Late adverse events in patients with pelvic cancer after oncologic treatment-intervention and treatment effect.

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 visits 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 visits 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 visits 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.

Effect of TENS and stabilization exercises on pelvic pain in pelvic cancer survivors following multimodal treatment: A clinical trial.

Background: Pelvic floor muscle (PFM) dysfunction and pain are common complications seen in pelvic cancers including the gynecological and genitourinary systems before and after treatments such as chemotherapy, radiotherapy, and surgeries and may contribute to significant morbidity as the survival rates increase in these patients. Objective: The objective of the clinical trial was to evaluate the effect of transcutaneous electrical nerve stimulation (TENS) and stabilization exercises on pelvic pain in pelvic cancer survivors following multimodal treatment. Materials and Methods: Thirty-one patients including both male and female adults treated for pelvic cancers were recruited in the study. Outcome measures in terms of pain were assessed at baseline and at the end of the study by the visual analog scale and genitourinary pain index (GUPI) scale, abdominal muscle strength by pressure biofeedback unit for transverse abdominal (TrA) muscle, and quality of life (QOL) by functional assessment of cancer therapy general questionnaire. Pelvic stabilization exercises and TENS were administered once daily approximately 30 min during the acute hospitalization. Results: Pelvic stabilization exercises and TENS demonstrated to be effective in ameliorating pelvic pain (P < 0.001) and improving in the GUPI scores of pain, incontinence, increasing strength of TrA musculature (P < 0.001), and improving overall QOL (P < 0.005). Conclusion: The trial suggests that a combination of pelvic stabilization exercises and conventional TENS may be used as a strategic tool to reduce pain and improve PFM strength after multimodal treatments in pelvic cancer survivors in the clinical setup of an Indian Scenario.

Treatment for local control of retroperitoneal and pelvis sarcomas: A review of the literature.

Retroperitoneal and pelvis sarcomas are uncommon tumors for which complete surgical resection is the mainstay of treatment. However, achieving complete gross resection with microscopically negative margins is challenging, and local recurrence rates can be high. Patients often succumb to uncontrolled local disease. Radiation therapy offers a potential means for sterilizing microscopic residual disease, although its use continues to be controversial. Chemotherapy alone or in combination with radiation continues to be investigated as an adjunct to surgery, along with immunotherapy and targeted therapies. In this review, we discuss the current management of retroperitoneal and pelvis sarcomas, focusing on studies of surgery and radiation therapy to maximize local control.

Utilization and outcomes of adjuvant therapy for stage II and III uterine leiomyosarcoma.

OBJECTIVES: The optimal adjuvant therapy for uterine leiomyosarcoma (uLMS) remains uncertain. We analyzed the utilization of adjuvant chemotherapy and radiation therapy for stage II and III uLMS and explored the association between use of adjuvant therapy and survival. METHODS: Patients with stage II or III uLMS treated from 2004 to 2016 and recorded in the National Cancer Database were identified. Multivariable regression models were fit to estimate predictors of use of either adjuvant radiation therapy or chemotherapy. To analyze the impact of chemotherapy on all-cause mortality, an inverse probability of treatment weighted (IPTW) propensity score method was used to account for measured confounders, and the receipt of radiation therapy was adjusted in the outcome model. The process was repeated to analyze the impact of radiation therapy on all-cause mortality by using an IPTW propensity score method and adjusting for the receipt of adjuvant chemotherapy. RESULTS: A total of 890 patients were identified. Adjuvant chemotherapy use increased from 62.2% in 2010 to 70.4% in 2016, whereas radiation usage decreased from 26.7% in 2010 to 10.4% in 2016. Patients with stage III (vs. stage II) disease were less likely to receive radiation therapy. After propensity score weighting, chemotherapy was associated with a 30% decreased risk of all-cause mortality in stage III patients (HR 0.70, 95% CI 0.45-0.98) but had no effect on mortality for stage II patients (HR 0.93, 95% CI 0.70-1.20). Radiation therapy was associated with a 26% decreased risk of mortality for stage II tumors (HR 0.74; 95% CI, 0.53-0.99) and a 57% decrease in mortality for stage III disease (HR 0.43, 95% CI 0.18-0.99). CONCLUSIONS: Among women with stage II-III uLMS, use of chemotherapy is increasing while use of radiation therapy is decreasing. Radiation therapy is associated with improved survival in both stage II and III disease, while there was no association between use of adjuvant chemotherapy and survival in stage II patients.

[Extramammary myofibroblastoma affecting the pelvic region: a case report]. / Myofibroblastome extramammaire de localisation pelvienne: à propos d'un cas.

Mammary myofibroblastoma is a rare soft-tissue tumor. Extramammary myofibroblastomas are particularly rare. We here report the case of a 78-year-old man presenting with pelvic pain relieved by defecation or urination. Rectal examination showed a mass in front of the anterior rectal wall. The magnetic resonance imaging (MRI) showed a well-circumscribed and heterogeneous mass measuring 10 x 6 x 8cm located behind the bladder which was pushed forward in front of the rectosigmoid. Immunohistochemical analyses showed diffuse co-expression on CD34 cells and desmin, Rb expression on most cells, oestrogen receptor expression, intense and diffuse P16 expression and a ki67 proliferation index of 25%. The patient had no recurrence 8 months after radiotherapy followed by surgery. Breast myofibroblastoma is a rare and benign tumor. Recurrence is hardly observed after local treatment. This study highlights the supporting role of radiotherapy in the efficacy of surgery.

Prognostic Value of Site-Specific Metastases and Therapeutic Roles of Surgery and Chemotherapy for Patients With Metastatic Renal Pelvis Cancer: A SEER Based Study.

BACKGROUND AND AIMS: There is a lack of research on metastatic renal pelvis cell carcinoma in the current literature. In this study, we aimed to detect distant metastatic patterns in renal pelvis cell carcinoma, and illustrated the affection of different metastatic sites, surgery to primary site and chemotherapy on prognosis outcomes in patients with diverse conditions. METHODS: We collected data between 2010 and 2015 from the Surveillance, Epidemiology and End Results database. Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 424 patients were included in the analysis, the median follow-up time was 5 months (interquartile range (IQR): 2-12) and 391 deaths (92.2%) in all patients were recorded. Among them, 192 (45.3%), 153 (36.1%), 137 (32.3%) and 127 (30.0%) patients were diagnosed with lung, bone, liver and brain metastases, respectively, while only 12 (2.8%) patients had brain metastases. The bi-organ, tri-organ and tetra-organ metastatic pattern was found in 135 (31.8%), 32 (7.5%) and 11 (2.6%) patients, respectively. The multivariate Cox analyses showed that distant lymph nodes (DL) metastases was not an independent prognostic factor for both OS and CSS (OS: Hazard ratios (HR) = 1.1, 95% CI = 0.8-1.4, P = 0.622; CSS: HR = 1.0, 95% CI = 0.8-1.3, P = 0.906). Besides, there was no significant difference of survival in patients with T3-T4 stage (OS: HR = 0.8, 95% CI = 0.5-1.2, P = 0.296; CSS: HR = 0.8, 95% CI = 0.5-1.2, P = 0.224), N2-3 stage (OS: HR = 0.8, 95% CI = 0.5-1.3, P = 0.351; CSS: HR = 0.7, 95% CI = 0.4-1.2, P = 0.259) and multi-organ metastases (OS: HR = 0.8, 95% CI = 0.5-1.3, P = 0.359; CSS: HR = 0.7, 95% CI = 0.4-1.2, P = 0.179) between surgery to primary site group and no-surgery to primary site group. CONCLUSION: we described the metastatic patterns of mRPCC and the prognosis outcomes of DL metastases, surgery to primary site and chemotherapy. Our findings provide more information for clinical therapeutic intervention and translational study designs.

An assessment of the use of patient reported outcome measurements (PROMs) in cancers of the pelvic abdominal cavity: identifying oncologic benefit and an evidence-practice gap in routine clinical practice.

BACKGROUND: Patient reported outcome measurements (PROMs) are emerging as an important component of patient management in the cancer setting, providing broad perspectives on patients' quality of life and experience. The use of PROMs is, however, generally limited to the context of randomised control trials, as healthcare services are challenged to sustain high quality of care whilst facing increasing demand and financial shortfalls. We performed a systematic review of the literature to identify any oncological benefit of using PROMs and investigate the wider impact on patient experience, in cancers of the pelvic abdominal cavity specifically. METHODS: A systematic review of the literature was conducted using MEDLINE (Pubmed) and Ovid Gateway (Embase and Ovid) until April 2020. Studies investigating the oncological outcomes of PROMs were deemed suitable for inclusion. RESULTS: A total of 21 studies were included from 2167 screened articles. Various domains of quality of life (QoL) were identified as potential prognosticators for oncologic outcomes in cancers of the pelvic abdominal cavity, independent of other clinicopathological features of disease: 3 studies identified global QoL as a prognostic factor, 6 studies identified physical and role functioning, and 2 studies highlighted fatigue. In addition to improved outcomes, a number of included studies also reported that the use of PROMs enhanced both patient-clinician communication and patient satisfaction with care in the clinical setting. CONCLUSIONS: This review highlights the necessity of routine collection of PROMs within the pelvic abdominal cancer setting to improve patient quality of life and outcomes.

Hyperthermic intraperitoneal chemotherapy (HIPEC) as another treatment modality for desmoplastic round cell tumour patients: first paediatric experience from UK.

We present the first young paediatric patient with desmoplastic small round cell tumour (DSRCT) treated in UK with hyperthermic intraperitoneal chemotherapy (HIPEC). A 7-year-old girl was diagnosed with abdominal DSRCT with peritoneal and liver metastases. After six cycles of chemotherapy she obtained a partial response, including almost complete resolution of the two liver metastases. It was decided to pursue cytoreductive surgery (CRS) combined with HIPEC, a procedure commonly performed in adults, but seldom in a child. The surgery was macroscopically complete and the HIPEC uncomplicated. She continued treatment without delays, including whole abdomino-pelvic radiotherapy and maintenance chemotherapy (cyclophosphamide/vinorelbine for 12 months). She is currently in complete remission 4 months after end of treatment and 26 months after diagnosis. HIPEC was made possible by successful collaboration between multiple teams. CRS-HIPEC proved to be safe and feasible and could be offered to other children with diagnoses of peritoneal malignancies across the UK.

[Pelvic irradiation and hematopoietic toxicity: A review of the literature]. / Irradiation pelvienne et toxicité hématopoïétique : revue de la littérature.

Pelvic bone marrow is the site of nearly 50% of total hematopoiesis. Radiation therapy of pelvic lymph node areas, and cancers located near the bony structures of the pelvis, exposes to hematological toxicity in the range of 30 to 70%. This toxicity depends on many factors, including the presence or absence of concomitant chemotherapy and its type, the volume of irradiated bone, the received doses, or the initial hematopoietic reserve. Intensity modulated radiation therapy allows the optimisation of dose deposit on at risk organs while providing optimal coverage of target volumes. However, this suggests that dose constraints should be known precisely to limit the incidence of radiation side effects. This literature review focuses firstly on pelvic lymph node areas and bony volumes nearby, then on the effects of irradiation on bone marrow and the current dosimetric constraints resulting from it, and finally on hematological toxicities by carcinologic location and progress in reducing these toxicities.

Management of voiding dysfunction associated with pelvic malignancies.

Voiding dysfunction is common after surgical and radiation treatments in patients diagnosed with non-urological pelvic malignancies. Presentation might vary with lower urinary tract symptoms and/or overactive bladder, urinary retention, or incontinence. We reviewed the most recent literature with the aim of describing various types of urinary dysfunction that manifest after radical treatments for non-urological pelvic malignancies. Radical surgical or radiation treatment adversely affect other adjacent pelvic organ function, including viscera, pelvic musculature and the peripheral nervous system. This results in direct organ and indirect functional damage to the genitourinary tract. Multiple surgical and radiation modifications are available nowadays, allowing urologists to offer various treatments for better functional lower urinary tract outcomes. Diagnosing and understanding the type and severity of voiding dysfunction plays a key role in tailoring an appropriate treatment plan. The objective to better functional results relies on maintaining adequate bladder compliance and capacity while permitting volitional emptying, ideally through voiding. Management should routinely start with conservative measures, including pelvic floor muscle training with or without a combination of oral medication for urgency incontinence and clean intermittent catheterization for the management of urinary retention. Concomitant or isolated urinary incontinence can be further managed through multiple established surgical approaches. We attempted to address various treatment available for known lower urinary tract symptoms that might have been caused secondary to non-urological pelvic surgery or radiation. We discuss different diagnostic and treatment modalities individualized for patients with various entities, to help achieve optimal urinary function and improve quality of life.

The efficacy and safety of probiotics for prevention of chemoradiotherapy-induced diarrhea in people with abdominal and pelvic cancer: A systematic review and meta-analysis based on 23 randomized studies.

BACKGROUND AND AIMS: We evaluated the efficacy and safety of probiotics for prevention of chemoradiotherapy-induced diarrhea in patients with abdominal or pelvic cancer. METHODS: We searched the Cochrane Library, PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases up to August 2019. We also hand searched the citation lists of included studies and previous systematic reviews identified to identify further relevant trials. The primary outcome was the incidence of chemoradiotherapy-induced diarrhea of all grades. The secondary outcomes were improvement of antidiarrheal medication use, stool form (Bristol scale), response rate, and adverse events (AEs). Diarrhea was graded according to the Common Toxicity Criteria system. Two reviewers assessed trial quality and extracted data independently. The included studies were analyzed using Review Manager ver. 5.2. RESULTS: Twenty-three randomized, placebo-controlled studies (N = 2570 participants) were included in the efficacy assessment. The incidence of all diarrhea (risk ratio [RR] 0.16; 95% confidence interval [CI] 0.51-0.73), grade ≥ 3 diarrhea (RR 0.36; 95% CI 0.18-0.72), and grade ≥ 2 diarrhea (RR 0.65; 95% CI 0.54-0.78), but not that of grade ≤ 2 diarrhea (RR 1.07; 95% CI 0.95-1.21), was significantly reduced in the probiotics compared to the placebo groups. No significant increase in the incidence of AEs was found in the probiotics group, although four studies reported a variety of AEs. CONCLUSIONS: Probiotics prevented chemoradiotherapy-induced diarrhea, particularly high-grade diarrhea. Probiotics rarely cause AEs.

Randomised clinical trial of a gastrointestinal care bundle to reduce symptoms in patients with pelvic cancer undergoing chemoradiotherapy.

OBJECTIVE: Pelvic radiotherapy is used to treat 17 000 people in the UK each year. Eight in 10 develop difficult bowel problems during pelvic treatment, especially diarrhoea, urgency and incontinence. Some cannot complete treatment, reducing the chance of cancer cure. Undertaking gastroenterologist-led investigation and management during pelvic radiotherapy has never been evaluated. In this study, we aimed to assess whether patients could successfully receive a novel gastrointestinal (GI) care bundle during chemoradiotherapy (feasibility aim) and would experience reduced symptom severity (clinical impact aim). DESIGN: This randomised controlled trial recruited patients with cervical and bladder cancers undergoing radical chemoradiotherapy. Participants were randomised to intervention or control groups. Questionnaire and anthropometric data were collected. All intervention group patients received individualised dietary counselling weekly throughout treatment, and if bowel symptoms developed they were offered rapid-access investigation and treatment for any identified pathology: lactose intolerance, bacterial overgrowth or bile acid malabsorption. RESULTS: Feasibility: 50 participants were recruited, 24 were randomised to the intervention group and 26 to the control group. All completed 20 fractions of external beam pelvic radiotherapy. It was possible to perform 57/72 (79%) of proposed intervention tests with no disruption of oncological management. CLINICAL IMPACT: All participants developed GI symptoms during radiotherapy. The median symptom score for each group increased from baseline at 6 weeks. This was from 0.156 (0.000-0.333) to 0.600 (0.250-1.286) in the control group, and from 0.00 (0.000-0.300) to 0.402 (0.000-0.667) in the intervention group. CONCLUSION: It was feasible to recruit to and deliver a randomised controlled trial of interventions in patients undergoing pelvic chemoradiotherapy. Lower median bowel scores were reported in the intervention group at 6 weeks, with fewer patients experiencing symptoms overall. TRIAL REGISTRATION NUMBER: ISRCTN783488.

Neoadjuvant (re)chemoradiation for locally recurrent rectal cancer: Impact of anatomical site of pelvic recurrence on long-term results.

BACKGROUND: Selection criteria to propose neoadjuvant (re)chemoradiation (CHRT) in locally recurrent rectal cancer (LRRC) are required, since re-irradiation is sometimes associated to severe adverse effects. Aim of the present study was to compare chances of R0 surgery and disease-free survival (DFS) in LRRC patients (pts) treated by neoadjuvant (re)CHRT followed by surgery vs. upfront surgery, stratifying pts by each localization of LRRC. METHODS: LRRC pts treated at the National Cancer Institute of Milan (Italy) were retrospectively divided into two groups: neoadjuvant (re)CHRT vs. upfront surgery. According to our Milan classification, LRRC were categorized as S1, if located centrally (S1a-b) or anteriorly (S1c) within the pelvis; S2, in case of sacral involvement; S3, in case of lateral pelvic wall infiltration. RESULTS: 152 pts were candidate for multimodal treatment: 49 (32.2%) by neoadjuvant (re)CHRT and surgery, including 33 re-irradiations, vs. 103 (67.8%) by upfront surgery. No difference was observed in R0 resection rates (respectively 47.6% vs. 51.0%). However, neoadjuvant (re)CHRT followed by surgery improved the DFS (p = 0.028), also in R1 procedures (p = 0.013), compared with upfront surgery. At multivariate analysis, the R+ surgery (p < 0.0001) strongly predicted unfavorable DFS, while neoadjuvant (re)CHRT followed by surgery was independently associated to better DFS (p = 0.0197). Stratifying by LRRC localization, the combined approach significantly improved DFS in the S1c (p = 0.029) and S2 (p = 0.004) subgroups compared to upfront surgery, but not in S1a-b and S3 pts. CONCLUSION: Anterior (S1c) and sacral-invasive (S2) pelvic recurrences significantly benefit in terms of DFS by combination of neoadjuvant (re)CHRT and radical surgery, also after R1 resection.

Epithelioid and spindle cell rhabdomyosarcoma with FUS-TFCP2 or EWSR1-TFCP2 fusion: report of two cases.

The WHO Classification of Tumors of Soft Tissue and Bone divides rhabdomyosarcoma (RMS) into alveolar, embryonal, pleomorphic, and spindle cell/sclerosing types. Advances in molecular diagnostics have allowed for further refinement of RMS classification including the identification of new subtypes. Very rare RMS with epithelioid and spindle cell morphology, female predominance, marked osseous predilection, ALK expression, EWSR1/FUS-TFCP2 gene fusions, and highly aggressive clinical behavior have recently been recognized with only 23 cases reported in the English language literature. Herein, we report two additional cases with detailed clinicopathologic description and molecular confirmation. In brief, two young women presented each with a primary bone tumor-one with a frontal bone tumor and another with an osseous pelvic tumor. Both tumors showed epithelioid to spindle cell morphology, ALK expression, and EWSR1/FUS-TFCP2 gene fusions. Both patients died of disease less than 17 months from diagnosis despite administration of multiple lines of aggressive treatment. In addition, we review the literature and discuss differential diagnostic and potential treatment considerations.

The physical and psychological sexual well-being of women with pelvic malignancy: how can we understand and improve our practice?

How can we better understand and improve our practice around the physical and psychological well-being of women treated with radiation therapy for pelvic malignancy? In this issue, Summerfield et al report the results of a nationwide survey capturing practices around the management of radiation therapy-induced vaginal adhesions and stenosis (RTVAS) across New Zealand. This study highlights the need for oncologists to improve care around a challenging but critically important aspect of women's health beyond a cancer diagnosis.

Circulating tumour cell liquid biopsy in selecting therapy for recurrent cutaneous melanoma with locoregional pelvic metastases: a pilot study.

OBJECTIVES: Circulating tumour cells (CTCs) from liquid biopsies provide an exceptional opportunity to obtain real-time tumour information and are under current investigation in several cancers, including cutaneous melanoma, but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that chemosensitivity assays using liquid biopsy-derived metastatic melanoma (MM) CTCs, from 7 patients with stage IIIC, BRAF wild-type metastatic melanomas, localized exclusively to the pelvic region, un-eligible for immunotherapy and treated with melphalan hypoxic pelvic perfusion (HPP), is both feasible and useful in predicting response to therapy. Viable MM CTCs (> 5 cells/ml for all 7 blood samples), enriched by transient culture, were characterised in flow cytometry-based Annexin V-PE assays for chemosensitivity to several drugs. RESULTS: Using melphalan as a standard, chemosensitivity cut-off values of > 60% cell death, were predictive of patient RECIST 1.1 response to melphalan HPP therapy, associated with calculated 100% sensitivity, 66.67% specificity, 33.33% positive predictive, 100% negative predictive, and 71.43% accuracy values. We propose that the methodology in this study is both feasible and has potential value in predicting response to therapy, setting the stage for a larger study. Trial registration Clinical Trials.gov Identifier NCT01920516; date of trial registration: August 6, 2013.

The Clinical Management and Outcomes of Pelvic Neuroblastic Tumors.

BACKGROUND: Pelvic neuroblastomas are rare and often present in children as massive tumors whose surgical resection can be associated with significant morbidity, given sacral nerve root involvement and close proximity to pelvic vascular structures. We sought to examine the characteristics of patients with pelvic neuroblastoma and the effect of extent of surgical resection on survival and surgical outcomes. MATERIALS AND METHODS: After institutional review board approval, a retrospective chart review was performed at Children's Hospital Los Angeles from 2000 to 2018. Collected data included tumor location, size, image-defined risk factors histology, stage and risk classification, amplification of the oncogene MYCN or N-myc, use of preoperative chemotherapy, and extent of surgical resection. Outcome variables included postoperative complications and survival. RESULTS: Ten patients with primary pelvic neuroblastoma tumors were identified. The median age at diagnosis was 4.2 y (3 mo to 11 y). Four patients presented with a localized pelvic tumor (stage I or stage II) and underwent upfront tumor resection. Six patients presented with advanced disease (stage III or stage IV) and underwent neoadjuvant chemotherapy, followed by partial resection (30%-90% debulked). One patient experienced a complication: lower extremity hypotonia after tumor resection. One patient died from extensive metastatic disease for which no resection was attempted. The mean postoperative follow-up was 3.9 y with 90% overall survival. CONCLUSIONS: Our data show that patients who undergo gross total resection for localized pelvic neuroblastoma or neoadjuvant chemotherapy, followed by partial resection for advanced disease have excellent survival. We recommend that small localized pelvic neuroblastoma undergo gross total resection and large unresectable tumors undergo neoadjuvant chemotherapy, followed by partial debulking resection to avoid neurovascular morbidity.

Intrafractional vaginal dilation in anal cancer patients undergoing pelvic radiotherapy (DILANA) - a prospective, randomized, 2-armed phase-II-trial.

BACKGROUND: The incidence of anal cancer is rising in the last decades and more women are affected than men. The prognosis after chemoradiation is very good with complete remission rates of 80-90%. Thus, reducing therapy-related toxicities and improving quality of life are of high importance. With the development of new radiotherapy techniques like IMRT (Intensity-modulated radiotherapy), the incidence of acute and chronic gastrointestinal toxicities has already been reduced. However, especially in female anal cancer patients genital toxicities like vaginal fibrosis and stenosis are of great relevance, too. Up to now, there are no prospective data reporting incidence rates, techniques of prevention or impact on quality of life. The aim of the DILANA trial is to evaluate the incidence and grade of vaginal fibrosis, to optimize radiotherapy by reducing dose to the vaginal wall to minimize genital toxicities and improve quality of life of anal cancer patients. METHODS: The study is designed as a prospective, randomized, two-armed, open, single-center phase-II-trial. Sixty patients will be randomized into one of two arms, which differ only in the diameter of a tampon used during treatment. All patients will receive standard (chemo) radiation with a total dose of 45-50.4 Gy to the pelvic and inguinal nodes with a boost to the anal canal up to 54-60 Gy. The primary objective is the assessment of the incidence and grade of vaginal fibrosis 12 months after (chemo) radiation depending on the extent of vaginal dilation. Secondary endpoints are toxicities according to the CTC AE version 5.0 criteria, assessment of clinical feasibility of daily use of a tampon, assessment of compliance for the use of a vaginal dilator and quality of life. DISCUSSION: Prospective studies are needed evaluating the incidence and grade of vaginal fibrosis after (chemo) radiation in female anal cancer patients. Furthermore, the assessment of techniques to reduce the incidence of vaginal fibrosis like intrafractional vaginal dilation as well as other radiotherapy-independent methods like using a vaginal dilator are essential. Additionally, implementation of a systematic assessment of vaginal stenosis is necessary to grant reproducibility and comparability of future data. TRIAL REGISTRATION: The trial is registered with clinicaltrials.gov (NCT04094454, 19.09.2019).

Which Factors Are Associated with Local Control and Survival of Patients with Localized Pelvic Ewing's Sarcoma? A Retrospective Analysis of Data from the Euro-EWING99 Trial.

BACKGROUND: Local treatment of pelvic Ewing's sarcoma may be challenging, and intergroup studies have focused on improving systemic treatments rather than prospectively evaluating aspects of local tumor control. The Euro-EWING99 trial provided a substantial number of patients with localized pelvic tumors treated with the same chemotherapy protocol. Because local control included surgical resection, radiation therapy, or a combination of both, we wanted to investigate local control and survival with respect to the local modality in this study cohort. QUESTIONS/PURPOSES: (1) Do patients with localized sacral tumors have a lower risk of local recurrence and higher survival compared with patients with localized tumors of the innominate bones? (2) Is the local treatment modality associated with local control and survival in patients with sacral and nonsacral tumors? (3) Which local tumor- and treatment-related factors, such as response to neoadjuvant chemotherapy, institution where the biopsy was performed, and surgical complications, are associated with local recurrence and patient survival in nonsacral tumors? (4) Which factors, such as persistent extraosseous tumor growth after chemotherapy or extent of bony resection, are independently associated with overall survival in patients with bone tumors undergoing surgical treatment? METHODS: Between 1998 and 2009, 1411 patients with previously untreated, histologically confirmed Ewing's sarcoma were registered in the German Society for Pediatric Oncology and Hematology Ewing's sarcoma database and treated in the Euro-EWING99 trial. In all, 24% (339 of 1411) of these patients presented with a pelvic primary sarcoma, 47% (159 of 339) of which had macroscopic metastases at diagnosis and were excluded from this analysis. The data from the remaining 180 patients were reviewed retrospectively, based on follow-up data as of July 2016. The median (range) follow-up was 54 months (5 to 191) for all patients and 84 months (11 to 191) for surviving patients. The study endpoints were overall survival, local recurrence and event-free survival probability, which were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) with their respective 95% CIs were estimated in a multivariate Cox regression model. RESULTS: Sacral tumors were associated with a reduced probability of local recurrence (12% [95% CI 1 to 22] versus 28% [95% CI 20 to 36] at 5 years, p = 0.032), a higher event-free survival probability (66% [95% CI 51 to 81] versus 50% [95% CI 41 to 58] at 5 years, p = 0.026) and a higher overall survival probability (72% [95% CI 57 to 87] versus 56% [95% CI 47 to 64] at 5 years, p = 0.025) compared with nonsacral tumors. With the numbers available, we found no differences between patients with sacral tumors who underwent definitive radiotherapy and those who underwent combined surgery and radiotherapy in terms of local recurrence (17% [95% CI 0 to 34] versus 0% [95% CI 0 to 20] at 5 years, p = 0.125) and overall survival probability (73% [95% CI 52 to 94] versus 78% [95% CI 56 to 99] at 5 years, p = 0.764). In nonsacral tumors, combined local treatment was associated with a lower local recurrence probability (14% [95% CI 5 to 23] versus 33% [95% CI 19 to 47] at 5 years, p = 0.015) and a higher overall survival probability (72% [95% CI 61 to 83] versus 47% [95% CI 33 to 62] at 5 years, p = 0.024) compared with surgery alone. Even in a subgroup of patients with wide surgical margins and a good histologic response to induction treatment, the combined local treatment was associated with a higher overall survival probability (87% [95% CI 74 to 100] versus 51% [95% CI 33 to 69] at 5 years, p = 0.009), compared with surgery alone.A poor histologic response to induction chemotherapy in nonsacral tumors (39% [95% CI 19 to 59] versus 64% [95% CI 52 to 76] at 5 years, p = 0.014) and the development of surgical complications after tumor resection (35% [95% CI 11 to 59] versus 68% [95% CI 58 to 78] at 5 years, p = 0.004) were associated with a lower overall survival probability in nonsacral tumors, while a tumor biopsy performed at the same institution where the tumor resection was performed was associated with lower local recurrence probability (14% [95% CI 4 to 24] versus 32% [95% CI 16 to 48] at 5 years, p = 0.035), respectively.In patients with bone tumors who underwent surgical treatment, we found that after controlling for tumor localization in the pelvis, tumor volume, and surgical margin status, patients who did not undergo complete (defined as a Type I/II resection for iliac bone tumors, a Type II/III resection for pubic bone and ischium tumors and a Type I/II/III resection for tumors involving the acetabulum, according to the Enneking classification) removal of the affected bone (HR 5.04 [95% CI 2.07 to 12.24]; p < 0.001), patients with a poor histologic response to induction chemotherapy (HR 3.72 [95% CI 1.51 to 9.21]; p = 0.004), and patients who did not receive additional radiotherapy (HR 4.34 [95% CI 1.71 to 11.05]; p = 0.002) had a higher risk of death. The analysis suggested that the same might be the case in patients with a persistent extraosseous tumor extension after induction chemotherapy (HR 4.61 [95% CI 1.03 to 20.67]; p = 0.046), although the wide CIs pointing at a possible sparse-data bias precluded any definitive conclusions. CONCLUSION: Patients with sacral Ewing's sarcoma appear to have a lower probability for local recurrence and a higher overall survival probability compared with patients with tumors of the innominate bones. Our results seem to support a recent recommendation of the Scandinavian Sarcoma Group to locally treat most sacral Ewing's sarcomas with definitive radiotherapy. Combined surgical resection and radiotherapy appear to be associated with a higher overall survival probability in nonsacral tumors compared with surgery alone, even in patients with a wide resection and a good histologic response to neoadjuvant chemotherapy. Complete removal of the involved bone, as defined above, in patients with nonsacral tumors may be associated with a decreased likelihood of local recurrence and improved overall survival. Persistent extraosseous tumor growth after induction treatment in patients with nonsacral bone tumors undergoing surgical treatment might be an important indicator of poorer overall survival probability, but the possibility of sparse-data bias in our cohort means that this factor should first be validated in future studies. LEVEL OF EVIDENCE: Level III, therapeutic study.