Mean symptom score by timing of chemotherapy. Significant values are \u003cstrong\u003ebolded\u003c/strong\u003e.\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBreath\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e2.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTired\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e2.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e3.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.498\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnxiety\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNausea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e1.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDepression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e1.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSleep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e3.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.218\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrowsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e1.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.961\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAppetite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.586\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eConstipation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e1.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.073\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall Wellness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpiritual Score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e\u003cstrong\u003e.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSum \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12%\"\u003e\n \u003cp\u003e20.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e21.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14%\"\u003e\n \u003cp\u003e25.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19%\"\u003e\n \u003cp\u003e.437\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Symptom management, Patient-reported outcomes, Penile cancer, ESAS","lastPublishedDoi":"10.21203/rs.3.rs-958776/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-958776/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective:\u0026nbsp;Patient reports of their symptom burden (i.e., patient-reported outcomes or PROs) have been shown to direct clinicians’ ability to personalize care and improve outcomes.\u0026nbsp;A disciplined assessment of PRO in the population of patients with penile cancer (PeCa) has not previously been undertaken.\u0026nbsp;Our center has both a significant cadre of patients with PeCa and a significant experience with a well-established PRO: the Edmonton Symptom Assessment Scale (ESAS).\u003c/p\u003e\u003cp\u003eMethods:\u0026nbsp;After IRB approval, we screened ESAS surveys of 14,781 patients completed between 2/2017 and 2/2021.\u0026nbsp;Of these, those with PeCa were divided into three cohorts: (A) Those after any partial penectomy procedure without lymph node dissection (LND); (B) Those after partial penectomy procedure with LND; and (C) Those after total penectomy and LND.\u0026nbsp;Patients with recurrent disease were analyzed separately.\u0026nbsp;ESAS scores were collated and compared both by individual symptom and cumulatively.\u003c/p\u003e\u003cp\u003eResults:\u0026nbsp;22 PeCa patients completed 122 ESAS surveys in this time and are included in this analysis: a median of 4 ESAS surveys (mean=5, range=1-19) were completed by each patient. The symptom with the highest median ESAS score was Tiredness (3.00). Patients with recurrent disease had the highest cumulative symptom score (median score = 30).\u0026nbsp;Patients after total penectomy with LND had a higher cumulative symptom score (14.4) than those with partial penectomy and LND (7.9).\u003c/p\u003e\u003cp\u003eConclusions:\u0026nbsp;PROs provide an insight into the morbidity of therapies for PeCa, and the most symptoms are reported by patients with recurrent disease.\u003c/p\u003e","manuscriptTitle":"Patient Reported Outcomes in Penile Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-11-09 17:29:17","doi":"10.21203/rs.3.rs-958776/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fcd6eac2-afde-483b-8b62-1c932c9bd4e8","owner":[],"postedDate":"November 9th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":8404237,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2021-12-16T13:03:55+00:00","versionOfRecord":[],"versionCreatedAt":"2021-11-09 17:29:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-958776","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-958776","identity":"rs-958776","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}