Reduction In Local Recurrence Research Articles

Abstract PO3-02-06: Predictive Factors for adjuvant radiation use in patients >70 years with pT1N0 HR+ breast cancers

Abstract Introduction: In 2004 the CALGB 9343 study reported that women >70 years of age with pT1NO hormone receptor positive breast cancer received no meaningful benefit from breast irradiation following lumpectomy. Although there was a modest reduction in local recurrence, there was no improvement in rates of mastectomy for local recurrence, distant metastases, 5-year overall survival (OS) and breast cancer specific survival therefore concluding that it was reasonable to omit radiation therapy in this group. An update of the CALGB 9343 study in 2013 with 10-year follow-up came to the same conclusion. Previous analysis of the National Cancer Database (NCDB) and the SEER database showed, however, that the majority of women with these characteristics were still receiving radiation therapy. We conducted this retrospective analysis from NCDB to identify factors associated with the use of radiation in this population. Methods: We reviewed the NCDB database and collected records of all breast cancer patients aged >70 years, who had hormone positive (HR+), pT1N0 disease between the years of 2004-2019. They were separated into radiation and non-radiation cohorts and then stratified based on ethnicity, age groups, insurance status, income quartiles, education quartiles, areas of residence, tumor size, comorbidities, diagnosis to treatment time, treatment facility type and geographic location. We then compared mortality between the two cohorts and completed a multivariate analysis to determine the demographic and clinical factors associated with the likelihood of receiving radiation. SAS was used for analysis and p-value < 0.05 was deemed as statistically significant. Results: 147,611 patients met the criteria of age > 70, pT1N0, HR+ treated with surgical lumpectomy. The majority of them were white, aged 70-75y, had Medicare, were in higher education and income quartiles and lived in metro areas (Table 1). 57.9% of the total study population received radiation. The possibility of receiving radiation decreased as age increased beyond 75 years. Uninsured patients, Medicare patients, those with comorbities, higher educational status as well as those who lived 20+ miles away from their treatment facility and treated at urban centers in central or south Atlantic areas were less likely to receive radiation. Those treated at Comprehensive community cancer programs and middle Atlantic areas were more likely to receive radiation. The possibility of radiation also progressively increased with tumor size. However, there were no differences observed when stratified by race, income status or chemotherapy use (Table 2). We also noted a small overall survival advantage for the radiation cohort (HR 0.77, p-value < 0.0001) which could be explained by the fact that patients without comorbidities were more likely to receive radiation. Discussion: Our results provide a real-world estimate of radiation use in pT1N0 HR+ early-stage breast cancer in women > 70 years. The major predictors of radiation use included younger age, low co-morbidities, insurance and institutions providing care. Lack of awareness about recent updates or concern about local recurrence could be contributing to the continued use of radiation. Although there are minor differences when stratified by demographics, it is concerning that the overall trend of radiation use has not significantly decreased over time. Since there is currently no data to support the routine use of radiation in this patient group as evidenced by randomized controlled trials, it is prudent to avoid radiation. This approach would help reduce healthcare costs, patient inconvenience and associated morbidity. Table 1 Baseline characteristics Table 2 Factors affecting radiation use Citation Format: Suma Sri Chennapragada, Runhua Shi, Shivani Sharma, Gary Burton. Predictive Factors for adjuvant radiation use in patients >70 years with pT1N0 HR+ breast cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-06.

Metastatic intradural primary spinal osteosarcoma: illustrative case.

Osteosarcomas are a common primary bone neoplasm among adolescents but represent 0.2% of all malignancies with an incidence of two to four cases per million persons annually worldwide. Although known to have significant metastatic potential, its rare incidence, treatment resistance, and poor prognosis have rendered it a poorly understood and infrequently documented pathology. Herein the authors present the first documented case of lumbosacral intradural metastasis of a primary osteosarcoma in a young patient, possibly via intradural dissemination following pinhole durotomy in a prior thoracic surgery. Osteosarcomas remain a difficult pathology to treat, particularly upon metastatic dissemination. The utility of adjuvant radiotherapy after resection of an osteosarcoma is increasingly evident in the reduction of local recurrence. In the context of intraoperative pinhole durotomies in resections of high-grade lesions, due consideration should be given to whole-spine radiation, although this remains an evidence-free zone.

Radial resection margin distinguishes between superficial versus deep resection in colorectal cancer: a retrospective study.

Randomized studies showed that robotic surgery was short-term useful and safe for cancer patients. We investigated whether robots improve deep resection margins or superficial resection margins for radial resection margins in terms of short-term results. From an institutional database, we selected all superficial groups (≤ 3mm) and deeper groups (≥ 4mm) with rectal cancer treated with resection for a year. We evaluated the short-term post-operative 90-day outcomes on a radial resection size-based margin differentiation, including the first bowel movement, length of hospital stay, sepsis, and harvested lymph node. The main results were grades III-IV on the Clavien-Dindo scale and complications. We found 120 patients who had oncologic resection of rectal cancer; 42 patients with a superficial radial resection margin of ≤ 3 mm, all the following outcomes improved: the harvested lymph node, proximal resection margin, TME, flatus time, liquid diet duration, anastomotic leakage, and sepsis. Among these advantages were a reduced risk of metastasis and an overall reduction in local recurrence.

Intra-operative radiation for pancreatic cancer: Initial experience at the Hadassah Medical Center.

634 Background: Prognosis following surgery for pancreatic cancer (PC) remains poor. Local recurrence is common and negatively impacts survival rate. In an effort to improve local control and potentially improve survival, we have adopted a strategy of adding intra-operative electron radiation therapy (IOeRT) to selected patients undergoing pancreatic resection (PR) for PC. Here we report our initial experience with this treatment modality. Methods: 14 patients (10 male, 4 female), age between 44 - 81 years (mean 66.17), who underwent PR (Head 7, Body7) between 1/2021-1/2023 were included in this analysis. Patients selected for IOeRT included patients that according to surgeon assessment were at risk not to achieve satisfactory resection margins by surgery alone. All had resectable or borderline resectable disease according to standard criteria. 8 patients underwent pre-op chemotherapy followed by stereotactic body radiotherapy (SBRT) to a dose of 25-40 Gy in 5 fractions to the tumor and regional lymphatics followed by PR (5 Whipple, 3 distal pancreatectomy) and IOeRT, 3 patients received preop SBRT followed by PR (3 distal pancreatectomy) + IOeRT, 2 patients underwent PR (whipple 1, distal pancreatectomy 1) + IoeRT, and 1 received neoadjuvant chemotherapy followed by SBRT only and did not undergo surgery due to tumor progression. Immediately following resection, mobile IOeRT accelerator using a 40-80mm applicator with a level of 0-15 degrees was directed at the tumor bed deemed at high risk for recurrence. 10-20 Gy was delivered using 6-8 MeV electrons to the 90% isodose line at the discretion of the treating radiation oncologist. Data including serial imaging, genomic analysis, radiation protocol, complications, pathological results and outcome was collected for analysis. Results: Mean follow up was 9.7 months (2-21). 8 patients are alive: 7 pts with no evidence of disease and 1 pt with liver metastases. 6 patients died: 4 with distant metastatic disease, 1 from disease progression prior to surgery and 1 from early post-op sepsis. Negative surgical margins were achieved in 10 patients of which 2 mutated BRCA gene carriers showed complete pathological response (both who received combined neoadjuvant chemotherapy followed by SBRT). Post-operative complications possibly attributed to RT included hepatic artery occlusion (1 pt), portal vein stenosis (1 pt) and prolonged GI tract dysfunction (1pt). Conclusions: Combining RT with resection appears feasible and safe. Our data possibly show a reduction in local recurrence following resection of PC, however, longer follow up is necessary. Refinements in patient selection and treatment protocol may further improve outcomes. Larger scale studies are required to determine the benefit of this modality.

Hybrid Argon Plasma Coagulation for Barrett's Esophagus and for Colonic Mucosal Resection-A Systematic Review and Meta-Analysis.

Hybrid argon plasma coagulation (hAPC) is a novel technique that combines conventional argon plasma coagulation and waterjet submucosal expansion. The aims of this metanalysis were to evaluate the efficacy and safety of hAPC in the setting of Barret's esophagus (BE) ablation and as an adjunct to colonic endoscopic mucosal resection (EMR). Four electronic databases were searched, and the results were analyzed by two independent authors. Random-effects meta-analyses of the proportions of endoscopic and histologic remission (for BE), recurrence, and post-procedure adverse events were performed using R. Studies' reporting quality was also assessed. From the 979 identified records, 13 studies were included (10 regarding BE and three colonic EMR). The pooled percentages of endoscopic and histologic remission after hAPC for BE were 95% (95% confidence interval [CI] 91-99, I2 = 34) and 90% (95%CI 84-95, I2 = 46), respectively, while major adverse events and recurrence were registered in 2% (95%CI 0-5, I2 = 41) and 11% (95%CI 2-27, I2 = 11), respectively. Concerning hAPC-assisted EMR, the pooled percentages of major adverse events and recurrence were 5% (95%CI 2-10, I2 = 0) and 1% (95%CI 0-3, I2 = 40). Evidence suggests that the main advantages of hAPC are the increase in safety in the setting of BE ablation and the reduction of local recurrence after colonic EMR. Trials comparing hAPC with standard strategies are required to support its use for these indications.

Lentigo maligna (melanoma): A systematic review and meta-analysis on surgical techniques and presurgical mapping by reflectance confocal microscopy.

Because of an increased risk of local recurrence following surgical treatment of lentigo maligna (melanoma) (LM/LMM), the optimal surgical technique is still a matter of debate. We aimed to evaluate the effect of different surgical techniques and reflectance confocal microscopy (RCM) on local recurrence and survival outcomes. We searched MEDLINE, Embase and PubMed databases through 20 May 2022. Randomized and observational studies with ≥10 lesions were eligible for inclusion. Bias assessment was performed using the Methodological Index for Non-Randomized Studies instrument. Meta-analysis was performed for local recurrence, as there were insufficient events for the other clinical outcomes. We included 41 studies with 5059 LM and 1271 LMM. Surgical techniques included wide local excision (WLE) (n=1355), staged excision (n=2442) and Mohs' micrographic surgery (MMS) (n=2909). Six studies included RCM. The guideline-recommended margin was insufficient in 21.6%-44.6% of LM/LMM. Local recurrence rate was lowest for patients treated by MMS combined with immunohistochemistry (<1%; 95% CI, 0.3%-1.9%), and highest for WLE (13%; 95% CI, 7.2%-21.6%). The mean follow-up varied from 27 to 63 months depending on surgical technique with moderate to high heterogeneity for MMS and WLE. Handheld-RCM decreased both the rate of positive histological margins (p < 0.0001) and necessary surgical stages (p < 0.0001). The majority of regional (17/25) and distant (34/43) recurrences occurred in patients treated by WLE. Melanoma-associated mortality was low (1.5%; 32/2107), and more patients died due to unrelated causes (6.7%; 107/1608). This systematic review shows a clear reduction in local recurrences using microscopically controlled surgical techniques over WLE. The use of HH-RCM showed a trend in the reduction in incomplete resections and local recurrences even when used with WLE. Due to selection bias, heterogeneity, low prevalence of stage III/IV disease and limited survival data, it was not possible to determine the effect of the different surgical techniques on survival outcomes.

Feasibility Study on the nIORT® Adjuvant Treatment of Glioblastoma Multiforme through the Irradiation Field of Fast Neutrons Produced by a Compact Generator

The glioblastoma multiforme (GBM) is the most malignant glial brain tumour with average survival time of 6÷18 months. Emerging evidence suggests that GBM cells appears to reprogram their tumour microenvironment, which is a highly heterogeneous and complex system, so that an efficient GBM radiotherapy (RT) should cover both the cells of the GBM and those of its microenvironment. Relying on a 5-year collaborative research study on the intra-operative radiotherapy (IORT) with fast neutrons - the so-called neutron-IORT (nIORT®) technique - the authors think that this objective could be achieved by using an ionizing radiation field of fast neutrons that behave in the biological tissues as a “foam field” hitting both the GBM cancer cells and the neighbouring microenvironment. The nIORT® research activities - conducted by TheranostiCentre Srl, Berkion Technology LLC and ENEA - led to the fabrication of the first prototype of a compact neutron generator (CNG) that, through the deuterium-deuterium fusion reaction, produces neutrons of 2.45 MeV energy having: i) high linear energy transfer; ii) very high relative biological effectiveness (RBE), about 16 times higher than X-rays (and electrons) used in standard RT and IORT treatments; iii) reduced oxygen enhancement ratio, and hence resulting be very effective in cancer cells necrosis and apoptosis. The CNG is self-shielded, limited in size and weight (~120 kg) and manageable remotely by a robotic arm. A new prototype equipped by a cylindrical applicator to be inserted in the surgical cavities is currently under construction, with some technical advancements making possible its installation in an operating room dedicated to nIORT® treatments without posing any safety and environmental concern. In this article the nIORT® potentiality was investigated in the view of the GBM treatment, but the study is however generalisable for the neutron irradiation of other brain cancer pathologies. Accurate Monte Carlo simulations, modelling the CNG equipped with a couple of cylindrical applicators of 4 and 6 cm in diameter inserted in the brain surgical cavity after craniotomy, demonstrated that the nIORT® device operated at 100 kV-10 mA DC supplies a neutron flux ~108 cm-2 s-1 and can deliver equivalent dose rates ~5 Gy (RBE)/min in the centre of the tumour bed. Thus, it could administer the clinical endpoints foreseen by the standard IORT protocols (~10-20 Gy (RBE)) in treatment times of few minutes, by providing a sort of “switching on and off neutron brachytherapy tool” without using needles of radioisotopes (e.g., 252Cf). The near isotropic neutron emission allows to irradiate the tumour bed margins, normally filled by potential quiescent cancer cells, with lower (but still significant) dose levels. This should improve the local control of the tumour through the reduction of local recurrences and metastasis in the tumour microenvironment, and at the same time to avoid adverse effects of the administered neutron radiation field on the surrounding brain central nervous system. Also, the rapid decrease in tissue depth of the dose gradient (within few centimetres) should avoid any adverse effect on normal brain tissues and the neighbouring organs.

Short-term outcomes of chemoradiotherapy and local excision versus total mesorectal excision in T2-T3ab,N0,M0 rectal cancer: a multicentre randomised, controlled, phase III trial (the TAU-TEM study)

The standard treatment of T2-T3ab,N0,M0 rectal cancers is total mesorectal excision (TME) due to the high recurrence rates recorded with local excision. Initial reports of the combination of pre-operative chemoradiotherapy (CRT) and transanal endoscopic microsurgery (TEM) have shown reductions in local recurrence. The TAU-TEM study aims to demonstrate the non-inferiority of local recurrence and the improvement in morbidity achieved with CRT-TEM compared with TME. Here we describe morbidity rates and pathological outcomes. This was a prospective, multicentre, randomised controlled non-inferiority trial including patients with rectal adenocarcinoma staged as T2-T3ab,N0,M0. Patients were randomised to the CRT-TEM or the TME group. Patients included, tolerance of CRT and its adverse effects, surgical complications (Clavien-Dindo and Comprehensive Complication Index classifications) and pathological results (complete response in the CRT-TEM group) were recorded in both groups. Patients attended follow-up controls for local and systemic relapse. NCT01308190. From July 2010 to October 2021, 173 patients from 17 Spanish hospitals were included (CRT-TEM: 86, TME: 87). Eleven were excluded after randomisation (CRT-TEM: 5, TME: 6). Modified intention-to-treat analysis thus included 81 patients in each group. There was no mortality after CRT. In the CRT-TEM group, one patient abandoned CRT, 1/81 (1.2%). The CRT-related morbidity rate was 29.6% (24/81). Post-operative morbidity was 17/82 (20.7%) in the CRT-TEM group and 41/81 (50.6%) in the TME group (P < 0.001, 95% confidence interval 42.9% to 16.7%). One patient died in each group (1.2%). Of the 81 patients in the CRT-TEM group who received the allocated treatment, 67 (82.7%) underwent organ preservation. Pathological complete response in the CRT-TEM group was 44.3% (35/79). In the TME group, pN1 were found in 17/81 (21%). CRT-TEM treatment obtains high pathological complete response rates (44.3%) and a high CRT compliance rate (98.8%). Post-operative complications and hospitalisation rates were significantly lower than those in the TME group. We await the results of the follow-up regarding cancer outcomes and quality of life.

Abstract 6279: Combination of metformin and local irradiation efficiently provokes abscopal effects in a murine rectal cancer model

Abstract Introduction; Neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer is effective for the reduction of local recurrence and improvement of postoperative QOL. However, CRT has little effects for metastatic lesions in distant organs and does not prolong the prognosis. Abscopal effect refers to a phenomenon of tumor regression at a distant tumor away from the irradiated primary tumor, presumably through the host immune system. Metformin, a widely used drug for the treatment of type 2 Diabetes Mellitus, has been shown to elicit anti-cancer effects partly through the activation of host immunity. However, how metformin modulates the abscopal effects of local radiation (RT) and metformin has not been well investigated. Method; Mice were subcutaneous inoculated by 1x106 cells of LuM1, a highly murine lung metastatic subclone of colon 26, at right flank of 7 weeks female BALB/c mice which were treated with metformin and/or RT. In RT groups, 4Gy X-ray was selectively given to subcutaneous tumors using lead shield under general anesthesia at day 13 and 15. Metformin hydrochloride (1mg/ml) were orally administrated from day13 continuously. At 28 days, mice were sacrificed, and we evaluated the weight of primary subcutaneous (s.c) tumor and the number of lung metastases. The phenotypes of splenocytes and blood were examined by flowcytometric analysis. Results: Local RT (4Gy x 2) suppressed the growth of s.c tumor to approximately half of control group although not statistically significantly (p=0.067). Metformin alone did not significantly suppress the tumor growth. However, when combined with RT, tumor weight at day28 was markedly reduced as compared with control group (p&amp;lt;0.01). Many lung metastases developed in all control group mice (Median (M)=120, 22-188) which was not changed by the treatment of metformin alone. The number of metastases tended to be reduced in RT group, although not significant (M=34, 3-78, p=0.12). In comparison, when metformin was combined to RT, the number of lung metastasis was markedly decreased (M=13, 0-70, p&amp;lt;0.01) with no metastases detected in 3 in 10 mice. The ratios of CD4(+) or CD8(+) T cells tended to be reduced in mice treated with RT alone, while increased in mice treated with RT and Metformin. CD49b(+)CD335(+) activated natural killer (NK) cells was significantly increase in combination group (1.1%±0.19% vs 2.6%±1.0%, p&amp;lt;0.05). The ratios PD-1(+) cells tended to be reduced, whereas those of IFN-γ (+) cells in T cell subpopulations after stimulation were significantly increased in mice treated with RT and metformin as compared with those in control group (CD4; 6.8±2.4% vs 10.4%±1.3%, p&amp;lt;0.05; CD8; 24.1±3.6% vs 40.4%±7.2%, p&amp;lt;0.01) Conclusion;Metformin restores T cell exhaustion and increase the number of activated NK cells in irradiated mice which may suppress the growth of lung metastases as abscopal effects. Citation Format: Mineyuki Tojo, Hideyo Miyato, Koji Koinuma, Hisanaga Horie, Hidenori Tsukui, Akira Saito, Yuki Kimura, Yuki Kaneko, Hideyuki Ohzawa, Hironori Yamaguchi, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama. Combination of metformin and local irradiation efficiently provokes abscopal effects in a murine rectal cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6279.

Noninferiority multicenter prospective randomized controlled study of rectal cancer T2–T3s (superficial) N0, M0 (T2T3sN0M0) undergoing neoadjuvant treatment and local excision (TEM) versus total mesorectal excision (TME): Preoperative, surgical, and pathological outcomes—The TAUTEM-study.

3501 Background: The standard surgical treatment of rectal adenocarcinoma above T1 is total mesorectal excision (TME), but it is associated with high morbidity and quality of life disorders. Transanal endoscopic microsurgery (TEM) achieves minimal postoperative morbidity rates. The treatment of T2, T3 superficial, N0, M0 rectal cancers is TME due to local excision achieving high recurrence rates. Initial reports of preoperative chemoradiotherapy (CRT) in association with TEM shows reduction in local recurrence. The TAU-TEM study aims to demonstrate the non-inferiority of the oncological outcomes and the improvement in morbidity and quality of life achieved with CRT-TEM compared with TME. Methods: Prospective, multicenter, randomized controlled non-inferiority trial including patients with rectal adenocarcinoma less than 10 cm from the anal verge and up to 4 cm in size, staged as T2T3sN0M0. Patients were randomized to: CRT-TEM (Arm A) or TME (Arm B). Postoperative morbidity and mortality were recorded and patients in both arms completed quality of life questionnaires when starting treatment and 6 months after surgery. Patients attended follow-up controls for local and systemic relapse. Trial registration: ClinicalTrials.gov Identifier: NCT01308190. Results: From July/2010 to October/2021, 173 patients from 17 Spanish hospitals were included (Arm A: 86, Arm B: 87). Ten were excluded after randomization (Arm A: 4, [3 re-staged &gt; T2T3sN0M0, 1 refused follow-up study]; Arm B: 6 [4 refused the arm, 2 re-staged &gt; T2T3sN0M0]). Therefore, the patients with modified intention to treat analysis were: TME, 81 and CRT-TEM, 82. There was no mortality after CRT. In this group, 2 patients abandoned neoadjuvant therapy; thus 80/82 (97.6%) completed CRT. The CRT-morbidity was low (25/82, 30%) and of low grade (95% G1-2). In the CRT-TEM group, MRI showed disease progression in 3 patients who were treated with TME. Finally, 77 patients underwent TEM surgery. One patient died in each arm (1.2%). Postoperative morbidity was 41/81 (50.6%) (Arm B) and 17/82 (20.7%) (Arm A) (p &lt; 0.001, 95 CI% 43.9 to 15.9). Median Comprehensive Complication Index was 8.7 (IQR 20.9) Arm B and 0 (IQR 0) Arm A (p &lt; 0.001). Median hospital stay was 7 days (IQR 7) Arm B and 2 days (IQR 2) Arm A (p &lt; 0.001). Complete response in Arm A was 45.3% (34/75 patients) with 5.3% ypT3 (4/75 patients) and in Arm B: pT1 (12.3%; 10/81patients), deep-pT3 (4.95; 4/81patients), pN1 (21%; 17/81). Conclusions: CRT-TEM treatment obtains high pathological complete response rates (45.3%), with a high CRT compliance rate (97.6%) and low morbidity. Postoperative complications and hospitalization are significantly lower in the CRT-TEM group. We await the results of the follow-up. Clinical trial information: NCT01308190.

Treatment strategies for locally recurrent rectal cancer

The evolution of rectal cancer treatment over the last two decades including advances in surgical technique (total mesorectal excision) [1], the advent of pre-operative MRI staging [2], and judicious use of neoadjuvant therapy [3] has resulted in a significant reduction in local recurrence of approximately 5–10% [4–6]. However, the effects of locally recurrent rectal cancer (LRRC) can be devastating, with a median survival of approximately 8 months and a multitude of distressing symptoms including pelvic pain, rectal bleeding and mucous discharge, all of which can adversely affect a patient's quality of life [7,8].

An analysis of a large multi-institutional database reveals important associations between treatment parameters and clinical outcomes for stereotactic body radiotherapy (SBRT) of oligometastatic colorectal cancer

PurposeIn recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for oligometastatic cancers. Here, we report radiation treatment parameters and clinical outcomes for patients with oligometastatic colorectal cancer (CRC) treated with SBRT using a large multi-institutional database. MethodsPatients with extra-cranial oligometastatic CRC (≤5 lesions) treated with SBRT at six large academic cancer centers were included. The primary outcome was local recurrence while secondary outcomes included overall survival (OS) progression free survival, oligo-progression, and widespread progression. Survival outcomes were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine the relationship between patient and treatment characteristics and clinical outcomes. ResultsWe identified 235 patients with a total of 381 oligometastatic CRC lesions. The 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year OS of 76.1% and 35.9%, respectively. On multivariable analysis, a BED10 of ≥120 Gy, and lung versus liver metastases were associated with a reduction in local recurrence. Larger total PTV size (≥17.5 cc) was associated with worse overall survival, progression free survival, and widespread progression. ConclusionThis large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is higher than expected for ablative radiation treatment. An increase in BED10 should be considered if feasible and safe.

Role of Radiation Therapy for Newly Diagnosed Retroperitoneal Sarcoma.

Soft tissue sarcomas (STS) are rare, aggressive, and heterogenous tumors, comprising approximately 1% of adult cancers with over 50 different subtypes. The mainstay of treatment for retroperitoneal sarcomas (RPS) includes surgical resection. The addition of radiation therapy (RT), either preoperatively or postoperatively, has been used to potentially decrease the risk of local recurrence. The recently published results from STRASS (EORTC-STBSG 62092-22092), which randomized patients to receive or not receive preoperative radiation, indicate no abdominal recurrence-free survival benefit (primary endpoint) nor overall survival benefit to date from the addition of preoperative RT prior to surgical resection in patients with RPS. Keeping in mind caveats of subgroup analyses, the data show a significant reduction in local recurrence with radiation therapy in resected patients and non-significant trends toward improved abdominal recurrence-free survival in all patients and improved local control and abdominal recurrence-free survival in patients with liposarcoma and low-grade sarcoma. Given the high rate of local failure with surgery alone, it is possible that higher RT dose and/or selective RT dose painting may improve outcomes. Prior to treatment, the authors encourage multidisciplinary review and discussion of management options at a sarcoma center for patients with RPS. Selective use of RT may be considered for patients at high risk of local recurrence.

Positive lateral pelvic lymph nodes in low rectal cancer: should we change our practice now?

The role of lateral lymph node dissection (LLND) in the treatment of patients with low rectal cancer with enlarged lateral lymph nodes (LLN+) is under investigation. Enthusiasm for LLND stems from a perceived reduction in local recurrence (LR). We aimed to compare the LR rate for LLN+ patients with LLN- patients, treated with neoadjuvant chemoradiotherapy (nCRT) and surgery, in a hospital that does not perform LLND. A retrospective study of all patients with clinical stage 3 low rectal cancer who completed nCRT and surgery between 2008 and 2017 at Western Health was performed. Outcomes for LLN+ patients were compared with LLN- patients. The primary outcome was LR. Secondary outcomes included distant metastases, disease-free survival and overall survival. There were 110 patients treated for stage 3 low rectal cancer over 10 years. There was no significant difference in the LR rate, with one LR from 28 LLN+ patients and one LR from 82 LLN- patients (4% versus 1.2%, P=0.44). There were no significant differences in median disease-free survival (41 versus 52 months, P=0.19) or mean overall survival (62 versus 60 months, P=0.80). Of all patients studied, 21% developed distant metastases. LR after nCRT and surgery in patients with stage 3 rectal cancer is rare, irrespective of lateral pelvic node status. These data, along with the uncertain benefit and known risks of LLND, supports the continued use of standard therapy in these patients. Strategies to address distant failure in these patients should be explored.

Neoadjuvant Short-Course Radiotherapy for Upper Third Rectal Tumors: Systematic Review and Individual Patient Data Metaanalysis of Randomized Controlled Trials.

There is no consensus on the use of neoadjuvant radiotherapy for tumors of the upper third of the rectum. Due to conflicting findings in high-quality trials and significant long-term side effects associated with neoadjuvant radiotherapy, the benefit of neoadjuvant radiotherapy for upper third rectal tumors is less certain than for lower two third rectal tumors. This metaanalysis compares oncological outcomes with neoadjuvant radiotherapy and surgery versus surgery alone for upper third rectal tumors. PubMed, Embase, and the Cochrane library databases were searched. Randomized controlled trials (RCT) comparing neoadjuvant radiotherapy and surgery versus surgery alone for resectable rectal cancer were included. Individual patient data were sought from the principal investigator of each eligible trial for comparative data on patients with upper third rectal tumors. The main outcomes measured were survival outcomes, oncological outcomes, postoperative morbidity, and late toxicity. Individual patient data from two RCTs examining outcomes in 758 patients were obtained. Published data from one further RCT containing comparable data on upper third rectal tumors were included in analysis of local recurrence. In patients with curative surgery, there was no significant reduction in local recurrence or significant improvement in overall survival or disease-free survival with neoadjuvant radiotherapy (LR RR: 0.38, 95% CI 0.14-1.04, p = 0.06) (OS RR: 1.10, 95% CI 0.98-1.24, p = 0.11) (DFS RR: 1.11, 95% CI 0.97-1.26, p = 0.13). The benefit of neoadjuvant radiotherapy for upper third rectal tumors is not certain, and surgery alone for patients with potentially curative disease at preoperative staging may be sufficient.

Recurrent Gluteal Sarcoma Managed with Unilateral Excision of Levator Ani Muscle: Case Report

Soft Tissue Sarcomas (STS) are rare malignant tumors that: arise from mesenchyme, 80% arise in soft tissue while 20% in bone, and they comprise 1% adult tumors. Gluteus maximus STS is site with frequently diagnoses of high- and low-grade STS. Low-grade STS respond well to surgery alone while high-grade STS require preoperative chemoradiation therapy, followed by surgery, and then postoperative chemotherapy. Work-up includes: a core needle biopsy for histopathological diagnosis, MRI for imaging of local disease and Contrast enhanced CT scan for pulmonary metastasis. Recurrence is viewed as a sign of poor local treatment and a risk for distant metastasis. Reduction of local recurrence does not lead to improved survival, but lack of disease progression with pulmonary metastasis does. In our patient, laparoscopy allowed total mesorectal excision dissection and sparing of rectum, as there was no metastatic spread of tumor to the rectum. Despite excision of right levator ani muscle, our patient maintained her continence, as shown by Fucini et al. [1] that continence would be maintained despite dissection and separation of levator ani muscle from the anal complex unit (external and internal anal sphincter) followed by unilateral excision of levator ani muscle, while achieving good oncologic and anal function outcome. We present our management of a 55-year-old lady with recurrent gluteal STS with extension into the ischiorectal fossa managed at Tata Memorial Hospital, in Parel, Mumbai, India, in the Department of Colorectal Surgery.

Analysis of Rectal Neoplasms Operated After Neoadjuvant Therapy in A Period of 10 Years

Background: With the advances of neoadjuvant chemoradiotherapy, the identification of complete tumor responses, and the reduction of local recurrence even with the adoption of expectant approaches aimed at sphincter preservation, several authors have published results analyzing these aspects with conflicting results, which require further investigation. Objectives: This study aims to evaluate the anatomopathological changes in surgical specimens of rectal resection due to adenocarcinoma in patients undergoing neoadjuvant therapy, including the complete response rate, in addition to estimating the sensitivity and specificity indexes of the imaging methods used in the preoperative period. Methods: This was an observational, retrospective, cross-sectional study in which 44 medical records of patients with cancer of the middle and lower rectum who underwent neoadjuvant chemoradiotherapy and subsequently underwent oncological surgical resections over 10 years were studied. Demographic data, CT scans, colonoscopies, anatomopathological reports and surgical reports were analyzed. Results: Abdominoperineal resection of the rectum (APR) was performed in 16 cases (36.4%), and abdominal rectosigmoidectomy (AR) was performed in 28 cases (63.6%). Preoperative computerized tomography (CT) showed a sensitivity of 75% and specificity of 77.8% for the detection of lymph node metastases. The complete pathological response to neoadjuvant chemoradiotherapy was found in 11.36% of cases. The local recurrence was detected in 23.9% cases and distant metastasis in 15.2% of the patients on the follow-up period, additionally, there was a 77.7% 5-years disease-free survival and the overall survival was 73.9%. Conclusions: The rate of complete pathological response to neoadjuvant therapy was 11.36%. Locally advanced disease and angiolymphatic embolization were associated with a higher frequency of lymph node involvement. CT obtained high rates of sensitivity and specificity for comparison with anatomopathological results.

Total Mesorectal Excision Technique-Past, Present, and Future.

While the treatment of rectal cancer is multimodal, above all, a proper oncological resection is critical. The surgical management of rectal cancer has substantially evolved over the past 100 years, and continues to progress as we seek the best treatment. Rectal cancer was historically an unsurvivable disease, with poor understanding of the embryological planes, lymphatic drainage, and lack of standardized technique. Major improvements in recurrence, survival, and quality of life have resulted from advances in preoperative staging, pathologic assessment, the development and timing of multimodal therapies, and surgical technique. The most significant contribution in advancing rectal cancer care may be the standardization and widespread implementation of total mesorectal excision (TME). The TME, popularized by Professor Heald in the early 1980s as a sharp, meticulous dissection of the tumor and mesorectum with all associated lymph nodes through the avascular embryologic plane, has shown universal reproducible reductions in local recurrence and improvement in disease-free and overall survival. Widespread education and training of surgeons worldwide in the TME have significantly impact outcomes for rectal cancer surgery, and the procedure has become the gold standard for curative resection of rectal cancer. In this article, we discuss the evolution of the standard abdominal approach to the TME, with emphasis on the history, relevant anatomy, standard procedure steps, oncologic outcomes, and technical evolution.

Is Treatment with Denosumab Associated with Local Recurrence in Patients with Giant Cell Tumor of Bone Treated with Curettage? A Systematic Review.

Denosumab, a monoclonal antibody that binds to receptor activation of nuclear factor-kappa ß ligand (RANKL), has been used as a drug to treat aggressive giant cell tumors of bone. It is unclear whether preoperative denosumab therapy is associated with the local recurrence risk in patients with giant cell tumors of bone treated with curettage. Early evidence suggests that denosumab treatment is associated with a reduction in local recurrence, but other studies have questioned that premise. Curettage after a short course of denosumab (3 to 4 months) has been recommended, especially for large, aggressive giant cell tumors in which complete curettage is difficult to achieve. No randomized studies have documented the benefit of this approach, and some investigators have reported higher local recurrence after denosumab treatment. Due to this confusion, we performed a systematic analysis of existing reports to attempt to answer this question and determine whether the appropriate preoperative denosumab therapy duration could be established. (1) Is the use of preoperative denosumab associated with local recurrence risk in patients with giant cell tumors of bone treated with curettage compared with those treated with curettage alone? (2) Is the preoperative denosumab therapy duration associated with local recurrence after curettage? We searched the PubMed, EMBASE, and CENTRAL databases on April 26, 2019 and included both randomized and non-randomized studies that compared local recurrence between patients who had giant cell tumors of bone and were treated with curettage after preoperative denosumab and patients treated with curettage alone. Two authors independently screened the studies. There were no randomized studies dealing with denosumab in giant cell tumors of bone, and generally, denosumab was used for more aggressive tumors. We assessed the quality of the included studies using the Risk of Bias Assessment tool for Non-randomized Studies, with a moderate overall risk of bias. We registered our protocol in PROSPERO (registration number CRD42019133288). We selected seven eligible studies involving 619 patients for the final analysis. The proportion of patients with local recurrence ranged from 20% to 100% in the curettage with preoperative denosumab group and ranged from 0% to 50% in the curettage-alone group. The odds ratio of local recurrence ranged from 1.07 to 37.80 in no more than 6 months of preoperative denosumab duration group and ranged from 0.60 to 28.33 in more than 6 months of preoperative denosumab duration group. The available evidence for the benefit of denosumab in more aggressive giant cell tumors is inconclusive, and denosumab treatment may even be associated with an increase in the proportion of patients experiencing local recurrence. Because there are no randomized studies and the existing studies are of poor quality due to indication bias (the most aggressive Campanacci 3 lesions or those where even a resection would be difficult and result in morbidity are generally the patients who are treated with denosumab), the evidence to suggest a disadvantage is weak. Denosumab treatment should be viewed with caution until more definitive, randomized studies documenting a benefit (or not) have been conducted. Furthermore, we could not find evidence to suggest an appropriate length of preoperative denosumab before curettage.

A literature review of the role of brachytherapy in the management of early-stage breast cancer

AbstractBackground:This review evaluates whether brachytherapy can be considered as an alternative to whole breast irradiation (WBI) using criteria such as local recurrence rates, overall survival rates and quality of life (QoL) factors. This is an important issue because of a decline in local recurrence rates, suggesting that some women at very low risk of recurrence may be incurring the negative long-term side effects of WBI without benefitting from a reduction in local recurrence and greater overall survival. As such, the purpose of this literature review is to evaluate whether brachytherapy is a credible alternative to external beam radiation with a particular focus on the impact it has on patient QoL.Methods:The search terms used were devised by using the Population Intervention Comparison Outcome framework, and a literature search was carried out using Boolean connectors and Medical Subject Headings in the PubMed database. The resultant articles were manually assessed for relevance and appraised using the Scottish Intercollegiate Guidelines Network tool. Additional papers were sourced from the citations of articles found using the search strategy. Government guidelines and regulations were also used following a manual search on the National Institute for Health and Care Excellence website. This process resulted in a total of 30 sources being included as part of the review.Results:Three types of brachytherapy were the foundation for the majority of the papers found: interstitial multi-catheter brachytherapy, intra-cavity brachytherapy and permanent seed implantation. The key themes that arose from the literature were that brachytherapy is equivalent to WBI both in terms of 5-year local recurrence rates and overall survival rates at 10–12 years. The findings showed that brachytherapy was superior to WBI for some QoL factors such as being less time-consuming and equal in terms of others such as breast cosmesis. The results did also show that brachytherapy does come with its own local toxicities that could impact upon QoL such as the poor breast cosmesis associated with some brachytherapy techniques.Conclusion:In conclusion, brachytherapy was deemed a safe or acceptable alternative to WBI, but there is a need for further research on the long-term local recurrence rates, survival rates and quality of life issues as the volume of evidence is still significantly smaller for brachytherapy than for WBI. Specifically, there needs to be further investigation as to which patients will benefit from being offered brachytherapy and the influence that factors such as co-morbidities, performance status and patient choice play in these decisions.