Oncoplastic breast surgery versus conventional breast conserving surgery - a prospective follow-up study of subjective loco-regional late morbidity.

Background and aim: Few studies have focused on the symptoms of loco-regional morbidity in shoulders, arms, and breasts related to oncoplastic breast surgery (OPS). This study aimed to determine if a difference exists in the prevalence or variety of subjective symptoms of shoulder, arm, and breast morbidity in patients undergoing OPS compared with patients receiving conventional breast conserving surgery (C-BCS). Cosmetic result and body image were included as secondary endpoints.Methods: This prospective follow-up study with 18 months of questionnaire-based follow-up included women with breast cancer or ductal carcinoma in situ. They were divided into two groups - C-BCS or OPS - depending on type of surgery performed. Furthermore, patient, disease, and treatment characteristics were recorded.Results: Among 334 completers, 229 (69%) received C-BCS and 105 (31%) received OPS. Participants were comparable regarding age, comorbidity, BMI, re-excision rate (15-16%), and axillary surgery. As for tumor characteristics, a more advanced disease stage was shown in the OPS than in the C-BCS group with larger tumor and lumpectomy size, more multifocality, and the corresponding following systemic adjuvant therapy.The questionnaire revealed that the two groups were comparable with no significant differences in frequency or variety of symptoms of shoulder and arm morbidity. Overall, participants were highly satisfied with the cosmetic results in both groups and no significant inter-group differences were observed.Conclusion: In patients with larger tumors, breast conserving surgery utilizing oncoplastic techniques yields results regarding subjective shoulder, arm, and breast morbidity as well as cosmetic outcome comparable with those of C-BCS performed on smaller tumors.Trial registration: ClinicalTrials.gov, registration number: NCT02159274 (2014).HIGHLIGHTSSubjective symptoms of shoulder, arm, and breast morbidity are comparable when oncoplastic breast surgery is compared to conventional breast conserving surgery.The variety of symptoms of shoulder and arm morbidity following oncoplastic surgery does not differ from symptoms following conventional breast conserving surgery.The cosmetic outcome following oncoplastic breast surgery is comparable to breast conserving surgery without oncoplastic techniques.

Lessons from radiochemotherapy and modern image-guided adaptive brachytherapy followed by hysterectomy.

PURPOSE: To analyze the clinical outcomes and the safety of radiochemotherapy (RCT) and image-guided adaptive brachytherapy (IGABT) and to evaluate the impact of hysterectomy (HT) as completion of treatment for cervical cancer. METHODS AND MATERIALS: 145 patients with locally advanced cervical cancer were treated at our institution. Patients underwent RCT and IGABT, then hysterectomy (HT) as completion of treatment was performed, with the exception of patients with surgical contraindications, para aortic metastatic disease or patients who refused surgery. Clinical outcomes and morbidity were retrospectively reviewed in both groups. Local relapse free survival (LRFS), pelvic relapse free survival (PRFS) and overall survival (OS) were analyzed. RESULTS: Completion HT was performed in 90 (62.1%) patients. Complete histological response and microscopic disease were found in 77 patients (85.6%). Local relapse was observed in 14 patients (9.6%) without differences between completion HT group and the definitive RCT and IGABT group (Odds Ratio OR = 1.73 [0.57-5.23], p = 0.33). The estimated 3-year LRFS and PRFS for the entire population were respectively 90% [84%-94%] and 93% [87%-96%], with no significant differences between them (respectively Hazard Ratio HR = 0.57 [0.20-1.64], p = 0.30 and HR = 0.37 [0.10-1.31], p = 0.12). The estimated 3-year OS rate for the whole population was 84% [75%-91%] with no significant differences between groups (HR = 0.81 [0.32-2.06], p = 0.65). Regarding morbidity, grade ≥ 2 vaginal toxicity was more frequent in the definitive RCT and IGABT group (43.6% vs 26.7%, p = 0.04). All grade 4 toxicity events were reported in the completion HT group. CONCLUSIONS: Due to high severe toxicity, RCT and IGABT with dose escalation followed by completion hysterectomy don't seem compatible. No benefit and increased severe late morbidity were observed. Combined intracavitary/interstitial technique is mandatory in large target volume at brachytherapy.

Prevalence, Risk Factors, and Impact of Obstructive Sleep Apnea in Adults with Congenital Heart Disease.

The objective of our study was to determine the prevalence, risk factors, and the impact of obstructive sleep apnea (OSA) in the adult with congenital heart disease (ACHD). One hundred forty-nine consecutive patients seen in our ACHD program were screened for OSA using the Berlin Questionnaire. Demographic and clinical details on subjects were collected through a chart review. Clinical variables were analyzed to determine risk factors for positive OSA screen, as well as associated outcomes. Seventy-seven (52%) of our cohort were females. The median age of the cohort was 33 years (range = 18-74) and median weight was 79 kg (range = 50-145 kg). Overall, 47 (31%) of our cohort were found to have a positive OSA screen using the Berlin questionnaire. Median age of the patients whom tested positive was 34 years. Compared to patients with a negative screen, patients with a positive OSA screen were more likely to be heavier with a median weight of 99 kg vs 71 kg (p < 0.01) and a larger BMI (31 vs 25 kg/m2, p < 0.01). Overall, 55% of patients whom screened positive were obese (defined as a BMI > 30) compared to 15% in the negative group (p < 0.02). Patients with a positive screen were more likely to have other co-morbidities including diabetes (p < 0.04), hypertension (p < 0.05), depression (p < 0.002), and were more likely to have decreased exercise capacity (p < 0.01) and a defibrillator (p < 0.007). Our data demonstrates that OSA is common in the ACHD patient and is associated with increasing weight and BMI. Patients with a positive screen are at increased risk for multiple co morbidities including diabetes, hypertension, and depression. We believe our data supports the use of screening protocols for OSA in the ACHD population in effort to identify early, treat, and potentially prevent late complications.

Late morbidity in cesarean section scar syndrome.

OBJECTIVE: To summarize recent knowledge on ethiology, diagnostic management and treatment possibilities of cesarean section scar syndrome (isthmocoele). DESIGN: Review article. SETTING: Department of Gynaecology and Obstetrics, Faculty Hospital and Palacky University, Olomouc; Department of Gynaecology and Obstetrics, Vítkovická nemocnice, Ostrava-Vítkovice. METHODS: A literature review of published data on cesarean section scar syndrome (isthmocoele). RESULTS: Cesarean section scar syndrome may be associated with subsequent complications including postmenstrual spotting or bleeding, dysmenorrhoea, abdominal pain, dyspareunia, infertility, scar pregnancy, a morbidly adherent placenta, scar dehiscence or rupture in later pregnancy. Ethiopathogenesis of isthmocoele remains poorly understood. Magnetic resonance, sonohysterography and transvaginal ultrasound are the gold standard imaging techniques for diagnosis. Surgical treatment is still controversial but should be offered to symptomatic women. CONCLUSIONS: Given the association between an isth-mocoele and gynaecological symptoms, obstetric complications and infertility, it is important to focus on preventive strategies of its development.

Late morbidity leading to hospitalization among 5-year survivors of young adult cancer: a report of the childhood, adolescent and young adult cancer survivors research program.

To estimate the risk of late morbidity leading to hospitalization among young adult cancer 5-year survivors compared to the general population and to examine the long-term effects of demographic and disease-related factors on late morbidity, a retrospective cohort of 902 five-year survivors of young adult cancer diagnosed between 1981 and 1999 was identified from British Columbia (BC) Cancer Registry. A matched comparison group (N = 9020) was randomly selected from the provincial health insurance plan. All hospitalizations until the end of 2006 were determined from the BC health insurance plan hospitalization records. The Poisson regression model was used to estimate the rate ratios for late morbidity leading to hospitalization except pregnancy after adjusting for sociodemographic and clinical risk factors. Overall, 455 (50.4%) survivors and 3,419 (37.9%) individuals in the comparison group had at least one type of late morbidity leading to hospitalization. The adjusted risk of this morbidity for survivors was 1.4 times higher than for the comparison group (95% CI = 1.22-1.54). The highest risks were found for hospitalization due to blood disease (RR = 4.2; 95% CI = 1.98-8.78) and neoplasm (RR = 4.3; 95% CI = 3.41-5.33). Survivors with three treatment modalities had three-fold higher risk of having any type of late morbidity (RR = 3.22; 95% CI = 2.09-4.94) than the comparators. These findings emphasize that young adult cancer survivors still have high risks of a wide range of late morbidities.

Androgen Deprivation Therapy Combined With Particle Therapy for Prostate Cancer: A Systematic Review.

PURPOSE: There is high-level evidence for addition of androgen deprivation therapy to photon-based radiotherapy of the prostate in intermediate- and high-risk prostate cancer. Little is known about the value of ADT in particle therapy of prostate cancer. We are conducting a systematic review on biochemical disease-free survival, overall survival, and morbidity after combined particle therapy and ADT for prostate cancer. METHODS: A thorough search in PubMed, Embase, Scopus, and Web of Science databases were conducted, searching for relevant studies. Clinical studies on prostate cancer and the treatment combination of particle therapy and androgen deprivation therapy were included. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO (CRD42021230801). RESULTS: A total of 298 papers were identified. Fifteen papers reporting on 7,202 patients after proton or carbon-ion therapy for localized prostate cancer where a fraction or all patients received ADT were selected for analysis. Three thousand five hundred and nineteen (49%) of the patients had received combined ADT and particle therapy. Primarily high-risk (87%), to a lesser extent intermediate-risk (34%) and low-risk patients (12%) received ADT. There were no comparative studies on the effect of ADT in patients treated with particles and no studies identified ADT as an independent prognostic factor related to survival outcomes. CONCLUSIONS: The review found no evidence to support that the effects on biochemical disease-free survival and morbidity of combining ADT to particle therapy differs from the ADT effects in conventional photon based radiotherapy. The available data on the topic is limited.

A randomized phase III trial for alleviating radiation-induced xerostomia with chewing gum.

BACKGROUND AND PURPOSE: Xerostomia is frequently reported after radiotherapy (RT) for head and neck cancer (HNC). The aim of this study was to reduce symptoms of radiation-induced xerostomia in HNC survivors, in which the experimental arm used chewing gum for a month. Primary endpoint was changes in scoring of dry mouth as defined by EORTC QLQ-H&N35 between arms. MATERIALS AND METHODS: Participants with any grade of physician-assessed xerostomia, ≥ six month after RT, disease-free and able to chew gum were, for a month, randomized (2:1) to: (Arm A) daily chewing gum or (Arm B) standard care. Xerostomia-related QOL was assessed using EORTC QLQ-H&N35 and GRIX questionnaires along with measurement of salivary flow and viscosity at inclusion and after one month. The study was registered on ClinicalTrials.gov (NCT03302676). RESULTS: Ninety-one participants were eligible for analysis (Arm A, n = 55; Arm B, n = 36). Comparing categorized scores for symptoms between arms, reduction of dry mouth was significantly higher for Arm A than Arm B (p = 0.05). A reduction in dry mouth scores was observed for xerostomia assessed by EORTC QLQ-H&N35 (question 41) for both arms. Salivary flow increased and viscosity decreased upon five minutes of stimulation within both arms (p < 0.001, respectively), however no significantly difference was observed between arms. CONCLUSION: Categorized scores found reduction of dry mouth to be significantly higher in Arm A than Arm B, but no difference was seen for salivary flow rate and viscosity.

Long-term urodynamic findings following radical prostatectomy and salvage radiotherapy.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are common following radical prostatectomy (RP) or intended curative radiotherapy in prostate cancer patients. One-quarter of those treated with RP experience biochemical failure and are subsequently offered salvage radiotherapy (SRT) to the prostatic bed. The aim of this study was to elucidate long-term LUTS after surgery and SRT. MATERIALS AND METHODS: Urodynamic parameters from 16 patients treated with RP and subsequent SRT in the period 2000-2010 were evaluated with uroflowmetry, filling cystometry, pressure-flow and urethral pressure profile (UPP). In conjunction with the urodynamic examination, all patients completed the Danish Prostatic Symptom Score (DAN-PSS) questionnaire, which evaluates the grade of LUTS. RESULTS: Median time from SRT to urodynamic examination was 7.7 years (range 5.8-10.0 years). The following urodynamic parameters were affected: bladder volume at maximal cystometric capacity, bladder compliance, bladder function, bladder outlet obstruction and UPP. The total DAN-PSS index combining all symptoms and their corresponding impact on patients was mild in six patients (≤ 7 points), moderate in seven patients (8-19 points) and severe in three patients (≥ 20 points). CONCLUSIONS: This urodynamic study is one of the first to evaluate long-term urodynamic characteristics in patients treated with SRT. Several urodynamic parameters were affected. This indicates that SRT primarily affects bladder compliance, maximal cystometric capacity and bladder outlet obstruction. LUTS were proven to be strongly related to urodynamic parameters.

Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study.

BACKGROUND/PURPOSE: This study describes late bowel morbidity prospectively assessed in the multi-institutional EMBRACE study on MRI-guided adaptive brachytherapy in locally advanced cervical cancer (LACC). MATERIALS/METHODS: A total of 1176 patients were analyzed. Physician reported morbidity (CTCAE v.3.0) and patient reported outcome (PRO) (EORTC QLQ C30/CX24) were assessed at baseline and at regular follow-up. RESULTS: At 3/5 years the actuarial incidence of bowel morbidity grade 3-4 was 5.0%/5.9%, including incidence of stenosis/stricture/fistula of 2.0%/2.6%. Grade 1-2 morbidity was pronounced with prevalence rates of 28-33% during follow-up. Diarrhea and flatulence were most frequently reported, significantly increased after 3 months and remained elevated during follow-up. Incontinence gradually worsened with time. PRO revealed high prevalence rates. Diarrhea ≥"a little" increased from 26% to 37% at baseline to 3 months and remained elevated, difficulty in controlling bowel increased from 11% to 26% at baseline to 3 months gradually worsening with time. Constipation and abdominal cramps improved after treatment. CONCLUSION: Bowel morbidity reported in this large cohort of LACC patients was limited regarding severe/life-threatening events. Mild-moderate diarrhea, flatulence and incontinence were prevalent after treatment with PROs indicating a considerable and clinically relevant burden. Critical knowledge based on the extent and manifestation pattern of treatment-related morbidity will serve future patient management.

Late urinary morbidity and quality of life after radical prostatectomy and salvage radiotherapy for prostate cancer.

OBJECTIVE: There is a paucity of knowledge of long-term urinary morbidity in patients treated for prostate cancer (PCa) with radical prostatectomy (RP) and salvage radiotherapy (SRT). Improved long-term survival calls for heightened awareness of late effects from radiotherapy after RP. The purpose of this study was to assess late urinary morbidity and its potential impact on quality of life (QoL) in patients treated with RP plus SRT compared with patients treated with RP alone. MATERIALS AND METHODS: Long-term morbidity and QoL were evaluated using a cross-sectional design with validated questionnaires in urinary morbidity [Danish Prostatic Symptom Score (DAN-PSS)] and QoL [European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)]. Included were a total of 227 patients treated with SRT and 192 treated with RP in the periods 2006-2010 and 2005-2007, respectively. RESULTS: Weak stream, straining, frequency and nocturia were significantly more prevalent in patients treated with RP + SRT than in patients treated with RP alone. Patients treated with RP + SRT generally suffered from more severe urinary symptoms. The QoL scores of the two treatment groups were not statistically significantly different, but a high level of urinary morbidity was significantly related to decreased QoL (p = 0.000). CONCLUSIONS: Patients treated with SRT have a higher rate of urinary morbidity than do patients treated with RP alone. Severe urinary morbidity was significantly related to decreased QoL, but did not differ between the two treatment groups.

Post radiation hysterectomy in locally advanced cervical cancer: Outcomes and dosimetric impact.

PURPOSES: Firstly, to evaluate the impact of completion hysterectomy after chemoradiation and image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. Secondly, to assess a potential differential dose-effect relationship for the rectum and bladder according to the realization of hysterectomy. MATERIAL AND METHODS: Two cohorts of patients were identified, differing by the realization of completion hysterectomy. Inclusions were limited to FIGO stage I-II, with no para-aortic involvement. All patients received a combination of pelvic chemoradiation followed by IGABT. Their outcomes and morbidity were reviewed. Log-rank tests were used to compare survivals. Probit analyses were performed to study dose-volume effect relationships. RESULTS: The two cohorts comprised 54 patients in the completion surgery group and 157 patients in the definitive radiotherapy group. They were well balanced, except for the mean follow-up, significantly longer in the post hysterectomy cohort and the use of PET-CT in the work-up, more frequent in the definitive radiotherapy cohort. Although less local relapses were reported in the hysterectomy group, the 5-year disease-free and overall survival did not differ between groups. The cumulative incidence of severe late morbidity was significantly increased in the hysterectomy cohort: 22.5% versus 6.5% at 5years (p=0.016). Dose-volume effects were observed for the bladder, with the D2cm3 corresponding with a 10% probability of late severe morbidity urinary events (ED10) of 67.8Gy and 91.9Gy in the hysterectomy and definitive radiotherapy cohorts, respectively. A D90 CTVHR of 85Gy (planning aim) corresponded with a 93.3% rate of local control in the definitive radiotherapy cohort whereas it corresponded with a 77.3% chance to have a good histologic response (complete response or microscopic residual disease) in the hysterectomy group. CONCLUSION: No benefit from completion hysterectomy in terms of overall or disease-free survival rates was observed, which was moreover responsible for an increase of the severe late morbidity. The realization of post-radiation hysterectomy resulted in a shift of the ED10 of 24.1Gy.

Development and validation of a scoring system for late anorectal side-effects in patients treated with radiotherapy for prostate cancer.

PURPOSE: To develop and validate a scoring system for evaluation of long term anorectal dysfunction following radiotherapy for prostate cancer. MATERIALS AND METHODS: Patients treated for prostate cancer with radiotherapy filled in questionnaires on anorectal function and quality of life. Items for the condensed anorectal dysfunction score (RT-ARD) were identified and weighted by binomial regression analysis. The score was tested in a separate patient material by receiver operating characteristic (ROC) analysis and correlations to quality of life domains. RESULTS: A total of 309 patients participated in the study. The items selected were "incontinence for solid stool", "ability to defer defecation", "unproductive call to stool", "clustering of stool", and "mucus in stool." Patients were grouped into three categories according to the RT-ARD score; 0-8 (no RT-ARD), 9-23 (minor RT-ARD), 24-45 (major RT-ARD). ROC analyses revealed high sensitivity (91%) and specificity (85%) for major RT-ARD. The prediction model demonstrated a perfect fit in 60%, moderate fit in 36% and no fit in 4%. There was good correlation between the RT-ARD score and quality of life. CONCLUSIONS: The RT-ARD score is a validated and simple instrument for evaluation of anorectal dysfunction following radiotherapy for prostate cancer, and the RT-ARD score correlates to the patient's quality of life.