Preoperative External Beam Radiotherapy Research Articles

Neoadjuvant pazopanib with radiation therapy in patients with localized sarcoma: Experience from a sarcoma center.

e23555 Background: Tissue oxygenation is critical to the success of radiation therapy (RT) in any tumor type. However, tumor vasculature is abnormally structured and dysfunctional. Anti-angiogenic molecules have been shown to stabilize the intratumoral vascular structures and improve tissue oxygenation, which may aid in the success of RT. Pazopanib (PAZO) is a multi-kinase inhibitor targeting the Vascular Endothelial Growth Factor Receptor. Here, we report the pathologic outcome and clinical correlates of concurrent use of neoadjuvant PAZO and RT in our cohort of patients with localized soft-tissue sarcoma (STS). Methods: This is a retrospective, single institution study of patients diagnosed with localized STS between January 2019 and October 2023. Patients who received concurrent PAZO and pre-operative external beam RT (50 Gy in 25 fractions) were included. Patients with metastatic disease, unplanned resections, and those requiring excisional biopsy/curettage for diagnosis were excluded. The primary endpoint was the rate of major pathologic response (mPR) defined by > 90% necrosis on surgical pathology specimen. The secondary endpoint was local relapse-free survival (RFS), distant metastasis-free survival (DMFS), and local and distant relapse rate (RR) at 6 months. All-grade toxicities from PAZO were recorded. Results: Ten patients with a median age of 51 years (Interquartile range (IQR): 34-76) were included. Undifferentiated pleomorphic sarcoma was the most common histologic subtype (50% patients). Median follow up was 24.2 months (IQR: 11-36). Six patients tolerated the maximum dose of PAZO until RT completion (800mg PO daily). The dose of PAZO was reduced in 4 patients due to grade 3 GI toxicity and HTN. Nine patients stayed on PAZO until RT completion. The median time to surgery after RT was 42 days (IQR: 37-77). The median largest tumor dimension prior to RT was 11.65 cm (IQR: 3.8 to 18), and 10.6 cm (IQR: 5.4 to 19.7) after RT completion. Nine of 10 patients had R0 resection, and 7 (70%) had mPR. Three of 7 (43%) patients had complete necrosis. All patients with R0 resection have no local recurrence after a median follow-up of 23 months (IQR: 11-36). Median local RFS was 20 months (IQR: 5-32), and DMFS was 6 months (IQR: 1-32). The local RR at 6 months was 10%, and the distant RR at 6 months was 30%. No correlation was observed between mPR and DMFS. Conclusions: Historically, neoadjuvant RT alone induces a mPR in ~30% of patients with localized STS. In our cohort, neoadjuvant PAZO with RT achieved an mPR in 70% of patients. Although dose reduction and grade 3 toxicity were noted in the majority of patients, these were reversible after stopping PAZO. There was no correlation between mPR and DMFS. However, a short course of PAZO with RT may help achieve R0 margins, which is the strongest predictor of better local RFS. A randomized trial is warranted to help understand the true impact of neoadjuvant PAZO with RT.

Understanding the Role of Radio-Sensitizing Nanoparticles in Enhancing Pathologic Response in Soft Tissue Sarcomas

High-atomic-number (Z) nanoparticles produce a cascade of low-energy secondary electrons and characteristic X-rays when ionized by X-ray irradiation. These secondary particles deposit their energy in the vicinity of the nanoparticles and, provided that the latter are selectively accumulated within tumor cells, this results in increased DNA damage and tumor cell deaths. This study reviews the utilization of high-Z nanoparticles in the treatment of soft tissue sarcomas (STS). Both in vitro and in vivo experiments demonstrated that the dose is enhanced by approximately 1.2 when polyethelyne glycol (PEG)-modified gold nanoparticles, and from 1.4 to 1.8 when hafnium oxide nanoparticles (NBTXR3, Nanobiotix SA, France) are introduced into tumor cells and activated by X-ray beams. In a phase 2/3 clinical trial investigating the therapeutic benefit of using nanoparticles in preoperative external beam radiotherapy for locally advanced STS, the proportion of patients with a pathological complete response in their resected tumor was doubled when NBTXR3 nanoparticles were used. Additionally, a higher percentage of patients with complete tumor resection was observed in the NBTXR3 plus radiotherapy group. Similar toxicity profiles were found for both the NBTXR3 plus radiotherapy and the radiotherapy alone patient groups. The incorporation of radio-sensitizing nanoparticles in the preoperative radiotherapy of STS could enhance treatment outcomes.

Image-Guided Brachytherapy for Rectal Cancer: Reviewing the Past Two Decades of Clinical Investigation.

Simple SummaryWith the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy (HDREBT). The advantage of this treatment is allowing for better sparing of normal tissues surrounding the tumor during treatment while delivering higher dose to the tumor. This diminishes the number and severity of side effects and results in more effective treatment. This manuscript summarizes two decades of technological evolution and progress in clinical studies to validate this treatment concept from the pre-operative setting to prevent tumor recurrence and, more recently, the introduction of the objective of cure without surgery; i.e., non-operative management (NOM) for patients with curable rectal cancer. HDREBT is a conformed radiation modality, shown to be safe and efficient both in the pre-operative setting and is presently being explored with interest in NOM in a multicenter study.(1) Background: The introduction of total mesorectal excision (TME) for rectal cancer has led to improvement in local recurrence (LR) outcomes. Furthermore, the addition of preoperative external beam radiotherapy to TME reduces LR to less than 6%. As a trade-off to these gradual improvements in local therapies, the oncology community’s work is now focusing on mitigating treatment-related toxicities. In other words, if a small proportion of 4–6% of rectal cancer patients benefit from additional local therapy beyond TME, the burden of acute and long-term side effects must be considered with care. (2) Methods: With the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy. The treatment concept was tested in phase I and II studies: first in the pre-operative setting, and then as a boost after external beam radiation therapy, as a dose-escalation study, to achieve higher local tumor control. (3) Results: HDREBT is safe and effective in achieving a high tumor regression rate and was well tolerated in a phase II multicenter and two matched-pair studies. (4) Conclusions: HDREBT is a conformed radiation therapy that is safe and effective, and is presently explored in a phase III dose-escalation study in the NOM of patients with operable rectal cancer.

Long-term experience with intraoperative electron radiation therapy boost in extremity sarcoma.

In patients with extremity soft tissue sarcoma (eSTS), we describe outcomes of preoperative external beam radiation therapy (EBRT), limb-sparing surgery (LSS), and intraoperative electron radiation therapy (IOERT). One hundred and eighteen patients with eSTS treated between October 17, 2002 and July 28, 2021 were identified. EBRT was delivered preoperatively followed by LSS and IOERT. The median follow-up was 24.9 months. The presentation was primary in 102 (94%) patients and recurrent in 6 (6%) patients. Tumor location was lower extremity in 82 (76%) patients and upper extremity in 26 (24%) patients. Stage distribution was as follows: 3 (3%) IA, 24 (22%) IB, 31 (29%) II, 24 (22%) IIIA, and 25 (23%) IIIB. Final surgical margins were negative in 96 (89%) patients. The 5-year local control, failure-free survival, and overall survival were 94%, 75%, and 64%, respectively. Univariate analysis identified age >50, lower extremity, and higher grade as significant negative prognostic factors for overall survival. Grade 3 fracture or osteoradionecrosis requiring surgical fixation, neuropathy, and lymphedema occurred in 7 (6%), 1 (1%), and 0 patients, respectively. This study represents one of the largest series using preoperative EBRT, LSS, and IOERT for eSTS, with high local control and a low rate of late severe toxicity.

Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial

BackgroundSoft-tissue sarcomas (STS) in the extremities and trunk treated with standard-of-care preoperative external beam radiation therapy (EBRT) followed by surgical resection are associated with local and distant relapses. In preclinical...

Pathological responses to low-dose irradiation and Pepleomycin in Oral squamous cell carcinoma are predictive of Locoregional control

BackgroundThe prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence.MethodsWe retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3–4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato.ResultsEight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively.ConclusionsThe present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.

Intraoperative radiation therapy (IORT) for soft tissue sarcoma – ESTRO IORT Task Force/ACROP recommendations

PurposeTo describe guidelines for the use of intraoperative radiation therapy (IORT) in the treatment of soft-tissue sarcomas (STS). MethodsA panel of experts in the field performed a systematic literature review, supplemented their clinical experience and developed recommendations for the use of IORT in the treatment of STS. ResultsBased on the evidence from the systematic literature review and the clinical experience of the panel members, recommendations regarding patient selection, incorporation into multimodal treatment concepts and the IORT procedure itself are made. The rationale for IORT in extremity and retroperitoneal STS is summarized and results of the major series in terms of patient and treatment characteristics, oncological outcome and toxicity are presented. We define surgical factors, volumes for irradiation, technical requirements, dose prescription, recording and reporting, treatment delivery and care during the course of IORT covering the main IORT techniques used for the treatment of STS.In extremity STS, evidence originates from a few small prospective and mainly from retrospective single centre studies. Based on those reports, IORT containing-approaches result in very high local control rates with low rates of acute and late toxicity.In retroperitoneal sarcomas, evidence is derived from one prospective randomized trial, a few prospective and a large number of retrospective studies. The randomized trial compared IORT combined with moderate doses of postoperative external-beam radiation therapy (EBRT) to high-dose postoperative EBRT alone after gross total resection, clearly favouring the IORT-containing approach. These results have been confirmed by the prospective and retrospective studies, which similarly showed high local control rates with acceptable toxicity, mainly favouring combinations of preoperative EBRT and IORT. ConclusionsIORT-containing approaches result in high rates of local control with low to acceptable toxicity rates. Based on the available evidence, we made recommendations for the use of IORT in STS. Clinicians and researchers are encouraged to use these guidelines in clinical routine as well as in the design of future trials.

Initial Clinical Experience with Uni-Directional LDR Brachytherapy in the Treatment of Retroperitoneal Sarcoma

Retroperitoneal sarcomas (RPS)s constitute 10%-15% of patients diagnosed with soft tissue sarcomas. Despite advances in cancer care and aggressive management, the 5-year overall survival rate is 47%-67%. The crude cumulative incidence of local recurrence (LR) is 26%. A previous trial combining preoperative external beam radiation therapy with post-operative brachytherapy found substantial toxicity and treatment related death. This report demonstrates the utility of unidirectional LDR brachytherapy for treatment of RPS. In this study, the unidirectional device employed is a permanent, Pd-103 brachytherapy device designed to be implanted during surgical resection for the treatment of anticipated positive or close surgical margins. The device consists of a plane of sources with an unidirectional gold shield backing to protect normal tissues yet direct radiation to the target margin(s). The sources are embedded in a bio-absorbable matrix membrane that may be cut to size to allow for conformal targeting of the surgical tumor bed. At surgery, patients were assessed and determined to have close or positive margins. The prescribed LDR brachytherapy dose averaged 34.7 Gy (range: 20 – 60 Gy) and covered an average area of 6060 mm2 (∼58 sources). Pd-103 has a half-life of 16.99 days and delivers therapeutic radiation dose over several weeks. The device was attached with sutures and tacks. Seven RPS patients have been implanted with the CivaSheet at 4 medical centers. Six patients had recurrent sarcoma in the retroperitoneum or pelvic side wall. One patient had locally advanced leiomyosarcoma with no previous treatment. Three patients had prior EBRT at first diagnosis (45 – 57.5 Gy). Five patients received neoadjuvant EBRT (35 – 57.5 Gy) prior to surgery plus brachytherapy. The patients tolerated the implant well with no complications following surgery. There have been 0 reports of source movement in RPS patients. At median 15 months (8-24 months) follow-up, 0/7 patients have demonstrated local recurrence as defined as the targeted field of brachytherapy radiation. One patient (1/7) recurred outside of the surgical field and subsequent brachytherapy radiation. There were 0 reported incidences of acute or late radiation toxicity despite the surrounding organs at risk, inclusive of the small intestine, ureter and kidneys. Unidirectional, planar Pd-103 LDR brachytherapy has demonstrated a 100% local recurrence free survival with no acute or late-term toxicities at a median of 15 months in our patient cohort. Application of uni-directional, planar Pd-103 LDR brachytherapy technology is very safe and easy, and should be considered to escalate dose or retreat to the high risk margins of RPS after resection.

Preoperative radiotherapy in soft tissue sarcoma: from general guidelines to personalized medicine.

This critical review aims to generate hypotheses when to adhere to guidelines and when it could be considered to individualize management of extremity soft tissue sarcomas.Based upon peer-reviewed publications using a PubMed search on the MeSH headings "soft tissue sarcoma" AND "preoperative radiotherapy", data were compiled. Titles and abstracts screened for data including "fraction size AND/OR total dose AND/OR overall treatment time", "chemotherapy", "targeted agents AND/OR tyrosine kinase inhibitors", were screened as well as their respective reference. Furthermore, new data presented in abstract form at international sarcoma meetings have been included as well as relevant clinical trial information available at the ClinicalTrials.gov website. Generally accepted guidelines suggest applying preoperative external beam radiotherapy (RT), conventionally fractionated in 25-28 fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy in 5-6 weeks This regimen aims to increase the local control probability as compared to surgery alone. This regimen inflicts both acute and late toxicities. The reasons for and results of hypofractionated and/or reduced dose regimens are summarized and discussed. Finally, RT could be combined with conventional chemotherapy as well as targeted agents and data are summarized. Outside the setting of well-designed prospective clinical trials, the conventional 50 Gy in 5-6 weeks schedule should be considered as standard. However, in individual cases and based upon current and future studies alternative fraction size, total dose, overall treatment time and/or combination with chemotherapy or targeted agents may be considered in order to increase efficacy with reduced late morbidities.

Preoperative radiation and complication rates after double free flap reconstruction of head and neck cancer

IntroductionIn this study, we explore whether preoperative external beam radiation affects complication rates in patients that have undergone double simultaneous free tissue transfer for head and neck defects. Study design, setting, subjects and methodsApproval was obtained from the JPS Institutional Review Board. We performed a retrospective analysis of patients who underwent double free flap reconstruction of head and neck defects between August 1997 and April 2017. Minimum follow up was 6 months. Patients were grouped according to preoperative radiation status (XRT vs non-XRT). The chi-squared test was used for all comparisons. P-values and 95% confidence intervals (CI) were reported as (P, 95% CI). Results90 flaps were performed on 45 patients. The most common flap combination utilized was fibula plus radial forearm free flap (RFF) in 17 out of 45 patients. There were no statistically significant differences in frequency of flap failure (0.35, −15.9–20.1), wound infection (0.75, −22.1–19.3), hematoma (0.16, −5.3–36.7), or fistula formation (0.69, −22.5–24.6). There were also no statistically significant differences in cardiac complications (0.57, −10.3–28.2) and DVT (0.22, −12.4–25.3). ConclusionOur findings suggest that double free flap patients who had preoperative radiation are not more likely to have complications compared to non- radiated patients. Simultaneous double free flaps should be reserved for the most complex cases. Extensive discussion should be had with the patient about possible morbidity and mortality.

Volume of interest delineation techniques for 18F-FDG PET-CT scans during neoadjuvant extremity soft tissue sarcoma treatment in adults: a feasibility study

BackgroundThis study explores various volume of interest (VOI) delineation techniques for fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT) scans during neoadjuvant extremity soft tissue sarcoma (ESTS) treatment.ResultsDuring neoadjuvant treatment, hyperthermic isolated limb perfusion (HILP) and preoperative external beam radiotherapy (EBRT), 11 patients underwent three 18F-FDG PET-CT scans. The first scan was made prior to the HILP, the second after the HILP but prior to the start of the EBRT, and the third prior to surgical resection. An automatically drawn VOIauto, a manually drawn VOIman, and two gradient-based semi-automatically drawn VOIs (VOIgrad and VOIgrad+) were obtained. Maximum standardized uptake value (SUVmax), SUVpeak, SUVmean, metabolically active tumor volume (MATV), and total lesion glycolysis (TLG) were calculated from each VOI. The correlation and level of agreement between VOI delineation techniques was explored. Lastly, the changes in metabolic tumor activity were related to the histopathologic response. The strongest correlation and an acceptable level of agreement was found between the VOIman and the VOIgrad+ delineation techniques. A decline (VOIman) in SUVmax, SUVpeak, SUVmean, TLG, and MATV (all p < 0.05) was found between the three scans. A > 75% decline in TLG between scan 1 and scan 3 possibly identifies histopathologic response.ConclusionsThe VOIgrad+ delineation technique was identified as most reliable considering reproducibility when compared with the other VOI delineation techniques during the multimodality neoadjuvant treatment of locally advanced ESTS. A significant decline in metabolic tumor activity during the treatment was found. TLG deserves further exploration as predictor for histopathologic response after multimodality ESTS treatment.

Hyperthermic isolated limb perfusion, preoperative radiotherapy, and surgery (PRS) a new limb saving treatment strategy for locally advanced sarcomas.

This feasibility study presents the results of a new intensive treatment regimen for locally advanced extremity soft tissue sarcomas (ESTS), consisting of hyperthermic isolated limb perfusion (HILP), preoperative external beam radiotherapy (EBRT), and surgical resection. From 2011 to 2016, 11 high grade locally advanced ESTS patients underwent this treatment regimen. Preoperative EBRT (12 × 3 Gy) started <4 weeks following the HILP (TNF-α and melphalan) and the surgical resection was planned to take place <2 weeks following the end of the EBRT. All patients completed the treatment. After a median follow-up of 32 (23-50) months, the limb was saved in 10 patients (91%), 1 patient (9%) developed a local recurrence, 5 patients (45%) developed distant metastases, and 3 patients (27%) died of their disease. During follow-up two patients (18%) developed a pathologic fracture of the treated limb and three patients (27%) developed a major wound complication requiring surgical intervention. The median overall treatment time (OTT) was 56 (49-69) days. This intensive treatment regimen is feasible and safe in locally advanced ESTS, and it achieves oncological results that are comparable with conventional HILP treatment. In addition, the major wound complication risk is comparable and the OTT is reduced.

Identification of predictors for wound complications following preoperative or postoperative radiotherapy in extremity soft tissue sarcoma

IntroductionIn extremity soft tissue sarcoma (ESTS), external beam radiotherapy (EBRT) has been used in addition to limb-sparing surgery (LSS). This study aims to identify predictors for major wound complication (MWC) development following EBRT and LSS in ESTS. MethodsThis retrospective study includes ESTS patients treated with EBRT and LSS between 2005 and 2017. Two groups were formed; Group I included preoperatively irradiated patients, whereas Group II included patients who underwent postoperative EBRT. Multivariate logistic regression analyses were performed to create a prediction model for MWC development. ResultsOne hundred twenty-seven patients were included, 58 patients (45.7%) in Group I and 69 patients (54.3%) in Group II. Some differences in baseline characteristics were found between the groups, e.g. in tumor size and grade, histological subtype and total RT dose. Twenty-three patients (39.7%) in Group I and 14 patients (20.3%) in Group II developed a MWC (p = 0.02). Preoperative EBRT was identified as independent predictor for MWC development, OR 2.75 (95%CI 1.21–6.26), p = 0.02. Furthermore, a trend towards an increased MWC risk was shown for patients' age (OR 1.02 (0.99–1.04)), delayed wound closure (OR 3.20 (0.64–16.02)) and negative surgical margins (OR 2.26 (0.72–7.11)). The area under the curve (AUC) of the model was 0.68 (0.57–0.79). ConclusionsThis study corroborates the increased MWC risk following preoperative EBRT in ESTS. It remains important to carefully weigh the MWC risk against the expected long-term functional outcome, and to consider the liberal use of primary plastic surgical reconstructions in an individualized multidisciplinary tumor board prior to treatment.

External Beam Radiation Therapy for Resectable Soft Tissue Sarcoma: A Systematic Review and Meta-Analysis.

The aim of this study was to evaluate the role of preoperative and postoperative external beam radiation therapy (EBRT) in the treatment of resectable soft tissue sarcomas (STSs) of different tumor locations. A systematic literature search was performed to identify studies investigating the effects of EBRT (versus no EBRT) on local recurrence (LR) and overall survival (OS) or comparing different EBRT sequences. Random effects meta-analyses were calculated and presented as cumulative odds ratios (ORs). Sixteen studies (n=3958 patients) comparing EBRT versus no EBRT, including one randomized controlled trial (RCT) in extremity sarcoma, were analyzed. EBRT appeared to reduce LR in both retroperitoneal tumors (OR 0.47, p<0.0001) and other locations (OR 0.49, p=0.001). OS was improved by EBRT in retroperitoneal STSs (OR 0.37, p<0.0001) but not in other tumor locations. Eleven studies (n=2140), including one RCT, compared preoperative and postoperative radiotherapy. LR was less frequent following preoperative EBRT in retroperitoneal STSs (OR 0.03, p=0.02), as well as in other tumor locations (OR 0.67, p=0.01), while wound complications in extremity sarcoma were more frequent following preoperative EBRT (OR 2.92, p<0.0001). Several studies included in this meta-analysis bear a high risk of bias and no RCT has been published for retroperitoneal STS. This meta-analysis supports the use of EBRT for local tumor control in patients with resectable STSs. Based on a small number of non-randomized studies, a positive effect on OS may exist in the subgroup of retroperitoneal STSs.

First-in-Human Study Testing a New Radioenhancer Using Nanoparticles (NBTXR3) Activated by Radiation Therapy in Patients with Locally Advanced Soft Tissue Sarcomas

Purpose: This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS).Experimental Design: Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks). Surgery was performed 6 to 8 weeks after EBRT completion.Results: Twenty-two patients completed NBTXR3 injection, EBRT, and surgery and were followed for a median 22 months (range, 6-40). At NBTXR3 20% of TV, two dose-limiting toxicities occurred: injection-site pain and postoperative scar necrosis. The RD was defined as 10%. No leakage of NBTXR3 into surrounding tissues occurred; intratumor NBTXR3 levels were maintained during radiotherapy. At the RD, median tumor shrinkage was 40% (range 71% shrinkage, 22% increase); median percentage of residual viable tumor cells was 26% (range, 10%-90%). Patients receiving 20% of TV demonstrated pathologic complete responses. Seven grade 3 adverse events occurred, which were reversible.Conclusions: A single intratumoral injection of NBTXR3 at 10% of TV with preoperative EBRT was technically feasible with manageable toxicity; clinical activity was observed. Clin Cancer Res; 23(4); 908-17. ©2016 AACR.

Clinical outcome of interstitial pulsed dose rate brachytherapy in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of incomplete microscopic resection

Objective: To evaluate the role of interstitial pulsed dose rate brachytherapy (PDR-BT) in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of microscopic incomplete resection (R1).Methods and material: A total of 73 consecutive patients (recurrent/primary: 40/33) were treated with PDR-BT between 2001 and 2010. Patients received preoperative external beam radiotherapy (EBRT) and concomitant chemotherapy. Following resection of the tumor and the involved pelvic organs, a median of four (3–8) catheters were sutured to the tumor bed with a distance of approximately 1 cm between the catheters. A target respecting the catheters with a margin of 5 mm was contoured on computed tomography (CT) and three-dimensional (3D) dose planning with a planning aim for BT of D90 > 30 Gy, (0.6 Gy/pulse, 1 pulse/h) was performed. Previously irradiated patients (27%) underwent surgery that was directly followed by PDR-BT. Postoperative EBRT was then applied to the tumor bed 3–5 weeks after PDR-BT.Results: A total of 23 patients (31%) received a radical resection (R0) and 45 patients (62%) received an R1 resection. Five patients (7%) received a macroscopic incomplete resection (R2). The five-year overall survival was 33%. Local control at five years was 67% for patients who received a R0 resection and 32% for patients who received an R1 resection. The five-year actuarial risk of a grade 3–4 BT-related complication was 5%.Conclusions: Meaningful disease control and survival can be obtained at an acceptable rate of late morbidity in selected patients with locally advanced primary and recurrent rectal or sigmoid cancer using (chemo) RT, extensive surgery and PDR-BT when a high risk of an R1 resection is expected.

Patterns of major wound complications following multidisciplinary therapy for lower extremity soft tissue sarcoma.

The purpose of this study was to determine the pattern and timing of major wound complications (MWCs) in patients at our institution who received multimodality treatment for lower extremity soft tissue sarcoma (LE-STS) and to evaluate the impact of MWCs on tumor control and patient outcomes. The medical records of 102 LE-STS patients treated with limb-sparing surgery and radiation therapy were reviewed. MWCs were defined as secondary operations with anesthesia, seroma/hematoma aspiration, admission for IV antibiotics, or persistent deep packing. MWCs occurred in 22% of patients, with 45% of events occurring >120 days after resection. On multivariate analysis, preoperative external beam radiation therapy (EBRT) (OR 4.29, 95% CI 1.06-17.40, P = 0.042) and skin graft placement (OR 6.39, 95% CI 1.37-29.84, P = 0.018) were found to be independent predictors of MWCs. MWC occurrence did not predict for chronic toxicity and did not impact tumor control or survival. A considerable proportion of MWCs occur >120 days from surgical resection with preoperative EBRT and skin graft placement independent predictors for MWCs. While an additional source of morbidity, MWC occurrence did not impact tumor control, nor did it predict for chronic toxicity. J. Surg. Oncol. 2016;114:385-391. © 2016 Wiley Periodicals, Inc.

Outcomes of Iatrogenic Genitourinary Injuries During Colorectal Surgery

To describe, categorize, and determine the outcomes of repairs of genitourinary (GU) injuries that occur during colorectal surgery. Presently, little is known regarding these injuries or the long-term outcomes of their repair. We performed a retrospective review of patients undergoing colorectal surgery between 2003 and 2013 who experienced iatrogenic GU injuries requiring surgical repair. GU repair failures were defined as development of urine leak, urinary fistula, or anastomotic stricture requiring secondary GU intervention. Possible risk factors associated with repair failures were examined and included age, American Society of Anesthesiology score, comorbidities, type of colorectal surgery, radiation, and chemotherapy. Of 42,570 colorectal surgeries performed, 75 GU injuries were identified (0.18%). Mean age was 57.5years (range, 22-91), and median follow-up was 19.5months (range, 1-128). Fifty-nine (59/75, 79%) patients required a single GU repair whereas 16 of 75 (21%) patients experienced repair failure requiring additional GU intervention. The most common GU injuries were cystotomy (26/75, 35%), incomplete ureteral transection (22/75, 29%), complete proximal and distal ureteral injuries (13/75, 17%; 11/75, 15%), urethral injury (2/75, 3%), and injury to a pre-existing ileal conduit (1/75, 1). Twenty-seven patients (36%) had prior radiation and 35 patients (47%) had prior chemotherapy. Preoperative radiation and chemotherapy were both associated with failure of the GU repair (P=.003; P=.013). Delayed repair of the GU injury was also associated with repair failure (P=.001). Iatrogenic GU injuries during colorectal surgery are rare, affecting only 0.18% of colorectal procedures. Preoperative external beam radiation therapy/chemotherapy and delayed GU repair are associated with worse outcomes of repairs of these injuries.

Neoadjuvant chemotherapy in 13 patients with locally advanced poorly differentiated thyroid carcinoma based on Turin proposal - a single institution experience.

BackgroundThere is a paradigm that chemotherapy is ineffective in thyroid carcinoma. The aim of our study was to find out whether neoadjuvant chemotherapy before thyroid surgery had an effect on the size of primary tumour in patients with poorly differentiated thyroid carcinoma (PDTC) based on Turin proposal.Patients and methods.Altogether, 13 patients (8 women, 5 men; median age 61 years) with PDTC based on Turin proposal were treated with neoadjuvant chemotherapy between 1986 and 2005. Tumour diameter was from 4.5 to 18 cm (median 9 cm). Regional and distant metastases were detected in 6 and 9 patients, respectively. Eight patients had pT4 tumour.ResultsAltogether, 29 (range 1–5) cycles of chemotherapy were given. Tumour diameter decreased in all the patients and by more than 30% in 5 patients (= 38%). Two of these five patients had also preoperative external beam irradiation (EBRT). Total thyroidectomy, lobectomy and neck dissection were performed in 10, 3 and 5 cases, respectively. R0 and R1 resection was done in 5 and 8 cases, respectively. Eight patients had postoperative EBRT of the neck and upper mediastinum. The 5-year and 10-year cause-specific survival rates of patients were 66% and 20%, respectively.ConclusionsAfter neoadjuvant chemotherapy a partial tumour regression was observed in 38% of patients with PDTC based on Turin proposal.

Management of Unplanned Excision for Soft-Tissue Sarcoma With Preoperative Radiotherapy Followed by Definitive Resection.

The purpose of this study was to review the outcomes after preoperative radiotherapy and definitive surgery for patients who initially had inadvertent excision for sarcoma. Treatment records of 44 consecutive patients, who initially underwent unplanned excision of soft-tissue sarcoma between January 2004 and January 2012, were reviewed. All patients had clinically localized disease before treatment and received preoperative external-beam radiotherapy followed by definitive oncologic surgery at our institution. The median follow-up was 36 months. Residual tumor after preoperative radiotherapy and wound bed excision was identified in 39% (17/44) of the cases. Kaplan-Meier estimates for 5-year local control, recurrence-free survival, and overall survival are 95% (95% confidence interval [CI], 80-99), 86% (95% CI, 69-94), and 94% (95% CI, 79-99) respectively. Perioperative morbidity occurred in 25% of patients (11/44.) All patients with perioperative wound complications had lower extremity sarcomas. Optimal management for unplanned excision of soft-tissue sarcoma is unknown. Our institution has adopted the approach of preoperative radiotherapy, followed by definitive surgery. In our series of 44 patients, local control was excellent at 95%, with perioperative complications seen only in patients with lower extremity sarcomas, suggesting that this is a reasonable approach to manage inadvertently resected sarcoma.