Advancements in nanomedicine: Precision delivery strategies for male pelvic malignancies - Spotlight on prostate and colorectal cancer.

BACKGROUND: Pelvic malignancies consistently pose significant global health challenges, adversely affecting the well-being of the male population. It is anticipated that clinicians will continue to confront these cancers in their practice. Nanomedicine offers promising strategies that revolutionize the treatment of male pelvic malignancies by providing precise delivery methods that aim to improve the efficacy of therapeutic outcomes while minimizing side effects. Nanoparticles are designed to encapsulate therapeutic agents and selectively target cancer cells. They can also be loaded with theragnostic agents, enabling multifunctional capabilities. OBJECTIVE: This review aims to summarize the latest nanomedicine research into clinical applications, focusing on nanotechnology-based treatment strategies for male pelvic malignancies, encompassing chemotherapy, radiotherapy, immunotherapy, and other cutting-edge therapies. The review is structured to assist physicians, particularly those with limited knowledge of biochemistry and bioengineering, in comprehending the functionalities and applications of nanomaterials. METHODS: Multiple databases, including PubMed, the National Library of Medicine, and Embase, were utilized to locate and review recently published articles on advancements in nano-drug delivery for prostate and colorectal cancers. CONCLUSION: Nanomedicine possesses considerable potential in improving therapeutic outcomes and reducing adverse effects for male pelvic malignancies. Through precision delivery methods, this emerging field presents innovative treatment modalities to address these challenging diseases. Nevertheless, the majority of current studies are in the preclinical phase, with a lack of sufficient evidence to fully understand the precise mechanisms of action, absence of comprehensive pharmacotoxicity profiles, and uncertainty surrounding long-term consequences.

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.

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.

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.

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.

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).

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.

Successful Full-term Pregnancies After High-dose Pelvic Radiotherapy for Ewing Sarcoma: A Case Report.

Survivors of childhood cancer are at risk of long-term sequelae that arise as a consequence of cancer treatment. Radiation and chemotherapy treatment in pediatric female patients can have detrimental impacts on fertility, particularly in those with pelvic tumor involvement. We report 2 successful natural full-term pregnancies with vaginal delivery in a woman 12 years after biopsy, irradiation (55.5 Gy), and multi-agent chemotherapy for treatment of pelvic Ewing sarcoma. Both children were born healthy, with no complications in pregnancy or delivery. Fertility preservation and risk assessment following chemotherapy/radiation therapy is evolving, providing new data to effectively counsel and treat young women.

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.

Role of pelvic chemoradiation therapy in patients with initially metastatic anal canal cancer: A National Cancer Database review.

BACKGROUND: Although the management of localized anal canal squamous cell carcinomas is well established, the role of pelvic chemoradiation (CRT) in the treatment of patients presenting with synchronous metastatic (stage IV) disease is poorly defined. This study used a national cancer database to compare the overall survival (OS) rates of patients with synchronous metastatic disease receiving CRT to the pelvis and patients treated with chemotherapy (CT) alone. METHODS: This study included adult patients with anal canal squamous cell carcinomas presenting with synchronous metastases diagnosed from 2004 to 2012. Multiple imputation and 2:1 propensity score matching were used to create a matched data set for testing. The proportional hazards model was used to estimate the hazard ratio (HR) for the effect of the treatment group on OS. With only patients in the matched data set, the OS of the treatment groups was estimated with the Kaplan-Meier method by treatment group. RESULTS: This study started with an unmatched data set of 978 patients, and 582 patients were selected for the matched data set: 388 in the CRT group and 194 in the CT-alone group. The HR for the group effect was 0.75 (95% confidence interval [CI], 0.61-0.92; P = .006). The median OS was 21.1 months in the CRT group (95% CI, 17.4-24.0 months) and 14.6 months in the CT group (95% CI, 12.2-18.4 months). The corresponding 5-year OS rates were 23% (95% CI, 18%-28%) and 14% (95% CI, 7%-21%), respectively. CONCLUSIONS: In this large series analyzing OS in patients with stage IV anal cancer, CRT was associated with improved OS in comparison with CT alone. Because of the lack of prospective data in this setting, this evidence will help to guide treatment approaches in this group of patients.

Adjuvant therapy in stage III endometrial cancer confined to the pelvis.

OBJECTIVE: To review outcomes of patients with stage III endometrial cancer confined to the pelvis treated with adjuvant pelvic radiotherapy (RT) or sequential chemoradiotherapy (CRT). METHODS: Between 1990 and 2012, 144 patients diagnosed with stage IIIA, B or C1 endometrial cancer were treated in our institution. All were treated with total hysterectomy, bilateral salpingo-oophorectomy ±â€¯lymph node dissection. Post-operatively, 67 patients received adjuvant RT alone, 37 CRT, 21 chemotherapy alone and 19 had no adjuvant therapy. This analysis focuses on the 104 patients treated with RT or CRT. RESULTS: The median follow-up was 61 months. Forty-six patients (44%) were stage IIIA, 6 (6%) were stage IIIB and 52 (50%) stage IIIC1. The 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) for patients treated by RT alone vs. CRT were, respectively, 67% vs. 61% (p = 0.55); 67% vs. 51% (p = 0.35); and 76% vs. 65% (p = 0.21). Grade 3 disease was an independent predictor for worse OS (HR = 6.01, p = 0.001), DFS (HR = 3.16, p = 0.03), and DSS (HR = 3.77, p = 0.02). In patients with grade 3 disease (n = 49), the 5-year OS was superior for the CRT (42% vs. 56%, p = 0.007). CONCLUSIONS: In patients with stage III endometrial cancer confined to the pelvis, the addition of adjuvant chemotherapy with RT significantly improved OS in grade 3 disease. Grade 3 histology is a strong predictor for poor outcome. Further randomized studies aiming specifically at stage III disease are warranted.

Tumors of the Ischiorectal Fossa: A Single-Institution Experience.

BACKGROUND: Ischiorectal fossa tumors are rare. OBJECTIVE: This study reviews a single institution's series of ischiorectal tumors with comparison against presacral tumors and assesses the utility of preoperative biopsy and angioembolization. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a quaternary referral center. PATIENTS: All patients with ischiorectal tumor treated between February 1995 and April 2017 were retrospectively reviewed. Tumors extending secondarily into the ischiorectal fossa and inflammatory pathologies were excluded. INTERVENTIONS: Preoperative biopsy, neoadjuvant therapy, angioembolization, and surgical excision of these tumors were reviewed. MAIN OUTCOME MEASURES: Demographic, perioperative, pathological, and oncologic outcomes were evaluated. RESULTS: Twenty-four patients (15 female; median age 54) were identified. Two-thirds were symptomatic. Forty-six percent had a palpable mass. All patients had CT and/or MRI. Fifty percent had a preoperative biopsy, of which 83% were diagnostic, and management was altered in 50%. All patients underwent surgical excision. Fifty-five percent had local excision, 38% had radical pelvic excision, and 8% had total mesorectal excision. Two patients had preoperative angioembolization. Both had successful R0 local excision. Morbidity occurred in 25%, with 1 major complication. There was no 30-day mortality. Histopathology demonstrated 17 soft tissue tumors (3 malignant), 2 GI stromal tumors, 1 neuroendocrine tumor, 1 Merkel cell carcinoma, 1 basaloid carcinoma, 1 epidermal cyst, and 1 lipoma. R0 resection was achieved in 75%. All patients were alive after a median follow-up of 33 months. Four patients developed recurrence at a median 10 months postoperatively. All recurrences were malignant, and 75% had had a R1 resection. LIMITATIONS: This study is limited by its small numbers. The quaternary institution source may introduce bias. CONCLUSIONS: Ischiorectal fossa tumors are heterogeneous and more likely to be malignant than presacral tumors. Biopsy can be useful if a malignant diagnosis is suspected and changes management in 50% of cases. Preoperative embolization may be useful for large vascular tumors. R0 resection is important to minimize recurrence. See Video Abstract at http://links.lww.com/DCR/A779.

Optimal treatment strategy for rectal cancer based on the risk factors for recurrence patterns.

BACKGROUND: For rectal cancer, multimodality therapeutic approach is necessary to prevent local recurrence and distant metastasis. However, the efficacy of additional treatments, such as neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (NAC), and lateral pelvic lymph node dissection (LPLND), has not been scrutinized. METHODS: Recurrence patterns were categorized into local recurrence and distant metastasis. Local recurrence was classified into two types: (1) pelvic cavity recurrence and (2) LPLN recurrence. First, we analyzed the risk factors for each recurrence pattern. Second, based on the status of clinically suspected involvement of circumferential resection margin (cCRM), the efficacy of additional treatments was investigated. RESULTS: A total of 240 patients was enrolled. nCRT was performed for 25 (10%), NAC was for 46 (19%), and LPLND was for 35 patients (15%). As the recurrence patterns, pelvic cavity recurrence occurred in 15 (6%), LPLN recurrence in 8 (3%), and distant metastasis in 42 patients (18%). Five-year overall survival and relapse-free survival were 87% and 70%, respectively. Multivariate analysis indicated that pelvic cavity recurrence was associated with cCRM status and tumor histology, that LPLN recurrence was with serum carcinoembryonic antigen level and LPLN swelling, and that distant metastasis was with clinical N category. In the cCRM-positive subgroup (n = 66), cumulative rate of pelvic cavity recurrence was lower in the nCRT group than in the NAC or non-NAC/nCRT group (P = 0.02 and 0.09, respectively). CONCLUSION: cCRM status was associated with pelvic cavity recurrence, and LPLN swelling was with LPLN recurrence. nCRT could reduce pelvic cavity recurrence in cCRM-positive subgroup.

Japanese clinical practice guidelines for sacrococcygeal teratoma, 2017.

BACKGROUND: Sacrococcygeal teratoma (SCT) is the most common extragonadal germ cell tumor in neonates and infants. Although most cases of infantile SCT are benign tumors by nature, some develop into extremely large lesions, leading to massive bleeding, high-output heart failure, disseminated intravascular coagulation, and even fatal outcomes during the neonatal period. In addition, some patients may present with tumor recurrence, malignant transformation, long-term sequelae (including bladder and bowel dysfunction) and lower leg palsy during the long-term follow up. SCT, however, is very rare, and there are few opportunities to encounter this disease, therefore general physicians without expert credentials currently lack information relevant to clinical practice. For this reason, the research project committee has compiled guidelines concerning SCT. METHODS: The purpose of these guidelines was to share information concerning the treatment and follow up of infantile SCT. The guidelines were developed using the methodologies in the Medical Information Network Distribution System. A comprehensive search of the English- and Japanese-language articles in PubMed and Ichu-Shi Web identified only case reports or case series, and the recommendations were developed through a process of informal consensus. RESULTS: The clinical questions addressed the risk factors, the efficacy of cesarean section, the initial devascularization of tumor feeding vessels, interventional radiology, recommended clinical studies for follow up and possible long-term complications. CONCLUSIONS: These are the first guidelines for SCT to be established in Japan, and they may have huge clinical value and significance in terms of developing therapeutic strategies and follow up, potentially contributing to the improvement of the prognosis and quality of life of SCT patients.

[A Case of Advanced Right Renal Pelvic Cancer with Left Supraclavicular Lymph Node Metastasis that Attained Long-Term Survival by Multidisciplinary Treatments].

A man in his 70s was referred to our hospital for further examination of a positive occult blood finding. Imaging studies showed that the patient had right renal pelvic cancer with interaortocaval, multiple paracaval and left supraclavicular lymph node metastases (cT3N2Ml). Induction chemotherapy was performed with 5 cycles of MEC (methotrexate/epirubicin/cisplatin) followed by 2 cycles of GT (gemcitabine/paclitaxel). After the combined chemotherapies, the residual lesions were the primary tumor in the right renal pelvis and the left supraclavicular lymph node. Right total nephroureterectomy combined with lymph node dissection of paraaortic, paracaval, and interaortocaval area and left cervical area were performed. Histopathologically the postoperative T stage of the primary tumor was determined as ypT3. As for lymph nodes dissected, an interaortocaval lymph node alone, but not the other nodes, contained viable cancer cells. Adjuvant chemotherapy was performed with 7 courses of GT therapy. The patient had intravesical recurrence once and received transurethral resection of bladder tumor followed by intravesical instillations of Bacillus Calmette-Guerin (BCG). Finally, the patient has been free from recurrence for 10 years after the final treatment.

Impact of para-aortic recurrence risk-guided intensity-modulated radiotherapy in locally advanced cervical cancer with positive pelvic lymph nodes.

OBJECTIVES: A previous study has suggested the benefit of sub-renal vein radiotherapy (SRVRT) for pelvic lymph node (PLN)-positive cervical cancer. In order to better select patients for SRVRT, this study aimed to evaluate the value of a risk-based radiation field based on PLN location and number in PLN-positive cervical cancer. METHODS: We reviewed 198 patients with FIGO stage IB2-IVA cervical cancer, positive PLNs, and negative para-aortic lymph nodes (PALNs) from 2004 to 2015 at two tertiary centers. All patients underwent pelvic radiotherapy (PRT) or SRVRT with IMRT. The SRVRT extended the PRT field cranially to the level of the left renal vein. The prescribed doses were 45-50.4Gy in 1.8Gy per fraction. RESULTS: Overall, 118 and 80 patients underwent PRT and SRVRT, respectively. The SRVRT group had more advanced disease based on FIGO stage, common iliac PLNs, and number of PLNs. The median follow-up was 63months (range: 7-151months). PALN failure was experienced by 28 patients (23.7%) in the PRT group and 1 patient (1.3%) in the SRVRT group (p<0.001). Compared with PRT, SRVRT significantly improved 5-year PALN recurrence-free survival (56.8% vs. 100%, p<0.001) and cancer-specific survival (56.5% vs. 93.9%, p<0.001) among patients with common iliac PLNs or ≥3 PLNs. No significant differences were observed in these outcomes among patients with PLNs below the common iliac bifurcation and 1-2 PLNs. The SRVRT did not increase severe toxicities. CONCLUSIONS: Risk-based radiation field based on PLN location and number could optimize outcomes for PLN-positive cervical cancer.

Lymphatic vessel diameter in female pelvic cancer-related lower extremity lymphedematous limbs.

BACKGROUND: Lymphaticovenular anastomosis (LVA) has become one of the useful surgical treatments for compression-refractory lower extremity lymphedema (LEL). It is important to anastomose larger lymphatic vessels with abundant lymph flows in LVA surgery. This study aimed to clarify factors associated with lymphatic vessel diameter. METHODS: One hundred thirty-four LEL patients who underwent pre-operative indocyanine green (ICG) lymphography and LVA from June 2009 to August 2014 in a single institution were included in this retrospective observational study. Clinical, ICG lymphography, and intraoperative findings were collected from medical charts. A lymphatic vessel with external diameters of 0.5 mm or larger was defined as a large lymphatic vessel (LLV). Independent factors associated with LLV were identified using logistic regression analysis. RESULTS: Nine hundred sixty-two lymphatic vessels were identified, among which 438 (45.5%) were LLVs. Independent factors associated with LLV were older age (odds ration [OR], 1.408; 95% confidence interval [CI], 1.026-1.931; P = 0.034), positive history of radiation (OR, 1.634; 95%CI 1.228-2.173; P = 0.001), incision site in the thigh/lower leg compared with in the groin (OR, 1.617/1.685; 95%CI 1.076-2.432/1.148-2.473; P = 0.021/0.008). Inverse associations were observed in S-region/D-region on ICG lymphography compared with L-region (OR, 0.537/0.048; 95%CI, 0.397-0.726/0.006-0.371; P < 0.001/0.004). CONCLUSIONS: D-region on ICG lymphography had the lowest OR to find LLV, representing that lymphatic vessels found in D-region on ICG lymphography would be significantly smaller than those in L-region. In LVA surgery, D-region should be avoided.

Neoadjuvant Chemotherapy Followed by Delayed Surgery: Is it Necessary for All Patients With Nonmetastatic High-Grade Pelvic Osteosarcoma?

BACKGROUND: Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy is the most-frequently employed strategy for patients with high-grade osteosarcoma. However, the contribution of neoadjuvant chemotherapy compared with postoperative adjuvant chemotherapy has not been tested rigorously in patients with nonmetastatic high-grade pelvic osteosarcoma. QUESTIONS/PURPOSES: (1) Does neoadjuvant chemotherapy followed by delayed surgery offer a survival benefit to patients with nonmetastatic high-grade pelvic osteosarcoma compared with immediate surgery and adjuvant chemotherapy? (2) Is the timing of chemotherapy and surgery associated with a difference in the survivorship free from local recurrence and the risk of complications? (3) Is the threshold of 90% necrosis after neoadjuvant chemotherapy appropriate to distinguish responders from nonresponders in patients with pelvic osteosarcoma? METHODS: Between 2000 and 2015, our center treated 112 patients with nonmetastatic high-grade primary pelvic osteosarcoma, of whom 93 underwent tumor resection with chemotherapy. Four patients (4%) were lost to followup before 24 months but were not known to have died; the remaining 89 patients were included in this retrospective study. Based on the timing of surgery and chemotherapy, patients were analyzed in two groups: (1) neoadjuvant chemotherapy followed by delayed surgery and adjuvant chemotherapy (n = 56; mean followup of 61 months, range 27-137 months), and (2) immediate surgery followed by adjuvant chemotherapy (n = 33; mean followup of 77 months, range 25-193 months). The total duration and intensity of chemotherapy was similar in both groups. During the period in question, we generally used neoadjuvant therapy followed by delayed surgery and adjuvant chemotherapy when patients received their biopsies in our center. We typically used immediate surgery with adjuvant chemotherapy when patients initially refused chemotherapy or when they had severe pain or poor walking function. Patients in the neoadjuvant chemotherapy group had a higher proportion of sacral infiltration; other factors such as sex, age and tumor size were well balanced between groups. We compared overall survival and local recurrence-free survival rates between the two groups. We completed univariate log-rank tests and multivariate Cox analyses in all patients to identify factors associated with survival and local recurrence using the Kaplan-Meier method. RESULTS: No survival benefit was found in the patients treated with neoadjuvant chemotherapy followed by delayed surgery compared with the group treated with immediate surgery and adjuvant chemotherapy. At 5 years, the overall survival (OS) was 42% (95% CI, 33-52) for all patients in this study, 43% (95% CI, 30-56) for the neoadjuvant group, and 40% (95% CI, 25-55) for the immediate surgery group; p = 0.709. With the numbers available, there was no difference in the likelihood of successful limb salvage (five of 56 patients [89%] in the neoadjuvant chemotherapy group versus three of 33 patients [91%] in the immediate surgery group; p = 0.557). The 5-year local recurrence-free survival was 67% (95% CI, 59-76) with no difference between the two groups (68%; 95% CI, 57-78% versus 67%; 95% CI, 52-81; p = 0.595). With the numbers available, there was no difference in survival between patients whose tumors demonstrated more than 90% necrosis; however, only four of 56 patients in the neoadjuvant chemotherapy group demonstrated 90% necrosis. CONCLUSIONS: We found no survival advantage with chemotherapy before surgery compared with immediate surgery in patients with nonmetastatic high-grade pelvic osteosarcoma. The decision on chemotherapy timing should be made for reasons other than survival. A prospective trial is needed to confirm this conclusion. LEVEL OF EVIDENCE: Level III, therapeutic study.

Does Extracorporeal Irradiation and Reimplantation After Acetabular Resections Result in Adequate Hip Function? A Preliminary Report.

BACKGROUND: Pelvic resections are challenging, and reconstruction of the resected acetabulum to restore mobility and stability is even more difficult. Extracorporeal radiation therapy (ECRT or extracorporeal irradiation) of autograft bone and reimplantation allows for a perfect size match and has been used with some success in the extremities. Although the risk of wound complications in pelvic surgery has discouraged surgeons from using ECRT of autografts in that anatomic site, we believe it may be a reasonable option. QUESTIONS/PURPOSES: In a small series, we asked: (1) What was the median surgical time and blood loss for these procedures, and what early complications were observed? (2) Is there evidence of osteonecrosis or cartilage loss at a minimum of 2 years after ECRT of acetabular autografts, and what functional scores were achieved? (3) What were the oncologic outcomes after ECRT? METHODS: Between March 2007 and September 2016, one surgeon performed 12 ECRT acetabular autografts and reimplantations after resections of pelvic or acetabular tumors. Of those, 10 with minimum 2-year followup are reported on here with respect to oncologic, functional, and radiographic assessment; all 12 are reported on for purposes of surgical parameters and early complications. During that period, we generally performed this approach when we judged it possible to achieve a tumor-free margin, adequate bone stock, and sufficient remaining hip musculature to allow use of the bone as an autograft with restoration of hip mobility. We generally did not use this approach when we anticipated a difficult resection with uncertain margins or where remaining bone was judged of poor strength for use as a graft or if both iliopsoas and abductors were sacrificed. Since 2010, this series represents seven of the 21 pelvic resections with reconstruction that we performed (five patients in this series had the procedure performed before 2010). Followup was at a median of 65 months (range, 33-114 months) for nine patients whose functional outcomes were evaluated. The median patient age was 30 years (range, 10-64 years). Clinical parameters were recorded from chart review; radiographic analysis for assessment of cartilage was performed by looking for any obvious loss of joint space when compared with the opposite side. Functional scoring was done using the Musculoskeletal Tumor Society score, which was obtained from chart review. Oncologic assessment was determined for local recurrence as well as metastases. RESULTS: Median surgical time was 8.6 hours and median blood loss was 2250 mL. There were no perioperative wound-related complications. Two patients underwent a second surgical procedure during the postoperative period, one for a femoral artery thrombus and another for a complete sciatic nerve deficit. No patients developed avascular necrosis of the femoral head. None of the patients who underwent osteoarticular grafting showed radiographic evidence of joint space narrowing. The median Musculoskeletal Tumor Society score was 28 (range, 17-30). No fractures in the radiated segment of reimplanted bone were seen in this small series. CONCLUSIONS: Results from this small series suggest that ECRT is a potential option in selected patients who have good bone stock and adequate soft tissue coverage. Although technically challenging, ECRT is a low-cost alternative to prostheses in providing a mobile and stable hip. Although we did not observe cartilage wear on plain radiographs, followup here was short term; it may appear as we continue to follow these patients. Future studies from retrieval specimens may shed light on the actual status of cartilage on the acetabulum. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Effectiveness of sacral nerve stimulation in fecal incontinence after multimodal oncologic treatment for pelvic malignancies: a multicenter study with 2-year follow-up.

BACKGROUND: To assess whether sacral nerve stimulation (SNS) is an effective treatment for severe fecal incontinence (FI) after radiotherapy (RT)/chemoRT (CRT) in combination with pelvic surgery. METHODS: A multicenter study was conducted on patients with FI that developed after multimodal therapy for pelvic tumors and was refractory to non-operative management, who were treated with SNS between November 2009 and November 2012. Data were prospectively collected and retrospectively analyzed. Cleveland Clinic FI score (CCFIS), FI episodes per week, FI Quality of Life (FIQoL), anorectal manometry and pudendal nerve terminal motor latency were evaluated before and after SNS. RESULTS: Eleven patients (seven females, mean age 67.3 ± 4.8 years) were evaluated in the study period. Multimodal treatments included surgery and CRT (four rectal, two cervical and one prostate cancers), surgery and RT (one cervical and two endometrial cancers) and CRT (one anal cancer). The mean radiation dose was 5.3 Gy, and mean interval between the end of RT and onset of FI was 43.7 ± 23 months. Before SNS, the mean CCFIS and the mean number of FI episodes per week were 15.7 ± 2.8 and 12.3 ± 4.2, respectively. At 12-month follow-up, mean CCFIS improved to 3.6 ± 1.8 (p = 0.003) and the mean number of FI episodes decreased to 2.0 ± 1.9 per week (p = 0.003). These results persisted at 24-month follow-up. Significant improvement was also observed for each of the four domains of FIQoL at 12- and 24-month follow-up. Anorectal manometry values did not change significantly at follow-up. CONCLUSIONS: SNS is feasible and may be an effective therapeutic option for FI after multimodal treatment of pelvic malignancies.