Late adverse events in patients with pelvic cancer after oncologic treatment -intervention and treatment effect
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Purpose: Few studies have focused on the late adverse events after oncologic treatment in pelvic cancer patients. Here, the treatment effect/interventions were studied on late side effects as GI, sexual and urinary symptoms in pelvic cancer patients who visited a highly specialized rehabilitation clinic in Linköping. Methods This retrospective longitudinal cohort study included 90 patients who had at least one visit at the rehabilitation clinic for late adverse events at Linköping University hospital between 2013 to 2019. The toxicity of the adverse events was analyzed by using the common terminology criteria for adverse events (CTCAE). Results By comparing the toxicity of symptoms between visit 1 and 2, we showed that the GI symptoms decreased with 36.6% ( P = 0.013), the sexual symptoms with 18.3% ( P < 0.0001) and urinary symptoms with 15.5% ( P = 0.004). Patients who received bile salt sequestrant had a significant improvement in grade of GI symptoms as diarrhea/fecal incontinence at visit 2 compared to visit 1 where 91.3% were shown to have a treatment effect ( P = 0.0034). The sexual symptoms (vaginal dryness/pain) significantly improved due to local estrogens between visit 1 and 2 where 58.1% had a reduction of symptoms ( P = 0.0026). Conclusion The late side effects as GI, sexual and urinary symptoms was significantly reduced between visit 1 and 2 at the specialized rehabilitation center in Linköping. Bile salt sequestrants and local estrogens are effective treatments for side effects as diarrhea and vaginal dryness/pain.
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Here, the treatment effect/interventions were studied on late side effects as GI, sexual and urinary symptoms in pelvic cancer patients who visited a highly specialized rehabilitation clinic in Linköping. Methods This retrospective longitudinal cohort study included 90 patients who had at least one visit at the rehabilitation clinic for late adverse events at Linköping University hospital between 2013 to 2019. The toxicity of the adverse events was analyzed by using the common terminology criteria for adverse events (CTCAE). Results By comparing the toxicity of symptoms between visit 1 and 2, we showed that the GI symptoms decreased with 36.6% ( P = 0.013), the sexual symptoms with 18.3% ( P < 0.0001) and urinary symptoms with 15.5% ( P = 0.004). Patients who received bile salt sequestrant had a significant improvement in grade of GI symptoms as diarrhea/fecal incontinence at visit 2 compared to visit 1 where 91.3% were shown to have a treatment effect ( P = 0.0034). The sexual symptoms (vaginal dryness/pain) significantly improved due to local estrogens between visit 1 and 2 where 58.1% had a reduction of symptoms ( P = 0.0026). Conclusion The late side effects as GI, sexual and urinary symptoms was significantly reduced between visit 1 and 2 at the specialized rehabilitation center in Linköping. Bile salt sequestrants and local estrogens are effective treatments for side effects as diarrhea and vaginal dryness/pain. Gastrointestinal urologic sexual late side effects oncologic treatment pelvic cancer Figures Figure 1 Figure 2 Introduction Gynecologic cancer is the second most common cancer in the world among women and in Sweden around 3000 women are diagnosed each year. Today, most gynecologic cancers are associated with a high 5-year survival of around 80%. An increasing incidence in cancer, coupled with improved treatments has resulted in a higher number of patients surviving their disease, and therefore, there is a growing need to improve the patients’ quality of life after oncologic treatment. Treatment for pelvic cancer often includes high doses of radiotherapy directed to the pelvic area. Many of these patients develop late side effects such as chronic changes of the gastrointestinal (GI) tract and for around 50% of these patients the symptoms affect their daily activity and quality of life [ 2 , 3 ]. In previous reports, roughly twenty symptoms from the GI tract were described and in 20–30% of these cases two or more symptoms existed concurrently [ 15 ]. The most common and the most troublesome GI symptom were fecal incontinence and fecal urgency, which often coexisted with sexual and urinary symptoms. Sexual symptoms included fragile vaginal mucous membranes and dyspareunia [ 5 ]. Urinary symptoms often included frequent visits to the toilet, leakage, difficulty in feeling the need to empty the bladder and difficulty to void [ 14 ]. During the past decades, the health care has mainly focused on optimizing the cancer therapy and to improve survival. But there is still a great unmet need for long-term rehabilitation. Therefore, the oncologic clinic at the University Hospital in Linköping decided to start a highly specialized rehabilitation clinic in 2013 for patients with late adverse events after oncologic treatment. The objective of the clinic was to be a referral center for patients diagnosed with pelvic cancer with severe late adverse events after oncologic treatment. Our center provides a multi-professional caring team with doctors, nurses, physiotherapists, dieticians, and psychologists, all with highly specialized competence to take care of the late adverse events that affects these patients. To our knowledge this is one of the few institutions that have adopted this multi-professional advanced rehabilitation structure. We were inspired by the Royal Marsden Hospital in London that established a weekly specialized clinic with a gastroenterologist who specifically helped patients with chronic GI symptoms after cancer treatment. The patients referred to this clinic had all been previously treated with pelvic radiotherapy and had severe GI side effects. Data from this clinic showed that patients treated with pelvic radiotherapy experienced a high number of co-existing side effects, where GI side effects were only one of them. Many side effects persisted and had a clear negative effect on the quality of life for these patients [ 8 ]. Multiple studies have concluded that improvement in the management of treatment related late side effects is needed, but few studies have analyzed the toxicity grade of the late adverse that occurs and further have analyzed the type of interventions and the treatment effects of each intervention used to mitigate these symptoms [ 3 , 4 , 7 , 11 , 16 ]. The aim of this study was to evaluate the toxicity (between visit number 1 and 2) of the late adverse events as GI, urologic and sexual symptoms by using the common terminology criteria for adverse events (CTCAE). Further, we wanted to study different treatment strategies as bile salt sequestrants for diarrhea, anticholinergic drugs for urge to pass urine/frequent visits to the toilet and local estrogens for vaginal dryness/pain in patients with pelvic cancers who received oncologic treatment. Materials And Methods Patients This retrospective longitudinal cohort study comprised 90 patients who had at least one visit to the clinic for late adverse events at Linköping university hospital between 2013 to 2019. This center started in 2013 and was devoted to patients who had newly diagnosed side effects more than three months after the end of the oncologic treatment or who had remaining symptoms several years after finishing treatment. All patients were women. The time point between the first visit and the end of the oncologic treatment varied between 7 months up to several decades (At most 29 years, mean 46 months). In total, 90 patients with pelvic cancer who received some type of oncologic treatment visited the center for late adverse events between 2013 to 2019. The patients had been referred to this clinic from other regions in Sweden, including the county council of Jönköping, Kalmar, Östergötland, Sörmland and Västmanland. All together, they included a population of ~ 1.5 million inhabitants. The patients in this study received treatment due to the following cancer diagnoses: cervical (n = 49), endometrial (n = 13), ovarial/tuba (n = 6) vulva (n = 6), vaginal (n = 3), anal (n = 7), rectal (n = 2) and other cancers (n = 4). The treatment included, radiotherapy, both external beam radiotherapy (ERBT) and brachytherapy (BT), surgery and chemotherapy. The treatments were given either in combination or as a single treatment as shown in Table 1 . All oncologic treatments were given according to the Swedish national guidelines. Table 1. Characteristics of 90 patients who visited the specialized rehabilitation clinic in Linköping. Variables N (%) Type of cancer Cervical 49 (54.5) Endometrial 13 (14.4) Vulva 6 (6.7) Vaginal 3 (3.3) Ovarial/Tubar/Peritoneal 6 (6.7) Anal 7 (7.8) Rectal 2 (2.2) Other 4 (4.4) Tumor stage I 47 (52.2) II 21 (23.3) III 13 (14.5) IV 2 (2.2) Unknown 7 (7.8) Type of oncologic treatment Radiotherapy 3 (3.3) Surgery Surgery + chemotherapy Surgery + chemotherapy + radiotherapy Radiotherapy + chemotherapy Surgery + radiotherapy 24 (26.7) 9 (10.0) 12 (13.3) 33 (36.7) 9 (10.0) Age at diagnosis (mean) Age* (mean) Performance status* 0 1 2 Disease free (cancer)* Yes No Other diseases** Hypertension Diabetes Hypothyroidism Cardiovascular disease Inflammatory bowel disease (IBS) 48.8 years 53.7 years 70 (77.8) 12 (13.3) 8 (8.9) 88 (97.8) 2 (2.2) 12 (13.3) 4 (4.4) 4 (4.4) 7 (7.8) 1 (1.1) *At first visit **Calculated in percent (%) of the 90 patients Data A review of the patient’s oncologic and surgical records was performed in all patients that had at least one visit at the center for late adverse events between the years of 2013 to 2019. The patient’s files were reviewed up to 13 months after their first visit and the number of visits varied from one to two. Table 2 a-b describes the different type of GI, sexual and urologic symptoms and measures/treatments that were used at our rehabilitation clinic. Table 2a. Different type of GI, sexual and urologic symptoms for the 90 patients who visited our specialized rehabilitation clinic GI symptoms Sexual symptoms Urologic symptoms Diarreha Pain at sexual intercourse Urge to pass urine Constipation Flatulence Feeling of dryness/rubbing sensation in vagina Urinary leakage Hematuria Melena Tight and stiff feeling in vagina due to adhesions Pain during bladder filling/emptying Mucous in stool Difficulties to empty the bowel Spasm in the vagina Foul-smelling discharge Cramping around urethra Difficulty emptying the bladder Fecal incontinence Swelling and redness of vulva Recurrent urinary tract infections Subileus Blister and sores in vulva/vagina Alternating hard and loose stools Bleeding Peeing with scattered stream of urine Reduced sex drive/ability to orgasm Feeling of disgust Table 2b. Different type of measures/treatments for GI, sexual and urologic symptoms used for the 90 patients who visited our specialized rehabilitation clinic. Measures/treatment GI symptoms Measures/treatment Sexual symptom Measures/treatment Urologic symptoms Bulking agents (inolaxol, vi-sibin) Local estrogens Anticholinergicum Loperamid Antibiotics Local estrogens Antiemetics Dietician/dietary advice Proton pump inhibitors Pain relivers for pain and cramps (diemtikon, saroten, egazil, papaverine) Antimycotic treatment Knots and relaxation exercise Vaginal dilatator Discussion on multidisciplinary team meetings (MDK) Counselor Referal to urologist for cystoscopy Pinch exercises Instillations via urologist with hyaluronic acid preparations Discussion on multidisciplinary team meetings (MDK) Bile acid sequestrants (cholestagel, lestid, questran) Hyperbar oxygen treatment Pancreas enzyme substitution (creon) Antibiotics (metronidazole/doxyferm) Medicines for rectal bleeding (xyloproct, scheriproct, asacol) Referal to gastroenterologist for coloscopy Hyperbar oxygen treatment Data of diagnosis, tumor stage, differentiation, performance status, oncologic treatment, and late adverse events were collected from the patients’ medical records. The adverse events were retrospectively graded between 1–5 according to the CTCAE grading system [ 1 ]. The CTCAE grading scale was chosen as it is the most used system for grading oncologic side effects. Regarding the toxicity grading, grade 0 meant no side effects, grade 1 meant mild side effects, grade 2 moderate side effects, grade 3 severe side effects, grade 4 life threatening side effects and grade 5 death related to side effects. No patients in our study had grade 4 or 5 side effects. The grade of symptoms was combined into two subgroups where grade 0–1 was considered as one group and grade 2–3 as the other group. Each intervention used as a treatment for the adverse events was documented. Sexual symptoms were determined and treatment with local estrogens prescribed by anamnestic and clinical findings and by a gynecological exam by an experienced senior specialist in gynecologic oncology. GI and urinary symptoms were determined by anamnestic findings and gynecological exam. Bile salt sequestrants and anticholinergic treatment were prescribed due to anamnestic findings without other investigation. All the patients who visited the center for late adverse events met the same doctor at both visit number 1 and 2. Some patients also met a dietician for dietary advice regarding their GI symptoms and a psychologist regarding their sexual symptoms and general well-being. The patients also had regular follow ups by phone by a nurse working at the rehabilitation center. The grading of toxicity for each patient was performed by two independent researchers’ (S. Iselius and A. Holmqvist). The study protocol was approved by the regional ethical committee in Stockholm, Sweden (Reference number: 2021–05034) and was in accordance with the Declaration of Helsinki. All patients have signed a written consent form. Statistical analyses The Chi-square method and the Fischer´s exact test was used to study the differences in the frequency and the toxicity of side effect between visit number 1 and 2. All comparisons were performed by using matched cases. The tests were two-sided and p-value of P < 0.05 was considered statistically significant. Results Patients Ninety patients with pelvic cancer who received oncologic treatment participated in the study. Patients with several different types of cancers were included. Most of the patients (85%) were diagnosed with gynecological cancer. The treatment included surgery, radiotherapy, and chemotherapy in different treatment combinations where 63.3% of the 90 patients received radiotherapy (Table 1 ). Most of the patients that received oncologic treatment were in stage I (52.2%), 23.3% were in stage II and 24.4% in stage III or IV. The tumor stage was unknown (due to no register data) for 7.8% of the patients. The mean age of the patients was 48.8 years (range 19–82) and the mean age at the first visit was 53.7 (range 19–86). Few patients had other diseases at the time for diagnosis (Table 1 ). Side effects At first, we studied the number of patients with late adverse events as GI, sexual and urinary symptoms. Here we showed that 74.4% of the patients had GI symptoms, 55.5% sexual and 37.8% urinary symptoms (Table 3 ). Two or more adverse events were present concurrently in 81.6% of the patients. Patients receiving radiotherapy experienced a higher frequency of late adverse events compared to patients who had surgery alone or surgery in combination with chemotherapy (Table 3 ). GI side effects were present in 71.6% of the patients with radiotherapy, 74.0% with sexual symptoms and 76.5% with urinary symptoms and radiotherapy. Most patients were free from side effects in the group with only surgery (Table 3 ). Table 3 Number of patients with late adverse events as GI, sexual and urinary symptoms due to different treatments at visit number 1. Visit number 1 (N = 90) Treatment GI symptoms Sexual symptoms Urinary symptoms No Yes No Yes No Yes Surgery 12 (52.2) 12 (17.9) 15 (37.5) 9 (18.0) 19 (33.9) 5 (14.7) Surgery + chemotherapy 2 (8.7) 7 (10.4) 5 (12.5) 4 (8.0) 6 (10.7) 3 (8.8) Radiotherapy +/- surgery +/- chemotherapy 9 (39.1) 48 (71.6) 20 (50.0) 37 (74.0) 31 (55.3) 26 (76.5) 23 (25.6) 67 (74.4) 40 (44.4) 50 (55.5) 56 (62.2) 34 (37.8) Difference in toxicity of the adverse events between different visits Further, we analyzed the changes in toxicity of the side effects as GI, sexual and urinary symptoms by comparing the frequency of symptoms between visit number 1 and 2 (Table 4 ). Here we showed that 36.6% had a reduction in GI symptoms ( P = 0.013), 18.3% in sexual symptoms ( P < 0.0001) and 15.5% in urinary symptoms ( P = 0.004) at visit 2 compared to visit 1 (Table 4 ). Only 4.2% had an increase in GI symptoms, 1.4% in sexual symptoms and 5.6% an increase in urologic symptoms between visit number 1 and 2 as shown in Table 4 . Table 4 Change in toxicity grade of GI, sexual and urinary symptoms between visit number 1 and 2 in 90 cancer patients who visited the specialized rehabilitation center in Linköping Change in CTCAE toxicity Visit 1 vs. 2 p -value GI Symptoms N = 71 (%) Less grade of symptoms (2–3 to 0–1) 26 (36.6) 0.013 Increased grade of symptoms (0–1 to 2–3) 3 (4.2) Unchanged grade 2–3 symptoms 14 (19.7) Unchanged grade 0–1 symptoms 28 (39.4) Sexual symptoms N = 71 (%) Less grade of symptoms (2–3 to 0–1) 13 (18.3) < 0.0001 Increased grade of symptoms (0–1 to 2–3) 1 (1.4) Unchanged grade 2–3 symptoms 13 (18.3) Unchanged grade 0–1 symptoms 44 (62.0) Urinary symptoms N = 71 (%) Less grade of symptoms (2–3 to 0–1) 11 (15.5) 0.004 Increased grade of symptoms (0–1 to 2–3) 4 (5.6) Unchanged grade 2–3 symptoms 7 (9.9) Unchanged grade 0–1 symptoms 49 (69.0) *All 71 cases were matched and analyzed by Chi-2-test and Fisher exact test. Grade 0 = no side effects, grade 1 = mild side effects, grade 2 = moderate side effects, grade 3 = severe side effects Interventions Patients received clinical consultation and treatment by an experienced oncologist at each visit. In case of more complicated findings, specialists in other fields were consulted and further/additional diagnostic measures were taken to rule out other illnesses or relapses of cancer. Twenty-four patients (30.3%) with severe diarrhea/fecal incontinence or other GI symptoms were prescribed bile salt sequestrants. Almost all patients (23 out of 24 patients) were still on medication at the follow up visit. Interestingly, out of these 23 matched cases, 21 patients (91.3%) showed a significant improvement in toxicity of GI symptoms at the follow up visit compared to the 1 visit ( P = 0.0034, Fig. 1 a). Fifty patients had sexual symptoms at visit number 1 and out of these 50 patients, 36 patients (72.0%) were prescribed local estrogens. Thirty-one of these 36 patients were matched cases (came to both visit 1 and 2). Here we showed that the sexual symptoms were improved in 58.1% (n = 18) of the 31 patients after applying local estrogens. Thirteen patients (41.9%) did not have any effect of the treatment. None got worse after having local estrogens ( P = 0.0026, Fig. 1 b). Next the urinary symptoms as urge to pass urine and frequent visits to the toilet were studied. Only 2 (2.2%) patients out of 90 received anticholinergic treatment at visit 1 and only one of these patients came to visit number 2. No further analysis was possible to perform in the group with anticholinergic treatment as there were too few patients. Time elapsed before occurrence of side-effects Further, we studied the time elapsed (months) between end of treatment and the first visit at our referral clinic. In general, the patients visited the clinic for the first time within a mean time of 21 months (range 2-345) after the end of treatment. The mean time for occurrence of GI side effects after finishing treatment was 19 months (range 2-340), for sexual symptoms 16 months (range 2-345) and for urinary symptoms 27 months (range 2-345, Fig. 2 ). The patients with urinary symptoms were few, but it seemed like these symptoms appeared later than the GI and sexual symptoms as shown in Fig. 2 . Discussion Several recent studies have analyzed the relationship between oncologic treatment and survival in pelvic cancer patients. However, few studies have evaluated if the late adverse events as GI, sexual and urologic symptoms can be managed more optimally at a specialized, multi-disciplinary rehabilitation clinic. Further, few studies have evaluated the effect of various pharmacological interventions in relation to the adverse events that develop after oncologic treatment in pelvic cancer patients [ 5 , 7 ]. All patients included in this study visited our highly specialized oncologic rehabilitation clinic at the University hospital in Linköping from 2013 to 2019. A comparison of the frequency of side effects between the first visit and the follow up visit at our specialized oncologic rehabilitation clinic showed a significant reduction in GI, sexual and urologic symptoms (36.6%, 18.3% and 15.5% respectively). Only 4.2% had increased GI symptoms, 1.4% sexual symptoms and 5.6% had increased urologic symptoms between visit number one and two. As far as we know this is the first study which has evaluated the change in toxicity/frequency of symptoms of late side effects between two visits after oncologic treatment in pelvic cancer patients. Further, our study demonstrated that the late adverse events as GI, sexual and urinary symptoms were significantly reduced at the follow up visit at our specialized rehabilitation clinic. Here, we showed that 74.4% of the pelvic cancer patients experienced GI side effects after oncologic treatment, which is a slightly higher frequency of symptoms compared to the EMBRACE-study where 63.9% of patients with treatment for cervical cancer reported diarrhea [ 11 ]. Both these studies had a median follow up time of around two years. The frequency of GI symptoms seems to decrease with time as shown in a study by Lind et al. (2011) where 49% had some grade of fecal urgency and 12% fecal incontinence more than 6 years after finishing oncologic treatment [ 14 ]. We also showed that 55.5% of the patients experienced sexual side effects which is a higher frequency compared to previous studies on cervical cancer patients treated with chemoradiotherapy where less than half of the patients reported vaginal dryness/shortening and/or tightening [ 5 , 12 ]. In a study with longer follow up time of 74 months after pelvic RT it was shown that 31% of the women had a reduced ability to have sexual intercourse [ 14 ]. We also showed that 37.8% of the patients had urinary symptoms such as urinary urgency and leakage (median follow up 27 months) which is the same level of symptoms as reported in other studies involving ERBT in endometrial cancer patients and pelvic RT in several different types of cancers [ 6 , 14 ]. We can, thus, conclude that whereas the urological symptoms remain constant in frequency over time, the GI and sexual symptoms seem to decrease with time. Our specialized rehabilitation clinic takes care of patients that have been referred from other clinics located in our catchment area who do not have the ability to handle patients with the complex symptomatology of severe late adverse events. Our center provides a multi-professional care team with doctors, nurses, physiotherapists, dieticians, and psychologists, all with highly specialized competence to take care of these late side effects. Most patients referred to this clinic have a complex symptomatology, often with a combination late adverse events such as GI, sexual, urologic, lymphedema and psychological problems. They are, thus, a more selected group of patients, which could partly explain the slightly higher frequency of GI and sexual symptoms observed in our study compared to others. Also differences in the type of treatment modalities could explain the differences in frequency of symptoms. In our patient cohort there were fewer patients who received curative RT and more patients underwent surgery alone compared to other studies [ 5 , 6 , 10 , 14 ]. Also, the median time from finishing treatment to the study measurement could be the reason for differences in frequency of symptoms. In line with previous reports, our patients experienced multiple late adverse events at the same time, where 81.6% of the patients had two or more adverse events simultaneously which reflects the complexity of symptomatology for these patients [ 15 , 17 ]. There was a large variation between different patients in the time point for being referred to our clinic after oncologic treatment. Some patients had their first visit just two months after having finished their treatment and others many years later. Different adverse events seem to start at different time points after oncologic treatment. The GI and sexual symptoms seem to occur earlier after diagnosis with a median time of 19 and 16 months whereas the urinary symptoms were more common later with a median of 27 months after diagnosis. The later appearance of urinary symptoms has also been described in previous reports [ 6 , 13 ]. Thus, our results suggest that GI and sexual symptoms appear earlier compared to the urinary symptoms after oncologic treatment in pelvic cancer patients. Further, we specifically evaluated the effect of treatment with bile salt sequestrants in patients with severe GI side effects including diarrhea and fecal incontinence. Ninety-one percent of the patients who were prescribed bile salt sequestrants had an improvement in grade of symptoms at their follow-up visit compared to their first visit. As far as we know, only one previous study has analyzed the treatment effect of bile salt sequestrants in cancer patients. In this study, 87 patients (33%) with various types of cancers were diagnosed with bile salt malabsorption (BAM) using a Selenium Homocholic Acid Taurine (SeHCAT) scan. In line with our results, 85% of the patients in this study diagnosed as having BAM had a beneficial effect of treatment with bile salt sequestrants [ 7 ], suggesting that bile acid sequestrants significantly improves the late side effect as diarrhea/fecal incontinence in pelvic cancer patients with oncologic treatment. Further, we continued to investigate the potentially beneficial effect of treatment with local estrogens in patients with sexual symptoms as vaginal dryness and pain. Here, we showed that 58% of the patients had an improvement of their sexual symptoms after local estrogen application. Forty-one patients did not have any effect at all, and no patients had an increase in symptoms with treatment. As far as we know no previous study have compared the treatment effect of local estrogens in cancer patients between two clinical visits. One study showed that estrogen (ER) receptors were reduced in the vaginal mucosa in cancer survivors after pelvic RT compared to healthy controls [ 9 ]. Others showed that local estrogens were used more frequently in the women with cervical cancer compared to the control group [ 5 ]. In a study on healthy postmenopausal women, it was shown that 60% had a treatment effect of local estrogens [ 4 ] which is the same level of treatment effect as in our study where 58% was shown to have reduced side effects with local estrogens. Thus, our results suggest that the majority of the pelvic cancer patients with oncologic treatment have a beneficial effect of treatment with local estrogens. Therefore, local estrogens should be recommended as treatment for sexual symptoms in most pelvic cancer patients with oncologic treatment. This highly specialized clinic for late adverse events is unique in Sweden and our study suggests that establishing similar clinics at other hospitals could make a difference for these patients. Today, most of the cancer patients survive their disease and there will therefore be an increasing number of patients who suffer from late side effects after cancer treatment. Gillespie et al. (2007) concluded that a specialist evaluation and management for chronic side effects is really needed [ 8 ]. It is also clear that pharmacological intervention with bile salt sequestrants and local estrogens has an ameliorative effect and provides symptomatic relief. A potential weakness in this study could be that the grading of symptoms was performed retrospectively by the author and no formula of patient reported outcome measurements was used to grade the patients’ own experience of side effects. This study was retrospective and based on a relatively small cohort of patients and the evaluation of the oncologic treatment was carried out using the patients’ medical records. Although our study is small, we consider it to be important, as few studies have focused on evaluating the effects of treatment interventions to mitigate late adverse events. Our study shows that a significant improvement can be made in the clinical care of patients experiencing late adverse events by reducing the toxicity of side effects. In conclusion, by reviewing the specialized rehabilitation clinic in Linköping the late adverse events as GI, sexual and urinary symptoms was significantly reduced between the first and the follow up visit. Bile salt sequestrants and local estrogens were shown to be effective treatments for side effects as diarrhea and vaginal dryness/pain. In the future, specialized rehabilitation centers such as ours needs to be established and may play an important role in reducing the side effects and improving quality of life for long-term cancer survivors after oncologic treatment. Declarations Author information Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Sofia Iselius M.D, Annica Holmqvist M.D, PhD Department of Oncology, Linköping, Sweden. Sofia Iselius M.D, Annica Holmqvist M.D, PhD, Rasmus Mikiver, Srinivas Uppugunduri PhD Regional cancer centre southeast, Sweden. Rasmus Mikiver, Srinivas Uppugunduri PhD Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sofia Iselius and Annica Holmqvist. The first draft of the manuscript was written by Sofia Iselius and Annica Holmqvist and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethical declaration This study was performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration. The study protocol was approved by the regional ethical committee in Stockholm, Sweden (Reference number: 2021-05034). Consent to participate All patients have signed a formal consent to participate in this study. Consent for publication Not applicable. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Conflict of interest The authors have no relevant financial or non-financial interests to disclose . References (2017) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. In: Editor (ed)^(eds) Book Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. U.S. Department of Health & Human Services, City. Abayomi J, Kirwan J, Hackett A (2009) The prevalence of chronic radiation enteritis following radiotherapy for cervical or endometrial cancer and its impact on quality of life Eur J Oncol Nurs 13: 262–267 Andreyev HJ (2007) Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future Clin Oncol (R Coll Radiol) 19: 790–799 Bannaga A, Kelman L, O'Connor M, Pitchford C, Walters JR, Arasaradnam RP (2017) How bad is bile acid diarrhoea: an online survey of patient-reported symptoms and outcomes BMJ Open Gastroenterol 4: e000116 Bergmark K, Avall-Lundqvist E, Dickman PW, Henningsohn L, Steineck G (1999) Vaginal changes and sexuality in women with a history of cervical cancer N Engl J Med 340: 1383–1389 de Boer SM, Nout RA, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Stenfert Kroese MC, Oerlemans S, Putter H, Verhoeven-Adema KW, Nijman HW, Creutzberg CL (2015) Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial Int J Radiat Oncol Biol Phys 93: 797–809 Gee C, Fleuret C, Wilson A, Levine D, Elhusseiny R, Muls A, Cunningham D, Kohoutova D (2021) Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre Cancers (Basel) 13 Gillespie C, Goode C, Hackett C, Andreyev HJ (2007) The clinical needs of patients with chronic gastrointestinal symptoms after pelvic radiotherapy Aliment Pharmacol Ther 26: 555–563 Hofsjo A, Bohm-Starke N, Bergmark K, Masironi B, Sahlin L (2019) Sex steroid hormone receptor expression in the vaginal wall in cervical cancer survivors after radiotherapy Acta Oncol 58: 1107–1115 Jensen NBK, Potter R, Kirchheiner K, Fokdal L, Lindegaard JC, Kirisits C, Mazeron R, Mahantshetty U, Jurgenliemk-Schulz IM, Segedin B, Hoskin P, Tanderup K, Group EC (2018) Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study Radiother Oncol 127: 431–439 Jensen NBK, Pötter R, Kirchheiner K, Fokdal L, Lindegaard JC, Kirisits C, Mazeron R, Mahantshetty U, Jürgenliemk-Schulz IM, Segedin B, Hoskin P, Tanderup K (2018) Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study Radiother Oncol 127: 431–439 Kirchheiner K, Nout RA, Tanderup K, Lindegaard JC, Westerveld H, Haie-Meder C, Petric P, Mahantshetty U, Dorr W, Potter R (2014) Manifestation pattern of early-late vaginal morbidity after definitive radiation (chemo)therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: an analysis from the EMBRACE study Int J Radiat Oncol Biol Phys 89: 88–95 Leddy LS (2018) Management of Lower Urinary Tract Symptoms After Pelvic Radiation in Females Curr Urol Rep 19: 106 Lind H, Waldenstrom AC, Dunberger G, al-Abany M, Alevronta E, Johansson KA, Olsson C, Nyberg T, Wilderang U, Steineck G, Avall-Lundqvist E (2011) Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study Br J Cancer 105: 737–745 Muls AC (2014) Acta Oncologica Lecture. Gastrointestinal consequences of cancer treatment and the wider context: a bad gut feeling Acta Oncol 53: 297–306 Muls AC, Watson L, Shaw C, Andreyev HJN (2013) Managing gastrointestinal symptoms after cancer treatment: a practical approach for gastroenterologists Frontline Gastroenterol 4: 57–68 Vistad I, Cvancarova M, Fossa SD, Kristensen GB (2008) Postradiotherapy morbidity in long-term survivors after locally advanced cervical cancer: how well do physicians' assessments agree with those of their patients? Int J Radiat Oncol Biol Phys 71: 1335–1342 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 13 Apr, 2023 Read the published version in Supportive Care in Cancer → Version 1 posted Editorial decision: Major revision 17 Feb, 2023 Reviews received at journal 15 Feb, 2023 Reviewers agreed at journal 31 Jan, 2023 Reviewers invited by journal 18 Dec, 2022 Editor assigned by journal 09 Nov, 2022 Submission checks completed at journal 09 Nov, 2022 First submitted to journal 07 Nov, 2022 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-2248214","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":150892257,"identity":"c895b345-ce3e-4f72-ab4e-45e1fdff55bf","order_by":0,"name":"Sofia Iselius","email":"","orcid":"","institution":"Linköping University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sofia","middleName":"","lastName":"Iselius","suffix":""},{"id":150892258,"identity":"daf4118e-b9ff-46ae-b4ba-1c30363bba42","order_by":1,"name":"Annica Holmqvist","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABbklEQVRIie3RMWvCQBQH8BcO4tCTWy8g8SucBILQfpgEIZMUoUuGEgKBTNquioNfIVLobDjIFJwDOliE0tHQIimINIk9K0X3QvMfksfd+3G5PIAqVf5oQhfAgFpRMgBSvI2T7cZh/QxBB0IVVxC53GX4DJF+CABlM7F+gZDxIAyH93BL0JW5wD3H0Racv63spdqceFH6Ye8wGXuBlNmC0OXcCIMI7hSv/nSNGaf63LLaRvyqsUjujBsxw3QZ9RCOj8ckXRauZDADXn9WhmxG9RjrzPS5GchYQ4qff1jegyRfiGZJ9kfiUK1PtiWZ+OS9JEWP9LkXhBVk6h8I3TBEGcZoVRA3wkhKc1L0QN0VpFWQ0QM1R/ld2hvGlWEs62DEPL+LpSGINdxKrB7HkSBq0tXS/vbGfKwNpomxcwjpo3Wa2Vxtenyd/yhVVZPO9CW7/zUaevLMByIKQPi7mMH5iE60OU45u9BapUqVKv8pXyZSjKLn726bAAAAAElFTkSuQmCC","orcid":"","institution":"Linköping University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Annica","middleName":"","lastName":"Holmqvist","suffix":""},{"id":150892259,"identity":"35ab9b57-1a1a-4f65-8763-847daef0c57c","order_by":2,"name":"Rasmus Mikiver","email":"","orcid":"","institution":"Linköping University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rasmus","middleName":"","lastName":"Mikiver","suffix":""},{"id":150892260,"identity":"905dfaca-5c4a-4a32-9e90-88eb409243ad","order_by":3,"name":"Srinivas Uppugunduri","email":"","orcid":"","institution":"Linköping University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Srinivas","middleName":"","lastName":"Uppugunduri","suffix":""}],"badges":[],"createdAt":"2022-11-07 19:14:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2248214/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2248214/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00520-023-07733-3","type":"published","date":"2023-04-13T20:27:07+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":29103998,"identity":"4979fc75-7056-4959-a554-a87306a1258d","added_by":"auto","created_at":"2022-11-15 20:00:32","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":49354,"visible":true,"origin":"","legend":"\u003cp\u003eChange in toxicity (grade) of GI side effects as diarreha after administration of bile acid sequestrants between visit number one and two (a). Change in toxicity of sexual side effects as vaginal pain/dryness after administration of local estrogens between visit number one and two (b).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2248214/v1/f21562224c0d582d80ef84f9.jpg"},{"id":29103999,"identity":"2c80afa9-5c60-4299-b08e-2ddf82c7cf91","added_by":"auto","created_at":"2022-11-15 20:00:32","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25398,"visible":true,"origin":"","legend":"\u003cp\u003eGI, sexual and urologic side effects, median time from end of oncologic treatment to the first vistit at the rehabilitation clinic in Linköping.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2248214/v1/dcfef11c301160cb6c39f177.jpg"},{"id":44724833,"identity":"9064fd18-bde6-4544-92a7-a06a8cdc2b4b","added_by":"auto","created_at":"2023-10-16 20:35:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":484184,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2248214/v1/6a0219ff-9107-4ee8-9684-2d6ccd73d681.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Late adverse events in patients with pelvic cancer after oncologic treatment -intervention and treatment effect","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGynecologic cancer is the second most common cancer in the world among women and in Sweden around 3000 women are diagnosed each year. Today, most gynecologic cancers are associated with a high 5-year survival of around 80%. An increasing incidence in cancer, coupled with improved treatments has resulted in a higher number of patients surviving their disease, and therefore, there is a growing need to improve the patients\u0026rsquo; quality of life after oncologic treatment.\u003c/p\u003e \u003cp\u003eTreatment for pelvic cancer often includes high doses of radiotherapy directed to the pelvic area. Many of these patients develop late side effects such as chronic changes of the gastrointestinal (GI) tract and for around 50% of these patients the symptoms affect their daily activity and quality of life [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In previous reports, roughly twenty symptoms from the GI tract were described and in 20\u0026ndash;30% of these cases two or more symptoms existed concurrently [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The most common and the most troublesome GI symptom were fecal incontinence and fecal urgency, which often coexisted with sexual and urinary symptoms. Sexual symptoms included fragile vaginal mucous membranes and dyspareunia [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Urinary symptoms often included frequent visits to the toilet, leakage, difficulty in feeling the need to empty the bladder and difficulty to void [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDuring the past decades, the health care has mainly focused on optimizing the cancer therapy and to improve survival. But there is still a great unmet need for long-term rehabilitation. Therefore, the oncologic clinic at the University Hospital in Link\u0026ouml;ping decided to start a highly specialized rehabilitation clinic in 2013 for patients with late adverse events after oncologic treatment. The objective of the clinic was to be a referral center for patients diagnosed with pelvic cancer with severe late adverse events after oncologic treatment. Our center provides a multi-professional caring team with doctors, nurses, physiotherapists, dieticians, and psychologists, all with highly specialized competence to take care of the late adverse events that affects these patients. To our knowledge this is one of the few institutions that have adopted this multi-professional advanced rehabilitation structure. We were inspired by the Royal Marsden Hospital in London that established a weekly specialized clinic with a gastroenterologist who specifically helped patients with chronic GI symptoms after cancer treatment. The patients referred to this clinic had all been previously treated with pelvic radiotherapy and had severe GI side effects. Data from this clinic showed that patients treated with pelvic radiotherapy experienced a high number of co-existing side effects, where GI side effects were only one of them. Many side effects persisted and had a clear negative effect on the quality of life for these patients [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultiple studies have concluded that improvement in the management of treatment related late side effects is needed, but few studies have analyzed the toxicity grade of the late adverse that occurs and further have analyzed the type of interventions and the treatment effects of each intervention used to mitigate these symptoms [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of this study was to evaluate the toxicity (between visit number 1 and 2) of the late adverse events as GI, urologic and sexual symptoms by using the common terminology criteria for adverse events (CTCAE). Further, we wanted to study different treatment strategies as bile salt sequestrants for diarrhea, anticholinergic drugs for urge to pass urine/frequent visits to the toilet and local estrogens for vaginal dryness/pain in patients with pelvic cancers who received oncologic treatment.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eThis retrospective longitudinal cohort study comprised 90 patients who had at least one visit to the clinic for late adverse events at Link\u0026ouml;ping university hospital between 2013 to 2019. This center started in 2013 and was devoted to patients who had newly diagnosed side effects more than three months after the end of the oncologic treatment or who had remaining symptoms several years after finishing treatment. All patients were women. The time point between the first visit and the end of the oncologic treatment varied between 7 months up to several decades (At most 29 years, mean 46 months).\u003c/p\u003e \u003cp\u003eIn total, 90 patients with pelvic cancer who received some type of oncologic treatment visited the center for late adverse events between 2013 to 2019. The patients had been referred to this clinic from other regions in Sweden, including the county council of J\u0026ouml;nk\u0026ouml;ping, Kalmar, \u0026Ouml;sterg\u0026ouml;tland, S\u0026ouml;rmland and V\u0026auml;stmanland. All together, they included a population of ~\u0026thinsp;1.5\u0026nbsp;million inhabitants.\u003c/p\u003e \u003cp\u003eThe patients in this study received treatment due to the following cancer diagnoses: cervical (n\u0026thinsp;=\u0026thinsp;49), endometrial (n\u0026thinsp;=\u0026thinsp;13), ovarial/tuba (n\u0026thinsp;=\u0026thinsp;6) vulva (n\u0026thinsp;=\u0026thinsp;6), vaginal (n\u0026thinsp;=\u0026thinsp;3), anal (n\u0026thinsp;=\u0026thinsp;7), rectal (n\u0026thinsp;=\u0026thinsp;2) and other cancers (n\u0026thinsp;=\u0026thinsp;4). The treatment included, radiotherapy, both external beam radiotherapy (ERBT) and brachytherapy (BT), surgery and chemotherapy. The treatments were given either in combination or as a single treatment as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All oncologic treatments were given according to the Swedish national guidelines.\u003c/p\u003e \n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Characteristics of 90 patients who visited the specialized rehabilitation clinic in Link\u0026ouml;ping.\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"640\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eType of cancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eCervical\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e49 (54.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eEndometrial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e13 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eVulva\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 6 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eVaginal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 3 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eOvarial/Tubar/Peritoneal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 6 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eAnal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 7 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eRectal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 2 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 4 (4.4)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e47 (52.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e21 (23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e13 (14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 2 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 7 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of oncologic treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eRadiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp; 3 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003cp\u003eSurgery + chemotherapy\u003c/p\u003e\n \u003cp\u003eSurgery + chemotherapy + radiotherapy\u003c/p\u003e\n \u003cp\u003eRadiotherapy + chemotherapy\u003c/p\u003e\n \u003cp\u003eSurgery + radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e24 (26.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 9 (10.0)\u003c/p\u003e\n \u003cp\u003e12 (13.3)\u003c/p\u003e\n \u003cp\u003e33 (36.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 9 (10.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis (mean)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAge* (mean)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePerformance status*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;2\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDisease free (cancer)*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Yes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;No\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOther diseases**\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Hypertension\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Diabetes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Hypothyroidism\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Cardiovascular disease\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Inflammatory bowel disease (IBS)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.65625%\"\u003e\n \u003cp\u003e48.8 years\u003c/p\u003e\n \u003cp\u003e53.7 years\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e70 (77.8)\u003c/p\u003e\n \u003cp\u003e12 (13.3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 8 (8.9)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e88 (97.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 2 (2.2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (13.3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 4 (4.4)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 4 (4.4)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 7 (7.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"82.34375%\"\u003e\n \u003cp\u003e*At first visit\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e**Calculated in percent (%) of the 90 patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"17.65625%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cbr\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData\u003c/h2\u003e \u003cp\u003eA review of the patient\u0026rsquo;s oncologic and surgical records was performed in all patients that had at least one visit at the center for late adverse events between the years of 2013 to 2019. The patient\u0026rsquo;s files were reviewed up to 13 months after their first visit and the number of visits varied from one to two. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea-b describes the different type of GI, sexual and urologic symptoms and measures/treatments that were used at our rehabilitation clinic.\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 2a.\u003c/strong\u003e Different type of GI, sexual and urologic symptoms for the 90 patients who visited our specialized rehabilitation clinic\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"728\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGI symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSexual symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eUrologic symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003eDiarreha\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003ePain at sexual intercourse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003eUrge to pass urine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003eConstipation\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFlatulence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003eFeeling of dryness/rubbing sensation in vagina\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003eUrinary leakage\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMelena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003eTight and stiff feeling in vagina due to adhesions\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePain during bladder filling/emptying\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003eMucous in stool\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDifficulties to empty the bowel\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003eSpasm in the vagina\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFoul-smelling discharge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCramping around urethra\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDifficulty emptying the bladder\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003eFecal incontinence\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003eSwelling and redness of vulva\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRecurrent urinary tract infections\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003eSubileus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003eBlister and sores in vulva/vagina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAlternating hard and loose stools\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003ePeeing with scattered stream of urine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003eReduced sex drive/ability to orgasm\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.79120879120879%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"36.4010989010989%\"\u003e\n \u003cp\u003eFeeling of disgust\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.807692307692307%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cbr\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2b.\u003c/strong\u003e Different type of measures/treatments for GI, sexual and urologic symptoms used for the 90 patients who visited our specialized rehabilitation clinic.\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"756\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMeasures/treatment\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGI symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMeasures/treatment\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSexual symptom\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMeasures/treatment\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eUrologic symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003eBulking agents (inolaxol, vi-sibin)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003eLocal estrogens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003eAnticholinergicum\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003eLoperamid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003eAntibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003eLocal estrogens\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003eAntiemetics\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDietician/dietary advice\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eProton pump inhibitors\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePain relivers for pain and cramps (diemtikon, saroten, egazil, papaverine)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003eAntimycotic treatment\u003c/p\u003e\n \u003cp\u003eKnots and relaxation exercise\u003c/p\u003e\n \u003cp\u003eVaginal dilatator\u003c/p\u003e\n \u003cp\u003eDiscussion on multidisciplinary team meetings (MDK)\u003c/p\u003e\n \u003cp\u003eCounselor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003eReferal to urologist for cystoscopy\u003c/p\u003e\n \u003cp\u003ePinch exercises\u003c/p\u003e\n \u003cp\u003eInstillations via urologist with hyaluronic acid preparations\u003c/p\u003e\n \u003cp\u003eDiscussion on multidisciplinary team meetings (MDK)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003eBile acid sequestrants (cholestagel, lestid, questran)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003eHyperbar oxygen treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003ePancreas enzyme substitution (creon)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003eAntibiotics (metronidazole/doxyferm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003eMedicines for rectal bleeding (xyloproct, scheriproct, asacol)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"38.75661375661376%\"\u003e\n \u003cp\u003eReferal to gastroenterologist for coloscopy\u003c/p\u003e\n \u003cp\u003eHyperbar oxygen treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"31.21693121693122%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.026455026455025%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cbr\u003e\u003cp\u003eData of diagnosis, tumor stage, differentiation, performance status, oncologic treatment, and late adverse events were collected from the patients\u0026rsquo; medical records. The adverse events were retrospectively graded between 1\u0026ndash;5 according to the CTCAE grading system [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The CTCAE grading scale was chosen as it is the most used system for grading oncologic side effects. Regarding the toxicity grading, grade 0 meant no side effects, grade 1 meant mild side effects, grade 2 moderate side effects, grade 3 severe side effects, grade 4 life threatening side effects and grade 5 death related to side effects. No patients in our study had grade 4 or 5 side effects. The grade of symptoms was combined into two subgroups where grade 0\u0026ndash;1 was considered as one group and grade 2\u0026ndash;3 as the other group. Each intervention used as a treatment for the adverse events was documented. Sexual symptoms were determined and treatment with local estrogens prescribed by anamnestic and clinical findings and by a gynecological exam by an experienced senior specialist in gynecologic oncology. GI and urinary symptoms were determined by anamnestic findings and gynecological exam. Bile salt sequestrants and anticholinergic treatment were prescribed due to anamnestic findings without other investigation.\u003c/p\u003e \u003cp\u003eAll the patients who visited the center for late adverse events met the same doctor at both visit number 1 and 2. Some patients also met a dietician for dietary advice regarding their GI symptoms and a psychologist regarding their sexual symptoms and general well-being. The patients also had regular follow ups by phone by a nurse working at the rehabilitation center. The grading of toxicity for each patient was performed by two independent researchers\u0026rsquo; (S. Iselius and A. Holmqvist). The study protocol was approved by the regional ethical committee in Stockholm, Sweden (Reference number: 2021\u0026ndash;05034) and was in accordance with the Declaration of Helsinki. All patients have signed a written consent form.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eThe Chi-square method and the Fischer\u0026acute;s exact test was used to study the differences in the frequency and the toxicity of side effect between visit number 1 and 2. All comparisons were performed by using matched cases. The tests were two-sided and p-value of \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003e Ninety patients with pelvic cancer who received oncologic treatment participated in the study. Patients with several different types of cancers were included. Most of the patients (85%) were diagnosed with gynecological cancer. The treatment included surgery, radiotherapy, and chemotherapy in different treatment combinations where 63.3% of the 90 patients received radiotherapy (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMost of the patients that received oncologic treatment were in stage I (52.2%), 23.3% were in stage II and 24.4% in stage III or IV. The tumor stage was unknown (due to no register data) for 7.8% of the patients. The mean age of the patients was 48.8 years (range 19\u0026ndash;82) and the mean age at the first visit was 53.7 (range 19\u0026ndash;86). Few patients had other diseases at the time for diagnosis (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSide effects\u003c/h2\u003e \u003cp\u003eAt first, we studied the number of patients with late adverse events as GI, sexual and urinary symptoms. Here we showed that 74.4% of the patients had GI symptoms, 55.5% sexual and 37.8% urinary symptoms (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Two or more adverse events were present concurrently in 81.6% of the patients. Patients receiving radiotherapy experienced a higher frequency of late adverse events compared to patients who had surgery alone or surgery in combination with chemotherapy (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). GI side effects were present in 71.6% of the patients with radiotherapy, 74.0% with sexual symptoms and 76.5% with urinary symptoms and radiotherapy. Most patients were free from side effects in the group with only surgery (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNumber of patients with late adverse events as GI, sexual and urinary symptoms due to different treatments at visit number 1.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eVisit number 1 (N\u0026thinsp;=\u0026thinsp;90)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eTreatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGI symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cb\u003eSexual symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eUrinary symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (52.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19 (33.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5 (14.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u0026thinsp;+\u0026thinsp;chemotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3 (8.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiotherapy +/- surgery +/- chemotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (39.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (71.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37 (74.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (55.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26 (76.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (25.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (74.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (44.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50 (55.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56 (62.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e34 (37.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDifference in toxicity of the adverse events between different visits\u003c/h2\u003e \u003cp\u003eFurther, we analyzed the changes in toxicity of the side effects as GI, sexual and urinary symptoms by comparing the frequency of symptoms between visit number 1 and 2 (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Here we showed that 36.6% had a reduction in GI symptoms (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), 18.3% in sexual symptoms (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and 15.5% in urinary symptoms (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) at visit 2 compared to visit 1 (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Only 4.2% had an increase in GI symptoms, 1.4% in sexual symptoms and 5.6% an increase in urologic symptoms between visit number 1 and 2 as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChange in toxicity grade of GI, sexual and urinary symptoms between visit number 1 and 2 in 90 cancer patients who visited the specialized rehabilitation center in Link\u0026ouml;ping\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in CTCAE toxicity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVisit 1 vs. 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGI Symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;71 (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess grade of symptoms (2\u0026ndash;3 to 0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (36.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncreased grade of symptoms (0\u0026ndash;1 to 2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged grade 2\u0026ndash;3 symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (19.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged grade 0\u0026ndash;1 symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSexual symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;71 (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess grade of symptoms (2\u0026ndash;3 to 0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncreased grade of symptoms (0\u0026ndash;1 to 2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged grade 2\u0026ndash;3 symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged grade 0\u0026ndash;1 symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrinary symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;71 (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess grade of symptoms (2\u0026ndash;3 to 0\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncreased grade of symptoms (0\u0026ndash;1 to 2\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged grade 2\u0026ndash;3 symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged grade 0\u0026ndash;1 symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (69.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e*All 71 cases were matched and analyzed by Chi-2-test and Fisher exact test. Grade 0\u0026thinsp;=\u0026thinsp;no side effects, grade 1\u0026thinsp;=\u0026thinsp;mild side effects, grade 2\u0026thinsp;=\u0026thinsp;moderate side effects, grade 3\u0026thinsp;=\u0026thinsp;severe side effects\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eInterventions\u003c/h2\u003e \u003cp\u003ePatients received clinical consultation and treatment by an experienced oncologist at each visit. In case of more complicated findings, specialists in other fields were consulted and further/additional diagnostic measures were taken to rule out other illnesses or relapses of cancer. Twenty-four patients (30.3%) with severe diarrhea/fecal incontinence or other GI symptoms were prescribed bile salt sequestrants. Almost all patients (23 out of 24 patients) were still on medication at the follow up visit. Interestingly, out of these 23 matched cases, 21 patients (91.3%) showed a significant improvement in toxicity of GI symptoms at the follow up visit compared to the 1 visit (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0034, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003ea).\u003c/p\u003e \u003cp\u003eFifty patients had sexual symptoms at visit number 1 and out of these 50 patients, 36 patients (72.0%) were prescribed local estrogens. Thirty-one of these 36 patients were matched cases (came to both visit 1 and 2). Here we showed that the sexual symptoms were improved in 58.1% (n\u0026thinsp;=\u0026thinsp;18) of the 31 patients after applying local estrogens. Thirteen patients (41.9%) did not have any effect of the treatment. None got worse after having local estrogens (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0026, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003eNext the urinary symptoms as urge to pass urine and frequent visits to the toilet were studied. Only 2 (2.2%) patients out of 90 received anticholinergic treatment at visit 1 and only one of these patients came to visit number 2. No further analysis was possible to perform in the group with anticholinergic treatment as there were too few patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eTime elapsed before occurrence of side-effects\u003c/h2\u003e \u003cp\u003eFurther, we studied the time elapsed (months) between end of treatment and the first visit at our referral clinic. In general, the patients visited the clinic for the first time within a mean time of 21 months (range 2-345) after the end of treatment. The mean time for occurrence of GI side effects after finishing treatment was 19 months (range 2-340), for sexual symptoms 16 months (range 2-345) and for urinary symptoms 27 months (range 2-345, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The patients with urinary symptoms were few, but it seemed like these symptoms appeared later than the GI and sexual symptoms as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eSeveral recent studies have analyzed the relationship between oncologic treatment and survival in pelvic cancer patients. However, few studies have evaluated if the late adverse events as GI, sexual and urologic symptoms can be managed more optimally at a specialized, multi-disciplinary rehabilitation clinic. Further, few studies have evaluated the effect of various pharmacological interventions in relation to the adverse events that develop after oncologic treatment in pelvic cancer patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. All patients included in this study visited our highly specialized oncologic rehabilitation clinic at the University hospital in Link\u0026ouml;ping from 2013 to 2019.\u003c/p\u003e \u003cp\u003eA comparison of the frequency of side effects between the first visit and the follow up visit at our specialized oncologic rehabilitation clinic showed a significant reduction in GI, sexual and urologic symptoms (36.6%, 18.3% and 15.5% respectively). Only 4.2% had increased GI symptoms, 1.4% sexual symptoms and 5.6% had increased urologic symptoms between visit number one and two. As far as we know this is the first study which has evaluated the change in toxicity/frequency of symptoms of late side effects between two visits after oncologic treatment in pelvic cancer patients. Further, our study demonstrated that the late adverse events as GI, sexual and urinary symptoms were significantly reduced at the follow up visit at our specialized rehabilitation clinic.\u003c/p\u003e \u003cp\u003eHere, we showed that 74.4% of the pelvic cancer patients experienced GI side effects after oncologic treatment, which is a slightly higher frequency of symptoms compared to the EMBRACE-study where 63.9% of patients with treatment for cervical cancer reported diarrhea [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Both these studies had a median follow up time of around two years. The frequency of GI symptoms seems to decrease with time as shown in a study by Lind et al. (2011) where 49% had some grade of fecal urgency and 12% fecal incontinence more than 6 years after finishing oncologic treatment [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. We also showed that 55.5% of the patients experienced sexual side effects which is a higher frequency compared to previous studies on cervical cancer patients treated with chemoradiotherapy where less than half of the patients reported vaginal dryness/shortening and/or tightening [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In a study with longer follow up time of 74 months after pelvic RT it was shown that 31% of the women had a reduced ability to have sexual intercourse [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. We also showed that 37.8% of the patients had urinary symptoms such as urinary urgency and leakage (median follow up 27 months) which is the same level of symptoms as reported in other studies involving ERBT in endometrial cancer patients and pelvic RT in several different types of cancers [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. We can, thus, conclude that whereas the urological symptoms remain constant in frequency over time, the GI and sexual symptoms seem to decrease with time.\u003c/p\u003e \u003cp\u003eOur specialized rehabilitation clinic takes care of patients that have been referred from other clinics located in our catchment area who do not have the ability to handle patients with the complex symptomatology of severe late adverse events. Our center provides a multi-professional care team with doctors, nurses, physiotherapists, dieticians, and psychologists, all with highly specialized competence to take care of these late side effects. Most patients referred to this clinic have a complex symptomatology, often with a combination late adverse events such as GI, sexual, urologic, lymphedema and psychological problems. They are, thus, a more selected group of patients, which could partly explain the slightly higher frequency of GI and sexual symptoms observed in our study compared to others. Also differences in the type of treatment modalities could explain the differences in frequency of symptoms. In our patient cohort there were fewer patients who received curative RT and more patients underwent surgery alone compared to other studies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Also, the median time from finishing treatment to the study measurement could be the reason for differences in frequency of symptoms.\u003c/p\u003e \u003cp\u003eIn line with previous reports, our patients experienced multiple late adverse events at the same time, where 81.6% of the patients had two or more adverse events simultaneously which reflects the complexity of symptomatology for these patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere was a large variation between different patients in the time point for being referred to our clinic after oncologic treatment. Some patients had their first visit just two months after having finished their treatment and others many years later. Different adverse events seem to start at different time points after oncologic treatment. The GI and sexual symptoms seem to occur earlier after diagnosis with a median time of 19 and 16 months whereas the urinary symptoms were more common later with a median of 27 months after diagnosis. The later appearance of urinary symptoms has also been described in previous reports [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Thus, our results suggest that GI and sexual symptoms appear earlier compared to the urinary symptoms after oncologic treatment in pelvic cancer patients.\u003c/p\u003e \u003cp\u003eFurther, we specifically evaluated the effect of treatment with bile salt sequestrants in patients with severe GI side effects including diarrhea and fecal incontinence. Ninety-one percent of the patients who were prescribed bile salt sequestrants had an improvement in grade of symptoms at their follow-up visit compared to their first visit. As far as we know, only one previous study has analyzed the treatment effect of bile salt sequestrants in cancer patients. In this study, 87 patients (33%) with various types of cancers were diagnosed with bile salt malabsorption (BAM) using a Selenium Homocholic Acid Taurine (SeHCAT) scan. In line with our results, 85% of the patients in this study diagnosed as having BAM had a beneficial effect of treatment with bile salt sequestrants [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], suggesting that bile acid sequestrants significantly improves the late side effect as diarrhea/fecal incontinence in pelvic cancer patients with oncologic treatment.\u003c/p\u003e \u003cp\u003e Further, we continued to investigate the potentially beneficial effect of treatment with local estrogens in patients with sexual symptoms as vaginal dryness and pain. Here, we showed that 58% of the patients had an improvement of their sexual symptoms after local estrogen application. Forty-one patients did not have any effect at all, and no patients had an increase in symptoms with treatment. As far as we know no previous study have compared the treatment effect of local estrogens in cancer patients between two clinical visits. One study showed that estrogen (ER) receptors were reduced in the vaginal mucosa in cancer survivors after pelvic RT compared to healthy controls [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Others showed that local estrogens were used more frequently in the women with cervical cancer compared to the control group [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In a study on healthy postmenopausal women, it was shown that 60% had a treatment effect of local estrogens [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] which is the same level of treatment effect as in our study where 58% was shown to have reduced side effects with local estrogens. Thus, our results suggest that the majority of the pelvic cancer patients with oncologic treatment have a beneficial effect of treatment with local estrogens. Therefore, local estrogens should be recommended as treatment for sexual symptoms in most pelvic cancer patients with oncologic treatment.\u003c/p\u003e \u003cp\u003eThis highly specialized clinic for late adverse events is unique in Sweden and our study suggests that establishing similar clinics at other hospitals could make a difference for these patients. Today, most of the cancer patients survive their disease and there will therefore be an increasing number of patients who suffer from late side effects after cancer treatment. Gillespie et al. (2007) concluded that a specialist evaluation and management for chronic side effects is really needed [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is also clear that pharmacological intervention with bile salt sequestrants and local estrogens has an ameliorative effect and provides symptomatic relief.\u003c/p\u003e \u003cp\u003eA potential weakness in this study could be that the grading of symptoms was performed retrospectively by the author and no formula of patient reported outcome measurements was used to grade the patients\u0026rsquo; own experience of side effects. This study was retrospective and based on a relatively small cohort of patients and the evaluation of the oncologic treatment was carried out using the patients\u0026rsquo; medical records. Although our study is small, we consider it to be important, as few studies have focused on evaluating the effects of treatment interventions to mitigate late adverse events. Our study shows that a significant improvement can be made in the clinical care of patients experiencing late adverse events by reducing the toxicity of side effects.\u003c/p\u003e \u003cp\u003eIn conclusion, by reviewing the specialized rehabilitation clinic in Link\u0026ouml;ping the late adverse events as GI, sexual and urinary symptoms was significantly reduced between the first and the follow up visit. Bile salt sequestrants and local estrogens were shown to be effective treatments for side effects as diarrhea and vaginal dryness/pain. In the future, specialized rehabilitation centers such as ours needs to be established and may play an important role in reducing the side effects and improving quality of life for long-term cancer survivors after oncologic treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eDepartment of Clinical and Experimental Medicine, Link\u0026ouml;ping University, Link\u0026ouml;ping, Sweden. Sofia Iselius M.D, Annica Holmqvist M.D, PhD\u003c/li\u003e\n \u003cli\u003eDepartment of Oncology, Link\u0026ouml;ping, Sweden. Sofia Iselius M.D, Annica Holmqvist M.D, PhD, Rasmus Mikiver, Srinivas Uppugunduri PhD\u003c/li\u003e\n \u003cli\u003eRegional cancer centre southeast, Sweden. Rasmus Mikiver, Srinivas Uppugunduri PhD\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sofia Iselius and Annica Holmqvist. The first draft of the manuscript was written by Sofia Iselius and Annica Holmqvist and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration. The study protocol was approved by the regional ethical committee in Stockholm, Sweden (Reference number: 2021-05034).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients have signed a formal consent to participate in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors have no relevant financial or non-financial interests to disclose\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e(2017) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. In: Editor (ed)^(eds) Book Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. U.S. Department of Health \u0026amp; Human Services, City.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbayomi J, Kirwan J, Hackett A (2009) The prevalence of chronic radiation enteritis following radiotherapy for cervical or endometrial cancer and its impact on quality of life Eur J Oncol Nurs 13: 262\u0026ndash;267\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndreyev HJ (2007) Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future Clin Oncol (R Coll Radiol) 19: 790\u0026ndash;799\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBannaga A, Kelman L, O'Connor M, Pitchford C, Walters JR, Arasaradnam RP (2017) How bad is bile acid diarrhoea: an online survey of patient-reported symptoms and outcomes BMJ Open Gastroenterol 4: e000116\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBergmark K, Avall-Lundqvist E, Dickman PW, Henningsohn L, Steineck G (1999) Vaginal changes and sexuality in women with a history of cervical cancer N Engl J Med 340: 1383\u0026ndash;1389\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Boer SM, Nout RA, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Stenfert Kroese MC, Oerlemans S, Putter H, Verhoeven-Adema KW, Nijman HW, Creutzberg CL (2015) Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial Int J Radiat Oncol Biol Phys 93: 797\u0026ndash;809\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGee C, Fleuret C, Wilson A, Levine D, Elhusseiny R, Muls A, Cunningham D, Kohoutova D (2021) Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre Cancers (Basel) 13\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGillespie C, Goode C, Hackett C, Andreyev HJ (2007) The clinical needs of patients with chronic gastrointestinal symptoms after pelvic radiotherapy Aliment Pharmacol Ther 26: 555\u0026ndash;563\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHofsjo A, Bohm-Starke N, Bergmark K, Masironi B, Sahlin L (2019) Sex steroid hormone receptor expression in the vaginal wall in cervical cancer survivors after radiotherapy Acta Oncol 58: 1107\u0026ndash;1115\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJensen NBK, Potter R, Kirchheiner K, Fokdal L, Lindegaard JC, Kirisits C, Mazeron R, Mahantshetty U, Jurgenliemk-Schulz IM, Segedin B, Hoskin P, Tanderup K, Group EC (2018) Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study Radiother Oncol 127: 431\u0026ndash;439\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJensen NBK, P\u0026ouml;tter R, Kirchheiner K, Fokdal L, Lindegaard JC, Kirisits C, Mazeron R, Mahantshetty U, J\u0026uuml;rgenliemk-Schulz IM, Segedin B, Hoskin P, Tanderup K (2018) Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study Radiother Oncol 127: 431\u0026ndash;439\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKirchheiner K, Nout RA, Tanderup K, Lindegaard JC, Westerveld H, Haie-Meder C, Petric P, Mahantshetty U, Dorr W, Potter R (2014) Manifestation pattern of early-late vaginal morbidity after definitive radiation (chemo)therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: an analysis from the EMBRACE study Int J Radiat Oncol Biol Phys 89: 88\u0026ndash;95\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeddy LS (2018) Management of Lower Urinary Tract Symptoms After Pelvic Radiation in Females Curr Urol Rep 19: 106\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLind H, Waldenstrom AC, Dunberger G, al-Abany M, Alevronta E, Johansson KA, Olsson C, Nyberg T, Wilderang U, Steineck G, Avall-Lundqvist E (2011) Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study Br J Cancer 105: 737\u0026ndash;745\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuls AC (2014) Acta Oncologica Lecture. Gastrointestinal consequences of cancer treatment and the wider context: a bad gut feeling Acta Oncol 53: 297\u0026ndash;306\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuls AC, Watson L, Shaw C, Andreyev HJN (2013) Managing gastrointestinal symptoms after cancer treatment: a practical approach for gastroenterologists Frontline Gastroenterol 4: 57\u0026ndash;68\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVistad I, Cvancarova M, Fossa SD, Kristensen GB (2008) Postradiotherapy morbidity in long-term survivors after locally advanced cervical cancer: how well do physicians' assessments agree with those of their patients? Int J Radiat Oncol Biol Phys 71: 1335\u0026ndash;1342\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Gastrointestinal, urologic, sexual, late side effects, oncologic treatment, pelvic cancer","lastPublishedDoi":"10.21203/rs.3.rs-2248214/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2248214/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eFew studies have focused on the late adverse events after oncologic treatment in pelvic cancer patients. Here, the treatment effect/interventions were studied on late side effects as GI, sexual and urinary symptoms in pelvic cancer patients who visited a highly specialized rehabilitation clinic in Link\u0026ouml;ping.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective longitudinal cohort study included 90 patients who had at least one visit at the rehabilitation clinic for late adverse events at Link\u0026ouml;ping University hospital between 2013 to 2019. The toxicity of the adverse events was analyzed by using the common terminology criteria for adverse events (CTCAE).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBy comparing the toxicity of symptoms between visit 1 and 2, we showed that the GI symptoms decreased with 36.6% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), the sexual symptoms with 18.3% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and urinary symptoms with 15.5% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). Patients who received bile salt sequestrant had a significant improvement in grade of GI symptoms as diarrhea/fecal incontinence at visit 2 compared to visit 1 where 91.3% were shown to have a treatment effect (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0034). The sexual symptoms (vaginal dryness/pain) significantly improved due to local estrogens between visit 1 and 2 where 58.1% had a reduction of symptoms (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0026).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe late side effects as GI, sexual and urinary symptoms was significantly reduced between visit 1 and 2 at the specialized rehabilitation center in Link\u0026ouml;ping. Bile salt sequestrants and local estrogens are effective treatments for side effects as diarrhea and vaginal dryness/pain.\u003c/p\u003e","manuscriptTitle":"Late adverse events in patients with pelvic cancer after oncologic treatment -intervention and treatment effect","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-15 20:00:27","doi":"10.21203/rs.3.rs-2248214/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-02-17T18:36:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-02-16T02:54:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3526f991-6545-484c-811c-46b58a9e8ed9","date":"2023-01-31T21:47:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-12-18T16:14:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-11-10T02:07:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-11-10T02:07:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2022-11-07T19:04:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6464af2c-8dfa-4004-a1c3-50d476e096f6","owner":[],"postedDate":"November 15th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T20:31:16+00:00","versionOfRecord":{"articleIdentity":"rs-2248214","link":"https://doi.org/10.1007/s00520-023-07733-3","journal":{"identity":"supportive-care-in-cancer","isVorOnly":false,"title":"Supportive Care in Cancer"},"publishedOn":"2023-04-13 20:27:07","publishedOnDateReadable":"April 13th, 2023"},"versionCreatedAt":"2022-11-15 20:00:27","video":"","vorDoi":"10.1007/s00520-023-07733-3","vorDoiUrl":"https://doi.org/10.1007/s00520-023-07733-3","workflowStages":[]},"version":"v1","identity":"rs-2248214","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2248214","identity":"rs-2248214","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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