Search

BACKGROUND Little level 1 evidence exists to guide multimodality treatment in retroperitoneal soft tissue sarcoma (RPS), which may lead to significant variation in therapeutic approaches. This analysis aimed to describe national RPS treatment trends and explore potential variability among low-/high-volume hospitals (LVH/HVHs). PATIENTS AND METHODS In total, 5992 patients who underwent resection for primary RPS were retrospectively identified in the National Cancer Database (2004-2017). Time trend analyses examined rates of multivisceral resection (MVR), radiation, and chemotherapy use. LVHs were defined as those carrying out fewer than ten resections per year (N = 5433), whereas HVHs were defined as those carrying out ten or more (N = 559). Descriptive statistics and logistic regression models compared trends between groups. RESULTS MVR was more frequent at HVHs (63.7% versus 43.5%, p < 0.001). Use of radiation varied widely by hospital volume. HVHs more frequently employed preoperative radiation as compared with LVHs (14.7% versus 8.1%, p < 0.001). Throughout the study period, LVHs increased utilization of preoperative radiation (2.6% to 12.0%, p < 0.001) whereas rates at HVHs remained stable. Overall, LVHs utilized postoperative radiation significantly more frequently as compared with HVHs (14.7% versus 2.7%, respectively, p < 0.001). Postoperative radiation at LVHs remained stable until 2013 and sharply declined thereafter (16.7% to 6.9%, p < 0.001). Rates of postoperative radiation use at HVHs remained lower than those at LVHs at all time points. CONCLUSIONS Strategies for resection and radiation use at LVHs have trended towards those of HVHs. Current national implementation of preoperative radiation, MVR, and chemotherapy remains heterogeneous. These findings inform future trial design and support standardization of care.

Myxoid liposarcoma are responsive to radiotherapy, particularly preoperative radiotherapy. The outcome of the preoperative radiation is a decreasing tumor size and major necrotizing area. With a good local control, organ functions can survive without any amputation. Preoperative radiotherapy can be given with or without chemotherapy. Conventional fractionation such as 25 x 2 Gy or hypofractionation 5 x 5 Gy could be an effective way to treat preoperative myxoid liposarcoma.

Objective To determine the durability of ureteroneocystostomy as well as pre- or post-operative factors that may be associated with failure to provide appropriate renal drainage. Methods A total of 290 patients who underwent ureteral reimplantation to native bladder between 2003 and 2015 were identified. After excluding pediatric patients and those without any follow-up, 255 patients, 3 of whom had a subsequent contralateral reimplantation were included, for 258 observations. Kaplan-Meier method and univariate Cox models were used to assess whether factors such as radiation, prior abdominal surgery, age at re-implantation, gender and BMI are associated with re-implantation failure. Results Among 258 observations, there were 27 failures. Median follow-up time was 1.1 years from re-implantation surgery among patients without a failure.1 and 5-year ureteral re-implantation failure is 7% (95% CI 4%, 12%) and 22% (95% CI 15%, 33%), respectively. On univariate analysis, post-operative radiation was found to be strongly associated with poorer ureteral re-implantation survival (HR: 6.62; CI 2.40, 18.29; P = .0003) No significant association between re-implantation failure-free survival and age at reimplantation, gender, BMI, previous abdominal surgery, preoperative radiation and adjuvant radiation was noted (all P > .4). Conclusions Ureteroneocystotomy in the malignant setting has reasonable success rates through five years. No preoperative factors were associated with re-implantation failure. While all patients need to be followed due to increasing rates of failure with time, patients receiving palliative or salvage radiation therapy appear to be more prone to failure requiring further intervention.

Background: Wound complications after a soft-tissue sarcoma surgery are common, occurring in up to 30% to 40% of patients who undergo preoperative radiation therapy. Although risk factors for developing complications are well-known, there is a paucity of literature on the increased healthcare costs after a wound complication. The purpose of this study was to detail these additional costs after a soft-tissue sarcoma surgery. Methods: A retrospective review of 99 patients from January 2013 to October 2019 was performed. Hospital and professional charges for the primary surgical procedure and any subsequent hospitalization or procedure related to a wound complication were compiled. Costs were inflated to 2019 dollars. Results: Total costs were 21.3% higher for patients who developed a wound complication (P = 0.006). Most patients (32 of 42; 76.2%) who developed a complication required a return trip to the operating room. The average number of return trips was 1.2 (range 0 to 5). For each return trip to the operating room because of a wound complication, an associated increased overall cost of 13.2% was noted (P < 0.001). Conclusion: Wound complications after a soft-tissue sarcoma resection are common and add considerable expense to the episode of care. A reduction in wound complications may markedly decrease the cost of treating soft-tissue sarcomas and continues to be an opportunity for improvement.

Purpose Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT. Methods and Materials Between 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction. Results A total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted. Conclusions ESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink.

Introduction: Response to preoperative chemoradiation (PRTCT) for rectal cancer predicts the long-term outcome. Context: Tertiary care hospital. Aims: The aim is to study the factors affecting the response to chemoradiation. Settings and Design: Retrospective. Materials and Methods: Twenty-three patients of rectal cancer undergoing PRTCT followed by surgery and adjuvant chemotherapy were followed up for 20–56 months. Postoperative response, tumor downstaging and nodal downstaging were correlated with the disease status. Results: Tumor downstaging was seen in 11 (50%) and nodal downstaging in 12 (63.15%) patients. Nodal downstaging was statistically significant with P = 0.004. Pathological complete response (PCR) was seen in one patient and partial response (PR) in 17 patients. Thirteen (72.2% of patients) were alive and disease free and the negative nodal status correlated with long-term control with P = 0.04. Conclusion: Most patients of rectal cancer show PR to PRTCT, and the benefit is more for node-positive patients. Nodal PCR is associated with a higher chance of long-term disease control.

Purpose The purpose of this study was to reduce radiation exposure during pediatric central venous line (CVL) placement by implementing a radiation safety process including a radiation safety briefing and a job-instruction model with a preradiation time-out. Methods We reviewed records of all patients under 21 who underwent CVL placement in the operating room covering 22 months before the intervention through 10 months after 2013–2016. The intervention consisted of a radiation safety briefing by the surgeon to the intraoperative staff before each case and a radiation safety time-out. We measured and analyzed the dose area product (DAP), total radiation time pre- and postintervention, and the use of postprocedural chest radiograph. Results 100 patients with valid DAP measurements were identified for analysis (59 preintervention, 41 postintervention). Following implementation of the radiation safety process, there was a 79% decrease in median DAP (61.4 vs 13.1 rad*cm2, P Conclusion A preoperative radiation safety briefing and a radiation safety time-out supported by a job-instruction model were effective in significantly lowering the absorbed doses of radiation in children undergoing CVL insertion. Type of study Case–control study. Level of evidence Level III.

Introduction Chemo-radiotherapy (CRT) has increasingly been employed for the treatment of laryngeal cancer at T3 or higher rather than total laryngectomy (TL), in order to preserve the larynx. However, TL is still frequently performed in patients with advanced laryngeal cancer, especially T4 disease. When CRT is performed for advanced cancer, there is a certain rate of residual disease or relapse, and TL is conducted as salvage surgery for those patients, but TL following CRT is associated with a high incidence of postoperative complications. Objective The purpose of this study was to investigate the influence of preoperative radiation therapy on the occurrence of postoperative complications of TL, particularly pharyngocutaneous fistula (PCF). Methods We retrospectively investigated 142 patients who underwent TL for laryngeal cancer whether postoperative complications were related to a history of radiation therapy or neck dissection. Detailed investigation of the 32 patients who underwent radiation therapy was also conducted. Results PCF was significantly higher after radiation therapy. Neck dissection was not related. As the time from radiation therapy to TL decreased, the incidence rate of postoperative PCF increased and the time to closure became significantly longer. Preoperative laboratory tests did not show a significant difference in Hb and Alb, but the lymphocyte count was significantly lower in patients with PCF.

Introduction: This study aimed to establish the urologic complications of radical type C2 hysterectomy in cervical cancer patients with or without ureteral stenting. Methods: This prospective randomized study included 76 (100%) patients with clinically and pathologically established cervical cancer stages I and II treated with radical type C2 hysterectomy with pelvic lymph node dissection for the last 5 years (2014–2019). Patients were randomized into two groups (2:1 ratio): group II received perioperative ureteral stenting ( n = 24, 31.6%) and group I did not ( n = 52, 68.4%). Urologic complications observed during follow-up include intraoperative ureter and urinary bladder lesions and postoperative ureterovaginal and vesicovaginal fistulas. Results: Of the 52 patients in group I who underwent surgery for cervical cancer, urologic complications were observed in 8 (10.5%) patients, 2 (2.6%) of whom underwent preoperative radiation therapy. In group II, urologic complications were observed in 2 (2.6%) patients, of which 1 (1.3%) received preoperative radiation therapy. Intraoperative urologic complications in group I (6.6%) included 3 (3.9%) ureteral lesions cases and 2 (2.6%) cases of urinary bladder lesions, wherein 1 patient received preoperative radiation therapy. One case of (1.3%) urinary bladder lesion was observed in group II. Postoperative complications were observed in 3 patients (3.9%) in group I, including 2 (2.6%) ureterovaginal fistula cases, wherein 1 (1.3%) patient received preoperative radiation therapy, and 1 (1.3%) case of vesicovaginal fistula. In group II, 1 (1.3%) patient who received perioperative radiotherapy developed postoperative vesicovaginal fistula. Discussion: Urologic complications are extremely common during and after radical surgery (hysterectomy type C2) for cervical cancer. The cervical cancer stage had a significant effect on intra- and postoperative urologic complication rates in this study; however, no such effect was observed for preoperative radiation therapy and ureteral stenting, and significant differences were observed between the two study groups.

Liposarcomas are a common subfamily of soft tissue sarcoma with several subtypes recognized by the World Health Organization: atypical lipomatous tumors (ALT)/well-differentiated liposarcoma (WDLPS), dedifferentiated liposarcoma (DDLPS), myxoid liposarcoma (MLPS), pleomorphic liposarcoma (PLPS), and myxoid pleomorphic liposarcoma (MPLPS). Despite shared adipocytic features among liposarcomas, the clinical approach to each subtype differs based on histology, location, clinical behavior, and specific oncogenic drivers. In this review, we highlight subtype-specific molecular features with the potential to generate novel therapies. We discuss recent clinical trials investigating the use of preoperative radiation therapy for retroperitoneal liposarcoma, chemotherapy, small molecule inhibitors, and innovative immunotherapy approaches and describe how we incorporate these advancements into the management of liposarcoma.

BACKGROUND All intraoperative navigation systems need a referencing procedure prior to utilization, usually requiring an additional computed tomography (CT) or cone beam computed tomograph (CBCT) scan. As new techniques in the field of Computer-aided design / Computer-aided manufacturing (CAD/CAM) have evolved, it seemed favourable to develop a new referencing method not relying on additional CT or CBCT scans. METHODS A digital maxillary dental scan was used to create a referencing splint by CAD/CAM containing four reference points. By matching scanned dental model and initial trauma-CT, the splints position and thus the reference points were digitally simulated. These splints data were imported into the navigation system in Standard Tessellation Language (STL) format. These data were also 3D printed and the resulting piece was placed on the anatomical models' teeth. The methods accuracy was then assessed in vitro. CONCLUSION Our method for referencing of intraoperative navigation can be feasible to avoid an additional CT or CBCT prior to navigation.

The patient was a 45-year-old male who initially presented with a left hydrocele. During radiographic work-up, a 26 cm right retroperitoneal lipoma was incidentally discovered. Despite a recommendation for preoperative radiation therapy followed by surgery from the sarcoma multispecialty team, the patient opted for surgery alone, in the hopes of avoiding damage or loss of his right kidney. Following surgical excision of the 39 cm well-differentiated liposarcoma, with removal of the perinephric fat adjacent to the tumor thereby preserving the kidney, he was discharged home after two nights in the hospital. Follow-up imaging eight months later showed no recurrence.

Retroperitoneal sarcomas (RPSs) are rare diseases, and the 5-year overall survival rate remains low. Management of RPSs is challenging, and the quality of treatment strategy is a crucial prognostic factor. Treatment decisions and the treatment department to which the patients is referred must be centralized. Overall survival rate is positively correlated with the number of patients treated in the centers. En bloc surgery is the standard of care for effective treatment and potential for cure, whereas perioperative chemotherapy or radiotherapy has not yet been validated. Pre- or postoperative radiotherapy was considered controversial, but the STRASS trial publication illustrated that preoperative radiation could be useful in some conditions. Retroperitoneal liposarcoma might become a future target of prospective trials. Furthermore, some retrospective studies have shown that preoperative radiotherapy increases the rate of R0-R1 resections. This article reviews the role of external beam radiotherapy in the management of RPS and highlights the optimal volumes, doses, and radiotherapy techniques for the treatment of RPS. As accurately predicting prognosis in patients with RPS is challenging, we also emphasize the utility of nomograms in the field of radiotherapy. However, these nomograms do not include radiotherapy as a predictive factor. Although some authors could conclude that use of radiotherapy should be avoided based on the results of the STRASS trial, some data argue that radiotherapy still has utility in select cases.

For localized extremity soft tissue sarcoma (eSTS), treatment is individualized and each patient needs to be evaluated by a multidisciplinary team at a referral sarcoma center specialized in the care of sarcoma. For a majority of patients, treatment for eSTS involves limb-salvage surgery, with or without the addition of radiation therapy. Surgery should only be performed by surgeons specifically fellowship trained in the resection of eSTS. Surgery alone may be considered for small, low-grade, and superficial tumors as long a wide (≥ 2 cm) margin can be achieved. In cases where a less than wide negative margin can be achieved, radiation therapy should be utilized to facilitate a planned close margin resection to preserve critical structures (such as nerves, blood vessels, and bone) without a significant impact on oncologic outcomes. Soft tissue sarcomas are rare, and as such patients often present following an inadvertent excision. In these situations, we recommend preoperative radiation and wide tumor bed re-excision, as rates of residual tumor can be high in this scenario. While there is large amount of evidence to support the use of radiotherapy to enhance local tumor control, the evidence to support the use of chemotherapy to enhance local tumor control is lacking, and as such cannot be recommended for all patients.

Patients with rectal cancer in whom the mesorectal fascia is threatened by tumour are more likely than all patients with stage II/III disease to benefit from preoperative radiotherapy (RT). The objective of this study was to assess whether the status of the mesorectal fascia versus a stage II/III designation can best inform the use of preoperative RT in patients undergoing major rectal cancer resection.We reviewed the charts of consecutive patients with primary rectal cancer treated by a single surgeon at McMaster University, Hamilton, Ontario, between March 2006 and December 2012. The status of the mesorectal fascia was assessed by digital rectal examination, pelvic computed tomography and, when needed, pelvic magnetic resonance imaging (MRI). Patients whose mesorectal fascia was threatened or involved by tumour received preoperative RT. The study outcomes were rates of positive circumferential radial margin (CRM) and local tumour recurrence.A total of 153 patients were included, of whom 76 (49.7%) received preoperative RT because of concerns of a compromised mesorectal fascia. The median length of follow-up was 4.5 years. The number of CRM-positive cases in the RT and no-RT groups was 16 (22%) and 1 (1%), respectively (The status of the mesorectal fascia, not tumour stage, may best identify patients for preoperative RT.Plus que tous les patients présentant une maladie de stade II/III, les patients atteints d’un cancer du rectum dont le fascia mésorectal est menacé par la tumeur sont de bons candidats à la radiothérapie (RT) préopératoire. L’objectif de cette étude était d’évaluer ce qui, entre l’état du fascia mésorectal et une désignation de stade II/III, permet le mieux de confirmer le bien-fondé d’une RT préopératoire chez les patients qui doivent subir une résection majeure pour cancer du rectum.Nous avons passé en revue les dossiers de patients consécutifs atteints d’un cancer rectal primaire traités par un seul chirurgien à l’Université McMaster, à Hamilton, en Ontario, entre mars 2006 et décembre 2012. L’état du fascia mésorectal a été évalué par toucher rectal, tomodensitométrie pelvienne et, au besoin, imagerie par résonnance magnétique (IRM) pelvienne. Les patients dont le fascia mésorectal était menacé ou affecté par la tumeur ont reçu une RT préopératoire. Les paramètres de l’étude étaient : taux de positivité de la marge radiale circonférentielle (MRC) et récurrence de la tumeur locale.En tout, 153 patients ont été inclus, dont 76 (49,7 %) ont reçu une RT préopératoire en raison d’une atteinte du fascia mésorectal. La durée moyenne du suivi a été de 4,5 ans. Dans les groupes soumis et non soumis à la RT, les nombres de cas MRC-positifs ont été respectivement de 16 (22 %) et de 1 (1 %), (C’est l’état du fascia mésorectal et non le stade de la tumeur qui peut le mieux permettre d’identifier les candidats à une RT préopératoire.

Neoadjuvant therapy (NT) is increasingly utilized for patients with pancreatic ductal adenocarcinoma (PDAC) but the nationwide incidence and long-term prognosis of a pathologic complete response (pCR) remains poorly understood.Patients with localized PDAC and known cT and pT stage who received NT prior to pancreatectomy from 2004 to 2016 were identified using the National Cancer Database. The clinicopathologic characteristics and long-term outcomes of patients who did and did not experience a pCR were compared.Among 7,902 patients who underwent NT prior to pancreatectomy, 244 (3.1%) experienced a pCR while 7,658 (96.9%) did not. On multivariable regression, longer duration of NT (OR 1.20, 95% CI 1.14-1.27 per month) and use of preoperative radiation (OR 9.98, 95% CI 3.05-32.71) were independently associated with a pCR. Median overall survival (OS) was longer among patients who experienced a pCR (77 vs 26 months, p 0.001). On multivariate analysis, pCR was the strongest predictor of improved OS (HR 0.43, 95%CI 0.32-0.58, p 0.001).A pCR following NT for PDAC occurs infrequently but is associated with significantly improved OS. Better predictors of response and more effective preoperative regimens should be aggressively sought.

Background There are several therapeutic strategies for the management of resectable stage IIIA/N2 non‐small‐cell lung cancer (NSCLC) patients. However, the role of radiotherapy as a preoperative adjuvant therapy is unclear. Methods We retrospectively analyzed the data of stage IIIA/N2 NSCLC patients who either underwent preoperative radiation (PrORT), or did not undergo preoperative radiation, collected from the Surveillance, Epidemiology and End Results (SEER) database, between 2004 and 2013. The primary endpoints were cancer‐specific survival (CSS) and overall survival (OS). Results Ultimately, 493 patients treated with preoperative radiation and 2675 patients treated who were not treated with preoperative radiation, were included in the analysis. Overall, preoperative radiation was associated with a better CSS (HR: 1.427 [1.297‐1.572], P = 0.014) and OS (HR: 1.220 [1.131‐1.493], P = 0.002) than that observed in patients who did not undergo preoperative radiation. After PSM, preoperative radiation still showed advantage in both CSS and OS. Only age, T stage, and preoperative radiation remained independent prognostic factors for both OS and CSS. In the subgroup analysis, the advantages of preoperative radiotherapy were more pronounced in patients with stage T3 tumors and highly differentiated tumors. Conclusions Preoperative radiation may improve the outcomes of resectable IIIA/N2 NSCLC patients. In IIIA/N2 NSCLC patients, particularly with T3 and highly differentiated tumors, clinicians should boldly apply preoperative radiotherapy to improve the patients' survival.

BACKGROUND Although surgery remains the cornerstone of gastric cancer therapy, the use of radiation therapy (RT) is increasingly being employed to optimize outcomes. We sought to assess outcomes following use of RT for the treatment of gastric adenocarcinoma. METHODS Using the National Cancer Data Base (NCDB) from 1998 to 2012, all patients with resected gastric adenocarcinoma were identified. Patients were stratified into four groups based on preoperative therapy: RT alone, chemotherapy only, chemoradiotherapy (CRT), and no preoperative therapy. Overall survival was estimated using multivariate Cox proportional hazards model. Adjusted secondary outcomes include margin positivity, lymph node harvest, LOS, 30-day readmission and mortality. RESULTS A total of 10 019 patients met study criteria. In the unadjusted analysis, patients undergoing CRT compared to chemotherapy alone had fewer positive margins (7.9% vs 15.9%; P

Results of preoperative radiation therapy for 119 patients with resectable rectal T3-4N0-1M0 cancer were analyzed. 52 patients received a short-term course of the large-fraction radiation therapy and 67 patients received a prolonged course of chemoradiation therapy. The results demonstrated that the prolonged course reduced clinical signs of the disease twice as much as the short course, it reduced the tumor size and increased the distance to the anorectal line (p

BACKGROUND: The purpose of this study was to examine the cost differences between preoperative and postoperative placement of gastrostomy tubes (G-tubes) in patients with head and neck cancer. METHODS: We conducted a retrospective chart review of patients with aerodigestive tract cancers from 2010 to 2015. Data included inpatient and postdischarge costs, demographics, tumor characteristics, surgical treatment, length of stay (LOS), time spent in the intensive care unit (ICU), and readmissions. RESULTS: Five hundred ninety patients were included in this study. There was a $7624 inpatient cost savings (P = .002) for those G-tubes placed preoperatively ($26 060) versus postoperatively ($33 754). Postdischarge costs did not differ significantly between groups (P = .60). There was a $9248 total costs savings (P = .009) for those patients with G-tubes placed preoperatively ($39 751) versus postoperatively ($48 999), despite patients with preoperative G-tubes having lower body mass index (BMI; P = .009), higher Association of Anesthesiologist (ASA) class (P = .02), more preoperative radiation (P < .001), and more free tissue transfer reconstruction (P = .007). CONCLUSION: There is potential for savings by placing G-tubes preoperatively, possibly driven by decreased LOS, despite data suggesting that patients with G-tubes placed preoperatively are higher risk.

BACKGROUND Intrathoracic fistulas pose unique challenges for thoracic and reconstructive surgeons. To decrease the incidence of fistula recurrence, pedicled flaps have been suggested to buttress the repair site. The authors aimed to report their experience with muscle flap transposition for the management of intrathoracic fistulas. METHODS A retrospective review of all patients who underwent intrathoracic muscle flap transposition for the management of intrathoracic fistulas from 1990 to 2010 was conducted. Patient demographics, surgical characteristics, and complication rates were abstracted and analyzed. RESULTS A total of 198 patients were identified. Bronchopleural fistula was present in 156 of the patients (79 percent), and 48 had esophageal fistula (24 percent). A total of 238 flaps were used, constituting an average of 1.2 flaps per patient. After the initial fistula repair, bronchopleural fistula complicated the course of 34 patients (17 percent), and esophageal fistula occurred in 13 patients (7 percent). Partial flap loss was identified in 11 flaps (6 percent), and total flap loss occurred in four flaps (2 percent). Median follow-up was 27 months. At the last follow-up, 182 of the patients (92 percent) had no evidence of fistula, 175 (89 percent) achieved successful chest closure, and 164 (83 percent) had successful treatment. Preoperative radiation therapy and American Society of Anesthesiologists score of 4 or greater were identified as risk factors for unsuccessful treatment. CONCLUSIONS Intrathoracic fistulas remain a source of major morbidity and mortality. Reinforcement of the fistula closure with vascularized muscle flaps is a viable option for preventing dehiscence of the repair site and can be potentially life-saving. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.

Radiotherapy (RT) is one of the cornerstones in the current treatment paradigm for glioblastoma (GBM). However, little has changed in the management of GBM since the establishment of the current protocol in 2005, and the prognosis remains grim. Radioresistance is one of the hallmarks for treatment failure, and different therapeutic strategies are aimed at overcoming it. Among these strategies, nanomedicine has advantages over conventional tumor therapeutics, including improvements in drug delivery and enhanced antitumor properties. Radiosensitizing strategies using nanoparticles (NP) are actively under study and hold promise to improve the treatment response. We aim to describe the basis of nanomedicine for GBM treatment, current evidence in radiosensitization efforts using nanoparticles, and novel strategies, such as preoperative radiation, that could be synergized with nanoradiosensitizers.

11550 Background: RPS often have local recurrence (LR) after surgery. Preoperative radiation (RT) to 50.4 Gy can reduce LR risk but is not uniformly effective, especially after (+) margin resections. Therefore, we conducted a multi-institutional, prospective Phase II study to assess efficacy and tolerability of preop IMPT with selective dose escalation to 63 GyRBE to the posterior RPS margin (clinical target volume [CTV] 2) at high risk for (+) margins to further reduce the risk of LR. This dose was tolerable in a prior phase I study (DeLaney T et al, 2017, PMID:28740917). Methods: Primary RPS patients (pts) >18 years received preop IMPT, 50.4 GyRBE in 28 fractions (fx) of 1.8 GyRBE to CTV1 (tumor plus adjacent tissue at risk of subclinical disease) with SIB to CTV2 to 63.0 GyRBE in 28 fx of 2.25 GyRBE. Pts with high-grade tumors could get chemotherapy(CTX) prior to IMPT. To avoid treatment delay, 11 fx of IMRT x-rays could be substituted for IMPT. Pts had restaging and surgery 4-8 weeks after IMPT. Primary study endpoint was local tumor control. Secondary endpoints included clinical and pathologic response, surgical margin status, and disease-free and overall survival. Results: We accrued 60 pts from January 2016 to February 2021. Histology: 35 liposarcoma(LPS) (19 dediff and 16 well diff), 22 leiomyosarcoma(LMS), and 3 undifferentiated pleomorphic sarcoma. IMPT was delivered per protocol in all pts. 51 pts have had surgery, 5 are awaiting surgery, and 4 had no surgery due to metastases(DM) on preop imaging. 22 pts had (+) margins. 2 pts had > 75% necrosis. With 23-month median (range 1-52 months) follow-up after start of RT, there were two LRs. A dediff LPS pt had a well diff LPS LR 26 months postop, resected, and is disease-free. A renal vein/IVC LMS pt treated with CTX and IMPT had LR and DM 4 months postop and died from disease. Surgical Clavien-Dindo morbidity scores: 0(21), 1(9), 2(8), 3a (4), 3b(4), 4a(2), 4(b)1, 5(2); the periop deaths were from sepsis(pneumonia) and duodenal ulcer. The grade 3-4 periop morbidity included abscess(3), treated by catheter(2) or operative(1) drainage, prolonged hospital stays (2 pts with IVC LMS), small bowel obstruction (1), and late sigmoid colon anastomotic failure (1). Readmissions for lymphopenia(1), pneumoperitoneum (1), and volume overload (1). One late neuropathy was seen in a Type II diabetic pt with transient postop weakness after femoral nerve dissection who later had significant lower extremity weakness 3.75 years postop. Study was amended to reduce IMPT dose in diabetic pts. Conclusions: Preoperative IMPT with selective dose escalation to 63 GyRBE to the high risk posterior RPS margin is feasible. Early local control results with this approach appear promising. Some peri-operative morbidity was noted but appears to be in the expected range for RPS resections. Clinical trial information: NCT01659203.

BACKGROUND Nipple-areola complex malposition after nipple-sparing mastectomy can be a challenging issue to correct. The current literature is largely limited to smaller series and implant-based reconstructions. METHODS A retrospective review of all nipple-sparing mastectomies from 2006 to 2016 at a single institution was performed. Incidence, risk factors, and corrective techniques of nipple-areola complex malposition were analyzed. RESULTS One thousand thirty-seven cases of nipple-sparing mastectomy were identified, of which 77 (7.4 percent) underwent nipple-areola complex repositioning. All were performed in a delayed fashion. The most common techniques included crescentic periareolar excision [n = 25 (32.5 percent)] and directional skin excision [n = 10 (13.0 percent)]. Cases requiring nipple-areola complex repositioning were significantly more likely to have preoperative radiation therapy (p = 0.0008), a vertical or Wise pattern incision (p = 0.0157), autologous reconstruction (p = 0.0219), and minor mastectomy flap necrosis (p = 0.0462). Previous radiation therapy (OR, 3.6827; p = 0.0028), vertical radial mastectomy incisions (OR, 1.8218; p = 0.0202), and autologous reconstruction (OR, 1.77; p = 0.0053) were positive independent predictors of nipple-areola complex repositioning, whereas implant-based reconstruction (OR, 0.5552; p < 0.0001) was a negative independent predictor of repositioning. Body mass index (p = 0.7104) and adjuvant radiation therapy (p = 0.9536), among other variables, were not predictors of nipple-areola complex repositioning. CONCLUSIONS Nipple-areola complex malposition after nipple-sparing mastectomy can be successfully corrected with various techniques. Previous radiation therapy, vertical mastectomy incisions, and autologous reconstruction are independently predictive of nipple-areola complex malposition. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.